Black and male children have an increased risk of palmoplantar psoriasis compared to White children.

A retrospective chart review of 332 pediatric psoriasis patients seen at a single academic institution from 2012 to 2022 was conducted to examine the risk factors associated with palmoplantar psoriasis (PP), a painful and treatment-resistant subtype of plaque psoriasis affecting hands and feet. Black patients have a 6.386-fold increase in the odds of having PP compared to White patients and males have a 2.241-fold increase in the odds of having PP. Black and Hispanic/Latino patients displayed a higher prevalence of nail and palm/sole involvement (p < .0001), whereas White patients exhibited more scalp involvement (p = .04). This study reveals the importance of considering the diagnosis of PP in Black male patients based on its demographic prevalence, which may in turn impact clinical care for these patients.

Agminated presentation of fusion-driven melanocytic neoplasms.

BACKGROUND: The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms. METHODS: We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed. RESULTS: Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis. CONCLUSIONS: We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation.

Idiopathic facial aseptic granuloma: case series and review of histological findings.

Idiopathic facial aseptic granuloma (IFG) is a benign condition that typically presents as asymptomatic nodules on the cheeks of pediatric patients. The underlying etiology of IFG remains unknown; however, increasing evidence supports the theory that IFG may lie on a spectrum with childhood rosacea. Typically, biopsy and excision are deferred due to the benign nature, high spontaneous resolution rates, and cosmetically sensitive location. As biopsy is infrequently used to diagnose IFG, a limited library of histopathologic findings exists to characterize the lesions. We present a single-center retrospective review of five cases of IFG diagnosed by histology after surgical excision.

Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity.

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

What's New in Genetic Skin Diseases.

The discoveries of new genes underlying genetic skin diseases have occurred at a rapid pace, supported by advances in DNA sequencing technologies. These discoveries have translated to an improved understanding of disease mechanisms at a molecular level and identified new therapeutic options based on molecular targets. This article highlights just a few of these recent discoveries for a diverse group of skin diseases, including tuberous sclerosis complex, ichthyoses, overgrowth syndromes, interferonopathies, and basal cell nevus syndrome, and how this has translated into novel targeted therapies and improved patient care.

Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease.

BACKGROUND: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to nuclear factor κB, c-Jun N-terminal kinase, and mechanistic target of rapamycin complex 1. Germline CARD11 mutations cause several distinct primary immune disorders in human subjects, including severe combined immune deficiency (biallelic null mutations), B-cell expansion with nuclear factor κB and T-cell anergy (heterozygous, gain-of-function mutations), and severe atopic disease (loss-of-function, heterozygous, dominant interfering mutations), which has focused attention on CARD11 mutations discovered by using whole-exome sequencing. OBJECTIVES: We sought to determine the molecular actions of an extended allelic series of CARD11 and to characterize the expanding range of clinical phenotypes associated with heterozygous CARD11 loss-of-function alleles. METHODS: Cell transfections and primary T-cell assays were used to evaluate signaling and function of CARD11 variants. RESULTS: Here we report on an expanded cohort of patients harboring novel heterozygous CARD11 mutations that extend beyond atopy to include other immunologic phenotypes not previously associated with CARD11 mutations. In addition to (and sometimes excluding) severe atopy, heterozygous missense and indel mutations in CARD11 presented with immunologic phenotypes similar to those observed in signal transducer and activator of transcription 3 loss of function, dedicator of cytokinesis 8 deficiency, common variable immunodeficiency, neutropenia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome. Pathogenic variants exhibited dominant negative activity and were largely confined to the CARD or coiled-coil domains of the CARD11 protein. CONCLUSION: These results illuminate a broader phenotypic spectrum associated with CARD11 mutations in human subjects and underscore the need for functional studies to demonstrate that rare gene variants encountered in expected and unexpected phenotypes must nonetheless be validated for pathogenic activity.

More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations.

BACKGROUND: Infant death in keratitis-ichthyosis-deafness (KID) syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood. OBJECTIVE: We sought to discover characteristics that account for poor outcomes in lethal KID syndrome. METHODS: We collected 4 new cases and 9 previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E. RESULTS: Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those 2 "lethal" mutations is likely multifactorial: during life all had ≥1 serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central carbon dioxide sensing of GJB2 p.A88V. LIMITATIONS: This clinical review was retrospective. CONCLUSION: GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electrophysiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All patients with KID syndrome may have subtle abnormalities beyond the eyes, ears, and skin. Early genotyping of KID syndrome births will inform prognostic discussion.

