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SLE Update 2014Donald Thomas, MD, FACP, FACR
Arthritis and Pain Associates of PG CountyAssistant Professor of Medicine
Uniformed Services University of the Health Sciences, Bethesda
SLE Update:What we will cover
- New “classification criteria” for systemic lupus- ANA up dates- “No evidence of lupus” workup- Plaquenil in all SLE patients- Prevent lupus triggers - AAO Anti-malarial guidelines
- Required tests + proper dosing
- “New” vaccine recommendations- IM steroids treatment for SLE (FLOAT trial)
SLICC- Systemic Lupus International Collaborating Clinics
- Formed in 1991 to develop lupus damage index for research
- 1998 expanded its work:- Establish cohort of newly diagnosed patients- Collect blood samples for future evaluation- Evaluate accelerated atherosclerosis- Evaluate neuropsychiatric disorders in lupus- Study cancer in lupus
American College of Rheumatology (ACR) Classification Criteria for SLE
1982- 4 out of 14 criteria = SLE- Classification criteria = for research purposes only
- Not recommended for diagnostic purposes
- 2004 SLICC embarked upon revision
SLICC: classification criteria improvements
- Missing in 1982 criteria- Low complements- Antiphospholipid antibodies
- 1982 weighted towards cutaneous dz (4 of 14 criteria)- Excluded biopsy proven lupus nephritis as sole
manifestation- Neuro lupus only included psychosis and seizures
- ACR lists 18 potential neurologic disorders in neuropsychiatric lupus
- Could only use one type of low blood count- LE cell prep no longer used
SLICC: classification criteria improvements
- Diagnosed SLE patients vs those meeting classification
- Many patients with early SLE don’t meet criteria- By the time they do they are:
- Older- Had established disease longer- More end-organ damage
- Confirmed by Alarcón, et al, 2013- SLICC criteria allowed earlier diagnosis of SLE
SLICC: SLE classification criteria- SLE occurs if
- Biopsy proven lupus nephritis + ANA or dsDNA
- OR- 4 out of 17 criteria- At least 1 from “Clinical Criteria” and from
“Immunologic Criteria”
SLICC SLE classification criteriaClinical Criteria (11)
- Renal (*** expanded definition) - Alopecia, nonscarring ***- Serositis (*** expanded definition) - Hemolytic anemia ***
- Oral and nasal ulcers- Neurologic (*** expanded definition)
- Synovitis (*** expanded definition) - Chronic cutaneous lupus (*** expanded definition) - Acute cutaneous lupus (*** expanded definition)- Leucopenia/lymphopenia ***- Platelets, low ***
photo credit: studyblue.com
SLE Clinical Criteria:Renal
- Random urine protein/creatinine ratio ≥ 0.500- 25 hour urine protein ≥500 mg protein/24 hours- Red blood cell casts on urine microscopy
SLE Clinical Criteria:Alopecia, nonscarring
- Diffuse thinning- Hair fragility, broken hair- “Lupus hair”- Rule out alopecia areata, drugs, iron deficiency,
androgenic alopecia- Grows back
CellCept
Photo credit: clinicalcases.org
SLE Clinical Criteria:Serositis
- Pleuritis- “Typical pleurisy” > 1 day- Pleural effusions- Pleural rub
- Pericarditis- “Typical pericardial pain” > 1 day (worse with lying,
better sitting forward)- Pericardial effusion- Pericardial rub- + ECG
Photo credit: en.wikipedia.org
SLE Clinical Criteria:Neuropsychiatric
- Seizures- Psychosis- Mononeuritis multiplex
- in absence of a 1° vasculitis- Myelitis- Peripheral or Cranial neuropathy
- R/o diabetes, infection (Lyme), 1° vasculitis- Acute confusional state
- R/o toxic, metabolic, uremia, infection, drugs
Photo credit: cdaarthritis.com
SLE Clinical Criteria:Synovitis
- ≥ 2 joints- Swelling or effusion OR- Tender joints + AM stiffness ≥ 30 minutes
Photo credit: entindia.info
SLE Clinical Criteria:Chronic cutaneous lupus
- Discoid lupus- Hypertrophic (verrucous) lupus- Lupus panniculitis (profundus)- Discoid lupus/lichen planus overlap- Lupus erythematosus tumidus- Chilblains lupus- Mucosal lupus
Photo credit: globalskinatlas.com
