Characterizing drug-induced epidermal necrolysis in a pediatric cohort.

This study aims to characterize the timeline and clinical features of onset, progression, and management of drug-induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti-epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window.

Imaging More than Skin-Deep: Radiologic and Dermatologic Presentations of Systemic Disorders.

BACKGROUND: Cutaneous manifestations of systemic diseases are diverse and sometimes precede more serious diseases and symptomatology. Similarly, radiologic imaging plays a key role in early diagnosis and determination of the extent of systemic involvement. Simultaneous awareness of skin and imaging manifestations can help the radiologist to narrow down differential diagnosis even if imaging findings are nonspecific. AIMS: To improve diagnostic accuracy and patient care, it is important that clinicians and radiologists be familiar with both cutaneous and radiologic features of various systemic disorders. This article reviews cutaneous manifestations and imaging findings of commonly encountered systemic diseases. CONCLUSIONS: Familiarity with the most disease-specific skin lesions help the radiologist pinpoint a specific diagnosis and consequently, in preventing unnecessary invasive workups and contributing to improved patient care.

Confluent and reticulated papillomatosis in pediatric patients at an urban tertiary care center.

Confluent and reticulated papillomatosis (CARP) is a dermatosis that often presents during adolescence. Prior studies have linked CARP to metabolic syndrome and comorbidities associated with insulin resistance, such as acanthosis nigricans and type 2 diabetes. Despite this, few studies have evaluated the clinical relationship between glucose dysmetabolism and CARP. In this report, we describe the characteristics of a large cohort of pediatric patients with CARP to further evaluate the potential relationship between CARP and metabolic syndrome in children.

Response to Alpelisib in Clinically Distinct Pediatric Patients With PIK3CA -related Disorders.

PIK3CA -related disorders include vascular malformations, potential overgrowth of various tissues, limb abnormalities, disordered soft tissue, and/or fatty hyperplasia that often leads to significant morbidity. Alpelisib, a targeted inhibitor of p110α, an enzyme encoded by the PIK3CA gene, has demonstrated success in a cohort of patients with PIK3CA -driven overgrowth syndromes. We describe the clinical course of 2 pediatric patients treated with alpelisib under the Novartis Managed Access Program. Both patients, though clinically distinct, demonstrate improvements in overgrowth volumes/extent, function of their affected limb, and quality of life, without significant adverse effects after prolonged treatment.

Normal Skin Findings and Cultural Practices in Pediatric Patients with Skin of Color.

The understanding of melanocytes is fundamental to the study of dermatology. These dendritic cells underly the most feared primary cutaneous malignancy, fuel escalating progress in immunotherapy strategies, and invariably underlie entire socioeconomic constructs consciously or unconsciously based on skin tone. Various ethno-genotypes combine with increasing frequency over time, increasing the diversity of skin types that may present with dermatologic diagnoses. Understanding the biology of a variety of skin tones and ethnic practices congruent with distribution of skin tone is invaluable to any physician who wishes to practice efficient and expert care, especially to pediatric patients of this category.

Features of Common Skin Disorders in Pediatric Patients with Skin of Color.

Many dermatologic conditions common in the pediatric population may have unique presentations in skin of color or occur with greater incidence. This may be due to ethnic origin, socioeconomic factors, or other influences. Awareness of the potential variations in skin of color may enhance prompt diagnosis, appropriate treatment, and/or reassurance as indicated.

Ichthyosiform changes in a patient with RAC1 mutation.

RAS-related C3 Botulinum Toxin Substrate 1 (RAC1) is a Rho GTPase that modulates numerous cellular functions including transcriptional regulation and actin-based structure turnover. Reported de novo RAC1 mutations are rare but generally manifest in developmental delay and brain malformations. In Rac1 knockout mice, a hairless phenotype has been observed, but little is known of other cutaneous phenotypes of RAC1 mutations. In this report, we describe the first known case of a RAC1 mutation with ichthyosiform changes.

Biallelic variants in RNU12 cause CDAGS syndrome.

CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations. We performed whole exome and Sanger sequencing to identify the underlying molecular cause in five patients with CDAGS syndrome from four distinct families. Whole exome sequencing revealed biallelic rare variants that disrupt highly conserved nucleotides within the RNU12 gene. RNU12 encodes a small nuclear RNA that is a component of the minor spliceosome and is essential for minor intron splicing. Targeted sequencing confirmed allele segregation within the four families. All five patients shared the same rare mutation NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide within the precursor U12 snRNA 3' extension. Each of them also carried a rare variant on the other allele that either disrupts the secondary structure or the Sm binding site of the RNU12 snRNA. Whole transcriptome sequencing analysis of lymphoblastoid cells identified 120 differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events in the patient. These findings provide evidence of the involvement of RNU12 in craniosynostosis, anal and genitourinary patterning, and cutaneous disease.

Kawasaki's disease and onychomadesis in a 17-month-old girl with non-SARS-CoV2 coronavirus.

Kawasaki disease is a vasculitis of medium-sized vessels and the most common cause of acquired heart defects in the United States. Although its etiology is unclear, an infectious trigger has been theorized, which has been highlighted by the recent pandemic. We present a case of a 17-month-old-girl with concurrent Kawasaki disease and non-SARS-CoV2 coronavirus infection and a sequela of onychomadesis.

