Dyshidrotic eczema (DE) is a chronic eczematous palmoplantar dermatosis characterized by deep-seated vesicles and intense pruritus.1 DE is challenging to treat and often resistant to topical agents – especially when associated with hyperkeratosis. Currently, there are no systemic therapies approved for the treatment of DE. Here, we present a case of DE successfully treated with upadacitinib, a Janus Kinase inhibitor (JAKi).
A 56-year-old healthy female presented to dermatology clinic for a two-year, pruritic eruption on the hands and feet (Figure 1). She described her presentation as severe and rated her worst itch as 10/10 and worst skin pain as 8/10 on numeric rating scales (NRS). Physical exam revealed palmar erythema with healed vesicles, hyperkeratotic plaques and fissuring on the plantar feet with ovoid scaly plaques over the medial ankles. Previous biopsy findings were equivocal, and she was previously treated for presumed psoriasis with numerous agents, including topical corticosteroids (TCS), retinoids, and coal tar, phototherapy, acitretin, methotrexate, apremilast, adalimumab, and guselkumab. Repeat plantar punch biopsy revealed acanthosis, spongiosis, hyperkeratosis, vesicle formation beneath a thickened orthokeratotic stratum corneum, and a perivascular mononuclear cell infiltrate (Figure 1). These findings were consistent with severe dyshidrotic eczema, and she subsequently started therapy with oral upadacitinib 15 mg once daily. Within two weeks, her pruritus and skin pain were completely resolved and within four weeks, her dermatitis and accompanying hyperkeratosis was completely clear.
Figure 1.
Dyshidrotic eczema with notable hyperkeratosis on the feet before and after 1 month of upadacitinib treatment; biopsy showing characteristic changes of dyshidrotic eczema, including acanthosis, spongiosis, hyperkeratosis, vesicle formation beneath orthokeratotic stratum corneum, and a perivascular mononuclear cell infiltrate (10x, hematoxylin and eosin)
DE presents with sudden onset of intensely pruritic vesicles on the hands and feet and follows a chronic relapsing course.2 DE can occur in the absence of comorbid atopic dermatitis (AD) or known triggers, though reported inciting factors include heat, hyperhidrosis, stress, contact allergens, and ultraviolet light. DE is a clinical diagnosis, but biopsy is important in cases demonstrating overlapping morphologies or recalcitrance to treatment. Histopathology classically reveals spongiosis and intraepidermal vesiculation with a superficial perivascular lymphohistiocytic infiltrate and variable hyperkeratosis. DE diagnosis can be quite challenging as clinical presentation may mimic other causes of hand dermatitis; in our case, the patient was treated multiple years for presumed psoriasis, highlighting importance of clinicopathologic correlation.
In addition to trigger avoidance and emollients, mainstays of DE treatment include TCS, topical calcineurin inhibitors, and targeted phototherapy. Multiple systemic agents have been reported to have variable efficacy, including alitretinoin, methotrexate, mycophenolate mofetil, cyclosporine, and dupilumab.3,4 However, none are officially indicated for DE, and most are associated with slow onset, limited efficacy, and/or increased risk of adverse events.
Upadacitinib, an oral JAKi, was recently approved for moderate-to-severe AD.5 JAK signaling plays a key role in the immune dysregulation and barrier dysfunction characteristic of AD. The efficacy of upadacitinib in our case suggests that JAK signaling may also occupy a central role in DE pathogenesis, even in the absence of comorbid AD. Currently, there are no published reports of oral JAKi treatment for DE.
This case highlights real-world complexity in diagnosis of palmoplantar dermatitis, importance of clinicopathologic correlation, and rapid and potent efficacy of upadacitinib for DE. Additional studies are needed to further characterize JAK inhibition as a treatment strategy for DE.
Abbreviations used:
- DE
dyshidrotic eczema
- JAKi
Janus kinase inhibitor
- NRS
numeric rating scales
- AD
atopic dermatitis
- TCS
topical corticosteroids
References:
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