USP6 rearrangement in pediatric nodular fasciitis.

Nodular fasciitis (NF) is a myofibroblastic proliferation that is uncommonly present in pediatric patients. These benign neoplasms can masquerade as more insidious sarcomatous proliferations on both clinical exam and initial histopathologic review, often prompting undue concern in patients, parents, and providers. While immunohistochemical analysis of NF can be variable, adding to the diagnostic uncertainty, molecular analysis documenting ubiquitin-specific protease 6 (USP6) gene rearrangement can help confirm the diagnosis as an association between NF and USP6 overexpression was first identified 10 years ago in an analysis that found rearrangements of the involved locus in over 90% of studied samples. In this report, we review one case of NF located on the chin of a nine-year-old girl in which molecular testing was essential to secure the correct diagnosis, and provide a summary of documented cases of USP6 overexpression in transient pediatric neoplasms.

Hand-foot-skin reaction related to use of the multikinase inhibitor sorafenib and hard orthotics.

Hand-foot-skin reaction is a distinct clinical condition arising in association with the use of multikinase inhibitors, including sorafenib. Because multikinase inhibitors are increasingly being used in children with cancer, recognition of this previously unfamiliar condition is of importance to pediatric dermatologists. We describe the diagnosis and successful treatment of a case of hand-foot-skin reaction in a child taking sorafenib for an unresectable desmoid tumor.

Evidence-based recommendations for the management of acne fulminans and its variants.

BACKGROUND: Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF. OBJECTIVE: To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research. METHODS: A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations. RESULTS: Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus. LIMITATIONS: Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available. CONCLUSION: These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.

Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment.

Infantile hemangiomas (IHs) are the most common vascular tumors in infants, appearing in early infancy and ultimately regressing with time. Clinical presentation may vary, with a minority of lesions causing impairment of vital function (e.g., respiratory or visual obstruction), permanent scarring, and/or disfigurement. The pathogenesis of IH is complex and poorly understood. Risk factors implicated in their development include preterm birth and placental anomalies. IH presents a myriad of clinical challenges, including correct diagnosis and whether or not to pursue treatment. This article is a review of the current literature regarding pathogenesis, clinical presentation, treatment, and prognosis of IH. Birth Defects Research 109:809-815, 2017. © 2017 Wiley Periodicals, Inc.

Infantile hemangiomas, complications and treatments.

Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. While the majority regress without the need for intervention, approximately 10%, often site dependent, can cause serious complications and require treatment. IH complications can be categorized as life threatening, obstructive, ulcerative or disfiguring. Life threatening complications include airway and hepatic IHs. Functional complications obstructing vital structures or impairing function include periocular, nasal, labial, parotid, auricular, and breast IHs. Local complications arise from ulceration or those in cosmetically sensitive areas. Therapeutic options for complicated IHs include pharmacologic (topical or systemic), surgical, or laser interventions. Topical agents are best employed for small, superficial, and localized IHs; while systemic therapy is reserved for larger IHs and those with more aggressive growth characteristics with propranolol as first-line therapy.

Update on Epidemiology, Diagnosis, and Disease Course of Atopic Dermatitis.

Studies of the prevalence of atopic dermatitis (AD) have provided insights into associated environmental risk factors, demonstrating the complex interactions between the presence of filaggrin (FLG) gene defects and environment. Among other important findings is that elevated transepidermal water loss (TEWL) in newborns is a strong predictor of AD, regardless of FLG status. Recently recognized predictors of disease course and severity include onset of AD signs and symptoms before 12 months of age and the presence of an FLG mutation and concomitant immunoglobulin E sensitization early in life. Semin Cutan Med Surg 35(supp5):S84-S88.

Review of Critical Issues in the Pathogenesis of Atopic Dermatitis.

About a decade age, loss-of-function mutations in the filaggrin molecule were first implicated in the pathogenesis of ichthyosis vulgaris and, subsequently, of atopic dermatitis and other atopic diseases. Since then, intensive study of the role of filaggrin null mutations have led to other milestones in understanding the pathologic pathways in these diseases, including the initiation, maintenance, and promotion of the disease processes. The result has been new and emerging clinical and pharmacologic strategies for early identification of and intervention in atopic diseases. Semin Cutan Med Surg 35(supp5):S89-S91.

Assessing the New and Emerging Treatments for Atopic Dermatitis.

The newer and emerging treatments for atopic dermatitis (AD) focus on blockade of inflammatory cytokines, especially those that derive from T helper cell type 2 (TH2) and are associated with a pathway of immunoglobulin E (IgE) sensitization. Among the proinflammatory cytokines that have been identified as promising therapeutic targets are chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2), IgE, thymic stromal lymphopoietin (TSLP), and several monoclonal antibodies that block key cytokine pathways in the innate immune response. Two agents that have been studied in phase III clinical trials are the boronbased phosphodiesterase-4 (PDE-4) inhibitor, crisaborole, and dupilumab, an antibody that inhibits the interleukin-4/ IL-13 receptor α chain. Semin Cutan Med Surg 35(supp5):S92-S96.

The Changing Paradigm of Atopic Dermatitis Therapy.

