Benign familial pemphigus

Author: Dr Steven Lamb, Dermatology Registrar, Waikato Hospital, Hamilton, New Zealand, 2001. Updated by Hon A/Prof Amanda Oakley, September 2016.

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?

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 viral infection (eczema herpeticum).

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.

General advice

Topical prescriptions

Oral prescriptions

Other treatments

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.[1] 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.

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