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Year : 2013  |  Volume : 58  |  Issue : 5  |  Page : 412
Hailey-Hailey disease on sun-exposed areas

Department of Dermatology, SVS Medical College, MBNR, Hyderabad, Andhra Pradesh, India

Date of Web Publication30-Aug-2013

Correspondence Address:
Angoori Gnaneshwar Rao
Department of Dermatology, SVS Medical College, MBNR, Hyderabad, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.117371

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How to cite this article:
Rao AG. Hailey-Hailey disease on sun-exposed areas. Indian J Dermatol 2013;58:412

How to cite this URL:
Rao AG. Hailey-Hailey disease on sun-exposed areas. Indian J Dermatol [serial online] 2013 [cited 2021 Oct 17];58:412. Available from:


 Hailey-Hailey disease More Details (HHD) was first described in 1939 as familial benign chronic pemphigus (FBCP). It is an autosomal dominant disorder with incomplete penetrance, with approximately two-thirds of the patients having a family history of the disorder. [1] The disease is due to a mutation of the ATP2C1 gene on chromosome 3q21-q24 which is responsible for controlling Ca 2+ concentrations in the cytoplasm and Golgi in human keratinocytes. [2],[3] Cytosolic Ca 2+ concentrations, in turn, play a major role in the regulation of keratinocyte differentiation. Involucrin, a protein that envelopes keratinocytes is expressed in response to increased intracellular Ca 2+ concentrations. It is responsible for keratinocyte adhesion. Alberg et al., found that the levels of involucrin are decreased in HHD. [4]

A 40-year-old lady presented with painful erythematous plaques of 20-day duration involving the front and sides of the neck and the extensor aspect of both forearms, associated with fever and itching. There was no history of joint pains and family history was negative for a similar ailment. She denied any history of herpes simplex or intake of drugs. Cutaneous examination revealed multiple tender erythematous plaques ranging from 2 to 6 cm. Margins of some of the plaques showed papules and pustules with scaling and central hyperpigmentation [Figure 1] and [Figure 2]. On the basis of clinical features, Sweet's syndrome was provisionally diagnosed. Tinea corporis was considered, as a few plaques showed marginal activity but fungal elements were absent on a potassium hydroxide (KOH) mount. Although erythema multiforme was considered in the differential diagnosis, target lesions were absent and history was negative for herpes simplex and drugs. Pemphigus erythematosus was also considered, but immunoglobulin G (IgG) antibodies to desmoglein-3 and direct immunofloresence (DIF) were negative. Routine laboratory investigations were unremarkable. Antibodies against herpes simplex virus 1 and 2 (HSV1 and 2) were negative. Test for antinuclear antibodies (ANA) was negative. A skin biopsy taken from the extensor aspect of the right forearm showed intraepidermal bulla with complete and partial acantholysis of suprabasal and upper layers of the epidermal keratinocytes giving the appearance of a 'dilapidated brick wall' which clinched the diagnosis of FBCP [Figure 3] and [Figure 4]. Direct immunofluoresence of skin biopsy did not show immune deposits. Ultraviolet (UV) provocation test could not be done as the patient did not give her consent. She was given a course of antibiotics and analgesics and her symptoms regressed. The case is being presented for its atypical presentation.
Figure 1: Erythematous plaques on the right side of neck and upper part of front of chest

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Figure 2: Erythematous plaque on the extensor aspect of right fore arm

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Figure 3: Histopathology of skin H and E, ×10 showing intraepidermal bulla with complete and partial acantholysis of suprabasal and upper layers of the epidermis giving the appearance of a 'dilapidated brick wall'

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Figure 4: Histopathology of skin H and E, ×40 showing complete and partial acantholysis of upper layers of epidermis

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Lesions in FBCP often begin in early adulthood and affect both sexes equally. Epidermis is the site of defect in FBCP. De bobbeleer et al. could reproduce in vitro classic histologic and ultrastructural features of FBCP by seeding suspension of lesional keratinocytes onto heterozygous dead de-epidermized dermis. [5]

Although the course of the disease is unpredictable, morbidity in majority of the patients declined where the duration of the disease was longer than 20 years. [6] HHD typically involves the axillary, genitocrural, and inframammary folds. [7] This is attributed to minor trauma in the form of maceration, heat, and friction. Lesions are usually symmetrical. However, our case presented with erythematous plaques on sun-exposed areas, that is, the right side of the neck and extensor aspects of both forearms. A review of the literature revealed a single case report of FBCP of six-month duration involving typical sites, who developed lesions later on sun-exposed areas. He was a 63-year-old man who had multiple diseases (chronic obstructive pulmonary disease, paroxysmal atrial fibrillation, degenerative joint disease) and was on various medications (warfarin, aminophylline, N-acetylcystiene, ipratropium bromide, prednisolone). [8] However, the reported case is a young healthy lady and not on any medication. The exact role of sunlight in the provocation of FBCP in the reported case could not be established as the patient did not consent to the UV provocation test which could have helped in establishing its role in the pathogenesis of FBCP.

Unusual sites include vulva, [9] conjunctiva, [10] and mucosa. [11] Rarely, it may present as erythroderma. [12] Lesions may be triggered by trauma, bacterial or fungal infections, and dermatoses. Eczema herpeticum may occur rarely in patients of FBCP. Such association was reported only in four cases in the literature. [13] Lesions tend to recur at sites of previous involvement. Longitudinal leukonychia, seen 71% in one study, may help in the diagnosis of HHD. [6] However, this nail finding was not observed in the reported case. Variants of classic HHD include segmental unilateral disease, seborrheic dermatitis, and perianal disease simulating condyloma accuminata.

