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

Hailey Hailey Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03849989
• Other study ID #: 64815
• Status: Completed
• Phase: N/A
• Start date: December 21, 2018
• Est. completion date: March 15, 2024

Study information

• Verified date: February 2019
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: March 15, 2024
• Est. primary completion date: March 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

1.Inclusion criteria 1.1.Hailey-Hailey patients

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 1.2. Patients without Hailey-Hailey disease
• >18 years old
• Clinically no symptoms of M. Hailey-Hailey
• 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

Related Conditions & MeSH terms

• Hailey Hailey Disease

Intervention

Procedure:
• Skin biopsy
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.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	hSPCA1 expression	Expression of the hSPCA1 calcium pump in keratinocytes before ablative treatment	Assessed at time point 0 weeks
Primary	hSPCA1 expression	Expression of the hSPCA1 calcium pump in keratinocytes after ablative treatment	Assessed 6 weeks after ablative treatment
Secondary	Ultrastructure of the skin before and after ablative treatment by electron microscopy and comparison to clinically uninvolved skin and skin of patients without Hailey-Hailey disease.	Cell-to-cell adhesion and desmosome ultrastructure before and after ablative treatment by electron microscopy and comparison to clinically uninvolved skin and skin of patients without Hailey-Hailey disease.	At 0 weeks and 6 weeks after ablative therapy
Secondary	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.	At 0 weeks and 6 weeks after ablative therapy

External Links

•   Carbon dioxide laser treatment for Hailey-Hailey disease: a retrospective chart review with patient-reported outcomes.
•   Carbon dioxide laser treatment in Hailey-Hailey disease: a series of 8 patients.
•   Efficacy of erbium:YAG laser ablation in Darier disease and Hailey-Hailey disease.
•   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.
•   Laser therapy for the treatment of Hailey-Hailey disease: a systematic review with focus on carbon dioxide laser resurfacing.
•   The coexistence of Darier's disease and Hailey-Hailey disease symptoms.