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

Not Applicable
Completed
Conditions
Hailey Hailey Disease
Interventions
Procedure: Skin biopsy
Registration Number
NCT03849989
Lead Sponsor
Maastricht University Medical Center
Brief 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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Hailey-Hailey diseaseSkin biopsyPatients 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 2mm punch biopsy of clinically uninvolved skin of the upper arm for electron microscopy Patients without Hailey-Hailey disease: 2mm punch biopsy of skin of the upper arm for electron microscopy
Primary Outcome Measures
NameTimeMethod
hSPCA1 expressionAssessed 6 weeks after ablative treatment

Expression of the hSPCA1 calcium pump in keratinocytes after ablative treatment

Secondary Outcome Measures
NameTimeMethod
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.At 0 weeks and 6 weeks after ablative therapy

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.

Expression and localization of desmosomal proteins before and after ablative therapy by immunofluorescence.At 0 weeks and 6 weeks after ablative therapy

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

Trial Locations

Locations (1)

Maastricht University Medical Center

🇳🇱

Maastricht, Limburg, Netherlands

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