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.

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.

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.

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.

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.

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.

Reliability assessment and validation of the postacne hyperpigmentation index (PAHPI), a new instrument to measure postinflammatory hyperpigmentation from acne vulgaris.

BACKGROUND: There are no validated outcome measures for postinflammatory hyperpigmentation (PIH). OBJECTIVE: We sought to determine the reliability and validity of an outcome measure for PIH after acne in patients with skin of color. METHODS: A postacne hyperpigmentation index (PAHPI) was developed. Six raters scored 21 patients with PIH twice. Reliability was determined within and between raters, whereas validity was evaluated by comparing scores with severity ranking by an independent dermatologist. The pigment intensity scores were compared with the melanin index of each patient using a narrowband reflectance spectrophotometer. A quality-of-life score (Skindex-29) was also compared with PAHPI scores. RESULTS: Total PAHPI scores showed good reliability within and between raters and were valid when compared with clinical severity and melanin indices. Good correlation was achieved between the total PAHPI score and the emotion subscale of the Skindex-29. LIMITATIONS: Generalizability of results is limited to African American females. CONCLUSION: The PAHPI shows good reliability and validity when scored on patients with PIH from acne vulgaris. The PAHPI also correlates well with the emotional impact of PIH as measured by the Skindex-29. Future studies should assess the ability of the PAHPI to change with improvement of PIH from acne after treatment.

Nevus comedonicus in oral-facial-digital syndrome type 1: a new finding or overlapping syndromes?

We report a patient with oral-facial-digital syndrome type 1 (OFDS1) who exhibited features overlapping those of nevus comedonicus syndrome, an unusual presentation that may potentially represent a new variant of OFDS1. OFDS1 and nevus comedonicus syndrome represent two rare syndromes with numerous overlapping features that have yet to be described in relation to one another. The features present in our patient led us to propose the possibility of a new variant of OFDS1 in which nevus comedonicus represents a cutaneous manifestation of the syndrome. Knowledge of this potential relationship is important for identification and management of the syndromes' accompanying manifestations in affected patients and may offer further insight into crossroads of pathogenesis.

Response to patient-initiated plant extract treatment for atopic dermatitis.

Ethnomedical practices are increasing in all parts of the world, including many urban centers. We describe a unique case of a 7-year-old girl with atopic dermatitis who was responsive to parent-initiated treatment with the extract of a plant from the Chenopodium genus. A brief discussion raises awareness of such practices to the practicing dermatologist.

Acquired protein energy malnutrition in glutaric acidemia.

We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica.

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.

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.

Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method.

BACKGROUND: The Melasma Area and Severity Index (MASI), the most commonly used outcome measure for melasma, has not been validated. OBJECTIVE: We sought to determine the reliability and validity of the MASI. METHODS: After standardized training, 6 raters independently rated 21 patients with mild to severe melasma once daily over a period of 2 days to determine intrarater and interrater reliability. Validation was performed by comparing the MASI with the melasma severity scale. The darkness component of the MASI was validated by comparing it with the difference between mexameter scores for affected versus adjacent normal-appearing skin. The area component of the MASI was validated by comparing it with the area of each section of the face determined by computer-based measurement software. RESULTS: The MASI score showed good reliability within and between raters and was found to be valid when compared with the melasma severity scale, mexameter scores, and area measurements. Homogeneity assessment by raters showed the least agreement and can be removed from the MASI score without any loss of reliability. LIMITATIONS: Patients were limited to Hispanic, African, and Asian backgrounds. CONCLUSION: The MASI is a reliable measure of melasma severity. Area of involvement and darkness are sufficient for accurate measurement of the severity of melasma and homogeneity can be eliminated.

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.

Emergent medical and surgical management of mediastinal infantile hemangioma with symptomatic spinal cord compression: case report and literature review.

PURPOSE: We report an extremely rare case of a patient with a large, cervical, and upper thoracic cutaneous hemangioma associated with a separate, underlying mediastinal hemangioma extending to the epidural space causing significant spinal cord compression. CASE REPORT: A 6-week-old female presented with decreased movement of her right arm and bilateral lower extremity hyperreflexia. Her arm weakness progressed to paralysis over the course of 24 h. She underwent emergent surgical decompression and medical therapy with propranolol and systemic corticosteroids. CONCLUSION: While several recent reports have described dramatic responses of hemangiomas to propranolol, this is the first case in which it was used as part of a multimodal approach to symptomatic spinal cord compression. The infant improved immediately after surgery. She is neurologically intact and has radiographic regression of the hemangiomas on follow-up examination 6 months later.

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.