What Is Hailey Disease?

Introduction 

Definition of Hailey-Hailey Disease 

Hailey-Hailey disease (HHD), also known as familial benign pemphigus, is a rare genetic condition that results in the development of painful, red, and scaly blisters on the skin. These blisters commonly appear in such areas as the armpits, neck, skin folds, and genital region. These lesions may heal spontaneously but can often recur.¹ The severity of HHD can range from mild to severe, with most patients leading normal lives, while others may experience discomfort that hinders their daily activities. 

In this article, our goal is to explore the causes, symptoms, management, and treatment for this rare disorder. 

Historical Background and Discovery

HHD was first described by the Hailey brothers, Howard and Hugh Hailey, in 1939¹. This rare disease is an autosomal dominant disorder, meaning that having one copy of the mutated gene in your cells is sufficient to cause the condition. HHD typically affects individuals from puberty to middle age. The initial signs of HHD can manifest in areas with opposing skin surfaces, such as the armpits or genitals, but they can also appear in non-skin fold areas.²

Causes of Hailey Hailey disease

Autosomal Dominant Inheritance 

HHD is an autosomal dominant disorder affecting one of your non-sex chromosomes, referred to as autosomes. It is caused by a mutation in the ATP2C1 gene on chromosome 3, which is responsible for ensuring that cells in the outer layer (epidermis) stick together. In HHD, the epidermis weakens when skin surfaces rub together. 

Mutation in ATP2C1 Gene

The ATP2C1 gene makes a protein called hSPCA1. The hsPCA1 protein uses energy to transport calcium ions across cell membranes and stores them in the Golgi apparatus within cells until they are needed.² This protein is crucial for maintaining the integrity of the epidermis, which plays a vital role in preserving moisture within the body and protecting the skin from bacteria, viruses, and UV radiation. When the epidermis is compromised, the risk of foreign invaders (such as bacteria) entering the body and causing infections increases. 

Signs and symptoms

Skin Manifestations

HHD presents as painful, blistering plaques or a skin rash.  This rash may be itchy,  cause a burning sensation, and even produce an unpleasant odour.¹ The skin lesions may resolve spontaneously and usually do not leave scars, but they can recur. Several factors can cause trigger these lesions to relapse, which can vary from person to person. 

Triggers and Aggravating Factors

The affected areas typically worsen due to sweating, weight gain, infection, and high exposure to ultraviolet (UV) radiation.¹ To reduce these triggers, consider switching high-intensity exercises that cause sweating to activities like swimming or gentle walking. Maintain a healthy weight,  eat nutritious foods, and apply sunscreen daily to minimize outbreaks.

Diagnosis 

While the symptoms of Hailey-Hailey disease are visually apparent and can be diagnosed through observation, they may resemble other conditions such as eczema, psoriasis, fungal infection, bullous dermatoses, and contact dermatitis, leading to possible misdiagnosis.  Therefore, a follow-up test may be required to confirm the diagnosis, such as a biopsy (skin sample taken during surgery). 

Early diagnostic tests for HHD may include:  

• Dermoscopy - A dermatologist uses a handheld instrument (dermatoscope)  to magnify the skin lesions by 10x. A gel or oil is applied to the area of the skin to be examined. This procedure is generally not painful, but the gel may feel cold. Photographs may be taken to monitor any changes over time if necessary. Dermoscopic features of HHD include irregular patterns in a pink-whitish background.³
• Reflectance Confocal Microscopy - This imaging tool utilizes a safe laser beam to penetrate the deep layers of your skin, allowing doctors to examine and diagnose HHD without surgery. Its high resolution enables clinicians to identify potential pathogens or skin parasites attached to the epidermis, which may not be visible to the naked eye. 
• Genetic testing - If a family member has HHD, you may be offered genetic testing before diagnosis to determine whether HHD has affected you or to help you make informed decisions about having children. This typically involves taking a  blood or saliva sample that will be sent to a  laboratory for analysis. 

