Clinical/Laboratory Clinical/Laboratory

features and Diagnosis offeatures and Diagnosis of

Wegener’s G. Wegener’s G.

Iraj Salehi-Abari, MD.

salehiabari@sina.tums.ac.ir

Iraj Salehi-Abari

Wegener G.

New terminology:New terminology:

o In January 2011In January 2011

o The name of Wegener’s granulomatosisThe name of Wegener’s granulomatosis

oWas changed to:Was changed to:

oGranulomatosis with polyangiitis Granulomatosis with polyangiitis

o Abbreviated as Abbreviated as GPAGPA

Iraj Salehi-Abari

Wegener G.

Definition:Definition:

o Systemic necrotizing vasculitisSystemic necrotizing vasculitis

o Small sized vesselsSmall sized vessels

oGranulomatous inflammationGranulomatous inflammation

. . EENTNT

. . LLungung

. . KKidneyidney

o Associated with ANCA positivity Associated with ANCA positivity

Iraj Salehi-Abari

Wegener G.

Epidemiology:Epidemiology:o Prevalence: 1/20,000-30,000Prevalence: 1/20,000-30,000

o F/M ratio:F/M ratio:

Systemic GPA: # 1Systemic GPA: # 1

Limited GPA: F > M Limited GPA: F > M

o Fourth & fifth decade: Mean = 40Fourth & fifth decade: Mean = 40

o Age onset < 19: 15%Age onset < 19: 15%

oWhite: 89-98%White: 89-98%

Iraj Salehi-Abari

Wegener G.

Clinical findings:Clinical findings:

ELKO ELKO findings:findings:

• EENT: > 80%NT: > 80%

• LLung: 45-90%ung: 45-90%

• KKidney: 50-80%idney: 50-80%

• OOthers thers ++ constitutional f. constitutional f.

Iraj Salehi-Abari

Wegener G.

Clinical triad:Clinical triad:

• EENTNT

• LLungung

• KKidneyidney

Iraj Salehi-Abari

Wegener G.

Initial presentation:Initial presentation:

EENTNT: most often: : most often: [Fowler 2012][Fowler 2012]

o Sinusitis: 1/2 to 2/3Sinusitis: 1/2 to 2/3 [Hoffman 1992][Hoffman 1992]

LLungung: may be: may be

KKidneyidney: sometimes: sometimes

Iraj Salehi-Abari

Wegener G.

ENT features:ENT features:

o . Nose. Nose

o . Sinuses. Sinuses

o . Throat. Throat

o . Ears. Ears

Iraj Salehi-Abari

Wegener G.

Nose:Nose:

o Nasal crusting, RhinitisNasal crusting, Rhinitis

o Nasal obstructionNasal obstruction

o Runny noseRunny nose

o Smell disturbancesSmell disturbances

o Purulent/Bloody nasal discharge: Purulent/Bloody nasal discharge: 63% 63% [Salehi-Abari, 2013] [Salehi-Abari, 2013]

o EpistaxisEpistaxis

Iraj Salehi-Abari

Wegener G.

Nose:Nose:

o Nasal ulcer: Nasal ulcer: 43% 43% [Salehi-Abari, 2013] [Salehi-Abari, 2013]

o Severe nasal painSevere nasal pain

o Nasal septal perforationNasal septal perforation

o Saddle-nose deformity: Saddle-nose deformity: 23% 23% [Salehi-Abari, 2013] [Salehi-Abari, 2013]

Iraj Salehi-Abari

Wegener G.

Saddle-nose deformity:Saddle-nose deformity:

Iraj Salehi-Abari

Wegener G.

Atypical Sinusitis (AtS) :Atypical Sinusitis (AtS) :

Was defined as one of the following conditions Was defined as one of the following conditions

accompanying sinusitisaccompanying sinusitis

o Recurrent Recurrent

o Chronic or intractableChronic or intractable

o Sinus massSinus mass

o RhinitisRhinitis

Iraj Salehi-Abari

Wegener G.

Atypical Sinusitis (AtS) :Atypical Sinusitis (AtS) :

oOtitisOtitis

oOrbital cellulitisOrbital cellulitis

o Dacryocystitis Dacryocystitis

oMastoiditisMastoiditis

o Severe pain in the noseSevere pain in the nose

o PansinusitisPansinusitis

Iraj Salehi-Abari

Wegener G.

