Benign Familial Pemphigus (Hailey-Hailey Disease)

What is Benign Familial Pemphigus (Hailey-Hailey Disease)?

Hailey-Hailey disease (also known by the scientific name of “benign familial pemphigus”) is a rare skin condition that was first brought to attention by the Hailey brothers in 1939. This disease is caused by weakened skin cell adhesion, which leads to skin breakage and damage.

The signs of Hailey-Hailey disease involve skin blisters and sores that are painful and usually form in areas where the skin has folds. This is a lasting condition that often involves periods of flare-ups and recovery, with triggers for the flare-ups commonly being sweat, slight skin injury, or other infections. Unfortunately, there is no current cure available for this unique disease. Methods of managing the disease can be difficult. In mild cases, patients may experience successful control of the disease through periodic treatments with topical corticosteroids (skin creams) and antibiotics.

What Causes Benign Familial Pemphigus (Hailey-Hailey Disease)?

Hailey-Hailey disease is a skin condition that’s passed down through families and affects everyone in a similar way, although symptoms can vary from person to person. Interestingly, about 15 to 30% of patients with this disease have no family history of it. This could be due to random genetic mutations or because other family members have mild versions of the disease that were never diagnosed.

The disease is caused by mutations in a gene known as ATP2C1. This gene provides instructions for a protein that helps regulate certain minerals in our body’s cells. Currently, scientists have identified more than 214 different mutations of this gene.

The protein created by the ATP2C1 gene plays a key role in controlling the levels of calcium and manganese within cells. In patients with Hailey-Hailey disease, however, the regulation of calcium is found to be flawed, leading to increased calcium levels inside the cells and decreased levels in the cell’s structures, especially the Golgi bodies.

There is a great deal of difference in how Hailey-Hailey disease appears and progresses within and between families. This could be due to the influence of environmental factors or other genetic factors that may affect how the disease presents itself. Although it’s not yet possible to predict the onset, severity, or progression of the disease based on specific mutations, scientists have noticed that some specific mutations correlate with milder symptoms or symptoms that affect the genital and perineal area.

Risk Factors and Frequency for Benign Familial Pemphigus (Hailey-Hailey Disease)

HHD, or Hailey-Hailey Disease, is not very common, but it is believed to be just as prevalent as Darier’s disease, which means about 1 in 50,000 people may have it. Men and women are equally likely to have this disease, and it doesn’t favor any particular ethnic group.

People usually start showing signs of the disease in their late teens or when they are in their 30s or 40s. However, there has been a case of a 5-year-old child who developed widespread lesions from the disease. Typically, in about half of all cases, the first symptoms appear in the neck area, then they manifest in the groin and underarm areas.

• HHD is estimated to affect about 1 in 50,000 people, similar to Darier’s disease.
• There is an equal chance of men and women having the disease.
• It does not favor any ethnic group.
• Early signs of HHD usually appear in late teens or during the 30s and 40s.
• A case has been reported of a 5-year-old child with the disease.
• Typically, the first noticeable symptoms appear in the neck, and then in the groin and underarm areas.

Signs and Symptoms of Benign Familial Pemphigus (Hailey-Hailey Disease)

Hailey-Hailey disease (HHD) is a skin condition that typically affects areas on the body where friction or skin-to-skin contact occurs. These areas include the sides and back of the neck, armpits, groin, and genital area. For women, the area beneath the breasts can also be affected.

The disease is recognized by the appearance of grouped, weak blisters and sores on either reddened or normal skin. This can lead to a foul-smelling discharge upon rupturing, and crusty sores are formed. Over time, the sores develop at the edges, forming a pattern that looks like the coils of a snake. With healing occurring from the center of the sores, they can take on the appearance of a ring. Continuous sores, especially those in the friction areas, may evolve into reddened, eroded patches that can be painful.

The condition usually exhibits a symmetrical pattern, on both sides of the body. It’s rare for the disease to spread, but if it does, it’s often due to a bacterial, viral, or yeast infection. Around 70% of people with HHD might notice white lines running down their fingernails. There are also reports of involvement of the mouth, esophagus, vagina, and eyes, but these are not common occurrences.

Two forms of HHD have been noted, which could be due to genetic variations. The first type shows a band-like pattern of sores and there is no family history of the disease. This is believed to be caused by a new genetic mutation during the early stages of embryonic development. The disease might be passed on to the next generation if this change in the DNA affects the reproductive cells. Genetic counselling before having children is recommended in these cases.

The second kind of HHD shows severe sores and there are other signs of the disease that do not display in a segmental pattern. The deeper parts of skin structures carry the genetic defect in the affected area. This type of HHD is believed to be caused by a genetic mutation with a loss of a certain kind of genetic diversity. People affected by this form of the disease have a 50% chance of passing it down to their children.

The skin lesions of this disease can be made worse by minor injuries, friction, heat, humidity, exposure to sunlight, and secondary infections. Bacterial infections, particularly staphylococcal infections, can intensify this by releasing toxins that cause severe skin flares up. If the sores smell bad or are growing, an infection might be suspected and treatment with antibacterial creams or pills might be advised.

This disease can significantly affect the quality of life. It can cause severe symptoms like itching, pain, a burning sensation, and bad body odor. It can lead to serious psychological distress and can interfere drastically with normal social activities. The impact it has on daily life is similar to other serious skin diseases like psoriasis. It’s also worth noting that the patient’s perception of the disease’s severity might not always match the doctor’s assessment, potentially leading to insufficient treatment.

Testing for Benign Familial Pemphigus (Hailey-Hailey Disease)

Hailey-Hailey disease can be initially identified through a simple medical checkup. To confirm the condition, doctors usually examine a sample of the patient’s skin under a microscope.

