Port wine stain (PWS) is a common congenital and progressive skin capillary malformation with poor clinical effects, which seriously affects the patients' appearance and social interaction. In the study, we found that it...Port wine stain (PWS) is a common congenital and progressive skin capillary malformation with poor clinical effects, which seriously affects the patients' appearance and social interaction. In the study, we found that itraconazole (ITRA), a common antifungal agent, showed preliminary clinical improvement in patients with PWS in our pilot observational case series; however, the underlying molecular mechanisms are still unclear. PWS pathogenesis is associated with somatic activating GNAQ R183Q mutations that constitutively activate the PI3K/AKT/mTOR pathway, and angiogenesis and fibroblast hyperplasia further play important roles in its occurrence and development. We isolated and cultured primary human umbilical vein endothelial cells (HUVECs) and PWS fibroblasts (PWSFs) by enzymatic digestion and used these cells as our cell models. In vitro, we found that ITRA inhibited proliferation, induced apoptosis, increased autophagosome formation and promoted autophagy flux of HUVECs and PWSFs. Furthermore, we explored the association between apoptosis and ITRA-induced autophagy. We found that ITRA induced autophagy, and inhibition of autophagy enhanced its pro-apoptotic and anti-proliferative effects of ITRA in PWSFs and HUVECs. In addition, ITRA may inhibit migration and angiogenesis of HUVECs by downregulating the VEGF/PI3K/AKT/mTOR signalling pathway. Together, our study presents a preliminary clinical pilot observation and a relative experimental study for the potential effects of ITRA in PWS via autophagy-apoptosis crosstalk.
Pereira RP, Sirena DH, de Azevedo SJ
… +5 more, da Silva MMF, da Luz Andrade MM, Ferreira CF, Heinen TE, Bakos RM
Exp Dermatol
· 2026 May · PMID 42101092
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Recently, new treatment strategies have been developed for advanced or metastatic basal cell carcinoma (BCC), including Hedgehog pathway inhibitors. Itraconazole has demonstrated clinical activity in such cases by blocki...Recently, new treatment strategies have been developed for advanced or metastatic basal cell carcinoma (BCC), including Hedgehog pathway inhibitors. Itraconazole has demonstrated clinical activity in such cases by blocking the smoothened (SMO) receptor. Such a strategy could be used in early disease. The objective of this Phase II study was to evaluate the clinical and molecular efficacy of Itraconazole in low-risk BCC patients who were primarily candidates for surgical excision. Lesions were assessed according to RECIST 1.1 criteria, with target lesions being at least 10 mm in size after confirmatory biopsy. Patients received itraconazole tablets 200 mg twice daily for 60 days before resection. The median tumour diameter before treatment was 14 mm (IQR 11-16 mm), and after treatment, 13 mm (IQR 11-15 mm), and this reduction in tumour size was statistically significant (p < 0.0001). Coupled with the decrease in tumour size, a decrease in the expression of CD105, an endothelial marker (p < 0.0001), was observed. In conclusion, neoadjuvant itraconazole for 2 months was able to reduce the diameter of low-risk BCC, and the effect was associated with a decrease in tumour angiogenesis and a favourable safety profile.
