DIFFUSE ALVEOLAR HEMORRHAGE SYNDROM Katarina Osolnik University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia Portorož, May 8th 2009

DIFFUSE ALVEOLAR HEMORRHAGE acute, life-threatening event repeated episodes can lead to: organizing pneumonia collagen deposition in small airways fibrosis

DIFFUSE ALVEOLAR HEMORRHAGE Wegener granulomatosis microscopic polyangiitis Goodpasture syndrome connective tissue disorders antiphospholipid antibody sy infectious or toxic exposures neoplastic conditions

CAUSES OF DIFFUSE ALVEOLAR HEMORRHAGE vasculitis or capillaritis pulmonary haemorrhage without capillaritis or vasculitis (»bland« pulmonary haemorrhage) alveolar bleeding associated with another process or condition

CLINICAL MANIFESTATIONS Acute or subacute (present for less than a week) dyspnea, cough, fever, haemoptysis are the most common clinical manifestations of DAH. *Haemoptysis may be absent at time of presentation in up to a third of patients.

DIAGNOSTIC EVALUATION Chest X-ray diffuse, bilateral consolidation or ground- glass opacities due to alveolar filling distributed in the perihilar regions, sparing the apices and costophrenic angels

DIAGNOSTIC EVALUATION HRCT better evaluate the extent of disease more sensitive in identifying ground- glass opacities, but not more specific

DIAGNOSTIC EVALUATION Laboratory tests anemia, leukocytosis  ESR,  CRP  blood urea and serum creatinine, abnormal findings of urin analysis in pulmonary-renal sy anti-GBM, ANCA, C3 and C4, anti-ds-DNA, antiphospholipid Ab Pulmonary function test increased diffusing capacity restrictive changes obstructive changes

DIAGNOSTIC EVALUATION Bronchoscopy to document alveolar hemorrhage by BAL to exclude airway sources of bleeding to exclude an associated infection Within the first 48 hours of symptoms the diagnostic yield is higher!

BAL is the method of choice by showing free red blood cells and hemosiderin-laden, iron-positive macrophages

BAL WITH IRON +AM GOLNIK (64+/84staining samples) vasculitis or capillaritis 29% pulmonary haemorrhage without capillaritis or vasculitis (»bland« pulmonary haemorrhage) 18% alveolar bleeding associated with another process or condition 39% pneumoconiosis 14%

BAL WITH IRON +AM GOLNIK vasculitis or capillaritis: 58% sistemic vasculitis 42% connective tissue disorders pulmonary haemorrhage without capillaritis or vasculitis: 66% drugs 17% infective endocarditis

BAL WITH IRON +AM GOLNIK alveolar bleeding associated with another process or condition: 48% infections 32% sarcoidosis 20% malignant conditions

TREATMENT OF DAH combination of treatment autoimmune destruction of the alveolare capillary membrane and the underlaying condition immunosupresive agents are the mainstay of therapy, especially if DAH is associated with systemic or pulmonary vasculitis, Goodpasture syndrome or conective tissue disorders treatment of small vessel vasculitis of the lung is largely the same, regardless of aetiology or whether it is isolated to the lung or a component of a systemic disease

TREATMENT OF DAH Immunosupresive agents Methylprednisolone and Cyclophosphamide are the mainstay of therapy. Plasmapheresis - clinical benefit in Goodpasture syndrome Recombinant activated human factor VII- successful in several case reports of treating alveolar hemorrhage due to allogenic hematopoietic stem cell transplantation, ANCA associated vascullitis, SLE or antiphospholipid syndrome.

TREATMENT OF DAH-other possible management measures: supplemental oxygen, bronchodilators, reversal of any coagulopathy, intubation with bronchial tamponade, protective strategies for the less involved lung, mechanical ventilation should be done in the course of the disease if they are needed.

CONCLUSION DAH can be a catastrophic illness if recognition and treatment are delayed. Diagnosis is often aided by other systemic findings, associated illnes and serological results. Patients with unexplained isolated DAH should undergo a lung biopsy with immunofluorescent studies and routine histological tests. During therapy close monitoring, due to potential complications of treatment and the possibility to relapses, is needed.