Background

F1000Research

2046-1402

F1000 Research Limited

London, UK

10.12688/f1000research.182187.1

Clinical Practice Article

Articles

Hyperkeratotic Hand Eczema Successfully Treated with Dupilumab Therapy: A Series of 3 Case Reports

[version 1; peer review: awaiting peer review]

S. Abdulwahhab

Waqas

Conceptualization Investigation Methodology Writing – Review & Editing 1 2 ZainAlAbdin

Sham

Conceptualization Data Curation Investigation Methodology Writing – Original Draft Preparation Writing – Review & Editing a 3 AlSuwaidi

Ayesha

Methodology Writing – Original Draft Preparation Writing – Review & Editing 3 Kendakji

Saba

Investigation Methodology Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0009-0003-5755-0070 3 Aburuz

Salahdein

Conceptualization Data Curation Methodology Writing – Review & Editing https://orcid.org/0000-0002-2478-3914 3 Akour

Amal

Data Curation Methodology Writing – Review & Editing 3 4 Eltalib

Dana

Data Curation Investigation Methodology Writing – Review & Editing 5 ElBahtimi

Reem

Data Curation Methodology Validation Writing – Review & Editing 6 1Department of Dermatology and Venereology, Al-Qassimi Hospital, Sharjah, UAE, Sharjah, United Arab Emirates 2Clinical Sciences Department, College of Medicine, Sharjah University, Sharjah, United Arab Emirates 3Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates 4Biopharmaceutics and Clinical Pharmacy Department, The University of Jordan School of Pharmacy, Amman, Amman Governorate, Jordan 5Department of Internal Medicine, Rashid Hospital, Dubai, United Arab Emirates 6Department of Pathology, International Dermpath Consult, Dubai, United Arab Emirates

a sham.zain@uaeu.ac.ae

No competing interests were disclosed.

8 6 2026

2026

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23 5 2026

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This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Hyperkeratotic hand eczema (HHE) is a distinct subtype of hand eczema characterized by sharply defined regions of hyperkeratosis on the palms and occasionally the fingers, with an unclear classification, a pathogenesis, and treatment. Dupilumab is an IgG4 monoclonal antibody used in the treatment of moderate-to-severe atopic eczema with highly satisfactory results; nevertheless, its role in HHE is inadequately characterized. This report offers the first assessment of dupilumab’s effectiveness in managing HHE in the Middle East and North Africa (MENA) region.

Methods

This case report presents three patients with HHE treated with dupilumab over a four-week period.

Results

All patients exhibited the characteristic symptoms of HHE, including sharply defined hyperkeratosis on the palms and fingers accompanied by painful fissures, mild itching, and minimal/absent redness. None showcased current atopic dermatitis or had a family history of atopy, palmoplantar keratoderma, or psoriasis. Previous treatments encompassed systemic and topical corticosteroids, acitretin, and biologics, yielding limited efficacy. Skin biopsies indicated the presence of spongiotic eczematous dermatitis, characterized by compact orthokeratosis, parakeratosis, epidermal acanthosis with mild spongiosis, and a mild lymphoid infiltrate devoid of eosinophils. Throughout dupilumab’s four-week course, all patients exhibited significant improvements, with no adverse drug reactions reported.

Conclusion

This report indicates that dupilumab may serve as an effective and safe treatment option for HHE and constitutes one of the first assessments of its effectiveness in (MENA) region.

Hyperkeratotic hand eczema palmar keratoderma Dupilumab IgG4 monoclonal antibody Interleukin (IL)-4 and IL-13 Case report

The author(s) declared that no grants were involved in supporting this work.

