Dermatology Research Center

Abstract The role of ion channel activity in high-grade glioma (HGG) pathophysiology remains poorly understood. Using weighted gene co-expression network analysis (WGCNA) of RNA-seq data, we identified a “neuronal regulation” module conserved across pediatric Diffuse Midline Glioma (DMG), non-brainstem HGG (NBS-HGG), and adult glioblastoma. Single-cell RNA-seq and spatial transcriptomics revealed this module is enriched at the leading edge. Significantly, we identified the γ-Aminobutyric acid type A receptor (GABAAR) genes, GABRA1 (α1) and GABRG2 (γ2), as central hubs within this module, whose expression in patient-resected tumour tissue co-localised with GABAergic synaptic markers. GABRA5 (α5), a component of non-synaptic GABAARs, was also upregulated in tumour cells in both patient tissue and glioblastoma organoids (GBOs). Pharmacologic targeting of GABAARs in GBOs using antagonists (S44819, GABA(A)-compound 1b) robustly suppressed tumour invasion and proliferation, with effects further enhanced by radiation and temozolomide. Our findings identify ion channel hubs at the glioma-invasive front as druggable vulnerabilities and highlight GABAAR-targeting as a promising strategy to disrupt tumour progression.

A 28-year-old Indian male with no previous medical or dermatological history presented with mildly pruritic linear skin lesions over the right anterior chest and arm. The lesions had been gradually progressing over the course of six years. Examination revealed multiple confluent, reddish-brown papules following Blaschko’s lines, along with punctate hyperkeratotic papules over the right hand, with sparing of the mucosa, scalp, and nails. Histopathological analysis demonstrated a cup-shaped epidermal invagination filled with a parakeratotic column, absence of the granular layer, and dyskeratotic keratinocytes, with an eccrine duct located at the base of the lesion - indicating an acrosyringial origin. These findings confirmed the diagnosis of porokeratotic eccrine ostial and dermal duct nevus (PEODDN). PEODDN is a rare hamartomatous disorder with eccrine differentiation. While it usually presents at birth or during childhood, adult-onset cases have been documented - particularly along Blaschko’s lines. The condition may present with porokeratotic plaques or comedo-like plugs on acral sites, and our case uniquely exhibited both features. Although its pathogenesis remains unclear, several theories suggest abnormal keratinization, structural defects in eccrine ducts, and possible genetic mutations. PEODDN may occasionally be associated with systemic or neoplastic conditions. Treatment options remain variable, and while no standard therapy offers complete resolution, our findings support the potential role of oral retinoids in improving lesion appearance and symptoms in adult-onset cases. Further evaluation of systemic retinoid therapy in PEODDN is warranted.

Pemphigus foliaceus (PF) is a rare autoimmune blistering skin disease characterized by superficial erosions and crusts due to autoantibodies targeting desmoglein 1. Diagnosis can be challenging, particularly when initial presentation mimics common dermatoses such as atopic dermatitis. We report the case of a 55-year-old Syrian female initially diagnosed with severe atopic dermatitis, who presented with widespread pruritic skin lesions unresponsive to corticosteroids. Clinical deterioration with new vesiculobullous lesions prompted re-evaluation. Histopathology and serologic testing confirmed PF. The patient achieved disease control with systemic corticosteroids and immunosuppressive therapy and remains in remission after two years of follow-up. This case underscores the diagnostic complexity of PF, especially in patients with overlapping or misleading dermatologic histories. A high index of suspicion, timely biopsy, and serological confirmation are essential for diagnosis. Long-term immunosuppressive therapy combined with corticosteroids proved effective in achieving sustained remission.

