The pathogenesis of severe blistering mucocutaneous reactions, including reactive infectious mucocutaneous eruptions, is unknown. We hypothesize that patients have genetic variations that predispose disease susceptibility from infectious factors. Subjects enrolled in our study and, if possible, their biological parents consented to DNA collection. Paired-end short-read whole-genome sequencing (30x) was performed. A standard pipeline removed low-quality variants. Analysis focused on rare (minor allele frequency < 1%), protein-altering variants. Reads were mapped to human reference genome GRCh38 with variant calling. Genetic ancestry was assessed via principal component analysis. Variants were annotated by allele frequency, predicted effect, pathogenicity, and clinical relevance. DNA was sequenced on 19/37 probands and 29/52 unaffected parents. On average, we identified 4.87M variants/ person including 4.32M single nucleotide variants and 500,000 insertions or deletions (62.7% intronic; 22% intergenic). 9,000+ protein altering variants/sample were identified. To identify causal variants, we analyzed trios for: 1) autosomal recessive, 2) de novo or autosomal dominant, or 3) X-linked variants. We gene mapped the variants and identified genes affected in ≥2 probands. We identified ∼240 rare de novo variants/family and 210 total mutated genes in the probands. Ongoing analysis will refine candidate genes by predicted variant effect, gene function, and population allele frequency.

Crohn disease (CD), a subtype of inflammatory bowel disease, may be complicated by extraintestinal manifestations. Although cutaneous findings are among the most frequent, metastatic Crohn disease (MCD), defined as mucocutaneous CD at sites noncontiguous with the gastrointestinal tract, is rare. Children with MCD are more likely than adults to develop genital inflammation. Case reports describe the vulva, scrotum, and penis as common locations of involvement in children with genital MCD. We report a case of a pediatric patient with systemic lupus erythematosus who developed vaginal discharge as a presenting symptom of MCD in the absence of an anorectal-vaginal fistula. We describe an unusual combination of clinical features and intend to improve awareness of uncommon extraintestinal manifestations of CD.

BACKGROUND:Pediatric skin-limited discoid lupus erythematosus (DLE-only) is rare, with limited data on risk factors for progression to systemic lupus erythematosus (SLE). OBJECTIVE:To assess incidence, risk factors, and phenotype of pediatric DLE-only progression to SLE. METHODS:In this 17-site retrospective cohort of pediatric DLE, the primary outcome was time to SLE diagnosis (American College of Rheumatology classification criterion ≥4). Kaplan-Meier estimates for 1-, 2-, and 5-year progression to SLE were generated. Cox proportional hazards modeling identified baseline predictors of progression to SLE. RESULTS:The 1-year progression rate from DLE-only to SLE was 14.4% (95% CI, 9.6-18.9). Progression to SLE was most strongly associated with baseline antinuclear antibody positivity (hazard ratio, 3.71) and older age (hazard ratio, 1.11/y). Antiphospholipid antibodies and cytopenias also predicted progression to SLE in multivariable analysis. The SLE phenotype was relatively mild, with most patients meeting mucocutaneous and laboratory criteria (22/236, 9%) and a few patients in whom other end-organ diseases developed (7/236, 3%). LIMITATIONS:Retrospective design, missing data. CONCLUSION:Antinuclear antibody-positive patients with DLE-only warrant close monitoring for progression to SLE, especially within the first year. Severe end-organ disease in patients with DLE who progress to SLE is uncommon. Future studies should test whether early recognition and intervention in DLE-only slows progression to SLE.

BACKGROUND:The field of pediatric dermatology continues to experience a critical workforce shortage, which negatively impacts specialized care for children with dermatologic conditions. OBJECTIVE:To analyze pediatric dermatology fellowship applicant data and match rate trends from 2009 to 2023, board certification of new pediatric dermatologists from 2010 to 2023, and assess workforce trends and identify potential challenges in the pipeline of pediatric dermatologists. METHODS:This retrospective study examined data provided by the Society of Pediatric Dermatology and San Francisco Match for pediatric dermatology fellowships from 2009 to 2023 and board certification information from the American Board of Dermatology. RESULTS:Our analysis revealed a limited number of board-eligible fellowship applicants despite the availability of multiple fellowship programs, with an average of 32% of programs failing to match fellows. Board certification rates varied, with an increase over time in non-board-eligible fellow applicants. The geographic distribution of fellowship-trained pediatric dermatologists showed regional disparities. LIMITATIONS:Some pediatric dermatology fellows may enter fellowship outside of the official match process, not captured in the data. We used a public search engine for practice data, and it is possible that misclassification occurred. CONCLUSION:In recent decades, the dire need for pediatric dermatologists has exceeded the available workforce, with numerous fellowship programs remaining unfilled.

