BACKGROUND: Pediatric atopic dermatitis (AD) is the most common inflammatory disease of childhood and is closely linked to the subsequent development of food allergy, asthma, and rhinitis. There is currently limited insi...BACKGROUND: Pediatric atopic dermatitis (AD) is the most common inflammatory disease of childhood and is closely linked to the subsequent development of food allergy, asthma, and rhinitis. There is currently limited insight into the occurrence of AD and allergic comorbidity in early childhood according to gestational maturity. OBJECTIVES: To investigate the occurrence of AD, food allergy, asthma, and rhinitis in term and preterm children from birth to age 4-5 years. METHODS: A prospective birth cohort of 389 children (261 term, 128 preterm) was followed from birth to 4-5 years. Clinical visits were conducted at birth, 2 months, and 12 months, with additional visits for skin signs of AD during the first two years. At age 4-5 years, parents completed a structured telephone interview. We compared the prevalence, age at onset, and persistence of AD and allergic comorbidities between preterm and term children using Mann-Whitney U and Fisher's exact tests. RESULTS: The overall prevalence of AD was 29.6% at age 2 years and 33.0% at 4-5 years. Preterm children had a lower prevalence of AD (19.2% vs. 39.8%, p < 0.0001), later AD onset (median 12.0 vs. 7.5 months, p < 0.01), milder disease severity (median EASI 1.4 vs. 4.8, p < 0.01), and less persistent AD (11.5% vs. 19.9%, p < 0.0001) than term children. Among children born preterm and term, the prevalence of food allergy, asthma, and rhinitis at ages 4-5 years was 1.6% vs. 3.1%, 20.0% vs. 13.0%, and 6.2% vs. 4.6%, respectively. No preterm children with AD (n=25) developed food allergies within 4-5 years compared to 6.7% among term-born children, whereas asthma prevalence was higher among preterm children with AD (36.0%) compared to term children with AD (17.3%) (p=0.05). CONCLUSION: In this cohort, preterm birth was associated with a lower observed incidence of AD, with later onset and a milder and less persistent disease course. Among children with AD, those born preterm had no food allergy and a higher prevalence of asthma compared with term-born children.
Ramessur R, Arham AGA, Saklatvala J
… +11 more, Thomas L, Brumpton BM, Hoff M, Videm V, Åsvold BO, Shin DB, Kim D, Smith CH, Simpson MA, Løset M, Gelfand JM
BACKGROUND: Topical corticosteroids (TCS) are widely used anti-inflammatory treatments for various dermatologic conditions. Although generally considered safe, concerns remain regarding systemic absorption and potentiall...BACKGROUND: Topical corticosteroids (TCS) are widely used anti-inflammatory treatments for various dermatologic conditions. Although generally considered safe, concerns remain regarding systemic absorption and potentially increase the risk of type 2 diabetes mellitus (T2DM). OBJECTIVE: To investigate the association between TCS exposure-considering potency, cumulative duration, and prescription frequency-and the prospective risk of developing T2DM. METHODS: We conducted a population-based longitudinal cohort study using the National Health Insurance Service database of South Korea. A total of 685 389 adults aged ≥20 years without diabetes at baseline were included. TCS exposure was assessed over a 5-year period based on any TCS use and further characterized by potency, cumulative duration, and prescription frequency, followed by a 6-year outcome ascertainment period. Incident T2DM was defined as the presence of an ICD-10 code (E11-E14) accompanied by at least one prescription for antidiabetic medication. RESULTS: Overall TCS use during a 5-year exposure period was not associated with an increased risk of T2DM after adjusting for potential confounders. However, potent TCS use (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04-1.26), higher prescription frequency (≥10 prescriptions) (aHR, 1.26; 95% CI, 1.12-1.42), and longer cumulative duration of exposure (≥6 months) (aHR, 1.45; 95% CI, 1.25-1.67) were associated with a higher risk of developing T2DM. In contrast, low-potency TCS use, exposure duration <6 months, and <10 TCS prescriptions were associated with a lower risk of T2DM (aHR, 0.83; 95% CI, 0.75-0.91, aHR, 0.95; 95% CI, 0.90-0.99, and aHR, 0.94; 95% CI, 0.90-0.99, respectively). CONCLUSIONS: In this large nationwide cohort, overall TCS use was not associated with incident T2DM. However, the use of high-potency formulations, longer cumulative duration, and frequent prescriptions were associated with an increased risk of T2DM. These findings underscore the importance of prudent prescribing and targeted metabolic monitoring in patients requiring potent or long-term TCS therapy.
