This document summarizes the case of a 56-year-old Thai woman who presented with hemoptysis and renal failure. She has a history of tuberculosis as a child and rheumatoid arthritis. On examination, she had coarse lung crepitations and signs of renal impairment. Tests showed p-ANCA positivity. She was diagnosed with microscopic polyangiitis and treated with plasma exchange, antibiotics, and steroids. Her condition gradually improved with treatment.
17. What to do next? Bronchoscope? CT scan? Dexamethasone? hemodialysis? Plasma exchange? Continue antibiotic? Kidney biopsy? Doppler ultrasound? Consult nephro? V/Q scan? CPR? Factor VIIa ? Echo? Cyclophosphamide? S p u t u m P C R - T B
20. What to do next? Bronchoscope? CT scan? Dexamethasone? hemodialysis? Plasma exchange? Continue antibiotic? Kidney biopsy? Doppler ultrasound? Consult nephro? V/Q scan? CPR? Factor VIIa ? Echo? Cyclophosphamide? S p u t u m P C R - T B
39. Granulocyte antigen of ANCA MPA, SLE, RA, UC, CD, PSC, AIH Clin Exp Rheumatol 2000: 18: 629-635.
40. Problem with pANCA detection Perinuclear staining by ANA granulocyte-specific ANA? Epitope conformation
41.
42. does ANCA has role in pathogenesis ? I have no MPO Anti-MPO Pauciimmune NCGN Systemic vasculitis lipopolysaccharide Now I have MPO Anti-PR3 and pauciimmune glomerulonephritis ! Normal mice reduced leukocyte rolling augmented adhesion and transmigration across the endothelium Nat Rev Rheumatol . 2010 Nov;6(11):653-64.
43. What does ANCA do with body ? Kelly’s textbook of Rheumatology, 8 th ed.
51. Clinical presentation Murray and Nadel’s Textbook of Respiratory Medicine, 5 th ed. 10–50% of patients . Mononeuritis multiplex reported cerebral infarction Neuro 35–60% of patients . Commonly purpura skin 35–55% of patients . Pain, bleeding, ischemia . Rare visceral aneurysms . GI 10–15% of patients . CHF and pericarditis have been described . Cardiac 0–30% of patients . Scleritis, episcleritis, uveitis . eyes Arthralgias and myalgias in at least 50% of patients musculoskeletal 5–30% of patients, with sinus disease most common Upper airway Segmental necrotizing glomerulonephritis and RPGN is almost universal . renal 25–55% of patients . 10–30% with diffuse alveolar hemorrhage . Fibrosis, focal infiltrates, effusions, pulmonary arterial hypertension pulmonary
52. Pathology Neutrophilic capillaritis without granuloma, fibrinoid necrosis and arterial wall disruption, intra alveolar RBC and hemosiderin-laden macrophages Focal segmental necrotizing glomerulonephritis
58. fine reticular pattern superimposed on a background of groundglass attenuation that is the crazy-paving pattern J Comput Assist Tomogr . 2004 Sep-Oct;28(5):710-6
59. F 74y MPO. F/U HRCT show new honeycombing at 5 months 3 mo.
60. M 60Y MPO resemble IPF CT show GGO and reticulation in subpleural region VAT Bx shows irregular interstitial fibrotic thickening, hemosiderin laden macrophages Radiology . 2010 May;255(2):322-41
Schematic representation of the immune mechanisms hypothetically involved with antineutrophil cytoplasmic antibody ( ANCA ) enhancement of vascular injury . An infectious trigger or other environmental stimulus leads to a burst of cytokines, which primes the neutrophils or monocytes and may lead to the local upregulation of adhesion molecules on endothelium . The priming process within the inflammatory cells leads to enhanced expression of ANCA antigens on the cell surface . Activated neutrophils or monocytes may degranulate and release reactive oxygen species and lysosomal enzymes, leading to endothelial injury and further activation of the endothelial cell surface . The magnitude of this effect is influenced by the specificity of ANCA for proteinase 3 ( PR3 ) or myeloperoxidase ( MPO ) , as well as different epitopes of these respective antigens . The reaction may be further influenced by the immunoglobulin G ( IgG ) and Fc γ receptor phenotype engaged . Products released from degranulated inflammatory cells become bound to endothelial cells and further serve as targets of ANCA . Release of chemotactic chemokines such as interleukin-8 ( IL-8 ) and macrophage chemoattractant protein-1 ( MCP-1 ) serve to augment chemotaxis and inflammatory cell transmigration, in conjunction with other adhesion molecules . Thus, the scheme provides the prerequisites for endothelial and vascular injury induced by ANCA : the presence of ANCA, the expression of target antigens for ANCA on primed neutrophils and monocytes, the interaction between primed neutrophils and endothelium via adhesion molecules, and, finally, the activation of endothelial cells and ultimate efflux of inflammatory cells to the extravascular and perivascular tissues . Fc γ R, Fc γ receptor;ICAM-1, intercellular adhesion molecule-1; PMN, polymorphonuclear leukocyte; TNF, tumor necrosis factor .
Rituximab versus cyclophosphamide for ANCA - associated vasculitis .
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