BACKGROUND/OBJECTIVES:The prototypical non-scarring alopecia is alopecia areata (AA), which can present in multiple forms on the scalp, including patchy, ophiasis, sisaipho, diffuse, and totalis. Not included within current alopecia classification systems is a variant characterized by macules < 1 cm in diameter. Our objective was to identify and describe this variant of alopecia not previously recognized. METHODS:We conducted an institutional review board-approved, single-center retrospective chart review of patients presenting with hair loss to a pediatric dermatology clinic. Potential subjects were identified through a search using ICD9 and ICD10 codes for AA, alopecia unspecified, or other non-scarring alopecia from ambulatory dermatology visits from 2/1/2011 to 2/01/2024. After review, 392 patients with a diagnosis other than patchy AA or macular alopecia were excluded. RESULTS:Of the 471 patients included in this study, 397 patients were categorized as patchy AA and 74 patients as macular alopecia. Compared to those with patchy AA, patients with macular alopecia had a female (57/74, 77%) and Hispanic/Latinx (46/74, 62%) predominance, with a younger median age of onset (5.9 years). Macular alopecia was located mainly near the parietal scalp. Patchy AA was located mainly on the occipital scalp. When follow-up data was available, resolution of hair loss without recurrence occurred in 63% of macular alopecia (median 5.0 months) and 20% of patchy AA patients (median 8.0 months), p < 0.001. CONCLUSIONS:We propose the term "macular alopecia" for this entity characterized by small macules and spontaneous resolution within months.

Deep-seated pyogenic granulomas (DSPG) are a rare variant of pyogenic granulomas and are commonly mistaken for other entities. Often, DSPG present as blue papulonodules without ulceration, and their clinical and histologic appearance can mimic other common subcutaneous nodules seen in pediatric patients, including hemangiomas, venous malformations, pilomatricomas, and kaposiform hemangioendotheliomas. Herein, we describe the clinical and histologic features of six pediatric cases of DSPG, as the clinicopathologic correlation of DSPG is scarce in the literature, especially in pediatric patients.

Recurrent macular vasculitis in hypergammaglobulinemia, previously termed hypergammaglobulinemic purpura of Waldenström (HGPW), is a rare disorder characterized by recurrent episodes of lower extremity purpura and edema with symptoms of stinging and burning. We report a pediatric case of recurrent macular vasculitis in hypergammaglobulinemia and enteropathy as the presenting clinical manifestation of activated phosphoinositide 3-kinase delta syndrome (APDS). APDS, a rare inborn error of immunity, has been infrequently described in association with vasculitis, and we suspect previously described cases could be more accurately classified as recurrent macular vasculitis in hypergammaglobulinemia.

Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is associated with significant morbidity despite therapeutic advances. Distinct clinical phenotypes have emerged, which can correlate with myositis-specific antibodies. Because translational data solidify the role of type I IFNs in JDM disease pathogenesis, integration of clinical and molecular phenotyping may impact the choice of targeted therapy. This paper reviews clinical and molecular phenotyping in JDM and translational insights into immune pathogenesis that have created emerging options for targeted therapy.

Importance Detecting activity of morphea can be complex but is crucial for adequate treatment and outcome assessment. The Morphea Activity Measure (MAM) was recently validated, but its responsiveness to change in disease activity has not been studied. Objective To evaluate the internal and external responsiveness of MAM to changes in disease activity in pediatric patients. Design, Setting, and Participants This multicenter prospective, longitudinal prognostic study was performed from October 2021 to January 2023 at 4 pediatric referral centers in North America. Consecutive pediatric patients with morphea who were available for data collection at baseline and at a follow-up visit at least 3 months later were studied. Exposure Patient demographics, clinical characteristics, and measurements of disease activity collected at baseline and the subsequent visit. Main Outcome and Measures Responsiveness of MAM to disease activity according to the modified Localized Scleroderma Severity Index (mLoSSI), the Physician Global Assessment (PGA), and a patient and parent global assessment (PtGA) was analyzed using mean and percentage change, standardized effect size, and standardized response mean (SRM) from baseline to follow-up 3 or more months later. Differences between patients whose activity improved vs did not improve were evaluated using the Mann-Whitney U test. The correlation between percentage change in MAM score and mLoSSI, the PGA, and the PtGA was calculated using Spearman rank correlation. Results A total of 43 patients (mean [SD] age at onset, 7.11 [3.18] years; 26 [60.5%] female) were included. The mean change and percentage change in MAM score were significantly larger in those whose disease activity improved by the PGA (mean: -18.75 [95% CI, -31.92 to -5.57] vs 2.73 [95% CI, -1.97 to 7.45]; percentage: -108.08% [95% CI, -155.21% to -60.95%] vs -24.11% [95% CI, -81.22% to 32.99%]) and by mLoSSI (mean: -24.15 [95% CI, -41.89 to -6.41] vs -1.30 [95% CI, -8.50 to 5.70]; percentage: -172.06% [95% CI, -263.68% to -80.45%] vs -21.57% [95% CI, -48.13% to 4.97%]) than in those whose activity did not change. The SRM of MAM was significantly different between groups for both measures; the responsiveness was large in those whose activity decreased by the PGA (-0.75 [95% CI, -1.29 to -0.22]) and mLoSSI (-0.97 [95% CI, -1.69 to -0.25]) and none to small in those whose activity did not change by the PGA (0.11 [95% CI, -0.08 to 0.30]) or mLoSSI (-0.05 [95% CI, -0.34 to 0.23]). Percentage change in MAM score correlated strongly and significantly with change in mLoSSI (rho = 0.69; P < .001) and PGA (rho = 0.65; P < .001), but there was no correlation with change in the PtGA (rho = 0.26; P = .09). Conclusions and Relevance In this prognostic study, MAM was found to be internally and externally responsive to changes in disease activity. Further evaluation in mixed cohorts of all ages and specialties is needed.

