Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare genetic skin disorder. It causes painful blisters and erosions in areas where your skin rubs together, such as the neck, armpits, groin, and other skin folds.^1,2 HHD can make daily living difficult and cause chronic discomfort. Because of the frequent, painful flare-ups, and the increased risk of infection associated with this condition, understanding how to manage this condition and its symptoms can greatly improve patients’ quality of life.^1,2,3  

Overview of hailey-hailey disease 

Hailey-Hailey disease is primarily caused by genetic mutations that disrupt your normal skin function. Specifically, it is caused by mutations in the ATP2C1 gene that lead to abnormal calcium levels in keratinocytes (skin cells). This prevents skin cells from bonding tightly, causing the breakdown of skin layers and triggering the formation of blisters and erosions.^1,2

Symptoms of hailey-hailey disease

Typically, HHD presents initially as a blistering and erosive rash on the skin. It is more common in areas like your armpits, neck, groins, under the breasts, and between the buttocks.^1,2 The common symptoms are:^1,2

• Lesions that develop a yellow, crusty layer. These lesions may crack and cause painful, open skin. Friction, heat, injury, and sun exposure can worsen these skin lesions, and they may reoccur
• A rash that may cause itching or a burning sensation
• Secondary skin infections lead to an unpleasant odour

Diagnosis

Diagnosis involves clinical evaluation and examination. Doctors will start by taking your full medical history. After this, a skin biopsy is usually done - where affected skin tissue is removed surgically and examined microscopically. The biopsy sample could show signs of HHD, such as abnormal keratinization (faulty keratin formation) and acantholysis (poor cell-to-cell adhesion). Your doctor may also perform blood tests to rule out autoimmune disorders like pemphigus, as individuals with Hailey-Hailey disease do not have detectable antibodies. Molecular genetic testing for ATP2C1 gene mutations is also carried out in order to obtain an accurate diagnosis.^1,2

Management of hailey-hailey disease

A comprehensive strategy is needed to manage HHD, which includes individualised pharmacological and non-pharmacological therapies, lifestyle modifications, and continuous monitoring. Together, these strategies can help to reduce symptoms and enhance quality of life. 

Pharmacological treatment

Topical therapies

Topical treatments are the primary way to manage Hailey-Hailey disease. These include antiseptics and anti-inflammatory treatments. Applying these to affected areas is useful, especially for controlling flare-ups of mild cases.³

Corticosteroids

Doctors frequently advise corticosteroid anti-inflammatory creams as the initial course of treatment for HHD. Patients usually experience a prickling, itching feeling just before a flare-up starts. Giving corticosteroid cream as soon as possible could prevent the rash from getting worse. Corticosteroid creams are usually applied once or twice daily until the skin improves. Nevertheless, they are usually only taken briefly because long-term use may have negative effects, such as skin thinning.^3,4

Zinc oxide paste

Zinc oxide paste creates a protective barrier on the skin, helping to reduce friction and moisture buildup. Applying zinc oxide paste (50%) two times a day can effectively treat HHD. Zinc also has antibacterial properties and can help heal skin by increasing calcium levels in skin cells, which strengthens the skin.³

Calcineurin inhibitors

Calcineurin inhibitors are used twice a day to reduce inflammation and discomfort. They are especially beneficial for long-term care because they do not thin the skin like steroids do. Most patients see improvement in two weeks after starting this therapy.

Examples are pimecrolimus 1% (cream) and tacrolimus 0.1% (ointment).³

Topical antibiotics

For brief periods of time, topical antibiotics like clindamycin, mupirocin, or antifungals (like ketoconazole creams) might be beneficial in treating HHD. However, they should only be used for short durations to lower the risk of antibiotic resistance.^1,3  

Other topical options

There are a few other topical treatments that doctors sometimes suggest. These include:³ 

• Calcitriol – a vitamin D analogue for lesions in the groin and scrotum areas
• 5-fluorouracil – for lesions in groin and scrotum areas
• Cadexomer iodine – antimicrobial that absorbs fluids and promotes healing
• Benzoyl peroxide – its antibacterial properties help reduce inflammation
• Calcipotriol cream – a vitamin D analogue that lowers inflammation

Systemic treatments

If you have HHD, your risk of getting a skin infection is higher. It is possible to become infected with pathogens like Staphylococcus bacteria. In these cases, your doctor will prescribe oral antibiotics for treatment.⁴

Other systemic treatments for HHD and the side effects it may cause include: 

