ldquoSystemic Sclerosis Recognition
of Systemic and multisystem
autoimmune Disease rdquo
November 15 2017
Patrick Cronin DOFACR
Clinical Instructor
Cooper Medical School of Rowan University
Cooper University Bone amp Joint Institute
Division of Rheumatology
American College of Rheumatology Systemic Sclerosis (1980) Classification criteria Diagnosis 1 major (or) 2 minor
Major criterion Proximal scleroderma
(proximal to the MCP joints)
Minor criteria Sclerodactyly
Digital pitting or scars or loss substance finger pad
Bibasilar pulmonary fibrosis
Classification Scleroderma
Systemic Sclerosis
Diffuse cutaneous
Progressive Systemic Sclerosis
Limited cutaneous
CREST (calcinosis Raynaudrsquos esophageal dysmotility sclerodactyly atelectasis) Syndrome
Scleroderma sine scleroderma
Scleroderma-Like Syndromes
Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)
Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma
Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)
Scleromyxedemamyxedema
Epidemiology Scleroderma
Female Male = 31 (Greater in African-American women)
Age Peak 35-65 years
Incidence 19 casesmillionyear
Prevalence 19-75 cases100000
Scleroderma Proposed Pathophysiology
Cytokines
Transforming Growth Factor β (TGF- β)
Platelet Derived Growth Factor (PDGF)
Endothelial damage ndash releases endothelin ndash increase fibroblast function
Collagen I
Fibronectin
Glycosaminoglycans
Endothelial injury
VasoconstrictionFibroblastuarr
Hypoxia -- uarr TGF β
Fibroblast uarr
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
American College of Rheumatology Systemic Sclerosis (1980) Classification criteria Diagnosis 1 major (or) 2 minor
Major criterion Proximal scleroderma
(proximal to the MCP joints)
Minor criteria Sclerodactyly
Digital pitting or scars or loss substance finger pad
Bibasilar pulmonary fibrosis
Classification Scleroderma
Systemic Sclerosis
Diffuse cutaneous
Progressive Systemic Sclerosis
Limited cutaneous
CREST (calcinosis Raynaudrsquos esophageal dysmotility sclerodactyly atelectasis) Syndrome
Scleroderma sine scleroderma
Scleroderma-Like Syndromes
Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)
Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma
Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)
Scleromyxedemamyxedema
Epidemiology Scleroderma
Female Male = 31 (Greater in African-American women)
Age Peak 35-65 years
Incidence 19 casesmillionyear
Prevalence 19-75 cases100000
Scleroderma Proposed Pathophysiology
Cytokines
Transforming Growth Factor β (TGF- β)
Platelet Derived Growth Factor (PDGF)
Endothelial damage ndash releases endothelin ndash increase fibroblast function
Collagen I
Fibronectin
Glycosaminoglycans
Endothelial injury
VasoconstrictionFibroblastuarr
Hypoxia -- uarr TGF β
Fibroblast uarr
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Classification Scleroderma
Systemic Sclerosis
Diffuse cutaneous
Progressive Systemic Sclerosis
Limited cutaneous
CREST (calcinosis Raynaudrsquos esophageal dysmotility sclerodactyly atelectasis) Syndrome
Scleroderma sine scleroderma
Scleroderma-Like Syndromes
Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)
Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma
Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)
Scleromyxedemamyxedema
Epidemiology Scleroderma
Female Male = 31 (Greater in African-American women)
Age Peak 35-65 years
Incidence 19 casesmillionyear
Prevalence 19-75 cases100000
Scleroderma Proposed Pathophysiology
Cytokines
Transforming Growth Factor β (TGF- β)
Platelet Derived Growth Factor (PDGF)
Endothelial damage ndash releases endothelin ndash increase fibroblast function
Collagen I
Fibronectin
Glycosaminoglycans
Endothelial injury
VasoconstrictionFibroblastuarr
Hypoxia -- uarr TGF β
Fibroblast uarr
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma-Like Syndromes
Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)
Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma
Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)
Scleromyxedemamyxedema
Epidemiology Scleroderma
Female Male = 31 (Greater in African-American women)
Age Peak 35-65 years
Incidence 19 casesmillionyear
Prevalence 19-75 cases100000
Scleroderma Proposed Pathophysiology
Cytokines
Transforming Growth Factor β (TGF- β)
Platelet Derived Growth Factor (PDGF)
Endothelial damage ndash releases endothelin ndash increase fibroblast function
Collagen I
Fibronectin
Glycosaminoglycans
Endothelial injury
VasoconstrictionFibroblastuarr
Hypoxia -- uarr TGF β
Fibroblast uarr
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleromyxedemamyxedema
Epidemiology Scleroderma
Female Male = 31 (Greater in African-American women)
Age Peak 35-65 years
Incidence 19 casesmillionyear
Prevalence 19-75 cases100000
Scleroderma Proposed Pathophysiology
Cytokines
Transforming Growth Factor β (TGF- β)
Platelet Derived Growth Factor (PDGF)
Endothelial damage ndash releases endothelin ndash increase fibroblast function
Collagen I
Fibronectin
Glycosaminoglycans
Endothelial injury
VasoconstrictionFibroblastuarr
Hypoxia -- uarr TGF β
Fibroblast uarr
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Epidemiology Scleroderma
Female Male = 31 (Greater in African-American women)
Age Peak 35-65 years
Incidence 19 casesmillionyear
Prevalence 19-75 cases100000
Scleroderma Proposed Pathophysiology
Cytokines
Transforming Growth Factor β (TGF- β)
Platelet Derived Growth Factor (PDGF)
Endothelial damage ndash releases endothelin ndash increase fibroblast function
Collagen I
Fibronectin
Glycosaminoglycans
Endothelial injury
VasoconstrictionFibroblastuarr
Hypoxia -- uarr TGF β
Fibroblast uarr
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Proposed Pathophysiology
Cytokines
Transforming Growth Factor β (TGF- β)
Platelet Derived Growth Factor (PDGF)
Endothelial damage ndash releases endothelin ndash increase fibroblast function
Collagen I
Fibronectin
Glycosaminoglycans
Endothelial injury
VasoconstrictionFibroblastuarr
Hypoxia -- uarr TGF β
Fibroblast uarr
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma ANA
Centromere Homogenous
Speckled Nucleolar
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Skin
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
ldquoRaynaudrsquosrdquo
Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Digital Artery
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Thermography Raynaudrsquos
Control 1 Raynaudrsquos Scleroderma
15 c
23 c
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Raynaudrsquos