List of abbreviations

Atopic dermatitis

ADRs

Adverse drug reactions

HECSI

Hand Eczema Severity Index

HHE

Hyperkeratotic hand eczema

Interleukin

MENA

Middle East and North Africa

Introduction

Hyperkeratotic hand eczema (HHE) is characterized by clearly demarcated areas of hyperkeratosis or thick scaling on the palms, which may extend to the palmar surfaces of the fingers. Little or no redness is present, and vesicles are usually absent. Involvement of the plantar aspects of the feet can also occur. Patients are usually middle-aged, and males are more commonly afflicted. This phenotype is currently included in the classification system of hand eczema. ¹ The pathogenesis of hand eczema is multifactorial and involves both genetic and environmental factors. Interleukin (IL)-4 and IL-13 play a key role in the pathogenesis of atopic dermatitis (AD) ² Hand eczema may also be a manifestation of allergic contact dermatitis. ³

Topical corticosteroids remain the mainstay of treatment for mild to moderate hand eczema in combination with emollients and moisturizers. ^{3,
4} Moisturizes which contain keratolytic ingredients can help reduce thickness and scaling in hyperkeratotic hand eczema. ³ Dupilumab is a monoclonal antibody that targets interleukin IL-4 and IL-13. It is currently approved for the treatment of atopic dermatitis (AD). ⁵ Effective treatment of hand eczema with dupilumab has been previously reported in a few patients ^{,
6–
9} however, there is insufficient data regarding its effectiveness in cases from the Middle East and North Africa (MENA) region.

In the current case series, we are presenting 3 patients with HHE who received multiple treatments before starting dupilumab, however the patient did not respond adequately to these treatments. This study aims to discuss the pathophysiology of HHE and assess the effectiveness and safety of dupilumab in its treatment.

Methods Study design, population, and setting

This clinical study is a case series that involved patients who experienced HHE and received Dupilumab over the course of treatment at Al-Qassimi Hospital in the United Arab Emirates.

Inclusion criteria

Patients exhibiting symptoms, signs, and histopathological findings consistent with HHE. The patients were recognized by their pruritic skin rashes with palmar involvement, and the histological results indicated the possibility of HHE.

Ethics/Consent

The study has been approved by the Research Ethics Committees at the Ministry of Health and Prevention in the UAE (Approval Reference No: MOHAP/DXB-REC/J.F.F. /No.07/2024). Since it is a series of 3 case reports, written informed consent for participation and publication of clinical details and images was collected from all patients before initiation of the study.

Case reports Patients’ data and outcomes

Demographic characteristics (age and gender), Physical examination (features and site of the lesions) patients’ medical history of any dermatologic conditions that may interfere with the diagnosis (such as atopic dermatitis), histopathological findings and clinical presentation (signs and symptoms) were collected and diagnosis of HHE was confirmed for each patient included in this study.

Safety and efficacy were examined after the intervention. Safety was evaluated by the reported adverse drug reactions (ADRs), where patients have an acceptable safety profile if they tolerate the treatment without any ADRs. While efficacy or clinical improvement was determined by the resolution of the lesions rate, where patients have a complete remission if the lesions have completely resolved and no future lesions have appeared after the course of therapy. Response to treatment or clinical improvement was assessed by the mean (percentage) change of the Hand Eczema Severity Index (HECSI). ¹⁰ The HECSI is a tool used to assess the intensity of six manifestations of HE (erythema, induration/papules, vesicles, fissures, scaling, and edema) and the size of the lesions on five specific regions of the hand, using standardized scales. The score ranges from 0 to 360, with higher values indicating greater illness severity. The term “improvement” was defined as a percentage of improvement/resolution of the lesions. In addition, the response to therapy was determined by the attainment of an outcome that was either ‘clear’ or ‘almost clear’. Furthermore, a more stringent criterion required the accomplishment of ‘clear’ or ‘almost clear’ together with at least two or more steps of improvement on the photographic guide as compared to the initial condition. ¹¹ Table 1 represents patients’ characteristics and clinical findings.

Table 1. Patients’ characteristics and health outcomes.

