Pulsed High-Dose Corticosteroids Combined With Low-Dose Methotrexate in Severe Localized Scleroderma

Abstract

Setting: Dermatology department at a university hospital in Bochum, Germany.Patients: Fifteen patients with histologically confirmed severe LS.Interventions: Oral methotrexate (15 mg/wk) combined with pulsed intravenous methylprednisolone (1000 mg for 3 days monthly) for at least 6 months.Main Outcome Measures: Treatment outcome was evaluated by means of a clinical score, 20-MHz ultrasonography, and histopathologic analysis. Safety assess-ment included the monitoring of adverse effects and clinical laboratory parameters.Results: One patient discontinued therapy. In most of the remaining 14 patients, significant elimination of all signs of active disease (inflammation) and remarkable softening of formerly affected sclerotic skin that resulted in a decrease of the mean±SD clinical score from 10.9±5.3 at the beginning to 5.5±2.5 at the end of therapy was observed (PϽ.001). Clinical improvement was confirmed by histologic and ultrasonographic assessments. No serious adverse effects were noted.Conclusions: These data suggest that pulsed high-dose corticosteroids combined with orally administered lowdose methotrexate therapy is beneficial and safe in the treatment of patients with LS. This treatment regimen should especially be considered for severe forms of LS in which conventional treatments have failed.

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

“…In our study, MTX was effective in more than two-thirds of patients, and the rate of efficacy was significantly higher than in the placebo group, in which a short course of prednisone was able to control the disease process in fewer than one-third of the patients (P ϭ 0.001). Our findings partially confirm those of previous retrospective studies in children, in which the rate of response to MTX ranged between 71% and 94% (4)(5)(6)(7)(8)27). However, the numbers of patients in those studies were small, the studies were not randomized controlled trials, and the outcome measures were mainly based on the subjective judgment of the physician.…”

“…The treatment response with definite clinical improvement in both arms of our study corresponds well with outcomes previously reported (4)(5)(6)27). In the only study in which oral corticosteroids (prednisone 0.5-1 mg/kg/day) were used as monotherapy, improvement was shown in most patients, with remission achieved in as many as 23.5% (19).…”

“…Furthermore, no patient discontinued MTX therapy due to adverse events. Over the years, many treatments of localized scleroderma have been reported, including topical and systemic corticosteroids (18,19), topical and systemic calcipotriol (18,(20)(21)(22), topical tacrolimus (23), interferon-␥ (24), phototherapy (25,26), and methotrexate (4)(5)(6)(7)(8)27,28). Only 2 double-blind placebo-controlled studies, both in adult patients, have been reported, and, perhaps because of small sample size and Type II error, neither demonstrated superior benefit of the tested treatment compared to placebo (22,24).…”

“…A few studies have demonstrated efficacy with MTX or oral corticosteroids as monotherapy for localized scleroderma (19,28), but in most recent studies these medications have been combined, with corticosteroids administered more commonly by an intravenous route than orally (4)(5)(6)(7)(8)27,28). In our study, MTX was effective in more than two-thirds of patients, and the rate of efficacy was significantly higher than in the placebo group, in which a short course of prednisone was able to control the disease process in fewer than one-third of the patients (P ϭ 0.001).…”

Laser Doppler flowmetry for assessing localized scleroderma in children

“…In children, the current treatment for severe localized scleroderma is a combination of systemic corticosteroids and low-dose methotrexate (5)(6)(7)(8). The management of severe localized scleroderma is challenging, and the detection of disease activity remains a fundamental problem, both in the evaluation of the need for treatment and the assessment of therapeutic efficacy over time.…”