M. Hailey-Hailey: hSPCA1 Expression and Skin Structure Upon Laser Therapy

Expression of hSPCA1 and Ultrastructural Analysis of the Skin Before and After Laser Therapy in Hailey-Hailey Disease

Hailey-Hailey disease is a genetic acantholytic dermatosis characterized by continuous erosion of the skin that results in a burning, painful sensation and restricts the patient in daily life. This disorder results from a genetic defect in a calcium pump, i.e. the hSPCA1 pump. Calcium pumps are crucial for the processing of cell-cell adhesion proteins such as E-cadherin, part of desmosomes, the major glue between keratinocytes in skin epidermis. Today therapy is mainly focussed on symptom relief and prevention of secondary infection. Ablative laser therapy is known to result in a speedy healing of the affected skin site within 2 weeks following laser therapy. The fact that the treated skin site remains clear from this acantholytic disorder in the months/years following ablation, regardless the existence of a germline mutation, suggests that an epigenetic modification occurs in the process of wound healing. Objective: to (1) study the expression of hSPCA1 in keratinocytes before and after laser therapy and (2) verify the loss of acantholysis by immunohistochemistry and electron microscopy of cell-cell adhesions before and after laser therapy

Patients with Hailey Hailey, diagnosis confirmed by histopathology or genetics, with therapy resistant skin lesions suitable for ablative lasertherapy. Skin biopsy specimens will be taken before and after lasertherapy at three time points. Before treatment: Affected skin 4 mm punch for immunofluorescence and RNA extraction 2 mm for electron microscopy Healthy skin within same anatomical region 4 mm punch for immunofluorescence and RNA extraction Immediately after treatment of the treated area: 2 mm punch for histopathology Six weeks after treatment: Treated skin 4 mm punch for immunofluorescence and RNA extraction 2 mm for electron microscopy

Skin biopsy: Tissue samples will be taken by punch biopsy according to the daily routine of the Department of Dermatology of the Maastricht UMC+. Steps: Skin desinfection with chlorhexidine digluconate 1% solution Local anaesthesia with lidocaine hydrochloride 1% Biopsy specimens are taken with sterile punch device (disposable biopsy punch delivered by kai medical) Biopsy specimens are retrieved with sterile pincer and cut with sterile blade Wound is stitched with a single transcutaneous stich using absorbable suture (vicryl 4.0). Wound will be treated with R/ fusidic acid ointment 3 to 5 times per day for two weeks In the first week after laser therapy the wound will be covered by R/ Urgotull non-adhesive gauze, R/ Cutisoft cotton non-sterile gauze and R/ Klinipress exsupad absorbing bandage.

Cell-to-cell adhesion and desmosome ultrastructure before and after ablative treatment by electron microscopy.

Expression and localization of desmosomal proteins before and after ablative therapy by immunofluorescence.

Expression and localization of desmosomal proteins before and after ablative therapy by immunofluorescence.

Inclusion Criteria: Clinically diagnosed M. Hailey-Hailey as confirmed by histopathology and/or genetic analysis. Indication for ablative laser therapy >18 years old Informed consent Exclusion Criteria: <18 years old Treatment with tetracyclines, topical hormones or oral retinoids within the last 30 days preceding participation Lack of informed consent

Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 in cultured keratinocytes.

https://www.ncbi.nlm.nih.gov/pubmed/?term=The+coexistence+of+Darier's+disease+and+Hailey-Hailey+disease+symptoms.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Efficacy+of+erbium%3AYAG+laser+ablation+in+Darier+disease+and+Hailey-Hailey+disease

https://www.ncbi.nlm.nih.gov/pubmed/?term=Carbon+dioxide+laser+treatment+for+Hailey-Hailey+disease%3A+a+retrospective+chart+review+with+patient-reported+outcomes.

Carbon dioxide laser treatment for Hailey-Hailey disease: a retrospective chart review with patient-reported outcomes.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Laser+therapy+for+the+treatment+of+Hailey-Hailey+disease%3A+a+systematic+review+with+focus+on+carbon+dioxide+laser+resurfacing.

Laser therapy for the treatment of Hailey-Hailey disease: a systematic review with focus on carbon dioxide laser resurfacing.