When Interferon Interferes: Updates in Childhood Connective Tissue Disease

Dr. Vikash Oza presented information about the diagnosis and treatment of children with connective tissue diseases, including juvenile dermatomyositis (JDM) and chronic cutaneous lupus (CCL). In multidisciplinary settings, dermatologists play an important role in the early identification, treatment, and monitoring of systemic diseases with cutaneous manifestations. Treatment for refractory skin disease in the setting of childhood connective tissue disease is often off label.

First, Oza described the clinical presentation, diagnosis, and treatment of JDM and CCL. JDM commonly presents with a malar rash, Gottron papules, and erythema on the knuckles. It typically begins around age 5–10 years. In some children, the disease lasts 2–3 years and resolves; others have multiple relapses or chronic disease. The work-up for JDM should include multiple muscle enzymes, as they are not always elevated. Myositis-specific antibodies may indicate a patient’s risk for additional complications, including calcinosis, ulceration, and interstitial lung disease.

First-line treatment for JDM includes methotrexate and systemic steroids. Muscle enzyme levels and function tend to improve within a few months of treatment; skin manifestations may persist for more than 1 year. Hydroxychloroquine is second-line treatment for JDM; its definitive impact on skin disease in JDM is debated but it may be used if the patient has a history of photosensitivity. Additional treatment options include intravenous immunoglobulin (IVIG), mycophenolate mofetil (MMF), azathioprine, and Janus kinase (JAK) inhibitors.

Cutaneous manifestations of lupus commonly affect the face; lesions may be indurated and appear in an annular pattern. Dr. Oza emphasized that not all children with discoid lupus erythematosus (DLE) have systemic lupus erythematosus (SLE). DLE is more likely to become systemic in patients with an older age of onset and widespread DLE. Treatment options include topical or intralesional steroids, hydroxychloroquine plus quinacrine, IVIG, MMF, methotrexate, thalidomide/lenalidomide, belimumab, and JAK inhibitors.

Second, Oza discussed the role of type 1 interferons (IFN1s) in skin diseases, including JDM and CCL. IFN1s are known for their role in detecting nucleic acids and fighting viral infections; the upregulation of IFN1 has been implicated in skin diseases, including JDM and CCL. IFN1 represents a potential therapeutic target for these diseases.

Third, Oza presented the case of a 9-year-old female with JDM who initially presented with muscle weakness and swelling without cutaneous symptoms. Despite aggressive treatment, after 8 months, the patient returned with severe weight loss, deep ulcers, interstitial lung disease, and profound muscle weakness that restricted her mobility. Endoscopy identified esophageal ulcers and an intestinal perforation that required a peritoneal drain.

Oza and a multidisciplinary team applied to the FDA for compassionate use of an experimental anti-IFNβ therapy (dazukibart). Improvement was seen in the skin and muscles 4 weeks after the first infusion. Two years later, the patient remains on dazukibart with no skin or muscle involvement. However, the patient developed calcinosis cutis that requires ongoing monitoring.

Finally, Oza showed additional cases demonstrating the efficacy of the anti-IFN therapy, anifrolumab, in patients with CCL, SAVI (STING-Associated Vasculopathy with onset in Infancy) syndrome, and CANDLE (Chronic Atypical Neutrophilic Dermatitis with Lipodystrophy and Elevated temperature) syndrome.

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