Tinea faciei starting at day two of life.

Dermatophyte infections are exceedingly rare in neonates, possibly due to the thin stratum corneum and high sebum content of neonatal skin. Only a handful of cases of tinea faciei have been reported in neonates, with the majority of reports occuring in India. Here, we report what to our knowledge is the earliest reported presentation of tinea faciei in the United States. We also provide a brief literature review of other reported cases of tinea faciei in neonates less than 30 days of age.

Pediatric ocular lichen planus and lichen planopilaris: One new case and a review of the literature.

When lichen planus involves the scalp, it is known as lichen planopilaris, and when it involves the eye, it is known as ocular lichen planus; both are rare. Early detection and targeted therapy are crucial in preventing hair loss and scarring conjunctivitis. Little is known regarding appropriate treatment for lichen planopilaris. The objective of this case study is to present a new case of pediatric ocular lichen planus and lichen planopilaris and to identify all reported cases of pediatric lichen planopilaris, highlighting disease involvement, treatment, and response to treatment.

Cutaneous neurofibromas in Neurofibromatosis type I: a quantitative natural history study.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by a predisposition to develop multiple benign tumors. A major feature of NF1 is the development of localized cutaneous neurofibromas. Cutaneous neurofibromas manifest in > 99% of adults with NF1 and are responsible for major negative effects on quality of life. Previous reports have correlated increased burden of cutaneous neurofibromas with age and pregnancy, but longitudinal data are not available to establish a quantitative natural history of these lesions. The purpose of this study is to conduct a prospective natural history study of 22 adults with NF1 over an 8-year period to quantify cutaneous neurofibroma number and size. RESULTS: The average monthly increase in volume for cutaneous neurofibromas was 0.37 mm3 in the back region (95% CI (0.23, 0.51), p < 0.0001), 0.28 mm3 in the abdominal region (95% CI (0.16, 0.41), p < 0.0001), and 0.21 mm3 in the arm/leg region (95% CI (0.08, 0.34), p = 0.0022). The number of cutaneous neurofibromas significantly increased in the back (slope = 0.032, p = 0.011) and abdominal (slope = 0.018, p = 0.026) regions, while the leg/arm regions retained a positive trend (slope = 0.004, p = 0.055). CONCLUSIONS: The number and volume of cutaneous neurofibromas significantly increased over an 8-year timespan; however, the rate of increase is variable by individual and body region. These findings may provide insight into cutaneous neurofibroma development and benefit researchers considering clinical trials targeting cutaneous neurofibromas.

Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis.

Importance: Bathing suit ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1). Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis. We identify novel and recurrent mutations in 16 participants with BSI. Objective: To expand the genotypic spectrum of BSI, identifying novel TGM1 mutations in patients with BSI, and to use BSI genotypes to draw inferences about the temperature sensitivity of TGM1 mutations. Design, Setting, and Participants: A total of 16 participants with BSI from 13 kindreds were identified from 6 academic medical centers. A detailed clinical history was obtained from each participant, including phenotypic presentation at birth and disease course. Each participant underwent targeted sequencing of TGM1. Main Outcomes and Measures: Phenotypic and genotypic characteristics in these patients from birth onward. Results: Of the 16 participants, 7 were male, and 9 were female (mean age, 12.6 years; range, 1-39 years). We found 1 novel TGM1 indel mutation (Ile469_Cys471delinsMetLeu) and 8 TGM1 missense mutations that to our knowledge have not been previously reported in BSI: 5 have been previously described in non-temperature-sensitive forms of congenital ichthyosis (Arg143Cys, Gly218Ser, Gly278Arg, Arg286Gln, and Ser358Arg), and 3 (Tyr374Cys, Phe495Leu, and Ser772Arg) are novel mutations. Three probands were homozygous for Arg264Trp, Arg286Gln, or Arg315Leu, indicating that these mutations are temperature sensitive. Seven of 10 probands with a compound heterozygous TGM1 genotype had a mutation at either arginine 307 or 315, providing evidence that mutations at these sites are temperature sensitive and highlighting the importance of these residues in the pathogenesis of BSI. Conclusions and Relevance: Our findings expand the genotypic spectrum of BSI and the understanding of temperature sensitivity of TGM1 mutations. Increased awareness of temperature-sensitive TGM1 genotypes should aid in genetic counseling and provide insights into the pathophysiology of TGM1 ichthyoses, transglutaminase-1 enzymatic activity, and potential therapeutic approaches.

Dermatological clues to the diagnosis of atypical complete DiGeorge syndrome.

