Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan

Abstract

To the Editors: Pulmonary alveolar proteinosis (PAP) is a rare syndrome that predominantly affects the lungs, and is characterised by the accumulation of surfactant lipids and proteins in the alveoli and terminal airways 1. In 1999, we published findings that high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralising autoantibodies were detected specifically in patients with idiopathic PAP 2. Recently, as a result of the excellent sensitivity and specificity of GM-CSF autoantibody assays in identifying this form of PAP 3, it has been proposed that the nomenclature for this condition should be changed to “autoimmune PAP” rather than “idiopathic PAP” 4. Secondary or hereditary PAP is not associated with GM-CSF autoantibodies but develops as a consequence of a separate underlying disorder or genetic background 5. Recently, we demonstrated that the characteristic high-resolution computed tomography (HRCT) findings in secondary PAP are distinct from those in autoimmune PAP 6. However, physicians may not suspect secondary PAP, even when encountering unexplained pulmonary opacities on chest radiograph or computed tomography in patients with pre-existing haematological or infectious diseases, since there is little information available on the clinical features. Here, we outline the clinical features of adult-onset secondary PAP based on our database of 40 pre-mortem cases in which serum GM-CSF autoantibodies were negative, and compare them with other cases in the literature. A total of 404 patients with pre-mortem cytologically or pathologically proven PAP were registered in our study group between 1999 and 2009. We obtained consent from all treating physicians for each identified case according to the guidelines for epidemiological studies from the Ministry of Health, Labour and Welfare 7, and all clinical data were de-identified. 360 (89%) cases were positive for serum GM-CSF autoantibody. The clinical features of 223 of the cases were previously published as …