Ear:Ear:

oOtitis media: Otitis media: 49% 49% [Salehi-Abari, 2013] [Salehi-Abari, 2013]

. Serous > Purulent. Serous > Purulent

oHearing lossHearing loss

. Conductive > SNHL. Conductive > SNHL

oMastoiditis: Mastoiditis: 14%14% [Salehi-Abari, 2013] [Salehi-Abari, 2013]

oVertigoVertigo

Iraj Salehi-Abari

Wegener G.

Otitis media:Otitis media:

o Persistent, intractablePersistent, intractable

o RecurrentRecurrent

o BilateralBilateral

o with Sensory neural hearing losswith Sensory neural hearing loss

o with Mastoiditiswith Mastoiditis

o Recurrent bilateral serous otitis Recurrent bilateral serous otitis mediamedia

Iraj Salehi-Abari

Wegener G.

Mouth:

oOral necrotic ulcer (Oral necrotic ulcer (23%23%) ) [Salehi-Abari, 2013] [Salehi-Abari, 2013]

oStrawberry gum hyperplasia:Strawberry gum hyperplasia:

PathognomonicPathognomonic

Iraj Salehi-Abari

Wegener G.

Ophthalmic:Ophthalmic:o ConjunctivitisConjunctivitis

o ScleritisScleritis

o KeratitisKeratitis

o Corneal ulcerCorneal ulcer

o UveitisUveitis

o DacriocystitisDacriocystitis

o Excessive tearingExcessive tearing

Iraj Salehi-Abari

Wegener G.

Ophthalmic:Ophthalmic:

o Proptosis:Proptosis: 14% 14% [Salehi-Abari, 2013][Salehi-Abari, 2013]

o Retinal vasculitisRetinal vasculitis

oOptic neuritisOptic neuritis

oOphthalmoplegiaOphthalmoplegia

o Red eye syndromeRed eye syndrome

Iraj Salehi-Abari

Wegener G.

Laryngotracheal:Laryngotracheal:

o Hoarseness Hoarseness

o StridorStridor

o Subglottic stenosis: Subglottic stenosis: 17% 17% [Salehi-Abari, 2013] [Salehi-Abari, 2013]

o Upper airway obstructionUpper airway obstruction

Iraj Salehi-Abari

Wegener G.

Lung:Lung:

Iraj Salehi-Abari

Wegener G.

o Asymptomatic: 1/3Asymptomatic: 1/3

o Cough & DyspneaCough & Dyspnea

o Hemoptysis: Hemoptysis: 31% 31% [Salehi-Abari, 2013][Salehi-Abari, 2013]

o Pleuritis (Pleuritis (++ pleural effusion) pleural effusion)

o Acute and fulminant alveolar hemorrhage Acute and fulminant alveolar hemorrhage

with respiratory failurewith respiratory failure

Lung:Lung:

Iraj Salehi-Abari

Wegener G.

Chest X-Ray or CT scan:Chest X-Ray or CT scan:

o . . Nodules: Nodules: 46% 46% [Salehi-Abari, 2013][Salehi-Abari, 2013]

o . Cavitation: . Cavitation: 34%34% [Salehi-Abari, 2013][Salehi-Abari, 2013]

o . Opacities. Opacities

o . Others. Others

Pneumonia:Pneumonia:

o Intractable pneumoniaIntractable pneumonia

o Recurrent pneumoniaRecurrent pneumonia

o Multiple lobe pneumoniaMultiple lobe pneumonia

o Cavitate pneumoniaCavitate pneumonia

o Fleeting pneumoniaFleeting pneumonia

o Hemorrhagic pneumoniaHemorrhagic pneumonia

o Pneumonia + SinusitisPneumonia + Sinusitis

Iraj Salehi-Abari

Wegener G.

Kidney: Kidney:

Renal involvement: Renal involvement: 51% 51% [Salehi-Abari, 2013][Salehi-Abari, 2013]

oMicroscopic hematuria Microscopic hematuria ++

o RBC castRBC cast

o ProteinuriaProteinuria

o pyuriapyuria

o AzotemiaAzotemia

Iraj Salehi-Abari

Wegener G.

Renal Pathology: Renal Pathology:

oFocal segmental necrotizing Focal segmental necrotizing

pauci-immune pauci-immune

Glomerulonephritis Glomerulonephritis

Iraj Salehi-Abari

Wegener G.

Attention please:

ProptosisProptosis in conjunction with: in conjunction with:

oENT orENT or

oLung disease orLung disease or

oGlomerulonephritis Glomerulonephritis

Is highly suggestive of the WG (Is highly suggestive of the WG (GPAGPA))

[Hoffman GS, 1992] [Hoffman GS, 1992] andand [Tarabishy AB, 2010] [Tarabishy AB, 2010]

Iraj Salehi-Abari

Wegener G.

