Allergy Overview

• Nomenclature
• Pathophysiology
• Diagnosis
• Management
 Allergy
• Allergic diseases are important

• Common
• Treatable
• Morbidity
•
•
•
Cost
Intensive treatment
Co-morbid conditions
} Effect quality of life
 What‟s in a name
? ATOPY
ALLERGY

HYPERSENSITIVITY
 Hypersensitivity
• An umbrella term

• „Describe objectively reproducible

symptoms or signs initiated by exposure to
a defined stimulus at a dose tolerated by
normal persons‟
 Allergy
• Hypersensitivity reaction - initiated by an
immunological mechanism
• Antibody mediated or cell mediated
• Majority of cases - IgE isotype
– IgE-mediated allergy
• Non-IgE mediated allergy
– Allergen-specific lymphocytes
– Eosinophilic diseases
– IgA coeliac
– Direct release mechanisms
 Atopy

• „Personal or familial tendency to produce IgE

antibodies in response to low doses of allergens,
and is accompanied by typical symptoms of
asthma, rhinoconjunctivitis or eczema/dermatitis‟

• Genetic predisposition to become IgE sensitised to

allergens

• IgE sensitisation (IgE in serum or +ve SPT)

 Allergen
• Antigen causing allergic disease
• Proteins
• Carbohydrate side chains
• LMW chemicals: Haptens (e.g. isocyanates,
anhydrides)
IgE Sensitisation and elicitation
Early & Late phase IgE reaction
Allergic inflammation
Allergic Diseases
 Allergic Diseases
• Food Hypersensitivity
• Eczema
• Rhinitis
• Conjunctivititis
• Asthma
• Urticaria
• Anaphylaxis
• Drug Hypersensitivity
• Insect sting or bite hypersensitivity
 Progression of allergy
• Allergy can progress from one form to another –
the march…
• Not all children progress
Progression of allergy
 Adverse Reactions to Foods

Toxic
Non toxic
(microbiological
(food hypersensitivity)
Pharmacological)

Immune mediated Non immune mediated

(food allergy) (Food intolerance)

IgE mediated Non IgE mediated Enzymatic Pharmacological Other

 IgE vs non IgE mediated
IgE Non IgE
• Quick onset • Delayed onset
• Obvious link between • Unclear link between
exposure and symptoms exposure and symptoms
• Well defined mechanism • Mechanism unclear
• Easy to diagnose • Harder to diagnose
• Validated tests • No validated tests
 Food allergy
• Urticaria and Angioedema
• Usually • Vomiting and Diarrhoea
affects the • Anaphylaxis
younger • Food refusal
child. • Oral allergy symptoms
• Eczema flares or Chronic eczema
• 1st 18
• Difficulty swallowing
months to • Reflux
2 years • Abdominal pain
• Chronic diarrhoea
• Failure to thrive
7 years 4 year brother
Past history: Past history:
Food allergy nil
Eczema
Asthma
 Common Food Allergens
Early Life Older Children and Adults

Egg White Fish (esp. shell fish)

Cows Milk Peanuts
Soya protein Other nuts
Fish Fruit
Wheat Vegetables
Peanut Seeds and Spices
 IgE Mediated Diagnosis
• Skin test or specific IgE
• Suspected allergens
• Common allergens not yet encountered
• Don‟t test if tolerated (but remember
delayed reactions)
• Common associations
• Interpreting results
Skin tests
 Treatment
• Avoidance diets
• Only if an allergen is identified
• May require an exclusion diet and rechallenge
• Ensure dietary adequacy
• Recognition of reactions
• Treatment of reactions
• Comorbidities
• Follow Up
Urticaria
 Urticaria
• Common in general population
• About 10% of population have urticaria at
some time in their lives! Historical estimates
up to 25%!
• Prevalence of chronic urticaria 0.1-1%
• Higher risk in atopic individuals
• Large proportion of consults at allergy clinics
Clinical classification of urticaria
• Acute: Less than 6 weeks
• Chronic: Persistent longer than 6 weeks

• Episodic: Short periods intermittently, but

recurring over months / years
 Non allergic urticaria
• Direct mast cell destabilisers
• Viral infections
• Exogenous histamine
• Physical stimuli
 Physical urticarias
• Dermatographism
• Acquired cold urticaria
• Cholinergic urticaria
• Delayed pressure urticaria
• Solar urticaria
• Aquagenic urticaria
• Vibration urticaria
Dermatographism
Cold urticaria
 Non IgE mediated allergic
urticaria
• Papular urticaria
Papular urticaria
Chronic Autoimmune Urticaria
2