Mansini AP, Bao L, Chhiba KD
… +8 more, Li J, Wang Y, Gainer H, McAlexander MA, McCrae C, Nazaroff CD, Kuang FL, Amber KT
Exp Dermatol
· 2026 May · PMID 42100993
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Bullous pemphigoid (BP) is an autoimmune blistering disease whereby the cutaneous antigens BP180 and BP230 are targeted by autoantibodies. Skin lesions in BP are characterized by an abundance of eosinophils. We recently...Bullous pemphigoid (BP) is an autoimmune blistering disease whereby the cutaneous antigens BP180 and BP230 are targeted by autoantibodies. Skin lesions in BP are characterized by an abundance of eosinophils. We recently demonstrated that the treatment of keratinocytes with antibodies from patients with BP induces a robust inflammatory response with release of numerous cytokines, chemokines, complement factors, and proteases. We thus questioned whether this keratinocyte inflammatory response was capable of directly inducing an inflammatory response in eosinophils. We therefore treated human eosinophils with conditioned media from keratinocytes treated with IgG from patients with BP (BP-IgG), or healthy controls (control-IgG) with or without supplemental IL-5. Flow cytometry revealed upregulation of CD107a/CD107b, markers of degranulation, on eosinophils treated with supernatants from BP-IgG relative to control-IgG treated keratinocytes. A decrease in CCR3 and CD101 was also identified. Functional activity of eosinophils was confirmed by performing a multiplex immunoassay on eosinophil supernatants. This revealed significant upregulation IL-6, IL-8, LIF, TGFα, MCP-4, MMP-9, and MMP-10. Supplemental IL-5 did not appear to significantly influence these responses. Our data demonstrate that the inflammatory activation of keratinocytes by BP-IgG affects eosinophils, driving phenotypic changes consistent with degranulation, as well as a pro-inflammatory and proteolytic response.
Oxidative stress is identified as a potential factor in vitiligo pathogenesis. We aimed here to evaluate whether USP11 regulates the oxidative stress of melanocytes in vitiligo. Human melanocyte PIG1 cells were induced w...Oxidative stress is identified as a potential factor in vitiligo pathogenesis. We aimed here to evaluate whether USP11 regulates the oxidative stress of melanocytes in vitiligo. Human melanocyte PIG1 cells were induced with 1 mM HO and pre-infected with lentiviruses for genetic intervention. The dorsal skin of C57BL/6J mice was applied with 5% HO, and genetic intervention was elicited through adenoviruses. USP11, SIRT3, and TRIM28 were reduced in melanocytes (Melan-A positive) from vitiligo mouse skin tissues and in the HO-induced PIG1 cells. TRIM28 transcriptionally activated USP11 to promote deubiquitination of SIRT3. HO decreased viability and melanin and tyrosinase contents and increased apoptosis and oxidative stress in PIG1 cells. HO induced severe depigmentation of the dorsal skin in mice, reduced melanin deposition in hair follicles, loss of melanocytes, and increased oxidative stress. Overexpression of either USP11 or TRIM28 inhibited HO-induced melanocyte damage and vitiligo, while combined knockdown of SIRT3 or USP11 reversed the effects of USP11 or TRIM28 overexpression. These findings suggest that TRIM28 exerts its effect by reducing oxidative stress in melanocytes through USP11-mediated SIRT3 deubiquitination. This observation provides a mechanistic insight that could inform future therapeutic exploration in vitiligo. Graphical abstract text. The diagram. TRIM28 inhibits oxidative stress damage in melanocytes and alleviates vitiligo by transcriptionally upregulating USP11 and promoting deubiquitination modification of SIRT3.
Although the core pathophysiological pathways of chronic urticaria (CU) are increasingly understood, the upstream triggers and factors contributing to disease chronicity remain poorly understood. Emerging evidence sugges...Although the core pathophysiological pathways of chronic urticaria (CU) are increasingly understood, the upstream triggers and factors contributing to disease chronicity remain poorly understood. Emerging evidence suggests that gut microbiota dysbiosis represents a potentially modifiable upstream factor, which has been predominantly investigated in patients with chronic spontaneous urticaria (CSU). Multi-omics and Mendelian randomization studies have provided convergent evidence linking gut dysbiosis to systemic inflammation and mast cell instability. This is characterized primarily by the depletion of short-chain fatty acid (SCFA)-producing taxa (e.g., Faecalibacterium, Roseburia and Bifidobacterium) and the relative enrichment of pro-inflammatory Proteobacteria (particularly Enterobacteriaceae). Mechanistically, these alterations may lower the mast cell activation threshold and promote systemic immune dysregulation through specific metabolic shifts, such as the depletion of SCFAs and unsaturated fatty acids, and the translocation of endotoxins (e.g., lipopolysaccharide) due to compromised intestinal barrier function. In this review, we discuss how the use of Mendelian randomization (MR) and germ-free mouse models can advance the gut-urticaria axis (with a primary focus on CSU) from mere correlation to causation, while highlighting the crucial need to account for clinical confounders. Finally, we evaluate the clinical translational potential and associated challenges of microbiome-targeted interventions (e.g., probiotics, faecal microbiota transplantation) as novel adjuvant therapies.
