Bronchiolitis Obliterans Organising Pneumonia (BOOP), Granulomatosis with Polyangiitis

פרופ' נוויל ברקמןפרופ' נוויל ברקמןמכון הריאהמכון הריאה

ביה"ח האוניברסיטאי הדסה עין-כרםביה"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 manifestationsOrgan involved % at disease onset

% throughout course of disease

Sinusitis 51 85Otitis media 25 44

Pulmonary infiltrates 25 66

Pulmonary nodules 24 58

Hemoptysis 12 30

Glomerulonephritis 18 77

Conjuctivitis, dacrocystitis

5 18

Arthritis, arthralgia 32 67

CNS, peripheral neuropathy

1 15-18

Hoffman GS: Ann Intern Med 1992;116:488

Granulomatosis with polyangiitis

Antineutrophil Cytoplasmic Antibodies (ANCA)

antigenic specificity disease specificty

c-ANCAcytoplasmic proteinase 3

WG (70-93%)

p-ANCAperinuclear

myeloperoxidaseCSS, MPA, PAN,

IBD

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 ArthritisPulmonary manifestations

• Pleural disease pleurisy (20%), effusion (4%), unilateral (80%), R>Lmiddle-aged male, any time during the illnessAssociated with nodules not arthritisFluid: exudate, LDH>1000, low glucose (<50mg% in 80%),low pH, lymphocytic, RF +, low complement

RA-cont.• Interstitial pneumonitis

identical to idiopathic pulmonary fibrosisfullblown in 2%, abnormal PFTs in 41%M>F, patients are RF positiveCough, dyspnea, dry rales, clubbinghypoxemia, restrictive PFTs, reduced DCOVariable response to steroidsPoor 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 menrelated to disease activity and skin nodulesasymptomatic, may cavitate, rarely hemoptysisperipheral, 0.3-7cm diametermay respond to steroids

• Caplan's syndrome: pulmonary nodules with RA in coal miners (coal miner's pneumoconiosis)

RA-cont.

• Bronchiolitis Obliteransairways obstruction, 60% of smokers, 30% of non-smokersperibronchial inflammatory infiltratemay be drug-induced

• Pulmonary hypertensionpulmonary arteritis

Systemic Lupus ErythematosisPulmonary 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 glomerulonephritisHematuria, proteinuria, renal failureHemoptysis, dyspnea, coughAnemiaArthralgia

Goodpasture's syndrome• Laboratory features:

X-ray: transient infiltratesUrine:red cells, castsIron-deficiency anemiaRestrictive defect on lung-function tests with increased diffusion capacity.

• Diagnosis:Hemosiderin-laden macrophagesAnti-GBM antibodiesRenal biopsy

• Treatment:Plasmapharesis, steroids, cyclophosphamide.