Hayley-Hayley disease is a hereditary disease belonging to the group of vesicular-bullous dermatoses. It is manifested by skin rashes, usually covering the outer sides of the neck, axillary pits, inner surfaces of the thighs, abdomen around the navel, folds of the mammary glands, groin area, perineum. Flat bubbles filled with a transparent liquid are formed, which later burst and turn into erosive plaques, often covered with green-brown crusts. The diagnosis is based on clinical and anamnestic data, the results of histological and cytological examination of the skin biopsy material. Treatment includes local anti-inflammatory drugs, antibiotic therapy, glucocorticoids.
ICD 10
Q82.8 Other specified congenital skin abnormalities
General information
Haley-Haley disease is named after two brothers of dermatologists V. Haley and H. Haley (USA). By 1939, they had collected clinical material and described a new form of bullous dermatosis caused by the presence of mutant genes. Synonymous names of the disease are benign familial chronic pemphigus, Gougereau-Haley-Haley disease, Haley-Haley pemphigus, hereditary bullous dyskeratosis. 60-70% of patients have close relatives with genetic dermatosis. Epidemiological indicators – 1 case per 50 thousand people. In many populations, the incidence is the same among both sexes, but in China, Great Britain and Tunisia, men are more likely to suffer, in Italy – women. The causes of these phenomena are still unknown. The manifestation of symptoms usually occurs at the age of 20 to 40 years.
Causes
The disease development factor is a change in the ATP2C1 gene, which is located on the 3q21-q24 chromosome, encodes ATP-dependent calcium pumps in the endoplasmic reticulum and Golgi complex. To date, more than 140 variants of mutations leading to benign chronic familial pemphigus have been identified. The type of their genetic transmission is autosomal dominant. Along with the genetic basis of the disease, there are factors that provoke the primary manifestation of symptoms:
- External irritating effects. Rashes appear after a mechanical violation of the integrity of the skin – in places of burns, friction, cuts, surgical sutures. In addition, the cause of the onset of the disease may be increased sweating, being in a hot and humid climate. In many patients, the condition worsens in the summer.
- Hormonal imbalance. In women, the disease develops against the background of menstrual disorders, during pregnancy, after childbirth and when taking oral contraceptives. At risk are adolescents during puberty, women of pre- and menopausal age.
- Infections, parasitic infestations. The trigger may be a bacterial or viral infection, invasion by arthropod parasites. Beta-hemolytic Streptococcus, Staphylococcus aureus, Pseudomonas aeruginosa, yeast-like fungi, herpes viruses and human papillomas are detected in the lesions.
Pathogenesis
Normally, the concentration of calcium inside the cells is low, and in the environment, the Golgi apparatus and the vesicles of the endoplasmic reticulum is high. The difference in electrolyte concentrations is supported by a system of active transport of calcium ions, the key component of which is a calcium pump – an enzyme called calcium ATPase. With Haley-Haley pemphigus, mutations in the ATP2C1 gene lead to a violation of the synthesis of Ca-ATPase in the cells of the epidermis – non-functional protein molecules are produced, as a result, the output of calcium from the endoplasmic network and the Golgi apparatus becomes abnormally fast. The connections between the cells of the epidermis are broken, the process of cellular renewal and restoration of demos is reduced, which is clinically manifested by the formation of vesicles on the skin.
Symptoms
The first clinical manifestations are more often diagnosed in patients aged 20-45 years, but can be detected in the elderly and children (the earliest case is 6 months). The course of the disease is chronic – the pathology lasts for years, relapses are replaced by partial or complete remissions with a duration of 2-3 months to several years. The key symptom is bubble rashes. Their typical location of Hayley-Hayley disease is on the neck, in the armpits and inguinal folds, under the mammary glands, on the inner side of the thighs, on the abdomen near the navel. There are generalized forms when the rash does not have a limited area of localization. Atypical variants are also possible, in which bubbles form on the cheeks and cheekbones, on the mucous membrane of the mouth, esophagus, larynx, conjunctiva, genitals.
