To further investigate the photoprotective properties of melanin and the role of skin-infiltrating neutrophils with respect to the damaging effects of solar radiation on human skin.
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
(a) Qualitative comparison of extra cellular matrix damage in longstanding sun
exposed vitiligenous skin and adjacent normal skin using standard haematoxylin
eosin and Elastica von Gieson staining procedures.
(b) Quantitative comparison of infiltrating neutrophils in vitiligenous and
adjacent normal skin following exposure to an equal physical dose of SSR.
(c) Determining the distribution of DNA photoproducts in vitiligenous and
adjacent normal skin following exposure to SSR.
(d) Determining the MED of Vitiligenous skin.
Secondary outcome
(a) Quantitative comparison of photoaging associated proteolytic and/or
neutrophil associated enzymes and cytokines: MMP-1, MMP-3, MMP-8, MMP-9,
Neutrophil elastase and IL-10 in irradiated vitiligenous and adjacent normal
skin.
(b) Measurement of surface markers of activation on infiltrating neutrophils:
CD11b, CD66b, CD63.
(c) Comparison of keratinocyte activation and keratinocyte apoptosis in
vitiligenous and adjacent normal skin following exposure to SSR.
Background summary
Exposure of white skin (skin phototype I-III) to erythemogenic doses of solar
simulating radiation (SSR) results in an influx of neutrophils. We have
previously shown that neutrophils are a major source of enzymatically active
photoaging-associated proteolytic enzymes. By this capacity they appear to be
important contributors to the process of photoaging of the skin. Furthermore we
have shown that neutrophils infiltrating the epidermis are a source of IL-10, a
cytokine which has been associated with photo-carcinogenesis.
Black skin (skin phototype VI) is better protected against the damaging effects
of solar radiation. Black skin is thus less susceptible to photocarcinogenesis
and photoaging. This is most likely due to abundant melanin pigment present in
the epidermis of black skin. We have shown that exposing white and black
skinned persons to equal physical doses of SSR induces a strong neutrophilic
infiltrate in white but not in black skin. Furthermore DNA photoproducts
following exposure to SSR are limited to the suprabasal epidermis in black skin
while they are distributed throughout the epidermis and upper dermis in white
skin. These findings support the hypothesis that melanin plays a major role in
the protection of skin against the deleterious effects of solar radiation.
Vitiligo is a skin disease in which melanocytes disappear from the skin and as
a consequence the production of melanin is halted. Literature shows
conflicting data on the susceptibility of vitiligenous skin to photoaging and
photo-carcinogenesis.
Study objective
To further investigate the photoprotective properties of melanin and the role
of skin-infiltrating neutrophils with respect to the damaging effects of solar
radiation on human skin.
Study design
Volunteers will be recruited from patients with vitiligo and black skin
visiting the UMC Utrecht dermatology & Allergology department and the Dutch
patient*s association for vitiligo will be approached to place an advertisement
on their website.
The first group of volunteers (n=6) will consist of elderly patients with
longstanding vitiligo. During a single visit (~ 15 minutes) two punch biopsies
(4mm diameter) will be taken from sun-exposed lesional and adjacent normal
skin.
The second group of volunteers (n=6) will visit our clinic on two consecutive
days (~ 50 and 15 minutes respectively). The minimal erythemal dose (MED) of
lesional skin will be determined (day 1) and an area of lesional and normal
skin will be exposed to 18 000 mJ per cm2 of SSR (day 1) from which two punch
biopsies (4mm diameter) will be taken twenty four hours later. Two additional
control biopsies will be taken from unexposed lesional and normal skin.
All procedures will be carried out by the principal investigator in the light
department of our outpatient*s clinic.
Intervention
see study design.
Study burden and risks
The lesions resulting from the biopsies taken may remain visible for a
prolonged period of time as hypopigmented areas. Induced redness of a small
area of the skin following determination of the MED and exposure to SSR should
cause no physical discomfort and may heal with some scaling within days.
Serious adverse events are highly unlikely. Any effect on the disease itself is
not expected. Patients will receive some financial compensation for their
participation.
Heidelberglaan 100
3584 CX Utrecht
Nederland
Heidelberglaan 100
3584 CX Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
Group I and II: adult, male or female, aged 18 years or over; patients with skin phototype VI and vitiligo; the patient must be willing and able to give written informed consent.
Group I specifically: chronic vitiligo, persistant for 10 years or more, localised on sunexposed skin.
Group II specifically: it must be technically possible to determine the minimal erythemal dose.
Exclusion criteria
sunlight allergy; tendency to hypertrophic scar or keloid formation; history of alcohol or drug abuse; treatment with phototherapy or systemic (immunosuppressive) therapy such as oral steroids and cyclosporin A during the study, or within 24 weeks prior to the study; treatment with oral and local antibiotics; treatment with topical steroids or tar in the tested locations during the last 2 weeks; clinically relevant cardiovascular, gastrointestinal, liver or renal disease and/or unstable metabolic or endocrine disorders; acute or chronic local bacterial, viral or fungal diseases; women of childbearing potential not using reliable contraception; pregnancy or breast feeding; psychiatric disease or history of noncompliance which, in the investigator*s assessment would interfere with appropriate protocol treatment and monitoring.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL18625.041.07 |