1
Autoimmune antibodies in C”I”U
40% OF CASES
• Anti-IgE (5%)
• Anti-IgE receptor (35%)

NB. Thyroid antibodies

15-25% in adults
about 4% in children
(parallel phenomenon)
ASST
ASST
 Drug treatment of chronic urticaria
• Antihistamines
2nd generation
3rd generation
Combinations
• Response to antihistamines*
Good 44%
Partial 39%
No response 17%
* Champion HC. Br J Dermatol 1998;138:635
 Additional therapy
• General advice
• Avoidance of triggers
• Antihistamine manipulation
• H2 receptor add on
• Leukotriene-receptor antagonists add-on
• Omalizumab*
• Low dose cyclosporin (short term)*
• Oral corticosteroids (short term) *
* Specialized units
 Additional therapy
• General Advice
• Explanation and information
• Counselling what urticaria is NOT
• Cooling lotions eg calamine, menthol in aqueous cream

• Avoidance of triggers
• Aspirin, NSAIDS, codeine, morphine, ACE inhibitors
• Stress, overheating, alcohol, tight clothes
• Strawberries, tomatoes, strong cheese, dark fish and
fermented foods

• Preservatives
• When indicated by history, food challenges or CAST tests
• Sulphur dioxide, sodium benzoate, salicylate and tartrazine
 Mimics of urticaria
• Urticarial vasculitis
• Urticaria pigmentosa / mastocytosis
• Erythema multiforme
• Cryopyrin associated periodic syndromes
• Hereditary angioedema
Hereditary angioedema
• Hereditory angio-edema (HAE) is an
autosomal dominant condition caused by
congenital deficiency of functional C1
inhibitor.
• Patients experience attacks of swelling that
may affect any part of the body.
• Untreated, attacks occur on average every 7 to
14 days.
• It is not associated with urticaria and patients
with both urticaria and angioedema without a
family history always have a normal C1
inhibitor level.
 Anaphylaxis
• a sudden, severe, potentially fatal, systemic
allergic reaction.
• skin, respiratory tract, gastrointestinal tract,
and cardiovascular system.
• Symptoms occur within minutes to two
hours after contact with the allergy-causing
substance.
Ig E mediated Antibiotics eg B lactams, bactrim
vanco, chloramph, ampho
Foods eg peanut, fish, legumes,
egg, metabisulphites
Foreign proteins eg serum, venoms, insulin
ACTH, PTH
Therapeutic agents eg SIT, vaccines
muscle relaxants, steroids

Immune complex Blood products eg Blood, plasma

immunoglobulins
or Complement
eg Methotrexate
Drugs
Arachidonic acid Drugs eg aspirin, NSAIDs
eg Tartrazine, benzoates
Additives
Direct Hist release Drugs eg Radiocontrast,
opiates
 Variation in manifestations
Perioperative anaphylaxis
less skin manifestations
More CVS effects

Non IgE mediated anaphylaxis

More skin effects
Less CVS effects
Less bronchospasm
Lower degrees of severity
Less death
 First aid treatment
Most reactions occur in the community.

Adrenaline is an essential drug

Catecholamines increased via camp
Narrow therapeutic window
Evidence for efficacy, though strong, is anecdotal.
(No RCT possible)
1  constriction, PV resistance, oedema
2  insulin, noradrenaline
1  inotrope, chronotrope
2  bronchodilation, vasodilation, glycogenolysis
mediator release from mast cells
 S/C vs IMI

IMI 2136 pg/ml

tmax 8 +- 2 minutes

S/C 1802 pg/ml

tmax 34 +- 14 minutes

Simons, F.E.R., Gu, X., Roberts, J.R.,

Simons, K.J. Epinephrine absorption in
children with a history of anaphylaxis.
J. Allergy Clin. Immunol. 1998;101:33-37.
 Vial & Syringe

Parents slower than doctors / nurses

Parents doses varied 40 fold !!
Parents times 140 secs +- 42 secs

Simons FER, Chan ES, Gu X, Simons KJ. Epinephrine for

the out-of-hospital (first aid) treatment of anaphylaxis in
infants: is the ampule/syringe/needle method practical?
J Allergy Clin Immunol 2001;108:1040-4
 Adrenaline
Life saving.
Narrow window, widely
dispensed, not used
IMI, in date, in time.
Only 2 doses.
Avoidance, medic Alert, Action plan
Antihistamines for isolated cutaneous reactions
Adrenaline appropriate for child & parent
 Atopic Eczema usually begins
100 in infancy
90
80
70
Cases (%)

60
50
40
30
20
10
0
0–1 years 1–5 years Over 5 years
Age at diagnosis of AD

Leung DYM. Clin Exp Immunol 1997;107(Suppl 1):25–30

 Atopic Eczema Evolution

Stages : Acute Vesicular

Subacute Erythema
Scaling
Crusting
Chronic Crusting
Lichenification
 Some features in more detail

Pruritis

Hallmark of AD : “An itch that rashes”.

