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. The diagnosis rests on clinical criteria, a positive family history and typical findings on histopathological examination, while immunofluorescence, typically used for this group of disorders, is negative.
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].
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.