Wegener’s Granulomatosis

Jason KiddMorning Report

11/18/2009

Wegener: Controversy

“Unlike doctors who joined the Nazi Party to be allowed to practice, Wegener joined the movement in 1932, before Hitler took power. He rose to a relatively high military rank and spent some of the war in a medical office three blocks from the Jewish ghetto in Lodz, Poland. Sketchy records suggest that he might have participated in experiments on concentration camp inmates.”

Feder, NY Times 1/22/2008

Definition“A distinct clinicopathologic entity

characterized by granulomatous vasculitis of the upper and lower respiratory tracts together with glomerulonephritis.”

Harrison’s

Incidence and PrevalenceEstimated prevalence: 3 per 100,0001:1 male to female ratioMean onset: 40

Harrison’s

Diagnostic Criteria: American College of Rheumatology proposed

clinical criteria for diagnosis of WG:Nasal or oral inflammationAbnormal CXR Abnormal urinary sediment: hematuria with or

without RBC castsGranulomatous inflammation on biopsy

Adapted from UpToDate and Harrison’s

DiagnosisAccording to the Chapel Hill Consensus

Conference:Granulomatous inflammation of respiratory

tractVasculitis of small to medium size vessels

Jennette JC et al, Arthritis Rheum 1994

Upper Respiratory TractUpper airway disease occurs in 90% of

patientsNasal involvement may present with

epistaxis, rhinorrhea, purulent dischargeOtitis media and eustachian tube blockage

can occurNasal septal perforation may occur, leading

to saddle nose deformitySubglottic tracheal stenosis can cause airway

obstruction

Pulmonary InvolvementCough, hemoptysis, dyspneaInfiltrates and cavitary lesions can be seen on

radiographyLung involvement typically appears as

bilateral, nodular cavitary infiltratesBiopsy: necrotizing granulomatous vasculitis

Renal InvolvementGenerally manifested with acute renal failureUrine sediment: red cells, red cell casts,

proteinuriaAccounts for most of the mortality of this

diseaseRenal biopsy: segmental necrotizing

glomerulonephritis

Urine Sediment

Renal Biopsy

Laboratory testsNonspecificLeukocytosis, thrombocytosis, elevated CRP,

elevated ESR can all be seen90-95% of patients with active Wegener’s are

ANCA positiveDiagnosis is confirmed by biopsy at site of

active disease

Other ManifestationsJoints: myalgias, arthralgiasEyes: episcleritis, uveitisSkin: palpable purpura, ulcerative lesionsCNS: cranial nerve abnormalitiesCardiac: pericarditis, coronary vasculitisHigh incidence of DVT

TreatmentDiagnosisRemission InductionRemission maintenanceRelapsing DiseaseRefractory Disease

Remission InductionGlucocorticoids

Dosing has not been examined in randomized trialsGenerally start 1 mg/kg/day10-20 mg daily at 12

weeksCyclophosphamide

Pulsed, IV is thought to be safer then oral Risk of myelosuppresion, infection, malignancy

Plasma ExchangeShown in small studies to improve chances of renal

recovery Recommended in lung hemorrhage

Jayne, Nephrology 2009

Remission MaintenanceAzathioprine or Methotrexate can be

substituted for Cyclophosphamide after 3-6 months

No standard length of treatment or regimenRelapses occur mostly in pt’s with continued

ANCA positivityRelapse in WG has been assoc with nasal

carriage of S. AureusUtility of TMP/SMX prophylaxis?

Jayne, Nephrology 2009

What happened?She received IV Cytoxan and Plex while

hospitalizedShe has received a total of 3 doses of IV

CytoxanBAL grew Penicillium, currently being

treated w/VoriShe developed LE petechiae and RLE DVTShe continues to be HD dependent

Sources Carruthers D et al, Evidence based management of ANCA vasculitis,

Best Practice & Research Clinical Rheumatology 2009, 23:367-378 Feder B, A Nazi Past Casts a Pall on Name of Disease, New York

Times, Jan 22 2008 Jayne D, Progress of treatment in ANCA-associated vasculitis,

Nephrology 2009, 14: 42-48 Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL,

Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92

Jennette JC, Falk RJ, Small Vessel Vasculitis, New England Journal of Medicine, 1997, 21: 1512-1523

Kasper et al, Harrison’s Principles of Internal Medicine, 2005 UpToDate 2009

Questions?

Anything is possible.