A 4-month-old male presented for a large, hypertrichotic brown patch on the upper back with several scattered 0.5-1.5 cm, round to oval, brown macules and patches on the trunk and extremities. The lesion was initially diagnosed as a giant congenital melanocytic nevus based on clinical exam and histopathology with immunohistochemical stains. The patient was later diagnosed with neurofibromatosis type 1, and the lesion on the back developed a "bag of worms" texture consistent with a plexiform neurofibroma and found to harbor a pathogenic variant in the NF1 gene. This case highlights the diagnostic challenge of differentiating these lesions and their overlapping clinical and histopathological features.

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is characterized by the presence of multiple small (1-2 cm in diameter) capillary malformations of the skin. This disorder has been described as two distinct entities: CM-AVM1 and CM-AVM2. The diagnosis of these disorders has been associated with pathogenic variants in the RASA1 gene for RASA1-CM-AVM, formerly known as CM-AVM1, and, more recently, the EPHB4 genes for EPHB4-CM-AVM, formerly known as CM-AVM2. Affected patients with either type may also have arteriovenous malformations and fistulas, which can cause life-threatening bleeding, congestive heart failure, or neurologic consequences such as stroke. These syndromes are typically either sporadic or inherited in an autosomal dominant manner with variable expressivity. We report a case series of a father and three daughters who have clinically diagnosed EPHB4-CM-AVM syndrome who were found to have a variant of uncertain significance (VUS) in EPHB4 that has only been reported once prior.

BACKGROUND:Migrants often face worse health outcomes in countries of transit and destination because of challenges such as financial constraints, employment problems, lack of a network of social support, language and cultural differences, and difficulties accessing health services. As understanding how the migrant context affects patient-provider engagement is critical to the provision of contextually appropriate care, this study aimed at understanding primary health care provider perspectives on challenges and opportunities of the intercultural care process for migrant patients with diabetes and obesity.METHODS:This qualitative study within a multimethod, participatory research project involved primary care providers in clinics and primary care networks in Edmonton, Alberta, between September 2019 and February 2020. We explored health care providers' approaches to diabetes and obesity management, and experiences of and challenges with intercultural care. We conducted a thematic analysis using an interpretive qualitative approach.RESULTS:We conducted 9 interviews and 4 focus groups and identified 3 themes: a shift from traditional weight loss-centred approaches; relationships and navigating cultural distance; and importance of and limitations in identifying and addressing root causes and barriers. Health care providers encounter considerable nonmedical challenges when supporting immigrant patients, such as navigating cultural distance and working with patients' financial constraints.INTERPRETATION:The nonmedical challenges we identified can hinder the process of chronic disease management. Thus, in addition to educational programs and trainings to enhance the cultural competency of health care providers, incorporating avenues for cultural brokering in health care can provide invaluable support in patient-provider engagements to mitigate these challenges.

