BRIEF ARTICLE Development of Psoriasis During Treatment with Weekly Dupilumab for Refractory Hailey-Hailey Disease

Hailey-Hailey Disease is a rare inherited disease that is often to treat. Several case reports have discussed the potential role of dupilumab for the treatment of Hailey-Hailey Disease. Our case presents a patient who required more frequent dosing of dupilumab than previously reported to manage his symptoms. His course was further complicated by development of psoriatic lesions which were successfully treated with topicals steroids, allowing continuation of dupilumab

2][3][4] In this article, we present the case of a patient with refractory HHD who was treated with dupilumab administered weekly and had significant improvement but developed newonset psoriasis during treatment.
A 30-year-old male presented with longstanding HHD.Physical examination revealed red-brown, fissured, and crusted papules and plaques involving the bilateral axillae, umbilicus, inguinal folds, mons pubis, penis, scrotum, perineum, and perianal skin (Figure 1).Numerous topical and systemic treatments, alone or in combination, had been used over time with minimal improvement including topical steroids and calcineurin inhibitors, topical antibacterial ointments, naltrexone, dapsone, glycopyrrolate, oxybutynin, gabapentin, acitretin, and several onabotulinumtoxinA injections.Courses of systemic antibiotics were required intermittently for treatment of bacterial superinfections.
After therapeutic failure of treatments listed above, the patient was started on dupilumab 600 mg SQ on day 1, then 300 mg SQ every other week.He reported near clearance with initial loading doses, followed by reversion to baseline disease status with maintenance dosing.Based on his report of marked improvement with loading doses, the maintenance dose of dupilumab was increased to 300 mg SQ once weekly with significant improvement (Figure 1).

INTRODUCTION CASE REPORT
Approximately 5 months into treatment with weekly dosing, the patient developed scaly papules and plaques on the trunk and extremities clinically and histologically consistent with psoriasis and acantholysis (Figure 2a, Figure 3).He initially stopped dupilumab but following swift resolution of the psoriasiform lesions with only 3 weeks of treatment with topical steroids, he re-started dupilumab 300 mg SQ weekly without further side effects to date (Figure 2b).
2][3][4] Our patient also had significant improvement soon after the 600 mg loading dose, but the improvement was not sustained with 300 mg every other week maintenance dosing.Subsequent increase to 300 mg weekly maintenance dosing led to significant disease improvement, but, unfortunately, our patient developed new-onset psoriasis approximately 5 months later (Figure 2).The biopsy was histologically consistent with psoriasis in association with suprabasal bulla formation and acantholysis (Figure 3).
While rare, there have been reports of patients developing psoriasis while on dupilumab; in fact, a recent systematic review of 26 studies examined the characteristics of 47 patients who developed psoriatic cutaneous eruptions while on dupilumab. 5The proposed mechanism posits that by targeting IL-4, dupilumab disinhibits T-helper 1 and T-helper 17 cells, and for susceptible patients, this shift leads to development of psoriasis. 5 Although standard maintenance dosing of dupilumab is 300 mg every other week, the safety of weekly dosing has been shown in previous studies demonstrating a similar incidence of adverse effects with weekly or every other weekly dosing of dupilumab in atopic dermatitis. 6Furthermore, a long term, open-label extension study of patients receiving dupilumab 300 mg weekly demonstrated a similar safety profile to the initial phase 3 studies. 7Therefore, it is unclear if the weekly dosing schedule for our patient contributed to or exacerbated the development of psoriasis.[3][4] Given the limited number of reports in the literature, further study will be required to determine the optimal dosing protocol and safety profile of dupilumab as a treatment for HHD.Nevertheless, dupilumab remains a promising emerging treatment option for this challenging disease.

Figure 1 .Figure 2 .
Figure 1.Red-brown, fissured, and crusted papules and plaques involving the patient's groin, buttocks, and axilla prior to treatment (a-d) and after treatment with weekly dupilumab for 3 months (e-h).

Figure 3 .
Figure 3. Biopsy was histologically consistent with psoriasis in association with suprabasal bulla formation and acantholysis.