Hailey–Hailey disease

Published on 19/03/2015 by admin

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Hailey–Hailey disease

Robin A.C. Graham-Brown and Susan M. Burge

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Hailey–Hailey disease (benign familial pemphigus) is a rare blistering disorder first described by two medical brothers in 1939 and characterized by recurrent vesicles and erosions, particularly involving flexural areas. Signs usually appear for the first time from the late teens to the third or fourth decades. The disease is generally of relatively limited extent, although widespread and severe involvement can occur. The most commonly affected sites are the axillae, groins, and other intertriginous areas such as the inframammary folds. The neck may be affected where the collar rubs. Lesions may also occur on the trunk. The disease may koebnerize into other inflammatory dermatoses, such as seborrheic dermatitis.

Hailey–Hailey disease is a dominantly inherited condition. The defective gene, ATP2C1, encodes an ATP-powered calcium channel pump on the Golgi membrane. There are clinical and histopathologic similarities with Darier disease and Grover disease (see relevant chapters).

Management strategy

The lesions of Hailey–Hailey disease are frequently precipitated by friction. Infections with various bacteria, yeasts, and viruses also appear to be aggravating factors in some patients. Thus, avoidance of precipitating trauma and skin infections can help to reduce the frequency and severity of outbreaks.

Simple anti-infective agents, topical or systemic, reduce the severity of exacerbations and remain the mainstay of treatment. Topical tetracyclines, fusidic acid, and imidazoles have all been recommended. Tetracyclines and semi-synthetic penicillins are probably the best systemic agents. If secondary infection with herpes simplex is suspected, appropriate oral antiviral therapy should be instituted.

Combining anti-infective therapy with topical corticosteroids seems to be particularly helpful, but corticosteroids alone may reduce the severity of lesions. Generally, moderate to potent agents are required, though some patients gain benefit from milder preparations. Caution should be exercised with long-term use because the skin of the axillae and groins is prone to atrophy. Topical calcineurin inhibitors tacrolimus and pimecrolimus, either alone or in combination with topical corticosteroids, have been reported to be effective and are certainly worth trying, although some authors dispute this. Some success has also been recorded with calcitriol. Analgesia is important.

Patients with Hailey–Hailey disease are at high risk of developing contact allergic dermatitis, and patch testing should be performed if there is a poor response to therapy.

Electron beam therapy has been used occasionally for recalcitrant disease.

Patients with major exacerbations may benefit from a short course of systemic corticosteroids, but control seldom lasts, and there may be a rebound of the disease on withdrawal.

Systemic alternatives that have been tried in severe disease include dapsone, cyclosporine, methotrexate, and retinoids, but there is little evidence for their effectiveness beyond anecdotal case reports.

There may be a place for surgical approaches to disease of limited extent, including excision and grafting, dermabrasion, the use of CO2 and other lasers. Injections of botulinum toxin have been advocated to reduce sweating in axillary Hailey-Hailey disease.

Unsurprisingly, perhaps, reports of treatment with biologic agents are beginning to appear in mainstream journals. It is much too soon to recommend their use routinely, even in severe disease.

Second-line therapies

image Topical calcineurin inhibitors E
image Calcitriol E
image Systemic corticosteroids E
image Dapsone E
image Cyclosporine E
image Botulinum toxin E

Third-line therapies

image Surgical excision (with healing by secondary intention or by grafting) E
image Dermabrasion E
image Laser therapy E
image Superficial irradiation (Grenz rays or electron beam) E
image Methotrexate E
image Oral retinoids E
image 5-Fluorouracil E
image Biologics E
image Photodynamic therapy E

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Hailey–Hailey disease

Robin A.C. Graham-Brown and Susan M. Burge

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Hailey–Hailey disease (benign familial pemphigus) is a rare blistering disorder first described by two medical brothers in 1939 and characterized by recurrent vesicles and erosions, particularly involving flexural areas. Signs usually appear for the first time from the late teens to the third or fourth decades. The disease is generally of relatively limited extent, although widespread and severe involvement can occur. The most commonly affected sites are the axillae, groins, and other intertriginous areas such as the inframammary folds. The neck may be affected where the collar rubs. Lesions may also occur on the trunk. The disease may koebnerize into other inflammatory dermatoses, such as seborrheic dermatitis.

Hailey–Hailey disease is a dominantly inherited condition. The defective gene, ATP2C1, encodes an ATP-powered calcium channel pump on the Golgi membrane. There are clinical and histopathologic similarities with Darier disease and Grover disease (see relevant chapters).

Management strategy

The lesions of Hailey–Hailey disease are frequently precipitated by friction. Infections with various bacteria, yeasts, and viruses also appear to be aggravating factors in some patients. Thus, avoidance of precipitating trauma and skin infections can help to reduce the frequency and severity of outbreaks.

Simple anti-infective agents, topical or systemic, reduce the severity of exacerbations and remain the mainstay of treatment. Topical tetracyclines, fusidic acid, and imidazoles have all been recommended. Tetracyclines and semi-synthetic penicillins are probably the best systemic agents. If secondary infection with herpes simplex is suspected, appropriate oral antiviral therapy should be instituted.

Combining anti-infective therapy with topical corticosteroids seems to be particularly helpful, but corticosteroids alone may reduce the severity of lesions. Generally, moderate to potent agents are required, though some patients gain benefit from milder preparations. Caution should be exercised with long-term use because the skin of the axillae and groins is prone to atrophy. Topical calcineurin inhibitors tacrolimus and pimecrolimus, either alone or in combination with topical corticosteroids, have been reported to be effective and are certainly worth trying, although some authors dispute this. Some success has also been recorded with calcitriol. Analgesia is important.

Patients with Hailey–Hailey disease are at high risk of developing contact allergic dermatitis, and patch testing should be performed if there is a poor response to therapy.

Electron beam therapy has been used occasionally for recalcitrant disease.

Patients with major exacerbations may benefit from a short course of systemic corticosteroids, but control seldom lasts, and there may be a rebound of the disease on withdrawal.

Systemic alternatives that have been tried in severe disease include dapsone, cyclosporine, methotrexate, and retinoids, but there is little evidence for their effectiveness beyond anecdotal case reports.

There may be a place for surgical approaches to disease of limited extent, including excision and grafting, dermabrasion, the use of CO2 and other lasers. Injections of botulinum toxin have been advocated to reduce sweating in axillary Hailey-Hailey disease.

Unsurprisingly, perhaps, reports of treatment with biologic agents are beginning to appear in mainstream journals. It is much too soon to recommend their use routinely, even in severe disease.

First-line therapies

image Anti-infectives and antibiotics C
image Topical corticosteroids C

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