On this page
Familial benign chronic pemphigus (Hailey-Hailey)
This condition typically begins in early adulthood and causes painful, recurring blisters in areas where skin touches skin, such as the neck, armpits and groin. Episodes often worsen with heat, friction and infection, significantly affecting quality of life.
Overview
Familial benign chronic pemphigus is a rare genetic skin condition that causes the outer layers of skin to separate and form blisters, particularly in areas where skin rubs together. The term 'pemphigus' refers to blistering conditions, whilst 'familial' indicates the disorder runs in families and 'benign' distinguishes it from more serious autoimmune forms of pemphigus. Most affected individuals first notice symptoms between ages 20 and 40, though onset can occur earlier or later.
The condition follows a relapsing and remitting pattern, with periods when skin appears relatively normal alternating with flare-ups triggered by factors such as heat, sweating, friction, bacterial or fungal infections, and occasionally stress. Whilst the blisters themselves are not life-threatening, they can break down to leave painful raw areas that are prone to secondary infection and may significantly impact daily activities and emotional wellbeing. The condition persists throughout life, though severity varies considerably between individuals.
Symptoms & clinical features
The hallmark feature is recurrent blistering affecting skin fold areas, particularly the neck, armpits, under the breasts, groin and between the buttocks. The blisters are typically fragile and rupture easily, leaving moist, red, raw areas that may ooze fluid and develop crusts. These lesions often have an unpleasant odour due to bacterial colonisation. The affected areas can be intensely itchy and painful, and friction from clothing or movement may worsen discomfort.
During flare-ups, the skin may appear thickened and darkened in chronically affected areas. Some individuals develop narrow cracks or fissures in the skin folds. The pattern and severity of symptoms vary considerably - some people experience only occasional mild episodes affecting small areas, whilst others have frequent, widespread involvement that substantially limits their activities. Symptoms typically worsen in warm weather and improve during cooler months.
Video: Genetics 101
Affected organs
Familial benign chronic pemphigus primarily affects the skin, specifically areas where two skin surfaces touch. The condition shows a strong predilection for intertriginous zones - body folds that remain warm and moist. The most commonly affected sites include the sides and back of the neck, the armpits, the area beneath the breasts, the groin, the perianal region, and occasionally between the toes.
In rare instances, the mucous membranes inside the mouth may be affected, though this is far less common than in autoimmune forms of pemphigus. The condition does not typically affect internal organs, and individuals with Hailey-Hailey disease generally have normal overall health apart from the skin manifestations.
Risks & severity
The severity of familial benign chronic pemphigus varies widely between affected individuals, even within the same family. Some people experience only occasional, limited flare-ups that respond well to simple measures, whilst others have frequent, extensive episodes requiring ongoing specialist care. The condition tends to be chronic and lifelong once it develops, though some individuals report that symptoms become less troublesome with advancing age.
Whilst the blistering itself is not dangerous, broken skin in warm, moist body folds creates an environment where bacterial and fungal infections readily develop, occasionally requiring antibiotic treatment. Chronic inflammation and repeated blistering may lead to skin thickening and pigment changes in affected areas. The visible nature of lesions, discomfort, and odour can substantially affect quality of life, social interactions and intimate relationships, with some individuals experiencing anxiety or depression related to their condition.
Genetic causes
Familial benign chronic pemphigus is caused by pathogenic variants in ATP2C1, which provides instructions for making a protein that acts as a calcium pump within cells. This pump, called SPCA1 (secretory pathway Ca2+-ATPase 1), moves calcium ions into a cellular compartment called the Golgi apparatus, where calcium plays essential roles in processing and modifying proteins before they are transported to the cell surface.
In skin cells called keratinocytes, proper calcium handling is crucial for maintaining connections between adjacent cells. These connections, known as desmosomes, function rather like Velcro to hold skin cells tightly together. When ATP2C1 variants disrupt the calcium pump's function, keratinocytes cannot maintain strong cell-to-cell adhesion, particularly under stress conditions such as heat, friction or infection. This leads to a process called acantholysis, where skin cells separate from one another, resulting in the characteristic blistering and raw areas seen in affected individuals.
- ATP2C1 ATPase secretory pathway Ca2+ transporting 1
Inheritance pattern
Familial benign chronic pemphigus follows an autosomal dominant inheritance pattern, meaning a pathogenic variant in just one copy of ATP2C1 is sufficient to cause the condition. Each child of an affected parent has a 50% chance of inheriting the variant and developing the condition. The disorder affects males and females equally.
