Familial benign pemphigus

The patient was diagnosed with familial benign pemphigus (FBP), commonly referred to as Hailey-Hailey disease—named after two brothers who first documented the condition in 1939.1 Inherited as an autosomal dominant condition, FBP is characterized by a recurring vesiculobullous eruption that frequently progresses to erosive, vegetative and erythematous plaques, often with fissures. Intertriginous areas, specifically the axillae, groin, and nape of the neck, are primarily affected. Patients usually present in their third or fourth decade of life.2 Lesions wax and wane over time; such aggravating factors as heat, sweating, and friction seem to trigger recurrences and symptomatic exacerbations.2-4 A characteristic fingernail finding of multiple, longitudinal white bands without nail pitting or fragility occurs in many affected individuals, frequently predating the cutaneous findings. When present, these nail changes may help distinguish FBP from other epidermal diseases such as psoriasis.2

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FBP is caused by a genetic defect in the desmosome, a complex transcellular structure responsible for cell-to-cell adhesion between keratinocytes of the epidermis.5,6 Inherited on chromosome 3, the mutation alters an ATP2C1 gene that codes for a Ca2/Mn2-ATPase within the Golgi apparatus of keratinocytes.7,8 Intracellular calcium homeostasis is adversely impacted, ultimately compromising intercellular cohesion.9 The term acantholyis is used to describe the histologic findings attributable to destruction of epidermal cell-to-cell adhesion. Lacking keratinocyte necrosis, the acantholytic process in FBP has a peculiar microscopic appearance, referred to as a “dilapidated brick wall.” 4-6 Immunofluorescence staining for autoantibodies in FBP is negative, readily distinguishing it from pemphigus vulgaris or pemphigoid. Since the acantholysis in pemphigus vulgaris and pemphigoid results from a destructive circulating autoantibody, immunfluorescence is generally positive.5,9

Lesional morphology of FBP is highly variable, complicating and frequently delaying the diagnosis. Other more common intertriginous diseases such as candida, seborrheic dermatitis, or even psoriasis may first be entertained.2,10 Similarly, when FBP affects the nape of the neck, the condition may be misdiagnosed as contact dermatitis or atopic dermatitis, especially in individuals with other manifestations of atopy. Patients frequently postpone medical attention because the natural history of FBP is to recur and remit. Further postponement may occur because empiric treatment with topical glucocorticoids, antibiotics, or antifungals provides symptomatic relief.2 Once suspected, however, the diagnosis can be readily confirmed with biopsy.

Although the recurrent nature of FBP is a nuisance, most patients have a good prognosis and experience improvement with age.2 Because of inherent epidermal damage, secondary infection is the major complication. Inflammation associated with colonization and infection can worsen acantholysis, exacerbating symptoms.3 Organisms commonly implicated include Staphylococcus aureus and Candida spp.10 Trauma or other causes of inflammation, such as irritant or allergic contact dermatitis, may trigger or potentiate lesions and symptoms.4

Overall management includes education. Patients should be educated regarding good skin hygiene to diminish the possibility of secondary infection and advised on how to avoid or ameliorate such aggravating factors as heat and friction.2 Genetic education is also a must since FBP is inherited from generation to generation.

Treatment includes topical corticosteroids and topical and/or oral antimicrobials. By reducing inflammation, topical steroids provide symptomatic relief and promote epidermal repair.10 Topical steroids may also limit disease if applied immediately after a lesion develops. Antibiotics and antifungals are not only useful antimicrobial agents, they may also have anti-inflammatory properties.2 This patient’s lesions responded well to topical triamcinolone, mupirocin, and nystatin cream.

For cases recalcitrant to topical therapy, other treatment options may be considered. Although used off-label, the literature supports oral retinoid and intralesional botulinum toxin therapy.2,11 More invasive therapies, such as carbon dioxide laser ablation or dermabrasion, have been used in severe cases of FBP.12 The potential adverse effects of these other options must be considered before using.

Mr. Kaufman is a third-year medical student at Virginia Commonwealth University School of Medicine in Richmond. Dr. Nunley is professor of dermatology at Medical College of Virginia Hospitals, also in Richmond. Neither has any relationship to disclose relating to the content of this article.

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References

  1. Hailey H, Hailey H. Familial benign chronic pemphigus. Arch Derm Syphilol. 1939;39:679-685.
  2. Burge SM. Hailey-Hailey disease: the clinical features, response to treatment and prognosis. Br J Dermatol. 1992;126:275-282.
  3. Burge SM, Millard PR, Wojnarowska F. Hailey-Hailey disease: a widespread abnormality of cell adhesion. Br J Dermatol. 1991;124:329-332.
  4. Foggia L, Hovnanian A. Calcium pump disorders of the skin. Am J Med Genet C Semin Med Genet. 2004;131C:20-31.
  5. Wilgram GF, Caulfield JB, Lever WF. An electron-microscopic study of acantholysis and dyskeratosis in Hailey’s disease. J Invest Dermatol. 1962;39:373-381.
  6. Gottlieb SK, Lutzner MA. Hailey-Hailey disease: an electron microscopic study. J Invest Dermatol. 1970;54: 368-376.
  7. Richard G, Korge BP, Wright AR, et al. Hailey-Hailey disease maps to a 5 cM interval on chromosome 3q21-q24. J Invest Dermatol. 1995;105:357-360.
  8. Hu Z, Bonifas JM, Beech J, et al. Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet. 2000;24:61-65.
  9. Szigeti R, Kellermayer R. Autosomal-dominant calcium channel ATPase disorders. J Invest Dermatol. 2006;126:2370-2376.
  10. Wolff K, Johnson RA. Familial benign pemphigus. In: Fitzpatrick TB, Johnson RA, Wolff K, Suurmond R, eds. Color Atlas and Synopsis of Clinical Dermatology, 6th ed. New York, N.Y.: McGraw-Hill; 2009:105.
  11. Hunt MJ, Salisbury EL, Painter DM, Lee S. Vesiculobullous Hailey-Hailey disease: successful treatment with oral retinoids. Australas J Dermatol. 1996;37:196-198.
  12. Freiman A, Hakim MD, Billick RC. Hailey-Hailey disease (benign familial pemphigus): carbon dioxide laser therapy. Mcgill J Med. 2002;6:100-103.

From the July 01, 2010 Issue of Clinical Advisor

Topics:

CME/CE Dermatology