Subconscious scratching, excoriation, secondary infection
Irritability, restlessness, poor sleep, poor school performance
Inflammatory changes and lichenification
Old (sedating) antihistamines good for treatment of AD itch.
 Some features in more detail
Distribution
Infantile Face involved , nappy area spared
Koebner phenomenon: linear changes where
scratching has occurred
Childhood Flexoral Knee involvement from crawling
Sides of neck
Discoid patches
lichenification

Adulthood As above
Areas of sweating
Vulva, nipples
Follicular accentuation
 Atopic eczema
• Environmental control
• Treatment of acute flares
• Control itching
• Treatment of secondary infection
• “New” treatments: elidel
• Dietary management
 Chronic Treatment
Bathing
Bathing ?frequency. No bubble baths.
Lubricants that moisten and rehydrate.
Only aqueous cream for cleansing.
Vaseline or HEB to damp skin immediately after bathing
Clothing
Non-scratch clothes.
Mild soap for washing clothes, no fabric softeners.
 Treatment of Acute flare
Trunk and extremities : Wet compresses, betadine cream
Moderate potency steroid +- antiseptic
(0.1 % Betamethasone : Lenovate)
Taper steroids  emollient or tar
Face : Wet compresses, betadine cream
Mild potency steroid +- antiseptic
(1 % Hydrocortisone : Procutan)
Emollient
Treatment of Secondary Infection
Bacterial : Beta haemolytic strep or Staph aureus
Swab if chronic
Empiric treatment with Flucloxacillin or erythromycin for 10 days

Eczema herpeticum : Herpes Simplex

Vesicular eruption with umbilicated center in atopic individual.
Diagnosis by viral culture or Tzanck test.
Symptomatic treatment
Acyclovir PO < 2 yrs 100 mg 5 x daily
PO > 2 yrs 200 mg 5 x daily
IVI 5 mg / kg tds
 Food allergy and eczema
• 40 % react to food challenge
• Test before exclusion: Severe cases, early onset,
associated acute reactions
• No role for indiscriminate or long term exclusion
of important foods
• Exclusion diet up to 6 weeks with rechallenge.
• Dietician in team. Supplement vitamins, calcium.
Drinking Cow‟s Milk 2 weeks later …
Drinking Soya Milk
 Allergic Rhinitis
Intermittent Persistent
• 4 days per week • > 4 days per week
• or 4 weeks • and > 4 weeks

Moderate - Severe
Mild
One or more items:
• Normal sleep and
• Abnormal sleep
• No impairment of daily
• Impairment of daily activities,
activities, sport, leisure and
sport, leisure
• Normal work and school and
• Abnormal work and school
• No troublesome symptoms
• Troublesome symptoms
Allergic Rhinitis
Allergic rhinitis and conjunctivitis
• 42% of patients with allergic rhinitis
experience symptoms of allergic
conjunctivitis
• Conjunctivitis is a typical feature of the
patient with intermittent symptoms due to
seasonal pollens
Rhinitis associations

Asthma
Sinusitis
Sore throats
Middle ear infections
Sleep problems
Behavioral effects
Educational effects
Emotional effects
 Management
• Avoidance of triggers
• Pharmacotherapy
• Immunotherapy
• Patient education
• Regular follow-up
 Step-wise therapy of rhinitis
Increase pharmacotherapy in a step-wise fashion until
adequate control is achieved Step 3
Consider
Step 2
immunotherapy
Step 1 Nasal steroids in
recommended
Oral/nasal dose
antihistamines
or nasal
cromones
 Asthma
• What is it?
Clinical Diagnosis
recurrent wheeze and/or cough
and/or dyspnoea
responsive to bronchodilators

Wheezing apart from colds

Personal or family history of atopy
Early morning cough
Exercise induced symptoms
Seasonal variation
 Exclude other conditions
Respiratory Cardiac
infections pulmonary oedema
worms myocarditis
foreign body congenital abnormalities
lymph nodes GIT
cystic fibrosis G-O reflux disease
Vocal cord
dysfunction
Smooth muscle
Spasm

