Hailey-Hailey Disease

• Hailey-Hailey disease, also known as benign familial pemphigus, is an autosomal dominant disease affecting intertriginous skin.
• Most common on the groin, axilla, and lateral neck.
• The primary blisters and erosions that develop as a result of loss of keratinocyte cohesiveness may become secondarily infected with bacteria or yeast and may itch mildly.
• Aggravated by hot and humid weather.

• HHD is caused by loss-of-function mutations in the ATP2C1 gene at 3q22.1, which encodes the ATP-powered calcium pump protein hSPCA1 that sequesters calcium into the Golgi apparatus.
• About 100 different mutations, distributed throughout theATP2C1 gene, have been described in patients with HHD.

• Onset usually in the second and third decades of life.
• Flexural areas involved in a symmetric fashion, and mucosal involvement is rare. Segmental forms present as unilateral, linear, patchy, or otherwise confined involvement. Linear lesions are often localized along the Blaschko lines.
• Flaccid vesicles on erythematous to normal skin are the first manifestation and are often not noticed.
• Large, macerated, exudative plaques of superficial erosions with crusting are usually seen at the time of the diagnosis.
• Further progression to large vegetative malodorous plaques with painful fissures can occur. Flexural disease may be disabling, especially if the groin is involved.
• Longitudinal white bands of the nails have been described in about 70 percent of patients with HHD and can be a clue to the diagnosis.
• HHD has a remitting and relapsing course with a substantial impact on the quality of life.

DDx:

• Candidiasis
• Inverse psoriasis
• Intertrigo
• Dermatophyte infection
• Pemphigus vulgaris
• Pemphigus foliaceus
• Cicatricial pemphigoid

• Hyperkeratosis with focal parakeratosis
• Acanthosis with elongation of rete ridges
• Suprabasal acantholysis induces the formation of small clefts ("lacunae") in early lesions
• Suprabasal vesiculation with acantholytic cells in established lesions
• Projections of papillary dermis lined by a single layer of basal keratinocytes ("villi") extend into the lumen of the lacunae or vesicles
• Full thickness, partial acantholysis ("dilapidated brick wall" appearance)
• Mild chronic inflammatory cell infiltrate in the underlying dermis

• Culture the skin for bacteria, yeast, and herpes simplex virus (HSV). Subclinical, coexistent infection can lead to worsening of the skin disease.
• Currently, there is no cure for this disease; thus, management is aimed at control of the disease. Avoidance of excess heat, moisture, and friction is essential.
• A mid-potency topical corticosteroid/antibacterial cream often decreases the inflammatory component.
• There should be a high index of suspicion for superinfection with treatment, as appropriate.

• There are anecdotal reports of squamous cell carcinomas arising in vulvar and penile lesions of HHD.
• However, it is unclear whether the chronic impairment of the epidermal barrier in HHD increases the risk of infection from oncogenic strains of HPV.
• Melanoma and other cancers have also been reported in patients with HHD.

Hailey-Hailey Disease

By Laura Jordan, OMS-4, LECOM-Bradenton

Histology

Diagnosis and Workup

Histology

A suprabasal blister with acantholytic changes in the lower half of the epidermis in the setting of Hailey-Hailey disease. A dense perivascular and interstitial lymphocytic infiltrate can be seen in the upper dermis (H&E, original magnification ×40).

Pathogenesis

Villi, or protruding dermal papillae lined with a single layer of basal cells, are evident. Above the villi, a few intact intercellular bridges remain, giving the appearance of a dilapidated brick wall (H&E, original magnification ×200). [Ohata C. Hailey-Hailey disease. Cutis. 2014 Jul;94(1):8,33-34.]

Overview

Clinical Presentation

Clinical Presenation

Treatment

Complications

References

• Burge SM. Hailey-Hailey disease: the clinical features, response to treatment and prognosis. Br J Dermatol. 1992 Mar;126(3):275-82. PubMed ID: 1554604.
• Gisondi P, Sampogna F, Annessi G, et al. Severe impairment of quality of life in Hailey-Hailey disease. Acta Derm Venereol 2005; 85:132.
• Holst VA, Fair KP, Wilson BB, Patterson JW. Squamous cell carcinoma arising in Hailey-Hailey disease. J Am Acad Dermatol 2000; 43:368.
• Hu Z, Bonifas JM, Beech J, et al. Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet 2000; 24:61.
• Hunt R, O'Reilly K, Ralston J, Kamino H, Shupack JL. Familial benign chronic pemphigus (Hailey-Hailey disease). Dermatol Online J. 2010;16(11):14. PubMed ID: 21163165.
• Majore S, Biolcati G, Barboni L, et al. ATP2C1 gene mutation analysis in Italian patients with Hailey-Hailey disease. J Invest Dermatol 2005; 125:933.
• McKibben J, Smalling C. Hailey-Hailey. Skinmed. 2006 Sep-Oct;5(5):250-2. PubMed ID: 16957441
• Mohr MR, Erdag G, Shada AL, et al. Two patients with Hailey-Hailey disease, multiple primary melanomas, and other cancers. Arch Dermatol 2011; 147:211.
• Ochiai T, Honda A, Morishima T, et al. Human papillomavirus types 16 and 39 in a vulval carcinoma occurring in a woman with Hailey-Hailey disease. Br J Dermatol 1999; 140:509.
• Ohata C. Hailey-Hailey disease. Cutis. 2014 Jul;94(1):8,33-34.
• Patterson DM, Lee SM. Glucarpidase following high-dose methotrexate: update on development. Expert Opin Biol Ther. 2010 Jan;10(1):105-11. PubMed ID: 19925307.
• Rabeni EJ, Cunningham NM. Effective treatment of Hailey-Hailey disease with topical tacrolimus. J Am Acad Dermatol. 2002 Nov;47(5):797-8. PubMed ID: 12399782.
• Tan B, Craft N, Fox LP, Goldsmith LA, Tharp MD. Hailey-Hailey Disease. VisualDx. 2013 Oct. Accessed on February 22, 2015, from https://www.visualdx.com/visualdx/visualdx6/getDiagnosisText.do?moduleId=7&diagnosisId=52672.
• Umar SA, Bhattacharjee P, Brodell RT. Treatment of Hailey-Hailey disease with tacrolimus ointment and clobetasol propionate foam. J Drugs Dermatol. 2004 Mar-Apr;3(2):200-3.PubMed ID: 15098980.

Thank you for such a wonderful rotation!

~Laura