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Raynaudrsquos
Episodic
Reversible digital color change
White to blue to red
Well-demarcated
Due to vasospasm
Usually cold-induced
Primary amp secondary
forms
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Raynaudrsquos
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Raynaudrsquos Cyanosis
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Capillary Microscopy
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Causes of Secondary Raynaudrsquos
Connective tissue diseases
Scleroderma systemic lupus erythematosus MCTD
undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others
Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease
Vascular injury Frostbite vibratory trauma
Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine
Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Raynaudrsquos
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Edematous Changes Hands
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Puffy Phase Hand
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Hands
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Skin Induration
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Acrosclerosis
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Acrolysis
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Acro-sclerosis amp Terminal Digit Resorption
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Digital Pitting Scars
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Limited Systemic Sclerosis Calcinosis
bullCalcinosis
(Hydroxyapatite)
bullColchicine
bullCalcium Channel
Blockers
Arthritis Rheum 1995 Nov38(11)1646-54
Treatment of calcinosis with diltiazem
Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR
Source
University of Tennessee at Memphis 38163 USA
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Calcinosis Cutis
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Calcinosis and Acrolysis
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Limited Systemic Sclerosis Calcinosis Arm
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Calcinosis
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Facial Changes
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Facial Changes
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Watermelon Stomach
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Dysmotility and Esophagus
Upper GI tract
GERD
Proton Pump Inhibitor
Aspiration Pneumonia
PPI vs Carafate
EsophagitisBarrettrsquos
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Bowel Dilatation
GI Malabsorption
Vitamin D
Difficult to treat
Bacterial Overgrowth
Metronidazole
Tetracycline
Ciprofloxacin
Weight LossCachexia
TPN
Pseudo-obstruction
Non-surgical
General Measures
Octreotide erythromycin
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Wide-Mouth Diverticula
Diverticula
Wide mouth
Rare diverticulitis
Pneumatosis Cystoides Intestinalis
Non-Surgical
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Pulmonary
Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA
6 minute walk
Echocardiogram ndash yrrsquoly PAP
PFT with DLCO ndash yrrsquoly compare DLCO
Cardiac
Contraction band necrosis - arrhythmias
Pericardial effusion ndash large non-tamp
Myocarditis
Scleroderma Pulmonary Cardiac
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Pulmonary HTN
PHTN ndash Echocardiogram or Right Heart Cath
High mortality ndash 52 at 3 years survival ()
Bosentan (next slide)
Sildenafil ndash SUPER-1 trial (1)
() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review
and meta-analysis
Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum
201365(9)2412
(1)Sildenafil citrate therapy for pulmonary arterial hypertension
Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F
Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
N Engl J Med 2005 Nov 17353(20)2148-57
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Kidney
Scleroderma Renal Crisis
High Renin State
Microangiopathic Hemolytic Anemia
HTN and active urine sediment
Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern
Treatment
ACE inhibitor ndash Calcium Channel Blocker
Minimize steroids
()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis
Steen VD Medsger TA Jr
Arthritis Rheum 1998 Sep41(9)1613-9
Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade
Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD
N Engl J Med 1979 3001417-1419
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Kidney
Scleroderma Renal Crisis renal biopsy with fibrinoid
deposition ldquoonion-ringrdquo muscular hyperplasia
Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)
inhibitors
Steen VD Costantino JP Shapiro AP Medsger TA Jr
Ann Intern Med 1990113(5)352
One year survival 15 without and 76 with ACE inhibitors (P lt 0001)
Courtesy of Carol Black MD Graphic 78330 Version 60
Courtesy of Helmut Rennke MD Graphic 70213 Version 20
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Raynaudrsquos Hands
Raynaudrsquos
Longer term use
Aspirin or pentoxifylline
Calcium Channel Blockers
Bosentan (PAH)
Short term use
Topical NTG
Prostacyclin IV
Phosphodiesterase Inhibitor
Others ndash SSRI ARBACE ect
Arthritis Rheum 2004 Dec50(12)3985-93
Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor
antagonist
Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu
V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N
Gaitonde M Black C
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Raynaudrsquos HomeostasisPrevention
Life-Style Changes Dry hands and feet
Avoid convection currents Wool socks and mittens
Layer chest wall for heat trapping
Quit tobacco limit caffeine and alcohol
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Queen Elisa Raynaudrsquos patient and spokesperson
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Scleroderma Treatment
Immunosuppression (Diffuse Disease only)
Traditional immunotherapy and antifibrotics
Methotrexate
D-penicillamine
Cyclophosphamide
Current clinical immunotherapy treatments
Mycophenolate mofatil
Abatacept
Tocilizumab
Rituximab
Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind
parallel group trial
Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C
Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J
Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K
Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators
Lancet Respir Med 20164(9)708 Epub 2016 Jul 25
Thank You Questions
Thank You Questions