Patient’s characteristics	Patient 1	Patient 2	Patient 3
Age	47-year-old	48-year-old	52-year-old
Gender	Male	Female	Male
Clinical history	- Recent mild pruritic skin rashes involving both palmar aspects. - No history of atopic dermatitis or psoriasis.	- 5-year history of mild pruritic skin rashes involving both palmar aspects. - No history of atopic dermatitis or psoriasis.	- 3-year history of mild pruritic skin rashes with palmar involvement. - No history of atopic dermatitis or psoriasis.
Previous treatments	- Topical corticosteroids - Systemic corticosteroids - Narrow-band ultraviolet B (NBUVB) - Ustekinumab injection since he was initially diagnosed with psoriasis There was no significant improvement with any of the treatments	- Topical corticosteroids - Systemic corticosteroids - Acitretin - Methotrexate There was no significant improvement with any of the treatments	- Topical corticosteroids - Systemic corticosteroids - Acitretin - Ixekizumab as an initial diagnosis of psoriasis was given All treatments failed to provide considerable improvement
Physical examination	Sharply demarcated hyperkeratotic plaques and thick scaling on the palms, which extended to the palmar aspects of the fingers with painful fissures and mild or no redness [ Figure 1]	Palms were marked by hyperkeratotic plaques and thick scaling, which extended to the palmar aspects of the fingers with painful fissures and little or no redness [ Figure 4]	Hyperkeratotic plaques and thick scaling were found on the palms and tips of his fingers, marked by painful skin fissures that had mild or no redness [ Figure 6]
Histopathology	Compact orthokeratosis, parakeratosis, acanthosis, mild spongiosis, mixed dermal infiltrate of lymphocytes, macrophages, and prominent dermal capillaries with no eosinophils [ Figure 2]	The surface was crusted with parakeratosis, serum, and rare neutrophils. The underlying epidermis was hyperplastic with mild spongiosis. Within the dermis, there was a mild chronic lymphocytic infiltrate with no eosinophils [ Figure 2]	Compact orthokeratosis, parakeratosis, serum, and neutrophils. The epidermis was hyperplastic with spongiosis with vesicle formation. Within the dermis, there was a mild lymphocytic infiltrate with no definite eosinophils [ Figure 2]
Other diagnostic tests	The patch test was negative to exclude allergic contact dermatitis. The clinical presentation and histopathological findings suggested HHE.
Clinical intervention	Dupilumab 600 mg was administered subcutaneously as a loading dose, followed by 300 mg every 2 weeks.
Clinical Outcomes	- Significant improvement within 2 weeks (with 75.0% improvement in HECSI score from baseline) and the hands were almost clear from the lesions, while 4 weeks after the first injection, 90.0% improvement in HECSI score was achieved, through which his lesions completely resolved with clear hands [ Figure 3] - Sustained dramatic clinical improvement for one year while being on the therapy	- Dramatic improvement within 2 weeks (with 75.0% improvement in HECSI score from baseline) with almost clear hands and after 4 weeks from the first injection where her lesions completely resolved achieving almost 100.0% improvement in HECSI score [ Figure 5] - Sustained complete clinical improvement for 2 years during her treatment with dupilumab	- Symptomatic improvement within 2 weeks with almost clear hands from lesions and with 75.0% improvement in HECSI score from baseline. Four weeks after the first injection, his lesions completely resolved and his hands were clear from lesions with almost 100.0% improvement in HECSI score [ Figure 7] - Sustained complete clinical improvement for 3 years throughout his treatment with dupilumab
Adverse drug reactions & Tolerability	Accepted safety profile without any reported adverse drug reactions

Clinical intervention

Initially, patients received dupilumab 600 mg administered subcutaneously as a loading dose, followed by 300 mg every 2 weeks. The course of therapy has been completed until clinical improvement is observed, and the exact duration of treatment was variable depending on disease response, patient’s perspectives, and tolerability of adverse drug reactions ( Table 1).

Physical examination of Patient 1 revealed sharply demarcated hyperkeratotic plaques and thick scaling on the palms, extending to the palmar aspects of the fingers ( Figure 1).

Figure 1. A 47-year-old male patient with sharply demarcated hyperkeratotic plaques and thick scaling on the palms, which extended to the palmar aspects of the fingers (Left hand: a, c; Right hand: b, d).

Histopathological findings in the included patients demonstrated compact orthokeratosis, parakeratosis, acanthosis, and mild spongiosis consistent with HHE ( Figure 2).