• To prevent blistering and skin breakdown, erythromycin and tetracycline are frequently used. If an infection is present, testing the bacteria can help doctors choose the right antibiotic³
• For recurring herpes virus infections, oral antivirals such as acyclovir are recommended
• Anticholinergic drugs like glycopyrrolate may be prescribed to control excessive sweating¹ 
• Corticosteroids like prednisolone help control severe flare-ups by reducing inflammation. However, it’s not ideal for long-term use because symptoms can return once the treatment ends³
• Retinoids can help by reversing some of the skin changes caused by HHD. These include acitretin, isotretinoin, alitretinoin, and etretinate^1,3
• For cases that do not respond to standard treatments, medications like dapsone and methotrexate have been used with some success based on individual reports. However, these treatments are not always widely tested or proven³
• Low-dose naltrexone is a medication typically used for other conditions. However, these have shown improvement in some HHD patients by reducing skin inflammation and helping control symptoms^1,3,5
• JAK inhibitors, like abrocitinib, are newer medications that target specific immune pathways. These have shown promise in helping people with treatment-resistant HHD¹

Surgery

Surgery may be an option if HHD results in severe and localised skin lesions that do not improve with medication. This includes either utilising skin grafts or completely excising the damaged skin layers and letting the region recover naturally.³ 

Other treatments

• These days, less invasive procedures with shorter recovery periods and fewer complications like removing the damaged skin with lasers are frequently chosen. Popular laser treatments are:^3,6
• CO₂ laser, which vaporises and removes damaged skin cells. It can help reduce symptoms and improve the appearance of the skin
• Er laser can be used for resurfacing the skin and can help with healing
• Pulsed dye laser can be used to improve wound healing. It works by targeting blood vessels in the skin, which can help reduce redness and promote better skin repair
• Dermabrasion – this method involves carefully removing the outermost layers of skin using a specialized instrument, such as a wire brush or spinning instrument. It's effective but causes more bleeding than lasers, so it is used less these days^3,7
• Photodynamic therapy – this involves applying a photosensitizing agent to the skin and then using light to activate it, which helps reduce inflammation and improve skin condition¹
• Corticosteroid injections – these injections are given directly into inflamed areas of the skin to reduce the inflammation of plaques^1,8
• Botulinum toxin injections – these are frequently used for controlling sweating in the groin and underarms. They can help prevent moisture buildup, which reduces the risk of infections and flare-ups³
• Afamelanotide implants – these are a type of skin-darkening treatment that, in some cases, have helped clear HHD by reducing inflammation and improving skin healing^1,9

Non-pharmacological management

General skincare

In addition to these treatments, maintaining proper skin hygiene is crucial for properly managing HHD. Following a few skincare routines can help to manage the condition effectively. 

• Once or twice a day, gently wash and pat dry the skin folds using a mild soap and water
• To prevent infections, wash your skin carefully with an antiseptic bath oil or antiseptic soap
• Take bleach baths twice a week to prevent skin infections
• Use wet compresses, such as those soaked in a 1:40 diluted solution of aluminium acetate or vinegar, to help dry out oozing areas^1,4,10

Environmental modifications

• Try to avoid trigger factors including sunburn, sweating, and friction
• When it is hot outside, remain indoors with a fan or air conditioning
• Minimise the amount of exercise you do that involves friction
• Try to wear loose, comfortable, and airy clothing that will not trap heat or moisture
• Clothing designs or materials that rub or aggravate afflicted regions should be avoided by patients^1,4,10 

Apart from these lifestyle adjustments, maintaining a healthy weight is important for managing HHD. Reducing your body fat if you are overweight can help reduce friction and pressure on the skin fold. It is also important to have a regular follow-up with your doctor to adjust the treatment plans and to address any emerging complications early.¹

Summary 

Hailey-Hailey disease is a rare skin disorder due to genetic mutations in the ATP2C1 gene. The condition is characterised by painful blistering of the skin, usually in skin folds. Effective management of this condition requires both pharmacologic and non-pharmacological approaches. Popular topical treatments include corticosteroids, zinc oxide paste, and calcineurin inhibitors, whereas systemic treatments may include oral antibiotics, antivirals, and retinoids. Other common approaches are surgery, laser treatments, and phototherapies. Non-pharmacological methods place a strong emphasis on taking care of the skin, avoiding triggers, and keeping a healthy weight. Finally, it is essential to follow up with medical professionals on a regular basis in order to modify treatments and manage concerns.