Improvement in Atopic Dermatitis and Recurrent Infection With Dupilumab in Children With Distinct Genetic Types of Hyper-IgE Syndrome: A Case Series and Literature Review.

Hyperimmunoglobulin E syndrome (HIES) is a group of rare genetic disorders characterized by severe atopic dermatitis and recurrent skin and pulmonary infections. The efficacy of dupilumab in pediatric patients with HIES-associated severe atopic dermatitis is relatively understudied. Here, we present a series of three children with HIES, two with AD-HIES caused by STAT3 mutations, and one with AR-HIES caused by biallelic mutations in ZNF341. In all cases, dupilumab treatment led to sustained clearance of severe atopic dermatitis over multiple years, as well as improvements in systemic symptoms of HIES.

Prevalence of Atopic Diseases Among Sexually Diverse Adults in the US.

This cross-sectional study assesses the prevalence of asthma, allergic rhinitis, or atopic dermatitis among sexually diverse adults compared with heterosexual adults in the US.

Systemic Therapy for Vascular Anomalies and the Emergence of Genotype-Guided Management.

Improved understanding of the genetic basis of vascular anomalies has uncovered a growing need for targeted medical therapies. This is especially important for lesions not amenable to surgical interventions or interventional radiologic techniques. Recent studies and case reports have documented the effective use of tailored medical therapies in several distinct types of vascular anomalies. Sirolimus, mitogen-activated protein kinase inhibitors, and phosphoinositide 3-kinase inhibitors have emerged as potential therapies. Although this remains a growing field with significant knowledge gaps, a more optimistic outlook for patients with previously devastating impact on function and quality of life seems now within reach.

Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study.

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.

Treatment of Childhood-Onset Lupus Erythematosus Panniculitis With Rituximab.

Importance: Childhood-onset lupus erythematosus panniculitis (LEP) is a rare and chronic disfiguring disease. A paucity of literature exists on the clinical manifestations of this disease and how best to treat it. Objectives: To describe the clinical features of childhood-onset LEP and report on the use of rituximab in treatment-refractory childhood-onset LEP. Design, Setting, and Participants: A retrospective, observational case series study was conducted of 4 patients with childhood-onset LEP who presented to a single-center, tertiary care clinic with pediatric dermatology and pediatric rheumatology clinics between July 1, 2014, and July 1, 2018, and were treated with rituximab. A literature review was conducted of the clinical features and treatment of childhood-onset LEP. Exposure: Rituximab therapy for childhood-onset LEP. Main Outcomes and Measures: Reduction in the number and size of erythematous and tender subcutaneous nodules (both visually and by palpation), reduction of facial atrophy (documented with serial photography), and tolerability of rituximab at 2 to 22 months after initiation of therapy. Results: Four patients (3 male; mean [SD] age at treatment, 15 [5.9] years) with refractory childhood-onset LEP were successfully treated with rituximab. All patients had a rapid and sustained response to therapy with rituximab. One patient (25%) had minor infusion reactions; otherwise, treatment was well tolerated. Conclusions and Relevance: This case series suggests that rituximab may hold promise as a treatment for refractory, childhood-onset LEP. Larger, prospective studies are needed to validate these findings; however, given the rarity of disease, large studies may be difficult to conduct.

Segmental infantile hemangioma and concomitant hypertension in three African American neonates.

We present three African American infants with segmental, ulcerated infantile hemangiomas and concomitant, persistent hypertension. When treated with beta-blocker therapy, the hemangiomas decreased in size and the ulcerations resolved, but there was no impact on the elevated blood pressure in one of our patients. We failed to identify any associations between infantile hemangioma and hypertension in the literature.

Tinea capitis: A single-institution retrospective review from 2010 to 2015.