Attention please:

Almost all cases with vasculitis including:Almost all cases with vasculitis including:

o Proptosis orProptosis or

o Sinonasal destruction orSinonasal destruction or

o Saddle nose deformity orSaddle nose deformity or

o Subglottic stenosisSubglottic stenosis

Are the cases of Are the cases of GPAGPA

Iraj Salehi-Abari

Wegener G.

Musculoskeletal:

oArthralgiasArthralgias

oMyalgiasMyalgias

oArthritis: < 1/3Arthritis: < 1/3

Iraj Salehi-Abari

Wegener G.

Arthritis:

Mono, Oligo, PolyarthritisMono, Oligo, Polyarthritis

Migratory, FixedMigratory, Fixed

Symmetric, AsymmetricSymmetric, Asymmetric

Small, LargeSmall, Large

Knee, AnkleKnee, Ankle

Positive RF: 50-60%Positive RF: 50-60%

Iraj Salehi-Abari

Wegener G.

Arthritis:

o RARA like: like: Symmetric polyarthritisSymmetric polyarthritis

o ReAReA like: like: Asymmetric lower limb oligoarthritisAsymmetric lower limb oligoarthritis

o ARFARF like: like: Migratory polyarthritisMigratory polyarthritis

Iraj Salehi-Abari

Wegener G.

Skin:Skin:

In ½ of the patientsIn ½ of the patients

oPalpable purpura, UlcerPalpable purpura, Ulcer

oNodule, Papule, VesicleNodule, Papule, Vesicle

oUrticaria, livedo reticularisUrticaria, livedo reticularis

oErythema nodosumErythema nodosum

oPyoderma gangrenosumPyoderma gangrenosum

Iraj Salehi-Abari

Wegener G.

Skin:Skin:

o Leukocytoclastic vasculitisLeukocytoclastic vasculitis: : most common most common

o Hemorrhagic blisterHemorrhagic blister

Iraj Salehi-Abari

Wegener G.

NeurologicNeurologic::

oPeripheral neuropathyPeripheral neuropathy

• Mononeuritis multiplexMononeuritis multiplex

• PolyneuropathyPolyneuropathy

oCranial neuropathy:Cranial neuropathy:

• 2, 6, 72, 6, 7

Iraj Salehi-Abari

Wegener G.

NeurologicNeurologic::

oCerebro-vascular accident (CVA)Cerebro-vascular accident (CVA)

oMeningeal inflammationMeningeal inflammation

HeadacheHeadache

o CNS massCNS mass

o Diabetes insipitusDiabetes insipitus

Iraj Salehi-Abari

Wegener G.

GI tract:GI tract:

oAsymptomatic Asymptomatic

oEnterocolitis:Enterocolitis:

• Abdominal painAbdominal pain

• Diarrhea, GI bleedingDiarrhea, GI bleeding

• Ulcer Ulcer Perforation Perforation

Iraj Salehi-Abari

Wegener G.

GI tract:GI tract:

oCholecystitisCholecystitis

oAscitisAscitis

oPerianal ulcerPerianal ulcer

oPancreatitis, Pancreatic massPancreatitis, Pancreatic mass

Iraj Salehi-Abari

Wegener G.

Heart:Heart:

oPericarditisPericarditis

oMyocarditisMyocarditis

oEndocarditisEndocarditis

oValvulitisValvulitis

Iraj Salehi-Abari

Wegener G.

Heart:Heart:

oCoronary vasculitis:Coronary vasculitis:

MI, AnginaMI, Angina

oArrhythmiasArrhythmias

oConduction defectsConduction defects

oNon-coronary > CoronaryNon-coronary > Coronary

Iraj Salehi-Abari

Wegener G.

Genitourinary:Genitourinary:

oUreteral obstruction

oHemorrhagic cystitis

oGranulomatous prostatitis

oUrethritis

oEpididymitis, Orchitis

oPenile necrosis

Iraj Salehi-Abari

Wegener G.

Paraclinic:Paraclinic:

oCBC, U/A, BUN/Cr, ESR, CRP, LFTCBC, U/A, BUN/Cr, ESR, CRP, LFT

oANCA serologyANCA serology

oSinus X-ray, CXR Sinus X-ray, CXR

oCT-scan of sinuses, HRCT of lungsCT-scan of sinuses, HRCT of lungs

oPathologyPathology

Iraj Salehi-Abari

Wegener G.

