The Anti-MDA5 Phenotype: Defining Clinical, Biochemical, and Radiological Features Suggestive of Anti-MDA5-Associated Rapidly Progressive Interstitial Lung Disease

Abstract

SESSION TITLE: Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: Anti-MDA5 (aMDA5) is a novel autoantibody associated with a characteristic cutaneous phenotype. Unlike anti-synthetase syndrome, aMDA5 has often been associated with rapidly progressive interstitial lung disease (RP-ILD), especially in the presence of elevated ferritin. The primary goal of our study was to define clinical, biochemical and radiological features predictive of aMDA5-associated RP-ILD that would justify empirical treatment, pending aMDA5 autoantibody confirmation. METHODS: We retrospectively analyzed 7 patients (pts) who presented in an inpatient setting with an aMDA5-associated RP-ILD phenotype. RESULTS: Six pts were men, 6 pts presented with dyspnea and all developed RP-ILD. aMDA5-associated cutaneous symptoms appeared within one month of respiratory symptoms in 6 pts, but were recognized at presentation in 2 pts. These included palmar papules and/or erythema (n=4 pts), lateral papules of the fingers (n=3), skin ulcerations (n=2) and mechanic's hands (n=4). Gottron papules and sign were sometimes psoriasiform. Shawl and V-signs were absent whereas periungueal erythema was always present. Profound weight loss over 1 to 2 months was present in all pts (mean 21.9 lbs, range 14-37 lbs,), as were articular symptoms. Raynaud phenomenon was seen in only 1 pt. Four pts were clinically amyopathic; only 1 pt had increased serum creatine kinase (CK). Hepatic enzymes were elevated in 6 pts. Initial imaging showed ground glass opacities with consolidation in 6 pts, isolated ground glass opacities in 1 pt and reticulations in 4 pts, overall in a bibasilar peripheral distribution in 6 pts. Nuclear or cytoplasmic fluorescence on ANA testing was absent. aMDA5 positivity was subsequently confirmed in 6 pts tested. Four pts died. Time from hospitalization to death ranged from 6 to 31 days. Survivors received mycophenolate mofetil and/or tacrolimus, concomitantly with corticosteroids. Hyperferritinemia (>1000 μg/L) upon admission was associated with a fatal outcome. CONCLUSIONS: In an inpatient setting, aMDA5-associated ILD is a severe, rapidly progressive condition with a high mortality. Cutaneous findings are subtle and may follow the respiratory symptoms. CLINICAL IMPLICATIONS: Dyspnea, aMDA5-associated cutaneous findings, profound weight loss, articular symptoms, normal CK with elevated hepatic enzymes and a negative ANA should alert clinicians to the possibility of aMDA5-associated RP-ILD. Early immunosuppressive therapy may prove lifesaving. DISCLOSURE: Marvin Fritzler: Shareholder: INOVA The following authors have nothing to disclose: Sabrina Hoa, Sandra Chartrand, Yves Troyanov, Ira Targoff, Anne-Marie Mansour, Eric Rich, Hind Boudabbouz, Josiane Bourré-Tessier, Marianne Landry, Martin Albert, Jean-Luc Senécal No Product/Research Disclosure Information