IN juvenile localized scleroderma, mycophenolate mofetil matched methotrexate in lowering activity, and had fewer fatigue symptoms.
Juvenile Localized Scleroderma Treatment Response
Juvenile localized scleroderma (JLS) is a rare, potentially disabling inflammatory skin disease, and there are currently no US Food and Drug Administration approved therapies for this population. Methotrexate is commonly used as first line systemic therapy, while mycophenolate mofetil has gained attention from small case series and from use in systemic sclerosis, where clinicians often weigh efficacy against long term tolerability.
A retrospective cohort study evaluated treatment response in clinician diagnosed juvenile localized scleroderma among participants in the National Registry of Childhood Onset Scleroderma. All patients were managed and followed by the same physician at UPMC Children’s Hospital of Pittsburgh, using consistent assessment practices. The analysis included data collected from January 2010 to January 2023, with first analyses performed in April 2023.
Investigators compared methotrexate monotherapy, mycophenolate mofetil monotherapy, and combination therapy of both agents. Treatment response was assessed through changes in disease activity using the Localized Scleroderma Cutaneous Assessment Tool, a standardized measure designed to track activity over time.
Tolerability Differences Between Methotrexate and Mycophenolate Mofetil
Among 114 patients with juvenile localized scleroderma, 68 received methotrexate, 28 received mycophenolate mofetil, and 18 received combination therapy. Baseline demographic characteristics, disease subtype, and disease severity did not differ significantly across groups, although the mycophenolate mofetil group had a longer disease duration.
Across all treatment strategies, mixed effects modeling showed statistically significant reductions in disease activity over follow up. Flare rates were also similar, with Kaplan Meier analysis showing no significant difference in time to flare between methotrexate and mycophenolate mofetil.
Notably, symptom burden differed. Patients treated with methotrexate reported higher rates of fatigue and nausea compared with those treated with mycophenolate mofetil. These tolerability findings, alongside comparable activity and flare outcomes, support mycophenolate mofetil as a potential first line option for juvenile localized scleroderma, while underscoring the need for prospective randomized noninferiority trials to confirm effectiveness and inform practice.
Reference: de Rosas EC et al. Methotrexate and Mycophenolate Mofetil and Clinical Response in Juvenile Localized Scleroderma. JAMA Dermatology. 2026;doi:10.1001/jamadermatol.2025.5662.