In recent years, the evaluation metrics for dermatology residency applications have changed, particularly following the transition of the United States Medical Licensing Examination (USMLE)Step 1 to a pass/fail grading system. This retrospective analysis examines dermatology residency match data from 2020 to 2024, focusing on trends in USMLE Step 2 Clinical Knowledge (CK) scores and research publications. Data extracted from the National Resident Matching Program documents revealed a notable increase in unmatched applicants with Step 2 CK scores above 250 and a decrease in matched applicants with similar scores. Concurrently, research output has risen, with matched applicants reporting over 25 publications increasing from 80 in 2020 to 121 in 2024, and a corresponding increase among unmatched applicants from 10 to 35 over the same period. Despite these improvements in individual metrics, the overall match rates for applicants with high Step 2 CK scores and extensive research portfolios have declined, suggesting that excellence in these areas alone does not guarantee a successful match.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, discovered in 2020, is an adult-onset autoinflammatory condition caused by somatic mutations in the UBA1 gene, resulting in systemic inflammation and hematologic abnormalities [1]. It frequently overlaps with rheumatologic and hematologic diseases such as relapsing polychondritis and myelodysplastic syndrome [2]. The relationship between VEXAS syndrome and concomitant substance use disorders (SUDs) remains unknown. Given the link between VEXAS syndrome and significant inflammatory dysregulation, we expected that individuals with VEXAS would have higher rates of SUDs due to common pathways involving immune dysfunction [3]. Using the TriNetX Database, we performed a large-scale, propensity-matched case-controlled analysis to investigate the relationship between VEXAS syndrome and SUDs. In February 2025, we found 403,404 patients with and 3,832,915 patients without the diagnosis of VEXAS syndrome on TriNetX using International Classification of Diseases, Tenth Revision (ICD-10) codes for relapsing polychondritis (M94.1), multisystem inflammatory syndrome (M35.81), thrombotic microangiopathy (M31.1), elevated white blood cell count, unspecified (D72.829), systemic involvement of connective tissue, unspecified (M35.9), and other specified disorders involving the immune mechanism, not elsewhere classified (D89.89) as VEXAS does not have an ICD-10 code yet. Various SUD comorbidities were analyzed after propensity score matching with 403,404 control patients, matched based on age, gender, ethnicity, and race. Results were reported with odds ratios (ORs) calculations with 95% confidence intervals (CIs) using Wald's method (Table 1). In patients with VEXAS syndrome, there is a statistically significant association with tobacco use (OR, 2.059; 95% CI, 2.02–2.098; p < 0.0001), anxiety disorders (OR, 1.952; 95% CI, 1.933–1.971; p < 0.0001), depression (OR, 2.078; 95% CI, 2.056–2.1; p < 0.0001), vaping-related disorders (OR, 3.679; 95% CI, 2.759–4.907; p < 0.0001), alcohol abuse (OR, 1.98; 95% CI, 1.931–2.031; p < 0.0001), nicotine dependence (OR, 1.811; 95% CI, 1.782–1.839; p < 0.0001), opioid abuse (OR, 3.092; 95% CI, 2.933–3.259; p < 0.0001), cannabis abuse (OR, 2.702; 95% CI, 2.574–2.835; p < 0.0001), other psychoactive substance abuse (OR, 2.985; 95% CI, 2.859–3.117; p < 0.0001), sedative abuse (OR, 2.814; 95% CI, 2.542–3.115; p < 0.0001), cocaine abuse (OR, 2.39; 95% CI, 2.263–2.524; p < 0.0001), hallucinogen abuse (OR, 1.855; 95% CI, 1.574–2.186; p < 0.0001), and inhalant abuse (OR, 1.892; 95% CI, 1.754–2.04; p < 0.0001). The relationship between SUDs and VEXAS syndrome was statistically significant. These findings are consistent with previous research showing that chronic inflammatory disorders frequently coexist with SUDs, possibly due to bidirectional interactions between immunological activation and substance use [2, 3]. Elevated cytokines in VEXAS syndrome can worsen neuropsychiatric symptoms and may explain the potential increased use in substance use disorders [4, 5]. Additionally, drugs such as alcohol and nicotine may further dysregulate immune responses, increasing VEXAS-related inflammation [2, 3]. Although we have demonstrated a statistically significant correlation between these two variables, it is almost impossible to discern if SUDs cause VEXAS syndrome or vice versa. The study possesses limitations. Although most patients included in the study for VEXAS syndrome were White (70.5%), consistent with the current literature, they were not male in majority (42.4%), which is inconsistent with the syndrome's X-linked etiology [1]. This is attributed to the fact that VEXAS syndrome may be diagnosed in various ICD-10 codes, which may lead to misrepresentation of the ORs in our analysis [5]. Furthermore, the retrospective methodology prohibits causal inference. These results highlight the necessity for integrated care strategies that treat inflammation and substance dependence in VEXAS patients. Future studies should investigate the genetic and epigenetic linkages between UBA1 mutations and substance-related pathways, including the effect of SUD treatment on inflammatory outcomes [4]. We gratefully acknowledge TriNetX participants for their contributions, without whom this research would not have been possible. We also thank the TriNetX database for making available the participant data [and/or samples and/or cohort] examined in this study. M.B.T. is an affiliated researcher with Castle Biosciences and Sanofi-Regeneron and is also an advisor for Boehringer Ingelheim, Novartis, UCB, and Pfizer. All other authors have no conflicts of interest to declare. This study was considered by our IRB to be nonhuman research and thus exempt from review. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

