Surfactant protein C dysfunction with new clinical insights for diffuse alveolar hemorrhage and autoimmunity.

IMPORTANCE

Surfactant protein C (SP-C) dysfunction is a rare disease associated with interstitial lung disease. Early therapies may improve outcomes but the diagnosis is often delayed owing to variability of manifestations.

OBJECTIVE

To investigate the manifestations and outcomes of SP-C dysfunction.

METHODS

We retrospectively analyzed the records of five pediatric patients who were diagnosed with SP-C dysfunction between February 2014 and April 2017 at Beijing Children's Hospital.

RESULTS

The five patients included two boys and three girls with a median age at diagnosis of 1.3 years. All patients presented with interstitial lung disease and had a heterozygous mutation, including an I73T mutation in three patients, a V39L mutation in one patient, and a Y104H mutation in one patient. In addition to common respiratory manifestations, hemoptysis and anemia were observed in one patient with the I73T mutation. Elevated levels of autoantibodies and a large number of hemosiderin-laden macrophages in bronchoalveolar lavage fluid were found in two patients with the I73T mutation, suggesting the presence of diffuse alveolar hemorrage and autoimmunity. Chest high-resolution computed tomography features included ground-glass opacities, reticular opacities, cysts, and pleural thickening. Transbronchial lung biopsy was performed in one patient with the I73T mutation, which revealed the presence of some hemosiderin-laden macrophages in alveolar spaces. All patients received treatment with corticosteroids; two received combined treatment with hydroxychloroquine. During follow-up, the two patients who received hydroxychloroquine showed improved symptoms; of the remaining three patients, two died after their families refused further treatment, while the final patient was lost to follow-up.

INTERPRETATION

This is the first report to describe a new phenotype of diffuse alveolar hemorrhage with autoimmunity in patients with I73T mutation. Treatment with hydroxychloroquine should be considered for patients with SP-C dysfunction.