Therapy for anogenital verrucae in preadolescent children with topical and systemic treatment.

BACKGROUND/OBJECTIVES: Anogenital verrucae (AV) are benign, human papillomavirus (HPV)-induced tumors of the anogenital skin and mucosa. Medical therapy for AV in preadolescents has not been well studied. We explore the efficacy and safety profile of sinecatechins 15% ointment and imiquimod 5% cream in the treatment of AV, alone and in combination therapy with other commonly used medications. METHODS: A single-institution, retrospective review of children under 12 years of age with AV treated with imiquimod 5% cream and sinecatechins 15% ointment was performed. Demographic data, side effects, and outcomes of therapy were recorded for each patient, and overall efficacy was determined. RESULTS: A total of 37 patients met inclusion criteria. Responses were seen in 8 out of 9 patients treated with sinecatechins 15% ointment (5 full, 3 partial, and 1 no response) and 9 out of 17 patients treated with imiquimod 5% cream (4 full, 5 partial, and 8 no response). Combination therapy with one or more of the following treatments (podophyllin, cimetidine, candida antigen injection, and HPV vaccine) were evaluated, but no combination was objectively superior to the others. No significant difference was found in overall efficacy between sinecatechins and imiquimod. Side effects were mild and limited to irritation and erythema. CONCLUSIONS: Both imiquimod 5% cream and sinecatechins 15% ointment are moderately effective in the treatment of AV in preadolescent children, with a trend toward greater effectiveness of sinecatechins. Combination therapy with other treatments did not significantly increase the effectiveness of topical therapies. Each modality has a tolerable side effect profile with a low risk of serious complications.

Pearls for Dermatologic Surgery in Pediatric Patients.

To achieve successful dermatologic surgery in a pediatric patient, several factors should be considered, including recognizing a child's inherent anxiety, ability to understand/comply with instructions, engaging their caregiver, and minimizing pain. Distraction techniques, including use of smart devices or classic play, have been shown to reduce anxiety, perception of pain, and increase overall satisfaction with the needed procedure. Customizing the child's need based on their stage of development and family preferences further improves how effectively the techniques are deployed. Because children are naturally playful, suturing techniques and dressing of surgical wounds may also require modification for best possible outcome.

Giant Congenital Melanocytic Nevus Treated With Trametinib.

Giant congenital nevi are melanocytic proliferations of the skin that may be complicated by melanoma, neurocutaneous melanocytosis, pain, pruritus, and disfigurement. Current treatment options include surgical resection and medical management of associated symptoms. There is limited efficacy in these modalities. No effective pharmacologic treatments are available for the treatment of these lesions. We present the case of a 7-year-old girl with a giant congenital melanocytic nevus that had an AKAP9-BRAF fusion and was treated with trametinib, which resulted in rapid resolution of the patient's lifelong, intractable pain and pruritus as well as dramatic improvement in the extent of her nevus.

Wardenburg syndrome type 2 in a woman with no genomic mutation commonly associated with the syndrome.

Waardenburg Syndrome (WS) is a condition characterized by pigmentary changes of the hair or skin, hearing loss, heterochromia iridis, and dystopia canthorum. There are four main types of WS, which can be commonly caused by mutations in the PAX3, MITF, EDNRB, EDN3, SNAI2, or SOX10 genes. Herein, we present a patient with Waardenburg Syndrome type 2 with no findings of mutations in the commonly associated genes.

Concurrent Chondrodysplasia Punctata Type 2 (Conradi-Hunermann-Happle Syndrome) and Ichthyosis Vulgaris in Teenaged Twin Girls.

We present concurrent X-linked chondrodysplasia punctata and ichthyosis vulgaris in adolescent fraternal twin girls, notable for initial presentation with dry skin in adolescence, characterized by dark-brown scale typical of ichthyosis vulgaris and blaschkolinear, atrophic, scaly plaques. This constellation of findings prompted further genetic investigation. Using a multigene approach to examine 39 genes associated with congenital ichthyosis, next-generation sequencing revealed a novel heterozygous missense mutation at a mutational hotspot in the EBP gene c.439C>T (p.R147C) in conjunction with a single nonsense mutation in the FLG gene (p.R501X) in both sisters. These individuals highlight the clinical variability of Conradi-Hunermann-Happle syndrome, illustrate the possibility of co-occurrence of rare and common forms of ichthyosis, and demonstrate the utility of multigene analysis.

A Novel Homozygous Missense Mutation in HOXC13 Leads to Autosomal Recessive Pure Hair and Nail Ectodermal Dysplasia.

Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development.

Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase Chain Reaction Detection of Human Papillomavirus 13.

Focal epithelial hyperplasia (FEH), or Heck's disease, is an uncommon benign proliferation of oral mucosa caused by the human papillomavirus (HPV), particularly subtypes 13 and 32. The disease typically presents in young Native American patients and is characterized by multiple asymptomatic papules and nodules on the oral mucosa, lips, tongue, and gingiva. The factors that determine susceptibility to FEH are unknown, but the ethnic and geographic distribution of FEH suggests that genetic predisposition, particularly having the human lymphocytic antigen DR4 type, may be involved in pathogenesis. We report a case of FEH with polymerase chain reaction detection of HPV13 in a healthy 11-year-old Hispanic girl and discuss the current understanding of disease pathogenesis, susceptibility, and treatment.