Extracutaneous Involvement Is Common and Associated with Prolonged Disease Activity and Greater Impact in Juvenile Localized Scleroderma

Objective To evaluate factors associated with extracutaneous involvement (ECI) in juvenile localized scleroderma (jLS). Methods A prospective, multi-center, 6-month observational study was performed. Collected data included disease features, global assessments, and subject symptoms. Bivariate and linear multilevel regression analyses were performed. Results Eighty-six jLS subjects (80% female, 80% Caucasian), median age of disease onset 7.7 years, were evaluated. Most had linear scleroderma or mixed morphea. Fourty-nine subjects (57%) had 125 extracutaneous problems (median 2 (IQR 1, 3) per subject) from 9 organ systems. Most of these subjects had multiple musculoskeletal problems. ECI was associated with more extensive cutaneous involvement, higher number of symptoms, family history of autoimmunity, and ANA and rheumatoid factor positivity. Subjects with ECI had higher scores for physician global assessment of damage (PGA-D), and parental global assessment of disease impact, but not baseline physician global assessment of disease activity (PGA-A). Although subjects with ECI received more methotrexate and glucocorticoid treatment, they had a slower reduction in PGA-A scores and symptoms over time, suggesting a poorer response to treatment. In logistic regression modeling, female sex had the largest effect on parental impact scores. Conclusions ECI occurred in the majority of subjects with jLS, and was associated with more medication use, longer treatment duration, higher PGA-D scores, and higher parental assessment of disease impact. Our findings suggest that jLS subjects with ECI have greater overall disease burden, both cutaneous and extracutaneous, and poorer response to treatment. More study of the treatment needs of this population is warranted.

Preliminary Evidence on Abatacept Safety and Efficacy in Refractory Juvenile Localized Scleroderma

Objectives To evaluate the safety and efficacy of abatacept treatment for refractory juvenile localized scleroderma (jLS) in a retrospective study. Methods A multicentre cohort study was performed to evaluate jLS subjects treated with abatacept with follow-up for 12 months to maximum of 24 months. Assessments at 6 month intervals included skin activity measures and physician global assessment of activity (PGA-A). Descriptive statistical analysis was performed. Results Eighteen subjects were studied with median age 13.4 years, the majority had linear scleroderma subtype, and musculoskeletal involvement. All had previously failed methotrexate and/or mycophenolate mofetil (MMF) treatment and glucocorticoids. Abatacept was added to the subject’s maintenance DMARD treatment; 13 also received glucocorticoids at start of abatacept. No serious adverse events occurred. Skin activity and PGA-A scores declined in nearly all by 6 months and continued to improve from 6 to 12 months. At 12 months, 15 (83%) subjects were considered responders, two (11%) treatment failures, and one dropped out for adverse event. Response was sustained for 11 (61%) subjects to 18 months and 8 (44%) to 24 months. Overall, 4 (22%) subjects were treatment failures and 3 (16.7%) discontinued abatacept for adverse event. Active musculoskeletal problems improved in most affected subjects. Ten subjects were able to discontinue initial glucocorticoid and 6 concomitant DMARD treatment. Conclusion Abatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept’s efficacy.

Mycophenolate mofetil for methotrexate-resistant juvenile localized scleroderma

Objectives To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma. Methods Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan–Meier analysis. Results MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy. Conclusion The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment.

Juvenile Localized Scleroderma. Questions of Treatment

Juvenile localized scleroderma (JLS) is a group of childhood diseases with the main symptom — skin and subcutaneous structures lesions, without any organ involvement. There is active (inflammatory) and fibrotic phase in development of JLS. The JLS treatment during active phase (when skin lesions are reversible) is the most effective. The management is determined by the area and depth of skin lesions, appearance and spread of new lesions, presence of extracutaneous signs of the disease. Topical and systemic immunosuppressants are the basic therapy for JLS. The use of antibiotics is not suggested. Clinical scores (LoSCAT), ultrasound, thermography and magnetic resonance imaging are recommended to estimate the treatment efficacy.