AB0935 ANTI-TIF-1 G-ANTIBODIES IN JUVENILE DERMATOMYOSITIS ARE ASSOCIATED WITH VARIOUS CLINICAL PHENOTYPES

Abstract

Background Juvenile dermatomyositis (JDM) is a rare heterogeneous autoimmune disease. The identification of myositis specific antibodies (MSAs) has allowed the characterization of subgroups of JDM patients who each have specific phenotypes. Antibody (Ab) against transcriptional intermediary factor-1-γ (TIF-1-γ or p155/140) is the most common MSA in JDM 1. In the American and English JDM cohorts, anti-TIF-1-γ associated JDM is classically associated with a larger proportion of caucasians, mild or moderate severity with typical cutaneous manifestations (Gottron’s papules, and/or heliotrope rash, photosensitivity), and a chronic disease course with a low mortality. The frequency of skin ulcerations and lipodystrophy differs between the two cohorts Objectives To report the clinical and muscle histology associations of anti-TIF-1-γ Ab in a series of patients with JDM followed in the French referral center for rare pediatric systemic autoimmune diseases. Methods Retrospective study of patients with JDM (according to the EULAR/ACR criteria) associated with anti-TIF-1-γ autoantibodies and included in our CEMARA database approved by the French National Committee on Informatics and Liberty. Results Thirteen patients were included (males: 5, females: 8; Caucasians: 6, Black Africans: 2, North Africans: 5). Age at diagnosis ranged from 1.5 to 11 years. Serum creatine kinase was elevated in 12 patients (range: 180-43 000 IU/L). Three different phenotypes were identified according to the severity and course. In group 1 (n=4), 3 patients had a moderate JDM: classical cutaneous manifestations and moderate muscle involvement; relapsing course, which remitted under methotrexate/corticosteroids; an additional 2-year-old girl had an amyopathic JDM. In group 2 (n=7), patients had a severe JDM : ulcerating skin lesions, severe muscle involvement, dysphagia, gastrointestinal vasculitis and/or requirement to an intensive care unit, and required more than two lines of treatment. In this group, 2/7 patients died from refractory JDM, comparing to a mortality rate of 2% in the remaining JDM patients tested for MSA and negative for anti-TIF-1-γ. Only 2/5 patients achieved a complete remission under treatment. Group 3 comprised two patients with severe muscle atrophy, calcinosis and lipodystrophy and a chronic course; one of them had a very-early-onset JDM at 1.5 year-old and the other an inherited neurological involvement, potentially suggestive of a genetic predisposing condition to JDM. None of the patients developed lung involvement or malignancy. Six patients underwent a muscle biopsy which was scored using the JDM severity score tool. The histo-pathologists’ overall severity score (VAS) varied from to 1 to 9/10; the highest scores were observed in the two patients who died. Conclusion In the present series of patients with JDM, TIF-1-γ Ab-associated-clinical phenotypes and ethnicities are more heterogeneous than previously reported. TIF-1-γ Ab is associated with a high mortality rate in a subset of patients.