Autoinflammatory diseases (AIDs) are characterized by abnormal responses of the innate immune system, accompanied by elevations in inflammatory biomarkers, in the absence of a physiologic crisis or infection. Certain mon...Autoinflammatory diseases (AIDs) are characterized by abnormal responses of the innate immune system, accompanied by elevations in inflammatory biomarkers, in the absence of a physiologic crisis or infection. Certain monogenic AIDs may present with acneiform or hidradenitis suppurativa-like cutaneous manifestations. In contrast, acne vulgaris, plaque psoriasis and hidradenitis suppurativa are complex, multifactorial inflammatory dermatoses situated along an autoinflammation-associated immunologic spectrum, involving both innate and adaptive immune pathways. There is a growing sphere of research dedicated to exploring dietary patterns as modifiable factors associated with inflammatory disease activity. The Mediterranean diet (MD)-which includes a high consumption of vegetables, whole grains, legumes, fruits, nuts, seeds, fish, wine and extra-virgin olive oil (EVOO)-has gained attention for its potential to modulate pathogenic inflammatory mechanisms. In this review, we summarize the current evidence examining associations between MD adherence and three autoinflammation-associated skin conditions: acne vulgaris, psoriasis and hidradenitis suppurativa. We highlight shared and disease-specific inflammatory pathways while emphasizing the predominance of observational data and the need for further interventional studies to clarify clinical implications.
Genetic studies mutations (IL36RN, CARD14 and AP1S3) account for only 28.6% of generalised pustular psoriasis (GPP) leaving much of its pathogenesis remained to be elucidated. Emerging evidence suggests Th17-mediated inf...Genetic studies mutations (IL36RN, CARD14 and AP1S3) account for only 28.6% of generalised pustular psoriasis (GPP) leaving much of its pathogenesis remained to be elucidated. Emerging evidence suggests Th17-mediated inflammation, potentially driven by specific HLA class alleles, may underlie dysregulated IL-36 signalling. This study explores the genotypic and phenotypic features of autochthonous GPP in Sarawak. A cross-sectional case-control study was conducted in Sarawak's three main dermatology centres. GPP patients (n = 43) fulfilling ERASPEN criteria between 1997 and June 2024 were included (23 with GPP alone); 20 with concomitant psoriasis vulgaris. HLA genotyping (HLA-A, -B, -C, -DR) was performed via polymerase chain reaction and sequence-specific oligonucleotide probe hybridisation (PCR-SSO) methods at the Institute of Medical Research (IMR). HLA frequencies were compared to 90 Sarawakian controls from Malaysian Stem Cell Registry. Female predominance was noted (1:4.4). Median age at GPP onset was 29 years. Family history of psoriasis was reported in 30.2%, with 16% females developing GPP during pregnancy. Treatment responses: corticosteroids (100%), ciclosporin (82.1%), acitretin (60%) and methotrexate (50%). While biologics were effective in 10 patients. Common alleles included HLA-DRB1*12:02, HLA-A*11:01 and HLA-C*07:02 while HLA-C06:02 was not observed. HLA-A*02:07 and HLA-B*46:01 were observed only in concomitant psoriasis patients. HLA-A*11:02 was seen in patients with ciclosporin non-response, HLA-A*24:02 in those with poorer responses to acitretin and methotrexate and HLA-B*38:02 in psoriatic arthritis. Lower frequencies of HLA-B*35:05 and HLA-C*04:01 were observed among Dayak patients. The absence of HLA-C*06:02 and variation in allele frequencies in this cohort may reflect population-specific patterns but require validation in larger studies.
