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].