Autoinflammatory Diseases/Periodic Fevers.

Children with intermittent fevers present to pediatricians and other primary care child health providers for evaluation. Most patients will have self-limited, benign infectious illnesses. However, the possibility of a periodic fever syndrome should be considered if febrile episodes become recurrent over an extended period and are associated with particular signs and symptoms during each attack. This review discusses the current conceptualization of autoinflammatory diseases with specific focus and detail on familial Mediterranean fever; tumor necrosis factor receptor-associated periodic syndrome; mevalonate kinase deficiency; NLRP3-associated autoinflammatory disease; and periodic fever, aphthous stomatitis, pharyngitis, and adenitis. The genetic mutations associated with these clinical entities are identified, along with the historical nomenclature that predates the current pathogenetic understanding of these diseases. The episodic signs and symptoms seen across these periodic fever syndromes can be overlapping, but there are some distinguishing features that can be useful, and these are described. The disease course and potential complications, particularly amyloidosis, which is a variable risk in these conditions and a potential source of significant morbidity and mortality, are addressed. Treatment strategies are outlined, highlighting the advances in therapy that have resulted from the advent of proinflammatory cytokine-targeting biological agents.

Transcriptomic Evaluation of Juvenile Localized Scleroderma Skin With Histologic and Clinical Correlation.

OBJECTIVE: Juvenile localized scleroderma (LS) is an autoimmune disease of the skin whose pathogenesis is not well understood due to the rarity of the disease. This study was undertaken to determine the skin transcriptome in skin biopsy tissue from children with juvenile LS compared to pediatric healthy controls, with identification of significant molecular targets using RNA sequencing (RNA-Seq). In this study, differentially expressed genes (DEGs) were assessed for correlations with histopathologic and clinical features in children with juvenile LS, and were used to group the children into distinct genetic clusters based on immunophenotype. METHODS: RNA-Seq was performed on sections of paraffin-embedded skin tissue obtained from 28 children with juvenile LS and 10 pediatric healthy controls. RNA-Seq was carried out using an Illumina HTS TruSeq RNA Access library prep kit, with data aligned using STAR and data analysis using a DESeq2 platform. A standardized histologic scoring system was used to score skin sections for the severity of inflammation and levels of collagen deposition. Histologic scoring was completed by 2 pathologists who were blinded with regard to the status of each sample. Spearman's rank correlation coefficients were used to assess significant correlations between DEG expression profiles and skin histologic findings in patients with juvenile LS. RESULTS: We identified 589 significant DEGs in children with juvenile LS as compared to healthy controls. Hierarchical clustering was used to demonstrate 3 distinct juvenile LS immunophenotype clusters. The histologic scores of skin inflammation (based on numbers and categories of inflammatory cell infiltrates) were significantly correlated with the expression levels of HLA-DPB1, HLA-DQA2, HLA-DRA, and STAT1 genes (rs > 0.5, P < 0.01). Collagen thickness correlated with the expression levels of collagen organization genes as well as with genes found to be correlated with the severity of inflammation, including genes for major histocompatibility complex (MHC) class I, MHC class II, and interferon-γ signaling. CONCLUSION: Among children with juvenile LS, 3 distinct genetic signatures, or clusters, were identified. In one cluster, inflammation-related pathways were up-regulated, corresponding to the histologic skin inflammation score. In the second cluster, fibrosis-related pathways were up-regulated. In the third cluster, gene expression in the skin corresponded to the patterns seen in healthy controls. Up-regulation of HLA class II genes was observed within the first cluster (characterized by predominant inflammation), a feature that has also been observed in the peripheral blood of patients with morphea and in the skin of patients with systemic sclerosis.

Linear Scleroderma of the Head - Updates in management of Parry Romberg Syndrome and En coup de sabre: A rapid scoping review across subspecialties.

To provide an update on the current management, including evaluation and treatment, and the available diagnostic tools for linear scleroderma of the head, i.e., Parry-Romberg Syndrome and en coup de sabre (PRS/ECDS). A rapid scoping review of the literature was conducted to include manuscripts published in English between 2010 and 2019. Literature searches were performed in PubMed and EMBASE databases. The were analyzed for descriptive statistic reporting. This study reviewed 215 manuscripts reporting these 1430 patients. Surgical reports comprised the majority of the reviewed literature. Most PRS/ECDS did not appear to receive comprehensive multisubspecialty evaluation for extracutaneous manifestations; 21% of cases noted neurological screening, 4% noted dental screening, and 3% noted ophthalmologic screening. Methotrexate and glucocorticoids remain the most frequent choice for immunosuppressive treatment, though fewer than 7% of patients reported receiving systemic medical therapies. Surgical procedures for cosmetic or functional improvement were common (59%) among the reported patients. Autologous fat grafting was the most frequently utilized cosmetic treatment (50% of procedures) followed by free flap transfers (24% of procedures). There is ongoing need for standardized evaluation, monitoring, and treatment to prevent morbidity in PRS/ECDS, especially in children. When these patients are managed by rheumatologists, methotrexate, and steroids remain the first-line treatment, but a review of the published literature reflects that this may be a minority. Most PRS/ECDS patients are not evaluated in a multidisciplinary fashion. We propose comprehensive evaluations across subspecialties at the baseline and follow-up levels to monitor disease activity and record extracutaneous manifestations, treatment algorithms, and surgical intervention considerations.