INTRODUCTION: Ultraviolet B (UVB) phototherapy is recommended in clinical guidelines for atopic dermatitis, but it is uncertain whether narrowband or broadband UVB is more effective and better tolerated. OBJECTIVES: The...INTRODUCTION: Ultraviolet B (UVB) phototherapy is recommended in clinical guidelines for atopic dermatitis, but it is uncertain whether narrowband or broadband UVB is more effective and better tolerated. OBJECTIVES: The objective of this parallel-group randomized clinical trial was to compare the efficacy and safety of broadband vs. narrowband UVB for the treatment of moderate-to-severe atopic dermatitis. METHODS: Participants were 18 years and older with moderate-to-severe atopic dermatitis refractory to topical corticosteroids. Participants were randomized 1:1 via a centralized computer randomization scheme to full-body broadband or narrowband UVB phototherapy, with ongoing concomitant topical therapy. Participants were blinded but treating and assessing clinicians were not. The primary outcome was change in Eczema Area and Severity Index (EASI) at 12 weeks. Secondary outcomes included achieving 0 or 1 and improvement of 2 or more on the validated Investor Global Assessment scale (vIGA) and change in Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numeric Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and Recap of atopic eczema RECAP). Efficacy analyses were conducted on a modified intention-to-treat population, including all randomized participants who receive at least one dose of phototherapy. RESULTS: 34 participants were randomized to broadband UVB and 35 to narrowband UVB. 32 participants received at least one dose of broadband UVB and 34 received at least one dose of narrowband UVB and were included in the modified intention-to-treat analysis. The mean age was 37.1 years in the broadband UVB arm and 33.2 in the narrowband UVB arm. The mean (95% credible interval) change in EASI score in the broadband UVB arm was -8.1 (-12.1 to -4.1) and in the narrowband UVB arm was -8.9 (-13.0 to -4.9). In the adjusted analysis, the difference between arms in change in EASI was -0.7 (-5.6 to 4.1). There were no significant differences between arms for any of vIGA, POEM, PP-NRS, DLQI or RECAP. There were 4 withdrawals from phototherapy due to adverse events in the broadband arm and 0 in the narrowband arm. CONCLUSIONS: In this study, broadband and narrowband UVB were similarly effective and narrowband UVB was better tolerated for the treatment of moderate-to-severe atopic dermatitis.
BACKGROUND: Bullous pemphigoid (BP) exhibits significant clinical heterogeneity. The molecular drivers underlying these distinct phenotypes remain poorly understood, hindering the development of precision medicine approa...BACKGROUND: Bullous pemphigoid (BP) exhibits significant clinical heterogeneity. The molecular drivers underlying these distinct phenotypes remain poorly understood, hindering the development of precision medicine approaches. OBJECTIVES: To correlate clinical phenotypes, defined by the Bullous Pemphigoid Disease Area Index (BPDAI), with molecular endotypes using serum proteomic profiling. METHODS: This cohort study enrolled 143 hospitalized patients with BP at a tertiary centre between January 2024 and June 2025. Patients were stratified into inflammatory BP (I-BP; BPDAI urticaria/erythema subscore ≥5) and pauci-inflammatory BP (PI-BP; subscore <5) based on the first quartile of the subscore. Clinical features, laboratory parameters, and treatment outcomes were compared. Serum proteomic profiling (Olink Target 96 Inflammation) was performed in a representative subset (n=37). RESULTS: Among 143 patients (mean age 73.9 years; 58.7% male), 108 (75.5%) were classified as I-BP and 35 (24.5%) as PI-BP. Compared to PI-BP, I-BP patients were younger, had more severe pruritus, and exhibited significantly elevated peripheral eosinophil counts (0.6 vs 0.2 ×109/L; P=0.001) and serum IL-5 levels (52.5 vs 3.9 pg/mL; P=0.007). Despite receiving more intensive therapy, I-BP patients required a longer median hospital stay (8 vs 7 days; P=0.029). Proteomic analysis identified eight differentially expressed proteins. IL-13, thymic stromal lymphopoietin (TSLP), oncostatin M (OSM), and MCP-4 were upregulated in I-BP and showed positive correlation with the urticaria/erythema subscore (P<0.05) but not with the erosions/blisters subscore. IL-13 demonstrated the highest diagnostic accuracy for the I-BP endotype (AUC=0.87). Functional enrichment analysis confirmed differential activation of type 2 inflammation and the JAK-STAT signaling pathway in the I-BP group. CONCLUSIONS: The BPDAI urticaria/erythema subscore serves as a reliable clinical surrogate for a Th2-driven molecular endotype in BP. The identification of a specific Th2-ligand/JAK-STAT-signaling circuit in the inflammatory phenotype supports a stratified treatment approach, suggesting that patients with a high inflammatory burden may benefit from targeted type 2 immunotherapies or JAK inhibitors, which warrants further prospective validation.
