Genetic and dermoscopic findings in a case series of children with oculocutaneous albinism.

Oculocutaneous albinism (OCA) is a genetic disease caused by disorders in melanin synthesis or distribution. In this descriptive study conducted in a tertiary care pediatric hospital, patients with a clinical diagnosis of OCA and genetic study were retrospectively recruited and underwent dermatological and ophthalmological exam, including optical coherence tomography (OCT) and digital dermoscopy. Our findings revealed milder OCA phenotypic expression in individuals harboring single pathogenic mutations in conjunction with polymorphisms, as well as in those with mutations of uncertain significance. Regardless OCA subgroup, severe phenotypes of OCA were associated with a higher number of mutations/polymorphisms in melanin biosynthesis genes and paler dermoscopic patterns, such as vascular pattern, which was the most common pattern in our series.

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.

Direct-to-consumer, store-and-forward teledermatology with dermoscopy using the pharmacist as patient point-of-contact.

OBJECTIVE(S): To evaluate the frequency of nonmelanoma skin cancer (NMSC), NMSC precursors, and melanoma on a store-and-forward dermatology model featuring the pharmacist as the patient's point-of-contact. The secondary objective was to define lesion changes and symptoms perceived by patients (clinical prediction rules by nonexpert observers) that can be predictive of malignity. METHODS: A cross-sectional study of teledermatology consultation was performed. All patients who underwent a teledermatology consultation between September 2018 and March 2020 were included. A patient could have more than 1 lesion per consultation. The object of the study was a defined dermatologic lesion. The differences between the variables were analyzed using a univariate model based on the chi-square test for independent qualitative variables and Fisher exact test in cases when the expected values in any of the cells of a contingency table were less than 5. Statistical significance was set at P < 0.05 (2-tailed). RESULTS: A total of 225 lesions in 218 patients were considered for this study; 53.8% (n = 121) of the lesions were classified as benign, 16.4% (n = 37) as dubious, 23.1% (n = 52) as NMSC precursors, 5.8% (n = 13) as NMSC, and 0.9% (n = 2) as melanomas. Of the reported clinical lesion changes, spontaneous pain, pruritus, surface texture changes, color changes, or form changes had no statistically significant relationship with the diagnostic group, whereas the presence of spontaneous bleeding (P = 0.015) and size changes (P = 0.026) were more frequently observed in the "dubious lesion" and "of oncological relevance lesion" groups. CONCLUSION: This "direct-to-consumer," store-and-forward teledermatology with dermoscopy model featuring the pharmacist as the patient's point-of-contact is useful for the diagnosis of melanoma, NMSC, and NMSC precursors when backed by a robust dermatology service.

Recalcitrant trametinib-induced paronychia treated successfully with topical timolol in a pediatric patient.

Paronychia has been described as a side effect in patients undergoing treatment with MEK (mitogen activated protein kinase enzyme) inhibitors. It is usually a recurrent condition that can have a significant impact in the quality of life. Topical beta blocker treatment has been described as an effective therapy in antineoplastic-induced pyogenic granulomas and in antineoplastic-induced paronychia. We describe the first case treated with topical timolol for a trametinib-induced paronychia in a pediatric patient that allowed to continue the third line antineoplastic therapy for his glioma.

Long-lasting contact dermatitis in patients with atopic dermatitis or psoriasis.