Figure 2. The hematoxylin and Eosin (H&E) stained section showed Compact Orthokeratosis, Parakeratosis, acanthosis, mild spongiosis, mixed dermal infiltrate of lymphocytes, macrophages, and prominent dermal capillaries with no eosinophils. a) 4X, b) 10X.

After 4 weeks of dupilumab therapy, Patient 1 showed almost complete resolution of lesions ( Figure 3).

Figure 3. 47-year-old male patient 4 weeks following treatment with Dupilumab with almost complete resolution of HHE lesions, palmar aspects of both hands.

Patient 2 presented with hyperkeratotic plaques and thick scaling involving the palms and fingers ( Figure 4).

Figure 4. A 48-year-old female patient showed hyperkeratotic plaques and thick scaling, which extended to the palmar aspects of the fingers with little or no redness (Right hand: a, b; Palmar aspects of both hands: c).

After 4 weeks of dupilumab therapy, Patient 2 demonstrated complete clinical resolution of the lesions ( Figure 5).

Figure 5. A 48-year-old female with complete resolution of HHE following 4 weeks of Dupilumab therapy (Right hand: a; Palmar aspects of both hands: b).

Patient 3 demonstrated hyperkeratotic plaques involving the palms and fingertips with painful fissures ( Figure 6).

Figure 6. A 52-year-old male patient showed hyperkeratotic plaques and thick scaling was found on the palms and tips of his fingers which had mild or no redness (Right hand: a, b; Palmar aspects of both hands: c; Fingertips of both hands: d).

Complete clinical resolution was observed in Patient 3 following dupilumab therapy for 4 weeks ( Figure 7).

Figure 7. A 52-year-old male patient with complete resolution of HHE following 4 weeks of Dupilumab therapy (Left hand: a; Palmar aspects of both hands: b; Fingertips of both hands: c, d). Discussion

The pathogenesis of HHE remains unclear ^{.
1} Nonetheless, multiple studies have demonstrated changes in epidermal proliferation, differentiation, and barrier function. Increased proliferative cell activity as determined by Ki-67 and decreased loricrin expression in palmar lesional skin biopsies with normalization following alitretinoin treatment were observed in a study examining gene and protein expression in 15 individuals with chronic hyperkeratotic-fissured hand eczema. ¹² Another study has also shown an increase in keratinocyte host defense proteins (S100A7, S100A8, and S100A9) in 6 patients with chronic hand eczema, including various subtypes, compared with healthy control skin. ¹³ Additionally, a study of protein expression in 7 individuals with HHE revealed an elevation in proliferative cell activity as shown by Ki-67, an upregulation of keratin (K)16, and a reduction in loricrin expression in lesional palmar skin relative to perilesional skin and healthy control skin. ¹ These data collectively indicate that HHE is marked by epidermal hyperproliferation and impaired barrier function, features that overlap with those observed in atopic dermatitis. Patients with atopic dermatitis who were treated with dupilumab have exhibited a considerable reduction in the gene expression of K16 and MKi67, a decreased expression of S100As genes, and an increase in loricrin expression following treatment. ¹⁴ Moreover, current evidence suggests that IL-4 and IL-13 are crucial cytokines in the pathogenesis of AD. ² Several studies have shown beneficial results of dupilumab on hand eczema in patients with atopic dermatitis and isolated vesicular hand eczema. ^{7,
9} Consequently, the positive effect of dupilumab on HHE may be related to shared epidermal pathology, as patients with AD and HHE exhibit similarities such as epidermal hyperproliferation and impaired barrier function. ¹⁵

A case series of 3 patients with non-atopic hyperkeratotic hand eczema who were treated with dupilumab demonstrated that 2 patients had major improvement after 4 weeks and their symptoms cleared completely after 16 weeks of treatment. However, one patient noticed minimal clinical response, although there was an improvement in itching and quality of life. The authors explained that the lack of improvement may be due to the patient’s occupational activities as a bricklayer, where his hand eczema was caused and worsened by frequent exposure to irritants and friction while working. ¹⁵ The successful treatment of occupational irritant hand dermatitis with dupilumab has been reported in only 1 case report. ¹⁶

Based on our current reports, all three patients demonstrated bilateral involvement of the palms and fingers with mild itching, while a previous case report published in 2021 included patients with HHE affecting only the palms and accompanied by severe itching. In addition, a significant clinical improvement and complete resolution of the lesions were also demonstrated in all our cases after receiving dupilumab compared to previous study. ¹⁵ Considerable efficacy and an acceptable safety profile were noted as well, which is consistent with previous records. ^{17,
18} We consider our case reports to be complementary to those previously published and support our suggestion that HHE is a distinct condition that should not be overlooked and considered as non-atopic variant of chronic hand eczema. Moreover, our case reports are the first to be published in the Middle East and North Africa (MENA) region.

