Chronic Hand Eczema: Understanding a Complex and Persistent Inflammatory Disease

J Clin Aesthet Dermatol. 2025;18(12 Suppl 2):S6–S11.

by Naiem T. Issa, MD, PhD; Walter Liszewski, MD; Kara Gooding, PA-C; and Christopher G. Bunick, MD, PhD

Dr. Issa is with Forefront Dermatology in Vienna, Virginia, the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami School of Medicine in Miami, Florida, and the George Washington University School of Medicine and Health Science in Washington, District of Columbia. Dr. Liszewski is Associate Professor of Dermatology at Northwestern University in Evanston, Illinois. Ms. Gooding is with the Center for Dermatology and Plastic Surgery, Sun Lakes, Arizona. Dr. Bunick is with the Department of Dermatology and Program in Translational Biomedicine, Yale University School of Medicine in New Haven, Connecticut.

FUNDING: Funding for this article was provided by LEO Pharma.

DISCLOSURES: Dr. Issa has received funding from the following entities either as a speaker, consultant, advisor, or investigator: Abbvie, Almirall, Apogee, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Castle Biosciences, DermTech, Galderma, Incyte, Janssen, Journey, LEO Pharma, Lilly, Novartis, Organon, Ortho Dermatologics, Pfizer, Primus, Regeneron, Sanofi, SUN Pharmaceuticals Industry, Topix, UCB, Verrica Pharmaceuticals. Dr. Liszewski has served as a speaker and consultant for LEO Pharma. Dr. Bunick has served as an investigator and/or consultant for AbbVie, Almirall, Alumis, Amgen, Apogee, Arcutis, Botanix, Castle Biosciences, Connect BioPharma, Daiichi Sankyo, Dermavant, Disc Medicine, Eli Lilly, EPI Health/Novan, Galderma, Incyte, LEO Pharma, Novartis, Ortho Dermatologics, Palvella, Pfizer, Regeneron, Sanofi, South Beach Symposium, Sun Pharma, Takeda, Timber, Teladoc, Triveni, UCB, and Veradermics. Ms. Gooding has served as a speaker and/or advisor for Arcutis, Incyte, Leo Pharma, Eli Lilly, Janssen, Amgen, UCB, Galderma, Ferndale and Pfizer.

ABSTRACT: Chronic hand eczema (CHE) is a common, relapsing inflammatory skin condition that affects up to 10% of the population and is marked by redness, fissures, scaling, pain, and persistent itching that can severely impair hand function and quality of life. With diverse clinical subtypes and complex immune pathways—including Th1, Th2, and Th17—CHE often proves difficult to diagnose and manage effectively. Many patients experience limited or unsustained relief from topical corticosteroids and systemic treatments, highlighting a significant unmet need. Delgocitinib, a topical pan-JAK inhibitor, offers a targeted, nonsteroidal approach that demonstrated promising results across CHE subtypes in clinical trials.
Keywords: Chronic hand eczema, JAK inhibitors, delgocitinib, topical treatments

Introduction

Chronic hand eczema (CHE) represents one of the most persistent and functionally disabling inflammatory skin disorders of adulthood. It manifests as erythema, fissures, scaling, and intense itching or pain that can markedly affect manual ability and psychosocial well-being.^1,2 The disease is defined by episodes lasting over three months or recurring repeatedly within a year, often driven by contact with irritants or allergens in occupational and domestic settings.³ Current management strategies are frequently inadequate; many patients either fail to respond to corticosteroids or experience adverse effects from prolonged use.⁴ The recent approval of delgocitinib, a topical pan-Janus kinase (JAK) inhibitor,⁵ introduces a new therapeutic pathway that directly targets the multifaceted inflammation underlying CHE.

Epidemiology and Burden

Hand eczema affects approximately one in ten people annually, and up to 14% to 15% will experience it during their lifetime.^6,7 Rates are consistently higher among women, likely reflecting both occupational and household exposures.^6,8-10 Around a third of patients have moderate to severe disease, and a similar proportion report a history of atopic dermatitis.⁶ In the pediatric population, prevalence estimates range from 5% to 10%,³ while among older adults it decreases to under 3%.

