Familial benign pemphigus, initially described in Hailey brothers in the 1930s (hence the term Hailey-Hailey disease), is a rare blistering skin disease caused by mutations in the ATP2C1 gene coding for cellular electrolyte transporters that are essential in maintaining cell-to-cell adhesion [1] [2] [3]. The autosomal dominant pattern of inheritance is the reason why family history is the most important risk factor for its development [4] [5] [6] [7]. The onset of symptoms is typically observed during the second, third, and fourth decades of life, although patients of all ages have been reported in the literature [4] [5]. The hallmark of familial benign pemphigus is the recurrent appearance of vesicles, erosions, and plaques in intertriginous areas (in a symmetrical fashion) - the groins, submammary regions, the axillae, and the neck [1] [4] [5] [6] [7]. Skin lesions are painful, often pruritic, and have a foul smell [1]. Furthermore, heat, excessive sweating, friction, trauma, stress, and constrictive clothes have been shown to aggravate symptoms [1] [4] [5] [6]. Nail fragility is an important non-cutaneous finding in these patients [4] [5]. Although the clinical course varies from patient to patient, the lesions heal spontaneously without therapy and recur several times throughout the patient's life [1] [8]. Unfortunately, some patients may experience a significant impairment of their quality of life due to familial benign pemphigus [8].

• Localized Pain

  Tolerance was overall acceptable with local pain during and shortly after irradiation being the main limiting factor. [ncbi.nlm.nih.gov]

• Gingival Ulceration

  The lesions involved neck, sub-mammary and inguinal folds, associated with frequent gingival ulcerations since the age of 36 years. Her mother, aunt and two sisters were also affected by cutaneous lesions only. [medicaljournals.se]

• Blister

  Benign familial pemphigus, also known as Hailey-Hailey disease, is a rare familial blistering skin disorder characterized by recurring skin lesions in intertriginous areas that are exacerbated by heat, sweating, and friction. [symptoma.com]

  The painful blisters break and sometimes become infected and raw, with new blisters forming over raw skin in a sometimes seemingly unending cycle of outbreaks. [en.wikipedia.org]

  These are crusty blisters that tend to form on your chest, back, and shoulders. They don’t hurt, but they do itch. How is Pemphigus Diagnosed? It can be tricky. That’s because a number of conditions can cause blisters. [webmd.com]

  Upregulation of P-cadherin may be involved in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases. [thedoctorsdoctor.com]

  Blisters can accompany some types of skin rashes and inflammatory conditions, including certain autoimmune diseases. Depending upon the cause of the blisters, blisters may occur singly or in groups. [medicinenet.com]

• Leukonychia

  Electron beam radiotherapy Dermabrasion Glycopyrrolate Afamelanotide Clinical images Images hosted on other servers: Hailey-Hailey in right axilla Hyperpigmented plaques over groin Hailey-Hailey lesions on left groin Figure 2b: Showing longitudinal leukonychia [pathologyoutlines.com]

  Patients with Hailey-Hailey disease may also have nail manifestation called ‘longitudinal leukonychia’ which are longitudinal white bands on the fingernails. [aocd.org]

  In patients with limited or atypical disease, longitudinal leukonychia may serve as a diagnostic clue. [therapeutique-dermatologique.org]

  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. [e-ijd.org]

• Palmar Hyperhidrosis

  Efficacy and safety of botulinum toxin type a in the treatment of palmar hyperhidrosis: A double-blind, randomized, placebo-controlled study. Dermatol Surg 2002;28:822-7. 10. Lowe PL, Cerdan-Sanz S, Lowe NJ. [ijdd.in]

The diagnosis of familial benign pemphigus can only be made with a detailed patient history and a meticulous physical examination that provides sufficient data for clinical suspicion of this rare blistering skin disorder. In addition to the assessment of the course and progression of symptoms, patients must be asked about the familial presence of symptoms, which may be the crucial detail in narrowing the differential diagnosis. On the other hand, observing typical cutaneous findings in intertriginous areas and associated symptoms can be quite helpful. One of the key features of familial benign pemphigus is the absence of antibody deposition on immunofluorescence testing [4] [5], the principal method for assessing and stratifying other blistering skin lesions (Pemphigus, Pemphigoid, etc.). For this reason, a histopathological examination of lesions is critical. Generalized suprabasal loss of cellular adhesions (known as acantholysis), resembling a dilapidated brick wall appearance, is the hallmark of familial benign pemphigus [4] [8]. Other notable findings on histology are dyskeratosis and preservation of the dermis [5] [8]. Thus, a combination of clinical criteria, a positive family history, and microscopic examination of the skin comprise the diagnostic workup of this rare, but potentially debilitating skin blistering disease.

• Polyps

  Upper and lower digestive endoscopies showed superficial erosions in the lower oesophagus, no lesion in the gastric or duodenal mucosa, a caecal polyp, and lesions of angiodysplasia in the left colon. [medicaljournals.se]

1. Hunt R, O'Reilly K, Ralston J, Kamino H, Shupack JL. Familial benign chronic pemphigus (Hailey-Hailey disease). Dermatol Online J. 2010;16(11):14.
2. Durr G, et al. The medial-Golgi ion pump Pmr1 supplies the yeast secretory pathway with Ca2+ and Mn2+ required for glycosylation, sorting, and endoplasmic reticulum-associated protein degradation. Mol Biol Cell. 1998;9:1149.
3. Hakuno M, 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.
4. Warycha M, Patel R, Meehan S, et al; Familial benign chronic pemphigus (Hailey-Hailey disease). Dermatol Online J. 2009;15(8):15.
5. Tchernev G, Cardoso JC. Familial benign chronic pemphigus (Hailey-Hailey Disease): use of topical immunomodulators as a modern treatment option. Rev Med Chil. 2011;139(5):633-637.
6. Graham PM, Melkonian A, Fivenson D. Familial benign chronic pemphigus (Hailey-Hailey disease) treated with electron beam radiation. JAAD Case Rep. 2016;2(2):159-161.
7. Gisondi P, Sampogna F, Annessi G, Girolomoni G, Abeni D. Severe impairment of quality of life in Hailey-Hailey disease. Acta Derm Venereol. 2005;85(2):132-135.
8. Arora H, Bray FN, Cervantes J, Falto Aizpurua LA. Management of familial benign chronic pemphigus. Clin Cosmet Investig Dermatol. 2016;9:281-290.