SLE Clinical Criteria:Acute cutaneous lupus ORSubacute cutaneous lupus
- Malar rash (don’t count discoid)- Toxic necrolysis variant of SLE- Maculopapular lupus rash- Photosensitive lupus rash- Bullous lupus- SCLE:
- Non-indurated psoriasiform- Annular polycyclic
SLE Immunologic Criteria (6)- ANA- Anti-ds DNA- Anti-Smith- Antiphospholipid antibodies
- Lupus anticoagulant- False positive RPR- Anticardiolipin antibody- Beta-2 glycoprotein antibody
- Low complements (C3, C4, CH50)- Direct Coombs’ test (in absence of hemolytic anemia)
Labs to add during your SLE workup:- If positive ANA by IFA
- CH50 complements- Direct Coombs’ test- Antiphospholipid antibodies
- RPR with reflex FTA- Anticardiolipin antibodies (IgM, IgG, IgA)- Lupus anticoagulant- Beta-2 glycoprotein I antibodies (IgM, IgG, IgA)
2012 criteria vs 1982criteria- Out of 702 patient scenarios……….- Misclassified patients: 7% vs 10%- Sensitivity: 94% vs 86%- Specificity: 92% vs 93% (not statistically different)
“… if you use the classification
criteria to diagnose SLE... I promise not
to tell anyone.”
Michelle Petri, MD: Medical Director Lupus Clinic Johns Hopkins
Order ANA by IIFA- Order ANA by IIFA
- Indirect Immunofluorescent Assay- Detects up to 150 autoantigens- Results = titer with pattern (eg 1:160 speckled)- Formal recommendation of the ACR- Recent international group = same recommendation
- Cheaper solid phase assays- Only detect 6-8 autoantigens- Higher number of false negatives- Value results given as a # units or as “neg” or “pos”
What to do with a negative ANA solid phase?
- Order ANA by IIFA- Can’t rule out a false negative in the workup of SLE
Antibodies occur before SLE dx- 115 out of 130 SLE patients
- Up to 9.4 years before diagnosis- Many times + earliest available samples- Most likely occur significantly earlier
- Average of 3.3 years- ANA (78%)- dsDNA (55%)- SSA (47%); SSB (34%)- Smith (32%); RNP (26%)- APLAs (18%)
What to do with that ANA consult- If nonspecific symptoms or fibromyalgia… check
autoantibodies. Don’t assume fibromyalgia- If specific autoantibodies are all negative:
- “You do not have any evidence for lupus or a systemic autoimmune disease at this time” … “this does not mean that you may not develop one in the future”
- If any clinical problems (low WBC, Raynaud’s, CTS)… follow the patient
- If + RNP, SSA, SSB, antiphospholipid antibody- Follow the patient clinically- RNP is very rare in the normal population- SSA/SSB are seen in “normal” population
- Doesn’t account for under diagnosis of Sjögren's syndrome
- +Smith or +dsDNA- Most likely will develop a systemic autoimmune disease- Follow closely
All SLE patients should be on Hydroxchloroquine (HCQ)
- Even if also on a strong immunosuppressant- HCQ more than doubles response to CellCept
- 2006: Johns Hopkins Lupus Cohort- WHO V lupus nephritis- Those on HCQ: 64% in remission after 12 months- Those not on HCQ: 22% in remission
Prevent triggers of lupus- Low vitamin D levels- UV light- Smoking- Sulfa antibiotics
Low vitamin D and SLE- WBC cellular membranes have Vit D receptors- Higher prevalence of low Vit D in SLE patients- More severe SLE at presentation associated with lower
Vit D- Lower Vit D levels occur during SLE flares- Low vitamin D correlated with flares (like dsDNA and
low complements)
Correcting low vitamin D as tx- Petri M et al, Vitamin D and SLE, Arthr &
Rheum;65(7):1865-71- 1006 patients, 128 weeks- 25[OH]D < 40 ng/mL- TX = 50,000 IU ergocalciferol (vit D2) + daily calcium with
200 IU vit D3
- Results:- - ≥ 20 ng/mL increase 25[OH]D associated with:
- .22 decrease in SELENA/SLEDAI (P = .032)- 21% decrease in having a SELENA/SLEDAI ≥ 5- Random urine/protein decreased by 2% (P = .0001)- 15% decrease in odds of having urine/prot > .5
Vit D as treatment for SLE- Treat patients with 25[OH]D < 40 ng/mL- Aim for a level of around 40 ng/mL or higher
Ultraviolet light
Ultraviolet light
Skin
cellNUCLEUS