ANCA:ANCA:

IF assay: more sensitiveIF assay: more sensitive

C-ANCAC-ANCA

P-ANCAP-ANCA

Atypical (non-C, non-P) ANCAAtypical (non-C, non-P) ANCA

Iraj Salehi-Abari

Wegener G.

ANCA:ANCA:

ELISA: more specificELISA: more specific

PR3-ANCAPR3-ANCA

MPO-ANCAMPO-ANCA

Iraj Salehi-Abari

Wegener G.

ANCA:ANCA:

C-C-ANCA:ANCA:

usually usually PR3-PR3-ANCAANCA

P-P-ANCA:ANCA:

usually usually MPO-MPO-ANCAANCA

Iraj Salehi-Abari

Wegener G.

ANCA in GPA:ANCA in GPA:

In active severe GPA: 90%In active severe GPA: 90%

in limited GPA: 60% in limited GPA: 60%

PR3-ANCA: 80-90%PR3-ANCA: 80-90%

Iraj Salehi-Abari

Wegener G.

ANCA in GPA:ANCA in GPA:

Sensitivity:Sensitivity:

60-90% (60-90% (63%63%)) [Salehi-Abari, 2013][Salehi-Abari, 2013]

Specificity:Specificity:

80-95%80-95%

Iraj Salehi-Abari

Wegener G.

Positive predictive value of Positive predictive value of c-ANCA for GPA: c-ANCA for GPA:

In systemic disease: In systemic disease: < 30%< 30%

In Chronic sinusitis: very Low (In Chronic sinusitis: very Low (< 15%< 15%) )

In Acute GN or RPGN: In Acute GN or RPGN: 98%98%

Iraj Salehi-Abari

Wegener G.

ANCA associated vasculitis:ANCA associated vasculitis:

oGranulomatosis with polyangiitis (GPA)

oMicroscopic polyangiitis (MPA)

oChurg-Strauss Syndrome (CSS)

oRenal limited vasculitis (RLV)

Iraj Salehi-Abari

Wegener G.

Other Positive ANCA Other Positive ANCA states:states:

oPolyarteritis nodosa

oGoodpastur’s disease

oSLE, RA, Myositis

o IBD, PSC

oEndocarditis, HIV, CF

oHydralazine, PTU, DP, MC

Iraj Salehi-Abari

Wegener G.

Pathologic triad:Pathologic triad:

. Necrosis. Necrosis

. Granuloma:. Granuloma: 57% 57% [Salehi-Abari, 2013][Salehi-Abari, 2013]

. Vasculitis (SVV):. Vasculitis (SVV): 66% 66% [Salehi-Abari, 2013][Salehi-Abari, 2013]

Iraj Salehi-Abari

Wegener G.

Diagnosis of GPA:Diagnosis of GPA:

Upon theUpon the Judgement ofJudgement of

o Clinical Clinical

o Laboratory andLaboratory and

o Imaging findingsImaging findings

ByBy anan expert Rheumatologist expert Rheumatologist In cooperation with In cooperation with

anan expert ENT man expert ENT man andand anan expert Infectious expert Infectious

disease specialist disease specialist

Iraj Salehi-Abari

Wegener G.

The 1990 ACR Classification The 1990 ACR Classification Criteria for Wegener’s G.:Criteria for Wegener’s G.:

oOral ulcer or bloody/purulent nasal dischargeOral ulcer or bloody/purulent nasal discharge

o CXR: Nodule, Fixed infiltration or CavityCXR: Nodule, Fixed infiltration or Cavity

o U/A: U/A: >> 5 RBC /HPF 5 RBC /HPF ++ RBC cast RBC cast

o Pathology: Granulomatous inflammationPathology: Granulomatous inflammation

• >> 2 out of 4 criteria 2 out of 4 criteria Dx. Dx.

• sensitivity: sensitivity: 80% 80% [Salehi-Abari, 2013][Salehi-Abari, 2013]

Iraj Salehi-Abari

Wegener G.

The 1990 ACR Classification The 1990 ACR Classification Criteria for Wegener’s G:Criteria for Wegener’s G:

o Not sensitive enough (< 80%)?Not sensitive enough (< 80%)?

o Can not make distinction between GPA & MPA?Can not make distinction between GPA & MPA?

o All criteria have similar price?All criteria have similar price?

o ANCA is not included in this CriteriaANCA is not included in this Criteria

Iraj Salehi-Abari

Wegener G.