The pathophysiology of atopic dermatitis (AD) is complex, and future treatment options will likely be incorporated in a multimodal approach to management. The new, directed therapies that have been developed will likely be used in conjunction with concomitant continuous or intermittent use of standard therapies; the goal is to optimize therapeutic outcomes while minimizing adverse impacts on safety and cost. Current data regarding disease course and expression throughout life suggest that treatment strategies also will need to be adjusted as a patient grows. Research also indicates that interventions begun in infancy-such as the use of emollients-may mitigate or prevent AD signs and symptoms in children at high risk for the disease. Semin Cutan Med Surg 35(supp5):S97-S99.

Imaging Pediatric Vascular Lesions.

Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation.

Onychoheterotopia Due to a Traumatically Transplanted Nail in a Child.

Onychoheterotopia is a rare condition characterized by ectopic nail tissue growth. It is a digital mass that is commonly misdiagnosed. We describe a 6-year-old girl who presented with onychoheterotopia after trauma to the digit. Her onychoheterotopia was incorrectly diagnosed as a common wart. It is important to include onychoheterotopia in the differential diagnosis of digital masses, especially in the setting of previous traumatic injury.

Can long-term alopecia occur after appropriate pulsed-dye laser therapy in hair-bearing sites? Pediatric dermatologists weigh in.

BACKGROUND: The risk of long-term alopecia after pulsed-dye laser (PDL) therapy is unknown. To identify how many practitioners treat hair-bearing sites with PDL and how commonly long-term alopecia occurs, the authors queried pediatric dermatologists about their experiences using this modality. METHODS: A survey was designed to evaluate the frequency of and factors contributing to long-term alopecia after PDL treatment of port-wine stains (PWS). "Long-term" was defined as no sign of hair regrowth after several years of nontreatment. The survey was administered to attendees at the 2014 Society for Pediatric Dermatology biannual meeting. RESULTS: Sixty-four pediatric dermatologists completed the survey, 50 of whom had experience using PDL. Of these physicians, 86% have used PDL to treat PWS of the eyebrow and 80% have treated PWS of the scalp. Over one-quarter of respondents (25.5%) using PDL on hair-bearing areas had at least 1 of their patients develop long-term alopecia after PDL treatment. The incidence of long-term alopecia after PDL treatment in the surveyed population was 1.5% to 2.6%. CONCLUSION: The occurrence of long-term alopecia at hair-bearing sites after treatment with PDL may be greater than previously thought. Because the majority of physicians using PDL treat hair-bearing areas, prospective studies are needed to more accurately determine the risk of long-term alopecia and the factors that contribute to it.

A randomized, controlled trial of oral propranolol in infantile hemangioma.

BACKGROUND: Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. METHODS: We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. RESULTS: Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. CONCLUSIONS: This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).

Beta blockers: an innovation in the treatment of infantile hemangiomas.

Infantile hemangiomas are benign vascular tumors seen in 4.5 percent of neonates and infants. While most infantile hemangiomas can be managed with active nonintervention, a subset of patients will require more aggressive management. Here the authors review the use of beta-blockers in the treatment of infantile hemangiomas, including oral, topical, and multimodal treatment options. They discuss the latest data on propranolol, including criteria for patient selection, dosing recommendations, and appropriate monitoring for side effects and efficacy. Lastly, they review indications for topical timolol treatment and the potential benefits of concomitant laser therapy.

Prepubertal male genitourinary metastatic Crohn's disease: report of a case and review of literature.

Chronic penile swelling in prepubertal boys is an uncommon problem. The differential diagnosis includes primary and secondary lymphedema, trauma, previous penile surgery, and extraintestinal metastatic Crohn's disease. We report a 6-year-old boy who presented with persistent penile edema as an extraintestinal manifestation of Crohn's disease. In this case, the penile edema preceded the overt bowel symptoms associated with Crohn's disease, and a high index of suspicion led to the underlying diagnosis. Few previous reports have reviewed the different treatment options and their associated outcomes for Crohn's disease in prepubertal boys with genital edema.

Plaque-like myofibroblastic tumor: report of three cases.

Plaque-like myofibroblastic tumor of infancy (PMTI) was first reported in 2007. The first two cases described large, plaque-like tumors presenting in infancy with microscopic features consistent with dermatofibroma but with immunohistochemical features of myofibrocytic lineage. We present three additional cases of PMTI, the first cases reported since the initial two cases, and describe additional clinical features of this condition, including presentation in early childhood as opposed to infancy, development of ulceration, and aggressive growth. We propose shortening the name of this condition to plaque-like myofibroblastic tumor because presentation can occur in infancy or in early childhood.

Infantile hemangiomas: an update on pathogenesis and therapy.

Infantile hemangiomas (IHs) are the most common vascular tumors of childhood, affecting ~5% of all infants. Although most lesions proliferate and then involute with minimal consequence, a significant minority can be disfiguring, functionally significant, or, rarely, life-threatening. Recent discoveries concerning hemangioma pathogenesis provide both an improved understanding and more optimal approach to workup and management. Important detrimental associations can be seen with IH, such as significant structural anomalies associated with segmental IH. Standards of care have dramatically changed evaluation and management of hemangiomas. The goal of timely recognition and therapy is to minimize or eliminate long-term sequelae. New modalities, such as oral propranolol, provide the caregiver with better therapeutic options, which can prevent or minimize medical risk or scarring, but the side effect profile and risk-benefit ratio of such interventions must always be evaluated before instituting therapy.