To determine the relationship between phenotypic, genetic and biochemical features of AD. , Relevant bimarkers of the skin barrier function including the levels of NMFs, inflammatory mediators (e.g. IL-1 cytokines), SC lipids and serine proteases…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Clinical and biochemical parameters in relation to the presence of AD and FLG
mutations.
Secondary outcome
Establishment of different phenotypes of AD based on the relationschip FLG
genotype and biochemical parameters
Background summary
Atopic dermatitis (AD) is the most common pediatric skin disorder in developed
countries affecting 15-30% of children. Since 2006 it is known that
loss-of-function mutations in the filaggrin gene (FLG) are a major predisposing
factor for AD and concomitant asthma1. Up to 40% of AD patients carry at least
one FLG mutation. Furthermore, infants with FLG mutations are associated with
early onset and more severe disease when compared to infants without this
mutation2. Approximately 10% of individuals of European ancestry are
heterozygous carriers of a loss-of-function mutation in FLG resulting in a 50%
reduction in expressed filaggrin protein1.
Filaggrin plays an important role in the formation of the epidermal barrier,
which is profoundly impaired in AD. Filaggrin is present in the granular layer
of the epidermis, where it aggregates keratin filaments, leading to the
collapse of the keratinocytes into the flattened corneocytes and thus the
stratum corneum (SC). Filaggrin is further metabolised into amino acids, the
so-called natural moisturizing factors (NMFs), which contributes to epidermal
hydration and maintaining of the acid skin mantle1. Recent studies have shown
that reduced levels of NMFs are associated with impaired skin barrier and dry
skin, altered composition of SC lipids, elevated pH, and enhanced levels of
IL-1 cytokines likely modified through altered activity of serine proteases
(KLK7 and KLK5).
Despite recent insights into AD pathogenesis many questions remain unanswered
about the mechanisms through which filaggrin deficiency and environmental
factors modify the course of AD. In particular, little is understood about the
role of intrinsic and environmental factors responsible for a large spectrum of
disease phenotypes seen in children, such as severity and persistence the
development of IgE mediated sensitization leading to clinical manifestation of
allergic rhinoconjunctivitis and asthma in some, but not all children, the
sensitivity of some children to develop frequent bacterial and viral
superinfections, and hypersensitivity to sunlight leading to exacerbation of AD
in some patients. Furthermore, some children develop an allergic contact
dermatitis on top of their AD, making it difficult to determine the true course
of the AD on itself. Beside these phenotypic variations in the clinical course
of AD, one can also distinguish phenotypic variations in clinical manifestation
of AD, such as for example AD with nummular eczema as the main presentation, AD
with a prominent prurigo nodularis component, AD that is more dominant on the
extensor surfaces in stead of the typical flexural locations, and a papular,
mainly acral, form of AD. These phenotypic variations seem to suggest that AD
is not just one disease, but a heterogeneous group of similar but separate
entities. It would be useful to try to separate these entities in well defined
clinical subgroups, in order to enable further prospective cohort or
intervention studies tailored to these different clinical phenotypes. Next to
clinical parameters, it is important to identify relevant biomarkers of skin
barrier and immune profile to define these clinical subgroups that might be
used in such studies
Study objective
To determine the relationship between phenotypic, genetic and biochemical
features of AD. , Relevant bimarkers of the skin barrier function including the
levels of NMFs, inflammatory mediators (e.g. IL-1 cytokines), SC lipids and
serine proteases will be investigated in relation to the presence of disease
and FLG mutations.
This may aid us in dissecting different AD subtypes, enabling individualised
therapeutic approaches.
Study design
mono-centre case - control cohort study.
Study burden and risks
there are no health risks and only minor burden associated with participation
in this study.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
100 children with atopic dermatitis, male or female, aged between 0 and 12 years, will be participating in this study.;50 children without any skin disorder or atopy (such as food allergy, allergic rhinoconjunctivitis and allergic asthma), as well as no atopy in first degree relatives, male or female, aged between 0 and 12 years, will be participating as controls
Exclusion criteria
For Cases:
No clinically skin lesion to obtain tape strips from.
Use of corticosteroids or other anti-inflammatory topical treatment on the skin lesion(s) selected for tape stripping 1 week prior to the procedure.
Use of emollients, soap, and cosmetics on the skin lesion(s) selected for tape stripping 48 hours prior to and during the hospital visit day.
Use of oral antihistamin 1 week prior to the hospital visit day.
- Onset of atopic dermatitis after the age of 2
- History of remission of atopic dermatitis without treatment (except emollients) for longer than 1 year ;For controls:
history of atopy or first degree relative with atopy
Use of emollients, soap, and cosmetics on the skin lesion(s) selected for tape stripping 48 hours prior to and during the hospital visit day.
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 | NL47401.018.13 |