Benign familial pemphigus

What is benign familial pemphigus?

Benign familial pemphigus is also known as Hailey–Hailey disease. It is a rare hereditary blistering skin disease first described by the Hailey brothers in 1939.

Unrelated to pemphigus vulgaris, Hailey-Hailey disease is not an autoimmune condition and has a differing prognosis.

Hailey-Hailey disease in axilla 

Hailey-Hailey disease of chest 

Hailey-Hailey disease in axilla 

Who gets benign familial pemphigus?

Benign familial pemphigus usually appears in the second to fourth decade, although it can occur at any age. It then tends to persist life-long. It can affect people of all races.

What is the cause of benign familial pemphigus?

Benign familial pemphigus is an inherited skin disorder, although occasionally sporadic cases arise without a family history. The defect responsible has now been identified on a gene called ATP2C1 found on chromosome 3q21-24. This gene codes for the protein SPCA1 (Secretory Pathway Calcium/manganese-ATPase), a calcium and manganese pump. The skin cells (keratinocytes) stick together via structures called desmosomes and it seems the desmosomes do not assemble properly if there is insufficient calcium.

The genetic defect in benign familial pemphigus causes the skin cells to become unstuck from one another. Normally the cells are packed together tightly in much the same way as bricks and mortar. Patients with Hailey-Hailey disease have defective ´mortar´ and the cells fall apart, like a dilapidated brick wall.

What are the clinical features of benign familial pemphigus?

Benign familial pemphigus typically begins as a symmetrical painful erosive and crusted skin rash in the skin folds. Common sites include the armpits, groins, and neck, under the breasts and between the buttocks. The lesions tend to come and go and leave no scars. As the lesions get bigger the centre clears leaving a typical ring shape. If the lesions are present for some time they may become thickened. The skin then tends to macerate leaving quite painful cracks.

Heat, sweating and friction often exacerbate the disease, and most patients have worse symptoms during the summer months.

Rarely, benign familial pemphigus can be unilateral or have a linear arrangement, or it may involve mucous membranes. White bands on the fingernails and pits in the palms can also occur.

 

 

 

What are the complications of benign familial pemphigus?

For many patients benign familial pemphigus is a mild condition, but for others, the pain and smell can be serious problems. Secondary bacterial infection, which is not uncommon, can give rise to an unpleasant smell. Herpes simplex can infect blistered sites and may evolve to widespread, painful viral infection (eczema herpeticum).

How is benign familial pemphigus diagnosed?

Usually, benign familial pemphigus is diagnosed by its appearance and family history, but it is often is mistaken for other skin problems. Impetigo, thrush, tinea cruris (jock itch) and other blistering conditions look similar.

Diagnosis may require a skin biopsy. The histology is characteristic, with layers of detached skin cells (‘acantholysis’) lining up like 'a row of tombstones'. Unlike pemphigus vulgaris, the immunofluorescence test for antibodies is negative.

As yet there is no diagnostic test available to family members.

How is benign familial pemphigus treated?

There is no cure for Hailey-Hailey disease. Treatment is aimed at reducing symptoms and preventing flares.

General advice

• Avoid trigger factors such as sunburn, sweating and friction where possible; when hot, stay indoors with a fan or air conditioning, and limit the amount of exercise taken.
• Wash and dry skin folds carefully, once or twice daily using mild soap and water.
• Wear soft, loose clothing, with absorbent pads in underwear.
• If overweight, try to decrease body fat to minimise friction.
• Apply wet compresses, eg with 1:40 diluted aluminium acetate or vinegar, to dry up oozing patches.
• Take bleach baths twice weekly reduce superficial infections.
• Apply zinc paste to inflamed patches.
• Use antiperspirants such as roll-on and cream forms of aluminium salts and dusting powder containing the anticholinergic drug, diphemanil 2%.

Topical prescriptions

• Corticosteroid (cortisone) creams used short-term (eg one to two weeks) are effective in treating inflamed lesions; they work best if started early.
• Topical antibiotics such as clindamycin or mupirocin are used short-term for localised infection but are best avoided long-term due to the risk of inducing bacterial resistance, eg MRSA.
• Short-term use of combination corticosteroid/ antibiotic creams may also be helpful.
• Benzoyl peroxide is a useful antiseptic available as cream or wash.
• Ketoconazole cream can be used in case of fungal infection.
• Calcipotriol cream is useful for some patients.
• Fluorouracil cream has been reported effective in at least one patient.
• Topical calcineurin inhibitors such as pimecrolimus cream or tacrolimus ointment have been reported to reduce the need for topical steroids.

Oral prescriptions

• Prolonged courses of oral antibiotics, such as tetracycline may be useful.
• If herpes virus infection is a recurrent problem, oral antivirals such as aciclovir are prescribed.
• Anticholinergic medications such as glycopyrrolate may be prescribed to reduce hyperhidrosis (excessive sweating).
• A number of other oral medications (retinoids, ciclosporin, dapsone, and methotrexate) have been reported in single cases as partially effective, but large trials have not been performed.

Other treatments

• Corticosteroid injections into inflamed plaques
• Botulinum toxin to reduce sweating in axillae and groins, thus reducing colonisation by microorganisms and flare-ups
• Phototherapy (ultraviolet light) has also been used.
• Photodynamic therapy has had varying success.
• Lasers have been reported to be useful in one study, eg CO₂ laser or Er:YAG laser vaporising the affected skin, or pulsed dye laser enhancing wound healing.
• In severe cases, surgery can be performed to remove the affected skin. Skin grafts are usually necessary to repair the wounds.
• Dermabrasion has been reported to give excellent long-term results.
• Afamelanotide implants cleared Hailey-Hailey disease in 2 patients.
• Several reports indicate Hailey-Hailey disease improvement with low-dose naltrexone treatment.
• JAK inhibitors, such as abrocitinib, have shown promising results in some treatment-resistant patients.

Will benign familial pemphigus improve in time?

Many patients have long remissions and an improvement with age does occur.