BACKGROUND/OBJECTIVE: Tinea capitis is a common infection of scalp hair in children. The prevalent etiologic organism has changed significantly over time, which may reflect the complex interaction of environmental factors, genetic predisposition, and movement of populations. We evaluate the prevalence of different infectious organisms causing tinea capitis and describe the clinical characteristics. METHODS: A retrospective chart review of patients diagnosed with tinea capitis with tissue culture confirmation, who were seen in pediatric dermatology at a tertiary care center from 2010 to 2015. Patient demographics, culture data, and clinical characteristics were evaluated. Inflammatory pattern, characterized by presence of pustules, bogginess, or lymphadenopathy, was noted. RESULTS: Forty-six patients with culture-positive tinea capitis were identified. In the 18 (42.9%) patients who were infected with either Trichophyton violaceum or Trichophyton soudanenese, all were of African ethnicity. In contrast, Trichophyton tonsurans was identified in a minority of African patients (3.8%), revealing a statistically significant difference between ethnicity and infective species (P-value < 0.001). T tonsurans was significantly more likely than T violaceum to exhibit an inflammatory pattern (68% vs 22%, P value < 0.027). CONCLUSIONS: While T tonsurans remained the most common cause of tinea capitis, T violaceum and T soudanense have increased in prevalence. As these latter agents are less inflammatory, clinical diagnosis may be delayed. Studying changes in the infectious cause of tinea capitis can help us create a snapshot to better understand the evolution of our population make-up, allowing us to provide crucial quality health care to all.

Inflammatory arthritis in pediatric patients with morphea.

BACKGROUND: Morphea or localized scleroderma is an inflammatory disorder resulting in fibrosis of the skin and subcutaneous tissues. Joint contractures, arthralgias, and functional compromise are recognized associations of pediatric morphea. The co-existence of inflammatory arthritis and morphea is not well-described in the literature. OBJECTIVE: To investigate the relationship between pediatric morphea and inflammatory arthritis with regards to cutaneous, musculoskeletal, and laboratory findings and treatment regimens. METHODS: A systematic retrospective chart review of 53 patients with pediatric morphea was performed and analyzed for morphea subtypes, arthritic joint involvement, serum autoantibodies, and therapeutic interventions. RESULTS: Eleven out of 53 patients had polyarthritis that involved joints unrelated to the site of the cutaneous morphea. These patients were mostly girls with either the linear or generalized subtypes of morphea. Serum levels of antinuclear antibodies were more significantly elevated in patients with arthritis. All children were treated with methotrexate in addition to other systemic or topical immunosuppressive agents. LIMITATIONS: This was a small, single-center retrospective study. CONCLUSION: Pediatric morphea co-existed with inflammatory arthritis in 11 of 53 children. Further understanding and appreciation of this relationship may direct more intensive therapy and musculoskeletal screening.

Perceptions and Practices Regarding Atopic Dermatitis: A Survey.

Parents (N = 392) completed a survey at the Minnesota State Fair in August and September 2015 addressing knowledge regarding the pathogenesis of atopic dermatitis (AD), basic skin care practices, and the perceived role of infection and food allergies in AD. Of participating parents, 82% identified food allergy or sensitivity in AD pathogenesis, whereas only 42% identified bacterial infection as an important factor in AD severity. Participants most often received education on skin health from their pediatrician (49%), followed by Internet-based sources (23%), rather than a dermatologist or pediatric dermatologist. Parents of children with AD overestimate the role of food allergies in this condition and are not as aware of the role of bacterial infection. Future educational directions from our specialty should focus on resources for pediatricians and families that emphasize these factors.

Follicular Psoriasis: Differentiation from Pityriasis Rubra Pilaris-An Illustrative Case and Review of the Literature.

The follicular presentation of psoriasis is a well-described but uncommon variant. In some cases, follicular psoriasis may clinically and histopathologically mimic pityriasis rubra pilaris. There are several reports discussing the resemblance of widespread follicular psoriasis in children to pityriasis rubra pilaris. We describe a case of follicular psoriasis in a 16-year-old black girl with acrally distributed follicular hyperkeratotic papules with associated keratoderma of her plantar surfaces resembling pityriasis rubra pilaris.

Vascular tumors and malformations in children, Introduction.

Over the past decade, I have been amazed at the growth in the field of vascular anomalies. The recognition of vascular birthmarks as a defined area of medicine is a relatively recent event. The International Society for the Study of Vascular Anomalies (ISSVA) was founded by Drs John Mulliken and Anthony Young in the late 1970s. Mulliken and Glowacki's sentinel 1982 paper on the biologic classification of vascular anomalies further established the field, by providing clarity of nomenclature and unifying concepts that had previously been lacking.

Congenital hemangiomas.

Congenital hemangiomas are rare solitary vascular tumors that do not proliferate after birth. They are characterized as either rapidly involuting congenital hemangiomas (RICHs) or noninvoluting congenital hemangiomas (NICHs) based on their clinical progression. NICHs have no associated complications, but are persistent. RICH, while usually asymptomatic, may ulcerate or bleed early in their presentation, but involute quickly during the first few months of life. Hepatic RICHs are not associated with cutaneous RICHs, but may result in high-output cardiac failure due to arteriovenous or portovenous shunting. In the following review, the clinical characteristics and current management specific to congenital hemangiomas is discussed.