To the Editor: Costello syndrome (CS) is caused by a pathogenic variant in the regulatory HRAS gene, leading to constitutive activation of the RAS/mitogen-activated protein kinase cell signaling pathway. Dysregulation of RAS/mitogen-activated protein kinase has long been implicated in cancer pathogenesis, but more recently it has been identified as the cause of several developmental syndromes termed RASopathies, which include CS. Due to the ubiquitous expression of HRAS, patients with CS can have multiorgan sequelae, including growth and developmental delays, cardiac anomalies, and neurologic issues. 1 Gripp K.W. Morse L.A. Axelrad M. et al. Costello syndrome: clinical phenotype, genotype, and management guidelines. Am J Med Genet. 2019; 179: 1725-1744https://doi.org/10.1002/ajmg.a.61270 Crossref PubMed Scopus (55) Google Scholar Distinctive dermatologic findings include cutaneous papillomas (particularly around the nares), palmoplantar keratoderma, acanthosis nigricans, and generalized hyperpigmentation. 2 Siegel D.H. Mann J.A. Krol A.L. Rauen K.A. Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development. Br J Dermatol. 2012; 166: 601-607https://doi.org/10.1111/j.1365-2133.2011.10744.x Crossref PubMed Scopus (64) Google Scholar In some patients, the papilloma burden can be quite high, and patients and parents may find the numerous lesions to be irritating or stigmatizing. The exact pathogenesis of these papillomatous lesions has yet to be elucidated, but the role of human papillomavirus (HPV) infection has been previously debated given the clinical and dermatopathological resemblance to verrucae (Fig 1). 2 Siegel D.H. Mann J.A. Krol A.L. Rauen K.A. Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development. Br J Dermatol. 2012; 166: 601-607https://doi.org/10.1111/j.1365-2133.2011.10744.x Crossref PubMed Scopus (64) Google Scholar , 3 Torrelo A. López-Avila A. Mediero I.G. Zambrano A. Costello syndrome. J Am Acad Dermatol. 1995; 32: 904-907https://doi.org/10.1016/0190-9622(95)91559-1 Abstract Full Text PDF PubMed Scopus (23) Google Scholar , 4 Gonzalez M.E. Blanco F.P. Garzon M.C. Verrucous papules and plaques in a pediatric patient—quiz case. Arch Dermatol. 2007; 143: 1201-1206https://doi.org/10.1001/archderm.143.9.1201-b Crossref PubMed Google Scholar

Lipofibromatosis-like neural tumors (LPF-NTs) are a recently discovered group of spindle cell tumors defined by the presence of a lipofibromatosis-like pattern, CD34 and/or S100 reactivity, and frequent neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangements. As new cases emerge, the spectrum of features observed in LPF-NTs continues to evolve. Here we describe the case of an 11-year-old with LPF-NT with a dermatofibrosarcoma protuberans-like honeycomb pattern, CD34 and S100 co-expression, and an NTRK1 rearrangement. We also review the clinical and molecular features of the 73 cases of LPF-NT previously described in the literature.

Context: Personalized healthcare strategies are recommended for diabetes and obesity. This approach helps to identify and address root causes and barriers to patients' health, and provides them with a sense of agency in healthcare. To develop such strategies for migrant patients, there should be a deeper understanding of their situation. Objective: To understand healthcare gaps and opportunities for enhancing diabetes and obesity care for immigrant and refugee populations in primary care. Study Design, Setting and Population Studied: A community-based research, involving 3 qualitative studies conducted in Edmonton, Alberta. Study participants were: 1) members of ethnocultural communities with diabetes and/or obesity; 2) Multicultural Health Brokers (MCHB) - community health workers (CHW) in these communities; and 3) Healthcare providers (HCP). Data set and Analysis: We generated data through interviews and focus groups. Community member (CM) study had 3 focus groups (two groups of 8 males & females (mixed); one of 13 females); and 22 interviews (5 males, 8 females). MCHB study had 10 interviews (females) and 2 observation sessions. HCP study had 4 focus groups (two groups of 6; 2 groups of 8 mixed) and 9 interviews (2 males, 7 females). Data were thematically analyzed. Outcome Measures: CM study explored lived experiences of diabetes and obesity. HCP study examined experiences with caring for patients with diabetes and obesity from ethnocultural communities. MCHB study examined broker roles in relation to primary care. Results: CM study showed that pre- and post-immigration stressors interact synergistically with the lived experience of diabetes and obesity thereby compounding the adverse disease effects. HCP study showed significant challenges navigating cultural distance and trying to address the non-medical issues of migrant patients. MCHB study illustrated their embeddedness in ethnocultural communities playing an invaluable but largely unrecognized role as partners in primary healthcare. Conclusions: Our findings highlight the challenges of intercultural care in primary care settings. CHWs like the MCHB can provide context for healthcare providers, thereby supporting a personalized and context-informed care that understands the intersecting realities of migrant populations. Collaborations with CHWs in primary care have widespread implications for improving healthcare and reducing health disparities for migrants with diabetes and/or obesity.