Delgocitinib is a pan-Janus kinase inhibitor approved for moderate-to-severe chronic hand eczema (CHE) in adults. However, real-world evidence remains limited. We prospectively evaluated 149 adult patients (mean age: 46.4 years; 60.4 % female) treated with delgocitinib for chronic hand eczema across 20 Italian dermatology centres between May and November 2025, with a four-month follow-up. Two-thirds of patients were non-occupationally exposed, and>80% had vesicular or atopic chronic hand eczema. At week 4, Physician Global Assessment (PGA)-chronic hand eczema 0/1 and Hand Eczema Severity Index (HECSI)-75 were achieved in 42.3% and 43.8% of patients, increasing significantly to 74.3% and 88.0% at week 16. Pruritus and pain Numerical Rating Scale (NRS) 0/1 were reported in 43.8% and 52.3% of patients at week 4, rising significantly to 74.4% and 86.5% at week 16. Hand Eczema Symptom Diary-Patient Global Impression of Severity (HESD PGI-S) 0/1 increased from 45.6% to 76.6%. Non-occupationally exposed patients showed significantly higher early response rates than occupationally exposed, with attenuation of differences by week 16. HECSI-75 responses were consistent across chronic hand eczema subtypes, particularly vesicular (94.0%) and atopic (90.0%). Treatment was well tolerated, with rare and no severe adverse events reported. These findings support delgocitinib as a rapid, effective and safe treatment option for chronic hand eczema.

Chronic hand dermatitis (CHD), also referred to as chronic hand eczema, is a persistent inflammatory skin disorder characterized by erythema, fissuring, scaling, lichenification, and significant pruritus and pain. The condition is often debilitating, particularly because the hands are constantly exposed to mechanical friction, detergents, irritants, and environmental stressors. Traditional treatments such as topical corticosteroids, calcineurin inhibitors, phototherapy, and systemic immunomodulators are limited by safety concerns, incomplete efficacy, or poor long-term tolerability. Delgocitinib 2% cream, a non-steroidal, topical pan-Janus kinase (JAK) inhibitor, represents the first targeted therapy specifically approved for moderate-to-severe CHD in adults. Through inhibition of JAK1, JAK2, JAK3, and tyrosine kinase 2, delgocitinib broadly suppresses multiple cytokine pathways involved in hand eczema pathogenesis. Clinical trials have demonstrated significant improvement in Investigator's Global Assessment scores, Hand Eczema Severity Index, pruritus, pain, and quality of life, along with sustained benefit in long-term extension studies. Safety data reveal minimal systemic absorption, no steroid-associated skin atrophy, and a favorable tolerability profile without box warnings. This review examines the pathophysiology of CHD and the clinical evidence supporting delgocitinib as an effective, steroid-sparing therapeutic option.

Background and Objectives: Oral alitretinoin (9-cis-retinoic acid), a dual retinoic acid receptor/retinoid X receptor agonist, is approved for severe chronic hand eczema (CHE) refractory to potent topical corticosteroids but is also prescribed off-label in routine practice. Long-term real-world data on both uses are limited. We evaluated 10-year prescribing patterns, effectiveness, tolerability, and lipid changes at one Korean academic center. Materials and Methods: Patients prescribed oral alitretinoin between January 2016 and December 2025 were identified from the hospital prescribing database; those with an evaluable course of ≥1 month formed the effective-treatment cohort and underwent chart review. Treatment success was defined as final chart-derived Investigator Global Assessment (IGA) 0/1. Success by initial dose was compared using Fisher exact test; paired lipid changes using paired t-test and Wilcoxon signed-rank test. Results: Of 161 patients, 38 (23.6%) received a single prescription; 99 formed the effective-treatment cohort (50 women, 49 men; mean age 50.7 ± 16.0 years). CHE was the leading indication (70/99, 70.7%), followed by palmoplantar pustulosis (PPP, n = 14), mycosis fungoides (MF, n = 6), parapsoriasis, porokeratosis, palmoplantar keratoderma, and Darier disease. Overall success was 66.7% (66/99) over a mean treatment duration of 12.4 months, highest in CHE (77.1%) and more variable off-label (PPP 42.9%; MF 33.3%). Initiation at 30 mg was associated with higher success than 10 mg (71.1% vs. 43.8%; p = 0.044), but this association did not persist after restriction to patients maintained on their initial dose (62.2% vs. 50.0%; p = 0.498) or after Firth penalized logistic regression adjusting for age, sex, and indication (adjusted odds ratio 1.84; 95% CI 0.56-5.90; p = 0.309). Adverse events occurred in 21 patients (21.2%), most commonly dyslipidemia (n = 12) and headache (n = 7); mean triglyceride rose 42.1 mg/dL and total cholesterol 14.0 mg/dL (both p < 0.001), and new elevation above conventional thresholds occurred in 25.8% (triglyceride) and 27.5% (total cholesterol) of patients with normal baseline values. Thirty patients (30.3%) discontinued, most often for insufficient effectiveness. Conclusions: Alitretinoin showed favorable effectiveness in CHE and variable, exploratory responses off-label. The apparent advantage of 30 mg initiation was not independent of indication and dose adjustment. Lipid elevation was common, supporting routine surveillance. Off-label findings, particularly in PPP and MF, should be interpreted cautiously given small subgroups and non-standardized retrospective assessment.

Background/Objectives: Occupational contact dermatitis (OCD) is the most common work-related skin disease, accounting for roughly 90-95% of occupational dermatoses and falling predominantly on the hands. It is rarely dangerous yet imposes a substantial burden through impaired quality of life, lost productivity, and premature exit from affected trades. The COVID-19 pandemic intensified this burden among healthcare workers, in whom the pooled one-year prevalence of self-reported hand eczema reaches around 27%; meta-analytic data link the increased risk principally to frequent handwashing and wet work rather than to alcohol-based hand rub. Methods: This narrative review, which follows a non-systematic, thematically organised search strategy rather than PRISMA methodology, integrates current evidence on the epidemiology, pathophysiology, diagnosis, prevention, and management of OCD, with particular emphasis on the self-reinforcing cycle linking skin barrier disruption, microbiome dysbiosis, and antimicrobial-peptide dysregulation to inflammation. Results: We critically appraise the prevention evidence, foregrounding the low certainty of the existing trial base and the tension between the randomised trials of primary and secondary prevention, which have been null, and the encouraging but uncontrolled results of structured tertiary-prevention programmes. We summarise recent therapeutic advances, including topical delgocitinib, and situate the field within the World Health Organisation's 2025 recognition of skin diseases as a global public health priority. Established evidence and hypotheses are kept separate throughout: we additionally advance, explicitly as a conjecture rather than as a demonstrated mechanism, a conceptual trans-kingdom dialogue model in which protease-generated LL-37 fragments may modulate staphylococcal quorum sensing, and each step of that model is labelled according to whether the supporting evidence is direct, extrapolated, or as yet untested. Conclusions: We argue that the prevention failure is less one of biology than of trial design and measurement, and outline the research needed to close the gap.

Occupational hand dermatitis (HD) is a chronic refractory hand eczema that is caused or exacerbated by workplace exposures. The hands are uniquely vulnerable to dermatitis from exposure to allergens and irritants in the workplace, including metals, preservatives, acrylates, rubber accelerators, food, water, plants, and fragrances. In occupational allergic contact dermatitis (ACD), patch testing plays a critical role in identifying contact allergens to help guide avoidance strategies that are key for clinical improvement. A coordinated return-to-work plan is essential for managing patients with occupational HD. In this article, we review practical considerations for evaluation and management of occupational HD, highlighting relevant exposures and pearls on workup and management.