Idiopathic calcinosis cutis in an infant: The importance of a wait-and-see approach.

A healthy 2-year-old girl presented with multiple asymptomatic subcutaneous nodules on both legs. Histologically demonstrated calcium deposition within the dermis and subcutaneous tissue consistent with calcinosis cutis. Laboratory abnormalities, underlying genetic conditions, and potential triggering factors were ruled out. The lesions resolved over an 18-month period without treatment, emphasizing the importance of the wait-and-see approach in idiopathic cases of calcinosis cutis.

Association Between VDR and CYP24A1 Polymorphisms, Atopic Dermatitis, and Biochemical Lipid and Vitamin D Profiles in Spanish Population: Case-Control Study.

BACKGROUND: Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD. OBJECTIVE: We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD. METHODS: A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined. RESULTS: Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels. CONCLUSIONS: The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.

Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma.

Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has been associated with dominant and recessive keratoderma. We report a patient with recessive erythrokeratoderma (EK) in which whole exome sequencing (WES) prioritized by human phenotype ontology (HPO) terms revealed the presence of the novel variant c.153C > A in the N-terminal region the PERP gene. This variant is predicted to have a nonsense effect, p.(Cys51Ter), resulting in a premature stop codon. We demonstrated a marked reduction in gene expression in cultured skin fibroblasts obtained from the patient. Despite the PERP gene is expressed at low levels in fibroblasts, our finding supports a loss-of-function (LoF) mechanism for the identified variant, as previously suggested in recessive EK. Our study underscores the importance of integrating HPO analysis when using WES for molecular genetic diagnosis in a clinical setting, as it facilitates continuous updates regarding gene-clinical feature associations.

Ichthyosis.

The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation and abnormal epidermal barrier formation. The resultant skin barrier dysfunction leads to increased transepidermal water loss and inflammation. Disordered cornification is clinically characterized by skin scaling with various degrees of thickening, desquamation (peeling) and erythema (redness). Regardless of the type of ichthyosis, many patients suffer from itching, recurrent infections, sweating impairment (hypohidrosis) with heat intolerance, and diverse ocular, hearing and nutritional complications that should be monitored periodically. The characteristic clinical features are considered to be a homeostatic attempt to repair the skin barrier, but heterogeneous clinical presentation and imperfect phenotype-genotype correlation hinder diagnosis. An accurate molecular diagnosis is, however, crucial for predicting prognosis and providing appropriate genetic counselling. Most ichthyoses severely affect patient quality of life and, in severe forms, may cause considerable disability and even death. So far, treatment provides only symptomatic relief. It is lifelong, expensive, time-consuming, and often provides disappointing results. A better understanding of the molecular mechanisms that underlie these conditions is essential for designing pathogenesis-driven and patient-tailored innovative therapeutic solutions.

Clinical and Sonographic Classification of Neurofibromas in Children with Neurofibromatosis Type 1 - A Cluster Analysis.

PURPOSE: High-frequency ultrasound allows the accurate identification of neurofibromas in neurofibromatosis type 1 (NF1). This study aimed to analyze the ultrasound features of neurofibromas in children with NF1, to establish a classification based on the clinical and sonographic patterns of the different types of neurofibromas, and to evaluate the interobserver correlation coefficient (κ) of this classification. MATERIALS AND METHODS: In this prospective, single referral center observational study, clinical and ultrasound findings of neurofibromas in children diagnosed with NF 1 were analyzed. To identify the ultrasound patterns, a cluster analysis allowing the inclusion of both clinical and ultrasound data was designed. The κ coefficient was calculated using 9 external evaluators. RESULTS: 265 ultrasound scans were performed on a total of 242 neurofibromas from 108 children diagnosed with NF1. Cluster analysis allowed the identification of 9 patterns (Snedecor's F, P < 0.001) classified as "classic" cutaneous neurofibroma, blue-red neurofibroma, pseudoatrophic neurofibroma, nodular subcutaneous neurofibroma, diffuse subcutaneous neurofibroma, congenital cutaneous neurofibroma, congenital plexiform neurofibroma, congenital diffuse and plexiform neurofibroma, and subfascial neurofibroma. The κ coefficient of the interobserver ratings was 0.82. CONCLUSION: Patterns identified in the cluster analysis allow neurofibromas to be classified with a very high interobserver correlation.

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.

