BACKGROUND: The primary cause of alopecia areata (AA) is autoimmune-mediated hair follicle destruction, while breakdown of immune tolerance due to Treg cell homeostasis disruption critically contributes to this process....BACKGROUND: The primary cause of alopecia areata (AA) is autoimmune-mediated hair follicle destruction, while breakdown of immune tolerance due to Treg cell homeostasis disruption critically contributes to this process. However, in AA, the factors leading to Treg cell impairment and the effective regulatory pathways remain unanswered. OBJECTIVES: To assess the therapeutic effects of sCD83 on AA and elucidate the crucial role of sCD83-mediated Treg cell activation in remodeling the perifollicular microenvironment. METHODS: Blood and scalp tissue were collected from AA patients and healthy controls to characterize sCD83 using ELISA, flow cytometry, and immunofluorescence. In graft-induced C3H/HeJ mouse model of AA, the therapeutic effect of sCD83 on early-onset AA was evaluated by H&E staining, immunofluorescence, and flow cytometry. In vitro, human hair follicle organ culture and primary outer root sheath keratinocyte (ORSK) culture were utilized to clarify the impact of sCD83 on the expression and activity of indoleamine 2,3-dioxygenase (IDO) in hair follicle. Co-culture of ORSKs and PBMCs, together with administration of an IDO inhibitor to AA mice, were performed to determine the necessity of IDO for Treg cell activation. Finally, GST-pulldown and co-IP assays were employed to identify potential sCD83 receptors on ORSKs. RESULTS: We showed here that AA patients exhibit sCD83 deficiency, which may be attributed to reduced sCD83 release from DCs, and that serum sCD83 levels are negatively correlated with disease severity. Supplementation with sCD83 in AA mouse reversed disease manifestations and promoted Treg cell proliferation. Mechanistically, IDO activity in ORSKs is essential for sCD83-mediated Treg cell activation, with TRX potentially serving as a sCD83 receptor to regulate IDO expression. CONCLUSIONS: Our study establish the functional role of sCD83 in AA, confirms the therapeutic potential of sCD83 supplementation, and provides some mechanistic insights.
Stein Gold L, Armstrong AW, Soung J
… +19 more, Vender RB, González Cantero Á, Hoffmann M, Guenthner ST, Hong HC, Murrell DF, Song EJ, Kircik L, Augustin M, Sauder M, Gerdes S, Reyes-Servin O, Edem BE, Campbell J, Cresswell K, Kephart L, Li S, Yang YW, Bissonnette R
BACKGROUND: Icotrokinra, a targeted oral peptide, precisely blocks the interleukin-23 receptor. In two phase 3 moderate-to-severe plaque psoriasis trials, ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604)...BACKGROUND: Icotrokinra, a targeted oral peptide, precisely blocks the interleukin-23 receptor. In two phase 3 moderate-to-severe plaque psoriasis trials, ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604), icotrokinra provided significantly higher skin clearance rates versus placebo at Week 16 and deucravacitinib at Week 16 and 24. OBJECTIVES: Report findings through Week 52 of ICONIC-ADVANCE 1&2. METHODS: ICONIC-ADVANCE 1&2 randomised (2:1:2/4:1:4) adults with moderate-to-severe plaque psoriasis (body surface area ≥10%, Psoriasis Area and Severity Index [PASI] ≥12, Investigator's Global Assessment [IGA] ≥3) to icotrokinra 200 mg, placebo (transition to icotrokinra at Week 16), or deucravacitinib 6 mg once daily (transition to icotrokinra at Week 24). Outcomes assessed through Week 52 included proportions of participants achieving IGA 0/1 (with ≥2-grade improvement from baseline), PASI 90, IGA 0, PASI 100, scalp-specific IGA (ss-IGA) 0/1, patient-reported outcomes (clinically meaningful improvement [CMI; ≥4-point reduction] in Psoriasis Symptoms and Signs Diary [PSSD] itch, PSSD symptom score 0, Dermatology Life Quality Index [DLQI] 0/1), and adverse events (AEs). RESULTS: ICONIC-ADVANCE 1&2 randomised 1505 participants (774/731). Across the studies, skin clearance rates among icotrokinra-randomised participants increased through Week 24 and were durable through Week 52, with ∼70%-75% exhibiting clear/almost clear skin (IGA 0/1, PASI 90) and ∼50% demonstrating completely clear skin (IGA 0, PASI 100) during Weeks 24-52. Among participants achieving clear/almost clear skin at Week 16, ∼85%-90% maintained response at Week 52. Response rates for ss-IGA 0/1 and patient-reported outcomes were also durable through Week 52. Participants who transitioned from placebo or deucravacitinib to icotrokinra exhibited increasing response rates that were comparable to icotrokinra-randomised participants through Week 52. The AE profile of icotrokinra was similar to placebo through Week 16 and showed lower AE rates than deucravacitinib through Week 24; no safety signals were observed through Week 52. CONCLUSIONS: Once-daily icotrokinra provided robust, durable skin clearance and symptom improvement, with no safety signals, through Week 52 in adults with moderate-to-severe plaque psoriasis. Participants transitioning from placebo or deucravacitinib to icotrokinra achieved similar increased response rates to icotrokinra-randomised participants through Week 52. Findings support icotrokinra as a systemic therapy with long-term robust disease control and a favourable safety profile.
