Benign Familial Pemphigus (Hailey Hailey Disease)

Definition: Benign familial pemphigus (BFP), also known as “Hailey- Hailey Disease”  is a rare autosomal dominant blistering dermatosis that was discovered in 1939.

Etiology: BPH is a hereditary skin disorder caused by variations or mutations in the ATP2C1 gene. This gene is found on chromosome 3q21-24 and is responsible for encoding the protein hSPCA1 (Human Secretory-Pathway Ca2+/Mn2+-ATPase Isoform 1) localized at the Golgi apparatus. These are primarily loss-of-function mutations. Due to resulting insufficient calcium, keratinocytes cannot stick together due to improper desmosome assembly. 15- 30% of cases are due to sporadic gene mutations or undiagnosed disease in other family members. 

Epidemiology: The prevalence of BFP is estimated to be 1/50.000. There is no clear predilection for the sexes or any ethnic groups. Clinical findings of BFP typically present in the third and fourth decades of life.

Signs: Studies suggest that environmental factors and genetic modification may alter the way BFP is expressed clinically. Lesions typically present as symmetrical crusted skin rashes involving the intertriginous regions, inframammary folds and the vulva (female), and rarely, the conjunctival, oral, esophageal, and vaginal mucosa. On fair skin tones, this irregular pattern has pink and white areas separated by pink furrows “cloud pattern”. On deeper skin tones, irregular brown-grayish-black areas with a “crumpled fabric pattern” and crusting may be evident.

Symptoms: BFP lesions are painful and erosive. Lesions that have been present for a long time may become thickened and macerated, which can worsen pain levels. Lesions are intermittent and may discharge a foul-smelling exudate upon rupture. Patients may experience worse symptoms where heat, sweating and friction exacerbate symptoms.

Differentials:  Darier disease, Grover disease, Candidiasis, Pemphigus vulgaris/vegetans

Diagnosis: Diagnosis of BFP is made clinically and supported by skin histopathology. Dermoscopy may be used in early diagnosis.

Treatment: There is no cure for BFP. Treatment focuses on alleviating symptoms and preventing flare-ups. You may be advised to avoid trigger factors such as heat and tight clothing. Topical corticosteroids and antibiotics may be prescribed to treat inflamed lesions.

References:

1.     Hailey-Hailey disease (benign familial pemphigus) | DermNet NZ. dermnetnz.org. https://dermnetnz.org/topics/benign-familial-pemphigus

2.     ‌Konstantinou MP, Krasagakis K. Benign Familial Pemphigus (Hailey-Hailey Disease). In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 14, 2023.

3.     Żychowska M, Kołt-Kamińska M, Kijowski R, Reich A. Hailey-Hailey disease exacerbated by scabies: the role of dermatoscopy in preventing misdiagnosis. Postepy Dermatol Alergol. 2023;40(4):567-570. doi:10.5114/ada.2023.130477

4.     Ben Lagha I, Ashack K, Khachemoune A. Hailey-Hailey Disease: An Update Review with a Focus on Treatment Data. Am J Clin Dermatol. 2020;21(1):49-68. doi:10.1007/s40257-019-00477-z