The hydroxycarboxylic acid receptor HCA2 is expressed in keratinocytes and immune cells. In mice, the anti-inflammatory potential of HCA2 receptor signalling in the skin was first described in experimental models of psor...The hydroxycarboxylic acid receptor HCA2 is expressed in keratinocytes and immune cells. In mice, the anti-inflammatory potential of HCA2 receptor signalling in the skin was first described in experimental models of psoriasis-like inflammation and bullous pemphigoid-like epidermolysis bullosa acquisita. We examined contact allergic immune responses to the obligate contact sensitiser DNFB in Hcar2 and wild-type C57BL/6 mice. Basal mRNA levels of pro-inflammatory mediators like IFNγ were already increased in the ear tissue of naïve Hcar2 animals. After sensitisation and challenge with DNFB, contact allergic ear swelling and infiltration of neutrophils and CD3+ T cells were increased in Hcar2 mice. To investigate the impact of HCA2 receptors on T cells, we performed in vitro co-stimulation assays with allergen-loaded dendritic cells and antigen-specific T cells, showing increased proliferation and IFNγ production of Hcar2 T lymphocytes. Adoptive transfer of sensitised lymphocytes and experiments with bone marrow chimeric mice indicated that HCAR2 exerts its anti-inflammatory effect in part through radio-resistant, skin-resident cells in the challenge phase. As a potential mechanism, we found that Hcar2 keratinocytes produced higher levels of the neutrophil-attracting chemokine CCL8. In summary, we show that HCA2 receptors are functionally expressed in lymphocytes and keratinocytes and participate in the attenuation of contact allergic immune responses. Our data indicate that the dominant anti-inflammatory effect of HCA2 signalling during the elicitation phase resides in radio-resistant, skin-resident cells, whereas effects on lymphocyte activation are likely to be modulatory. The precise contribution of distinct skin-resident cell populations and the role of endogenous ligands driving HCA2 signalling in this context remain unresolved.
Atopic dermatitis (AD) is a chronic inflammatory dermatosis characterised by skin barrier disruption and immune dysregulation. Current clinical scoring systems (e.g., SCORAD) often fail to quantify subclinical pathophysi...Atopic dermatitis (AD) is a chronic inflammatory dermatosis characterised by skin barrier disruption and immune dysregulation. Current clinical scoring systems (e.g., SCORAD) often fail to quantify subclinical pathophysiology or characterise the biopharmaceutical interface. This review synthesises the 'bioelectric profile' of AD, integrating electrical impedance spectroscopy (EIS) and current perception threshold (CPT) to construct a precision phenotyping framework. Evidence indicates that EIS non-invasively quantifies barrier integrity, with specific parameters (e.g., EIS) that correlate positively with terminal differentiation proteins such as filaggrin, serving as a surrogate marker of molecular permeability. Concurrently, neuroselective CPT assessment reveals abnormal C-fibre sensitisation in non-lesional skin, distinguishing extrinsic from intrinsic AD phenotypes. Furthermore, we explore reciprocal interactions between bioelectric parameters, Th2/Th22 cytokines (e.g., IL-31, IL-13) and the microbiome. Finally, we discuss translating these signatures into closed-loop theranostic strategies for feedback-controlled drug delivery. This bioelectric panorama provides a unique biophysical perspective on AD pathogenesis and a theoretical foundation for future precision medicine.
