Wegeners Granulomatosis

Wegeners GranulomatosisJason KiddMorning Report11/18/2009Wegener: ControversyUnlike 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 1/22/2008DefinitionA distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tracts together with glomerulonephritis. HarrisonsIncidence and PrevalenceEstimated prevalence: 3 per 100,0001:1 male to female ratioMean onset: 40

HarrisonsDiagnostic 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 HarrisonsDiagnosisAccording 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 obstructionPulmonary 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 glomerulonephritisUrine Sediment

Renal Biopsy

Laboratory testsNonspecificLeukocytosis, thrombocytosis, elevated CRP, elevated ESR can all be seen90-95% of patients with active Wegeners are ANCA positiveDiagnosis is confirmed by biopsy at site of active disease14Other ManifestationsJoints: myalgias, arthralgiasEyes: episcleritis, uveitisSkin: palpable purpura, ulcerative lesionsCNS: cranial nerve abnormalitiesCardiac: pericarditis, coronary vasculitisHigh incidence of DVTTreatmentDiagnosisRemission InductionRemission maintenanceRelapsing DiseaseRefractory DiseaseRemission InductionGlucocorticoidsDosing has not been examined in randomized trialsGenerally start 1 mg/kg/day10-20 mg daily at 12 weeksCyclophosphamidePulsed, IV is thought to be safer then oral Risk of myelosuppresion, infection, malignancyPlasma ExchangeShown in small studies to improve chances of renal recovery Recommended in lung hemorrhage Jayne, Nephrology 2009Remission MaintenanceAzathioprine or Methotrexate can be substituted for Cyclophosphamide after 3-6 monthsNo standard length of treatment or regimenRelapses occur mostly in pts 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

SourcesCarruthers D et al, Evidence based management of ANCA vasculitis, Best Practice & Research Clinical Rheumatology 2009, 23:367-378Feder B, A Nazi Past Casts a Pall on Name of Disease, New York Times, Jan 22 2008Jayne D, Progress of treatment in ANCA-associated vasculitis, Nephrology 2009, 14: 42-48Jennette 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;37:187-92Jennette JC, Falk RJ, Small Vessel Vasculitis, New England Journal of Medicine, 1997, 21: 1512-1523Kasper et al, Harrisons Principles of Internal Medicine, 2005UpToDate 2009

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