Multiple rhabdomyomatous mesenchymal hamartomas in a patient with mosaic Barber-Say syndrome.

Barber-Say syndrome (BSS) is a rare congenital ectodermal dysplasia with few cases reported in the literature. We describe a 9-year-old boy with congenital generalized hypertrichosis and multiple rhabdomyomatous mesenchymal hamartomas (RMHs) on his nose and periocular region. Next-generation sequencing, performed in DNA from a blood sample, and RMH tissue, revealed a pathogenic variant in the TWIST2 gene, which was not detected in a salivary sample of the patient, nor in his parents. Therefore, we consider this variant as de novo mosaicism. To our knowledge, this is the first case of multiple RMHs associated with BSS.

Clinical Approach to Patients with Moderate-to-Severe Atopic Dermatitis: A Spanish Delphi Consensus.

Despite emerging evidence and advances in the management of atopic dermatitis there a lack of consensus regarding the diagnostic criteria, therapeutic approach, method to assess severity, and patient follow-up for this condition. An expert consensus study was conducted to provide recommendations on the management of patients with moderate-to-severe atopic dermatitis. The study used Delphi-like methodology based on a literature review, a summary of the scientific evidence, and a 2-round survey. The agreement of 60 panellists on 21 statements was evaluated. Consensus was pre-defined as ≥ 80% agreement of all respondents. In the first round 6 statements reached consensus. Unanimous consensus was achieved regarding therapeutic goals and patient satisfaction (maintained in the long term and periodic goals reassessment recommended every 3-6 months). In the second round, half of the statements reached consensus, all related to patient follow-up, treatment goals, and atopic comorbidities. The statements that did not reach consensus were related to diagnosis (biomarkers, allergy, and food testing) and starting patients on conventional systemic treatment rather than advanced treatment. The study assessed expert opinion regarding a variety of topics related to the clinical approach to patients with moderate-to-severe atopic dermatitis, in order to provide guidance on the diagnosis and management of patients with atopic dermatitis.

Report of a case of RAVEN, hair heterochromia and autism in the setting of FGFR2 mutation.

A newborn presented with extensive rounded and velvety epidermal nevus (RAVEN) with a genetic study of the cutaneous lesions revealing a heterozygous mutation in FGFR2 (p.Cys382Arg). By 2 years of age, the patient developed hair heterochromia and autism spectrum disorder. Although RAVEN was initially associated with fibroblast growth factor 3 (FGFR3) mutations, three cases of RAVEN have been identified with mutations in FGFR2 (p.Ser252Trp) and one case of linear keratinocytic epidermal nevi has been identified with the same mutation as the mutation identified in our patient. This strongly supports the pathogenic role of these mutations.

Hydrocolloid dressing for the treatment of severe diaper dermatitis.

Diaper dermatitis is a common dermatosis that usually responds to adequate hygiene and topical treatment, but can be a therapeutic challenge. Continuous exposure to feces and urine can cause extensive erosions and pain. The use of hydrocolloid dressings may be helpful in keeping the skin isolated from stool and urine, reducing pain, and enabling skin lesions to heal. We explain an easy technique, utilizing stoma powder and a hydrocolloid dressing, for parents to apply at home.

Safety Profile and Tolerability of Topical Phosphodiesterase 4 Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Objective: Evaluate the safety profile and tolerability of topical phosphodiesterase 4 (PDE4) inhibitors versus vehicle as treatment for atopic dermatitis in published studies. Methods: A search was performed in Medline/PubMed, Web of Science, and Cochrane Library databases on September 27, 2021, by 1 evaluator, without restrictions on publication dates or languages. Terms such as atopic dermatitis, phosphodiesterase 4 inhibitors, calcineurin inhibitors, and randomized controlled trials were included. The database searches were carried out by 1 evaluator. The titles and abstracts were reviewed for the identification and evaluation of potentially eligible studies. Study selection was made by two reviewers, so there was no intra-examiner statistic at the study selection step. The full-text articles were reviewed to determine whether or not they would be included in the systematic review. Global analyses, which included studies with both unclear and low risk of bias and subanalyses of studies with a low risk of bias were performed. Results: Out of 237 identified articles, 14 clinical trials were included in the meta-analysis. In global analyses of studies with low and unclear risk of bias, topical treatment with PDE4 inhibitors did not differ from vehicle treatment in global treatment emergent adverse events (relative risk = 0.99; 95% CI, 0.87-1.14; P = 0.94) or in serious emergent adverse events appearance (relative risk = 0.92; 95% CI, 0.39-2.20; P = 0.86). In subanalyses of studies with a low risk of bias, a reduced rate of atopic dermatitis exacerbation was observed in PDE4 inhibitors compared with the vehicle (relative risk = 0.62; 95% CI, 0.39-0.98; P = 0.04) and risk of pain at the application site was confirmed (relative risk = 2.59; 95% CI, 1.27-5.28; P = 0.01). Conclusions: PDE4 inhibitors did not show differences from vehicle treatment in treatment emergent adverse events or serious emergent adverse events incidence. In studies with low risk of bias, PDE4 inhibitors had a statistically significant risk of producing pain and reduced occurrence of atopic dermatitis exacerbation.

