Autoimmune pulmonary alveolar proteinosis in children

Abstract

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children. Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach. The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults.

FIGURE 1

a) Autoimmune pulmonary alveolar proteinosis. Computed tomography scan of a child aged 14 years 8 months with 2 days of fever and dyspnoea. Note the ground-glass opacities and interlobar septal thickening giving the image of nonpathognomonic “crazy paving” pattern. b) Coronavirus disease 2019 pneumonia in a child aged 3 years 2 months with trisomy 21. Note the bilateral ground-glass and consolidating pattern. Both children had comparable degrees of respiratory insufficiency at the time of imaging.