Juvenile localized scleroderma (jLS) is a rare chronic inflammatory and fibrosing disorder associated with considerable morbidity (1
). Differences in disease subtype, duration, and long-term sequelae associated with jLS result in a more severe disease phenotype than is seen in adult-onset LS. For example, linear scleroderma, the most common jLS subtype, frequently affects muscle and bone in addition to skin, while the most common adult subtype, circumscribed superficial morphea (i.e., plaque morphea), is typically confined to the dermis (3
). Mean disease duration has been reported to be twice as long for jLS than adult-onset disease (13.5 versus 5.8 years) (5
), and both relapsing and chronic-active disease are reported at relatively high frequency. Two recent pediatric studies documented recurrence rates of 28-44% at a mean of 16-20 months after discontinuing methotrexate, and a study of adults with childhood-onset disease reported a recurrence rate of 59% (6
). Continuously active disease was reported in 30% of adults with childhood-onset LS (8
), while another study reported active disease in 20% of jLS patients after 20 years (9
). In addition, over 20% of jLS patients develop extracutaneous manifestations (ECM), including arthritis, seizures, and uveitis (4
Because jLS can present early in development and persist for years, the morbidity of jLS can be substantial. Children with jLS are at risk for major growth disturbance, including limb length differences, joint contractures, and facial atrophy. Review of a prospective registry of >100 jLS patients found that 38% had muscle atrophy, limb shortening, hemifacial atrophy, and/or joint contractures, and 25% had limited functional capacity (11
). In a long term follow-up study of jLS patients, 25% reported mild to moderate disability after 20 years (9
). Similarly, in a study of adults with childhood-onset LS, more than 50% reported permanent sequelae, including limited range of motion, deep tissue atrophy, and limb length differences (8
Optimal therapy for jLS is not known. The lesions of jLS are characterized histologically by an early inflammatory stage followed by late stage fibrosis resulting in replacement of normal structures by abnormal collagen (1
). A variety of therapeutic strategies for jLS have been proposed; however, the majority of published reports are case series with only a few comparative or placebo-controlled studies described (12
). There is a profound lack of consensus on treatment among clinicians involved in the care of patients with jLS. To begin, there is a substantial division in therapeutic choices between subspecialty services receiving referrals for jLS, with pediatric rheumatologists treating disease beyond superficial circumscribed plaque morphea primarily with methotrexate (MTX) and systemic corticosteroids (CS), while dermatologists commonly utilize topical agents and phototherapy (6
). Even more striking, when asked to detail their recommendations for treatment of a hypothetical patient with moderate to severe linear scleroderma, pediatric rheumatologists in the U.S. and Canada reported a nearly complete absence of agreement on details of the treatment regimens employed. Although more than 95% recommended MTX and CS for treatment in a linear scleroderma case vignette, when dose, route of administration, duration of treatment, and tapering or maintenance schedule were considered, there were 82 discrete MTX and 86 unique CS regimens described by 114 responders () ((15
), and unpublished data). In effect, the majority of clinicians are following their own unique protocol for treatment of jLS, making it impossible to establish a valid comparison of outcomes.
Standardization of corticosteroid and methotrexate treatment regimens for juvenile localized scleroderma
An important limitation in the design and assessment of treatment studies in jLS, and a major source of variability in clinical practice, has been the lack of specific biomarkers and an absence of agreement on standards for quantifying disease activity and damage (19
). Although several clinical assessment methods have been published, including the DIET (Dyspigmentation, Induration, Erythema, Telengiectasias) score, modified Rodnan Skin Score (mRSS), and Localized Scleroderma Skin Index (LoSSI) (21
), all of these are severity measures, assessing activity and damage together, and each evaluates only a limited subset of the clinical parameters reported to reflect changes in disease state. Furthermore, the lack of validated treatment response criteria limits the ability of clinicians to make judgments regarding the efficacy of treatments.
In the interest of standardizing clinical practice and to establish a basis for the design and conduct of comparative effectiveness studies in pediatric rheumatic disorders, members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) have established a series of workgroups tasked with developing standardized clinical assessment and management plans (consensus treatment plans, CTPs). The aim is to develop CTPs that are consistent with best available evidence in the literature and differ only modestly from current practice for the majority of patients among the majority of participating clinicians, such that physicians will feel comfortable using the developed CTPs to treat their patients. Limiting practice variability in this fashion will allow comparison of data from diverse providers and enable the development of evidence-based standards of care.