The large multinational survey of more than 60,000 adults identified CHE in 4.7% of respondents, most commonly in women and individuals aged 30–39 years.¹¹ Chronicity is a defining feature, with median disease duration exceeding a decade.⁴ The recurrent itching, pain, and fissuring result in marked quality-of-life impairment—patients frequently describe embarrassment, frustration, and anxiety, while the visible nature of the condition may lead to stigmatization.¹² From a socioeconomic perspective, CHE imposes high direct and indirect costs, with estimates between €1,813 and €7,738 annually per patient in Europe.¹³ Job absenteeism, reduced productivity, and career changes are common, particularly in occupations that involve frequent hand wetting or irritant exposure.

Itch is almost universal in CHE, affecting up to 80% of patients and correlating strongly with clinical severity.^14–16 Persistent scratching can provoke secondary infection and further barrier breakdown. Pain, reported in roughly 40% to 50% of cases, adds another dimension of morbidity and often necessitates regular analgesic use.^16,17

Clinical Spectrum and Influencing Factors

CHE does not represent a single entity but a cluster of overlapping clinical and etiologic subtypes.^18,19 Irritant contact dermatitis (ICD), the most common, results from cumulative exposure to irritants such as detergents or solvents, particularly on the dorsum and interdigital areas. Allergic contact dermatitis (ACD) arises from sensitization to specific allergens and can manifest with vesicles, erythema, or localized pain. Atopic hand eczema occurs in genetically predisposed individuals and frequently coexists with atopic dermatitis. Protein contact dermatitis combines immediate and delayed hypersensitivity reactions to high-molecular-weight proteins, progressing from transient wheals to chronic eczema.²⁰

Other variants include hyperkeratotic, vesicular, and nummular forms. The clinical pattern often shifts over time, and in more than half of patients, mixed morphologies coexist.^1,21 Environmental and lifestyle contributors further modify disease course. Cigarette smoking is a recognized aggravating factor for vesicular and hyperkeratotic types,^22,23 while evidence linking alcohol, obesity, or exercise is inconsistent.²⁴ Psychological stress is frequently reported as a flare trigger.

Occupational hand eczema (OHE) remains the most prevalent occupational skin disorder, especially among healthcare, cleaning, and hairdressing professionals.^25,26 Because clinical morphology alone cannot reliably reveal etiology, diagnosis requires detailed exposure history and patch testing. Molecular diagnostic tools, including transcriptomic classifiers, are emerging to refine differentiation between eczema subtypes.^27–29

Immunopathogenesis

The pathobiology of CHE reflects a convergence of skin barrier impairment and dysregulated immune signaling. Damaged keratinocytes release cytokines such as interleukin (IL)-1β, IL-6, and TNF-α, amplifying inflammation through recruitment of immune cells.²⁰ Depending on the subtype, distinct T-helper cell pathways dominate: Th2/Th22 cytokines (IL-4, IL-13, IL-31) drive pruritus and barrier dysfunction typical of atopic forms,³¹ while Th1/Th17 cytokines (IFN-γ, IL-17A) are elevated in hyperkeratotic and irritant variants. Vesicular eczema exhibits mixed Th2/Th17 activation, whereas allergic variants may engage Th1, Th2, or Th17 pathways depending on the allergen. Protein contact dermatitis adds an IgE-mediated immediate component.³²

Despite phenotypic diversity, these immune cascades converge on the JAK–STAT signaling pathway, which mediates cytokine transmission across Th1, Th2, Th17, and Th22 responses.³³ Th2 cytokines activate JAK1/JAK3–STAT6, while Th1 and Th22 rely on JAK1/JAK2–STAT1/3. This shared signaling hub provides the biological basis for JAK inhibition as a targeted strategy for broad-spectrum inflammatory suppression in CHE.^34,35

