Neutrophilic Intraepidermal Pustular Dermatosis Mimicking Immunoglobulin A Pemphigus in a Patient with Hailey–Hailey Disease

Dear Editor, Hailey–Hailey disease (HHD) is an autosomal dominant genodermatosis caused by mutations in ATPase calcium - transporting type 2C member 1 and is characterized histologically by suprabasal acantholysis with the classic “dilapidated brick wall” appearance.[1] Immunoglobulin A (IgA) pemphigus is an autoimmune intraepidermal blistering disorder mediated by IgA autoantibodies against keratinocyte surface antigens; histopathology typically shows intraepidermal neutrophilic pustules with variable acantholysis, and direct immunofluorescence (DIF) usually demonstrates intercellular IgA deposition.[2] We report the case of a patient with long-standing HHD who developed a vesiculopustular eruption showing a neutrophilic intraepidermal pattern closely mimicking IgA pemphigus, highlighting an important clinicopathological overlap. A 30-year-old man with a 5-year history of HHD previously confirmed by histopathology presented with worsening of preexisting lesions [Figures 1 and 2]. Before the current episode, his HHD had been under reasonable control with intermittent topical corticosteroids. The flare was marked by intense pruritus followed by widespread fluid-filled blisters that ruptured spontaneously with yellowish serosanguinous discharge. The eruption began over the abdomen and gradually extended peripherally, evolving into erythematous annular plaques with diffuse crusting involving the abdomen, axillae, and groin [Figure 3]. Because of severe nocturnal pruritus and a recent history of contact with a family member with similar complaints, scabies was initially suspected. He was treated with oral ivermectin and topical permethrin; however, there was no improvement over 4 weeks, and new vesiculopustular lesions continued to appear over the abdomen and back. In view of the atypical progression and poor response to antiparasitic therapy, differential diagnoses, including IgA pemphigus, Grover disease, pemphigus foliaceus, and other neutrophilic dermatoses, were considered, and a repeat punch biopsy was obtained from a fresh vesicle. While awaiting histopathological results, he was managed symptomatically with emollients and antihistamines. Histopathology revealed intraepidermal pustules with prominent neutrophilic infiltration and acantholysis, producing an IgA pemphigus-like pattern. DIF was inconclusive, and intercellular IgA deposition could not be demonstrated. Nevertheless, oral dapsone 100 mg/day produced marked improvement within 2 weeks, with a reduction in pruritus and resolution of active lesions. On follow-up for 2 months, there was marked subsidence of lesions with no recurrence.Figure 1: Clinical photograph showing preexisting erosive plaques in intertriginous areas, consistent with Hailey–Hailey diseaseFigure 2: Histopathology of Hailey–Hailey disease showing suprabasal acantholysis producing a “dilapidated brick wall” appearance, with loss of keratinocyte cohesion. The epidermis exhibits irregular acanthosis and vesicle formation above the basal layer (Hematoxylin and Eosin, original magnification ×40)Figure 3: Clinical photograph showing annular erythematous plaques with vesiculopustules and crusting over the trunkThe occurrence of vesiculopustular or autoimmune blistering-like eruptions in patients with inherited acantholytic disorders is uncommon but clinically significant.[3] Although bullous pemphigoid has previously been reported in association with HHD,[4] an IgA pemphigus-like pustular eruption in this setting appears to be rare. One possible, but unproven, explanation is epitope spreading. In chronic inflammatory or acantholytic dermatoses, repeated epidermal injury and barrier disruption may expose normally concealed keratinocyte adhesion molecules and desmosomal antigens, potentially promoting secondary immune responses.[5] In HHD, recurrent acantholysis, epidermal fragility, and repeated cycles of erosion and repair may produce clinicopathological appearances that resemble autoimmune blistering disease. A previous report of pemphigus foliaceus occurring in a patient with HHD provides contextual support for the rare coexistence of autoimmune blistering phenomena in this background, although it does not establish the same mechanism in this case.[6] The diagnostic difficulty is further increased by histopathological overlap. Although acantholysis in HHD is classically suprabasal, it may extend into the spinous layer, producing the characteristic dilapidated brick wall appearance, whereas the newer eruption showed intraepidermal pustulation with acantholysis. This overlap may explain the IgA pemphigus-like clinicopathological appearance in this case and highlights the need for cautious interpretation in the absence of confirmatory immunological evidence [Figures 4 and 5].[7,8]Figure 4: Histopathology showing an intraepidermal pustule with neutrophilic infiltrate and acantholysis (Hematoxylin and Eosin, original magnification ×40)Figure 5: Higher magnification showing intraepidermal neutrophilic pustulation with associated acantholysis (Hematoxylin and Eosin, original magnification ×400)Other neutrophilic pustular dermatoses, including subcorneal pustular dermatosis, pustular psoriasis, and acute generalized exanthematous pustulosis, should also be considered because they may mimic clinical and histological features of IgA pemphigus. Subcorneal pustular dermatosis was considered due to the neutrophil-rich intraepidermal pustules and favorable response to dapsone; however, the presence of acantholysis and the established background of HHD favored an IgA pemphigus-like neutrophilic dermatosis in this case. Pustular psoriasis was less likely due to the absence of characteristic clinical features and supportive histological findings such as regular acanthosis and confluent parakeratosis. Acute generalized exanthematous pustulosis was also unlikely in the absence of a drug trigger, systemic symptoms, or an acute generalized presentation. Because DIF yielded inconclusive results and serological testing for desmoglein or desmocollin antibodies was not available, the findings are best interpreted as a neutrophilic intraepidermal pustular dermatosis mimicking IgA pemphigus rather than immunologically confirmed IgA pemphigus. This case highlights the importance of reevaluating patients with long-standing HHD when lesions become widespread, treatment-refractory, or morphologically distinct and underscores the value of clinicopathological correlation to avoid overinterpretation. Where feasible, repeat biopsy and perilesional DIF from a fresh, noneroded lesion may improve diagnostic certainty. Declaration of patient consent Written informed consent for publication was obtained from all participants included in this study. Ethical policy and Institutional Review Board statement Ethical approval was not required for this case report. Informed consent was obtained from all individual participants included in the study. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.