Download Allergic Diseases

Allergy and Allergic Diseases
• Incidence steadily rising
• Trebling in the last 20 years
• 1/ /3 of the population will develop clinical
allergic condition
• Amongst the highest rates in the World
• Costs – Quality of Life issues
3 million consultations costing £300 million;
70,000 Admissions costing £80 million; £1
billion drugs expenditure
Allergic Diseases – adverse,
heightened immunological responses
(hypersensitivity) to external agents
“The Atopic March”
Food Allergy
Infancy
Atopic Eczema Dermatitis
Toddlers
Allergic Rhinitis
Age
Asthma
School Age
Anaphylaxis
Acute Urticaria
Allergic disease prevalence
• Asthma
X 6 in Children
X 3-4 in Adults
Population Prevalence
12 – 15%
Atopic Dermatitis
Allergic Rhinitis
Food Allergy …also
increasing
Anaphylaxis… 7-fold
Asthma / Allergic Disease Genetics
• Strong Genetic Association
Cytokine genes – IL-4, IL-5, IL-10, TGF-b
IgE receptor genes
LPS responsiveness genes
Skin barrier function genes - fillagrin
Twin Concordance 75%
1 affected parent - 40%
2 Affected Parents - 60%
Same Disease - Even Higher
… but genes do not explain the growing prevalence
Asthma Epidemiology
Socioeconomic factors
•West Germany Vs East Germany
Prevalence Studies
Inverse relationship with:
• Family Size
•Family Order
•Day Care in Early Years Outside the Home
Asthma Prevalence Vs GNP per
capita; adapted from ISAAC study
•Place of residence – Farm / Animal exposure Vs City
The Hygiene Hypothesis
Western Countries
•Less Infectious Diseases
•More Antibiotic Use
•Better Sanitation
Centers for Disease Control, Atlanta
… Promotion of Allergic Immune Responses
The Infant Immune System
TH2 Bias
•All Infants
TH1
Increasing Age
•TH1-mediated diseases
are also increasing
X2 Multiple Sclerosis
X3 Crohn’s Disease
•TH1 and TH2 diseases coexist in many patients
The Infant Immune System – Normal Maturation
TH2 Bias
•All Infants
TH1
Increasing Age
Regulatory T
IL-4, IL-5, IL-13
TNF-a; IFNg; IL-10;
TGF-b
Controlled Inflammation
Allergy Investigation
• HISTORY
• Laboratory tests (RASTs)
/ in-vivo – skin testing –
IgE-dependent
• Challenges – Useful;
Experienced; Monitored
setting
• Usefulness – Disease /
Interpreter
• Alternative testing – no
basis in logic
Allergy Management
Anti-Inflammatory Treatments
•Corticosteroids
•Leukotriene Inhibitors
•Anti-histamines
Effector Antagonists
b-2 agonists
•Adrenaline
Allergen Avoidance
•Variable effects a
disease
Allergy Management cont./
Immune Manipulation
•Conventional Immunosuppression
Variable
Not Widespread
•Allergen Desensitization Therapy / Immunotherapy
Molecular engineering
Allergen sequencing
IgG4 / TGF-b production
•TH Redirection
M. Vaccae
Probiotic therapies
Allergen / Cytokine / CpG motif Conjugate “Vaccines”
Allergy Management cont. 2/
Anti-IgE Therapy
•Humanised Mouse MAb
Omalizumab
•Asthma
Reduced steroid use;
hospitalization; rescue
treatments
Reduced IgE; IgE
Receptor
FDA Approval 2003
Incorporation in Asthma
Guidelines
Stopping the Cascade
ANAPHYLAXIS
+/ - Stridor; Breathing / Speaking Difficulty; Hypotension; Collapse;
GI Symptoms
Epidemiology
•Sharp increase
•Under-reported
•30 – 950 / 100,000 / year – US
meta-analysis
•0.5 – 2.0% lifetime
prevalence
•1 / 12 / year recur
•UK – 75 / 100,000 / year
•Fatalities – 1 / 2.5 million /
year; lower in children
Triggers
• Potentially anything – careful history
Commonest • Foods – peanuts; Other tree nuts; fish and
shellfish; milk
• Venoms – wasp, bee
• Drugs – penicillins; anaesthetics; ASA and
NSAIDs; ACEIs
• Other Medical – Contrast media; Latex
Why Does This Happen?
Foods
peanut; egg; milk;
seafoods
Drugs
penicillins; suxamethonium; Mabs
Latex
Venoms
Adrenaline Autoinjectors
• UK Resuscitation Council Guidelines
• Irish Consensus Document from IGI – IMJ Jan
2008
– Definite
–
–
–
–
Anaphylaxis in Asthma
Limited access to care
Trace amount triggers
Severe hypotension ( venoms)
– Probably
– High incidence of Severe reactions ( nuts / shellfish)
– Comorbidities
– No
– Asthma alone; positive skin tests alone; clear avoidable trigger;
positive family history
Food Sensitivity and Other Allergic
Disorders
• Does Food Allergy
Cause Other
Conditions?
• Asthma
• Severe acute reactions
• Early food allergy positively
predicts later asthma
• Younger > Older
• Consider in difficult asthma
• Urticaria
• Atopic Eczema
• Co-existence of
conditions
• High Frequency of
RAST / PST Positivity
• Severe > Mild; Younger
> Older
• Exclusions
• Challenges
Asthma / Allergy Prevention
•Food allergen avoidance /
Breastfeeding
- food allergy prevention
-Other allergic disorders ?
Early Allergen Exposure
•Exposure to allergens in infancy e.g.
house dust mite; food antigens; pollens
-- IgE production
Early food exposure as a preventative in
at risk infants?
•Conflicting evidence re: pet exposure
•RESEARCH