Hailey and Hailey Disease - Literature review Example

Hailey and Hailey Disease Chronic skin diseases are challenging to dermatologists and allied health services because of the waxing and waning nature of the disease, difficulty in establishing diagnosis and possible side effects to the treatment. Etiologies vary and genetic disorders often run in families. One such chronic genetic skin disorder is Familia lbenign pemphigus, commonly known as Hailey and Hailey disease. The disease is autosomal dominant and affects only specific areas of skin where heat, friction and perspiration occur like axilla, groin, under the breast, etc (Warycha et al, 2009). The lesions are symmetrical, itchy and burning. Sometimes some foul smelling discharge can be present which can contribute to the misery of the patient. The disease is difficult to diagnose and challenging to treat. Many treatment modalities are available and there are no clear guidelines as to who has to be treated with what medication. Complications can occur, which are however not life-threatening. It is very important to understand the pathophysiology of the disease process to establish diagnosis and provide appropriate treatment. In this research article, the causes, pathophysiology and few treatment aspects of the disease will be discussed through review of appropriate literature. Hailey and Hailey disease, also known as Familial benign pemphigus, is an inherited skin disorder (Helm, 2012). It is a chronic autosomal disorder with incomplete penetrance. It was first described by Hailey brothers in 1939 and hence the name (Helm, 2012). According to Rooks Text Book of Dermatology, “Familial benign chronic pemphigus or Hailey–Hailey disease (Mendelian Inheritance in Man (MIM) accession number 169600) is a rare intraepidermal, blistering disease that is inherited as an autosomal dominant with a prevalence of around 1 in 50 000.” (Burns et al, 2010). Patients with this condition present with lesions of the skin. The lesions are mainly erythematous plaques and vesicles with overlying crusts. Areas which are mainly involved are genital regions, axillary regions, under the breasts, neck and chest (Helm, 2012). The lesions have a burning sensation and are itchy. There can be a malodorous discharge when a secondary bacterial infection occurs. The disease mainly involves the skin and not the mucosa. Nails also can get involved, but they are asymptomatic. Nails can have white longitudinal bands. Pits can also occur in the palms. Longitudinal leukonychia may help in establishing the diagnosis (Rao, 2013). The lesions leave no scars when they go. As the lesions become bigger, the central area clears, giving a typical ring shape. However, if the lesions remain for sometime due to either lack of appropriate treatment or non-response to treatment, they become thickened. The thickened skin macerates and leads to painful cracks. Family history is noted in most of the cases (Helm, 2012). Symptoms typically occur in the 3rd or 4th decade of life. Hower, there are some cases reported in late childhood and adolescence (Helm, 2012). Secondary fungal and bacterial infections are common. The course of the disease involves multiple relapses and remissions (Helm, 2012). The lesions are usually symmetrical. Unusual sites of involvement are conjunctiva, vulva and mucosa. Hailey and hailey disease may rarely present as erythroderma. Often, the lesions are triggered by dermatoses, infectionsrelated to bacteria or fungi and trauma. One of the rare complications is eczema herpeticum. It is common for the lesions to recur in sites of previous involvement (Rao, 2013). The main pathogenesis is decreased number of desmosomes in the skin (Helm, 2012). Desmosomes hold the keratinocytesin the skin togenther. They have calcium-binding transmembrane glycoproteins because of which cellular adhesion occurs. In this disease, there is a primary defect in the calcium pump protein, ATP2C1, localized on chromosome 3 and this leads to keratinocyte adhesion defect. ATP2C1 mainly encodes the Ca2+/Mn2 ATPase (hSPCA1) secretory pathway. Rarely, sporadic cases occur (Helm, 2012; Sudbrak, 2000). When mutation of this occurs as in Hailey and Hailey disease, it leads to loss of sensitivity to calcium and manganese ion binding and transport. When calcium ion levels are low within the Golgi bodies, impairment of protein processing occurs (Helm, 2012). The calcium ion concentrations of cytosol play a major role in the regulation of the differentiation of keratinocytes. Increased intracellular calcium ions trigger the expression of a protein called involucrin that enveloped the keratinocytes (Leinonen et al, 2009). This particular protein is responsible for keratinocyte adhesion (Rao, 2013). In addition to the genetic defect, contributing factors which can exacerbate the disease are infection, friction and heat which result in separation of keratinocytes, especially in the intertriginous areas. Other pathological changes include changes in keratinocyte morphology like retracted tonofilaments, reduced number of desmosomes and elongated membrane