Treatment of Recalcitrant Hailey-Hailey Disease with Dupilumab: A Case Report

J Clin Aesthet Dermatol. 2025;18(4):18–20.

by Caroline Sulich-Moore, DNP, FNP-C; David Altman, MD, FAAD; and Stuart Gildenberg, MD, FAAD

All authors are with the Midwest Center for Dermatology and Cosmetic Surgery in Warren, Michigan.

FUNDING: No funding was provided for this article.

DISCLOSURES: Drs. Sulich-Moore and Gildenberg have no conflicts of interest to declare. Dr. Altman reports speaking fees from AbbVie, Amgen, Arcutis, BMS, Dermavant, Incyte, Janssen, Lilly, and UCB.

ABSTRACT: Hailey-Hailey disease is a rare autosomal dominant genodermatosis clinically characterized by recurrent flaccid bullae, erosive plaques, and linear epidermal tears primarily affecting intertriginous areas. This case report describes a 34-year-old White female with a 15-year history of severe, treatment-refractory Hailey-Hailey disease affecting multiple intertriginous areas. After failing numerous topical and systemic therapies, the patient initiated dupilumab therapy with a 600mg loading dose followed by 300mg administered every two weeks as maintenance. Within four months, the patient demonstrated approximately 80 percent clinical improvement with significant reduction in pain and pruritus. The authors speculate dupilumab’s efficacy may extend beyond calcium homeostasis regulation, potentially addressing an unrecognized autoimmune component of Hailey-Hailey disease wherein desmosomal disruption may expose normally protected epitopes to immune surveillance. The rapid clinical response to dupilumab in this previously treatment-refractory case warrants further investigation into the immunopathogenesis of Hailey-Hailey disease and supports dupilumab as a promising therapeutic option for this debilitating condition.

Hailey-Hailey disease is a rare autosomal dominant genodermatosis caused by a heterozygous mutation of the ATP2C1 gene. This gene encodes transmembrane protein hSPCA1, which regulates homeostasis of intracellular calcium and is preferentially expressed in keratinocytes.¹ Disruption of the calcium gradient regulated by hSPCA1 leads to altered desmosome adhesion and resulting acantholysis of the stratum spinosum. The disease’s characteristic flaccid bullae and linear epidermal tears are typically confined to intertriginous zones, as the compromised desmosomal adhesion proteins are subject to maceration and friction in these areas.²

Case Report

This case describes a 34-year-old White female patient with a 15-year history of Hailey-Hailey disease presenting as erosive, vesicular plaques affecting the back (Figure 1), inframammary region (Figure 2), axillae (Figure 3), neck, and popliteal fossae. Multiple topical agents, including calcipotriene, clobetasol, clotrimazole-betamethasone, tazarotene, and mupirocin were utilized in rotating combinations over eight years, providing only modest relief. Similarly, systemic therapies and supplements, including amoxicillin, amoxicillin-clavulanate, cephalexin, dapsone, minocycline, glycopyrrolate, apremilast, naltrexone, prednisone, nicotinamide, and magnesium (some used concurrently, others sequentially over the disease course) yielded limited improvement in her condition. The patient developed comorbid conditions, including superimposed impetigo and eczema herpeticum. Presumably due to extreme pain from skin erosions in the right popliteal fossa and resulting lack of mobility, she also developed a deep thrombosis of the right popliteal vein (Figure 4). She reported substantial physical and emotional disease burden.

The patient consented to initiation of therapy with dupilumab. A loading dose of 600mg was administered subcutaneously and the patient initiated 300mg dosing every two weeks thereafter. Within two months of dupilumab initiation, the patient noted reduced pain associated with lesions. After four months of therapy, marked clinical improvement was observed (Figures 5–7). Although the patient continues to exhibit periodic exacerbations and attenuations of her disease state, the authors estimate an 80-percent improvement using a modified Eczema Area Severity Index score with substantially reduced patient reported pain and itch from baseline. 

Discussion

We highlight this case both to suggest a therapeutic alternative in Hailey-Hailey disease and to speculate as to the pathogenesis of this condition. In short, why does dupilumab provide benefit in this condition? 

Previous reports have suggested that dupilumab works to regulate intracellular calcium homeostasis via blockage of interleukin (IL)-4 and IL-13.³ This mechanism addresses the lack of adhesion between keratinocytes that is thought to be the underlying defect in this disease. However, it does not completely explain the inflammatory nature of clinical presentations of Hailey-Hailey disease. The authors’ speculation is that failure of the calcium-dependent intracellular junctions may only constitute one element of the pathophysiology of this condition. It is possible that, as the junctions lose integrity, protein antigens that would normally hold a relatively immune-protected status may be unmasked and subsequently exposed to immune surveillance. This epitope unmasking may lead to a primary B-cell-mediated autoimmune response similar to that seen in pemphigoid and pemphigus. This proposed mechanism would explain the substantial inflammation observed in patients with Hailey-Hailey disease, as well as the response to anti-inflammatory medications. Dupilumab’s effect may relate to its indirect reduction of B-cell activation and eosinophil chemotaxis.⁴ The rapid improvement of Hailey-Hailey disease with the use of dupilumab in this patient and in similar case reports illustrate the need for further research in order to elucidate the exact nature of this condition.^5,6 In doing so, we are able to provide novel therapeutic avenues for patients suffering from this debilitating disease. 

References

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2. Dajani ZAW, Mutasim DF. Ectopic facial Hailey-Hailey disease. J Am Acad Dermatol. 2011;65(1):223–234.
3. Ramesh M, Chellappan B, Ross L. Significant improvement of persistent Hailey-Hailey disease with dupilumab: a case report. Skin (Milwood). 2024;8(4)1747–1751.
4. Ilaria P, Nevena S, Ersilia T, et al. Potential indications of dupilumab in Th-2 inflammatory disease. Rev Recent Clin Trials. 2024;19(1):53–61.
5. Alamon-Reig F, Serra-García L, X Bosch-Amate X, et al. Dupilumab in Hailey-Hailey disease: a case series. J Eur Acad Dermatol Venereol. 2022;36(10):e776–e779. 
6. Alzahrani  N, J Grossman-Kranseler R, Swali R, et al. Hailey-Hailey disease treated with dupilumab: a case series. Br J Dermatol. 2021;185(3):680–682.