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.

Bench to bedside review of myositis autoantibodies

“…Clinically, DM anti-MDA5 positive patients present low grade/absent muscle inflammation and acute or subacute RP-ILD [ 55 , 56 ], which is considered the major negative prognostic factor of this subgroup [ 57 ].…”

Rapidly progressive melanoma differentiation–associated protein 5–positive amyopathic dermatomyositis in an HIV-positive patient

“…Anti-MDA5 positivity was reported to be associated with a specific presentation of CADM featuring painful ulcerations over extensor surfaces and nailfolds, hyperferritinemia, and frequent treatment-resistant, rapidly progressive ILD associated with poor prognosis 3, 13. Interestingly, MDA5 protein functions as an intracellular pathogen sensor involved in the recognition and mounting of immune response to viral RNA 3, 4. Hence, there could be an association between CADM and viral infections perhaps explaining the incidence of ILD.…”

“…In addition to multiorgan involvement, adult patients with DM may have up to a 30% risk of associated malignancy. Clinically amyopathic DM (CADM) accounts for approximately 20% of all cases and is diagnosed based on the presence of pathognomonic cutaneous involvement 2, 3. Antibody against melanoma differentiation–associated protein 5 (MDA5) was recently found to be specific for CADM associated with rapidly progressive interstitial lung disease (ILD) 4 .…”

Eyelid edema as first manifestation of anti‐MDA5 positive dermatomyositis with rapidly progressive interstitial lung disease: A case report

“…However, anti-MDA5 autoantibodies are associated with inflammatory arthritis and ILD in predominantly Caucasian cohorts, and with rapidly progressive ILD with high mortality rates in East Asian cohorts [2]. Dermatologically this DM subtype has been associated with skin ulceration on extensor surfaces of joints, tender palmar papules (particularly over the metacarpophalangeal or interphalangeal joint creases) and oral pain/ulceration, in addition to classical heliotrope rash, Gottron's sign and shawl sign [4][5][6]. Regarding prevalence, Ceribelli et al carried out a retrospective study in which they detected anti-MDA5 autoantibodies in 5 out of 34 (15 %) consecutive dermatomyositis patients of Caucasian descent [7], although further studies in larger cohorts are required.…”