Postgraduate Medical Journal | 2019
Pulmonary alveolar proteinosis
Abstract
The patient was a 2-year-old boy who was hospitalised due to dyspnoea with primary clinical impression of pneumonia. Laboratory tests were normal except mild leucocytosis (white cell count=13.09×10/L, haemoglobin=155 g/L, platelet=378×10/L, blood sugar=90 mg/dL, blood urea nitrogen=10 mg/dL, creatinine=0.5 mg/dL, sodium=140 meq/L, potassium=5 meq/L). Blood culture, urine culture and bronchoalveolar lavage culture for tuberculosis, fungi and bacteria were negative. Chest X-ray showed bilateral consolidation which was more prominent at hilar regions (figure 1A). Chest high resolution computerised tomography revealed bilateral septal thickening and ground glass opacities (figure 1B). Histopathology findings of transbronchial biopsy showed a dense granular eosinophilic material in alveoli with oval bodies and cholesterol cleft (figure 1C). The eosinophilic material was positive in periodic acid schiff with diastase (figure 1D). Pulmonary alveolar proteinosis (PAP) was first recognised by Rosen et al. It is a rare diffuse lung disease characterised by the accumulation of surfactant derived lipoproteins in alveolar spaces with an incidence of 0.2 per million. Surfactant is mainly composed of phospholipids (90%) and proteins (10%) which are produced by alveolar pneumocytes type II and its catabolism is highly influenced by GM-CSF (granulocyte monocyte colony stimulating factor) as a mediator of macrophage maturation. PAP is aetiologically classified into primary (associated with autoimmune processes leading to anti-GM-CSF antibodies), secondary (associated with malignancy or inhalation of finely divided dusts like silica), hereditary (associated with GM-CSF receptor mutation) and unclassified (idiopathic). Autoimmune PAP (90%) is the most common type followed by secondary type (10%). Its usual clinical manifestations are shortness of breath (dyspnoea) (50%–90%), cough (can be productive), malaise, chest discomfort and weight loss. However, one-third of patients can be asymptomatic. 6 Although imaging findings are non-specific in PAP, presence of chronic symptoms should raise its possibility. Chest X-ray usually shows bilateral alveolar infiltrates and a bat wing appearance when it is more prominent in hilar regions. High resolution CT typically show bilateral ground-glass opacities with interlobar septal thickening termed ‘crazy paving’. Characteristic histopathological feature of PAP is filling of alveolar and air spaces by coarsely granular eosinophilic material containing oval and elongated bodies. Cholesterol clefts can also be observed in the eosinophilic material. There are different therapeutic modalities for PAP patients like segment by segment whole lung lavage, GM-CSF therapy, rituximab, plasmapheresis, lung transplantation, bone marrow transplantation, removal of offending exposures and treating underlying medical disorders. Symptomatic patients without any evidence of lung fibrosis or infection and no evidence of improvement after close observation become candidate for segment by segment whole lung lavage and GM-CSF therapy. If the symptoms recur or worsen, this treatment should be repeated. In the case of refractory PAP, other modalities like rituximab with or without plasmapheresis or lung transplantation should be considered. If the patients are asymptomatic, preventive measures like avoidance of exposure to toxic substances, smoking cessation, vaccination and patient’s monitoring with serum biomarkers like lactate dehydrogenase, pulmonary function tests like forced vital capacity, diffusing capacity of the lungs for carbon monoxide, oximetry and chest X-ray (every 3–6 months) should be considered. Mohammad Vasei, Mohammadreza Modaresi, Moeinadin Safavi