Ultraviolet light
Skin
cellNUCLEUS cell
NUCLEUS
damage
Ultraviolet light
Skin
cellNUCLEUS
Antinuclear antibodiesCause increased lupus activity
Dose of UV light = Strength X Time
X 15 minutes
Dose of UV light = Strength X Time
X 15 minutes
X all day long
UV protection = SLE treatment- Wear sunscreen daily even if don’t go outside- Reapply if go outside- Use sunscreen vs UVA and UVB + waterproof + high
SPF- Wide brimmed hat- UV protectant clothes- Add Rit Sunguard to wash- Avoid outside 10 AM – 3 PM
Stop smoking if have lupus- Tobacco contains hydrazine
- Hydrazine known to increase lupus activity
- Smoking decreases effectiveness of Plaquenil- Smoking is associated with increased lupus prevalence- Smoking associated with more severe lupus
Avoid sulfa antibiotics in SLE- Increased risk for lupus flares- Ask patients to include Bactrim and Septra in
allergies
2011 Revised recommendations for HCQ: American Academy of Ophthalmology
- Base HCQ dosing on ideal body weight (<6.5 mg/kg)- Most SLE patients are overweight or obese- HCQ doesn’t distribute in fat- Table included in handout
- Women 5’1/2” – 5’6.5”= 300 mg a day
- Baseline eye exams within year 1; Yearly at year 5- Earlier or more often in elderly, DM, renal/hepatic
insufficiency- Eye tests of choice:
- VF 10-2 every time +- Either:
- SD-OCT (spectral domain optical coherence tomography)- FAF (fundus autofluorescence)- mfERG (multifocal electroretinogram)
Infection = #2 cause of death in SLE- Make sure all patients get yearly flu shot- Pneumovax if immunosuppressed or ≥ 65 yo
- Repeat after 5 years
- Prevnar PCV-13 pneumococcal vaccine- Immunosuppressed patients per CDC 2013- 8 weeks prior to getting Pneumovax OR- Must wait at least 1 year after Pneumovax
HPV-associated cancers = high in SLE- Dreyer L et al, High Incidence of Potentially Virus-
Induced Malignancies in SLE, Arth & Rheum, 2011;63(10):3032-37
- Increased HPV-associated cancers - Anal cancer- Vulvovaginal- Cervical- Non-melanoma skin cancer
- Nath R et al, High risk of Human Papillomavirus Type-16 infections and of development of squamous intraepithelial lesions in systemic lupus erythematosus patients, A&R, 2007;57(4):619-25
- High levels of HPV-16 infection and abnormal colposcopy in newly diagnosed SLE women
photo credit: beasleyallen.com
All patients ≤ 26 yo should receive Gardasil series
IM steroids for mild – moderate flare- FLOAT (Flares in Lupus: Outcomes Assessment
Trial)- Johns Hopkins Lupus Cohort: 2006- 50 patients randomized, mild – moderate flare- Medrol dose pak vs 100 mg triamcinolone IM (2.5cc
Kenalog-40)- 4% of IM steroids flare resolved day 1- No patients on Medrol Dose Pak responded the first few days- Week 1 = similar improvements- Week 4:
- Medrol Dose Pak = ¼ complete response, 67% at least partial response
- IM steroid = 1/3 complete response, 74% at least partial response
- IM steroids work faster and may last longer
Summary- SLICC new SLE classification criteria
- 4 out of 17: at least 1 from “clinical” and 1 from “immunologic”- Initial workup: Include ANA IIF, direct Coombs, CH50,
APLAs, random urine protein/creatinine- Don’t dismiss patient with + autoantibodies- TX: HCQ, Vitamin D, sunscreen, no cigarettes- VF 10-2 + either FAF, SD-OCT, or mfERG yearly after 5 years- <400 mg HCQ in most (300 mg/d if female < 5’7” tall)- Vaccines:
- Diligent with flu shots and Pneumovax- Gardasil series if ≤ 26yo- Prevnar-13 if on immunosuppressants
- IM steroids work faster for flares + safe
photo credit: customink.com
The Walk to End Lupus: April 19, Pennsylvania AveLupus Foundation of America DC/MD/VA
DCLupusWalk.org
Nick CannonGrand Marshall
References 1:Agmon-Levin N et al. International recommendations for the
assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis. 2014;73:17-23
Amital H et al. Serum concentration of 25-OH vitamin D in patients with SLE are inversely related to disease activity. Ann Rheum Dis.2010,69:1155-57.