Two techniques, dermatoscopy and reflectance confocal microscopy, can also aid in diagnosing Hailey-Hailey disease early. In a dermatoscopy, doctors may notice a variety of blood vessels within a pinkish-white setting, which is a common characteristic of Hailey-Hailey disease. In a reflectance confocal microscopy, they may find that the cells have separated from each other and that there are inflamed areas and widened blood vessels in the skin.

Although not regularly performed, a gene test can be useful in cases where it’s tough to diagnose the disease. The genetic test looks for mutations in the ATP2C1 gene, which are responsible for Hailey-Hailey disease.

Treatment Options for Benign Familial Pemphigus (Hailey-Hailey Disease)

Hailey-Hailey Disease (HHD) is a chronic illness with no known cure. Treatment plans are focussed mainly on controlling outbreaks, enhancing the patient’s life quality, and achieving extended relapses. Since HHD is a recurring disease, the data from individual case reports and other small uncontrolled studies are limited.

Management involves changes in lifestyle and avoiding triggers like mechanical stress, heat, sun exposure, and sweating. Patients are advised to maintain a healthy weight, wear loose clothing, limit physical activities involving friction and avoid applying occlusive dressings. Regular hygiene practices, including gentle daily cleaning with non-soap-based products, can also help manage HHD.

In terms of topical treatments, zinc paste and moderate to strong topical corticosteroids are used to manage mild cases of HHD. Additionally, applying topical calcineurin inhibitors like tacrolimus and pimecrolimus twice a day can further help control HHD and avoid skin thinning caused by steroids. Other topical agents like calcitriol, 5-fluorouracil, and cadexomer iodine might also be beneficial.

Infections from certain kinds of bacteria and fungus might worsen HHD lesions. Antibiotics, both topical and oral, can help against these microbes. However, long-term use can result in bacterial resistance. The tetracycline antibiotics doxycycline and minocycline have been found beneficial in some HHD patients. These antibiotics have anti-inflammatory properties that can be useful in treating HHD.

Oral treatments are generally aimed at removing inflammation in the skin. Oral corticosteroids and retinoids have been found useful, and several other immunosuppressive agents like methotrexate, cyclosporine, and azathioprine have shown promising results in case reports, although further studies are needed to support their use.

In severe cases that don’t respond to other medical treatments, surgeries such as full-thickness excision and split-skin grafting are considered. Other interventional treatments include ablative techniques like laser therapy, electrodesiccation, mechanical dermabrasion and photodynamic therapy. Botulinum toxin injection can also help by blocking sweat production, a known trigger for HHD.

Besides, new potential treatments for HHD are being explored, such as oral anticholinergic drugs like oxybutynin and glycopyrrolate, afamelanotide, oral magnesium chloride, oral naltrexone, apremilast, and dupilumab. However, it’s important to remember that the current evidence for these emerging treatments is based on a limited number of cases and needs further validation.

What else can Benign Familial Pemphigus (Hailey-Hailey Disease) be?

When diagnosing a condition known as Hailey-Hailey disease, the medical professionals have to make sure that it’s not one of the following conditions, since they have similar symptoms:

• Darier’s Disease
• Grover’s Disease
• Common types of skin conditions like Pemphigus vulgaris or vegetans
• A type of Psoriasis called ‘inverse psoriasis’
• Jock itch (Tinea Cruris)
• A skin condition caused by yeast or fungus known as ‘Intertriginous Candidiasis’
• A skin infection caused by bacteria known as ‘Erythrasma’
• Galli-Galli disease

So, the doctor needs to conduct relevant tests to ensure they get the right diagnosis.

What to expect with Benign Familial Pemphigus (Hailey-Hailey Disease)

Hailey-Hailey disease is a condition that can change over time, often showing periods of flares and remissions that can last from months to years. Some individuals can see their condition improve as they get older. However, it’s also possible for some people not to show any improvement or may even see their condition getting worse.

Possible Complications When Diagnosed with Benign Familial Pemphigus (Hailey-Hailey Disease)

Secondary infections are fairly common, especially on the damaged and soggy patches often seen in Hailey-Hailey disease. These infections can trigger a spike in symptoms or even cause the illness to spread rapidly. Infections from bacteria (like Staphylococcus aureus, or Streptococcus pyogenes), fungi (like Candida species), and viruses (like herpes simplex, poxvirus, or human papillomavirus), require immediate treatment to control the disease. Certain types of bacteria can lead to certain immune responses in skin cells, which reduces the expression of a specific protein implicated in Hailey-Hailey disease.

Consistent inflammation of stubborn, hard-to-treat patches of Hailey-Hailey disease can lead to the development of a type of skin cancer known as squamous cell carcinoma. This has been mostly reported in scientific literature in reference to genital lesions and in some cases was linked to a human papillomavirus infection.

Preventing Benign Familial Pemphigus (Hailey-Hailey Disease)

To prevent the worsening of Hailey-Hailey disease, it’s crucial to avoid factors that could trigger it, and understanding these factors can help patients make the needed changes in their lifestyle. This includes maintaining cleanliness with a gentle daily wash and an antiseptic solution to prevent additional infections, and limiting exposure to the sun. Outbreaks often happen in summer due to heat and humidity. Patients may also need to avoid activities causing friction and tight clothes. For patients who are overweight, losing weight can lessen friction in body folds and is strongly encouraged.

Hailey-Hailey disease, both non-segmental and type 2 segmental, are inherited, meaning they can be passed on from parents to children. Type 1 segmental patients have a chance of passing on the non-segmented form of the disease to their children if they have what’s called gonadal mosaicism. Therefore, patients with Hailey-Hailey disease should consider genetic counseling.