Reduced H3K27me3 Expression Is Common in Nodular Melanomas of Childhood Associated With Congenital Melanocytic Nevi But Not in Proliferative Nodules.

The formation of a nodule within a congenital melanocytic nevus (CMN) raises concerns about possible melanoma. Most new nodular growths that develop during childhood, however, are benign proliferative nodules (PN); melanoma is very rare. The distinction of melanoma from PN can at times be difficult clinically and histopathologically, requiring ancillary molecular tests for diagnosis. Although the application of molecular methods has revealed new insights into the mutational and genomic landscape of childhood melanomas, little is known about epigenetic events that may drive the growth of a melanoma or PN in a CMN. In this study we compared the expression of H3K27me3, a key regulator in chromatin remodelling-controlled transcription, in PNs and pediatric nodular melanomas arising within medium-sized to large CMN by immunohistochemistry. Significant loss of H3K27me3 expression was seen in 4 of 5 melanomas, but not in any of the 20 PNs. This observation suggests that epigenetic events likely play a role in the pathogenesis of melanoma developing in the dermis or subcutis of CMN. Furthermore, assessing for H3K27me3 expression by immunohistochemistry may be diagnostically useful for problematic cases.

From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis.

BACKGROUND: An urgent need exists in the United States to establish treatment goals in psoriasis. OBJECTIVE: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. METHODS: The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. RESULTS: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. LIMITATIONS: Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. CONCLUSION: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.

Beyond Psoriasis: Novel Uses for Biologic Response Modifiers in Pediatric Dermatology.

Dermatologists have witnessed the increasing availability of novel biologic response modifiers for the treatment of inflammatory and autoimmune diseases in recent years. The most common dermatologic indication for the use of biologic response modifiers in adults is psoriasis, but the U.S. Food and Drug Administration has not approved any of these agents for use in any dermatologic disease in children with the exception of omalizumab, and as such, use in this population is considered off-label. In this review, we focus on the use of these agents in children to treat inflammatory skin diseases other than psoriasis, including atopic dermatitis, hidradenitis suppurativa, pemphigus vulgaris, bullous pemphigoid, and toxic epidermal necrolysis, with an emphasis on the use of etanercept, infliximab, rituximab, omalizumab, and ustekinumab. By highlighting novel uses of these agents, particularly for the treatment of dermatologic conditions for which optimal therapies are yet to be established, we hope to raise awareness of the potential use of this class of medications to treat inflammatory skin diseases in children.

Obesity and the metabolic syndrome in pediatric psoriasis.

Psoriasis is a common, chronic inflammatory dermatosis that often has its onset during childhood. There is increasing evidence that psoriasis in adults is associated with obesity, the metabolic syndrome, and associated comorbidities, including insulin resistance/type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. This association is postulated to arise, at least in part, as a result of a systemic proinflammatory state that is mediated by adipose tissue. Several recent observational studies suggest that children and adolescents with psoriasis may be at increased risk of being overweight and obese as well as having an increased risk for features of the metabolic syndrome. Such an association raises concern with regards to the long-term health implications for children and adolescents with psoriasis and suggests that better awareness, evaluation, and management of overweight and obese patients and associated metabolic disease are warranted in this population.

Biologic response modifiers and pediatric psoriasis.

The efficacy and safety of biologic response modifiers such as etanercept, adalimumab, infliximab, and ustekinumab have been demonstrated in the treatment of psoriasis in adults, but none are currently approved for the treatment of psoriasis in children in the United States, and only etanercept is approved for the treatment of psoriasis in children in the European Union. Through case reports, case series, and a large clinical trial of the use of etanercept, the literature supports the use of these agents to treat psoriasis in children. Data on the use of the tumor necrosis factor-α antagonists etanercept, adalimumab, and infliximab in the treatment of other inflammatory diseases in children-namely Crohn's disease, juvenile arthritis, and uveitis--support their safety profile in children.

Psoriasis in childhood: effective strategies to improve treatment adherence.

