DISCUSSION:
Hailey-Hailey Disease(HHD), a relatively uncommon genodermatosis, was described initially by the Hailey Brothers in 1939. It has an estimated incidence of 1 in 50000 with equal predilection towards either sex [1]. It is usually diagnosed after puberty, predominantly in the third and fourth decade of life, however symptoms have been known to develop at any age[5].
Hailey Hailey disease is inherited in an autosomal dominant pattern [1]. It is associated with mutations in the ATPase calcium-transporting type 2C member 1 gene(ATP2C1) gene[3]. The ATP2C1, located on chromosome 3q22 was initially recognized as the causative gene responsible for HHD by two independent studies in 2000 [6,7]. This 27 exon gene is responsible for encoding SPCA1, a secretory pathway Ca2+/Mn2+-ATPase, which is responsible for regulating intracellular Ca2+ homeostasis. Misfolding or downregulation of the SPCA1 protein interferes with Ca2+ sequestration, leading to Ca2+ depletion in the Golgi lumen [8]. Golgi Ca2+ is vital for protein processing, and its depletion may impair the processing of junctional proteins necessary for cell-to-cell adhesion [9].
Hailey-Hailey disease(HHD) commonly presents as flaccid vesicles or bullae, which may progress to crusted erosions and macerations. The most commonly implicated areas are the intertriginous regions [10]. Extracutaneous symptoms are not evident and systemic involvement is not seen. There are rare instances of mucosal involvement, however cases of conjunctival, oral, vulvar and esophageal involvement have been reported [11]. In our study, the patient presented with a history of pruritic skin lesions affecting bilateral groin, scrotum and axilla, primarily affecting intertriginous areas.In addition, no mucosal or systemic symptoms were noted in the patient. HHD is known to have a chronic course with episodes of remission and relapses, and is usually aggravated by mechanical factors such as sweating, heat, infection and friction [12]. In our case, the patient was found to have a relapsing-remitting course of the disease, as well as similar aggravating factors were noted.
Differential diagnosis includes intertrigo, fungal infection, psoriasis, extramammary Paget’s disease, acanthosis nigricans, Darier’s disease and pemphigus vulgaris [13]. HHD poses a significant diagnostic challenge to the dermatologist due to its close resemblance to other dermatoses of flexural areas [4]. In our case, the delay in the diagnosis of HHD resulted in a prolonged disease course of 3 years with multiple episodes of relapses.
Diagnosis is usually based on histopathological findings which shows lacunae formed by suprabasal acantholysis, which later progresses to acantholytic vesicles and bullae. A characteristic dilapidated brick wall appearance is often present [14].
There is no specific therapy for HHD therefore, management primarily includes control of aggravating factors, secondary skin infections and cutaneous inflammation. Which includes topical, systemic therapy wide excision of lesion or laser therapy. Topical therapy involves application of antibiotics , steroids, tacrolimus and calcitriol whereas systemic therapy with antibiotics, steroids, methotrexate, tacrolimus, dapsone and thalidomide can be used [15,16,17]. Wide excision of affected area and replacement by split graft can be done for recalcitrant lesions[18]. Erbium-YAG and CO2 laser ablation are other effective treatment options[19,20].