EMAEMA** diagnostic criteria of systemic diagnostic criteria of systemic GPA in the absence of biopsy:GPA in the absence of biopsy:

o CXRCXR: : Fixed infiltrations, nodules or cavitations > one Fixed infiltrations, nodules or cavitations > one month or bronchial stenosismonth or bronchial stenosis

o ENTENT: : Bloody nasal discharge and crusting > 1 month or Bloody nasal discharge and crusting > 1 month or nasal ulceration; Sinusitis, Otitis media or mastoiditis > nasal ulceration; Sinusitis, Otitis media or mastoiditis > 3 months; Retro-orbital mass; Subglottic stenosis; 3 months; Retro-orbital mass; Subglottic stenosis; Saddle nose deformity/destructive sinonasal diseaseSaddle nose deformity/destructive sinonasal disease

o GlomerulonephritisGlomerulonephritis: : RBC + RBC casts or > 10 dysmorphic RBCRBC + RBC casts or > 10 dysmorphic RBC 2 + hematuria or 2+ proteinuria2 + hematuria or 2+ proteinuria

o Positive ANCAPositive ANCA

* * Is very low sensitive tooIs very low sensitive too

** European Medicine Agency algorithmEuropean Medicine Agency algorithm

Iraj Salehi-Abari

Wegener G.

TheThe ‘Iran criteria’‘Iran criteria’** for diagnosis of for diagnosis of GPAGPA

Entry Criteria: No other diagnosis upon Hx & Ph.EEntry Criteria: No other diagnosis upon Hx & Ph.E

ELK ELK criteria:criteria:

o EENT up to 3 pointsNT up to 3 points

o LLung up to 2 pointsung up to 2 points

o KKidney up to 1 pointidney up to 1 point

AB AB criteria:criteria:

o AANCA up to 2 pointsNCA up to 2 points

o BBiopsy up to 3 points Total points = iopsy up to 3 points Total points = 1111

**. Iraj Salehi-Abari, . Iraj Salehi-Abari, M Motassaddi z., M Hasibi, et al., . . .Indian M Motassaddi z., M Hasibi, et al., . . .Indian Journal of Rheumatology, Journal of Rheumatology, 20132013, . . ., . . .ELSEVIER ELSEVIER

Iraj Salehi-Abari

Wegener G.

The The EENT criterion NT criterion Up to 3 Up to 3 pointspoints

• More than one episode of bloody nasal discharge with nasal crusting, or More than one episode of bloody nasal discharge with nasal crusting, or

nasal ulcer or severe nasal pain 1 p. nasal ulcer or severe nasal pain 1 p.

• Oral necrotic ulcer, or strawberry gum hyperplasia 1 p. Oral necrotic ulcer, or strawberry gum hyperplasia 1 p.

• Sinusitis; persistent or recurrent or intractable 1 p.Sinusitis; persistent or recurrent or intractable 1 p.

• Otitis media; persistent or recurrent or intractable or bilateral, or otitis Otitis media; persistent or recurrent or intractable or bilateral, or otitis

media with SNHL 1 p.media with SNHL 1 p.

Iraj Salehi-Abari

Wegener G.

The The EENT criterion NT criterion Up to 3 Up to 3 pointspoints

• Proptosis 2 p.Proptosis 2 p.

• Saddle nose deformity 2 p.Saddle nose deformity 2 p.

• Subglottic stenosis 2 p. Subglottic stenosis 2 p.

CT-scan findings: CT-scan findings:

• Pansinusitis or sinus mass 1 p.Pansinusitis or sinus mass 1 p.

• Sinonasal destruction 2 p.Sinonasal destruction 2 p.

• Mastoiditis 1 p.Mastoiditis 1 p.

Iraj Salehi-Abari

Wegener G.

The The LLung criterion: ung criterion: Up to 2 Up to 2 pointspoints

• Hemoptysis 1 p.Hemoptysis 1 p.

CXR or HRCT:CXR or HRCT:

• Nodules 2 p.Nodules 2 p.

• Cavity 2 p.Cavity 2 p.

• Fixed infiltration 1 p. Fixed infiltration 1 p.

Iraj Salehi-Abari

Wegener G.

The The KKidney criterion idney criterion Up to 1 Up to 1 pointpoint

o Hematuria:Hematuria:

• > 5 RBC or> 5 RBC or

• > 1+ or> 1+ or

oProteinuria:Proteinuria:

• > 1+ or> 1+ or

oRBC castRBC cast

Iraj Salehi-Abari

Wegener G.

The The AANCA criterion NCA criterion Up to 2 Up to 2 pointspoints

• Positive ANCA or p-ANCA or Anti-MPO 1 p.Positive ANCA or p-ANCA or Anti-MPO 1 p.