Inter- and intra-observer variability in the selection of therapy for infantile hemangiomas among pediatric dermatologists in Spain.

BACKGROUND: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. OBJECTIVE: The objective was to analyze the inter- and intra-observer agreement among pediatric dermatologists in the choice of treatment for IH. METHODS: We performed a cross-sectional inter-rater and intra-rater agreement study within the Spanish infantile hemangioma registry. Twenty-seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra-rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). RESULTS: Twenty-four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter-rater agreement on the treatment decision was fair (AC1  = 0.39, 95% confidence interval [CI]: 0.30-0.47). When stratified by risk category, good agreement was reached for high-risk hemangiomas (AC1  = 0.77, 95% CI: 0.51-1.00), whereas for intermediate- and low-risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16-0.46 and AC1  = 0.38, 95% CI: 0.27-0.48, respectively). Propranolol was the main option for high-risk hemangiomas (86.4%), timolol for intermediate-risk (36.8%), and observation for low-risk ones (55.9%). The intra-rater agreement was good. The inter-rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate- and low-risk hemangiomas.

Evaluation of the educational intervention "living with the sun" by preschool and first-year primary school students: a pilot study

Background: "Convive con el Sol" (Living with the sun) is an educational programme to promote education about sun exposure and healthy photoprotection habits among Spanish children. Objectives: This study evaluated the effects of the "Convive con el Sol" school-based sun protection programme on the sun safety habits, attitudes, knowledge, and practices in preschool and first-year primary school students. Materials & Methods: A quasi-experimental pilot study was established with a pre-test/post-test design and without a control group to evaluate the efficacy of the "Convive con el Sol" programme in children aged 3-8 years. Two questionnaires were used to evaluate the programme: the CHRESI questionnaire and the SolSano questionnaire. Results: Seven educational centres participated in the study. The number of completed baseline questionnaires was 351 for the CHRESI survey and 226 for the SolSano survey. After the intervention, the students improved their sun protection practices; fewer students went to the beach or swimming-pool at noon (9.8% vs 5.5%; p = 0.03), and more schoolchildren used cream with an SPF rating >15 (37.6% vs 76.2%; p <0.01) and repeatedly applied sunscreen if continuously exposed (67.4% vs 82.7%; p <0.01). Conclusion: Our findings show that the "Convive con el Sol" educational intervention improved photoprotection practices in children aged 3-8 years, but did not reduce the percentage of sunburned children. This pilot study serves as a starting point for designing educational interventions, targeting students, teachers, and families.

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia.

BACKGROUND: H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. CASE PRESENTATION: 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. CONCLUSIONS: We report the most severe disease course produced by HS described so far in the literature. Our patient's manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.

Intralesional photodynamic therapy in hidradenitis suppurativa: Getting closer to the target.