Evolution of incidence of chilblain-like lesions in children during the first year of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has brought innumerable reports of chilblains. The relation between pernio-like acral eruptions and COVID-19 has not been fully elucidated because most reported cases have occurred in patients with negative microbiological tests for SARS-CoV-2. METHODS: A retrospective study of 49 cases of chilblains seen during the first year of the pandemic in a children's hospital in Madrid, Spain. The incidence of these skin lesions was correlated with the number of COVID-19 admissions and environmental temperatures. Patients were separated into two groups depending on the day of onset (strict lockdown period vs. outside the lockdown period). RESULTS: Most chilblains cases presented during the first and third waves of the pandemic, paralleling the number of COVID-19 admissions. The first wave coincided with a strict lockdown, and the third wave coincided with the lowest ambient seasonal temperatures of the year. Systemic symptoms preceding chilblains were more frequent in the first wave (45.8% vs. 8.0%, p = .002), as was the co-occurrence with erythema multiforme-like lesions (16.7% vs. 0%, p = .033). Laboratory test and skin biopsies were performed more frequently in the first wave (75.0% vs. 12.0%, p < .001; and 25.0% vs. 0%, p = .007; respectively). Five patients developed recurrent cutaneous symptoms. CONCLUSIONS: An increased incidence of chilblains coincided not only with the two major waves of the pandemic, but also with the strict lockdown period in the first wave and low seasonal temperatures during the third wave. Both increased sedentary behaviors and cold environmental temperatures may have played an additive role in the development of COVID-19-related chilblains.

Scabies in a 14-year-old girl with superficial epidermolytic ichthyosis.

A 14-year-old girl who reported generalized scaling and hyperkeratosis since age 1 year presented with severe pruritus of several months' duration. Scabies mites were detected, and molecular genetic analysis subsequently revealed a rare pathogenic variant in the keratin 2 (KRT2) gene, confirming a diagnosis of superficial epidermolytic ichthyosis. Treatment with oral ivermectin led to complete remission of symptoms. Disorders of keratinization can mimic clinical signs of scabies, leading to a delay in diagnosis.

Erythematous rash and postinfectious acral desquamation due to Streptococcus dysgalactiae subspecies equisimilis infection in a child.

Streptococcus dysgalactiae subspecies equisimilis infection is an emerging pathogen. Cutaneous and systemic manifestations resemble those of other pyogenic streptococci. However, the rapid group A antigen detection test used to diagnose Streptococcus pyogenes infection is usually negative, making the diagnosis difficult. If clinical suspicion of streptococcal infection is high, a tonsillar culture should be performed to confirm the diagnosis.

Addressing Frequently Asked Questions and Dispelling Myths About Melanocytic Nevi in Children.

Melanocytic nevi are congenital or acquired benign melanocytic neoplasms. The reason for the appearance of melanocytic nevi is not precisely known. Melanocytic nevi frequently occur in children, constituting a common reason for consultation in pediatric dermatology clinics. In our experience, many parents and caregivers present doubts and fears based more on popular beliefs than on data with valid scientific evidence. This review answers their frequently asked questions, such as the risk of malignancy, the importance of nevi location, the warning signs of malignant transformation, best prevention strategies, and optimal management, based on the most recent scientific evidence available.

Conradi-Hünermann-Happle syndrome with minimal signs.

A 4-year-old girl presented with congenital patches of scalp alopecia, which on physical examination, was consistent with blaschkolinear alopecic patches with mild epidermal atrophy. Similar atrophic hypopigmented patches were seen on the trunk and proximal extremities. With the clinical suspicion of Conradi-Hünermann-Happle syndrome, genetic testing was performed and revealed a mutation in the EBP gene. Despite characteristic cutaneous findings, no skeletal, ocular, or other anomalies were found on further evaluation.

Diffuse reticulate purpura in two adolescents with anorexia nervosa and severe malnutrition.

Anorexia nervosa is an eating disorder frequently associated with cutaneous manifestations. A rare type of purpura, known as diffuse reticulate purpura, has been described in patients with anorexia nervosa and severe malnutrition. Typical characteristics of this condition include a purpuric reticulate rash predominantly affecting the trunk that rapidly resolves with adequate feeding. We report two male adolescent patients with anorexia nervosa and severe malnutrition who developed diffuse reticulate purpura.

Mucocutaneous manifestations in children hospitalized with COVID-19.

BACKGROUND: Cutaneous manifestations in hospitalized children with SARS-CoV-2 have not been studied systematically. OBJECTIVE: To describe the mucocutaneous involvement in pediatric patients with COVID-19 admitted to a pediatric institution in Madrid (Spain), located in a zone reporting among the highest prevalence of COVID-19 in Europe. METHODS: A descriptive, analytical study was conducted on a series of 50 children hospitalized with COVID-19 between March 1, 2020, and November 30, 2020. RESULTS: Twenty-one patients presented with mucocutaneous symptoms: 18 patients with macular and/or papular exanthem, 17 with conjunctival hyperemia, and 9 with red cracked lips or strawberry tongue. Eighteen patients fulfilled criteria for multisystem inflammatory syndrome in children. Patients with mucocutaneous involvement tended to be older and presented to the emergency department with poor general status and extreme tachycardia, higher C-reactive protein and D-dimer levels, and lower lymphocyte counts than patients without skin signs. Mucocutaneous manifestations pose a higher risk of admission to the pediatric intensive care unit (odds ratio, 10.24; 95% confidence interval, 2.23-46.88; P = .003). CONCLUSIONS: Children hospitalized with COVID-19 frequently had mucocutaneous involvement, with most symptoms fulfilling criteria for multisystem inflammatory syndrome in children. Patients with an exanthem or conjunctival hyperemia at admission have a higher probability of pediatric intensive care admission than patients without mucocutaneous symptoms.