The diagnosis of HHE is often a challenge by dermatologists as it can be confused with another differential diagnosis of palmar keratoderma, such as psoriasis, atopic dermatitis, occupational hand eczema, hereditary keratoderma, lichen planus, or pityriasis rubra pilaris. ¹⁹ A later age of onset, pure hands involvement, mild itching, negative family history of atopy or psoriasis, absence of nail and joint involvement, and histopathological findings excluding other causes of keratodermas, minimal response to conventional therapy can be considered as criteria for diagnosis of HHE. Our view is that HHE should be classified as a separate entity to be presented alongside other causes of acquired keratoderma. Considering dupilumab’s positive effect on HHE, it might be hypothesized that, despite differences in clinical phenotype, there are similarities in the underlying pathogenesis with an IL-4/IL-13-driven inflammation between different subtypes of hand eczema. ¹⁵ As such, dupilumab serves as a promising agent for hyperkeratotic hand eczema. However, further investigations are recommended on a larger population to determine the safety and efficacy of dupilumab in HHE.

Conclusion

Dupilumab appears to be an effective and well-tolerated treatment for HHE, particularly in patients unresponsive to conventional treatments. These findings also suggest that HHE may share underlying inflammatory mechanisms with other forms of hand eczema, particularly those driven by IL-4 and IL-13 pathways. However, further studies on larger populations are needed to confirm its efficacy and safety in this condition.

Strengths and limitations

This case series has several strengths, including comprehensive clinical, histopathological, and therapeutic characterization of patients with HHE, a type of hand eczema that is relatively under-recognized. All patients demonstrated significant and sustained clinical improvement after receiving dupilumab therapy, supported by objective assessment utilizing the Hand Eczema Severity Index. Furthermore, this report represents one of the first reports describing dupilumab use in HHE within the MENA region. However, this study also has certain limitations, including the limited sample size and observational nature of the case series, which restrict the generalizability of the findings and the ability to establish a causal relationship between dupilumab and clinical improvement. Larger, controlled studies are needed to further evaluate the efficacy and safety of dupilumab in this patient population.

Patient perspective

All patients acknowledged significant satisfaction with dupilumab therapy, observing rapid improvement of hand lesions, alleviation of painful fissures, and improved ability to engage in daily activities. No treatment-associated discomfort or side effects were reported during the follow-up period.

Ethical approval

All subjects participated voluntarily. The Declaration of Helsinki was adequately addressed. The study was approved by the institutional review board of the Research Ethics Committee at AlQasimi Hospital, UAE (2022/379).

Consent

Written informed consent for publication of anonymized clinical details and clinical images was obtained from all patients prior to submission of the manuscript.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Extended data

Figshare: CARE Checklist for “Hyperkeratotic Hand Eczema Successfully Treated with Dupilumab Therapy: A Case Series of Three Patients”. https://doi.org/10.6084/m9.figshare.32186112 ²⁰

This project contains the following extended data: -

CARE checklist (completed)

Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).

Reporting guidelines

This case series was reported in compliance with the CARE guidelines. The completed CARE checklist is available as extended data.

Acknowledgments

Not applicable.