ObjectivesEnlarged forehead veins are common, with the supratrochlear vein being a frequent patient concern. Given the potential morbidity of sclerotherapy and phlebectomy, endovenous laser ablation (EVLA) may be a viable treatment option.MethodsWe present a patient with an enlarged right supratrochlear forehead vein treated with a single session of 1320nm EVLA.ResultsClinical eradication was demonstrated at 3 months posttreatment with only self-limited edema and delayed ecchymosis.ConclusionsPilot preliminary evidence demonstrates that EVLA of the supratrochlear vein has a high benefit-to-risk ratio.

Xylazine, a veterinary sedative, has emerged as a significant adulterant in the illicit drug supply, particularly in opioids. Its prevalence has risen dramatically, with detection rates reaching 80% in some areas of the Northeastern United States. Xylazine-associated skin lesions present a unique challenge for healthcare providers, characterized by deep, necrotic ulcers that progress rapidly and are resistant to healing. These wounds often occur both at and away from injection sites due to the vasoconstrictive properties of xylazine. Diagnosis requires a comprehensive approach, including patient history, specialized toxicology screening, and imaging studies. Management of xylazine-associated wounds involves a multidisciplinary strategy encompassing wound care, infection control, and addiction treatment. The DIME (Devitalized tissue, Infection control, Moisture balance, and periwound Edge) framework has been adopted by some clinics for treating these complex injuries. As xylazine contamination continues to spread, healthcare providers must be prepared to recognize and manage its unique clinical presentations.

Rationale: Rademikibart (formerly CBP-201) is an IL-4Rα-targeting antibody. Objectives: We sought to evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma. Methods: In this global Phase 2b trial, 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, after a 600-mg loading dose) or a placebo group; rademikibart or placebo was administered subcutaneously for 24 weeks. Measurements and Main Results: Prebronchodilator (trough) forced expiratory volume in 1 second (FEV1) at Week 12 (primary endpoint) improved with rademikibart at 150 mg and 300 mg: Least squares mean changes (95% confidence interval), above placebo, were 140 ml (44-236 ml; P = 0.005) and 189 ml (92-286 ml; P < 0.001), respectively. Prebronchodilator (trough) FEV1 improvements occurred rapidly during Week 1, were sustained through Week 24, and were greatest in patients with high baseline blood eosinophils (patients with ⩾300 eosinophils/ml experienced placebo-adjusted FEV1 improvement at Week 24 of 420 ml [95% confidence interval = 239-600 ml] in the 300-mg group). Rapid and sustained statistically significant improvements were also observed in percent predicted FEV1 and Asthma Control Questionnaire score across 24 weeks. Through Week 24, proportions of patients with one or more exacerbations were 7.5% (150 mg) and 9.3% (300 mg) versus 16.7% (placebo). Eighty-eight percent of patients completed treatment. Treatment-emergent adverse events were generally similar to placebo, and no eosinophilia was observed. Injection site reactions were mostly mild. The most common treatment-emergent adverse events (10-12% of patients) were cough, coronavirus disease (COVID-19), and dyspnea. Conclusions: Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy. Clinical trial registered with www.clinicaltrials.gov (NCT04773678).