Treatment is difficult; however, there are report of improvement with systemic or topical antistaphylococcal antibiotics, antifungals, corticosteroids, cyclosporine, [14] retinoids, [15] topical calcineurin inhibitors and calcitriol, botulinum toxin, dapsone, dermabrasion, [16] carbon dioxide (CO 2 ) laser, [17] photodynamic therapy, [18] and grafting. [19] FBCP patients have an increased risk of developing contact allergy to topical therapy. [20] Skin grafting with split-thickness skin graft is indicated in recalcitrant cases of FBCP. Topical gentamicin was found to be effective in inducing remission in an FBCP patient. It can induce readthrough of premature stop mutations in the epidermis. [21]

   References Top

1.Hailey H, Hailey H. Familial benign chronic pemphigus. Arch Dermatol 1939;39:679.  Back to cited text no. 1
2.Durr G, Strayle J, Plemper R, Elbs S, Klee SK, Catty P, et al. The medial-Golgi ion pump Pmr1 supplies the yeast secretory pathway with Ca 2+ and Mn 2+ required for glycosylation, sorting, and endoplasmic reticulum-associated protein degradation. Mol Biol Cell 1998;9:1149-62.  Back to cited text no. 2
3.Hakuno M, Shimizu H, Akiyama M, Amagai M, Wahl JK, Wheelock MJ, et al. Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease. Br J Dermatol 2000;142:702-11.  Back to cited text no. 3
4.Aberg KM, Racz E, Behne MJ, Mauro TM. Involucrin Expression is decreased in Hailey-Hailey keratinocytes owing to increased involucrin mRNA degradation. J Invest Dermatol 2007;127:1973-9.  Back to cited text no. 4
5.De bobbeleer G, De Graef C, M'Pondi E, Gourdain JM, Heenen M. Reproduction of the characteristic, morphologic changes of FBCP in cultures of lesional keratinocytes on dead deepidermadized dermis. J Am Acad Dermatol 1989;21 (5 Pt 1):961-5.  Back to cited text no. 5
6.Burge SM. Hailey-Hailey disease: The clinical features, response to treatment prognosis. Br J Dermatol 1992;126:275-82.  Back to cited text no. 6
7.Lyles TW, Knox JM, Richardson JB. Atypical features in familial benign chronic pemphigus. AMA Arch Dermatol 1958;78:446-53.  Back to cited text no. 7
8.Choi DJ, Oh CW, Yoon TJ, Kim TH. Hailey-Hailey disease on sunexposed areas. Photodermatol Photoimmunol Photomed 2002;18:214-5.  Back to cited text no. 8
9.Wieselthier JS, Pincus SH. Hailey-Hailey disease of the vulva. Arch Dermatol 1993;129:1344-5.  Back to cited text no. 9
10.Oguz O, Gökler G, Ocakoðlu O, Oðuz V, Demirkesen C, Aydemir EH. Conjunctival involvement in familial chronic benign pemphigus q (Hailey-Hailey disease). Int J Dermatol 1997;36:282-5.  Back to cited text no. 10
11.Vaclavinkova V, Neumann E. Vaginal involvement in familial benign chronic pemphigus (Morbus Hailey-Hailey). Acta Derm Venereol 1982;62:80-1.  Back to cited text no. 11
12.Marsch WC, Stuttgen G. Generalized Hailey-Hailey disease. Br J Dermatol 1978;99:553-60.  Back to cited text no. 12
13.Lee GH, Kim YM, Lee SY, Lee YL, Park YL, Whang KU. A case of eczema herpeticum with Hailey-Hailey Disease. Ann Dermatol 2009;21:311-4.  Back to cited text no. 13
14.Berth-Jones J, Smith SG, Graham-Brown RA. Benign familial chronic pemphigus (Hailey-Hailey disease) responds to cyclosporin. Clin Exp Dermatol 1995;20:70-2.  Back to cited text no. 14
15.Berger EM, Galadari HI, Gottlieb AB. Successful treatment of Hailey-Hailey disease with acitretin. J Drugs Dermatol 2007;6:734-6.  Back to cited text no. 15
16.Hamm H, Metze D, Bröcker EB. Hailey-Hailey disease: Eradication by dermabrasion. Arch Dermatol 1994;130:1143-9.  Back to cited text no. 16
17.Don PC, Carney PS, Lynch WS, Zaim MT, Hassan MO. Carbon dioxide laserabrasion: A new approach to management of familial benign chronic pemphigus (Hailey-Hailey disease). J Derm Surg Oncol 1987;13:1187-94.  Back to cited text no. 17
18.Ruiz-Rodriguez R, Alvarez JG, Jaén P, Acevedo A, Córdoba S. Photodynamic therapy with 5-aminolevulinic acid for recalcitrant familial benign pemphigus (Hailey-Hailey disease). J Am Acad Dermatol 2002;47:740-2.  Back to cited text no. 18
19.Menz P, Jackson IT, Connolly S. Surgical control of Hailey -Hailey disease. Br J Plast Surg 1987;40:557-61.  Back to cited text no. 19
20.Riebamo S, Ramitz A, Lauermo AI, Forstorm L. Contact allergies in patients with Familial Benign Chronic Pemphigus. J Am Acad Dermatol 1989;21 (3 Pt 1):506-10.  Back to cited text no. 20
21.Kellermayer R, Szigeti R, Keeling KM, Bedekovics T, Bedwell DM. Aminoglycosides as potential pharmacokinetic agents in the treatment of Hailey-Hailey disease. J Invest Dermatol 2006;126:229-31.  Back to cited text no. 21


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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