Sustainable modern management of hand eczema

Chronic forms of hand eczema in particular can be associated with considerable suffering. The fact that, in addition to avoiding allergenic factors, consistent basic care is the best prevention is highly topical in times of the corona pandemic.

Lifetime prevalence in the general population averages 15%, with an increase in incidence reported in the context of corona pandemic [1,2]. Fear of COVID-19 infection is currently the main cause of new diagnoses of hand eczema as recent data show, according to Prof. Margitta Worm, MD, Charité Universitätsmedizin Berlin (D) [2,20]. It is known from previous studies that hand eczema is prevalent among hospital staff, with intensive hand cleaning and disinfection and glove use contributing significantly [3,4]. In a survey conducted in 2020 among medical staff in hospitals (n=526) a statistically significant association was found between the frequency of hand cleaning (>10 x/d) and an increased risk of skin damage in the hand area (OR 2.17; p=0.01) [5,6].

Frequent occurrence in times of corona pandemic

Because not only medical personnel but the entire population wash and disinfect hands more frequently during the corona pandemic, an increase in the prevalence of hand eczema in the general population is suggested. Hand eczema is associated with a disturbed skin barrier, which promotes drying of the skin and associated itching. Moisturizing care products and washing products without irritants are recommended to protect the skin despite frequent cleaning [6,7]. A recent study by a research group in Denmark found that Corona-induced hand washing resulted in hand eczema in half of the students [8]. “After each disinfection and after each hand washing, the skin should be additionally creamed with a care product to support the regeneration of the skin barrier,” says Prof. Dr. med. Andrea Bauer, deputy chairwoman of the Working Group for Occupational and Environmental Dermatology in the DDG [9,10].

In which cases is epicutaneous testing required?

The cause-effect relationship is not always obvious in eczematous changes in the area of the hands. In the majority of cases, hand eczema is multifactorial and a careful history and assessment of the clinical picture is required to achieve sustained improvement and healing of hand eczema. In addition to seborrheic eczema, the most important differential diagnoses include palmoplantar psoriasis (Overview 1).

The most important risk factors for a chronic course of hand eczema are pronounced extension, allergic or atopic genesis, eczema in childhood, and disease onset before 20 years of age [1]. About half of all hand eczema is partially caused by contact allergies. Especially if the symptoms occur for longer than three months, an allergological clarification is useful. In these cases, epicutaneous testing is indicated in addition to atopy screening by prick testing or in vitro determination of specific IgE antibodies to common inhalant allergens and total IgE. The following type IV sensitizations to standard-range contact allergens are associated with at least a twofold higher risk of occupational allergic contact dermatitis [1]: Thiuram mix (rubber accelerators), epoxy resin (synthetic resin), mercaptobenzothiazole and derivatives (rubber accelerators), IPPD (rubber antioxidant in black rubber [e.g., car tires]), and biocides (MCI/MI, MDBGN, formaldehyde). If no clear diagnosis can be made on the basis of the medical history and subsequent epicutaneous test, or in refractory cases, histopathological examination of a skin biopsy can be informative [11].

Mutations in the filaggrin gene and other factors

Allergic hand eczema is etiologically differentiated from irritant hand eczema, with mixed forms occurring not infrequently. A common feature is that contact with exogenous acutely toxic, cumulatively toxic, or sensitizing noxious agents are triggers. Allergic involvement is a type IV reaction according to Coombs and Gell [21]. Allergenic substances include mainly nickel, cobalt, dichromate, rosin, tea tree oil and fragrances [12]. In irritant hand eczema, triggers are in particular water, cleaning agents, solvents and disinfectants, lubricants and cutting oils. Mechanical damage to the skin barrier or occlusion may also play a role. Chronic hand eczema is one of the most common causes of occupational disability, and at-risk groups are primarily hairdressers, employees in the healing and nursing professions, cleaners, workers in the construction, paint, metal and food industries, and in agriculture [12].

In addition to atopic skin diathesis, other genetic risk factors are discussed [12]. According to data from twin studies, the risk of developing hand eczema is determined 41% by genetic factors and 59% by environmental factors [13]. Thus, several single nucleotide polymorphisms, deletions, and loss-of-function mutations of different gene loci have been described for which an association with hand eczema of different etiopathogenesis is suspected. Loss-of-function mutations in the filaggrin gene show a particularly strong association [14–16]. Filaggrin plays an important role in the aggregation of keratin filaments in the stratum corneum and contributes to the mechanical resilience of the skin barrier; the formation of natural moisturizing factor (NMF) is also influenced by filaggrin.

According to the 2015 JDDG guideline for the diagnosis, prevention, and treatment of hand eczema, topical glucocorticosteroids for the treatment of acute symptoms of hand eczema are the first-line therapy, but it is noted that use for a treatment period longer than six weeks should be exceptional [17]. In severe chronic hand eczema, alitretinoin is considered second-line therapy.

In the therapy scheme according to the guideline, three stages are distinguished (Fig. 1) [17,19]. In the case of mild hand eczema (therapy level I), antipruritic and antiseptic agents, among others, have proven effective in addition to steroid-containing products of strength class 1-2 and topical calcineurin inhibitors. For moderate and severe hand eczema, topical glucocorticosteroids of strength class 3-4, UV therapy, and systemic alitretinoin (off label) may be used in addition to measures of level I. In the case of chronic recurrent and persistent hand eczema, systemic immunomodulatory substances are suggested in addition to measures of the previous stage. These include alitretinoin, ciclosporin, systemic glucocorticosteroids (short-term, for acute relapse), and possibly other systemic therapeutics (if approved first- and second-line therapies are not sufficiently effective or are contraindicated). The S1 guideline on the treatment of contact dermatitis published in 2014 notes the efficacy of UVA1 and narrowband UVB spectrum light therapy and PUVA (psoralen plus UVA) for the treatment of chronic hand eczema [11]. In therapy-resistant hand eczema, prolonged oral administration of ciclosporin A may be goal-directed; if there is no response, other immunomodulators such as azathioprine, mycophenolate mofetil, or methotrexate may be used as alternatives.

Topical JAK inhibitors as a future alternative to local steroid therapy?

Potential new agents currently under investigation include delgocitinib, a novel pan-Janus kinase (JAK) inhibitor that specifically targets JAK1, JAK2, JAK3 and tyrosine kinase 2. Topical application of delgocitinib was shown to be effective compared with vehicle in a significantly greater proportion of patients after an 8-week period in a prospective, randomized, double-blind phase IIa study. According to the authors, this is a potential future treatment alternative for lack of response to topical glucocorticoids. Steroid-containing local therapy has been shown to be effective, but long-term use can lead to atrophy of the dermis, which is counterproductive with regard to further progression, explains Prof. Worm, speaker and first author of the study [18].

Source: FomF (D) Dermatology and Allergy 2020

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