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What Is This Woman’s Itchy, Blistering, and Persistent Rash?

R. Blake Steele, BSc, Adam B. Blechman, MD, and Barbara B. Wilson, MD

Volume 55 - Issue 11 - November 2015

A 25-year-old female patient was seen in clinic for a 2-year history of a recurrent pruritic rash on her neck and shoulders. She described the rash as blisters that quickly rupture and become crusted. 

History

The patient was on no medications other than oral acyclovir for recurrent herpes simplex virus type 2 infection. Her other medical history was positive for 1.5-year history of benign right cervical lymphadenopathy.

Hailey-Hailey disease

Physical Examination

Examination revealed erythematous hyperkeratotic plaques with overlying crust and erosions on her bilateral neck, shoulders, and left arm with mild involvement of both axillae. A biopsy of her left shoulder showed acantholytic dermatosis with a dilapidated brick wall appearance.

Laboratory Tests

Direct immunofluorescence was negative for intraepidermal immunoglobulin. A bacterial culture from a crusted plaque on the right shoulder grew methicillin-sensitive Staphylococcus aureus. A herpes simplex type 1 and 2 culture was negative.

What’s Your Diagnosis?

 

(Answer and discussion on next page)

Answer: Hailey-Hailey Disease

Discussion

Hailey-Hailey disease, also known as benign familial pemphigus, is a blistering disorder most commonly localized to the skin folds, including the neck, axilla, groin, and inframammary area. It is a genetic disorder due to a mutation in the ATP2C1 gene. This gene codes for a calcium/manganese ATPase pump that helps desmosomes (structures connecting skin keratinocytes) to function properly. The desmosomal decomposition that results from this gene mutation leads to loss of cohesion between epidermal keratinocytes, a process known as acantholysis.1 This acantholysis leads to recurrent flaccid vesiculobullous lesions. The vesicular lesions soon evolve into eroded plaques with a fissured appearance. These can eventually develop crust, scale, and hypertrophic vegetations.2  They also frequently become secondarily infected with bacteria and fungi. Other disorders with similar findings of acantholysis that should be in the differential include Pemphigus, Darier’s disease, and Herpes simplex infection. Pemphigus should be ruled out with direct immunofluorescence testing of a perilesional skin biopsy.

The onset of Hailey-Hailey disease typically begins in the third and fourth decades and is usually inherited in a autosomal-dominant fashion with variable expressivity; however, about 30% of cases are due to de novo mutations.3 The disease waxes and wanes throughout the years and is known to flare due to certain triggers, such as trauma, pregnancy, infections, drugs, excessive ultraviolet light, and sweating.1

Treatment

First line therapy includes ultra-potent topical steroids and topical calcineurin inhibitors. Also, secondary infection should be treated with topical or oral antimicrobials. Topical mupirocin and systemic tetracyclines work well as antimicrobial therapy, but other systemic options include penicillin, dapsone, and erythromycin. Dilute bleach baths can also be helpful in treating and preventing infections. Avoiding activities that cause sunburn, friction and sweating is recommended.

Refractory cases have been treated with CO2 laser or dermabrasion therapies.2  Cyclosporine, methotrexate, photodynamic therapy, and pulsed dye laser therapy, acitretin, among other treatments, have all been reported as successful treatment modalities.4-6 Botulinum A toxin injection has also been found beneficial in treating this disease.3 Ultimately, the condition becomes less severe and troublesome with age.

The author explains the case in this podcast:

References:

  1. Engin B, Kutlubay Z, Çelik U, et al. Hailey-Hailey disease: A fold (intertriginous) dermatosis. Clin Dermatol. 2015;33(4):452-455.
  2. Disorders Presenting in the Skin and Mucous Membranes. In: Wolff K, Johnson RA, Saavedra A. Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw Hill; 2013:92.
  3. Chiaravalloti A, Payette M. Hailey-Hailey disease and review of management. J Drugs Dermatol. 2014;13(10):1254-1257.
  4. Varada S, Ramirez-Fort MK, Argobi Y, Simkin AD. Remission of refractory benign familial chronic pemphigus (Hailey-Hailey disease) with the addition of systemic cyclosporine. J Cutan Med Surg. 2015;19(2):163-166.
  5. Yan XX, Tian HQ, Wang CL, et al. Successful treatment of hailey-hailey disease with aminolevulinic acid photodynamic therapy. Ann Dermatol. 2015;27(2):222-223.
  6. Hunt K, Jensen JD, Walsh SB, et al. Successful treatment of refractory Hailey-Hailey disease with a 595-nm pulsed dye laser: a series of 7 cases. J Am Acad Dermatol. 2015;72(4):735-737.