• C-ANCA or Anti- PR3 2 p.C-ANCA or Anti- PR3 2 p.

Iraj Salehi-Abari

Wegener G.

The The BBiopsy criterion iopsy criterion Up to 3 Up to 3 pointspoints

• Small vessel vasculitis (“SVV”) without Small vessel vasculitis (“SVV”) without

Eosinophilia 1 p.Eosinophilia 1 p.

• ““Granulomatous” inflammation without Granulomatous” inflammation without

Eosinophilia 2 p. Eosinophilia 2 p.

Iraj Salehi-Abari

Wegener G.

New GPA typing:New GPA typing:

Limited GPALimited GPA: E &/or L: E &/or L E + LE + L EE LL

Systemic GPASystemic GPA: [(E &/or L) + K] : [(E &/or L) + K] E + L + KE + L + K E + KE + K L + K L + K

Iraj Salehi-Abari

Wegener G.

TheThe ‘Iran criteria’‘Iran criteria’** for diagnosis of for diagnosis of GPAGPA

o ENT; up to 3 p.ENT; up to 3 p.//Lung; up to 2 p.Lung; up to 2 p.//Kidney; up to 1 Kidney; up to 1

p. p. // ANCA; up to 2 p. ANCA; up to 2 p.//Biopsy; up to 3p.: Biopsy; up to 3p.:

With total points of With total points of 1111

[(E &/or L) + K] [(E &/or L) + K] & & >> 5 5 points out of 11 points out of 11 Systemic GPASystemic GPA

(E &/or L) & (E &/or L) & >> 44 points out of 11 points out of 11 Limited GPALimited GPA

*. Sensitivity: 100%*. Sensitivity: 100%

Iraj Salehi-Abari

Wegener G.

““Amir Alam Hospital approach”Amir Alam Hospital approach”** toward diagnosis of GPA (Wegener’s):toward diagnosis of GPA (Wegener’s):

Step IStep I: : o History and General physical examinationHistory and General physical examination

o ENT examination by ENT manENT examination by ENT man

o U/A, ANCA serology, CBC, BUN/Cr, ESR, LFTU/A, ANCA serology, CBC, BUN/Cr, ESR, LFT

o Sinus X-rays, CXRSinus X-rays, CXR

o R/O TB, CSS, MPA, Mucormycosis, Cocaine abuse according to above findingsR/O TB, CSS, MPA, Mucormycosis, Cocaine abuse according to above findings

Step IIStep II::o CT- scan of sinusesCT- scan of sinuses

o HRCT of lungsHRCT of lungs

Step IIIStep III: : o ENT endoscopy and biopsy: 1. Sinus, 2. Nose, 3. Middle earENT endoscopy and biopsy: 1. Sinus, 2. Nose, 3. Middle ear

Step IVStep IV: : o Skin biopsySkin biopsy

o Kidney biopsyKidney biopsy

o Lung biopsy: 1. Transbronchial, 2. Thoracoscopic, 3. Open thoracotomyLung biopsy: 1. Transbronchial, 2. Thoracoscopic, 3. Open thoracotomy

*.*. Iraj Salehi-Abari Iraj Salehi-Abari,, M. Motassaddi z., M. Hasibi, et al., . . . ,Indian Journal of M. Motassaddi z., M. Hasibi, et al., . . . ,Indian Journal of Rheumatology, Rheumatology, 20132013,……,……ELSEVIERELSEVIER

Iraj Salehi-Abari

Wegener G.

““Amir Alam Hospital Amir Alam Hospital recommendation”recommendation”** for early detection of for early detection of GPA in atypical sinusitisGPA in atypical sinusitis

“ “Early Rheumatologic consultation in the patients with Early Rheumatologic consultation in the patients with

atypical sinusitis for early detection of Granulomatosis atypical sinusitis for early detection of Granulomatosis

with polyangiitis”with polyangiitis”

o Definite GPA in 13% of AtSDefinite GPA in 13% of AtS

o Probable GPA in another 13% of AtSProbable GPA in another 13% of AtS

*.*. Iraj Salehi-Abari Iraj Salehi-Abari, M Motassaddi Z., M Hasibi, et al.,, M Motassaddi Z., M Hasibi, et al., …, Rheumatology Current …, Rheumatology Current

Research, Research, 20122012, …., , …., USA USA OMICS PUBLISHINGOMICS PUBLISHING

Iraj Salehi-Abari

Wegener G.

