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.

Treatment for Benign Familial Pemphigus focuses on managing symptoms and preventing flare-ups. Topical treatments, such as corticosteroids and antibiotics, can help reduce inflammation and prevent secondary infections. In some cases, systemic medications like oral antibiotics or immunosuppressants may be prescribed. Patients are advised to avoid triggers such as heat and friction, and to maintain good skin hygiene. Moisturizers and barrier creams can help protect the skin and reduce irritation.

The prognosis for Benign Familial Pemphigus is generally good, as the condition is not life-threatening. However, it is a chronic disorder with no cure, and patients may experience recurrent episodes throughout their lives. With appropriate management, most individuals can control symptoms and lead normal lives. The severity and frequency of flare-ups can vary widely among patients, and some may experience long periods of remission.

Benign Familial Pemphigus is caused by mutations in the ATP2C1 gene, which plays a crucial role in regulating calcium levels in skin cells. These mutations lead to impaired cell adhesion, resulting in the formation of blisters and erosions. The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene from an affected parent can cause the disorder.

Benign Familial Pemphigus is a rare condition, with an estimated prevalence of 1 in 50,000 individuals. It affects both males and females equally and typically presents in adulthood, although symptoms can appear at any age. The condition is more common in individuals with a family history of the disorder, reflecting its genetic basis.

The pathophysiology of Benign Familial Pemphigus involves a defect in the ATP2C1 gene, which encodes a calcium pump essential for maintaining cell adhesion in the skin. This defect leads to a breakdown in the connections between skin cells, resulting in the formation of blisters and erosions. The condition is exacerbated by factors that increase friction and sweating, which further disrupt cell adhesion.

Currently, there is no known way to prevent Benign Familial Pemphigus, as it is a genetic disorder. However, individuals with a family history of the condition can take steps to minimize flare-ups by avoiding known triggers such as heat, friction, and sweating. Maintaining good skin care practices and using protective clothing can also help reduce the risk of exacerbations.

Benign Familial Pemphigus is a rare genetic skin disorder characterized by recurrent blistering and erosions in areas of friction. It is caused by mutations in the ATP2C1 gene and is inherited in an autosomal dominant pattern. While there is no cure, the condition can be managed with topical and systemic treatments, and by avoiding triggers. The prognosis is generally good, with most patients able to control symptoms and maintain a good quality of life.

If you have been diagnosed with Benign Familial Pemphigus, it's important to understand that while the condition is chronic, it is not life-threatening. Managing the disease involves regular skin care, avoiding triggers, and using prescribed treatments to control symptoms. Keep in close contact with your healthcare provider to monitor your condition and adjust treatments as needed. Remember, you are not alone, and support is available to help you manage this condition effectively.

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.