Zigang Xu

Background: Piebaldism is a rare autosomal dominant pigmentary disorder characterized by congenital depigmented patches and a white forelock, primarily caused by pathogenic variants in KIT . A subset of patients additionally exhibit Café-au-lait macules (CALMs) and intertriginous freckling, resulting in considerable phenotypic overlap with neurofibromatosis type 1 (NF1) and complicating diagnosis. However, the clinical and molecular characteristics of Chinese patients with this uncommon phenotype remain poorly defined. Methods: We retrospectively analyzed five unrelated Chinese patients with piebaldism accompanied by CALMs from Beijing Children’s Hospital and systematically reviewed ten previously reported Chinese cases. Clinical manifestations, family history, and genetic findings were evaluated. Whole-exome sequencing followed by Sanger sequencing validation was performed in newly recruited patients. Variants were interpreted according to the ACMG/AMP guidelines. Phenotypic severity was classified based on depigmentation extent. Genotype-phenotype correlations were analyzed by integrating the present cohort with published Chinese cases. Results: Fifteen patients were included. All exhibited congenitial depigmentation and multiple CALMs, while six (40.0%) also presented with axillary and/or inguinal freckling. Eleven patients (73.3%) showed severe phenotypes. Heterozygous KIT variants were identified in all patients, including five previously unreported variants detected in our cohort. Notably, 80% of variants were located within the tyrosine kinase (TK) domain, with significant enrichment in TK1 subdomain (66.7%). Patients with freckling exclusively carried TK domain variants. No pathogenic variants in NF1 or SPRED1 were detected. Although one patient carring an extracellular-domain variant also exhibited CALMs, TK domain variants were strongly associated with hyperpigmented manifestations. Conclusion: This study expands the clinical and mutational spectrum of Chinese patients with piebladism accompanied by CALMS. Our findings further support an association between KIT TK-domain variants and complex pigmentary characrized by CALMs and freckling, while also indicating that this correlation is not absolute. Recognition of this phenotype is essential for distinguishing KIT- related pigmentary disorders from NF1 and avoiding unnecessary surveillance and genetic conseling.

Background: Atopic dermatitis (AD) and vitiligo are pediatric immune-mediated inflammatory skin diseases with distinct but potentially overlapping immune mechanisms. Dupilumab targets interleukin (IL)-4 and IL-13 signaling and is effective for moderate-to-severe AD. However, the coexistence, emergence, or progression of vitiligo during dupilumab therapy may create therapeutic challenges when both eczematous inflammation and melanocyte-directed autoimmunity require control. Methods: We retrospectively reviewed four children aged 6–11 years with AD complicated by pre-existing or emerging vitiligo during dupilumab therapy. Clinical features, timing of vitiligo onset or progression, response to dupilumab, subsequent targeted treatment, follow-up outcomes, and safety data were summarized. Vitiligo was diagnosed clinically and supported by Wood's lamp examination when available. Results: Two patients had vitiligo before dupilumab initiation, whereas two developed hypopigmented or depigmented lesions during dupilumab treatment. One patient with severe AD showed no obvious improvement after dupilumab; instead, original eczematous lesions became more erythematous and swollen, and new hypopigmented patches appeared around the ankle regions. Dupilumab was discontinued in all patients. Three patients were switched directly to a Janus kinase (JAK) 1 inhibitor. One patient was initially switched to a JAK3/TEC family kinase inhibitor but later changed to a JAK1 inhibitor because of AD recurrence. During follow-up, all patients showed improvement of AD and stabilization or repigmentation of vitiligo. No serious adverse events were observed. Conclusion: This case series describes a pediatric AD-vitiligo overlap phenotype in which final transition to JAK1 inhibition was associated with improvement of both diseases after dupilumab discontinuation. Causality between dupilumab and vitiligo cannot be established. JAK1 inhibition may be considered in carefully selected children requiring simultaneous control of AD and active vitiligo.