BACKGROUND: Psoriasis is a non-communicable inflammatory skin disease that affects approximately 2%-3% of the world's population. Given its high impact on quality of life and the fact that a subset of patients exhibits s...BACKGROUND: Psoriasis is a non-communicable inflammatory skin disease that affects approximately 2%-3% of the world's population. Given its high impact on quality of life and the fact that a subset of patients exhibits suboptimal or secondary loss of response to current treatments, identifying new therapeutic strategies is crucial. Proliferation-associated protein 2G4 (PA2G4) is a transcription factor that has been exclusively studied in cancer research, where it promotes cell growth and enhances tumourigenesis by inhibiting apoptosis. However, its role in inflammatory skin diseases remains largely unknown. OBJECTIVES: This study focused on the pathophysiological and immunological functions of PA2G4 in psoriasis and evaluated its potential as a therapeutic target. METHODS: Bulk, single-cell, and spatial RNA sequencing combined with immunohistochemistry were used to assess PA2G4 expression in psoriatic skin compared with that in non-lesional controls. Functional studies were performed in primary human keratinocytes and reconstructed human epidermis (RHE) models using the CRISPR/Cas9-mediated knockout (KO) of PA2G4 and pharmacological inhibition of PA2G4 with the small-molecule WS6. The regulatory effects of PA2G4 on cellular processes, such as proliferation, differentiation, and survival, were investigated using RNA-seq, western blot analysis, scratch assays, and annexin V staining. RESULTS: PA2G4 was highly abundant in psoriasis, and its expression was predominantly restricted to basal proliferating keratinocytes. Its gene expression is positively correlated with psoriasis severity, the degree of acanthosis, neutrophil infiltration, and genes which are upregulated in psoriasis. PA2G4 KO in primary human keratinocytes activated differentiation pathways while suppressing proliferation pathways, resulting in the downregulation of proliferation- and inflammation-related genes (e.g. MKI67, IL20, VEGFA, and HIF1A) and the upregulation of differentiation and cell adhesion markers (e.g. KRT6C, LCE2C, and DSG4). Functionally, the PA2G4 KO reduced keratinocyte proliferation in scratch assays, attenuated interleukin-22-induced acanthosis in RHE models, and promoted keratinocyte death. Pharmacological inhibition of PA2G4 using the small-molecule inhibitor WS6 similarly downregulated genes associated with proliferation and cell survival. CONCLUSIONS: PA2G4 could promote keratinocyte hyperproliferation and survival in psoriasis, thereby critically influencing epidermal homeostasis. Therefore, inhibition of PA2G4 may represent a new treatment option for psoriasis.
BACKGROUND: Unicentric Castleman disease (UCD), a rare lymphoproliferative disorder, is frequently complicated by paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous syndrome with high mortality. The hyaline-vasc...BACKGROUND: Unicentric Castleman disease (UCD), a rare lymphoproliferative disorder, is frequently complicated by paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous syndrome with high mortality. The hyaline-vascular (HV) histological subtype predominates in UCD-PNP, yet the mechanisms driving vascular hyalinization and stromal dysregulation remain poorly defined. OBJECTIVES: To elucidate the cellular and molecular pathogenesis of UCD-PNP through integrated transcriptomic and cellular analyses, focusing on stromal-immune crosstalk and mechanisms underlying extracellular matrix (ECM) dysregulation. METHODS: We performed bulk RNA sequencing (RNA-seq) of lymph node (LN) samples from 33 patients with pathologically confirmed UCD-PNP and single-cell RNA-seq (scRNA-seq) in 5 of them. Analytical approaches included differential expression, pathway enrichment, cellular deconvolution, developmental trajectory inference, ligand-receptor interaction analysis, and spatial validation. Functional consequences of identified interactions were assessed using bulk RNA-seq and proteomic analysis. RESULTS: Bulk RNA-seq highlighted extracellular matrix (ECM) dysregulation, with significant upregulation of collagen genes in UCD-PNP. scRNA-seq of 58,811 cells revealed expansion of endothelial cells (ECs), pericytes, and fibroblasts, alongside diminished follicular dendritic cells (FDCs). Cell-cell communication analysis identified ECs as primary contributors to collagen/laminin overproduction via COL4A1-ITGA1/ITGB1 and LAMB1-ITGA6/ITGB1 signaling, directly linking EC activity to perivascular hyalinization. UCD-PNP also featured marked plasmablast expansion, IgG class-switching, and memory CD4+ T cells driving B-cell hyperactivity. In addition, ligand-receptor analysis revealed a pivotal interaction between EC-derived COL4A1 and CD44 on B cells. Mechanistically, COL4A1 overexpression in ECs upregulated genes involved in ECM organization and remodeling. Furthermore, proteomics revealed that endothelial-B cell crosstalk drived vascular basement membrane accumulation (Perlecan/HSPG2) and pro-inflammatory cytokine release (CCL4) in functional co-cultures. CONCLUSIONS: UCD-PNP pathogenesis centers on aberrant EC expansion and dysregulation, driving simultaneous vascular hyalinization via excessive ECM deposition. Pathological endothelial-B cell interactions, directly link basement membrane accumulation to pro-inflammatory signaling. Targeting this EC-driven stromal-immune crosstalk presents a novel therapeutic strategy for UCD-PNP.
Bouadi N, Ayoub A, Croitoru D
… +2 more, Piguet V, Auger N
Br J Dermatol
· 2026 Apr · PMID 42007899
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This longitudinal cohort study of 2.6 million pregnancies suggests that patients with a pre-pregnancy history of Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are at risk of severe maternal morbidity...This longitudinal cohort study of 2.6 million pregnancies suggests that patients with a pre-pregnancy history of Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are at risk of severe maternal morbidity at delivery. In contrast, patients who develop SJS/TEN during pregnancy are not at risk of severe maternal morbidity, but are at risk of preterm birth and caesarean delivery.