Background/Purpose

Localized scleroderma (LS) is an autoimmune disease characterized by inflammation of the skin and underlying tissue leading tissue damage including atrophy, dyspigmentation, and fibrosis.  More recent literature supports childhood-onset LS as a chronic relapsing condition which may cause significant physical and psychological disability into adulthood.  Often, initial control of the disease is obtained using systemic therapy regimens including methotrexate (MTX) combined with a corticosteroid (CS).  For unknown reasons, patients may exhibit a relapse of LS activity following a period of disease remission.  This study was designed to evaluate the clinical characteristics of patients exhibiting LS flares after an initial disease response (inactive disease) to a standardized MTX and CS regimen with the goal of identifying predictors of LS activity relapse.

Methods

Pediatric-onset LS patients at a single scleroderma center with at least 2 years of follow-up and three or more clinical visits were included in the analysis.  Clinical data, including patient demographics, laboratory parameters, and treatment regimens were evaluated. Flare of LS was defined as a relapse of disease activity from inactive disease, as determined by the modified Localized Scleroderma Severity Index (mLoSSI) and the Physician Global Assessment of Disease Activity.  Chi-square and Fisher’s Exact test were used to compare rates of categorical variables, and independent sample t-tests were used to compare continuous variables between groups (α < 0.05).

Results

Seventy-seven patients were followed for greater than two years and 35 patients (46%) were found to experience LS flare after an initial response to MTX and CS.  Demographic and laboratory data are summarized in Table 1.  Patients that flared were significantly older at age of onset and were more likely to be ANA positive.  Unexpectedly, flare patients were less likely to have an extracutaneous manifestation (ECM). 

^{*Laboratory parameters not obtained for all patients}

Conclusion

Our assessment of a cohort of LS patients has shown older age at onset of disease and ANA positivity to be potential risk factors for reactivation of disease.  ANA positivity may reflect a higher propensity for immune system reactivity after disease remission, and older onset might indicate that the immune system is more developed, hindering a sustained the effect of treatment.  Surprisingly, the presence of joint contractures and other accepted measures of LS severity do not seem to represent an inherent risk of flare after disease remission.  A possible explanation may be closer patient follow-up and adherence to medication regimen given physician’s judgment of more severe disease when an ECM is present. We suggest that these risk factors, ANA positivity and older age of onset, serve as indicators for more extensive treatment or follow-up to avoid disease flare in at-risk LS patients.