<prompt> Anti-neutrophil cytoplasmicantibodies ANCAis seen in:Wegeners GranulomatosisDiabetes mellitusRheumatoid arthritisChurg-Strauss syndrome  <response>: Ans. a. Wegeners Granulomatosis Ref: Harrison 19e p2182, 18e p2786Anti-neutrophil cytoplasmic antibodies ANCA are seen in Wegeners Granulomatosis. Wegeners Granulomatosis: c-ANCAs are present in the serum in up to 95 of the patients with active generalized disease, and this appears to be a good marker for disease activity.ANCA Antineutrophilic cytoplasmic antibodies ANCA are antibodies directed against certain proteins in cytoplasmic granules of neutrophils and monocytes. There are two major categories:C-ANCACytoplasmic protein 3 is the target antigenP-ANCAPerinuclear myeloperoxidase is the major target antigen Wegners GranulomatosisQ 90-95 Microscopic PAN microscopic poiyangitisQ Churg-Strauss syndromeQ Crescentic GlomerulonephritisQ Good Pasteurs syndromeQHistory of chronic sinusitis, nasopharyngeal ulcers, cavitatory lung nodules and renal failure are suggestive of Wegeners Granulomatosis. Wegeners Granulomatosis is c-ANCA positive small vessel vasculitisQ c-ANCA levels are required for diagnosis.The histopathologic hallmarks of granulomatosis with polyangiitis Wegeners are necrotizing vasculitis of small arteries and veins together with granuloma formation, which may he either intravascular or extravascular. Lung involvement typically appears as multiple, bilateral, nodular cavitary infiltrates, which on biopsy almost invariably reveal the typical necrotizing granulomatous vasculitis. Upper airway lesions, particularly those in the sinuses and nasopharynx, typically reveal inflammation, necrosis, and granuloma formation, with or without vasculitis. -- Harrison 19e p2182The specificity of a positive antiproteinase-3 ANCA for granulomatosis with polyangiitis Wegeners is very high, especially if active glomerulonephritis is present. However, the presence of ANCA should he adjunctive and, with rare exceptions, should not substitute for a tissue diagnosis. -- Harrison 19e p2184ANCA Antineutrophilic cytoplasmic antibodiesANCA are antibodies directed against certain proteins in cytoplasmic granules of neutrophils monocytes.There are two major categories:Wegeners GranulomatosisCharacterized clinically by granulomatous vasculitis of the upper lower respiratory tracts together with glomerulonephritis variable degrees of disseminated vasculitis involving both small arteries veins.c-ANCA positive small vessel vasculitisQPathology:Necrotizing vasculitisQ of small arteries veinsQIntravascular extravascular granuloma formationQGranulomas contain multiple well defined multinucleated giant cellsQBronchoalveolar lavage fluid contains high percentage of neutrophils compared to other granulomatous diseases which contains increased number of LymphocytesClinical Features:Fever, skin manifestation in the form of papules, vesicles, palpable purpura etc, eye manifestations, joint manifestations, cardiac manifestations nervous system manifestationCharacteristic Triad of Wegeners GranulomatosisVasculitis of upper respiratory tractQ ENTVasculitis of Lower respiratory tractQ LungVasculitis of Kidney MC 95 Otitis mediaQ conductive deafness Paranasal sinus pain drainage Septal perforationQ Sinusitis, subglottic stenosisQ Strawberry gum gum ulcersQ Mucosal ulcerations of nasopharynx 2nd MC 85-90 Cough, hemoptysis, dyspneaQ Multiple bilateral cavitatory nodular infiltrates cavitatory lesions in the lungQ Seen in 80 patients Rapidly progressive renal failureQ Crescentic glomerulonephritisQ Present with hematuria, proteinuria RBC cast in urineQLess common Vasculitis associated with Wegeners GranulomatosisOrgan involvedManifestationsSkin 46 Palpable purpura, subcutaneous nodulesQ, ulcers, vesicobullous lesions, splinter hemorrhages, digital ischemia gangreneJoints Arthralgia migratory arthritisQEyes 52 Orbital pseudotumors behind the eye leading to proptosis visual loss Scleritis, keratitis, conjunctivitis uveitisPeripheral nerve Mononeuritis multiplexQCharacteristic laboratory findings of Wegeners Granulomatosis Positive c-ANCAQ Elevated ESR, RFQmild elevation Anemia, leukocytosis thrombocytosisQ Hypergammaglobulinemia particularly IgA classQ Hypocomplementemia is not seen despite presence of circulating immune complexesQTreatment:Treatment of choice: CyclophosphamideQCyclophosphamide is given in doses of 2 mgkg per day together with glucocorticoidsQ 