Hailey-Hailey disease (also known as benign familial pemphigus) is an autosomal dominant disorder affecting the skin. It’s characterized by loss of cellular adhesions between keratinocytes in the epidermis resulting in vesicles and erosions in the skin folds. The malodour and pain associated with the lesions can be debilitating for some patients.

Hailey-Hailey disease is found worldwide, with a prevalence of approximately 1 in 50,000. Males and females are equally affected. It’s not apparent at birth and typically presents between ages 10 and 30 years, but sometimes may not present until patients are in their 40s. The phenotype often varies between patients and within affected families.

Hailey-Hailey disease is caused by a mutation in an intracellular calcium pump. Signalling within skin cells may be altered causing disruption in intercellular adhesion molecules.

Clinical features

The erosive plaques of Hailey-Hailey disease have a predilection for the skin folds, especially axillae, groin, inframammary and neck. There can also be seborrheic-dermatitis-like lesions in the scalp. Lesions typically start as a flaccid blister on erythematous or normal skin. Intact blisters are rare; instead, patients are often found to have eroded macerated plaques, sometimes said to resemble a dried riverbed. As they become more extensive, they can become malodorous with painful fissures. Lesions that heal often leave residual pigmentation.

Exacerbating factors include mechanical rubbing (e.g. tight fitting clothing), hot weather and sweating (e.g. summer heat and humidity) and infections (bacteria, yeast, viruses), which can aggravate the disease in some patients.

Complications include secondary bacterial, fungal and viral (i.e. herpes simplex virus) infections. Malodour and thicker crusting suggest bacterial infection. It remains unclear whether or not there’s an increased risk of developing squamous cell carcinoma in affected areas.

Diagnosis

Hailey-Hailey disease can be mistaken for irritant dermatitis, candidiasis, erythrasma, inverse psoriasis, Darier’s disease and pemphigus vegetans.

A skin biopsy (e.g. punch biopsy) is recommended to confirm the diagnosis. Also consider a skin swab for bacteria and/or viral culture. A dermatologist will often perform another skin biopsy, of perilesional skin, for immunofluorescence to rule out pemphigus.

Management

Hailey-Hailey disease is frequently irritating and disfiguring. As such, it can be very bothersome to patients. The disease usually runs a chronic course with exacerbations and remissions. Sometimes the disease improves with age. Spontaneous remissions are rare, but effective treatment options exist.

Once diagnosed, patients should be educated — there are handouts and support groups available. Also refer them for genetic counselling.

A major aim of therapy is irritation control. Encourage patients to keep skin dry and cool with loose fitting cotton clothing and to use mild soaps or soap substitutes.

Topical or systemic antimicrobial therapy helps control the severity and frequency of exacerbations. Topical options include fusidic acid, tetracyclines and imidazoles (e.g. ketoconazole). Tetracyclines are a good starting point for antibiotic therapy. Consider systemic antivirals if there’s evidence of herpetic superinfection.

Topical steroids alone are good options for mild disease. Be cautious regarding steroid potency, however, and use in flexural areas where skin is thin and particularly sensitive to side effects (e.g. atrophy, striae). Topical calcineurin inhibitors (e.g. pimecrolimus, tacrolimus) may also be used. Combination with anti-microbial therapy may enhance disease response.

For some extensive forms of the disease, a variety of other systemic agents have been used, including a short course of corticosteroids. Control is limited and relapses upon discontinuation are common. Other systemic options include cyclosporine and dapsone. Likewise, there are also reports of using systemic retinoids and methotrexate. These agents are reserved for severe disease, though, as evidence to support their use is limited and primarily anecdotal.

For severe disease not responsive to any topical or systemic therapy, destructive therapy (e.g. CO₂ laser, dermabrasion) or surgical excision with grafting may be considered. Patients should be cautioned regarding the likely potential for recurrences.