Background: Mycoplasma pneumoniae–induced rash and mucositis (MIRM) is a unique entity distinct from both erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis. There are limited data on pediatric cases of MIRM in China.Objective: To evaluate the clinical characteristics and recurrence frequency of pediatric cases of MIRM and to summarize the co-infections beyond M. pneumoniae infection.Methods: This retrospective study was conducted through a chart review of patients with MIRM admitted to dermatology inpatient department from September 2017 to July 2021. Pediatric patients with MIRM 4 years to 12 years who met Canavan's criteria were included in the study.Results: A total of 23 patients with MIRM aged 7.86 ± 2.92 years were included. Oral mucosa was the most common site of mucosal involvement. Average number of involved mucous membranes was 2.83 ± 0.89. Average length of hospital stay was 10.30 ± 3.34 days. Length of hospital stay in recurrent cases was shorter than isolated cases (6.3 days vs. 10.17 days). Recurrence was observed in 21.7% of patients. The number of mucosal membranes involved was more in the first episode of recurrent cases than isolated cases (3.2 vs. 2.72). Of all patients, 47.8% were co-infected with pathogens apart from M. pneumoniae. Recurrence rate of the co-infection group was 36.4%.Conclusion: We report observations from the largest pediatric cohort with MIRM in China. Patients with younger age at onset had more severe skin and mucosal involvement, even similar to SJS/TEN. A higher recurrence rate and incidence of co-infections were observed in our cohort. The co-infection group had a higher recurrence rate, which further supports the concept of reactive infectious mucocutaneous eruption.

Secukinumab is an IL-17A inhibitor that selectively binds to IL-17A and inhibits its interaction with IL-17 receptors, thereby reducing the production of pro-inflammatory cytokines, chemokines, and tissue-damaging mediators. Secukinumab has been proven to rapidly improve erythema and pustules in adult and paediatric generalized pustular psoriasis (GPP) patients. Here, we report a case study of erythema multiforme-like drug eruption induced by secukinumab and provide an overview of all cases reported so far. A systematic literature search of publications was conducted from inception to September 2024 via PubMed and Web of Science Core Collection, in order to identify all cases of drug hypersensitivity reactions associated with secukinumab. We conducted a search for retrospective and prospective studies, case series, case reports, and data from Phase II and III clinical trials related to immune-related (or potentially immune-related) adverse events associated with the use of secukinumab. In total, four cases of drug hypersensitivity reactions associated with secukinumab were identified. Drug hypersensitivity reactions associated with secukinumab are relatively rare. The recognition of potential rare adverse events by clinicians is important and may expand our understanding of immune-mediated diseases.

Hemoporfin, a porphyrin derivative photosensitizer, has been approved for the treatment of port‐wine stain (PWS) in adults. However, its optimal dose for the pediatric population remains unclear. This study aimed to explore appropriate dosing for pediatric patients with PWS through population pharmacokinetics (PopPK) and exposure‐response (ER) analysis. Data from a prospective pilot study of hemoporfin photodynamic therapy in pediatric PWS patients, as well as a phase I study in healthy adult volunteers, were utilized for the analysis. The pharmacokinetics of hemoporfin in the pediatric population can be described by a three‐compartment model with linear elimination following allometric scaling rules. Simulations indicated that simply scaling down the approved adult dose of 5 mg/kg based on weight for the pediatric population, which is a common practice among clinicians, may lead to reduced drug exposure in pediatric patients. Mean C_max and AUC_0–30min in pediatric patients were 18.7% and 30.5% lower than those in adults, respectively. A positive relationship was identified between AUC_0–30min and the probability of investigators or patients giving high ratings for efficacy, suggesting that improved efficacy may be achieved with higher hemoporfin exposure. A series of dosing regimens were explored to match exposure in the pediatric population to that of the adult population. These findings may accelerate the development of pediatric indications for hemoporfin and help address the unmet medical needs of pediatric patients with PWS.