Therapeutic Landscape

High-potency topical corticosteroids remain the foundation of CHE therapy but are constrained by skin atrophy, fissuring, and tachyphylaxis with long-term use.^35,36 Clobetasol propionate and triamcinolone provide short-term improvement but rarely induce durable remission.^36,37 Calcineurin inhibitors such as tacrolimus and pimecrolimus serve as steroid-sparing alternatives, with modest benefit in steroid-resistant or occupational subtypes.^37–39

Among nonsteroidal topicals, calcipotriol has demonstrated comparable efficacy to topical corticosteroids,⁴⁰ and the PDE4 inhibitor crisaborole improved symptoms in retrospective analyses of hand atopic dermatitis.^41–43 Topical ruxolitinib, a selective JAK1/2 inhibitor, achieved significant clinical improvement in a Phase 2 trial of moderate-to-severe CHE.⁴⁴ In addition, tapinarof (an aryl hydrocarbon receptor AhR agonist) and roflumilast (a high-potency PDE-4 inhibitor) creams, though not specifically approved for CHE, may offer targeted anti-inflammatory benefits for the atopic dermatitis–associated subtype based on their efficacy in AD and related inflammatory pathways.

For patients with severe or refractory disease, systemic therapy is often required. Alitretinoin remains the only oral agent formally approved in Europe for CHE unresponsive to topical treatment, achieving clearance in up to half of treated patients.^45,46 Other systemic immunosuppressants, including corticosteroids such as prednisone, cyclosporin, methotrexate, and mycophenolate mofetil, are used off-label but carry substantial safety concerns.^31,47 The biologics dupilumab and tralokinumab, approved for atopic dermatitis, has shown encouraging results for atopic CHE in clinical trials.^48–50 Oral JAK inhibitors such as abrocitinib and upadacitinib are also utilized with success but require lab monitoring.⁵¹

Delgocitinib as the first-in-class pan-JAK inhibitor for CHE. Delgocitinib, initially developed as an oral pan-JAK inhibitor targeting JAK1, JAK2, JAK3, and TYK2, was reformulated topically to minimize systemic immunosuppression while maintaining efficacy in immune-mediated skin disease.⁵² Topical delgocitinib 2% cream demonstrated minimal systemic absorption (C_max 0.21–0.50 ng/mL) and a favorable safety profile in Phase 1 and 3 studies involving adults with moderate-to-severe CHE, including multiple subtypes such as atopic, hyperkeratotic, irritant, allergic, and vesicular hand eczema.^35,53,54 In Phase 3 DELTA 1 and 2 trials, delgocitinib significantly improved IGA-CHE success (24.3% vs 8.4%), HECSI-75, HECSI-90, and patient-reported itch, pain, and DLQI scores compared with vehicle, with rapid effects observed as early as Day 1 for itch and Day 3 for pain.^55–57 Long-term data from DELTA 3 showed sustained efficacy over 36 weeks, including intermittent treatment holidays, with consistent improvement across all CHE subtypes.^58–60 Head-to-head comparison against oral alitretinoin and indirect comparison with dupilumab further demonstrated superior or comparable efficacy, rapid onset of action, and a favorable safety profile, while molecular analyses confirmed normalization of Th1, Th2, Th17, and JAK pathway gene expression and restoration of skin barrier markers.^61–63

Topical Discussions in CHE

The following expert discussions (authors KG, WL and, CGB) provide “real-world” insights on important topics in CHE and the impact that delgocitinib cream 1% has had on patients and clinicians.