Swollen mucosa

Secretions

Scarring

Set alight-ness
 What is inflammation?
Inflammation is characterized by the presence of
activated inflammatory cells, the presence of cellular
mediators and their consequences,

which include tissue injury, and abnormal tissue

repair and restructuring (remodelling)

Inflammation and remodelling may result from

parallel or sequential pathways.
 What is inflammation / remodelling?
• Collagen deposition: basement membrane
thickening
• Increased smooth muscle mass
• mucous gland hyperplasia
• persistence of chronic inflammatory cellular
infiltrates
• release of fibrogenic growth factors
• Elastolysis
• Increased number and size of airway wall vessels
• Fragile epithelium, desquamation and
permeability in both directions
What is remodelling?
 Clinical effect of remodelling
Smooth muscle Severe bronchospasm
mass increase during exacerbations

Mucous glands Mucous secretion during

increase exacerbations

Inflammatory cell Ongoing inflammation

persistence

Subepithelial Collagen deposition on RBM

fibrosis and ECM

Elastolysis Reduced elasticity of airway

wall
 Asthma
medication
• Controllers
(preventers)
– Inhaled steroid pumps
– Long acting B2 agonists
– Leukotriene receptor
antagonists
• Relievers
– Bronchodilator pumps
– Nebulised bronchodilators
 Asthma Management

• Intermittent asthma: Beta2-agonists as needed

• Mild persistent asthma:
• Mod persistent asthma:
• Severe asthma:
Inhaled steroid (low dose)
LTRA
Inhaled steroid (med dose)
add on LABA or LTRA
Inhaled steroid (high dose)
add on LABA or LTRA
Theophylline LA
Oral steroids

Assess Control and wean down or increase

 Asthma Management

• Intermittent asthma: Beta2-agonists as needed

• Mild persistent asthma:
• Mod persistent asthma:
• Severe asthma:
Inhaled steroid (low dose)
LTRA
Inhaled steroid (med dose)
add on LABA or LTRA
Inhaled steroid (high dose)
add on LABA or LTRA
Theophylline LA
Oral steroids

Assess Control and wean down or increase

 Asthma Management

• Intermittent asthma: Beta2-agonists as needed

• Mild persistent asthma:
• Mod persistent asthma:
• Severe asthma:
Inhaled steroid (low dose)
LTRA
Inhaled steroid (med dose)
add on LABA or LTRA
Inhaled steroid (high dose)
add on LABA or LTRA
Theophylline LA
Oral steroids

Assess Control and wean down or increase

 Asthma Management

• Intermittent asthma: Beta2-agonists as needed

• Mild persistent asthma:
• Mod persistent asthma:
• Severe asthma:
Inhaled steroid (low dose)
LTRA
Inhaled steroid (med dose)
add on LABA or LTRA
Inhaled steroid (high dose)
add on LABA or LTRA
Theophylline LA
Oral steroids

Assess Control and wean down or increase

 Asthma Management

• Intermittent asthma: Beta2-agonists as needed

• Mild persistent asthma:
• Mod persistent asthma:
• Severe asthma:
Inhaled steroid (low dose)
LTRA
Inhaled steroid (med dose)
add on LABA or LTRA
Inhaled steroid (high dose)
add on LABA or LTRA
Theophylline LA
Oral steroids

Assess Control and wean down or increase

 Education
Written care plans are recommended
Symptom based action plans recommended.
Aspects of education
How to use medication
Difference between controllers & relievers
How to assess severity
A crisis plan including rescue remedy
Medic alert disc
Avoidance of precipitants
 Prevention of allergy
• Primary prevention
– Family history (but most still have –ve FH)
– Both parents 60-80%, one parent 50-80% (higher with mom)
– Neither parent 20%
• Avoid precipitants
– No dietary changes in pregnancy
– Breast feed (No diet restriction)
– If high risk and cannot BF  hydrolysed formulae (not CM,
AAF or soy)
– Introduce solids from 4-6 months. No data on later or earlier.
– Avoid exposure to cigarette smoke
– Mixed data on pets &HDM so no environmental interventions
– Mixed data on probiotics and prebiotics
 Prevention of allergy
• Secondary prevention
– Rhinitis : Better treatment helps asthma
– Immunotherapy for rhinitis reduces sensitisations and may
prevent asthma
– Asthma : Better treatment helps rhinitis
– Food allergy : Treats eczema
– Eczema … May prevent food allergy and onset of asthma
– Drugs ETAC and EPAAC