Chronic hand eczema (CHE) is a multifactorial skin condition that poses significant diagnostic challenges and severely impacts patients’ quality of life. However, emerging JAK inhibitors offer promising new treatment options.
Clinical Overview
Patients with CHE may experience periodic flares rather than constant symptoms. CHE is defined as persisting for at least three months or recurring more than twice within a 12-month period. Clinically, CHE presents with a variety of symptoms, including pruritus, pain, fissures, stinging, burning, and sleep disturbances. The disease can negatively affect mood and quality of life and often carries a significant occupational burden. Morphologically, erythema, scaling, hyperkeratosis, vesicles, and nail dystrophy are frequently observed.
Diagnostic Challenges
CHE often involves a mixed etiology, including irritant contact dermatitis, allergic contact dermatitis, atopic dermatitis, and protein contact dermatitis. The presence of overlapping pathophysiologic pathways, such as Th1, Th2, Th17, and Th22, adds complexity to diagnosis and treatment. A careful history and physical exam are essential. Diagnostic aids may include KOH prep for fungal involvement, patch testing for allergens, prick testing for protein exposures, biopsies, and cultures for suspected infection. The German CARPE registry highlighted the prevalence of mixed subtypes, showing that 50% of CHE cases involve more than one etiology. This underscores the importance of a multifaceted diagnostic approach tailored to each patient’s history and exposure risks.
New Therapeutic Developments
Currently, there are no FDA-approved therapies specifically for moderate to severe CHE. Traditional treatment has relied heavily on topical corticosteroids, which pose risks such as skin atrophy, especially with long-term use on the hands. Emerging therapies target the JAK-STAT pathway, which plays a central role in the inflammatory processes of CHE, regardless of etiology.
Delgocitinib (Anzupgo; Leo Pharma)
Delgocitinib, a topical pan-JAK inhibitor, has shown promise in clinical trials. In a 16-week study, about 40% of participants with moderate to severe CHE achieved “clear” or “almost clear” status. The improvement began as early as week 1 and was maintained through 36 weeks in a long-term extension study. Delgocitinib also demonstrated minimal systemic absorption—even in studies involving extensive skin application—suggesting a favorable safety profile for long-term use.
Ruxolitinib (Opzelura; Incyte) Cream
Ruxolitinib, a topical JAK1/2 inhibitor already approved for atopic dermatitis, has also been evaluated in patients with CHE. In a phase 2 study, patients showed statistically significant improvement compared to placebo, with positive safety and tolerability outcomes.
Looking Ahead
Indirect comparisons have suggested that topical JAK inhibitors may offer efficacy comparable to systemic agents like dupilumab, particularly in non-atopic CHE subtypes. Ongoing trials are expanding investigations into adolescent populations and broader adult cohorts.
Conclusion
CHE is a multifactorial, burdensome disease that requires accurate diagnosis and careful therapeutic planning. With limited approved options, emerging topical JAK inhibitors such as delgocitinib and ruxolitinib present promising, well-tolerated alternatives for patients with moderate to severe disease. As further evidence accumulates, these agents may offer a new standard of care in managing this complex dermatologic condition.
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