State-of-the-State Update: Chronic Hand Eczema

Image Credit: © IIIRusya - stock.adobe.com

I’ve been a patch tester for the past 20 years and authored one of the few textbook chapters on chronic hand eczema (CHE) (Fisher’s Contact Dermatitis, 7th edition), so the condition has been near and dear to my heart for a long time.

The reason there isn’t a ton about CHE in literature is that it is extremely difficult to sort out the etiology in any given patient outside seeing their response to therapy. If they improve after avoiding irritants, it’s irritant contact dermatitis (ICD). If they improve by avoiding allergens, it’s allergic contact dermatitis (ACD). If they improve with dupilumab (Dupixent; Regeneron Pharmaceuticals, Inc), it’s atopic dermatitis (AD). However, most don’t improve with any of these in isolation because most cases have overlap between ACD, ICD, and AD.

It makes it difficult to do research on something when you go into the study saying, “I don’t know what the participants actually have.”

It’s further compounded by the fact that topical steroids significantly impair barrier function, even with 3 days of use. So the only broad-spectrum anti-inflammatories that we had available actually made a component of CHE worse. But we finally have a solution. As it turns out, Janus kinase (JAK) inhibitors, especially pan-JAK inhibitors such as delgocitinib cream (LEO Pharma), are just as good as steroids in terms of broad-spectrum anti-inflammatory activity. However, they don’t impair barrier function, meaning they are basically as close as we could get to a perfect topical for a mixed-etiology entity such as CHE. It’s an exciting time to be a dermatologist!

Matthew Zirwas, MD, is a board-certified dermatologist based at DOCS Dermatology in Columbus, Ohio. He has specialized in contact dermatitis, pruritus, atopic dermatitis, and seborrheic dermatitis for the past 20 years and emphasizes the importance of figuring out the real, practical, take-home messages from medical literature.

Matthew Zirwas, MD

Test Your Knowledge

Chronic hand eczema (CHE) is a heterogeneous, long-lasting inflammatory skin disease with varying clinical presentations that complicate diagnosis and management. The condition can significantly impact quality of life, with visible symptoms leading to psychosocial and socioeconomic burdens. Use the quiz below to test your knowledge on a few clinical pearls about the condition.

Quiz

Current Trends and Future Directions

Navigating Complexities and Unmet Needs of Chronic Hand Eczema

Chronic hand eczema (CHE) is a challenging and multifaceted condition that significantly impacts patients’ quality of life, according to Christopher Bunick, MD, PhD, an associate professor of dermatology and translational biomedicine at Yale University School of Medicine and Dermatology Times’ 2024 winter editor in chief. In an interview, Bunick emphasized CHE’s clinical variability, psychosocial burden, and the therapeutic gap in its management.

“Chronic hand eczema is defined as hand eczema that occurs for more than 3 months in a year or relapses twice or more in a given year. Another way to think about chronic hand eczema is that it is a heterogeneous, long-lasting, fluctuating inflammatory skin disease of the hands,” Bunick explained.

CHE encompasses multiple clinical or etiologic subtypes, with more than half of patients presenting with overlapping forms, including atopic and nonatopic variants.¹ Symptoms such as itching, pain, fissures, erythema, and thickened skin fluctuate in severity, complicating both diagnosis and treatment. Bunick stressed the importance of a personalized, subtype-specific approach to management given the disease’s heterogeneity.

CHE’s impact on quality of life is profound, he said, with many patients facing visible skin changes that lead to stigmatization and psychosocial stress. “The hands are highly visible in daily life, which amplifies the psychosocial burden of this disease,” Bunick explained. He also noted that CHE may have economic consequences—such as job loss and reduced productivity, often stemming from repeated irritant exposure—and that psychiatric comorbidities, including anxiety, depression, and suicidal ideation, also are common, underscoring the need for a holistic approach to patient care.

Despite CHE’s burden, therapeutic options for moderate to severe CHE remain limited in the United States. “There are no FDA-approved treatments for this condition in the US,” Bunick said, pointing out that corticosteroids, though commonly used, pose risks such as skin atrophy and rebound flares. Patients’ concerns about these risks often lead to corticosteroid phobia and poor adherence. Calcineurin inhibitors provide a steroid-sparing alternative for atopic subtypes, he noted, but their long-term efficacy is limited.