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin.

Imiquimod-induced subacute cutaneous lupus erythematosus-like changes.

Imiquimod is a topical immunomodulator used to treat genital warts and cutaneous malignancies that exerts its effects via induction of proinflammatory cytokines through activation of toll-like receptor (TLR) 7. Although subacute cutaneous lupus erythematosus (SCLE) has been reported in association with multiple systemic medications, SCLE in patients treated with topical agents has not been widely reported. We report the case of a 50-year-old woman with local induction of lesions that clinically and histologically resembled SCLE following treatment with topical imiquimod.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome associated with neonatal epidermolysis bullosa acquisita.

We report the case of a 2-week-old boy who presented with a vesiculopustular, bullous eruption in the setting of autoimmune enteropathy, hypothyroidism, membranous nephropathy, Coombs-positive hemolytic anemia, and persistent eosinophilia. Immunologic testing revealed a deficiency of FOXP3-expressing regulatory T cells, and a diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome was made. Histologic analysis, immunofluorescence, and enzyme-linked immunosorbent assay confirmed the bullous eruption as epidermolysis bullosa acquisita with associated collagen VII autoantibody production. The skin lesions responded to systemic immunosuppressant therapy and have regressed after allogeneic bone marrow transplantation.

Management of difficult infantile haemangiomas.

Infantile haemangiomas are common vascular tumours of infancy. They typically present shortly after birth, undergo a period of rapid proliferation, and then slowly involute over many years. Although most patients require no intervention, appropriate investigation and treatment may be necessary in a minority of cases. Identifying which patients require further investigation or intervention can be difficult due to the heterogeneity of clinical presentation. This is compounded by a lack of rigorous randomised controlled trials on haemangioma management. Therefore, the rationale for treatment is not always straightforward. Haemangiomas occur anywhere on the body, have superficial, deep or mixed morphology, and depending on anatomic location, size and subtype, can be associated with underlying structural anomalies and many other potential complications. Generally, the management of difficult haemangiomas is best approached on a case-by-case basis. Over the last few years, there have been several advances in our understanding of haemangiomas, together with some exciting new therapeutic options. In the following review, the authors discuss the various possible complications of infantile haemangiomas, the rationale for treatment and appropriate possible interventions.

Management of capillary malformations.

Capillary malformations (CMs) are the most common vascular malformations. They are comprised of the small vessels of the capillary network in skin and mucous membranes. In the vast majority of affected individuals, CMs are isolated and not associated with any underlying abnormalities. Depending on size and location, however, they may cause significant morbidity due to disfigurement or stigmatization and, rarely, herald the presence of an underlying syndrome.

Early white discoloration of infantile hemangioma: a sign of impending ulceration.

OBJECTIVE: To evaluate the relationship between early white discoloration of infantile hemangioma (IH) and ulceration. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: A case series of 11 infants with early white discoloration of IH are described. An additional 55 infants with IH, aged 3 months, were evaluated retrospectively from a photograph archive to further explore the relationship between early white discoloration and presence or development of ulceration. MAIN OUTCOME MEASURES: Patient demographics and hemangioma size, location, and subtype are documented. Sensitivity and specificity of white discoloration in relationship to ulceration are estimated. RESULTS: Ten of the 11 infants in the case series were girls (90%); all IHs were of segmental or indeterminate subtype. Average age at first ulceration was 2.6 months, with average age at healing 5.2 months. No intervention halted progression of ulceration. Of the 55 additional 3-month-old infants, 14 had white discoloration and 12 of these 14 had or developed ulceration (86%). When the hemangioma was either white or slightly white, sensitivity for predicting ulceration was 1.00 (95% confidence interval [CI], 0.78-1.00), with a specificity of 0.68 (95% CI, 0.51-0.81). In contrast, in infants with either slightly white or no white discoloration, the sensitivity for not developing ulceration was 0.80 (95% CI, 0.52-0.96), with a specificity of 0.95 (95% CI, 0.83-0.99), suggesting that a lack of substantial white discoloration early in infancy indicates low risk of ulceration. CONCLUSION: Early white discoloration of infantile hemangioma is highly suggestive of impending ulceration.