Burden of CHE. Kara Gooding, PA-C: In my clinical experience, chronic hand eczema carries a profound burden that often extends far beyond what we see on the skin. Patients frequently report that it affects not only the appearance of their hands, but also their ability to perform everyday activities such as typing, cooking, or caring for children. Many patients describe limitations in work productivity or social interactions because they are self-conscious about visible lesions. I’ve seen cases where patients avoid handshakes, high-fives, or even cooking for their families because of discomfort or embarrassment. Beyond the functional impact, there is a significant mental health burden. Anxiety and depression are not uncommon, and I’ve encountered patients who describe feelings of hopelessness or frustration after years of ineffective treatments. This makes patient-centered metrics, such as pain, itch, and functional limitations, incredibly important in assessing the true burden of disease. Asking specifically, ‘Do your hands hurt?’ has become a routine question in my practice, and it often uncovers a dimension of suffering that standard clinical scoring systems like HECSI or IGA may miss. CHE is not merely a cosmetic issue; it is a chronic disease that impacts quality of life on multiple levels, and we as clinicians must recognize and address that reality.

Walter Liszewski, MD:  I often find that CHE is underreported because patients have adapted to living with discomfort. Some patients come to clinic only when the disease severely interferes with work or daily life. Others may normalize their symptoms, thinking there’s nothing that can be done. From my perspective, understanding prevalence is challenging—population-based data suggest rates between 5% and 10%, but in my daily practice, it feels even higher. For instance, if I see 40 patients in a typical day, at least three to four will have some form of hand eczema. The burden is cumulative: it’s not just the acute flare, but repeated cycles of irritation, cracking, and fissuring that create long-term functional and psychosocial stress. I also observe that social and occupational impacts are sometimes overlooked. Hands are highly visible, and people use them for communication and interaction. Consequently, CHE can lead to avoidance behaviors, impacting relationships and social engagement. My approach is to proactively screen for CHE in routine visits and use patient narratives to identify those who might otherwise be missed, which allows me to intervene earlier and mitigate both physical and psychosocial burdens.

Christopher G. Bunick, MD, PhD: From my own clinical practice, I can confidently say that CHE is a high-burden condition. Roughly one in ten patients I see in a typical clinic day has chronic hand eczema, and the burden extends beyond the skin. I describe it as a triple threat: appearance, itch, and pain. The visual impact alone can be distressing, but the pain and itching further erode daily functioning. Many patients simply do not volunteer this information unless asked, so I make it a point to inquire about hand discomfort, functional limitations, and social impact at each visit. I also recognize that CHE has long-term implications for mental health. Patients with chronic conditions like this are more likely to experience anxiety, depression, or even suicidal ideation, particularly when the disease interferes with work or personal life. I find that empathy and active listening are key: understanding the patient’s experience allows me to tailor interventions that improve not just the appearance of the skin, but also the patient’s overall quality of life. With the availability of therapies like delgocitinib, I feel empowered to make meaningful improvements in their daily lives.

Physical evaluation and patch testing. KG: When I assess a patient with CHE, I conduct a detailed examination of both hands, including the dorsal and palmar surfaces, fingertips, nails, and wrists. I document erythema, scaling, fissuring, lichenification, and swelling, as well as the extent of functional limitation. Equally important is the history: understanding occupational exposures, frequency of hand washing, prior treatments, and triggers provides context for the physical findings. I employ patch testing selectively. For example, if a patient’s history suggests occupational exposure to chemicals or repeated contact with specific allergens, patch testing can help identify triggers and guide avoidance strategies. However, I do not perform patch testing universally because it is time-consuming and may not alter initial management, especially when pan-JAK therapies like delgocitinib are available and effective across subtypes. Additionally, systemic immunomodulators may influence patch test results, particularly if the patient is on oral corticosteroids or other systemic therapies. Therefore, I weigh the potential benefits against the cost and convenience for the patient. Ultimately, my evaluation integrates clinical signs, patient history, and selective diagnostic testing to guide treatment decisions efficiently and empathetically.

WL: My approach to physical evaluation emphasizes both observation and narrative. I carefully inspect hands for erythema, fissures, scaling, swelling, and any signs of chronicity such as lichenification. Swelling is particularly important because it can indicate early or subtle inflammatory processes, and sometimes it is mistaken for other conditions such as arthritis or erythromelalgia. I also focus on functional impairment, asking patients about difficulties with manual tasks or limitations at work. Patient history provides key clues: occupational exposures, hobbies, hand hygiene practices, and prior interventions can reveal potential drivers of the disease. I view patch testing as a tool to complement, not replace, clinical judgment. I typically use it in patients with a suspected allergic component or when the patient requests it. In my experience, integrating physical assessment with patient narrative ensures a holistic understanding of CHE and informs both treatment selection and patient education.”

