MDA5-positive dermatomyositis: an uncommon entity in Europe with variable clinical presentations

Abstract

Clinically amyopathic dermatomyositis (CADM), described almost 50 years ago, is defined on the basis of still not validated criteria and characterized by skin findings almost without muscle weakness. Autoantibodies directed against the cytosolic pathogen sensor MDA5 (CADM 140) can mark this subtype of dermatomyositis which has been reported to associate, in particular ethnic groups, with severe progressive interstitial lung disease, poor prognosis and an hyperferritinemic status resembling hemophagocytic-like syndromes. MDA5 may be relevant in that Interferon-signature claimed to characterize inflammatory myopathies and dermatomyosits itself, but its role is not clear. However, the titre of anti-MDA5 autoantibodies seems to correlate with the outcome. In Caucasian populations the association between anti-MDA5 positive CADM and rapidly progressive interstitial lung disease seems to be weaker, but the limited numbers of patients described so far could explain the lack of statistical significance. As a fact, European patients with circulating anti-MDA5 autoantibodies may be clinically inhomogeneous and exhibit different rates of severity. The two patients affected by anti-MDA5 positive dermatomyositis described hereafter provide a clear example of the extreme variability of the disease in terms of laboratory findings and clinical features.

Keywords: CADM; Clinically amyopathic dermatomyositis; Dermatomyositis; MDA5.

Fig. 1

Severe involvement of eyelids at the admission into the Dept. (a), after pulse therapy with steroids (b) and during treatment with IVIg, Cyclosporine A and hydroxychloroquine (c)

Fig. 2

Violaceous erythema of the abdomen (a), Gottron’s sign (b), tender palm papules (c) with signs of necrosis (d arrows) of patient #1 at admission

Fig. 3

Disease activity and its relationship with autoantibodies. The graphic shows the relationship between ferritin values (ng/ml black triangles) as index of disease activity, levels of anti-MDA5 antibodies (red dots) and anti-Ro52 kDa (black asterisks both expressed as Arbitrary Levels, AL), as determined by a commercial immunoblot, and therapeutic interventions in patient #1. Normal values of ferritin are below 272 ng/ml (red dotted line), levels of autoantibodies are considered as negative below 10, as indicated by the manufacturer (Euroimmun AG). CS corticosteroids (methilprednisolone, prednisone); CyA cyclosporine A; IVIg immunoglobulins; HyQ hydroxychloroquine. Upward pointing arrow indicates iv pulse therapy