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Pulmonary vasculitis. Sanitra Sirithangkul M.D. Division of Pulmonary and Critical care Department of Pediatrics Phramongkutklao Hospital. Systemic diseases and the lung. • relatively rare in pediatric practice • CNT diseases : SLE, dermatomyositis • Pulmonary vasculitis
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Pulmonary vasculitis Sanitra Sirithangkul M.D. Division of Pulmonary and Critical care Department of Pediatrics Phramongkutklao Hospital
Systemic diseases and the lung • relatively rare in pediatric practice • CNT diseases : SLE, dermatomyositis • Pulmonary vasculitis • Inherited CNT disorders : Ehlers-Danlos • Mucopolysaccharidoses, familial dysautonomia, sarcoidosis •LCH, pulmonary lymphangiomatosis Pediatr Respir Rev 2005;6:181-189
Systemic diseases and the lung • may cause significant respiratory complications • treatment : often requires corticosteroids & immunosuppressants • outcome : variable • when they affect the lung, carry a small but significant mortality Pediatr Respir Rev 2005;6:181-189
Systemic vasculitis •true incidence in children is not known • around 2-5 cases/million/year • pathology of vasculitis : cellular inflammation, vessel destruction, tissue necrosis • clinical features : site, size and type of vessel involved
Classification ของในโรคในกลุ่ม Vasculitis Primary idiopathic vasculitis - Small vessel • Wegener’s granulomatosis • Microscopic polyangitis • Churg-Strauss syndrome • Idiopatic pauci-immune rapidly progressive glomerulonephritis • Isolated pauci-immune pulmonary capillaritis
Primary idiopathic vasculitis - Medium vessel • Polyarteritis nodosa • Kawasaki disease - Large vessel • Giant cell arteritis • Takayasu’ s arteritis Primary immune complex-mediated vasculitis • Goodpasture’s syndrome • Henoch-Schonlein purpura • Behcet’s disease
Classification ของในโรคในกลุ่ม vasculitis (cont.) Secondary vasculitis - Classic autoimmune disease • Systemic lupus erythematosus • Rheumatoid arthritis • Polymyositis / dermatomysitis • Scleroderma • Antiphospholipid antibody syndrome
Secondary vasculitis • Essential cryoglobulinemia • Inflammatory bowel disease • Hypocomplementemic urticarial vasculitis • Drug-induced (e.g., propylthiouracil, diphenylhydantoin) • Paraneoplastic • Infection
Pulmonary vasculitis • one component of systemic vasculitis • pathology : fibrin thrombi, fibrinoid necrosis • the inflammation may lead to - a progressive destruction of pulmonary circulation - granuloma formation - end – organ failure
โรคในกลุ่ม vasculitis ที่ทำให้เกิดพยาธิสภาพที่ปอด • Pulmonary involvement common • - Wegener’s granulomatosis* • - Goodpasture’s syndrome* • - Idiopathic pulmonary hemosiderosis • - Kawasaki disease • * Positive serum anti-neutrophil cytoplasmic antibody (ANCA)
โรคในกลุ่ม vasculitis ที่ทำให้ เกิดพยาธิสภาพที่ปอด (ต่อ) B. Pulmonary involvement uncommon - Henoch-Shonlein purpura - Churg-Strauss vasculitis* - Polyarteritis nodosa* - Takayasu arteritis - Temporal arteritis - Serum sickness - Cryoglobulinemia * Positive serum anti-neutrophil cytoplasmic antibody (ANCA)
Clinical scenarios suggestive of vasculitis 1. Diffuse alveolar hemorrhage (DAH) - hemoptysis - diffuse alveolar infiltration in CXR - a drop in hematocrit
สาเหตุของ Diffuse alveolar hemorrhage With pathologic capillaritis - Primary idiopathic small vessel vasculitis - Primary immune complex-mediated vasculitis - Secondary vasculitis
