Cutaneous reactions are common in children receiving trametinib. Identification of these reactions is the initial step in establishing treatment guidelines that will minimize skin eruptions and subsequent interruption of trametinib treatment.

Summary Background Recessive dystrophic epidermolysis bullosa (RDEB) is a severe systemic genodermatosis lacking therapies beyond supportive care for its extensive, life‐limiting manifestations. Objectives To report the safety and preliminary responses of 10 patients with RDEB to bone marrow transplant (BMT) with post‐transplant cyclophosphamide (PTCy BMT) after reduced‐intensity conditioning with infusions of immunomodulatory donor‐derived mesenchymal stromal cells (median follow‐up 16 months). Methods BMT toxicities, donor blood and skin engraftment, skin biopsies, photographic and dynamic assessments of RDEB disease activity were obtained at intervals from pre‐BMT to 1 year post‐BMT. Results Related donors varied from haploidentical (n = 6) to human leucocyte antigen (HLA)‐matched (n = 3), with one HLA‐matched unrelated donor. Transplant complications included graft failure (n = 3; two pursued a second PTCy BMT), veno‐occlusive disease (n = 2), posterior reversible encephalopathy (n = 1) and chronic graft‐versus‐host disease (n = 1; this patient died). In the nine ultimately engrafted patients, median donor chimerism at 180 days after transplant was 100% in peripheral blood and 27% in skin. Skin biopsies showed stable (n = 7) to improved (n = 2) type VII collagen protein expression by immunofluorescence and gain of anchoring fibril components (n = 3) by transmission electron microscopy. Early signs of clinical response include trends toward reduced body surface area of blisters/erosions from a median of 49·5% to 27·5% at 100 days after BMT (P = 0·05), with parental measures indicating stable quality of life. Conclusions PTCy BMT in RDEB provides a means of attaining immunotolerance for future donor‐derived cellular grafts (ClinicalTrials.gov identifier NCT02582775). What's already known about this topic? Severe, generalized recessive dystrophic epidermolysis bullosa (RDEB) is marked by great morbidity and early death. No cure currently exists for RDEB. Bone marrow transplant (BMT) is the only described systemic therapy for RDEB. What does this study add? The first description of post‐transplant cyclophosphamide (PTCy) BMT for RDEB. PTCy was well tolerated and provided excellent graft‐versus‐host disease prophylaxis, replacing long courses of calcineurin inhibitors in patients receiving human leucocyte antigen‐matched sibling BMT. What is the translational message? The PTCy BMT platform permits identification of a suitable related donor for most patients and for subsequent adoptive transfer of donor nonhaematopoietic cells after establishment of immunological tolerance.

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IMPORTANCE Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. OBJECTIVES To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. DESIGN, SETTING, AND PARTICIPANTS This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. EXPOSURES Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). MAIN OUTCOMES AND MEASURES Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. RESULTS Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. CONCLUSIONS AND RELEVANCE The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.

Background Systemic sirolimus (rapamycin) has recently been found effective in treating complex vascular anomalies by reducing the size and associated complications. Many vascular anomalies have a cutaneous component, and thus, we sought to determine whether topical administration of sirolimus may be an effective therapy, as data on the use of topical sirolimus are limited. Objective We reviewed the efficacy and tolerability of topical formulations of sirolimus in the treatment of various simple and combined vascular malformations and tumors. Methods Eighteen patients with any vascular anomaly treated exclusively with topical sirolimus were retrospectively reviewed. Results Eleven patients had combined venous lymphatic malformations, three had tufted angiomas, two had a lymphatic malformation, one had a venous malformation, and one had a verrucous venous malformation. All (100%) patients reported some degree of improvement and 50% of patients reported marked improvement in one or more symptoms, most commonly blebs and lymphatic drainage, and bleeding. Limitations The retrospective nature, small number of patients, and differences in topical preparations limit the broad application of the results. Conclusion Topical sirolimus appears to be a safe and useful non‐invasive therapy that is well‐tolerated in the treatment of the cutaneous portion of a variety of vascular anomalies.

We present two pediatric cases of recurrent mucositis associated with influenza B infection, both in patients with prior episodes of Stevens‐Johnson syndrome (SJS) due to Mycoplasma. Influenza B is an uncommon cause of both rash and mucosistis and SJS.

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.

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