Benign familial pemphigus
What is benign familial pemphigus?
Benign familial chronic pemphigus or Hailey-Hailey disease is a rare hereditary blistering skin disease first described by the Hailey brothers in 1939.
Who gets benign familial pemphigus?
Benign familial pemphigus usually appears in the third or 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 a 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 exacerbates 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?
How is benign familial pemphigus diagnosed?
Usually benign familial pemphigus is diagnosed by its appearance and the family history, but it is often is mistaken for other skin problems. Impetigo, thrush, tinea (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?
Unfortunately there is no cure for Hailey-Hailey disease. Treatment is aimed at reducing symptoms and preventing flares.
- Avoid trigger factors such as sunburn, sweating and friction where possible; eg when hot, stay indoors with fan or air conditioning, limit amount of exercise taken.
- Wash and dry skin folds carefully, once or twice daily using mild soap and water.
- Wear soft, loose clothing, with absorbant pads in underwear.
- If overweight, try to decrease body fat to minimise friction.
- Apply wet compresses, eg wtih 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.
- 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 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 in 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 need for topical steroids.
- 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.
- Corticosteroid injections into inflamed plaques
- Botulinum toxin to reduce sweating, 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.
New hope for the treatment of benign familial pemphigus
In 2014, researchers in Italy reported that afamelanotide implants had cleared Hailey-Hailey disease in 2 patients. The results of a formal clinical trial in a further 10 patients with the disease have not yet been reported.
Are there any complications in benign familial pemphigus?
For many patients benign familial pemphigus is a mild condition, but for others the pain and smell can be serious problems. If the lesions get infected with herpes virus a sudden severe flare can occur, which often needs prompt treatment (see above).
Will benign familial pemphigus improve in time?
Many patients have long remissions and an improvement with age does occur.