Management and Treatment 

There is currently no cure for HHD, but available therapeutics have demonstrated the ability to reduce flare-ups and enhance the quality of life. The type of treatment you receive depends on the severity of the disease and your overall health. In general, it is advisable to avoid triggers that can worsen the condition. Avoid strenuous physical activities that cause friction and opt for loose clothing and underwear.³ 

Topical Therapies 

A  wide range of topical treatments are available, typically serving as the first line of therapy for mild HHD. These include:³ 

• Topical Corticosteroids 
  • Doctors may prescribe a daily application of topical corticosteroids to the affected area until your skin improves. In some cases, the corticosteroid cream may be prescribed in combination with an antibiotic cream to treat infections. When used correctly, side effects are rare, and you may experience a burning or tingling sensation during application, which typically improves over time.  
  • How to use: Apply a thin layer onto your skin. Wash your hands before and after you’ve applied the medicine. 
  • It is essential to periodically review your treatment with your doctor, as long-term use may lead to severe side effects such as skin thinning, easy bruising, and growth inhibition in children. 

• Antiseptics soap
  • Antiseptics are commonly used to clean the skin and wounds to reduce or prevent bacterial growth.  
  • How to use: Be gentle with your skin when washing the affected area with antiseptics. Wash your hands before and after. Dry the wound gently with a clean cloth and apply to the skin to stop the infection. 
  • Overuse of antiseptics can result in the drying of the skin. 

• Topical Calcineurin Inhibitors
  • These may be used as a second-line treatment to control the disease and prevent severe side effects associated with topical corticosteroids. Common side effects include a burning and stinging sensation that generally improves as your skin becomes accustomed to the treatment. 
  • Examples include Tacrolimus ointment, Pimecrolimus cream
  • How to use: Apply a thin layer to the affected skin twice a day or as advised by your doctor.

• Antibiotics
  • There’s an increased chance of developing a skin infection with bacteria such as Staphylococcus, which requires treatment with antibiotics.  Antibiotics may be helpful to reduce or prevent bacteria growth.
  • It is advised to use only for a short period as long-term use of antibiotics can cause the germs to be resistant. You may experience some side effects which do not usually cause any problems such as being or feeling sick, bloating, indigestion and diarrhoea.
  • Examples include: Minocycline, Clindamycin, Gentamicin 
  • How to use: Take antibiotics as instructed by your doctor. Your doctor will discuss with you if antibiotics are necessary. 

Systemic Medications 

Systemic therapies are considered when the lesions do not respond well to topical treatments or when the condition is widespread across the body. This treatment has been shown to improve skin over time, although relapses can still occur. Examples of systemic treatments for HHD include:⁴

• Retinoids – these are vitamin A derivatives that improve the texture and appearance of the skin. It increases collagen production, giving your skin a fresh and plump appearance. It’s commonly used to treat acne and help reduce the appearance of wrinkles.  Retinoids come in many forms, including gels or creams. For the treatment of HHD, oral retinoids are used and may be used in addition to the patient’s primary treatment.
  • How to use: Take as advised by your doctor. You should avoid using oral retinoids if you’re pregnant or breastfeeding. You may experience side effects such as depression, hair loss, dry skin and coughing. Any concerns should be discussed with your GP. 
  • Examples include Acitretin, Isotretinoin, Etretinate and Alitertinion

Phototherapy

Phototherapy is a type of light therapy that uses ultraviolet light with anti-inflammatory properties. Before the procedure, ensure you are protected with eye goggles, proper covering of the genitals and a face shield. A lotion is applied to the affected area, making the skin cells more sensitive to light, followed by exposure to a red lamp.

Surgical Options

Surgery is another approach to remove the affected areas if previous treatments have proven ineffective in managing the lesions. However, there is a risk of recurrence and scar formation, so it’s essential to have an open discussion with your doctor about the best possible option.³

Lifestyle and Coping Strategies 

Living with HHD can be challenging,  especially due to frequent skin flare-ups.  Seeking support from loved ones and a psychologist can help you understand your emotions and manage the condition while maintaining a regular life.  Practice self-care and engaging in activities that benefit your mind and body is important. Ensure you take your medications as prescribed by your doctor and avoid potential triggers. 

Summary

Hailey-Hailey disease is a rare genetic condition caused by a mutation in the ATP21C1 gene, weakening the epidermis of the skin. This leads to painful, red, and itchy lesions in skin folds prone to high friction.  If you are at high risk of Hailey-Hailey disease, genetic testing and diagnostics tests are advisable. If diagnosed with HHD, appropriate treatment can be initiated, along with hygiene measures to manage the condition and reduce irritation.