Chronic inflammatory skin diseases (CISDs) such as psoriasis (PsO), atopic dermatitis (AD), and hidradenitis suppurativa (HS) involve both cutaneous and systemic immune dysregulation, whereas commonly used scores rely largely on subjective clinical features and insufficiently reflect underlying inflammatory activity or cardiovascular risk. This review summarizes evidence across three biomarker domains: tissue-level pathways (the Fas/FasL and interleukin (IL)-21/IL-21R), circulating inflammatory mediators, and hematology-derived indices (the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), pan-immune-inflammation value (PIV), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI)) in relation to disease activity, therapeutic response, and cardiometabolic burden. A targeted literature search was performed in PubMed/MEDLINE, Scopus, and the Cochrane Library (January 2000 to November 2025), supplemented by artificial intelligence (AI)-assisted retrieval, manual screening of reference lists, and citation tracking. Studies providing patient-derived clinical or translational data were included and summarized in structured comparative tables. The findings indicate that dysregulated Fas/FasL signaling contributes to keratinocyte apoptosis resistance and chronic epidermal inflammation in PsO and AD, with limited data in HS. IL-21 is elevated in PsO and AD, correlating with clinical severity and epidermal hyperplasia, whereas its role in HS remains unexplored despite the strong Th17 and B-cell signature of the disease. Complete blood count-derived indices demonstrate associations with systemic inflammation and increased cardiometabolic risk, particularly in PsO and HS, yet diagnostic performance varies and methodological standardization is lacking. Taken together, these biomarkers provide insights into local and systemic aspects of disease biology but are not yet validated for clinical use. Integrating tissue-specific mediators, soluble biomarkers, and hematologic indices into multimodal panels may ultimately strengthen precision monitoring of disease activity, treatment response, and cardiovascular risk in CISDs. Prospective, multicenter studies are needed to establish clinically actionable, biomarker-driven strategies that enable more mechanism informed and personalized care.

Prurigo nodularis (PN) is a chronic inflammatory dermatosis with severe, persistent pruritus and limited effective therapies. Janus kinase (JAK) inhibition has emerged as a targeted strategy for PN. This phaseI/II, randomized, double-blind, vehicle-controlled, multicenter clinical trial was conducted in China to evaluate the safety, pharmacokinetics, and efficacy of topical 1.5% ruxolitinib gel (HDM3010) in adults with PN. Adult patients with PN were randomized 2:1 to receive HDM3010 or vehicle, administered once daily (QD) or twice daily (BID), during a 4-week double-blind treatment period. Forty-nine patients were randomized. HDM3010 demonstrated a safety profile characterized by treatment-emergent adverse events in 18.8% of QD and 25.0% of BID patients, compared with 12.5% of vehicle QD and 55.6% of vehicle BID patients. Treatment-related adverse events were infrequent (4.1%) and limited to mild-to-moderate severity. Pharmacokinetic analyses showed low systemic exposure, with mean peak plasma concentrations below 7ng/mL at steady state. Compared with vehicle, HDM3010 was associated with higher proportions of ≥ 4-point Worst Itch Numerical Rating Scale (WI-NRS) responders and greater improvements in WI-NRS, Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA PN-S), and Investigator's Global Assessment for Prurigo Nodularis-Activity (IGA PN-A) scores. HDM3010 demonstrated a favorable safety profile, minimal systemic exposure, and positive trends in reducing pruritus and lesions in adults with PN. Chinese Clinical Trial Registry ( http://www.chictr.org.cn ): ChiCTR2500096434 (registered January 23, 2025).

Chronic prurigo (CPG) is a chronic neuroinflammatory skin disease characterized by persistent itch, repeated scratching, and the presence of multiple skin lesions. CPG is a highly burdensome disease that significantly impairs patients' quality of life. The objective of these consensus recommendations is to summarize available evidence and provide standardized guidance for the diagnosis and management of patients with CPG. These recommendations were developed using a Delphi methodology, conducted over two rounds of online voting by the participation of 23 Portuguese dermatologists. The strength of consensus was defined as strong consensus (≥ 95% agreement), consensus (≥ 75%), and majority agreement (≥ 50%). The diagnosis of CPG requires the concomitant presence of a ≥ 6-week history of pruritus; a history of repeated excoriation; and multiple skin lesions (including nodules, papules, umbilicated lesions, and linear lesions, among others). Diagnosis should be based on patient history and physical examination, and complemented by laboratory tests and additional investigations if needed. Treatment should follow a personalized protocol, according to disease severity and guided by both clinician- and patient-reported outcomes. Systemic therapeutic options for eligible patients include CPG-approved biological agents (dupilumab and nemolizumab), gabapentinoids, and antidepressants. Additional treatment options may be considered, including interleukin (IL)-13 inhibitors, Janus kinases (JAK) inhibitors, opioid receptor modulators, methotrexate, and cyclosporine. Treatment efficacy should be regularly assessed to ensure clinical improvement and patient adherence. This study provides guidance on the diagnosis and treatment of CPG supporting diagnosis and treatment decision-making.