Atypical Sinusitis (AtS) :Atypical Sinusitis (AtS) :

Was defined as one of the following conditions Was defined as one of the following conditions

accompanying sinusitisaccompanying sinusitis

o Recurrent Recurrent

o Chronic or intractableChronic or intractable

o Sinus massSinus mass

o RhinitisRhinitis

Iraj Salehi-Abari

Wegener G.

Atypical Sinusitis (AtS) :Atypical Sinusitis (AtS) :

oOtitisOtitis

oOrbital cellulitisOrbital cellulitis

o Dacryocystitis Dacryocystitis

oMastoiditisMastoiditis

o Severe pain in the noseSevere pain in the nose

o PansinusitisPansinusitis

Iraj Salehi-Abari

Wegener G.

GPA manifestations:GPA manifestations:

ELKOELKO• EENTNT• LLungung• KKidneyidney• OOthersthersABAB• AANCANCA• BBiopsyiopsy

Iraj Salehi-Abari

Wegener G.

Different GPA Different GPA patterns:patterns:• (E (E ++ O) + A O) + A

• (E (E ++ O) + B O) + B

• (E (E ++ O) + AB O) + AB

• (L (L ++ O) + A O) + A

• (L (L ++ O) + B O) + B

• (L (L ++ O) + AB O) + AB

Iraj Salehi-Abari

Wegener G.

Different GPA Different GPA patterns:patterns:• (EL (EL ++ O) + A O) + A

• (EL (EL ++ O) + B O) + B

• (EL (EL ++ O) + AB O) + AB

• (LK (LK ++ O) + A O) + A

• (LK (LK ++ O) + B O) + B

• (LK (LK ++ O) + AB O) + AB

Iraj Salehi-Abari

Wegener G.

Different GPA Different GPA patterns:patterns:• (EK (EK ++ O) + A O) + A• (EK (EK ++ O) + B O) + B• (EK (EK ++ O) + AB O) + AB• (ELK (ELK ++ O) + A O) + A• (ELK (ELK ++ O) + B O) + B• (ELK (ELK ++ O) + AB O) + AB• EL EL ++ O O• ELK ELK ++ O Total: 20 patterns O Total: 20 patterns

Iraj Salehi-Abari

Wegener G.

Different GPA patterns:Different GPA patterns:

• In 6 patterns out of 20: No ENT In 6 patterns out of 20: No ENT

• In 6 patterns out of 20: No LungIn 6 patterns out of 20: No Lung

• In 10 patterns out of 20: No KidneyIn 10 patterns out of 20: No Kidney

• In 3 patterns out of 20: No Lung, No KidneyIn 3 patterns out of 20: No Lung, No Kidney

• In 3 patterns out of 20: No ENT, No KidneyIn 3 patterns out of 20: No ENT, No Kidney

Iraj Salehi-Abari

Wegener G.

Different GPA patterns:Different GPA patterns:

• In 8 patterns out of 20: ANCA negativityIn 8 patterns out of 20: ANCA negativity

• In 8 patterns out of 20: nl BiopsyIn 8 patterns out of 20: nl Biopsy

• In 2 patterns out of 20: negative ANCA, nl BxIn 2 patterns out of 20: negative ANCA, nl Bx

• In 2 patterns out of 20: No ENT, (-) ANCAIn 2 patterns out of 20: No ENT, (-) ANCA

• In 2 patterns out of 20: No ENT, nl Biopsy In 2 patterns out of 20: No ENT, nl Biopsy

Iraj Salehi-Abari

Wegener G.

Attention pleaseAttention please

o Normal ENT: No R/O GPANormal ENT: No R/O GPA

o Normal Lung: No R/O GPANormal Lung: No R/O GPA

o Normal Kidney: No R/O GPANormal Kidney: No R/O GPA

o (-) Biopsy: No R/O GPA(-) Biopsy: No R/O GPA

o (-) ANCA: No R/O GPA(-) ANCA: No R/O GPA

o nl ENT & (-) Biopsy: No R/O GPAnl ENT & (-) Biopsy: No R/O GPA

Iraj Salehi-Abari

Wegener G.

Attention pleaseAttention please

o nl ENT & (-) ANCA: No R/O GPAnl ENT & (-) ANCA: No R/O GPA

o (-) ANCA & (-) Biopsy: NO R/O GPA(-) ANCA & (-) Biopsy: NO R/O GPA

o nl Lung & nl Kidney: No R/O GPAnl Lung & nl Kidney: No R/O GPA

o nl Lung, nl Kidney, (-) Biopsy: No R/O GPAnl Lung, nl Kidney, (-) Biopsy: No R/O GPA

o nl Lung, nl Kidney, (-) ANCA: No R/O GPA nl Lung, nl Kidney, (-) ANCA: No R/O GPA

But: But:

o nl ENT, nl Lung, nl Kidney: R/O GPAnl ENT, nl Lung, nl Kidney: R/O GPA

Iraj Salehi-Abari

Wegener G.