Initially, flat flabby bubbles filled with liquid appear. The skin at the site of the rash remains unchanged or becomes slightly hyperemic. With a slight mechanical impact, the vesicle shell ruptures, reddish erosions are exposed. Gradually they are grouped, combined to form an infiltrate. On the patient’s body, no longer watery bubbles are revealed, but extensive erosive areas with scalloped and other bizarre outlines – erythematous plaques. Their average area is 5-10 cm, the borders are clear, bright. A pathognomonic sign of the disease is the presence of deep cracks, resembling the convolutions of the brain, on the surface of plaques.
The open wet surface of the lesions is suppressed a second time, dried exudate and blood accumulate in it, yellowish, greenish and brownish crusts are formed. It is possible to attach vegetations – growths of papillae of the skin and interstitial epidermal processes, similar in shape to cock scallops. Scaly layers and ulcers are also formed a second time. Patients with Hayley-Hayley disease complain of itching and burning sensation in the affected areas. Pain is usually of low intensity or absent.
Complications
The chronic course of Hayley-Hayley disease negatively affects the quality of life of patients. Rashes interfere with habitual physical activity, restrict mobility, as friction causes pain and slows down the healing of the skin surface. Many patients limit social contacts, experiencing embarrassment because of their own appearance. During periods of exacerbation of the disease, they are forced to use a sick leave, and sometimes – to change the type of employment. Forced lifestyle changes cause neurotic disorders – anxiety, depression, hypochondria. According to recent studies, it is assumed that patients have an increased risk of hypertension, Alzheimer’s disease, Crohn’s disease, gastroesophageal reflux, colon polyps, hypothyroidism, hyperestrogenism, diabetes mellitus.
Diagnostics
The examination begins with the collection of clinical data, family history and examination of the patient’s skin. Differential diagnosis is carried out by a dermatologist, provides for the distinction of familial benign pemphigus with follicular dyskeratosis Darya, true pemphigus, herpetiform dermatitis During. A comprehensive examination of the patient includes the following procedures:
- Survey and inspection. The hereditary nature of the symptoms, the presence of a factor provoking their onset, testifies in favor of Hayley-Hayley disease. Typical signs include the location of bullous eruptions in natural folds, places of friction, sweating (axillary pits, inner thighs, etc.), transparent contents of bubbles, the formation of greenish-brown crusts on erosive plaques, clear edges of lesions.
- Histological examination. Intraepidermal cracks, papules and blisters, uneven thickening of the spiny layer, incomplete keratinization of epidermal cells are found in the biopsy material. The upper part of the dermis is moderately infiltrated by lymphoid cells and histiocytes.
- Cytological examination. Acantholytic cells are detected on erosion prints. Unlike cells with true pemphigus, they do not have degenerative changes. Some of them, located inside the bubbles, are at the stage of keratinization.
Treatment
In most cases, therapeutic procedures are performed on an outpatient basis. Treatment is aimed at eliminating inflammatory and purulent processes, restoring the integrity of the epidermis. The duration and nature of medical care are determined individually, depend on the prevalence of lesions, their depth, the presence of an autoimmune component, the attachment of infection. The full range of treatment includes:
- Local therapy. The treatment of rash sites is carried out with external drugs with antiseptic, antimicrobial and antifungal action (for example, fucorcin). Immunosuppressive and fluoride-containing corticosteroid ointments are used to reduce inflammation.
- Anti-inflammatory, antibacterial therapy. With prolonged course, signs of secondary infection, antibiotics (erythromycin, clindamycin) and glucocorticoids are used. Severe symptoms are relieved by intravenous administration of antibacterial drugs.
- Skin transplantation. In the presence of limited foci that are not amenable to medical treatment, a skin graft operation is performed. Before surgery, active anti-inflammatory and antibacterial therapy is prescribed in order to achieve a state of remission.
Prognosis and prevention
With proper treatment and regular dispensary supervision, it is possible to achieve a prolonged remission, in which bullous rashes do not appear for many years. It is impossible to prevent the genetic transmission of the disease. Preventive measures of Hayley-Hayley disease are aimed at reducing the likelihood of developing pathology under the influence of external factors. Persons at risk are recommended to exclude increased insolation, avoid exposure to chemicals and mechanical irritants on the skin, and treat skin infectious diseases in a timely manner.
