Cutaneous Ulceration in Dermatomyositis: Association With Anti–Melanoma Differentiation–Associated Gene 5 Antibodies and Interstitial Lung Disease

Abstract

Objective To identify clinical and serologic correlates of cutaneous ulcers in dermatomyositis (DM). Methods We retrospectively examined a cohort of 152 DM patients. We compared the features of patients with ulcers to those without ulcers using chi-square or Fisher’s exact tests and used univariate and multivariate logistic regression models to assess the association between ulcers and clinical features such as malignancy, interstitial lung disease (ILD), and amyopathic disease. Results Forty-three patients (28%) had cutaneous ulcers. Nearly half the patients had ulcers present in more than 1 location: 24 (56%) had ulcers over the extensor surfaces of joints, 18 (42%) at the digital pulp or periungual areas, and 25 (58%) had ulcers located elsewhere. In univariate analysis ulcers were associated with Asian race, but not with other clinical and demographic features, including malignancy or ILD. In multivariate analysis ulcers were significantly associated with anti–melanoma differentiation gene 5 (anti-MDA5) antibodies (odds ratio 10.14, 95% confidence interval 1.95–52.78, P = 0.0059) and this was greatest for ulcers located at the digital pulp. In patients with cutaneous ulcers, ILD risk was specifically increased only in patients with anti-MDA5+ antibodies. Conclusion We confirmed the strong association between anti-MDA5 antibodies and cutaneous ulcers, with the novel finding that the association of cutaneous ulcers with ILD depends upon the presence of anti-MDA5 antibodies. DM patients who display this cutaneous phenotype should undergo appropriate evaluation for ILD.

Gottron Papules and Gottron Sign with Ulceration: A Distinctive Cutaneous Feature in a Subset of Patients with Classic Dermatomyositis and Clinically Amyopathic Dermatomyositis

“…A Japanese dermatomyositis cohort showed that skin ulcers are associated with reduced survival, and that the majority of these patients died of ILD 29 . A study has confirmed the strong association between anti-MDA5 antibodies and cutaneous ulcers 28 , and that ulcers are associated with the presence of ILD primarily in anti-MDA5-positive patients.…”

“…However, true vasculitis with fibrinoid necrosis of vessel walls and leukocytoclastic figures was observed in only 3% of the patients with skin necrosis or ulcers. Most of these cases showed obliterative microvasculopathy, such as thickening of vascular wall obstruction or narrowing of vascular lumen or perivascular lymphocytic infiltration 26,28 . In our study, skin biopsy of ulcerative Gottron papules/Gottron sign confirmed the presence of vasculopathy and intraluminal thrombosis.…”

“…In addition, not only is the anti-MDA5 antibody-positive rate associated with the incidence of cutaneous ulcerations, but the antibody level is well correlated with the severity of the cutaneous ulcerations. Several studies demonstrated that the similar obliterative microvasculopathy may be involved in the pathogenesis of ILD in the MDA5-positive patients, and have also postulated a role for endothelial injury in the development of ILD and cutaneous ulcers 28,39,40 . Chaisson, et al suggested that the link between all of these clinical findings was autoimmunity to MDA5 36 .…”

Cutaneous Manifestations in Dermatomyositis: Key Clinical and Serological Features—a Comprehensive Review

“…Fiorentino et al showed that skin ulcerations, palmar papules (inverse Gottron), mechanic's hands, Gottron sign (elbow/knee), hand swelling, diffuse hair loss, panniculitis, and oral pain and/or ulcers were associated with this antibody [36]. They also demonstrated a strong association between location of skin ulcer at the digital pulp/periungual region and this antibody in a subsequent study [37]. Anti-MDA5 antibodies were associated with ILD largely in patients with skin ulcers.…”

Anti-MDA5-Positive Dermatomyositis Presenting as Fever of Unknown Origin

“…[6][7][8][9][10][11] Anti-MDA5-positive-DM patients typically present with prominent skin manifestations, including heliotrope rash, Gottron's papules as well as cutaneous ulceration and tender palmar papules, the latter of which are unique to anti-MDA5-positive-DM (Table 1). 6,[12][13][14] Oral manifestations-including oral ulceration, mucosal pain, and hoarseness-are common, as are arthritis, arthralgia, and fever. 6,7,9,15 This patient initially • Mucosal pain • Alopecia had fever and later developed hoarseness, pharyngeal ulceration, arthritis, and arthralgia.…”