Attention pleaseAttention please

o The suggestion of GPA may be easy but The suggestion of GPA may be easy but

confirmation of the diagnosis of GPA may be confirmation of the diagnosis of GPA may be

one of the most important medical challenges one of the most important medical challenges

for a Rheumatologist in the world.for a Rheumatologist in the world.

o You have to know that less than 1% of You have to know that less than 1% of

Rheumatologists are expert in GPA in the world. Rheumatologists are expert in GPA in the world.

Iraj Salehi-Abari

Wegener G.

Granulomatous diseases of nose Granulomatous diseases of nose and paranasal sinuses:and paranasal sinuses:

o InfectionsInfections: TB, Leprosy, Rhinoscleroma, : TB, Leprosy, Rhinoscleroma,

Syphilis, Histoplasmosis, Leishmaniasis, Syphilis, Histoplasmosis, Leishmaniasis,

RhinosporidiosisRhinosporidiosis

o VasculitidesVasculitides: GPA, CSS: GPA, CSS

oMalignancyMalignancy: lethal midline granulomatosis, : lethal midline granulomatosis,

Nonkeratinizing nasopharyngeal carcinomaNonkeratinizing nasopharyngeal carcinoma

oOtherOther: Sarcoidosis, Cocaine abuse,…: Sarcoidosis, Cocaine abuse,…

Iraj Salehi

Wegener G.

The most important differential The most important differential diagnosis of Limited GPA :diagnosis of Limited GPA :

MucormycosisMucormycosis:: Rhino-Sinu-Orbito-Cerebral syndrome ??!! Rhino-Sinu-Orbito-Cerebral syndrome ??!!

Angiocentric LymphomaAngiocentric Lymphoma:: Lethal midline granuloma Lethal midline granuloma

Cocaine abuseCocaine abuse

Iraj Salehi-Abari

Wegener G.

The most important differential The most important differential diagnosis of Systemic GPA :diagnosis of Systemic GPA :

Mucormycosis:Mucormycosis:

[(ENT [(ENT ++ Lung) + Kidney] features ??!! Lung) + Kidney] features ??!!

CSS, MPACSS, MPA

Sarcoidosis, TBSarcoidosis, TB

Iraj Salehi-Abari

Wegener G.

Amir Alam Hospital (AAH) Amir Alam Hospital (AAH) big achievement:big achievement:

o In the world: about 80% of Limited GPA In the world: about 80% of Limited GPA

cases eventually will become systemic cases eventually will become systemic

with kidney involvementwith kidney involvement

o But in But in Amir Alam HospitalAmir Alam Hospital: only : only 51%*51%* of of

these cases become systemic, due to the these cases become systemic, due to the

earlier diagnosis and management of GPAearlier diagnosis and management of GPA

*. Iraj Salehi-Abari, *. Iraj Salehi-Abari, M Motassaddi z., M Hasibi, et al., . . .Indian Journal of M Motassaddi z., M Hasibi, et al., . . .Indian Journal of

Rheumatology, Rheumatology, 20132013,……,……ELSEVIER ELSEVIER

Iraj Salehi-Abari

Wegener G.

In the world:In the world:

oMany cases of Angioinvasive Rhino-Sinu-Orbito-Many cases of Angioinvasive Rhino-Sinu-Orbito-

Cerebral syndrome of Mucormycosis are wrong and Cerebral syndrome of Mucormycosis are wrong and

they are missed cases of GPA or Overlap of both.they are missed cases of GPA or Overlap of both.

oMucormycosis has still been over diagnosed and Mucormycosis has still been over diagnosed and

there is still under estimation of the diagnosis of there is still under estimation of the diagnosis of

GPA in the world. GPA in the world.

Iraj Salehi-Abari

Wegener G.

In Amir Alam Hospital:In Amir Alam Hospital:o There is the most important tertiary otolaryngology There is the most important tertiary otolaryngology

referral center of Iran referral center of Iran and:and:

o There is one of the best expert Infectious disease There is one of the best expert Infectious disease

specialist of Iran specialist of Iran but: but:

o There is not an expert Rheumatologist There is not an expert Rheumatologist and: and:

oWe need more cooperation for the earlier diagnosis We need more cooperation for the earlier diagnosis

of GPA of GPA

Iraj Salehi-Abari

Wegener G.