The approval of delgocitinib (Anzupgo; LEO Pharma A/S), a topical pan–Janus kinase inhibitor, in Europe and Japan offers hope for improved treatment options.² However, as the US market awaits this and similar advancements, Bunick underscored the urgent need for nonsteroidal, targeted therapies that can address CHE’s diverse immune pathways and enhance adherence.

Prevalence, Severity, and Treatment CHECK Data for Chronic Hand Eczema

At the 16th Congress of the European Society of Contact Dermatitis in Dresden, Germany, LEO Pharma A/S presented pivotal findings on chronic hand eczema (CHE), highlighting its prevalence, severity, and treatment challenges.³ The data were drawn from 2 landmark studies: CHECK, a large-scale multinational survey, and RWEAL, a follow-up study validating CHECK’s findings through physician-reported outcomes and medical chart reviews.

The CHECK study involved more than 60,000 adult participants from the general population in Canada, France, Spain, Italy, Germany, and the United Kingdom. Results showed that 5.6% of participants experienced CHE symptoms in the past year, with 4.7% receiving a physician diagnosis.⁴ Notably, 1 in 5 patients attributed their condition to occupational exposure, and 1 in 3 linked it to household or leisure activities.⁵ Despite treatment, many patients with diagnosed CHE continued to report persistent symptoms.⁶

The RWEAL study, which included nearly 300 physicians and nearly 2000 patients from the same regions, confirmed these findings. Among patients with moderate to severe CHE, 1 in 4 required escalation from topical corticosteroids to phototherapy or systemic therapies.⁷

Patient perspectives on corticosteroids add another layer of complexity. Research published in the Journal of the American Academy of Dermatology revealed widespread corticosteroid phobia, with many patients fearing systemic absorption and long-term health effects. These concerns were particularly prominent among patients with severe CHE, underscoring the need for better education and alternative therapies.⁸

Kreesten Meldgaard Madsen, chief development officer at LEO Pharma, emphasized the significance of the studies: “It is a privilege to present the results from the largest real-world studies LEO Pharma has ever completed. Our findings…show the needs among people living with this debilitating disease and the immense impact it can have on quality of life.”³

The implications of these studies are substantial to research. According to Sonja Molin, MD, lead CHECK study author and chair of the Division of Dermatology in the Department of Medicine at Queen’s University in Ontario, Canada, large-scale research fills critical gaps in our understanding of CHE prevalence and burden, offering valuable insights for clinicians and researchers. “The heavy burden of chronic hand eczema is well understood,” she said.³ “But prevalence has been historically understudied in the general population.”

Together, the CHECK and RWEAL findings emphasize the unmet needs in CHE management, offering opportunities for future innovations in treatment.

Tofacitinib Targets TH1/TH2 Cytokine Imbalance in Chronic Hand Eczema

Sardana et al assessed the efficacy of tofacitinib (Xeljanz; Pfizer, Inc) and analyzed the tissue expression of cytokines of helper T cells type 1 (TH1) and type 2 (TH2) in patients with hyperkeratotic chronic hand eczema (CHE).⁹ Tofacitinib is an oral Janus kinase (JAK) inhibitor that targets both TH1 and TH2 cell lines and was found to be effective in reducing symptoms of CHE. The imbalance between TH1 (interferon [IFN]-γ, TNF-α) and TH2 (IL-4, IL-13, IL-2) responses can lead to persistent skin inflammation and tissue remodeling, contributing to the thickening of the skin commonly observed in patients with CHE.

