פרופ' נוויל ברקמן מכון הריאה ביה"ח האוניברסיטאי הדסה עין-כרם Bronchiolitis Obliterans Organising Pneumonia (BOOP), Granulomatosis with Polyangiitis פרופ' נוויל ברקמן מכון הריאה ביה"ח האוניברסיטאי הדסה עין-כרם

Brochiolitis Obliterans and Organising Pneumonia (BOOP) Clinico- Pathological Diagnosis Clinical Radiological Pathological

Brochiolitis Obliterans and Organising Pneumonia (BOOP) Differential Diagnosis Idiopathic (Cryptogenic Organising Pneumonia) Infection Post-transplantation Collagen vascular disease Irradiation Drugs Other

Idiopathic BOOP (Cryptogenic Organising Pneumonia) M=F, any age (mean 58). Acute or subacute onset of cough, fever, fatigue, weight loss, dyspnea "slowly or non-resolving pneumonia" Inspiratory crackles, leukocytosis, raised ESR X-ray: Bilateral diffuse alveolar infiltrates, peripheral, nodular, lower lobes, pleural effusion is rare.

COP- cont. PFTs: restriction, reduced diffusion, obstruction (20%), hypoxemia. Diagnosis: characteristic pathology with fibrotic buds in alveoli (organising pneumonia) and bronchiolitis obliterans. Treatment: Steroids, cyclophosphamide. 2/3 respond, others have progressive disease.

Pulmonary Vasculitis Granulomatous vasculitis syndromes Granulomatosis with polyangiitis (GPA) Wegener's vasculitis Eosinophilic Granulomatosis with polyangiitis (EGPA) Churg-Strauss vasculitis Lymphomatoid granulomatosis Pulmonary-renal syndromes Microscopic polyangiitis (overlap polyangiitis syndrome) pauci-immune glomerulonephritis Classical polyarteritis nodosa Giant cell arteritis Takayasu's disease Behcet's disease

Granulomatosis with polyangiitis (GPA) Definition A multi-organ disease histologically characterized by necrotizing vasculitis involving the small vessels, extensive necrosis & granulomatous inflammation

Granulomatosis with polyangiitis Clinical manifestations Hoffman GS: Ann Intern Med 1992;116:488

Granulomatosis with polyangiitis

Antineutrophil Cytoplasmic Antibodies (ANCA)

Granulomatosis with polyangiitis Pathology Necrotizing vasculitis: arterioles, venules & capillaries Granulomatous inflammation Geographical parenchymal necrosis Hemorrhagic infarcts Fibrosis

Granulomatosis with polyangiitis Treatment Mortality >80% within 3 years without adequate treatment Treatment of choice: Prednisone 1mg/kg/day Cyclophosphamide 1-2mg/kg/day (orally) Remission is achieved in 70-93%

Eosinophilic granulomatosis with polyangiitis Churg-Strauss syndrome History of asthma Marked blood eosinophilia (up to 10000/ul) Vasculitis, eosinophilic tissue infiltration Sinusits Skin (70%)- nodules,purpura, urticaria Nervous system- mononeuritis muliplex (66%), CNS GIT- abdominal pain (60%), diarrhea (33%), bleeding Cardiac- cardiac failure (50%), pericarditis, hypertension Renal- dysfunction (50%) fever, lymphadenopathy

Churg-Strauss cont. Lungs- infiltrates (>70%), usually transient and patchy, also nodules , interstitial infiltrates, pleural effusion (1/3). Obstructive PFTs, elevated IgE, anemia, elevated ESR BAL- eosinophilia (33%), eosinophils in pleural fluid Biopsy- necrotising giant cell vasculitis (small arteries and veins), eosinophils, granulomas. Treatment: Steroids, cyclophosphamide.

Rheumatoid Arthritis Pulmonary manifestations Pleural disease pleurisy (20%), effusion (4%), unilateral (80%), R>L middle-aged male, any time during the illness Associated with nodules not arthritis Fluid: exudate, LDH>1000, low glucose (<50mg% in 80%),low pH, lymphocytic, RF +, low complement

RA-cont. Interstitial pneumonitis identical to idiopathic pulmonary fibrosis fullblown in 2%, abnormal PFTs in 41% M>F, patients are RF positive Cough, dyspnea, dry rales, clubbing hypoxemia, restrictive PFTs, reduced DCO Variable response to steroids Poor prognosis (survival 3-5 years) May be drug-induced (methotrexate, gold, penicillamine)

RA-cont. Nodules: single (1/3) or multiple (2/3), more common in men related to disease activity and skin nodules asymptomatic, may cavitate, rarely hemoptysis peripheral, 0.3-7cm diameter may respond to steroids Caplan's syndrome: pulmonary nodules with RA in coal miners (coal miner's pneumoconiosis)

RA-cont. Bronchiolitis Obliterans Pulmonary hypertension airways obstruction, 60% of smokers, 30% of non-smokers peribronchial inflammatory infiltrate may be drug-induced Pulmonary hypertension pulmonary arteritis

Systemic Lupus Erythematosis Pulmonary manifestations Pleura:- pleuritis or effusion, 50-75% of patients, presenting symptom in 1/3, fluid is an exudate, PMNs, raised ANF, LE cells Interstitial pneumonitis:- acute (fever,cough, progressive hypoxemia) or chronic Pulmonary thromboembolic disease:- lupus anticoagulant positive patients Diaphragmatic dysfunction Atalectasis:- subsegmental, bibasilar INFECTION!

Goodpasture's syndrome Alveolar hemorrhage Glomerulonephritis Anti-glomerular basement membrane antibody

Goodpasture's syndrome Young males Autoimmune disorder Clinical features: Rapidly-progressive glomerulonephritis Hematuria, proteinuria, renal failure Hemoptysis, dyspnea, cough Anemia Arthralgia

Goodpasture's syndrome Laboratory features: X-ray: transient infiltrates Urine:red cells, casts Iron-deficiency anemia Restrictive defect on lung-function tests with increased diffusion capacity. Diagnosis: Hemosiderin-laden macrophages Anti-GBM antibodies Renal biopsy Treatment: Plasmapharesis, steroids, cyclophosphamide.