Methotrexate treatment in juvenile localized scleroderma: A randomized, double-blind, placebo-controlled trial

Abstract

Objective. Juvenile localized scleroderma is a chronic progressive fibrotic disorder of the skin that causes permanent disability and aesthetic damage. This study was undertaken to assess the safety and efficacy of methotrexate (MTX) in the treatment of juvenile localized scleroderma.Methods. In this double-blind study, patients with active juvenile localized scleroderma were randomized (2:1) to receive oral MTX (15 mg/m 2 , maximum 20 mg) or placebo once weekly, for 12 months or until treatment failure. Both groups received oral prednisone (1 mg/kg/ day, maximum 50 mg) for the first 3 months. A target lesion was evaluated clinically, with infrared thermography and using a computerized scoring system with skin score rate (SSR) evaluation. Response to treatment was defined as the absence of new lesions, SSR <1, and a decrease in lesion temperature of at least 10% compared to baseline. Treatment failure was defined as the occurrence of new lesions, SSR >1, or increased lesion temperature. All analyses were done on the intent-totreat population.Results. Of the 85 patients screened, 70 (ages 6-17 years) were randomized (46 to the MTX group, 24 to the placebo group). The mean disease duration was 2.3 years. After an initial response in all patients, disease relapsed in 15 MTX-treated patients (32.6%) and 17 placebo-treated patients (70.8%) (P < 0.005). New lesions appeared in 3 MTX-treated patients (6.5%) versus 4 placebo-treated patients (16.7%). The mean SSR decreased from 1 to 0.79 in the MTX group and increased from 1 to 1.1 in the placebo group, and the mean target lesion temperature decreased by 44.4% in the MTX group versus 12.1% in the placebo group. Twenty-six patients in the MTX group (56.5%) and 11 patients in the placebo group (45.8%) developed mild side effects related to treatment. None of the side effects were severe enough to necessitate treatment discontinuation.Conclusion. Our findings indicate that MTX is efficacious in the treatment of juvenile localized scleroderma and is well tolerated.

Scleroderma: Nomenclature, etiology, pathogenesis, prognosis, and treatments: Facts and controversies

“…50 If systemic immunosuppression is required, treatment with methotrexate in combination with a prednisone taper is supported by the strongest data. [71][72][73][74] In adults with morphea there is data showing improvement with methotrexate alone. 75 Linear morphea of the extremities, as well as the head and neck, should be treated aggressively, particularly in children given the significant morbidity associated with untreated disease.…”

“…Based on data from a randomized placebocontrolled trial, prospective case series, and expert opinion, linear morphea should be treated with methotrexate and a taper of systemic corticosteroids. [49][50][51][71][72][73][74] In some instances, linear morphea is a superficial process that does not involve the underlying tissues. In these cases, topical therapies noted above or phototherapy are appropriate treatment options.…”

A long-term follow-up study of methotrexate in juvenile localized scleroderma (morphea)

“…7 During the 12-month study period, new scleroderma lesions appeared in 6.5% of the patients on MTX compared with 16.7% of those treated with prednisone alone.…”

Overlap between linear scleroderma, progressive facial hemiatrophy and immune-inflammatory encephalitis in a paediatric cohort

“…For localized scleroderma, a randomized therapeutic trial did demonstrate a beneficial effect of methotrexate in association with systemic steroids [20], but the efficacy of this combination in PFH has not been convincingly demonstrated. Some case reports suggest a positive effect of immunosuppressive therapy for PFH [8], but in other patients, those therapies did not prove to be helpful.…”