Hand eczema is a socially significant disease because of its high prevalence, morbidity and the associated loss of working time due to sick leave.1 Clinically, this disease can manifest only on the hand or foot or both on the hand and foot at the same time, and its manifestations vary from vesiculous and erosive to hyperkeratotic and desquamative with a wide spectrum of severity and chronicity.2 Because of the wide diversity of etiological and clinical factors, standard treatment approaches are frequently difficult.3 According to the current knowledge of the clinical phenotype of atopic dermatitis (AD) in adults, 65% AD patients present hand dermatitis, and, therefore, recently, new therapeutics, such as biologics and topical Janus kinase inhibitors or PDE4 inhibitors, for the treatment of AD have shown that hand eczema patients may benefit from them.4

Dupilumab is the first FDA (Food and Drug Administration)-approved human monoclonal antibody for the treatment of moderate-to-severe atopic dermatitis. However, new possible indications that dupilumab was used in non-AD dermatologic conditions are increasingly being explored. Skin diseases, such as prurigo nodularis, nummular eczema, allergic contact dermatitis, chronic hand eczema, spontaneous chronic urticaria, bullous pemphigoid, and alopecia areata.5,6 Additionally, nonskin diseases, such as asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic gastrointestinal disorders and food allergies, are new research fields.7,8 Here, we describe a patient with very severe and refractory hand and foot eczema who was quickly treated with dupilumab. Furthermore, we systematically reviewed the literature to identify studies of hand eczema treated with dupilumab.

A man as a gym teacher in his 45s suddenly suffered very severe hand and foot eczema, multiple severe vesicles, bullae and pustule on the palmar aspects of both hand and foot recurred for 1.5 years, and he experienced no episodes of spontaneous improvement but progressively worsened. He and his family had no previous or concurrent atopy diseases and no allergies. His quality of life was severely affected by this disease, and he had to stop the teacher work.

From 2018 to 2020, he was treated with different medical treatments in other clinics, including high-potency topical corticosteroids (halometasone 0.05%, clobetasol propionate 0.05%), potassium permanganate baths, bifonazole cream 1%, and oral itraconazole beyond three months due to suspected mycoses but no improvement. After that, the biopsy of the palm showed parakeratosis, epidermal spongiosis and intraepidermal vesicles, and neutrophils, lymphocytes and a few eosinophils were seen in the blister as well as a mixed-cell perivascular dermal infiltrate, consistent with dyshidrotic eczema. Patch testing did not reveal any contact allergens. Laboratory test results showed eosinophils 1.15 × 10e9/L and serum total IgE >200 IU/mL but no positive allergen-specific IgE. Subsequently, he was treated intermittently with a multitude of systemic drugs, including oral compound glycyrrhizin, tripterygium glycoside, and corticosteroid therapy, intermittently. All of those systemic therapies just improved the lesions briefly, but on the contrary, lesions were exacerbated with every recurrence. The first time he came to our clinic, the lesions on the palm and plantar showed not only yellowish vesicles, blisters, bullae, and even bloody bulla, swelling and scabs accompanied by intense itching and pain that made it incapacitated for the hands and feet (Figure 1A and B). His dyshidrotic eczema was very severe according to photographic guide. The patient explicitly refused to accept the previous local and systemic medications, so we just gave cyclosporine as the therapy in order to control the symptoms as soon as possible. After one week of oral cyclosporine, 50 mg twice a day, he could not tolerate the itching and painful symptoms and required a new treatment regimen. Then, 600 mg dupilumab subcutaneously initiated with a loading dose followed by 300 mg once every 2 weeks was added to the treatment. Just three days later, the lesions and symptoms achieved dramatic improvement; one week later, the blisters dried up, swelling subsided, and symptoms were completely cleared. Three weeks after the first dose, the patient almost healed, with only a small amount of blood scab remaining, so he was able to resume his work, and cyclosporine was discontinued. At week 6, the hands and feet were completely normal without relapse (Figure 1C and (D), and after 16 weeks of treatment, there was no recurrence or adverse events at 1.5 years of discontinuation. This study was approved by the ethics committee of Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (No. 2022-1024). Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Figure 1 Clinical improvement of patients after 6 weeks of dupilumab treatment. (A and B) at baseline; (C and D) after 6 weeks of treatment.