Without pathologic capillaritis (bland hemorrhage) - Idiopathic pulmonary hemosiderosis - Coagulopathy - Mitral stenosis - Inhalation injury - Goodpasture syndrome - Systemic Lupus erythematosus - Bone marrow transplantation (associated with diffuse alveolar damage) - Drug – associated disease (e.g., chemotherapeutic agents)
Clinical scenarios suggestive of vasculitis 2. Acute glomerulonephritis - rapidly progressive glomerulonephritis (RPGN) - to be considered SLE, post-infectious GN, IgA nephropathy, MPGN, ANCA-associated vasculitis
Clinical scenarios suggestive of vasculitis 3. Pulmonary-renal syndrome - DAH / pulmonary capillaritis + glomerulonephritis 4. Destructive upper airway lesions 5. Chest imaging findings 6. Palpable purpura 7. Mononeuritis multiplex 8. Multisystem disease
Specific testing 1. Antineutrophil cytoplasmic antibodies (ANCA) - circulating autoantibodies against intracellular antigens found in neutrophils - cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA)
แสดงการเปรียบเทียบ c-ANCA และ p-ANCA
แสดงการเปรียบเทียบ c-ANCA และ p-ANCA
Specific testing 2. Radiographic imaging - CT chest : cavity, nodule, diffuse ground glass opacification - CT sinus 3. Bronchoscopy - assess for infection / alveolar hemorrhage / endobronchial lesion
Specific testing 4. Diagnostic biopsy - skin, sinus or upper airway lesions - renal biopsy - lung biopsy - collect tissue in saline for culture - frozen tissue for immunofluorescence - formaline-fixed tissue for H&E
Wegener’s granulomatosis (WG) • the most common of the ANCA-associated vasculitis • triad : upper airway disease, lower respiratory tract disease, glomerulonephritis • abnormal CXR findings : alveolar, interstitial, mixed infiltration nodule/cavity
Wegener’s granulomatosis (WG) • c-ANCA / antiPR3 positive 85-95% of active, systemic WG • poor outcomes : advanced age, severe renal involvement, alveolar hemorrhage, anti PR3 positive
Microscopic polyangiitis (MPA) • long prodromal phase of constitutional symptoms → development of RPGN • pulmonary involvement seen in up to 30% • most common pulmonary involvement : DAH with pulmonary capillaritis
Microscopic polyangiitis (MPA) • p-ANCA +ve 50-70%, anti MPO +ve 35-65%, c-ANCA +ve 10-15% • pathology : focal, segmental necrotizing vasculitis, mixed inflammatory infiltrate without granuloma
Churg-Strauss syndrome (CSS) • to be considered when other eosinophilic lung diseases are in the differential or • difficult-to-control asthmatic patients develop significant cardiac, GI or neurologic disease • triad : asthma, hypereosinophilia, necrotizing vasculitis
Churg-Strauss syndrome (CSS) • pulmonary hemorrhage and glomerulonephritis : less common • p-ANCA /anti MPO +ve 50-75%, c- NCA +ve 10% • mortality & morbidity due to cardiac complications, GI, status asthmaticus & respiratory failure
Therapy •induction of remission : 12 months •maintenance : 12-18 months - cyclophosphamide → azathioprine/ methotrexate - additional agents : mycophenolate mofetil (MMF), leflunomide, cyclosporine - Pneumocystis carinii prophylaxis with trimetroprim-sulfametoxazole
Monitoring •to minimize morbidity & mortality of the vasculitides and their therapy •differential diagnosisin pts with clinical deterioration - infection - drug toxicity - disease relapse - a new unrelated problem
Take home message •Pulmonary vasculitis is one component of a variety of systemic vasculitis • Early diagnosis using common clinical scenarios and appropriate investigations
Take home message • Aggressive early treatment to minimize disease related mortality & irreversible damage • Regular monitoring for disease activity and medication toxicity