All 21 patients involved in the trial had used 1 or more other treatment options, including topical corticosteroids, methotrexate, and acitretin. Lesional and nonlesional tissue samples were assessed for cytokines related to TH1 IFN–γ, tumor necrosis factor [TNF]–α) and TH2 (IL-4, IL-13, IL-2) before initiating tofacitinib 5 mg twice daily for 4 weeks. Investigators performed cytokine analysis in 11 of the 21 participants and found elevated TH1 and TH2 cytokines in affected skin, indicating that these immune responses are involved in disease progression. More specifically, the analysis showed an upregulation of IL-4 (n = 5 of 11; 1.87-fold increase), TNF-α (n = 5 of 11; 5.13-fold increase) and IFN-γ (n = 6 of 11; 1.98-fold increase) vs uninvolved skin. Fifteen patients were treated with tofacitinib, and researchers found that therapy with tofacitinib led to a reduction in cytokine levels and to improvements in skin appearance, pruritus, and overall disease severity. The average Hand Eczema Severity Index score decreased from 90 to 20 after 4 weeks of treatment. Adverse effects were observed in 4 patients, and 3 patients experienced a relapse in CHE symptoms 7 months after discontinuing tofacitinib.

The study authors concluded that tofacitinib was effective in patients with refractory CHE with predominant tissue expression of TH1/TH2-related cytokines and that the agent can be particularly beneficial for patients who do not respond well to conventional treatments. However, further studies are needed to confirm these findings and to assess the long-term safety and efficacy of tofacitinib for hyperkeratotic CHE.

References

1. Ho JSS, Molin S. A review of existing and new treatments for the management of hand eczema. J Cutan Med Surg. 2023;27(5):493-503. doi:10.1177/12034754231188325
2. European Commission approves LEO Pharma’s Anzupgo (delgocitinib) cream for adults with moderate to severe chronic hand eczema (CHE). News release. LEO Pharma A/S. September 23, 2024. Accessed December 2, 2024. https://www.businesswire.com/news/home/20240923751725/en/European-Commission-Approves-LEO-Pharma%E2%80%99s-Anzupgo%C2%AE-delgocitinib-Cream-for-Adults-with-Moderate-to-Severe-Chronic-Hand-Eczema-CHE
3. LEO Pharma presents data from the largest-ever multinational real-world studies of chronic hand eczema (CHE) in adults at the ESCD 2024 Congress. News release. LEO Pharma A/S. September 5, 2024. Accessed December 2, 2024. https://www.businesswire.com/news/home/20240905505670/en/LEO-Pharma-Presents-Data-from-the-Largest-Ever-Multinational-Real-World-Studies-of-Chronic-Hand-Eczema-CHE-in-Adults-at-the-ESCD-2024-Congress
4. Apfelbacher C, Bewley A, Molin S, et al. Prevalence of chronic hand eczema in adults: a cross-sectional multi-national study of 60,000 respondents in the general population. Presented at: 16th Congress of the European Society of Contact Dermatitis; September 4-7, 2024; Dresden, Germany. Poster presentation No. 3.
5. Crepy MN, Molin S, Gimenez-Arnau AM, et al. Exploring the relationship between chronic hand eczema occupation, and household/leisure activities. Presented at: 16th Congress of the European Society of Contact Dermatitis; September 4-7, 2024; Dresden, Germany. Poster presentation No. 19.
6. Dubin C, Del Duca E, Guttman-Yassky E. Drugs for the treatment of chronic hand eczema: successes and key challenges. Ther Clin Risk Manag. 2020;16:1319-1332. doi:10.2147/TCRM.S292504
7. Gimenez-Arnau AM, Bewley A, Apfelbacher C, et al. Physician-reported treatment patterns in chronic hand eczema — results from the multinational RWEAL medical chart review. Presented at: 16th Congress of the European Society of Contact Dermatitis; September 4-7, 2024; Dresden, Germany. Poster presentation No. 27.
8. Christensen MO, Sieborg J, Nymand LK, et al. Prevalence and clinical impact of topical corticosteroid phobia among patients with chronic hand eczema—findings from the Danish Skin Cohort. J Am Acad Dermatol. 2024;91(6):1094-1103. doi:10.1016/j.jaad.2024.07.1503
9. Sardana K, Sharath S, Khurana A, et al. Th1 and Th2 cytokine expression in hyperkeratotic chronic hand eczema and the role of tofacitinib a oral JAK inhibitor. Arch Dermatol Res. 2024;316(10):682. doi:10.1007/s00403-024-03438-7