This case highlights the speed and effectiveness of dupilumab in a patient with hand and foot dyshidrotic eczema that was extremely refractory to therapy and severely reduced the patient’s quality of life. A literature search of PubMed, Web of Science, Embase, and ClinicalTrials.gov was performed using the following search terms: “dupilumab”, “dyshidrotic eczema”, “hand eczema”, “hand dermatitis”, “foot eczema”, “foot dermatitis”, “hand and foot dermatitis”, “treatment”, and “anti-IL- 4”, “anti-IL- 13”. Cross-references were retrieved, but these did not identify additional studies, and studies published until October 2022 were included. Six case reports, 5 case series, 2 prospective observational studies and 1 retrospective review with a total of 150 patients were identified and summarized in Table 1. Three trials exploring dupilumab treatments in patients with hand and foot eczema are presently being recruiting or active but are not recruiting (ClinicalTrials.gov, 19-Oct-22) and no trial with results available. The numbers of male and female patients were 77 vs 73.

Table 1 Published Patient Cases with Hand Eczema Treated with Dupilumab

Patients were treated with the standard approved dosing of dupilumab, 600 mg subcutaneously at day 0, then 300 mg every two weeks, and one patient used 300 mg every 3 weeks due to the high cost.14 The duration of hand eczema ranged from 6 months to 68 years. Patients and their family history of atopy, patients’ skin lesion localizations did not receive much attention. Almost all treatment options were exhausted when dupilumab treatment was started; the prior treatments included emollients, topical corticosteroids, calcineurin inhibitors, antimicrobials, ultraviolet-A, narrowband ultraviolet-B, ultraviolet-B, psoralen ultraviolet-B, psoralen ultraviolet-A, and systemic drugs such as histamine antagonists, corticosteroids, methotrexate, cyclosporine, antimicrobials, alitretinoin, acitretin, azathioprine, mycophenolic acid, mycophenolate mofetil, tacrolimus, apremilast and psoriasis-related biologic medications. Every patient was treated with at least one or more systemic drugs. Efficacy evaluation for dupilumab showed that two patients achieved 1 week of improvement and 6 weeks of clearance after initial treatment.15,16 The skin lesions were clear as fast as 4 weeks.12 Most patients achieved complete skin clearance at 16 weeks. The two prospective observational studies including the same patients from the BioDay registry showed no difference in response between hand eczema subtypes at 16 weeks and 52 weeks.20,21

Regarding dupilumab-associated adverse events, 1 case report showed injection site pain and ongoing pruritic conjunctivitis;10 1 case series reported 2 facial redness and 1 ocular surface disease;19 2 cases mentioned no adverse events associated with dupilumab;13,14 the prospective observational study showed 27.8% mild conjunctivitis, 3 severe conjunctivitis with limbitis, 1 multiple verrucae filiforme and blood eosinophilia;21 and the other studies did not report related adverse reactions. That means dupilumab is safe in patients with hand eczema, consistent with dupilumabin special populations.23

Literature reports often focus on improving time and clearing time; 4 weeks and 16 weeks were the most reported, respectively. Case reports do not focus on the duration and efficacy of long-term treatment. One of the limitations of the research on hand eczema reported thus far is that patients in the prospective observational study and the retrospective review with AD, for hand eczema patients without AD, need more evidence. Additionally, the clinical manifestations and the affected area of hand and foot eczema are highly variable and involve pruritus and pain, and the subjective and objective evaluation tools are not unified. Existing reports have not quantified pruritus or pain in patients and have mainly focused on improvement in skin lesions.

Dupilumab appears to be a safe and effective alternative for the treatment of patients with refractory hand and foot eczema, which has a significant negative impact on patients’ activity level and quality of life. Larger studies with a homogenous design, including refinement of population, disease categories and standardized measures, are needed.

The Zhejiang Provincial Natural Science Foundation [LY20 H110001 to Y.L.L.] funded this work.

The authors report no conflicts of interest in this work.

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