This summary was compiled from the tweets posted by allergists/immunologists who attended the 2013 annual meeting of the American Academy of Allergy Asthma and Immunology (AAAAI) (see the list at the end). The tweets were labeled #AAAAI. The text was edited and modified by me.Alan Irvine MD presented on the Role of filaggrin mutations in human disease and allergic sensitization.
Filaggrin is a filament aggregating protein. Stratum corneum is compromised in patients with filaggrin mutation. Staphylococcus aureus colonization can be increased in patients with filaggrin mutation, due to dysregulation of skin pH.
Filaggrin mutations are highly associated with eczema and ichthyosis vulgaris. Early onset asthma in patients with atopic dermatitis is also highly associated with filaggrin mutation. Other associations with filaggrin mutation include peanut sensitization.
Allergic (atopic) march (click here to enlarge the image).
10% of population has a filaggrin mutation (1:10 European carries 1 null filaggrin mutation). One null allele is associated with milder atopic dermatitis than having no filaggrin at all.
Cat exposure in patients with filaggrin mutation is nearly always associated with atopic dermatitis.
The bottom line is that a filaggrin mutation in patients with eczema markedly increases risk of developing atopic sensitization and asthma. Overall risk is asthma increased by 50% with filaggrin mutation and AD. 40% of people carrying Filaggrin null allele develop asthma.
Peanut allergy risk is 5.4 times higher with filaggrin mutation.
Vicious cycle: FLG mutation --> defective skin barrier --> allergen entry/sensitization --> Th2 inflammation --> inhibits FLG expression.
AD cycle: 1. Mutational defect, 2. Defective barrier, 3. Entry of allergens, 4. Th2 based inflammation, then go back to 1.
For known FLG deficient patient siblings, avoid cat exposure and soaps.
Keep in mind that filaggrin is not the only genetic problem that leads to atopic dermatitis and atopy.
Atopic dermatitis
Dr. Donald Leung presented on atopic dermatitis and the skin barrier.
Scratching
If children with atopic dermatitis are allowed to scratch they will develop chronic papules with lichenification that are hard to heal. Damaged skin barrier from excoriation then becomes a nidus for infection and allergen absorption.
TSLP
Tape stripping of the skin is a model of scratching - it causes a sharp rise in TSLP levels within an hour of the stripping. TSLP is the "master switch" to polarize towards Th2 responses - hence it is an exciting target to block in novel therapeutics for AD.
Th22 cells infiltrate acute AD lesions, produce IL-22 and promote skin damage; they are also important in the chronic phase.
Filaggrin
Reminder that AD skin is filaggrin-deficient, leading to increased permeability; it increases risk of food allergy and eczema herpeticum. Filaggrin mutations/deficiency also associated with respiratory allergy as well. Filaggrin deficiency also predisposes to damage mediated by Staph aureus alpha toxin. Phenotypes of AD are very different if Filaggrin deficient vs. not filaggrin deficient; better prognosis if filaggrin levels normal.
Lisa Beck has published a detailed review of atopic dermatitis in the Feb 2013 volume of J Allergy Clin Immunol.
Laminin is a basement membrane protein - there are recently identified mutations in its gene in some patients.
Figures:
Allergists are on Twitter - follow them
Allergists increased Twitter use 470% in one year - 25 allergists reached 250,000 individuals from the 2012 #AAAAI meeting (see the references here). This summary was compiled from some of the tweets posted by the following allergists:
https://twitter.com/allergistmommy
https://twitter.com/ananth720
https://twitter.com/DrAnneEllis
https://twitter.com/IgECPD
https://twitter.com/DrYesimDem
https://twitter.com/MatthewBowdish
This is a list of the allergists who used Twitter to post updates from the 2013 #AAAAI meeting. The list is open for edit, please feel free to add your own info.
I would strongly encourage you to post updates on Twitter from the CME conferences that you are planning to attend in the future. Here is how to do it: Twitter for Physicians: How to use Twitter to keep track of the latest news and scientific meetings, and share information with colleagues and patients.
Disclaimer: The text was edited, modified, and added to by me. This is one of a series of posts that will be published during the next few weeks.