Brent J. Doolan

SMARCAD1-palmoplantar epidermal differentiation disorder (formerly known as Huriez syndrome) is a rare SMARCAD1-associated genodermatosis with variable clinical expression and cutaneous cancer risk. We describe a multigenerational family with a SMARCAD1 splice-site duplication affecting the skin-specific isoform, associated with marked phenotypic heterogeneity. This article highlights the importance of molecular diagnosis for cancer surveillance and family counselling.

Background: Vitiligo is an acquired depigmenting disorder resulting from melanocyte loss. Although drug-associated vitiligo has been increasingly reported following exposure to immunomodulatory, oncological and other pharmacological therapies, implicated drug classes, clinical patterns and underlying mechanisms remain incompletely characterized. Objectives: Our aim was to systematically review reported cases of drug-associated vitiligo, identify implicated therapies, characterize clinical features and evaluate proposed pathogenic mechanisms. Methods: A systematic review was conducted according to the PRISMA guidelines and a prospectively registered protocol (PROSPERO: CRD42025648719). PubMed, Embase Classic + Embase and Ovid MEDLINE ALL were searched from January 1975 to April 2025, with an updated PubMed search performed to January 2026. Studies reporting new-onset vitiligo following exposure to a pharmacological agent were included. Demographic, clinical, treatment and outcome data were extracted and synthesized narratively. Results: In total, 184 publications comprising 258 individual cases were included. The most frequently implicated drug classes were immune checkpoint inhibitors (72 of 258, 27.9%), topical immune modifiers and sensitizers (46 of 258, 17.8%), biologic immunomodulators (44 of 258, 17.1%) and targeted therapies (43 of 258, 16.7%). The most commonly reported agents were imiquimod 5% cream (n = 30), nivolumab (n = 30), diphenylcyclopropenone (n = 18), pembrolizumab (n = 17), interferon-α (n = 17) and ribociclib (n = 16). Vitiligo most commonly involved the upper extremities (n = 127), face (n = 119) and trunk (n = 101). Among 256 cases with reported latency, vitiligo most frequently developed 3–6 months following treatment initiation (66 of 256, 25.8%), although distinct temporal patterns were observed between therapeutic classes. Among malignancy-associated cases with available outcome data, favourable oncological outcomes were reported in 74 of 95 patients (78%), including 38 of 42 melanoma-associated cases (90%). Recurrent mechanistic themes included immune-mediated melanocyte destruction, direct melanocyte toxicity and local inflammatory triggering. Conclusions: Drug-associated vitiligo represents a heterogeneous spectrum of disorders spanning multiple therapeutic classes. While recurrent clinical patterns and biologically plausible mechanisms support a contributory role for several drug classes, causality remains uncertain for many reported associations. Recognition of characteristic clinical and temporal patterns may improve patient counselling, inform treatment decisions and guide future pharmacovigilance and mechanistic research.

Molecular confirmation of neurofibromatosis type 1 (NF1) is essential for accurate diagnosis, reproductive counseling, and lifelong surveillance, yet genomic DNA (gDNA)‐based next‐generation sequencing (NGS) panels may miss deep intronic or complex structural variants. We report five children meeting the 2021 NF1 clinical diagnostic criteria who had negative DNA‐based NGS testing but were subsequently diagnosed using NF1 cDNA‐based testing ( NF1 cDNA testing), which identified three deep intronic variants, one 5′UTR variant, and one exonic insertion, including three novel variants. Four of the five variants produced abnormal‐to‐normal transcript ratios of approximately 1:1, consistent with complete loss of normal transcript from the affected allele. These variants, detected by NF1 cDNA testing, are predicted to result in the same clinical phenotype and natural history as NF1 exonic variants, underscoring the value of NF1 cDNA testing as a second‐tier test when clinical suspicion remains high despite negative gDNA‐based tests.

This case series outlines a proposed simplified and cost‐effective alternative to expensive laboratory‐based autologous non‐cultured epidermal suspension (NCES). In all five adult participants, 75%–100% repigmentation was observed at 6 months, with one participant experiencing unsatisfactory colour mismatch and one participant experiencing hypertrophic scarring. Larger, randomised controlled trials with extended follow‐up are needed to determine the long‐term efficacy and safety profile of our clinical NCES protocol.

Brent J Doolan, Bjorn R Thomas; Bursting the bubble on diagnostics: Artificial intelligence in autoimmune bullous disease, British Journal of Dermatology,

Genetic hair disorders, also known as genotrichoses, are characterized by abnormalities of hair structure, growth or differentiation, giving rise to a spectrum of phenotypes such as hypertrichosis, hypotrichosis and atrichia. These disorders may present as isolated phenotypes or be part of more complex phenotypes including abnormalities in skin or other organs. Genetic discoveries for hair disorders have been recently augmented with the advent of next-generation sequencing (NGS) technologies. We reviewed the literature and summarized disease–gene associations for inherited hair disorders, as well as genodermatoses presenting with hair abnormalities discovered by NGS technologies. We identified 28 nonsyndromic hair disorders, involving 25 individual genes and four unidentified genes. We have also discovered that approximately 30% of all the genodermatoses that were identified by NGS approaches demonstrated hair abnormalities as part of their phenotype. This review underscores the huge impact of NGS technologies in disclosing the genetics of hair disorders and the potential these discoveries provide for future translational research and new therapies.

Background/Objectives: Sequential digital dermoscopic imaging (SDDI) and total body photography (TBP) are recommended as a two‐step surveillance method for individuals at high‐risk of developing cutaneous melanoma. Dermoscopic features specific to melanoma have been well described, however, dynamic changes on serial imaging are less understood. This study aims to identify and compare dermoscopic features in developing melanomas and benign naevi that underwent SDDI and TBP to understand which dermoscopic features may be associated with a malignant change.Method: Histopathology reports from a private specialist dermatology clinic from January 2007 to December 2019 were reviewed. Histopathologically confirmed melanoma and benign naevi that underwent SDDI and TBP with a minimum follow‐up interval of 3 months were included.Results: Eighty‐nine melanomas (38.2% invasive, median Breslow thickness 0.35 mm, range: 0.2–1.45 mm) and 48 benign naevi were evaluated by three experienced dermatologists for dermoscopic changes. Features most strongly associated with melanoma included the development of neovascularisation, asymmetry and growth in pigment network, additional colours, shiny white structures, regression, structureless areas and change to a multi‐component pattern. The presence of atypical vessels (p = 0.02) and shiny white structures (p = 0.02) were significantly associated with invasive melanoma.Conclusion: Evaluation for certain evolving dermoscopic features in melanocytic lesions monitored by SDDI and TBP is efficient in assisting clinical decision making. SDDI with TBP is an effective tool for early detection of melanoma.

Glanzmann's thrombasthenia is a rare clotting disorder caused by impaired platelet function that can present with unexplained bruising. We present a 4-month-old