References 1

Politiek

Loman

Pas

: Hyperkeratotic hand eczema: Eczema or not?. Contact Derm. 2020;83(3):196–205. 32333380

10.1111/cod.13572

PMC7496397

Napolitano

Vico

di Ruggiero

: The hidden sentinel of the skin: An overview on the role of interleukin-13 in atopic dermatitis. Front Med (Lausanne). 2023;10:1165098. 37144036

10.3389/fmed.2023.1165098

PMC10151557

Thyssen

Schuttelaar

MLA

Alfonso

: Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Derm. 2022;86(5):357–378. 34971008

10.1111/cod.14035

Bissonnette

Agner

Taylor

: Hand eczema—Part 2: Prevention, management, and treatment. J. Am. Acad. Dermatol. 2025;93(5):1213–1224. 10.1016/j.jaad.2024.09.049

761055s070lbl.pdf:[cited 2026 May 5]. Reference Source

Oosterhaven

JAF

Voorberg

Romeijn

GLE

: Effect of dupilumab on hand eczema in patients with atopic dermatitis: An observational study. J. Dermatol. 2019;46(8):680–685. 31187925

10.1111/1346-8138.14982

PMC6771665

Waldman

DeWane

Sloan

: Dupilumab for the treatment of dyshidrotic eczema in 15 consecutive patients. J. Am. Acad. Dermatol. 2020;82(5):1251–1252. 31926220

10.1016/j.jaad.2019.12.053

Lee

Chipalkatti

Zancanaro

: A Retrospective Review of Dupilumab for Hand Dermatitis. Dermatology. 2019;235(3):187–188. 30726838

10.1159/000496481

Halling

Zachariae

Thyssen

: Severe treatment-resistant acute and recurrent vesicular chronic hand eczema successfully treated with dupilumab. Contact Derm. 2020;83(1):37–38. 32087035

10.1111/cod.13501

Held

Skoet

Johansen

: The hand eczema severity index (HECSI): a scoring system for clinical assessment of hand eczema. A study of inter- and intraobserver reliability. Br. J. Dermatol. 2005;152(2):302–307. 15727643

10.1111/j.1365-2133.2004.06305.x

Coenraads

Van Der Walle

Thestrup-Pedersen

: Construction and validation of a photographic guide for assessing severity of chronic hand dermatitis. Br. J. Dermatol. 2005;152(2):296–301. 10.1111/j.1365-2133.2004.06270.x

Kumari

Timm

Kühl

: Impact of systemic alitretinoin treatment on skin barrier gene and protein expression in patients with chronic hand eczema. Br. J. Dermatol. 2016;175(6):1243–1250. 27480504

10.1111/bjd.14921

Molin

Merl

Dietrich

: The hand eczema proteome: imbalance of epidermal barrier proteins. Br. J. Dermatol. 2015;172(4):994–1001. 25244099

10.1111/bjd.13418

Guttman-Yassky

Bissonnette

Ungar

: Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J. Allergy Clin. Immunol. 2019;143(1):155–172. 30194992

10.1016/j.jaci.2018.08.022

Loman

Diercks

GFH

Schuttelaar

MLA

: Three cases of non-atopic hyperkeratotic hand eczema treated with dupilumab. Contact Derm. 2021;84(2):124–127. 32864776

10.1111/cod.13693

PMC7891406

Zhu

Honari

: Dupilumab for occupational irritant hand dermatitis in a nonatopic individual: A case report. JAAD Case Rep. 2020;6(4):296–298. 32258302

10.1016/j.jdcr.2020.02.010

PMC7109358

Abdulwahhab

Alamiri

Mehair

: Punctal Stenosis a Rare Complication of Dupilumab Therapy for Atopic Dermatitis: A New Case Report. J Cosmet Dermatol Sci Appl. 2021;11(2):96–100. 10.4236/jcdsa.2021.112010

Abdulwahhab

Mehair

: Dupilumab Injection in the Management of Steroid-Induced Rosacea: A New Case Report. J Cosmet Dermatol Sci Appl. 2021;11(1):10–17. 10.4236/jcdsa.2021.111002

Sharquie

Abdulwahhab

: Keratoderma of palms and soles is an umbrella for the first manifestation of different skin diseases. 2023.

CARE checklist for Hyperkeratotic Hand Eczema Successfully Treated with Dupilumab Therapy A Series of 3 Case Reports.

figshare. 2026 [cited 2026 May 22]. 10.6084/m9.figshare.32186112.v1

Reference Source