BACKGROUND: Lymphocytic thrombophilic arteritis is a distinctive but poorly understood lymphocytic vasculitis. There is a need to better define this entity. OBJECTIVE: We conducted a case-series analysis of all patients...BACKGROUND: Lymphocytic thrombophilic arteritis is a distinctive but poorly understood lymphocytic vasculitis. There is a need to better define this entity. OBJECTIVE: We conducted a case-series analysis of all patients with a diagnosis of lymphocytic thrombophilic arteritis known to St Vincent's Hospital Melbourne Dermatology Unit, in Victoria, Australia, a referral centre for cutaneous vasculitis and lymphocytic thrombophilic arteritis, to better characterise the clinicopathological features of this entity. METHODS: All patients who met our clinicopathological criteria for this condition were included. Diagnostic clinical features included the presence of widespread blanchable livedo racemosa and/or macular pigmentation. Diagnostic histological features included the presence of a lymphocytic arteritis with fibrin deposition affecting vessels in the deeper dermis and/or upper subcutis.Cases of lymphocytic thrombophilic arteritis were assessed for demographics, comorbidities, clinical features, histopathology, treatments, and clinical response. RESULTS: Thirty-six cases were identified including 26 female and 10 male patients with an average age of onset of 32.7 years. A high proportion of cases with Asian descent was noted (44.4%). Most cases (94.4%) presented with widespread livedo racemosa. Less common manifestations included petechiae (16.7%), macular pigmentation (22.2%), neuropathy (33.3%), and ulceration (33.3%). A significant association was noted between ulceration and superficial dermal vessel involvement on biopsy, similar to livedoid vasculopathy.All cases demonstrated a neutrophil-poor lymphocytic perivascular infiltrate with fibrinoid change in the deeper dermis/upper subcutis. A variety of vessels were affected; 44.4% involved vessels in the superficial dermis as well as the deep dermis/upper subcutis. A discrete concentric fibrin ring (41.7%) was not essential for diagnosis.Treatments targeting vascular fibrin deposition appeared effective for all manifestations other than livedo for which no cases responded. CONCLUSION: Lymphocytic thrombophilic arteritis has distinctive clinicopathological features and may lie on a spectrum with livedoid vasculopathy. Although livedo racemosa persists, other manifestations respond to antithrombotic treatments.
Siegfried EC, Baselga E, de Graaf M
… +12 more, Simpson EL, Boguniewicz M, Flohr C, Eichenfield LF, Paller AS, Ramien M, Gao XH, Ahn J, Capozza K, Ma Y, Bates L, Rossi AB
BACKGROUND: Bathing, even in tap water, alters skin physiology. Frequent infant bathing may increase the risk of eczema developing. OBJECTIVE: To undertake a randomised controlled feasibility trial of an intervention to...BACKGROUND: Bathing, even in tap water, alters skin physiology. Frequent infant bathing may increase the risk of eczema developing. OBJECTIVE: To undertake a randomised controlled feasibility trial of an intervention to reduce infant bathing frequency and intensity. METHODS: Randomised controlled trial. 105 pregnant women (≥ 16 years) with family history of atopy, carrying a healthy singleton child (54 male, 51 female) were randomised in a 1:1 ratio during pregnancy, or postnatally prior to the first infant bath. The intervention group were asked to reduce bathing frequency (no more than once a week for the first six months of age) and intensity (keep baths short, not too hot and washing in plain water is usually sufficient). The control group received the routine postnatal infant care advice offered in their maternity unit.The primary feasibility outcome was the proportion of eligible families willing to be randomised to the intervention. The secondary clinical outcome was a blinded assessment of infant eczema at age 6 months, using an adaptation of the UK Working Party Diagnostic Criteria for Atopic Dermatitis. RESULTS: : 261 pregnant women were screened, of whom 21 were ineligible and 105/240 (44%) were randomised to the intervention (52) and control (53) groups. Adherence to the intervention was high with 79.6% (35/44) in the intervention arm bathing their infant once a week or less, compared to 28.6% (14/49) in the control group. In the intervention group 95% (38/40) agreed or strongly agreed that the intervention was acceptable. There was minimal contamination of the control group (1/46). Follow-up was high with 89% (93/105) of families completing the final 6-month questionnaire and 82% (86/105) attended the final visit. Eczema outcomes occurred less frequently in the intervention arm compared to the control arm: visible eczema 15.8% (6/38) vs 29.2% (14/48); parent reported eczema 9.1% (4/44) vs 12.2% (6/49); and doctor diagnosed parent reported eczema 6.8% (3/44) vs 10.2% (5/49). No noteworthy adverse effects of the intervention were reported. CONCLUSIONS: These findings support the feasibility of randomising infants during pregnancy to a reduced frequency and intensity bathing intervention for eczema prevention. TRIAL REGISTRATION: ISRCTN51491794 (Registered 24/07/2023).
Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by skin and internal organ fibrosis, vasculopathy and immune dysregulation. Skin fibrosis, commonly assessed using the modified Rodnan ski...Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by skin and internal organ fibrosis, vasculopathy and immune dysregulation. Skin fibrosis, commonly assessed using the modified Rodnan skin score (mRSS), remains a defining feature of SSc and is associated with disease severity and prognosis. However, conventional clinical assessment provides limited insight into the molecular heterogeneity underlying cutaneous involvement. Single-cell RNA sequencing and spatial transcriptomics have shown that SSc skin contains distinct fibroblast states, immune-stromal interactions and spatially organised fibrotic niches. These data challenge the view of cutaneous fibrosis as a uniform process and instead support a model in which different cellular and spatial programmes may contribute to clinically similar patterns of skin involvement. In this review, we synthesise findings from single-cell and spatial multi-omics studies of SSc skin published between 2021 and 2025, examine the extent to which molecular heterogeneity relates to clinical phenotype, and discuss the implications for cutaneous assessment, treatment-response heterogeneity and biologically informed patient subgrouping. Because skin biopsy is clinically accessible and can be repeated over time, it provides a practical setting in which these molecular observations can be studied. Whether they improve patient stratification, treatment selection or cutaneous outcome assessment will depend on prospective validation in larger and clinically well-characterised cohorts.