Pemphigus chronicus benignus familiaris Q82.8

Authors: Prof. Dr. med. Peter Altmeyer, Pia Nagel

All authors of this article

Last updated on: 25.02.2022

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chronic pemphigus; chronic recurrent acantholysis; Dyskeratoid dermatosis; Dyskeratosis bullosa; dyskeratosis bullosa hereditaria; familial benign pemphigus; Familial benign pemphigus; Familial pemphigus benign; Gougerot- Hailey-Hailey disease; Gougerot-Hailey-Hailey disease; Hailey-Hailey disease; M. Hailey-Hailey; OMIM 169600; Pemphigus familiaris chronicus benignus; Pemphigus Gougerot-Hailey-Hailey; recurrent herpetiform dermatitis repens

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Gougerot, 1933; Howard Hailey and Hugh Hailey (brothers), 1939

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Eminently chronic, recurrent genodermatosis characterized by inflammatory, weeping and macerated areas in the large folds of the body. Frequent familial occurrence. No nosological relationship to pemphigus vulgaris. Provocation is possible by sun, heat, rubbing and microbial infections (Candida). Probably a variant of Darier's disease.

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Autosomal dominant inheritance with variable penetrance. Also new mutations. Detected multiple mutations in the ATP2C1 gene mapped to chromosome 3q21-24. The ATP2C1 gene encodes a Golgi-associated Ca-ATPase (SERCA2) responsible for Ca content in the Golgi apparatus (Deng H et al. 2017). Decreased Ca levels lead to defective processing of various adhesion molecules(E-cadherin), insufficient cell-to-cell adhesion, and acantholysis. See also Dyskeratosis follicularis.

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First manifestation rarely before the age of 10 LJ, usually after the age of 20.

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Especially the cervical, axillary and inguinal regions are affected. More rarely occurring on the trunk.

Clinical features
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Initially solitary or grouped, elongated vesicles or blisters, severe itching or burning. Due to confluence formation of itchy, reddened, roundish, oval or circulatory plaques covered by greasy scale crusts, usually sharply defined with typical transverse fissures. Often secondary infections (e.g. with Candida). Nikolski Phenomenon I and Nikolski Phenomenon II are positive.

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Acanthosis, acantholysis with formation of wide-area, intraepidermal clefts and blisters, which may affect entire rete cones and also continue over the papillae tips; dyskeratotic transformation of the acantholytic cells especially in the stratum granulosum, frequently corps ronds and grains (dyskeratoses), parakeratotic cells in the blister roof. Dermal shows a dense lymphohistiocytic infiltrate.

Electron microscopy: sparse desmosomes, desmolysis.

DD: Pemphigus vulgaris: In contrast to P.v., eosinophilic granulocytes are absent in the intraepidermal lumina and follicular involvement is absent.

IF: Negative!

Differential diagnosis
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Reminder. In the case of non-healing intertriginous "mycoses", always think of pemphigus chronicus benignus familiaris!

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Secondary infections.

General therapy
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Avoid provocative factors, e.g. tight underwear or jeans.

External therapy
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Therapy for smaller foci with weak to moderate strength topical glucocorticoids such as 0.5% hydrocortisone creams/lotions(e.g. Hydro-Wolff, R123 ), 0.1% triamcinolone acetonide (e.g. Triamgalen), 0.25% prednicarbate cream(e.g. Dermatop). Instead of glucocorticoid externals, lesions can also be carefully injected with glucocorticoid crystal suspension, e.g., triamcinolone (e.g., Volon A 10-20 mg diluted 1:2 with LA such as 1% scandicaine solution).

Successful therapy attempts with Tacrolimus (e.g. Protopic) are described casuistically (off-label use!).

Often the lesions are bacterially or mycotically superinfected, therefore alternating therapies with local disinfectants are recommended, e.g. polihexanide (Serasept) or octenidine (Octenisept). Dyes are less practical in daily use (discoloration of the surrounding area).

Alternatively, glucocorticoid/antiseptic or glucocorticoid/antiseptic/antifungal combinations can be used, such as 0.5% clioquinol/hydrocortisone cream R051, clioquinol/flumethasone cream (Locacorten Vioform), triclosan/flumethasone(Duogalen), or nystatin/fluprednidene acetate paste(e.g., Candio-Hermal Plus paste). Caveat. There is an increased risk of local glucocortical side effects in intertrigines!

Internal therapy
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The overall therapy is not satisfactory. Positive treatment results with DADPS (e.g. dapsone fatol) 50-100-150 mg/day p.o. or acitretin (Neotigason) 10-20 mg/day, permanently 10 mg every 2nd day p.o.(not very effective according to own experience) have been reported in single cases.

Systemic immunosuppressants such as ciclosporin A (e.g. Sandimmun) or methotrexate (e.g. MTX) cannot be recommended due to long-term side effects.

Success with the biologic etanercept as well as the phosphodiesterase-4 inhibitor apremilast (Kieffer J et al. 2018) has been reported.

Single case reports have described success with botulinum toxin A (Kothapalli A et al. 2019), low-dose naltrexone (3.0-4.5 mg/night; Albers LN et al. 2017; Jaros J et al. 2019). The possible mechanism may be that low-dose naltrexone affects opioid or toll-like receptor signaling to enhance calcium mobilization and promote keratinocyte differentiation and wound healing.

Operative therapie
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Cryosurgery. In open spray procedure, briefly ice lesional skin, allow to thaw and immediately follow 2nd cycle. If this therapy modality does not lead to permanent success, complete excision and secondary wound healing or plastic covering with meshgraft.

Alternative: Dermabrasion of the epidermal portion can lead to complete healing, but one to several repetitions are sometimes necessary.

Alternative: Treatment with ablative laser such asCO2 or Erbium YAG laser.

Alternative: Photodynamic therapy (Yan XX et al. 2015).

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Chronic recurrent course with remissions. In about 50% of the patients leukonychia striata longitudinalis.

Case report(s)
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Medical history and clinical findings:

In a 53-year-old woman, there have been coin-sized erythema and plaques for years, partly with, partly without moist-crusty overlays, in places small-surface, painful erosions. In the area of both axillae extensive, red, rough plaques, interspersed with multiple fissures. Pronounced fetid odor here. Diagnostically groundbreaking, streak-like and punctate erosions when the skin is stretched. Nikolski phenomenon I + II positive. Currently no blisters. However, the patient had already observed these.

Histological findings:

Formation of intraepidermal clefts and blisters, In the stratum granulosum evidence of corps ronds and grains. Superficial, perivascular and interstitial infiltrate of lymphocytes with some eosinophilic granulocytes.

Direct immunofluorescence: o.B.

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Last updated on: 25.02.2022