Psoriasis is a relatively common chronic inflammatory skin disease in children for which there is no cure. Most children have mild disease that can be managed with topical therapy as opposed to phototherapy or systemic therapy. Despite the mild presentation of psoriasis in most children, the disease can have a significant impact on quality of life due to the need for ongoing treatment, the frequently visible nature of the cutaneous manifestations, and the social stigma that is associated with psoriasis. Adherence to treatment, in particular topical therapy, is often poor in adults and compromises response to therapy and medical provider management strategies. Multiple factors that may contribute to nonadherence in adults with psoriasis have been identified, including lack of education on the disease and expectations for management, issues related to ease of use and acceptability of topical medications, and anxiety regarding possible medication side effects. There is currently no published data on adherence in the pediatric psoriasis population; however, poor adherence is often suspected when patients fail to respond to appropriate therapy. General strategies used to assess adherence in other pediatric disease populations can be applied to children with psoriasis, and interventions that reflect experience in other chronic dermatologic disorders such as atopic dermatitis may also be helpful for medical providers caring for children with psoriasis.

Retrospective analysis of beta-blocker instituted for treatment of hemangiomas (RABBIT study).

OBJECTIVE: To evaluate the safety and efficacy of our institutional beta-blocker protocol for treatment of complicated infantile hemangiomas (IH). STUDY DESIGN: A retrospective descriptive study of 76 infants/children with IH treated with oral propranolol at the Children's Hospital of Philadelphia between June 2008 and August 2010 was performed, assessing both the safety and efficacy of propranolol. Based on preliminary data showing hemangioma recrudescence off-treatment, we reviewed 9 additional patients with recrudescence between August 2010 and December 2011. RESULTS: Mild adverse events included asymptomatic bradycardia, gastrointestinal symptoms, asymptomatic hypotension, cool hands/feet, asymptomatic hypoglycemia, and sleep disturbance. Sixteen patients had recrudescence of IH off-treatment, with propranolol discontinued at a median age of 14 months (interquartile range 10-15 months). CONCLUSIONS: Propranolol appears to be associated with minor, not severe symptomatic adverse events. Propranolol appears to be effective in treating complicated IH. Recrudescence can occur off-treatment, even with discontinuing propranolol as late as 15 months of age.

Diagnosis and treatment of pediatric psoriasis: current and future.

Psoriasis is a common yet complex inflammatory dermatosis that may be seen in infants, children, and adolescents. The clinical presentation and course may be quite variable, and while patients with mild disease are often easily managed, those with recalcitrant or more severe disease often present a therapeutic dilemma given the number of therapies available and the relative lack of data on the efficacy and safety of use of these therapies in children. This review presents the reader with an overview of the current understanding of the pathophysiology, diagnosis, and treatment of pediatric psoriasis, with an emphasis on the available data in the literature that pertains to the use in children of currently available topical and systemic therapies, including topical corticosteroids, vitamin D analogs, phototherapy, systemic immunosuppressive medications, and biologic agents.

Congenital myofibroma masquerading as an ulcerated infantile hemangioma in a neonate.

We report a case of a solitary infantile myofibroma masquerading as an ulcerated infantile hemangioma. Infantile myofibroma is a rare soft tissue tumor that has a good prognosis in the solitary form. It may be difficult to distinguish clinically from more common tumors of infancy such as an infantile hemangioma or from other rare entities and therefore requires a biopsy for definitive diagnosis.

Nail disorders as signs of pediatric systemic disease.

Herein, we describe some of the more common changes in the nail unit that can be seen in systemic diseases in children. Changes that can be seen are not limited to those discussed in the following pages. The presence of changes on multiple nails is suggestive of a systemic cause in an ill child. However, multiple nails can also be affected in primary inflammatory disorders and infections of the nail unit. When evaluating a pediatric patient with a nail disorder, it is important to perform a complete physical examination of the skin and oral mucosa, as other clues to the diagnosis of the nail problem may be found. A comprehensive family history is also important to uncover possible syndromic associations with nail disease or diseases that can manifest with nail changes.