Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the unique features of the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. We discuss future directions in better understanding the pathophysiology of and how to better treat pediatric LS.
Sturge-Weber syndrome (SWS) is characterized by capillary malformation, glaucoma, leptomeningeal vascular anomalies, and variable facial overgrowth. The purpose of this study was to document the prevalence and morbidity of facial hypertrophy in 2 cohorts: group 1, surveyed patients registered in the SWS Foundation, and group 2, patients treated at our Vascular Anomalies Center. Predictive variables included age, sex, region of capillary stain, and ocular or cerebral involvement. Outcome variables were soft-tissue and bony overgrowth, as well as the type of operative correction. In group 1, the response rate to our questionnaire was 29.3% (108/368). Facial overgrowth was documented in 60.0% of patients. Soft-tissue hypertrophy was present in 55.0%; the lip (81.0%) was the most commonly affected site. Skeletal hypertrophy was reported in 22% of patients; the maxilla (83.0%) was the most frequently overgrown bone. Overall, 23.0% of patients (36.5% with overgrowth) had an operation: 34.0% of patients with soft tissue hypertrophy and 9.0% with skeletal enlargement. In group 2, 47 patients with SWS were treated at our center: 83% had facial overgrowth, either a localized cutaneous lesion (18.0%), soft-tissue enlargement (70.0%), or bony hypertrophy (45.0%). As in group 1, the lip (75.0%) and maxilla (94.0%) were the most commonly enlarged structures. Operations were necessary for localized cutaneous lesions (86.0%), soft-tissue hypertrophy (53.0%), or skeletal overgrowth (11.0%). In conclusion, facial hypertrophy is a major component of SWS; these patients should be counseled about the risk of overgrowth and about the types of possible operative correction.
Juvenile-onset systemic sclerosis (jSSc) is a rare and severe autoimmune disease with associated life-threatening organ inflammation and evidence of fibrosis. The organ manifestations of jSSc resemble adult SSc, but with better outcomes and survival. The etiology of jSSc appears to reflect adult-onset SSc, with similar inflammatory mediators and autoantibodies, but with a significant population of children with uncharacterized anti-nuclear antibodies. The genetics of patients with jSSc differ from women with SSc, resembling instead the genes of adult males with SSc, with additional HLA genes uniquely associated with childhood-onset disease. Current treatments are aimed at inhibiting the inflammatory aspect of disease, but important mechanisms of fibrosis regulated by dermal white adipose tissue dendritic cells may provide an avenue for targeting and potentially reversing the fibrotic stage.
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