BACKGROUND: The aetiology of contact dermatitis, a common inflammatory skin disorder, is often complex and multifactorial. OBJECTIVES: To describe the characteristics of patients with contact dermatitis who also have concomitant atopic dermatitis or psoriasis. METHODS: Between 2000 and 2011, adult patients with chronic contact dermatitis (six months or more), which also had concomitant atopic dermatitis or psoriasis, were recruited for a descriptive retrospective study in a tertiary care Spanish hospital. Univariate and multivariate analyses were used for the analysis of the collected data. RESULTS: 76 patients with atopic dermatitis and 130 with psoriasis were recruited. The most frequent site of contact dermatitis in both groups was the hands. The most frequent clinically relevant allergen in both groups was nickel sulphate. According to multivariate logistic regression, a statistically significant association was found between facial contact dermatitis and atopic dermatitis (adjusted OR 0.2 95% CI: 0.05-0.8; P = 0.022). No differences were found between the groups for patch test results (adjusted OR 0.6 CI 95%: 0.3-1.3; P = 0.194). CONCLUSIONS: Although the number of patients was limited, our results provide valuable insight on the behaviour of contact dermatitis in patients with atopic dermatitis and with psoriasis. Facial contact dermatitis was positively associated with atopic dermatitis. No differences were found with respect to rates of contact hypersensitivity or positivity to different allergens.

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.).

Congenital tufted angioma: A multicenter retrospective study of 30 cases.

BACKGROUND: Recent reports indicate that tufted angioma is a rare vascular neoplasm that manifests more frequently at birth than previously thought. Few studies specifically address congenital presentation. OBJECTIVES: We analyzed the clinicopathological characteristics, clinical course, and treatment of congenital tufted angioma (cTA) and evaluated variables that were indicative of problematic lesions. METHODS: We performed an observational retrospective study of 30 patients with cTA in 9 Spanish hospitals over a 14-year period. Histopathology and immunohistochemistry studies were performed. RESULTS: Congenital tufted angioma mainly affected the limbs (56.67%), followed by the face and/or neck (23.33%). Almost three-quarters of facial cTA were located over the mandibular area. Immunohistochemically, proliferating cells expressed markers of endothelial cells, with some clusters of cells, especially at the periphery of the aggregates, showing positivity for podoplanin. As no associated complications were observed in 66.67% of cases, no treatment was started. LIMITATIONS: Data were collected retrospectively. CONCLUSIONS: Our findings emphasize the clinical features and course of cTA. The possibility of cTA should be considered when a poorly defined congenital infiltrative vascular tumor with(out) overlying hirsutism appears over the mandibular area. Location on the face and/or neck requires a more comprehensive workup, since potentially severe complications often appear early.

Iatrogenic Calcinosis Cutis Successfully Treated with Topical Sodium Thiosulfate.

Calcinosis cutis is a term used to describe a group of disorders in which calcium salt deposits form in the skin and subcutaneous tissue. We report a 6-year-old boy with hypoparathyroidism after thyroidectomy who was admitted to the hospital for severe hypocalcemia being treated with calcium gluconate intravenous infusion through peripheral veins. Within a few days we made a diagnosis of iatrogenic calcinosis cutis and treatment with 10% topical sodium thiosulfate was prescribed; complete resolution of lesions was achieved after 6 months, with no local or systemic adverse effects. Because of the lack of noninvasive alternatives and the good tolerance of the treatment, especially in childhood, we suggest the topical use of this drug as an option for this condition.

"Sky Full of Stars" Pattern: Dermoscopic Findings in a Desmoplastic Giant Congenital Melanocytic Nevus.

Desmoplastic giant congenital melanocytic nevus (DGCN) is an uncommon variant of congenital nevus, presenting as a progressive induration and hypopigmentation of the lesion that occasionally causes hair loss and even total or partial disappearance of the nevus. A 6-month-old girl with a giant congenital melanocytic nevus that involved the entire posterior side of the right thigh was seen in our department. Nine months later, the peripheral area of the nevus presented as a marked induration with hypopigmentation. Dermoscopy demonstrated a reticular pattern exclusively located in the perifollicular areas, with a radial distribution from the follicular ostium that mimicked a "sky full of stars." We report a case of DGCN, including a dermoscopic description of the findings noted in the indurated and hypopigmented areas that appear as a "sky full of stars" image.

Effectiveness of propranolol in the treatment of infantile hemangioma beyond the proliferation phase.