BACKGROUND: The successful treatment of hidradenitis suppurativa (HS) with intralesional photodynamic therapy (IL-PDT) has been previously reported in some case series published a few years ago. We present additional data and patient outcome for this form of PDT. METHODS: This is an observational retrospective study including all patients diagnosed with HS and treated with IL-PDT in the Hospital Universitari Son Espases from February 2019 to February 2020. Under local or general anesthesia, 5-aminolevulinic acid (5ALA) in gel 2 % or solution 1 % was introduced in the lesion. After two hours, the lesion was intralesionally irradiated (1.4 W, fluence 168 J/cm2) with the tip of a 0.4-mm thick optical fiber connected to a continuous 630-nm diode laser. The main outcome variable was the result (remission, improvement or no change) for each lesion 3 months after the therapy. The result at 6 months and the side effects were secondary outcomes. A multivariate analysis was carried out in order to obtain adjusted odds ratios for no change vs improvement or remission at 3 months for significant variables. RESULTS: A total of 117 lesions (28 nodules and 89 fistulae) were treated in 42 patients. At 3 months, 26 lesions (22.2 %) had resolved, 73 (62.4 %) had improved in size or symptoms, and 18 (15.4 %) experienced no change. The most frequent side effects were skin burns (53 lesions, 45.3 %), and abscess formation (8 lesions, 6.8 %). In the multivariate analysis, significant variables for no benefit were: a higher International Hidradenitis Suppurativa (IHS4) score, active smoking and gluteal and inguinal location. CONCLUSIONS: Although our results did not present the level of remission of the previous studies, IL-PDT was useful in most of our patients. Early interventions in patients with lower inflammatory burden were the most valuable.

Chronic urticaria in children under 15 years of age: Clinical experience beyond the clinical trials.

BACKGROUND/OBJECTIVES: The aim of the study was to describe the clinical characteristics, management, and outcome of a series of children with chronic urticaria (CU). METHODS: We retrospectively studied children aged <15 years diagnosed with CU in a tertiary teaching hospital in Palma de Mallorca, Spain, between January 2014 and March 2019. CU was defined as persistence of symptoms of wheals, with or without angioedema, for >6 weeks. RESULTS: Twenty-nine patients (17 girls, mean age 8 years) were included. Family history of atopy was found in 31% of the cases. In 41.3% of patients, episodes of CU were associated with angioedema. Physical triggers were found in 34.5% of the cases. Most episodes of CU were successfully managed with the recommended (60.7%) or double the recommended dose (17.2%) of H1-antihistamines. Quadruple the recommended dose of H1 antihistamines was used in six patients, five of whom were finally treated with off-label omalizumab. Treatment with anti-leukotrienes was needed in one patient. Associated thyroiditis was diagnosed in one patient, which was controlled with levothyroxine. CONCLUSIONS: Pediatric CU showed features similar to CU in adulthood, including a greater predominance in females and frequent association with personal or family history of atopy. Adult guidelines for the treatment of CU are currently extrapolated to the pediatric population. Specific tools for the assessment of disease activity and impairment of quality of life in pediatric CU are needed for use in prospective studies aimed to define treatment strategies for children with CU.

Facial hemihypertrophy in a girl with sturge-weber syndrome: Treatment with oral sirolimus.

In the last few years, the use of oral sirolimus has shown promising results in the treatment of some complex vascular anomalies, and recently, it has been used in patients with Sturge-Weber syndrome (SWS). We present the case of an 11-year-old girl with the diagnosis of SWS and hemifacial overgrowth treated with oral sirolimus. Throughout the eight months of follow-up, improvement of the port-wine birthmark, intraocular pressure, and neurocognitive development was noted. The mTOR inhibitors may be useful in the treatment of some patients with SWS.

Exserohilum rostratum, a rare cause of opportunistic skin infection in children: Case report and review of the literature.

Exserohilum species are environmental molds that may rarely cause skin and nasal infections, especially in immunocompromised children. We present a 3-year-old girl with acute leukemia who presented with a skin infection caused by Exserohilum rostratum. Previously published cases of skin infections by Exserohilum spp. in children are reviewed.

Expanding the phenotypes of congenital hemangiomas.

Congenital hemangiomas (CH) are benign vascular tumors that are present at birth and do not stain for the marker Glut-1. Herein, we describe five cases of CH with atypical presentations: 3 with late growth, 1 with slow involution, and 1 that partially involuted rapidly then manifested late growth.

Consensus on the Clinical Approach to Moderate-to-Severe Atopic Dermatitis in Spain: A Delphi Survey.

BACKGROUND: The purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice. METHODS: A cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of ≥80% of participants coincided in the categories of a 5-point Likert scale for that item. RESULTS: A total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients. CONCLUSION: This study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain.