Autoimmune Pulmonary Alveolar Proteinosis Treated With Whole Lung Lavage and Rituximab: A Case Report

Abstract A 39-year-old female non-smoker who enjoyed good past health, was hospitalized for persistent dyspnoea. She denied significant exposure to humidifiers, disinfectants, crops nor any animal contact. Physical examination showed bilateral lower zone crepitations. Serial chest X-ray showed progressive bilateral lung lower lobe opacities. There was no clinical evidence of rheumatological disease. Baseline blood tests for complete blood count, liver and renal function tests were unremarkable. Autoimmune markers, myositis panel and aspergillus antibody were negative. Eosinophil count, C-reactive protein and erythrocyte sedimentation rate were not elevated. Computed Tomography (CT) Thorax revealed patchy ground glass opacities in both lungs associated with intralobular septal thickening. Serial CT scan showed increasing patchy ground glass opacities with peripheral and basal predominance. Bronchoscopy with targeted transbronchial biopsy showed proteinaceous material in a few alveolar spaces with neutrophilic infiltrates at the alveolar wall, but there was insufficient tissue for further testing. Microbiological workups including bacterial culture, fungal culture and Acid-fast bacillus culture were negative. The patient was referred to cardiothoracic surgeon for surgical lung biopsy, which showed focal chronic inflammation and fibrosis without evidence of interstitial lung disease. The patient suffered from further reduction in exercise tolerance. Follow-up CT showed further worsening of ground glass opacities in bilateral lower lobes with crazy paving pattern. Repeated bronchoscopy with transbronchial biopsy showed distended alveoli cells with granular eosinophilic matter. Contents of the alveolar spaces are positive for Periodic acid-Schiff (PAS) stain. Blood for Anti-GM-CSF antibody was arranged, and came back positive with a high activity level seen on the neutralizing assay. A diagnosis of autoimmune pulmonary alveolar proteinosis (PAP) was made. Whole lung lavage and intravenous Rituximab infusion were arranged. There was both clinical and radiological improvement post treatment. Lung function test and 6-minute walk test were improved, and the patient remained asymptomatic and free from hospitalization. Pulmonary alveolar proteinosis is a rare disease, and a high level of clinical suspicion is needed in cases of dyspnoea with bilateral lower zone opacities on chest imaging. Typical CT findings include smooth thickening of interlobular and intralobular septal lines and ground glass opacities, also known as crazy paving pattern. PAS stain should be arranged during biopsy. The increasing availability of anti-GM-CSF blood testing can facilitate the diagnosis of autoimmune PAP. Treatment options include early referral to tertiary centers with expertise in whole lung lavage and Rituximab.