Psoriasis is a common chronic immune-mediated inflammatory skin disorder and begins in childhood in almost one-third of the cases. Although children present with the same clinical subtypes of psoriasis seen in adults, lesions may differ in distribution and morphology, and their clinical symptoms at presentation may vary from those reported by adult patients. Nevertheless, diagnosis of psoriasis is primarily based on clinical features. Pediatric psoriasis can have a profound long-term impact on the psychological health of affected children. Additionally, pediatric psoriasis has been associated with certain comorbidities, such as obesity, hypertension, hyperlipidemia, diabetes mellitus and rheumatoid arthritis, making early diagnosis and management essential. As guidelines are lacking and most (systemic) treatments are not approved for use in children, treatment of pediatric psoriasis remains a challenge. A prospective, multicenter, international registry is needed to evaluate these treatments in a standardized manner and ultimately to develop international guidelines on pediatric psoriasis. This article reviews current concepts in pediatric psoriasis including epidemiology, clinical features, diagnosis, the role of topical and systemic agents and the association with other morbidities in childhood.

The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies.

Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud’s phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.

Objective Investigate the relationship of excess and central adiposity with pediatric psoriasis severity. Design, Setting and Participants Multi-center, cross-sectional study of 409 psoriatic children. Psoriasis was classified as mild (worst Physician’s Global Assessment (PGA) <3 with body surface area (BSA) <10%) or severe (worst PGA >3 with BSA >10%). Children were enrolled from 9 countries July 2009-December 2011. Main Outcome Measures Excess adiposity (body mass index (BMI) percentile) and central adiposity (waist circumference (WC) percentile and waist-to-height ratio). Results Excess adiposity (BMI >85th percentile) occurred in 37.8% (n=155) of psoriatics vs. 20.5% (n=42) of controls, but did not differ by severity. The odds of obesity (BMI >95th percentile) overall in psoriatics vs. controls were OR=4.29, 95% CI=1.96-9.39, but were higher with severe (OR=4.92, CI=2.20-10.99) than mild (OR=3.60, CI=1.56-8.30) psoriasis, particularly in the U.S. (OR=7.60, CI=2.47-23.34, and OR=4.72, CI=1.43-15.56, respectively). WC >90th percentile occurred in 9.3% (n=19) of controls, 14.0% (n=27) of mild, and 21.2% (n=43) of severe psoriatics internationally, and especially in the U.S. (12.0% of controls, 20.8% of mild, and 31.1% of severe psoriatics). Waist-to-height ratio was significantly higher in psoriatic (0.48) vs. control (0.46) children, but unaffected by psoriasis severity. Children with severe psoriasis at their worst, but mild at enrollment, showed no difference in excess or central adiposity from children who remained severe at enrollment. Conclusion Globally, children with psoriasis have both excess adiposity and increased central adiposity, regardless of severity. The increased metabolic risks associated with excess and central adiposity warrant early monitoring and lifestyle modification.

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis.

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NCT02067962; Results.