Pemphigus chronicus benignus familiaris Q82.8

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

All authors of this article

Last updated on: 18.12.2020

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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. Several mutations were detected on the genes BCPM and ATP2C1, which are mapped on chromosome 3q21-24. The ATP2C1 gene encodes a Golgi associated Ca-ATPase (SERCA2), which is responsible for the Ca content in the Golgi apparatus. A decrease of the Ca level leads to defective processing of different adhesion molecules (E-cadherin), insufficient cell-to-cell adhesion and acantholysis. S.a.u. 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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Intertrigo; candidiasis; tinea corporis; pemphigus vegetans; dyskeratosis follicularis; tinea inguinalis.

Notice. In 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 in smaller foci with weak to moderately strong 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 externa the 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 like 1% Scandicain Lsg.)
  • Successful therapy attempts with Tacrolimus (e.g. Protopic) are described casuistically (Off-Label-Use!).
  • Often the foci 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 environment).
  • Alternatively, glucocorticoid/antiseptic or glucocorticoid/antiseptic/antifungal combinations can be used, e.g. 0.5% Clioquinol/Hydrocortisone Cream R051, Clioquinol/Flumethasone Cream (Locacorten Vioform), Triclosan/Flumethasone (Duogalen) or Nystatin/Fluprednide Acetate Paste(e.g. Candio-Hermal Plus Paste). Cave! In Intertrigines there is an increased risk of local glucocortical side effects!

Internal therapy
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  • The therapy as a whole 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 individual 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 (Albers LN et al. 2017; Jaros J et al. 2019).

Operative therapie
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  • Cryosurgery. In the open spray procedure, briefly freeze lesional skin, allow to thaw and immediately follow with the 2nd cycle. If this therapy modality does not lead to a permanent success, complete excision and secondary wound healing or plastic covering with meshgraft.
  • Alternative: Dermabrasion of the epidermal portion may lead to complete healing, but repetition once or several times is sometimes necessary.
  • Alternative: Treatment with ablative lasers such asCO2 or Erbium-YAG lasers.
  • 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 coin-sized erythema and plaques have been present for years, partly with and partly without moist crusty deposits, in some cases with painful erosions of small areas. In the area of both axillae large, red, rough plaques, interspersed with multiple fissures. Pronounced foetal odour here. Diagnostically path-breaking, lineal and punctiform erosions when the skin is tightened. Nikolski phenomenon I + II positive. Currently no blisters. However, the patients have already observed them.
  • Histological findings:
  • Formation of intraepidermal clefts and blisters, in the stratum granulosum evidence of corps ronds and grains. Superficial, perivascular and interstitial infiltrate from lymphocytes with some eosinophil granulocytes.
  • Direct immunofluorescence: o.B.

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  1. Albers LN et al (2017) Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone. JAMA Dermatol 153:1018-1020.
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  3. Choi DJ et al (2002) Hailey-Hailey disease on sun-exposed areas. Photodermatol Photoimmunol Photomed 18: 214-215.
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  5. Gougerot H (1933) Forme de transition entre la dermatite polymorphe douloureuse de Brocq-Duhring et le pemphigus congénital familial héréditaire. Annales de dermatologie et de syphiligraphie (Paris) 5: 255
  6. Hailey H, Hailey H (1939) Familial benign chronic pemphigus. Report of 13 cases in 4 generations of a family and report of 9 additional cases in 4 generations of a family. Arch Derm Syph 39: 679-685
  7. Hamm H et al (1994) Hailey-Hailey Disease. Eradication by dermabrasion. Arch Dermatol 130: 1143-1149
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  11. Kieffer J et al (2018) Treatment of Severe Hailey-Hailey Disease With Apremilast. JAMA Dermatol 154:1453-1456.
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Last updated on: 18.12.2020