Severe gastrointestinal involvements in adult dermatomyositis patients with anti-NXP2 antibody
Description
Objective: Gastrointestinal (GI) involvements were scarcely reported in adult anti-NXP2 dermatomyositis (NXP2+DM). In this study, we investigated the clinical, pathological, and molecular features as well as treatment options of this rare yet life-threatening disease.
Patients and Methods: We retrospectively collected the data of the cohort of NXP2+ DM from 2012 to 2022 in our hospital. RNAseq was performed in intestinal samples of perforated patients compared to healthy controls dataset.
Results: A total of 56 adult NXP2+DM patients were collected including 10 cases with GI involvements. Abdominal pain and melena were the initial manifestations for GI involvements with a median 10-month time lag after the diagnosis of NXP2+DM when myositis largely subsided. Within weeks, GI perforation occurred in eight of ten patients, while five patients underwent eight surgical interventions subsequently. The short-term mortality was observed in four patients. NXP2+DM with GI involvements presented with more extramuscular systemic manifestations such as interstitial lung disease and subcutaneous calcinosis. The GI pathological features encompassed vasculitis/vasculopathy with high MxA expression, intestinal smooth muscle necrosis, and serosal calcinosis. Gene expression profile validated the type-I interferon activation and revealed that epithelial mesenchymal transition and focal adhesion pathway may also contribute. Finally, Vedolizumab, an anti-α4β7‑integrin monoclonal antibody, exhibited promising therapeutic signals which should be further investigated.
Conclusions: GI involvement is an unique complication in adult NXP2+ DM patients. Timely recognition and targeted therapy may turn out to be lifesaving.