Exp Dermatol
· 2026 Apr · PMID 41969209
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Chronic spontaneous urticaria (CSU) remains challenging to manage in patients who do not respond adequately to antihistamines or currently available immunomodulatory therapies. Intramuscular injection of autologous total...Chronic spontaneous urticaria (CSU) remains challenging to manage in patients who do not respond adequately to antihistamines or currently available immunomodulatory therapies. Intramuscular injection of autologous total IgG (autologous immunoglobulin therapy: AIGT) has demonstrated clinical efficacy, safety and immunomodulatory effects in patients with moderate-to-severe atopic dermatitis in a randomized placebo-controlled clinical trial. However, the clinical usefulness of AIGT in patients with CSU has not been evaluated. We conducted a prospective open-label pilot study to assess the efficacy and safety of AIGT in antihistamine-refractory CSU. Fifteen adults with CSU received nine weekly intramuscular injections of 100 mg autologous IgG from Week 0 through Week 8 (inclusive). The primary outcome was the change in Urticaria Activity Score over 7 days (UAS7) at Week 12 from baseline. Secondary outcomes included the Urticaria Control Test (UCT), chronic urticaria-specific quality of life (CU-QoL) scores and patient-reported disease burden using a visual analogue scale (VAS). The median change in UAS7 at Week 12 from baseline was -13.0 (p < 0.001). Significant improvements in UCT, CU-QoL and VAS were also observed at Week 12 from baseline (p < 0.05). In longitudinal analyses, improvements in symptom burden and quality of life were detectable from Week 4 and were maintained through Week 24. Serum total IgG increased by a median of +68.0 mg/dL from baseline to Week 12 (p < 0.05). No serious adverse events occurred. In conclusion, AIGT improved disease activity, urticaria control, quality of life and patient-reported burden in patients with antihistamine-refractory CSU. Further studies are needed to evaluate the clinical usefulness of AIGT in CSU.
Obesity reduces response to biologic therapy in psoriasis, but comparative evidence across drug classes in Chinese patients is limited. A real-world cohort of 891 adults with moderate-to-severe psoriasis initiating biolo...Obesity reduces response to biologic therapy in psoriasis, but comparative evidence across drug classes in Chinese patients is limited. A real-world cohort of 891 adults with moderate-to-severe psoriasis initiating biologics between 2020 and 2025 was divided by baseline BMI (< 24 vs. ≥ 24 kg/m). PASI90 achievement at 2, 4, 6 and 12 months and drug survival were compared amongst IL-17, IL-23 and TNF-α inhibitors. Amongst IL-17 users, PASI90 rates in the non-overweight group were consistently higher at 4, 6 and 12 months (all p < 0.05), whereas no BMI-related differences were seen with TNF-α or IL-23 blockade. Within the non-overweight stratum, IL-17 and IL-23 agents outperformed TNF-α inhibitors at month 6 and yielded fewer switches (p < 0.05). In the overweight/obese stratum, IL-23 blockade achieved the highest PASI90 rates and longest drug survival versus both IL-17 and TNF-α inhibitors (p < 0.05). In this real-world cohort of Chinese psoriasis patients, BMI was observed to correlate with biologic effectiveness in a drug-specific manner. Our findings suggest that whilst IL-17 or IL-23 inhibitors showed favourable outcomes for non-overweight individuals, IL-23 blockade may be associated with a more sustained response in those categorised as overweight or obese.
Psoriasis is a chronic inflammatory skin disease characterised by keratinocyte hyperproliferation and immune cell infiltration driven by cytokines such as IL-17A. The dual-specificity phosphatase 6 (DUSP6) is a negative...Psoriasis is a chronic inflammatory skin disease characterised by keratinocyte hyperproliferation and immune cell infiltration driven by cytokines such as IL-17A. The dual-specificity phosphatase 6 (DUSP6) is a negative regulator of MAPK signalling and was previously reported to be a key mediator of arthritis severity. Here, we examine the role of DUSP6 in a mouse model of psoriasis. Psoriasis was studied in the imiquimod-induced model (IMQ). The skin of DUSP6+/+ and DUSP6-/- mice was treated with IMQ cream. Disease severity was assessed using well-established clinical and histologic systems. Skin inflammatory genes were quantified by qPCR.DUSP6-/- mice exhibited significantly reduced skin inflammation with lower PASI clinical scores (mean DUSP6-/- 1.8 and DUSP6+/+ 8.4; p < 0.0001). Histologic scores for epidermal thickening, parakeratosis and immune cell infiltration were decreased in the DUSP6-/- mice (p < 0.0005), and mRNA levels of IL1β, IL17A and STAT3 were lower in DUSP6-/- skin (p ≤ 0.05) compared with DUSP6+/+. In conclusion, DUSP6 is required for the development of psoriasis-like skin inflammation in mice. In the absence of DUSP6, mice were protected and had significantly lower levels of pathogenic genes, suggesting a new and central role for DUSP6 in skin inflammation and a potential therapeutic target in psoriasis.