Risankizumab (RZB) and deucravacitinib (DEU) are both approved for the treatment of moderate-to-severe psoriasis. Physicians value head-to-head comparisons between available therapies to make evidence-based treatment decisions. This study evaluates the safety and efficacy of RZB compared with DEU for the treatment of patients with moderate psoriasis who have not previously received biologic treatment. Patients with moderate psoriasis, eligible for systemic treatment and without prior biologic exposure, were enrolled in a 1:2 ratio to RZB or DEU, respectively. The 52-week treatment was divided into two periods: period A (baseline to week 16) and period B (weeks 16-52). Results from period A are presented here. In period A, patients either received a single subcutaneous injection of RZB 150mg on day 1 and week 4 or oral DEU 6mg daily. The coprimary endpoints in period A were achievement of ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) and achievement of sPGA 0 or 1 (sPGA 0/1) with at least a two-grade improvement from baseline. Ranked secondary endpoints for period A included the achievement of PASI 100 and sPGA 0 with at least a two-grade improvement from baseline at week 16. Additional endpoints were also assessed. Safety was based on assessment of treatment-emergent adverse events (TEAEs). A significantly higher proportion of patients treated with RZB achieved PASI 90 (57.3% versus 22.9%), sPGA 0/1 (80.2% versus 39.7%), PASI 100 (27.5% versus 6.5%), and sPGA 0 (27.5% versus 6.9%) compared with patients treated with DEU at week 16 (P < 0.0001). The proportion of patients with TEAEs was 33.6% (RZB) and 42.9% (DEU). Safety was consistent with the known profiles of RZB and DEU. In this 16-week analysis, treatment with RZB demonstrated superior efficacy compared with DEU in adults with moderate psoriasis. No new or unexpected safety signals were identified. ClinicalTrials.gov identifier: NCT06333860.

Delgocitinib cream is a topical pan-Janus kinase inhibitor approved for adults with moderate to severe Chronic Hand Eczema (CHE) in the USA, Canada, European Union, and multiple other countries. Here, we assessed the systemic exposure of twice-daily topical application of delgocitinib cream 20 mg/g in adults with moderate to severe CHE treated under normal or maximal use conditions in the DELTA 2 trial and compared with the systemic exposure in adults with moderate to severe atopic dermatitis (AD) from a delgocitinib cream phase 1 AD trial. Blood sampling was performed 2-6h after delgocitinib cream application at weeks 1, 4, and 16 in DELTA 2. In the delgocitinib cream phase 1 trial, blood sampling was performed prior to application and at six timepoints (0-12h) post-application on day 1 and day 8. Geometric mean delgocitinib plasma concentrations were calculated in DELTA 2 and peak delgocitinib plasma concentrations (geometric mean Cmax) were calculated in the phase 1 trial. In DELTA 2, patients treated with delgocitinib cream under normal (n = 294; body surface area [BSA], 1.48%; application, 7.3g/week) or maximal use conditions (n = 19; BSA, 2.17%; application, 13.7g/week) showed geometric mean delgocitinib plasma concentrations at week 1 of 0.19ng/mL (n = 268) and 0.58ng/mL, respectively. In the phase 1 trial, patients (n = 14; BSA, 33.6%; application, 72.3g/week) showed a geometric mean Cmax of 1.20ng/mL (n = 13) on day 8. Delgocitinib cream 20mg/g resulted in minimal systemic exposure among adults with moderate to severe CHE, including those treated under maximal use conditions. Low systemic exposure was also observed in adults with moderate to severe AD, despite substantially greater BSA involvement and higher delgocitinib cream usage, highlighting the properties of delgocitinib cream's novel formulation. NCT03826901 (phase 1, delgocitinib cream); study start date: 20 February 2019; primary completion date: 29 October 2021; study completion date: 29 October 2021. NCT04872101 (DELTA 2); study start date: 25 May 2021; primary completion date: 27 December 2022; study completion date: 6 January 2023.

Zasocitinib (TAK-279) is an investigational, once daily,oral, allosteric, highly selective, and potent tyrosine kinase 2 inhibitor. Post hoc analyses of a 12-week phase IIb trial in patients with moderate-to-severe plaque psoriasis evaluated zasocitinib 15mg or 30mg efficacy versus placebo by baseline characteristic subgroups, Psoriasis Area and Severity Index (PASI) improvements by body region and component scores, and patient-reported and other clinical outcomes. Disease severity assessments included PASI, Physician's Global Assessment (PGA), body surface area (BSA), Dermatology Life Quality Index (DLQI) 0/1, and PGA × BSA. Subgroups included weight, sex, age, race, disease duration, prior biologic use, and PASI score. Body regions included head, trunk, and upper and lower extremities. Scoring components included erythema, induration, and desquamation. DLQI 0/1 attainment was assessed by PASI. At week 12, zasocitinib 15mg or 30mg demonstrated greater response rates in PASI 75/90/100 and PGA 0/1 in nearly all patient subgroups versus placebo. A greater proportion of patients receiving zasocitinib achieved PASI 75/90/100 across all PASI body regions and scoring components versus placebo. Reductions in BSA or PASI were greater in zasocitinib groups as early as week 2 and through week 12 versus placebo; most patients attaining PASI ≤ 1 or ≤ 2 or PASI75/90/100 also achieved DLQI 0/1. Absolute PASI and PGA × BSA improvements were strongly positively correlated (ρ = 0.95), with PGA × BSA 75 and PASI75 showing high agreement. Zasocitinib demonstrated consistent improvements in skin clearance, irrespective of baseline disease characteristics, PASI body region, and scoring component, with meaningful quality of life improvements. Graphical abstract available for this article. ClinicalTrials.gov Identifier:NCT04999839.