Because symptoms typically begin in early adulthood rather than childhood, some individuals may not realise they carry a disease-causing variant until after they have had children. The severity can vary considerably even amongst affected family members carrying the same genetic variant, suggesting that other genetic or environmental factors influence how the condition manifests. Occasionally, a person with familial benign chronic pemphigus has no known family history, which may occur because the variant arose newly in that individual or because relatives have such mild symptoms they were never diagnosed.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of familial benign chronic pemphigus typically begins with clinical assessment by a dermatologist, who examines the characteristic distribution and appearance of lesions. A skin biopsy is usually performed to examine tissue under the microscope, which reveals the distinctive pattern of cell separation throughout the epidermis (the outer skin layer) - a feature that helps distinguish Hailey-Hailey disease from other blistering conditions.
Genetic testing can confirm the diagnosis by identifying a pathogenic variant in ATP2C1. Within the NHS Genomic Medicine Service, testing may be arranged through dermatology or clinical genetics services for individuals with suggestive clinical features and family history. Confirmation of the genetic cause can be valuable for family planning, helping relatives understand their risks, and distinguishing this inherited condition from acquired blistering disorders that require different treatment approaches.
Management & lifestyle
Management of familial benign chronic pemphigus focuses on reducing triggers, treating flare-ups, and preventing secondary infections, as there is currently no cure for the underlying genetic cause. General measures include keeping affected areas cool and dry, wearing loose-fitting clothing made from breathable fabrics, using antiperspirants to reduce moisture in skin folds, and maintaining good hygiene whilst avoiding harsh soaps that may irritate skin.
During active flare-ups, treatment options may include topical corticosteroids to reduce inflammation, topical or oral antibiotics if secondary bacterial infection develops, and occasionally antifungal preparations for yeast overgrowth. Some individuals benefit from short courses of oral corticosteroids for severe episodes. For people with frequent, troublesome flares unresponsive to conservative measures, dermatologists may consider other approaches such as laser therapy or, rarely, surgical removal of chronically affected skin, though recurrence in treated areas can occur. Regular follow-up with a dermatologist experienced in managing rare skin conditions helps optimise individual treatment strategies and quality of life.
UK care pathway
Within the NHS, individuals with suspected familial benign chronic pemphigus are typically referred to dermatology services, where specialists can perform skin biopsy and arrange appropriate investigations to confirm the diagnosis and exclude other blistering conditions. For those with confirmed or suspected genetic causes, referral to clinical genetics services may be arranged to discuss genetic testing, inheritance patterns and implications for family members.
Genetic testing for ATP2C1 variants is available through the NHS Genomic Medicine Service for appropriate cases. A genetic counsellor can help individuals and families understand test results, recurrence risks for future children, and options for relatives who may wish to clarify their own genetic status. Ongoing dermatological care typically remains with local NHS dermatology services, with input from specialist centres for complex or treatment-resistant cases.
Frequently asked questions
Will my symptoms get worse as I get older?
The natural course varies between individuals. Some people find their symptoms remain stable or even improve with age, whilst others experience persistent or worsening flares. Many affected individuals report that learning to recognise and avoid their personal triggers helps reduce the frequency and severity of episodes over time.
Can anything be done to prevent flare-ups?
Whilst flare-ups cannot always be prevented entirely, many people find that keeping skin folds cool and dry, using antiperspirants, wearing loose breathable clothing, maintaining good hygiene, and promptly treating any infections significantly reduces the frequency of episodes. Some individuals identify specific triggers such as heat or stress that they can then try to minimise.
If I have Hailey-Hailey disease, what is the chance my children will inherit it?
Because the condition follows autosomal dominant inheritance, each of your children has a 50% chance of inheriting the genetic variant. However, even if they inherit the variant, the severity of their symptoms may differ considerably from yours. A genetic counsellor can discuss these risks and available options in detail.
Is there a cure for familial benign chronic pemphigus?
There is currently no cure that corrects the underlying genetic cause. However, most affected individuals can achieve good symptom control through a combination of trigger avoidance, good skin care, and appropriate treatment during flare-ups. Research continues into understanding the condition better, which may lead to improved treatments in future.