Segmental vitiligo (SV) is a distinct subtype of vitiligo characterized by an early onset, unilateral distribution, and rapid stabilization. Although traditionally considered neurogenic in origin, recent evidence suggest...Segmental vitiligo (SV) is a distinct subtype of vitiligo characterized by an early onset, unilateral distribution, and rapid stabilization. Although traditionally considered neurogenic in origin, recent evidence suggests an immune-mediated pathomechanism. However, the molecular mechanisms underlying SV remain poorly characterized, and therapeutic options are limited. Topical calcineurin inhibitors (TCI) are widely used in immune-mediated dermatoses, but clinical data supporting their use in SV are scarce. We conducted a retrospective observational study of paediatric patients with SV treated with TCI, recording demographics, disease duration and 3-month clinical response. In parallel, selected public transcriptomic datasets were re-analysed to examine enrichment of TCR/Ca2 + -calcineurin/NFAT-related pathways as supportive mechanistic context. Five of eight patients (62.5%) achieved significant repigmentation (VNS ≥ 4) after 12 weeks, with shorter disease duration correlating with better outcomes (p = 0.0002451). Early intervention determined good clinical response even in cases with leukotrichia, and no adverse effects were observed. Transcriptomic re-analysis provided supportive, descriptive signals consistent with activation of T-cell signalling and Ca2 + -calcineurin/NFAT pathways in SV blood, while proxy datasets from non-segmental vitiligo skin did not show similar enrichment. Overall, in this small retrospective paediatric case series, early use of topical calcineurin inhibitors was associated with favourable clinical outcomes in SV and demonstrated a good safety profile. Larger, prospective studies are warranted to confirm these preliminary findings and refine therapeutic strategies.
de Moraes-Souza R, Bornia MJP, Chater RC
… +8 more, Piscazzi F, de Albuquerque MB, Mesquita Y, Lapenda I, Servera-Negre G, Hernández-Cano N, Sarto R, Herranz-Pinto P
Exp Dermatol
· 2026 Apr · PMID 41891530
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Chronic hand eczema (CHE) is associated with substantial functional impairment and reduced quality of life. Delgocitinib, a pan-Janus kinase (JAK) inhibitor, has emerged as a promising topical treatment for CHE. A system...Chronic hand eczema (CHE) is associated with substantial functional impairment and reduced quality of life. Delgocitinib, a pan-Janus kinase (JAK) inhibitor, has emerged as a promising topical treatment for CHE. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of topical delgocitinib 20-30 mg/g compared with vehicle in patients with CHE. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, EU CTR, and WHO ICTRP were searched up to 15 February 2026. The primary outcome was treatment success at week 16, defined as clear or almost clear skin with a ≥ 2-point improvement on the Investigator's or Physician's Global Assessment (IGA/PGA). Secondary outcomes included treatment success at weeks 4 and 8, changes in Hand Eczema Symptom Diary (HESD) itch and pain scores, and safety outcomes. Relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Three publications reporting four RCTs involving 1154 patients were included, with 752 receiving delgocitinib and 402 receiving vehicle. At week 16, treatment success was significantly higher with delgocitinib (RR 3.17; 95% CI 1.78-5.65; p < 0.01), corresponding to an absolute risk difference of 16.9% and a number needed to treat (NNT) of 6 (95% CI 3-16). Similar results at weeks 4 and 8. Delgocitinib also led to significantly greater improvements in HESD itch and pain scores. No significant differences were found in overall adverse events (AEs), treatment-related AEs, or serious AEs. Discontinuation due to AEs was lower in the delgocitinib group. Delgocitinib 20-30 mg/g demonstrated greater efficacy than vehicle and a favourable safety profile, supporting its use as a topical treatment for CHE.