Nemolizumab is a humanized monoclonal antibody that specifically inhibits the receptor for interleukin-31, the major pruritogen in atopic dermatitis (AD). While the patient profile associated withtheearly therapeutic responseto nemolizumab in AD has been increasingly delineated, the characteristics of patients who benefit from long-term nemolizumab therapy remain unclear. This study aimed to identify early clinical features predicting long-term improvement in pruritus Visual Analog Scale (VAS) scoreamong patients receiving nemolizumab. This study included patients participating in two Japanese clinical trials (JP01 and JP02) who did not achieve a 50% improvement in pruritus VAS score (VAS50) at week 16 after initiation of nemolizumab treatment. Patients who achieved VAS50 at week 52 were classified as responders, and those who did not were nonresponders. A machine-learning decision tree model was developed using 213 candidate variables. Model performance was evaluated using the F1 score. Shapley additive explanation (SHAP) values were used to interpret variable importance. Among 118 eligible patients, the final model achieved an F1 score of 0.737. The two strongest predictors of long-term response were the absence of worsening of AD and/or the occurrence of other cutaneous disorders until week 16, and a weekly mean itch scale score < 2.1 at week 16. Patients meeting both criteria were highly likely to achieve VAS50 by week 52. Machine-learning identified straightforward and clinically applicable predictors of long-term nemolizumab efficacy in patients who did not have early VAS improvement. These findings may support decision-making for treatment continuation beyond week 16. JapicCTI-173740 (JP01), and JapicCTI-183894 (JP02).

This is a summary of the original article "Apremilast improves skin outcomes in pediatric plaque psoriasis of shorter disease duration: 52-week results from the SPROUT phase3 trial". Enrolled patients were aged 6-17years with moderate to severe plaque psoriasis (PsO) inadequately controlled by, or inappropriate for, topical therapy (NCT03701763).Patients were randomized to apremilast or placebo for 16weeks, after which all patients transitioned to apremilast through 52weeks. The efficacy of apremilast was assessed by disease duration at baseline (shorter, < 2years; medium, ≥ 2 to < 5years; longer, ≥ 5years). In this post hoc analysis, patients had generally similar baseline characteristics across disease durations. At week16, patients receiving apremilast vs placebo experienced numerically greater improvements in most skin clearance outcomes across all disease durations, particularly in patients with disease duration < 2years. Through week52, patients experienced numerical improvements across all disease durations, with the most pronounced efficacy in patients with disease duration < 5years. These findings suggest early intervention with a systemic therapy such as apremilast in pediatric patients with moderate to severe PsO may mitigate disease burden.

In pooled LIBERTY-PN PRIME/PRIME2 trials on prurigo nodularis (PN), at week24, the stringent composite endpoint of a ≥ 4-point reduction from baseline in Worst Itch Numeric Rating Scale (WI-NRS) score combined with an Investigator's Global Assessment for PN-Stage (IGA PN-S) score of 0/1 (clear/almost clear skin) was achieved by 35.3% of dupilumab versus 8.9% of placebo-treated patients. This optimal response may not capture the full experience of treatment in the remaining patients. This study assessed additional efficacy endpoints in the remaining dupilumab (64.7%) and placebo (91.1%) PRIME/PRIME2 recipients without optimal response at week24. Additional week24 endpoints included ≥ 9-point reduction from baseline in Dermatology Life Quality Index (DLQI) score, Patient Global Impression of Severity (PGIS) score of "none"/"mild," ≥ 75% healed lesions from Prurigo Activity and Severity (PAS-75), and a concomitant reduction from baseline of ≥ 3 points in WI-NRS score and ≥ 1 point in IGA PN-S score. Data from 99 dupilumab-treated and 144 placebo-treated patients without optimal response were analyzed. Among dupilumab-treated patients, 61.1% achieved a ≥ 9-point reduction from baseline in DLQI score, 55.8% a PGIS score of "none" or "mild," 53.7% PAS-75, and 45.7% the less stringent itch and skin lesion composite endpoint (nominal P vs placebo significant for all). Dupilumab treatment versus placebo resulted in nominally significant improvements in signs, symptoms, and quality of life in patients with PN without optimal response by week24, supporting the benefits of continued treatment. These results highlight the need to develop a treat-to-target strategy for the long-term management of PN. ClinicalTrial.gov Identifiers: NCT04183335 and NCT04202679 (registered December 2019).