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The Allergic March

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Overview

Increase in allergic conditions

  • The allergic march
  • Relationship between atopic conditions:
  • Eczema and food allergy
  • Food allergy and asthma
  • Allergic rhinitis and asthma

Allergy epidemic

Allergic conditions (eczema, food allergy, asthma, allergic rhinitis) affect 52% of UK children

Commonest long-term childhood condition in the UK

12.5 million GP visits per year

Increasing prevalence eczema 6-7yrs

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Gupta et al. Increasing hospital admissions for systemic allergic disorders in England: analysis of national admissions data. BMJ 2003;327:1142

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Asthma

Most common long-term condition to affect UK children (1 million). Phase 3 ISAAC 2000-2003 age 13-14 years

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Decreasing prevalence asthma 13-14yrs

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Asher MI, Montefort S, Bjorksten B, Lai CK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases 1 and 3 repeat multicountry cross-sectional surveys. Lancet 2006; 368(9537):733–743.

The Allergic March

Allergic conditions often co-exist

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Atopy and allergic disease

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What is the relationship?

Eczema and food allergy:

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Food allergies in children with eczema

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Clues to food allergy in eczema

  • Atopic family history
  • Early onset of eczema
  • Severity of eczema
  • Resistant to treatment
  • Gastrointestinal symptoms
  • Faltering growth

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Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

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Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

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The brick wall analogy of the stratum corneum of the epidermal barrier. In healthy skin the corneodesmosomes (iron rods) are intact throughout the stratum corneum. At the surface, the corneodesmosomes start to break down as part of the normal desquamation process, analogous to iron rods rusting (A). In an individual genetically predisposed to AD, premature breakdown of the corneodesmosomes leads to enhanced desquamation, analogous to having rusty iron rods all the way down through the brick wall (B). If the iron rods are already weakened, an environmental agent, such as soap, can corrode them much more easily. The brick wall starts falling apart (C) and allows the penetration of allergens (D).

Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

Arachis oil containing creams

90% of peanut allergic children with eczema were exposed to creams containing Arachis (peanut) oil in the first 6 months of life

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Evidence for cutaneous sensitisation

  • Severe eczema is associated with food allergy
  • The skin barrier is impaired in children with eczema
  • Topical exposure to peanut oil is associated with peanut allergy
  • High exposure to environmental peanut is associated with peanut allergy

Household peanut consumption a risk factor for peanut allergy

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Environmental exposure to food?

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Eczema modifies effect of environmental peanut exposure on peanut allergy 

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Eczema and Food allergy – Conclusions

  • 33-81% of children with moderate – severe eczema have immediate food allergies
  • Think about food allergy driving eczema in severe, early onset eczema
  • Children with inflamed, porous skin may become allergic to foods through the skin
  • Importance of using emollient to maintain the skin barrier in eczema

Food allergy and asthma

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Food allergy causes respiratory symptoms

  • 50% of food allergic children have allergic reactions involving respiratory symptoms
  • Ingested and aerosolised foods can induce allergic reactions
  • Fish, egg and cow’s milk are known to aerosolise

53. Synek M. Anto JM. Beasley R. Frew AJ. Holloway L. Lampe FC. Lloreta JL. Sunyer J. Thornton A. Holgate ST. Immunopathology of fatal soybean dust-induced asthma. European Respiratory Journal 1996; 9:54-7.

