Three cases of non‐atopic hyperkeratotic hand eczema treated with dupilumab

A unique point of this case is the development of anaphylactoid reactions several hours after exposure to the hair dyes, which gradually worsened over the following several days. PPD and its derivatives may cause delayed-typeas well as immediate-type-like reactions, although the related mechanism is not clearly understood. The current case might likely be due to combined immediate and delayed hypersensitivity to hair dye, though the immediate hypersensitivity observed in this patient was atypical. The positive skin reactions to PPD and PTD-containing HD-A suggests that the patient might be allergic to both PPD and PTD. Unfortunately, as PTD was unavailable to us, we could not test it. The negative result of PPD-containing HD-B in the open test might be due to a lower PPD concentration in HD-B, as this was a “light hair colour” shade. Unexpectedly, the patient experienced systemic anaphylactoid reactions 16 hours after closed patch testing. As she had been hospitalized during the skin tests, we could respond promptly. Therefore, caution must be exercised, especially for patients with a history of anaphylactoid symptoms, to avoid possible systemic reactions during skin tests for hair dye.

F I G U R E 1 Open test with p-phenylenediamine and the colour solution of hair dye A shows a strong positive reaction on day 3 (D3). Note the reactions in the form of spreading erythema in addition to the papules Dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4 and IL-13 signaling, is currently approved for the treatment of atopic dermatitis (AD). Effective treatment of hand eczema with dupilumab has been reported previously in case series, two small retrospective cohorts, and one prospective observational study including atopic, irritant and vesicular hand eczema subgroups. [1][2][3][4] However, the effect of dupilumab on isolated hyperkeratotic hand eczema (HHE) has not yet been described.

METHODS
Three patients with moderate to severe HHE were treated with dupilumab 600 mg subcutaneously on day 1, followed by 300 mg subcutaneously every 14 days. A minimum washout of topical treatment of 2 weeks was applied. All patients underwent patch testing and no relevant contact allergies were detected. Concomitant fungal infections were ruled out and the diagnosis HHE was confirmed by histopathology.
Age, sex, disease duration, occupation, smoking status, treatment history, exposure to irritants, atopic comorbidities, and specific immunoglobulin E (IgE) inhalant allergens were assessed at baseline. Therapeutic response was evaluated every 4 weeks up to 16 weeks of treatment by the hand eczema severity index (HECSI), 5 the photographic guide, 6

RESULTS
Two males and one female, of respectively 65, 47 and 65 years of age, were treated (Appendix S1). All of them were previously treated with ultra-potent topical corticosteroids and at least two different systemic therapies, alitretinoin, among others. Case 1 had an inadequate response to alitretinoin, Cases 2 and 3 were intolerant to alitretinoin.

DISCUSSION
The pathogenesis of HHE remains largely unclear. A previous study on the gene and protein expression of hand eczema, including 15 patients with chronic hyperkeratotic-fissured hand eczema showed, among others, increased proliferative cell activity indicated by Ki-67, and a decreased expression of the terminal differentiation marker loricrin in palmar lesional skin biopsies, which was normalised following alitretinoin treatment. 8 Another study showed an upregulation in keratinocyte host defence mechanism proteins (S100A7/S100A8/S100A9) in six patients with chronic hand eczema, including different subtypes, compared to healthy control skin. 9 A study on protein expression in seven patients with HHE, showed also increased proliferative cell activity indicated by Ki-67 and a strong upregulation of keratin (K)16 with, in addition, a decreased expression of loricrin in lesional palmar skin compared to perilesional skin and healthy control skin. 10 In patients with AD treated with dupilumab a significantly reduced gene expression of K16 and MKi67, a reduced expression of S100As genes, and an increase in loricrin expression is seen after treatment. 11 Therefore, the good effect of dupilumab on

CASE REPORT
A 28-year-old man was referred to us for 12 itchy and eczematous patches with well-defined borders on the anterior aspect of the chest, abdomen, and back, corresponding to the contact areas of smokeless packages with ignited moxa in metal boxes for indirect moxibustion ( Figure 1). Four days before, the patient purchased a moxibustion device from an online store, to achieve the purpose of strengthening the body's resistance and eliminating pathogens from the body. The method is to insert the moxa cone (burning at one end) into the box and close it, and then put the moxibustion box into the smokeless bag and fix the moxibustion area with an elastic band ( Figure 2). According to this procedure, moxibustion was performed on his chest, abdomen, and back in turn, each for 20 minutes and without discomfort.