Patients with anti-SAE+ dermatomyositis display refractory and difficult-to-treat skin manifestations: case series from two Italian cohorts and review of literature.

Aim: We aimed to describe the clinical and serological characteristics of anti-small ubiquitin-like modifier-activating enzyme (SAE)-positive cases from a multicentric cohort of patients affected with idiopathic inflammatory myopathies (IIMs). Methods: Anti-SAE antibody-positive patients (determined by line immunoassay) from a prospective cohort of patients with IIM were retrospectively evaluated. We considered features at disease onset and during follow-up. Muscular involvement was evaluated by the Manual Muscle Test-8, creatine phosphokinase (CK) levels, and/or magnetic resonance imaging; interstitial lung disease (ILD) was evaluated by high-resolution computed tomography; and skin and joint involvement was evaluated by clinical judgment. The therapeutic approach was also reported in all patients, and a literature review was also provided. Results: Out of 170 patients with IIM, 10 (5.9%) were anti-SAE positive, all classified as having dermatomyositis; therefore, among 80 patients with dermatomyositis, the prevalence of anti-SAE antibodies was 12.5%. The female-to-male ratio was 9:1. The median time from onset of symptoms to diagnosis was 1 year (range 0-2 years), and the mean age at onset of symptoms was 55.5 years (range 34-77 years). All patients had skin manifestations, including photosensitive rash, heliotrope rash, and Gottron's sign and/or papules (one with ulcerations). Refractory features requiring multiple lines of immunosuppressants were observed in 60% of cases. Four patients had arthritis and/or inflammatory arthralgia; four had muscular involvement, usually mild; and none had ILD. One patient had a history of malignancy. All patients were treated with glucocorticoids and received different immunosuppressants, including cyclophosphamide. Conclusions: All patients with anti-SAE antibody positivity were classified as having dermatomyositis, with severe and refractory skin manifestations in most cases. One case of malignancy was described; therefore, cancer screening should be warranted in all anti-SAE patients.