Atypical complete DiGeorge syndrome (DGS) is an extremely rare congenital disease characterized by an eczematous dermatitis, lymphadenopathy, and an oligoclonal T-cell proliferation. Because its initial presentation may be confused with other types of eczematous dermatitis, diagnosis and treatment are usually delayed. We describe herein a case of an infant with atypical complete DGS to draw attention to the clinical and histopathological findings that lead us to the diagnosis.

Mycophenolate mofetil therapy for pediatric bullous pemphigoid.

Bullous pemphigoid (BP) is a common autoimmune blistering disease in the adult population, but extremely rare in the pediatric population. Childhood BP usually has a favorable prognosis and responds well to topical and oral steroids. However, for patients that do not respond to corticosteroids, therapeutic alternatives are scarce. We report a case of a toddler with recalcitrant BP who was successfully treated with mycophenolate mofetil (MMF).

Utility of Wood's light in margin determination of melanoma in situ after excisional biopsy.

BACKGROUND: Margin evaluation of melanoma in situ (MIS) is difficult because of its ill-defined clinical borders. Wood's light examination is commonly used to help delineate MIS margin before excision. OBJECTIVE: To prospectively study the accuracy of preoperative Wood's light examination for margin assessment of MIS. MATERIALS AND METHODS: The authors evaluated 60 patients before excision of MIS under white light and Wood's light. Staged excision was performed using the square procedure technique. After achieving clear margins, they compared final wound size with expected wound size if surgical margins had been based on Wood's light examination. RESULTS: Seven patients (11.7%) had Wood's light enhancement beyond the visible margin of the biopsy site. In all 7, increased wounding would have occurred if the surgical margins had been based on Wood's light examination. In 1 of the 7, use of the Wood's light examination would have reduced the surgical stages needed by 1 stage but would have increased the wound size by 83.3%. CONCLUSION: Wood's light examination has limited utility if complete excisional biopsy of MIS is performed before treatment. In this study, surgical margin based on the Wood's light examination would have resulted in an increased average wound size and would not have reduced the number of stages needed when performing the square procedure.

Validity and interexaminer reliability of a new method to quantify skin neurofibromas of neurofibromatosis 1 using paper frames.

BACKGROUND: Skin neurofibromas represent one of the main clinical manifestations of neurofibromatosis 1, and their number varies greatly between individuals. Quantifying their number is an important step in the methodology of many clinical studies, but counting neurofibromas one by one in individuals with thousands of tumors is arduous, time-consuming, and subject to intra and interexaminer variability. We aimed to evaluate the efficacy of a new methodology for skin neurofibromas quantification using paper frames. METHODS: The sample comprised 92 individuals with NF1. Paper frames, with a central square measuring 100 cm2, were placed on the back, abdomen and thigh. Images were taken, transferred to a computer and two independent examiners counted the neurofibromas. The average number of neurofibromas/100 cm2 of skin was obtained from the mean of the three values. The differences in the quantity of neurofibromas counted by two examiners were evaluated with Intraclass correlation coefficient (ICC), paired t-test, Bland-Altman and survival-agreement plots. To evaluate the predictive value of the method in obtaining the total number of neurofibromas, 49 participants also had their tumors counted one by one. Reproducibility was assessed with Pearson's correlation coefficients and simple linear regression model. RESULTS: There was excellent agreement between examiners (ICC range 0.992-0.997) and the total number of skin neurofibromas could be predicted by the adhesive frames technique using a specific formula (P < 0.0001). CONCLUSIONS: In this article we describe a reliable, easy and rapid technique using paper frames to quantify skin neurofibromas that accurately predicts the total number of these tumors in patients with NF1. This method may be a useful tool in clinical practice and clinical research to help achieve an accurate quantitative phenotype of NF1.

Epidermolysis bullosa nevus in a patient with recessive dystrophic epidermolysis bullosa: a case report.

We present a case of a 6-year-old girl with recessive dystrophic epidermolysis bullosa (EB) who presented with a large pigmented lesion clinically concerning for melanoma. After histological examination and fluorescent in situ hybridization analysis, diagnosis of EB nevus was performed. EB nevi are benign melanocytic neoplasms with histological findings similar to recurrent nevi occurring in all types of EB. They often mimic melanoma clinically, dermatoscopically, and histopathologically. The ability to recognize an EB nevus is essential for appropriate management of the patient. Unnecessary surgical excision in patients with already high-risk EB should be avoided. Close monitoring of these lesions is recommended because no cases of transformation to melanoma have been described.