Clinical bottom line
Chronic hand eczema (CHE) in adults remains a challenging condition to manage, particularly in moderate-to-severe cases refractory to topical therapies. Recent advances in systemic treatments, including novel Janus kinase (JAK) inhibitors such as delgocitinib, offer promising efficacy with acceptable safety profiles. However, evidence is still emerging, and long-term benefit-risk assessments are limited. Clinicians should consider patient preferences, comorbidities, and prior treatment responses when integrating these new systemic options into practice.
What the evidence shows
Systemic treatment options for CHE have historically included retinoids and immunosuppressants such as mycophenolate mofetil, but these carry variable efficacy and tolerability (Agner et al., 2014; Sasseville et al., 2014). More recently, pan-JAK inhibitors have been investigated due to their broad immunomodulatory effects relevant to CHE pathogenesis.
Delgocitinib, a topical pan-JAK inhibitor, has demonstrated efficacy in moderate-to-severe CHE with a favorable safety profile in phase 3 trials, including the DELTA-2 study (Gooderham et al., 2024). Systemic exposure from topical application was low, minimizing systemic adverse effects. Termini et al. (2026) provide an updated review highlighting delgocitinib’s mechanism and clinical potential across cutaneous inflammatory diseases, including CHE.
Comparative effectiveness data remain limited. The BEACON trial (Pink et al., 2023) and the ISRCTN80206075 study (Wittmann et al., 2015) have explored systemic treatments for eczema broadly but did not focus exclusively on CHE or include newer agents like JAK inhibitors. Patient preference studies emphasize the importance of balancing efficacy with side effects and treatment burden in severe CHE (Journal of the American Academy of Dermatology, 2014).
Caveats and uncertainty
Despite encouraging data on delgocitinib and other systemic agents, several uncertainties remain. Long-term safety beyond trial durations is not fully established, particularly regarding immunosuppression risks. Most evidence derives from topical formulations rather than oral systemic JAK inhibitors, which may have different safety profiles.
Heterogeneity in CHE phenotypes and triggers complicates generalization of trial results. Many studies have small sample sizes or are open-label, limiting robustness. Moreover, direct head-to-head comparisons between systemic treatments for CHE are scarce, leaving clinicians reliant on indirect evidence and clinical judgment.
Patient-reported outcomes and quality-of-life measures require further integration into trials to better capture treatment impact. Finally, cost and access considerations for novel agents may influence real-world applicability.
How this may change practice
The introduction of JAK inhibitors such as delgocitinib expands the therapeutic armamentarium for moderate-to-severe CHE, particularly for patients inadequately controlled by topical corticosteroids or calcineurin inhibitors. Dermatologists should remain vigilant about monitoring for adverse effects and counsel patients on realistic expectations.
Systemic retinoids and immunosuppressants remain relevant options, especially where JAK inhibitors are contraindicated or unavailable. Shared decision-making incorporating patient preferences and benefit-risk trade-offs is essential.
Ongoing and future trials will clarify optimal treatment sequencing, dosing, and long-term outcomes. Clinicians should stay informed on emerging evidence to tailor systemic therapy for CHE effectively.