More food allergies = more asthma

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More severe food allergy = more asthma

 

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Fatal / near-fatal anaphylactic food reactions are associated with asthma 

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Patients with food allergies  and asthma should always have immediate access to inhaled beta-agonist and self-injectable adrenaline

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Food allergy and Asthma – Conclusions

  • 4 – 8 % of asthmatic patients have food allergy
  • About 50% of food allergic patients have asthma
  • Food allergy, especially multiple food allergies is associated with an increased risk of asthma
  • Severe asthmatics have 3.3 times increased risk of anaphylaxis vs. non asthmatics

Allergic rhinitis and asthma

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Allergic rhinitis and asthma

  • Asthma is increased in allergic rhinitis
    19–38% allergic rhinitis vs. 3–5% general population
  • Allergic rhinitis almost always present in asthma
    78% asthmatics vs 20% general population
  • Allergic rhinitis increases asthma severity risk
    3-fold risk of frequent wheezing attacks
    10-fold risk of frequent GP visits for asthma

Risk of developing asthma

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Allergic rhinitis treatment improves asthma control

  • Treatment of allergic rhinitis
    lower risk of asthma-related A&E visits
    lower risk of asthma-related hospitalisation
  • 47% did not have an asthma-related event
  • Hospitalisation reduced by 61%

Immunotherapy for AR prevents asthma

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Allergic rhinitis & Asthma – Conclusions

  • 80% of asthmatic patients have allergic rhinitis
  • Patients with allergic rhinitis have an increased risk of developing asthma
  • Especially patients with house dust mite allergy
  • United airway approach
  • Allergic rhinitis increases risk of asthma severity
  • Treating allergic rhinitis improved asthma control

Look for all allergic conditions

  • Active and early treatment of eczema to repair the skin
  • Think about food allergy in early onset severe eczema
  • Patients with food allergies and asthma
  • Need to ensure that asthma is well controlled
  • Should always have immediate access to an inhaled beta-agonist and self-injectable adrenaline
  • Treatment of allergic rhinitis improves asthma control
  • Immunotherapy in allergic rhinitis may prevent asthma

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Acknowledgements

  • Gideon Lack
  • George Du Toit
  • Adam Fox
  • Kerry Richards
  • Asha Sudra
  • Alexandra Santos
  • Victor Turcanu
  • Alick Stephens
  • Martin Penagos
  • Suzana Radulovic
  • Monica Basting
  • Adnan Custovic
  • Angela Simpson
  • Nicolaos Nicolaou
  • Irwin McLean
  • Sara Brown
  • Hugh Sampson
  • Andy Liu
  • Scott Sicherer
  • Marshall Plaut
  • Peter Sayre
  • Action Medical Research
  • National Peanut Board
  • Immune Tolerance Network
  • Food Allergy Research & Education
  • Biomedical Research Centre

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Learning Early About Peanut Allergy

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Talk about:

  • These data are out of date – NS survey / audit
  • Evolution of immune system development during first year of life
  • Immune tolerance – low dose Treg vs high dose thymic effects
  • Manifestations of GI food allergy change with age
  • Rates of waning of allergy differ with different food allergens

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Cutaneous Route

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Hygiene hypothesis

Breast-feeding
Conflicting evidence (protective vs. risk)
Reverse causality
Unable to do RCT (Belarus study had no effect)

Breastfeeding has been associated repeatedly with a protective effect against both eczema (72) and asthma in early life (73). However, recent studies, including one from our
group, have linked both breastfeeding and prolonged breastfeeding with increased eczema (74) and asthma risks (75,76). Methodological issues may explain the discrepancies between studies that assess the association between breastfeeding and allergic diseases (77). Ethically it is not possible to randomize mother-baby pairs to breastfeeding. A recent study overcame this by randomizing maternity hospitals in Belarus with historically lowrates of breastfeeding to either a breastfeeding promotion arm or no intervention (78). Despite increased breastfeeding in the intervention groups, there was no significant difference in the rate of asthma, allergic rhinitis, or eczema between the groups. In summary, the role of breastfeeding as a risk factor for both eczema and asthma is far from clear.

The premise of the hygiene hypothesis is that exposure to microbial factors in infancy induces the immune system to switch from the dominant Th2 response present at birth to a dominant Th1 response associated with normal immune function (79). If that switch is not made and the Th2 response remains dominant, the immune system is primed for allergic diseases

 

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