CGB: I examine all aspects of the hands and wrists, including the dorsal and palmar surfaces, fingers, nails, and interphalangeal joints. Approximately half of my patients have multiple drivers of CHE, meaning that visual inspection alone is insufficient to fully understand the disease. That’s why I use patch testing in roughly 30% of cases—especially when the history indicates a possible allergic trigger or when patients explicitly request evaluation. Swelling is a critical observation, often overlooked; it can be misattributed to arthritis or systemic disease. I also consider chronicity markers, such as lichenification, and integrate the patient’s reported symptoms into my assessment. If a patient fails multiple topical or systemic treatments, I don’t hesitate to perform a biopsy to rule out rare mimics like cutaneous T-cell lymphoma. My evaluation approach combines meticulous clinical assessment, patient narratives, selective diagnostic testing, and vigilance for atypical presentations.

Gaps in current guidelines. KG: In the United States, we lack formal, disease-specific guidelines for CHE. European guidelines provide useful references, particularly for defining etiologic and morphologic subtypes, but they don’t always align with US practice or available therapies. One critical gap is guidance on the duration and escalation of topical therapy. With the advent of nonsteroidal advanced topical treatments, it is increasingly important to define what constitutes steroid failure. In my view, a two-week course of a potent corticosteroid is sufficient to determine non-response in CHE, which is shorter than the four-week period often cited in psoriasis. Clear guidance on when to escalate from topical steroids to advanced therapies like delgocitinib would improve patient outcomes and reduce prolonged suffering. Additionally, current guidelines insufficiently address patient-reported outcomes such as pain, functional impairment, and social impact, which are critical in determining the true success of therapy.

WL: I also see significant gaps in CHE management guidelines. There is little clarity on when to escalate therapy, how to select treatments based on subtypes, and how to integrate patient-centered outcomes into clinical decision-making. The current focus on clinical severity scales, such as the Hand Eczema Severity Index (HECSI) or Investigator Global Assessment (IGA), is important but does not fully capture the impact of CHE on daily living. Updated guidelines should address both efficacy and quality of life, incorporating functional and patient-reported outcomes. They should also consider the rapid adoption of pan-JAK inhibitors and advanced topicals, providing clear guidance for when these therapies are appropriate. Clinicians need a framework that balances science-driven treatment selection with practical, patient-centered considerations.

CGB: From my perspective, defining steroid failure is paramount. In my practice, a single two-week course of a potent topical corticosteroid is enough to determine whether a patient needs an advanced topical or systemic therapy. Guidelines should recommend moving to nonsteroidal topicals, like delgocitinib, after steroid failure, but clinicians should retain flexibility to escalate therapy quickly for severe or rapidly progressing cases. I also think guidelines should reflect the heterogeneity of CHE. Many patients present with mixed subtypes or multiple drivers, and therapies like pan-JAK inhibitors are uniquely positioned to address this complexity. Overall, the goal should be to provide a framework that ensures patients are treated promptly and effectively while leaving room for clinician judgment.

Treatment repertoire and innovations. KG: My treatment approach has expanded significantly with new therapies. Topical pan-JAK inhibitors, such as delgocitinib, are now central to my practice because they address multiple CHE subtypes simultaneously. I also consider other advanced topicals including roflumilast and ruxolitinib as well as systemic therapies like dupilumab, tralokinumab or lebrikizumab or oral JAK inhibitors for patients with more severe or widespread disease. My strategy is to match therapy to the patient’s phenotype and reported outcomes. For example, if a patient reports significant pain and functional limitation but has minimal visible lesions, I prioritize therapies that rapidly relieve inflammation and restore function, rather than focusing solely on skin appearance. I also consider combination strategies, using advanced topicals with systemic agents when needed, guided by safety data and minimal systemic absorption, particularly with delgocitinib.

