Hailey–Hailey disease (HHD), or familial benign chronic pemphigus or familial benign pemphigus, was originally described by the Hailey brothers (Hugh Edward and William Howard) in 1939. It is a genetic disorder that causes blisters to form on the skin.

Signs and symptoms

HHD is characterized by outbreaks of rashes and

blister A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...

s on the skin. Affected areas of skin undergo repeated blistering and inflammation, and may be painful to the touch. Areas where the skin folds, as well as the

armpit The axilla (: axillae or axillas; also known as the armpit, underarm or oxter) is the area on the human body directly under the shoulder joint. It includes the axillary space, an anatomical space within the shoulder girdle between the arm an ...

groin In human anatomy, the groin, also known as the inguinal region or iliac region, is the junctional area between the torso and the thigh. The groin is at the front of the body on either side of the pubic tubercle, where the lower part of the abdom ...

, neck,

buttocks The buttocks (: buttock) are two rounded portions of the exterior anatomy of most mammals, located on the posterior of the pelvic region. In humans, the buttocks are located between the lower back and the perineum. They are composed of a lay ...

and under the breasts are most commonly affected. In addition to blistering, other symptoms which accompany HHD include

acantholysis Acantholysis is the loss of intercellular connections, such as desmosomes, resulting in loss of cohesion between keratinocytes,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. ...

erythema Erythema (, ) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not associated with pathology inc ...

and

hyperkeratosis Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathol ...

. It typically begins in late teenage years or in a person's 30s or 40s.

Causes

The cause of the disease is a

haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

of the enzyme ATP2C1; the ATP2C1 gene is located on

chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans more than 201 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA ...

, which encodes the protein hSPCA1. A mutation on one copy of the gene causes only half of this necessary protein to be made and the cells of the skin do not adhere together properly due to malformation of intercellular

desmosome A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like ad ...

s, causing

, blisters and rashes. There is no known cure.

Diagnosis

Classification

While the term ''

pemphigus Pemphigus ( or ) is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes. The name is derived from the Greek root ''pemphix'', meaning "blister". In pemphigus, autoantibody, autoantibodies form against de ...

'' typically refers to "a rare group of blistering autoimmune diseases" affecting "the skin and mucous membranes", Hailey–Hailey disease is not an autoimmune disorder and there are no

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

. According to Pemphigus Pemphigoid Foundation (IPPF), "familial benign chronic pemphigus, or Hailey–Hailey disease, is a different condition from Pemphigus".

Differential diagnosis

The differential diagnosis includes

intertrigo Intertrigo, commonly called “skin fold dermatitis”, refers to a type of inflammatory rash (dermatitis) of the superficial skin that occurs within a person's body folds. These areas are more susceptible to irritation and subsequent infection d ...

candidiasis Candidiasis is a fungal infection due to any species of the genus '' Candida'' (a yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the ...

, frictional or

contact dermatitis Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes ...

, and

inverse psoriasis Inverse psoriasis or flexural psoriasis is a form of psoriasis that selectively, and often exclusively, involves the folds, recesses, and flexor surfaces such as the ears, axillae, groin folds, inframammary folds, navel, intergluteal cleft, peni ...

. A biopsy and/or family history can confirm. The lack of oral lesions and intercellular antibodies distinguishes familial benign pemphigus from other forms of pemphigus.

Treatment

Topical steroid preparations often help outbreaks; use of the weakest

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

that is effective is recommended to help prevent thinning of the skin. Drugs such as

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

s, corticosteroids,

dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment an ...

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

thalidomide Thalidomide, sold under the brand names Contergan and Thalomid among others, is an oral administered medication used to treat a number of cancers (e.g., multiple myeloma), graft-versus-host disease, and many skin disorders (e.g., complication ...

etretinate Etretinate (trade name Tegison) is a medication developed by Hoffmann–La Roche that was approved by the FDA in 1986 to treat severe psoriasis. It is a second-generation retinoid. It was subsequently removed from the Canadian market in 1996 and t ...

cyclosporine Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, ecz ...

and, most recently, intramuscular

alefacept Alefacept is a genetically engineered immunosuppressive drug. It was sold under the brand name Amevive in Canada, the United States, Israel, Switzerland and Australia. In 2011, the manufacturers made a decision to cease promotion, manufacturing, d ...

may control the disease but are ineffective for severe chronic or relapsing forms of the disease. Intracutaneous injections of

botulinum toxin Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon en ...

to inhibit perspiration may be of benefit. Maintaining a healthy weight, avoiding heat and friction of affected areas, and keeping the area clean and dry may help prevent flares. Some have found relief in laser resurfacing that burns off the top layer of the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

, allowing healthy non-affected skin to regrow in its place. Secondary bacterial, fungal and/or viral infections are common and may exacerbate an outbreak. Some have found that outbreaks are triggered by certain foods, hormone cycles and stress. In many cases

naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol use or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been ...

, taken daily in low doses, appears to help.

References

External links

{{DEFAULTSORT:Hailey-Hailey disease Genodermatoses Rare diseases Diseases named after discoverers