Approach to Diffuse Alveolar Hemorrhage (DAH) and Pulmonary Vasculitis Kevin O. Leslie, MD Mayo Clinic Arizona Case Study 71-year-old man - Hemoptysis - Arthralgias - Skin nodules - Diffuse infiltrates - c-ANCA: positive WG presenting as diffuse alveolar hemorrhage Case Study Diagnosis: Acute and organizing pulmonary hemorrhage, histologically nonspecific (consistent with Wegener's granulomatosis given + cANCA ). Follow-up: The patient was treated as an ANCA+ alveolar hemorrhage syndrome, completely responded, and was alive and well without evidence of any significant disease 7 years later. Photo courtesy A. Churg MD Significance of Blood in Lung Tissue ANCA-ASSOCIATED Traumatic/procedure-related VASCULITIS IN THE LUNG Passive congestion Smoking Thromboemboli WG: 90% ANCA positive (c >> p) Local hemorrhage from: tumor, aspergilloma, broncholith, etc. MPA: 80% ANCA positive (p > c) Bronchiectasis Component of another lesion (e.g. DAD, CSS: 70% ANCA positive (p > c) infection) Coagulopathy Diffuse alveolar hemorrhage (immune) Diffuse alveolar hemorrhage (DAH) Diffuse Alveolar Hemorrhage (DAH) Definition Stereotyped histologic reaction pattern 1. Pulmonary hemorrhage not due to trauma, 1. RBC’s, fibrin, hyaline membranes airway disease, tumors, or heart failure 2. Hemosiderin deposition 2. Usually recurrent; may be acute or chronic 3. Airspace organization (variable) 3. Typical presentation: dyspnea, hemoptysis, 4. When chronic… airspace infiltrates, and anemia a. Interstitial thickening/slight fibrosis b. Type II cell proliferation 4. Associated renal disease common Iron encrustation of Capillaritis in DAH Chronic hemorrhage: elastic fibers with giant cell reaction 1. Capillaritis is common in DAH 2. Lung capillaritis is analogous to small vessel vasculitis in other organs 3. Capillaritis is not specific 4. Capillaritis is not a disease 5. The “best” capillaritis is seen in WG Immunologic classification DAH in LUNG BIOPSY MATERIAL of diffuse alveolar hemorrhage Associated Conditions (34 Cases)* ANCA-associated: WG, MPA, pulmonary renal Vasculitis/capillaritis (esp. WG) 14 syndromes, isolated alveolar hemorrhage Goodpasture’s (anti GBM disease) 4 Antibasement membrane antibody: Goodpasture's Collagen vascular disease 4 syndrome, isolated alveolar hemorrhage Idiopathic (including IPH) 4 Immune complex deposition: Collagen vascular IgA nephropathy 1 diseases, IgA disease, pulmonary renal Idiopathic GN 2 syndromes, isolated alveolar hemorrhage Unclassified 5 Immunologic mechanism not identified: IPH, *Travis et al., AJSP 14:112, 1990 isolated alveolar hemorrhage Immune complex DAH Anti-GBM Granular deposits of IgG by IF in SLE Disease DAH Linear IF IF courtesy of M. Schwartz MD DAH in SLE Key Points The histologic features of diffuse alveolar hemorrhage (DAH), regardless of cause, Immune complex are often nonspecific deposition by EM DAH is a reaction pattern EM courtesy A. Churg Alveolar Hemorrhage Syndromes Summary A few words about 1. Assess histology: Nonspecific vs. specific changes “Classical WG”… 2. Correlate with clinical/serologic findings 3. Clinicopathologic diagnosis …now “Granulomatosis with 4. 10-20% of cases remain unclassified polyangiitis” (GPA) Friedrich Wegener WEGENER'S GRANULOMATOSIS Presentation Alveolar hemorrhage syndrome Parenchymal consolidation/nodule formation with or without cavitation Necrosis in Inflammatory background in WG WG Geographic and basophilic Confluence of microabscesses Inflammatory background in WG The Eosinophilic Variant of ’ Wegener s Granulomatosis (Yousem and Lombard in Hum Pathol 1988; 19: 682) 4 cases with numerous eosinophils histologically; otherwise all were typical of WG clinically Nasal WG Bronchiolocentric WEGENER GRANULOMATOSIS lesions in WG (Jennette and Falk, 1997) "Granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels (e.g. capillaries, venules, arterioles, and arteries). Necrotizing glomerulonephritis is common." WEGENER GRANULOMATOSIS PATHOLOGY OF WG Presentation WG is an inflammatory disease that is more than a vasculitis Alveolar hemorrhage syndrome Pathology of WG can be grouped as: Vasculitis (including capillaritis) Parenchymal consolidation/nodule Necrosis (granulomatous with giant cells) Inflammatory background formation with or without cavitation Features vary from case to case WG with cavitated nodules Questions .