A novel dermato-pulmonary syndrome associated with MDA-5 antibodies: report of 2 cases and review of the literature

Abstract

Melanoma differentiation-associated protein 5 (MDA-5) is a novel autoantibody frequently characterized by interstitial lung disease and a distinct cutaneous phenotype with palmar papules, ulceration, and rash. Virtually all patients have underlying dermatomyositis, but many lack the characteristic clinical myopathy associated with it. In the setting of amyopathic disease, the absence of clinically available biomarkers or clear pathologic diagnosis can complicate effective prognostic and therapeutic intervention. Until recently the presence of MDA-5 antibody associated dermato-pulmonary syndrome was described only in Asian populations. We present 2 cases of MDA-5-associated dermato-pulmonary syndrome and provide a comprehensive review of available literature.

Fig 1

A) CT scan of chest with intravenous contrast 10 days before admission. The representative slice shows areas of patchy consolidation in the posterior portions of the lower lobes bilaterally. B) CT scan without intravenous contrast, taken on the day of admission, showing significant consolidation in the posterior aspects of the bilateral lower lobes, surrounded by patchy ground-glass infiltrates. C) Fingers of Case 1 showing dry, crackling skin at the fingertips, typical of mechanic’s hands. D) Hematoxylin and eosin stain of the left lingula showing areas of extensive interstitial fibroplasia and marked pneumocyte atypia and interstitial inflammation consistent with organizing diffuse alveolar damage with associated bronchopneumonia.

Fig 2

Confirmation of anti-MDA-5 antibodies in the sera of Cases 1 and 2 using an immunoprecipitation assay. ³⁵S-methionine-labeled MDA-5, generated by in vitro transcription/translation, was immunoprecipitated using serum from Cases 1 and 2 (lanes 2 and 3) or 2 different normal controls (lanes 4 and 5). Input ³⁵S-methionine-labeled MDA-5 (not subjected to immunoprecipitation) is shown in lane 1. These data demonstrate that Cases 1 and 2 have anti-MDA-5 antibodies.

Fig 3

A) Thoracic CT images with intravenous contrast enhancement showing scattered peripheral interstitial thickening throughout both lungs and multiple subcentimeter ground-glass pulmonary nodules throughout all lobes of both lungs. B) Cutaneous ulceration of the dorsal third metacarpophalangeal joint of the left hand.