WL: I view CHE treatment as a multi-modal strategy. I integrate topical steroids, nonsteroidal advanced topicals, biologics, and oral JAK inhibitors depending on disease severity, subtype, and patient priorities. I place a strong emphasis on matching therapy to the underlying drivers of disease, which may include atopic, irritant, or allergic components. My decision-making balances efficacy with convenience, patient adherence, and potential adverse effects. For example, in patients who struggle with hand function due to fissuring or pain, I may prioritize rapid-acting topicals or systemic agents to restore quality of life quickly. This personalized approach has improved outcomes and patient satisfaction in my practice.

CGB: My treatment repertoire includes topical delgocitinib, roflumilast, ruxolitinib, and systemic agents like dupilumab and oral JAK inhibitors. I have also observed that delgocitinib provides biologic-level efficacy as a topical therapy, effectively treating multiple CHE subtypes and mixed presentations. In Europe, oral alitretinoin is also an option, though delgocitinib has outperformed it in head-to-head trials. I often start with a pan-JAK topical following steroid failure, but I retain flexibility to escalate to systemic therapy for severe or refractory cases. The minimal systemic absorption of delgocitinib allows me to combine it safely with other systemic therapies when clinically indicated, providing a highly effective and flexible approach to CHE management.

Refining the dermatologist approach. KG: I’ve refined my approach to CHE by prioritizing patient-centered outcomes, particularly pain and function. I ask patients directly about their ability to perform daily tasks and the presence of hand discomfort. Sometimes, addressing a single domain—such as pain—can dramatically improve quality of life even if other symptoms persist. I also emphasize education and shared decision-making, helping patients understand their treatment options, expected outcomes, and potential triggers. By focusing on functional recovery and patient-reported outcomes, I can deliver meaningful improvements beyond what is captured by traditional scoring systems.”

WL: My approach emphasizes a holistic, personalized strategy. I consider clinical severity, subtype, patient lifestyle, and functional impairment when selecting therapy. I balance detailed diagnostic workup with pragmatic interventions that restore hand function and alleviate suffering. CHE is often complex and multi-factorial, so I maintain flexibility in therapeutic sequencing, incorporating patient preferences and goals into decision-making. Ultimately, my aim is to improve both disease control and quality of life.

CGB: Delgocitinib has revolutionized my approach to CHE. It increases disease awareness, allows treatment of all subtypes, and reduces the need for extensive diagnostic workup in many cases. Some clinicians may pursue detailed phenotyping, patch testing, or mechanistic studies, but the pan-JAK therapy allows us to manage mixed or complex cases effectively. That said, I always remain vigilant: patients who fail multiple therapies may require biopsy to rule out conditions such as cutaneous T-cell lymphoma. Above all, I focus on empathy, patient experience, and restoring function. I like to describe it as helping patients ‘high-five with confidence.’ This captures both functional restoration and the emotional benefit of feeling comfortable using their hands again. CHE is not just a skin disease—it’s an opportunity for dermatologists to connect with patients, alleviate suffering, and improve daily life in a meaningful way.

Conclusion

The 2023 S2K European guideline for CHE reinforces the importance of structured diagnosis, including timely patch testing, alongside a stepwise, severity-based treatment strategy.⁶³ The approval of delgocitinib cream introduces a highly effective, steroid-free topical option that can be implemented early, reducing the need for phototherapy or systemic immunosuppression in many patients. Its rapid improvement of inflammation and symptoms allows clinicians to safely delay patch testing when appropriate, benefiting patients by enhancing comfort and improving the reliability of allergen identification once the skin has stabilized. Overall, delgocitinib supports a patient-centered approach that prioritizes early symptomatic relief while preserving the guideline’s emphasis on comprehensive etiologic evaluation.

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