During the last 5 years, many studies have shown the efficacy of propranolol as first-line treatment for infantile hemangiomas (IHs), but not much has been written about the role of propranolol beyond the proliferation phase of IH (>1 year). Our aim was to assess propranolol efficacy and safety in the treatment of patients older than 1 year. A retrospective study of patients older than 1 year diagnosed with IH and treated in our vascular anomalies clinic between 2009 and 2013 was performed. Eighteen patients older than 1 year with a diagnosis of IH (15 girls, 3 boys) were identified. The mean age at the time of initiation of treatment was 25.7 months (range 13-72 mos). Single lesions were observed in 13 patients and multiple lesions in 5. Fifteen patients had focal lesions and three had segmental. The median duration of treatment with oral propranolol was 11.8 months (range 2-33 mos). Complete response was observed in 72.2% of the patients and partial response in 27.8%. Recurrence was observed in three patients 4.7 months after completion of therapy (range 0.3-8 mos). These patients required further therapy with propranolol for 6 more months. Bradycardia was documented in two patients and night terrors in one patient, which led to discontinuation of treatment. In our experience, propranolol may be useful in the treatment of IHs beyond the proliferation phase (>1 year old), but more studies are needed to support this observation.

Oral Nadolol for Children with Infantile Hemangiomas and Sleep Disturbances with Oral Propranolol.

BACKGROUND/OBJECTIVE: Oral propranolol has been shown to be safe and effective in infants with infantile hemangioma (IH). Side effects such as sleep disturbances have been associated with propranolol. The aim of this study was to evaluate the efficacy and safety of oral nadolol in a small series of patients whose propranolol therapy was discontinued due to sleep disturbances. METHODS: A retrospective study of patients with IHs who were treated with oral nadolol due to propranolol-related sleep disturbances at a pediatric tertiary care center between July 2008 and March 2013. Clinical response to oral nadolol and disappearance of propranolol-related side effects were analyzed. RESULTS: A total of 97 patients presenting IH received oral propranolol. Nine patients (9.3%) developed sleep disturbances. Oral propranolol was discontinued in seven patients and switched to oral nadolol, with resolution of these side effects in 5 (71%) of the cases. One patient developed sleep disturbances again after four months of oral nadolol. LIMITATIONS: The sample size was too small to draw generalizable conclusions and to draw any statistical inference as to the incidence of sleep disturbances with nadolol therapy. CONCLUSIONS: The use of oral nadolol in the treatment of IH in our series of 7 patients, resolved the propranolol-related sleep disturbances in 5 (71%), while in one patient the symptoms recurred after 4 months of oral nadolol at a dose of 2 mg/kg/day. In most cases, switching beta-blockers did not compromise efficacy, and is recommended when sleep disturbance necessitates discontinuation of beta-blocker therapy of IH.

Somatic and germ-line mosaicism of deletion 15q11.2-q13 in a mother of dyzigotic twins with Angelman syndrome.

Angelman syndrome (AS, OMIM105830) is a neurogenetic disorder caused by different genetic mechanisms. Determining the genetic mechanism is essential to establish the recurrence risk and the accuracy of genetic/reproductive counseling. The majority of AS patients present with a deletion of the 15q11.2-q13 region on the maternally derived chromosome. The other genetic mechanisms are: paternal disomy of chromosome 15, imprinting center defects, and mutations in the ubiquitin-protein ligase E3A gene (UBE3A). Different recurrence risks are associated with each specific genetic mechanism involved. We report on the study of dizygotic twins with classic phenotypic AS due to deletion of the same maternally derived chromosome 15. The mother presented with hypopigmented macular lesions on the inner side of both arms. Fibroblast culture studies of the maternal hypopigmented skin areas from both arms showed mosaicism for a normal cell line and for a second cell line with a 15q11.2-q13 deletion. This family represents the first demonstrated case of maternal somatic and germ line mosaicism for 15q11.2-q13 deletion as the cause of AS.

Lumbosacral abortive hemangioma with intradural extension.

Abortive hemangioma (AH) is a true hemangioma of infancy that expresses glucose transporter-1 protein in the endothelial cells, with an arrested growth cycle. We present the rare case of a lumbosacral AH with intramedullary extension.