microvilli (Helm, 2012). The common differential diagnoses for Hailey and Hailey disease include intertrigo, erythrasma, autoimmune pemphigus diorders, pyoderma vegetans, tinea corporis and tinea cruris. Variants of Hailey and hailey disease include seborrheic dermatitis and segmental unilateral disease. Perianal disease may simulatecondyloma accuminata (Rao, 2013). The main diagnostic test is biopsy and histopathological examination. Characteristic histopathological finding is intraepidermal and suprabasilar acantholysis (Warycha et al, 2009). Layers of detached keratinocytes is described as acantholysis. Direct immunofluorescence test is negative and this differentiates from pemphigus vulgaris. Nikolsky sign is also negative and Tzanck test does not reveal giant cells as in herpes virus infection (Helm, 2012). The disease waxes and wanes inintensity. The most commonly used treatment is cold soothing compression with aluminium acetate 1:40 dilution (Helm, 2012). During exacerbations, intermittent use of mild class 5 or class 6 corticosteroids are recommended along with topical antibiotics like clindamycin and erythromycin. If the flares are widespread systemic antibiotics will need to be administered to cause suppression of protease activation and acantholysis. The most favored antibiotics are erythromycin and tetracycline. Appropriately antibiotic therapy may be instituted using bacterial culture and sensitivity (Warycha et al, 2009). Refractory and severe cases may need advanced treatments like systemic corticosteroids, dapsone therapy, methotrexate, retinoids and etretinate. Topical tacrolimus ointment is also useful in controlling flares of the disease. Another useful treatment modality in recalcitrant cases is photodynamic therapy with 5-aminolevulinic acid. There are some reports that low doses of botulinum toxin type A may be useful in certain cases. Hyperhidrosis isone of the main aggravating factor of the disease and controlling it is considered to be a novel approach in preventing relapses in Hailey and Hailey disease (Helm, 2012). Most of the patients with Hailey and Hailey disease can be treated successfully on out-patient basis (Warycha et al, 2009). Those who are involved in manual labour may need to take off from work so that their folds can heal properly. Patients with Hailey and Hailey disease need regular evaluation to monitor secondary infection and side effects of long term corticosteroid therapy. Those on intermittent sytemic corticosteroids must be evaluated for osteoporosis and adequate diet to maintain normal bone density must be advised. Any suspicious infiltrated area must be investigated with biopsy. Other treatments which have been used with some success rates in difficult cases are oral acitretin, intramuscular alefacept, topical cadexomer iodine powder, narrow band ultraviolet B phototherapy and long-pulsed alexandrite laser (Warycha et al, 2009). Surgical options for the patients are carbondioxide laser abrasion, dermabrasion and pulsed dye laser therapy (Helm, 2012). Patients are advised to shed excess weight by consuming appropriate diet to avoid friction as a exacerbating factor. Patients are advised to live and work in areas that do not contribute to heat, friction and moisture. They must dress appropriately to avoid these exacerbating factors (Helm, 2012). To conclude, Hailey and Hailey disease is also known as familial benign pemphigus. It is an autosomal dominant disorder with incomplete penetrance. Two third of the patients with the disease have a family history of the disorder. It occurs due to mutation of the ATP2C1 gene on chromosome 3q21-q24. This gene is responsible for controlling the concentrations of calcium ions in the Golgi apparatus and cytoplasm in the keratinocytes of human beings. Treatment of the condition is difficult. But improvement can be established by a wide range of drugs including systemic or tropical antibiotics, antifungals, corticosteroids, retinoids, dapsone, topical calcineurin inhibitors, botulinum toxin, dermabrasion, photodynamic therapy, carbondioxide laser and grafting. References Burns, T., Breathnach, S., Cox, N., Griffiths, C. (2010). Hailey–Hailey disease. In: Rooks Textbook of Dermatology. Pg 437- 448. Helm, T.N. (2012). Familial Benign Pemphigus (Hailey-Hailey Disease) Clinical Presentation. Medscape Reference. Retrieved on 25th March 2014 from http://emedicine.medscape.com/article/1063224-clinical#a0218 Leinonen, P.T., Hagg, P.M., Peltonen, S., et al. (2009). Reevaluation of the normal epidermal calcium gradient, and analysis of calcium levels and ATP receptors in Hailey-Hailey and Darier epidermis. J Invest Dermatol. Jun 2009;129(6):1379-87. Rao, A.G. (2013). Hailey–Hailey Disease on Sun-Exposed Areas. Indian Journal of Dermatology, 58(5), 412. Sudbrak, R., Brown, J., Dobstone, C., et al. (2000). Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Calcium pump. Human Molecular Genetics, 9(7), 1131- 1140. Warycha, M., Patel, R., Meehan, S., et al. (2009). Familial benign chronic pemphigus (Hailey-Hailey disease). Dermatol Online J., 15(8), 1. Read More