Interferon signature guiding therapeutic decision making: ruxolitinib as first-line therapy for severe juvenile dermatomyositis?

Abstract

Dear Editor, JDM is a rare systemic inflammatory disorder of childhood primarily affecting muscles and skin, which is associated with vasculopathies and a constitutive type I IFN activation [1]. Patients with positive anti-nuclear matrix protein-2 (NXP2) autoantibodies account for ∼25% of JDM cases, and this is associated with calcinosis and severe muscle disease [2]. Standard immunosuppressive treatments do not always control severe JDM and may have serious side effects. We report the case of a 14-year-old boy with NXP2-positive JDM. He is the second child of non-consanguineous Caucasian parents without a family history of rheumatic diseases. He was first diagnosed with JDM at the age of 3 years. After almost 10 years in remission, he experienced a severe relapse, which was initially treated with prednisolone (2 mg/kg/d), HCQ (200 mg/d) and MTX (15 mg/m2) for 6 weeks. When transferred to our center, swallowing difficulties due to severe myositis required monitoring in the intensive care unit. Furthermore, he presented with classical heliotrope and erythematous rash on his cheeks, eyelids and upper sternum, pronounced symmetrical muscular weakness leaving him bedridden. His initial Childhood Myositis Assessment Scale (CMAS) score was six out of a possible 52. Laboratory investigations revealed highly elevated levels of creatinine kinase activity (116 µmol/second×l; normal range <3.17), myoglobin (955 µg/l; normal range <72) and von-Willebrand antigen (>400%; normal range 59.6–210.5), along with a strong IFN signature (score of 864.53; normal range <12.49), consistent with the diagnosis of relapsed JDM (Fig. 1A) [3]. MRI of the lower extremities showed severe myositis with partial fatty muscle atrophy (Fig. 1B).

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