Moltrasio C, Roncarà S, Ura B
… +7 more, Nardacchione EM, Sommella E, Moura R, Derlino F, Marzano AV, Crovella S, Tricarico PM
Exp Dermatol
· 2026 Apr · PMID 41891520
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Hidradenitis suppurativa (HS) is an autoinflammatory keratinisation disease affecting the pilosebaceous unit and hallmarked by a complex and multifactorial pathogenesis. Although genomic and transcriptomic investigations...Hidradenitis suppurativa (HS) is an autoinflammatory keratinisation disease affecting the pilosebaceous unit and hallmarked by a complex and multifactorial pathogenesis. Although genomic and transcriptomic investigations have substantially advanced our understanding of key mechanisms underlying HS pathogenesis, proteomic studies remain limited, despite the significant potential of serum proteomics to identify molecular signatures reflecting both cutaneous and systemic inflammatory activity. This exploratory study presents a serum proteomic analysis of patients with moderate-to-severe HS, identifying 306 differentially abundant proteins out of 3153 profiled (FDR q < 0.10). Sensitivity analysis at q < 0.05 (194 proteins) confirmed a robust inflammatory signature, while the FDR q < 0.10 threshold was necessary to preserve markers of epidermal homeostasis, which are inherently diluted in systemic circulation. Enrichment analyses revealed dysregulated pathways related to keratinisation, epidermal differentiation and extracellular matrix (ECM) remodelling, indicating impaired skin barrier function. Concurrent higher abundance of immune-related pathways, including defence response to bacterium, complement activation and neutrophil degranulation, suggest systemic inflammation potentially linked to microbial dysbiosis. These findings suggest the dual role of epithelial dysfunction and autoinflammation in HS pathogenesis. Integration of proteomic data with genomic and transcriptomic findings underscores the value of multi-omics approaches in guiding targeted therapeutic development.
Ng BD, Whelan C, Alkon N
… +3 more, Kurowski A, Jonak C, Brunner PM
Exp Dermatol
· 2026 Apr · PMID 41888970
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Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma, a disease characterized by malignant T cells that home to the skin. In early stages, clinical presentation is often indistinguishable f...Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma, a disease characterized by malignant T cells that home to the skin. In early stages, clinical presentation is often indistinguishable from benign chronic inflammatory skin diseases such as atopic dermatitis (AD), posing a challenge for proper diagnosis and treatment. Previous studies have established that MF is characterized by the expansion of a single T-cell clone, whereas benign skin conditions are polyclonal in nature. In this study, we aimed to use single-cell RNA sequencing data to detect distinct transcriptomic features of early-stage MF in comparison to AD skin. In early-stage MF, we observed gene expression differences in cells of both the stroma and the immune system, with keratinocytes exhibiting increased interferon response and proliferation (STAT1, ICAM1, HLA-DRA, GJB2), while fibroblasts displayed tumour-associated programs (CXCL2, TNFAIP6, CEBPD). Myeloid cells exhibited expression of immunomodulatory genes (RUNX3, DDIT4, IL4I1), and malignant T-cells expressed exhaustion-associated markers (CXCL13, SOCS3, F2R, ETV1), as opposed to AD and healthy control samples. Thus, our results provide a novel insight into the immune-stroma crosstalk in the tissue microenvironment of early-stage MF vs. AD skin lesions.