Arbuckle MR et al. Development of Autoantibodies before the clinical onset of systemic lupus erythematosus. NEJM. 2003;349(16):1526+
Birmingham DJ et al. Evidence that abnormally large seasonal declines in vitamin D status may trigger SLE flare in non-African Americans. Lupus. 2012;21(8):855-64
Bonakdar ZS et al. Vitamin D deficiency and its association with disease activity in new cases of systemic lupus erythematosus. Lupus.2011;20:1155-60
References 2:Boeckler P et al. Association of cigarette smoking but not
alcohol consumption with cutaneous lupus erythematosus. Arch of Derm. 2009;145(9):1012-16
Cooper G et al. Occupational and environmental exposures and risk of systemic lupus erythematosus: silica, sunlight, solvents. Rheum (Oxford). 2010;49(11):2172-80
Danowski A et al. Flares in lupus: Outcomes assessment trial (FLOAT), a comparison between oral methylprednisolone and intramuscular triamcinolone. J of Rheum. 2006;33(1):57-60.
Dreyer L et al. High incidence of potentially virus-induced malignancies in systemic lupus erythematosus. Arth & Rheum. 2011;63(10):3032-37
References 3:Ghaussy NO et al. Cigarette smoking and disease activity in
systemic lupus erythematosus. J of Rheum. 2003;30:1215-21Kasitanon N et al. Hydroxychloroquine use predicts complete
renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis. Lupus. 2006;15(6):366-70
Isenberg DA et al. The Systemic Lupus International Collaborating Clinics (SLICC) group – It was 20 years ago today. Lupus. 2011;20:1426-32
Marmor MF et al. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118(2):415-22
Merrill JT. Reply to The rarity of antinuclear antibody negativity in systemic lupus erythematosus: comment on the article by Merrill et al. Arthr & Rheum. 2011;63(4):1157-58
References 4:Mok CC et al. Vitamin D deficiency as marker for
disease activity and damage in systemic lupus erythematosus. Lupus. 2012;21:36-42
Nath Ret al. High risk of human papilloma virus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arth & Rheum. 2007;57(4):619-25
Petri M et al. Vitamin D in SLE. Arth & Rheum. 2013;65(7):1865-71
Petri M et al. Derivation and validation of the systemic Lupus International Collaborating Clinics classification criteria for SLE. Arthr & Rheum. 2012:2677-86
References 5:Petri M & Magder L. Classification criteria
for SLE. Lupus. 2004;13:829-37Pons-Estel GJ et al. The ACR and the SLICC
criteria for SLE in two multiethnic cohorts. Lupus. 2014;23:3-9
Rahman P et al. Smoking interferes with efficacy of antimalarial therapy in cutaneous lupus. J of Rheum. 1998;25:1716-19
Ruiz-Irastorza G et al. Changes in vitamin D levels in patients with SLE. Arthr Care & Research. 2010;62(8):1160-65