Rare Childhood Form of Hailey–Hailey Disease Comes Into Focus in New Review

Hailey–Hailey disease, a rare blistering skin disorder that most dermatologists encounter only a handful of times in their careers, has long been considered an affliction of adulthood. A new short report in the Archives of Dermatological Research challenges that assumption by pulling together nearly everything the medical literature has recorded about children who develop the condition before their thirteenth birthday. The study, led by Olivia Katamanin of the Department of Dermatology at Northwestern University Feinberg School of Medicine, together with Julia M. Riley and Kelsey S. Flood, offers the most consolidated picture to date of a disease so rare in childhood that individual clinicians may see only a single case in a lifetime.

Hailey–Hailey disease, also known as benign familial chronic pemphigus, is caused by mutations in a gene called ATP2C1, which encodes a calcium transporter responsible for moving calcium ions into the Golgi apparatus of skin cells. When that pump fails, calcium signaling inside keratinocytes is disrupted, and the molecular glue that holds skin cells together weakens. The result is a process dermatologists call acantholysis: the epidermis literally falls apart, producing recurrent vesicles, blisters, and raw erosions, typically in intertriginous areas where skin folds rub against itself, such as the armpits, groin, and neck. The condition follows an autosomal dominant inheritance pattern, meaning a child of an affected parent has a fifty percent chance of carrying the mutation.

What makes the pediatric form so poorly understood is its sheer rarity. The disease classically appears in the second to fourth decades of life, and textbooks rarely mention early onset. To fill that gap, the Northwestern team conducted a scoping review, searching PubMed and Google Scholar for combinations of the terms Hailey–Hailey disease, familial benign chronic pemphigus, pediatric, and child. They included case reports, case series, and clinical studies, extracting variables such as age, gender, clinical and histopathologic features, anatomic distribution, and treatments. After screening the literature, they identified eight published reports describing a total of nine pediatric patients, a dataset that underscores just how sparse the evidence base remains.

The numbers that emerged from those nine cases are striking. The mean age at symptom onset was 2.6 years, but the median was just six months, meaning most of these children developed their first lesions before they could walk or talk. The mean age at presentation to medical attention was 4.7 years, with a median of 4.5 years. That gap between onset and presentation, and the further delay before a correct diagnosis, illustrates one of the central problems the authors highlight: pediatric Hailey–Hailey disease is so far outside the expected clinical picture that it is often mistaken for more common childhood rashes, including diaper dermatitis, atopic dermatitis, or bacterial and fungal infections.

Clinically, the children in the reviewed reports presented with recurrent vesiculobullous or erosive eruptions accompanied by pruritus, irritation, and pain, mirroring the symptom profile of adult patients. The distribution of lesions varied, with some cases occurring at unusual sites for the disease, a feature that has historically complicated recognition. One of the earliest documented cases, published in 1963, described chronic benign pemphigus in an Indian child, and subsequent reports have described relapsing linear acantholytic dermatosis in young boys and segmental disease affecting the vulva. Together these accounts sketch a condition that, while rare, can appear almost anywhere on a child’s skin and can follow a relapsing course punctuated by flares and partial remissions.

Histopathology provided the diagnostic anchor in these cases. Under the microscope, biopsies from affected children revealed intraepidermal acantholysis with the characteristic dilapidated brick wall appearance, in which the upper layers of the epidermis separate like a crumbling masonry facade. This finding, combined with the clinical history and, in some cases, genetic testing for ATP2C1 mutations, allows clinicians to distinguish Hailey–Hailey disease from its close mimic, Darier disease, which is caused by a mutation in a related calcium transporter gene, ATP2A2. The literature reviewed includes an infant case with a previously unreported ATP2C1 mutation, as well as two sporadic childhood-onset cases involving superimposed mosaicism, a phenomenon in which a second genetic alteration arises in some cells and can modify the disease’s distribution and severity.

Treatment remains the most frustrating aspect of managing these young patients. Because no definitive treatment guidelines exist for the pediatric population, clinicians have borrowed from the adult repertoire, deploying topical corticosteroids, topical antifungals, topical and systemic antibiotics, and topical calcineurin inhibitors with mixed outcomes. The heterogeneity of the reported approaches reflects the absence of controlled trials; with nine patients scattered across decades of case reports, no meaningful comparison of therapies is possible. Some children experienced spontaneous resolution or symptomatic improvement with conservative management alone, a hopeful signal that early-onset disease may occasionally run a milder course, though the reviewed evidence is too limited to predict which patients will fare well.

The report’s authors, who are based at Northwestern University Feinberg School of Medicine in Chicago, emphasize that the fundamental challenge is diagnostic delay. A toddler with recurring erosions in skin folds is far more likely to be treated repeatedly for candidal or bacterial infection before anyone considers a genetic acantholytic disorder. Each misdirected treatment cycle prolongs the child’s pain and irritation and postpones genetic counseling for the family, which matters because an autosomal dominant diagnosis has implications for siblings and future offspring. Raising awareness that Hailey–Hailey disease can begin in infancy, the authors argue, is the first step toward shortening that journey.

The scientific significance of the pediatric cases extends beyond the clinic. Because ATP2C1 governs Golgi calcium handling in keratinocytes, childhood-onset cases offer a natural experiment in how severely, or mildly, impaired calcium transport manifests when it acts on developing skin. The documented cases of superimposed mosaicism, in which children carried the mutation in only a subset of cells, are particularly informative, since they can reveal how the proportion and distribution of affected cells shape the pattern of blistering. Insights from these rare presentations feed into a broader research effort, reflected in recent therapeutic reviews, to develop targeted treatments that restore calcium homeostasis or stabilize keratinocyte adhesion rather than merely suppressing inflammation.

For now, the takeaway from the Northwestern review is a call for vigilance rather than a new therapy. Pediatric Hailey–Hailey disease is a rare acantholytic dermatosis whose features closely resemble adult-onset disease, but whose early appearance invites misdiagnosis and for which no pediatric-specific treatment algorithm exists. By synthesizing eight reports and nine patients into a single reference point, the authors have given dermatologists a clearer baseline: know the median onset of six months, recognize the dilapidated brick wall on biopsy, consider ATP2C1 testing when erosions recur in folds, and counsel families about inheritance. In a field where the entire published pediatric experience fits into a handful of pages, even a short report can meaningfully reshape how the next affected child is diagnosed and treated.

Subject of Research: Pediatric-onset Hailey–Hailey disease, an ATP2C1-related acantholytic skin disorder

Article Title: Pediatric Hailey–Hailey disease: Short report

Article References: Katamanin, O., Riley, J. M., & Flood, K. S. (2026). Pediatric Hailey–Hailey disease: Short report. Archives of Dermatological Research, 318(1), Article 451. https://doi.org/10.1007/s00403-026-04961-5

Image Credits: AI Generated

DOI: 10.1007/s00403-026-04961-5

Keywords: Hailey–Hailey disease, ATP2C1, pediatric dermatology, acantholytic dermatosis, benign familial pemphigus, scoping review, calcium transporter, blistering skin disease, genetic skin disorders, diagnostic delay, intertriginous eruptions, superimposed mosaicism