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Allergy and anaphylaxis
• Definitions
• Basic immunology of allergy
• Testing for specific IgE
• Food allergy
• Insect allergy
• Drug allergy
• Anaphylaxis
• Management of anaphylaxis
Definitions (EAACI/WAO)
• Hypersensitivity is objective reproducible symptoms
or signs, initiated by exposure to a defined stimulus
that is tolerated by normal subjects
• Allergy is immune mediated hypersensitivity
• Allergens are antigens, usually proteins, that cause
allergy
• Atopy is a personal and/or familial tendency to
become sensitised (ie. produce IgE) in response to
normal exposure to allergens, with development of
asthma, rhinoconjunctivitis and eczema
• Anaphylaxis is a severe potentially life-threatening
systemic allergic reaction characterised by rapid
onset of life-threatening airway breathing of
circulatory problems, and is usually but not always
associated with skin or mucosal changes
Allergy Nomenclature
Hypersensitivity
Allergic hypersensitivity
(immunological mechanism
defined or strongly suspected)
Non-allergic hypersensitivity
(immunological mechanism
excluded)
IgE-mediated Non IgE-mediated
IgE
Mast cells
Sensitisation
1.1
Sensitisation
1.2
Allergy = allergen specific IgE and symptoms upon
exposure to allergen
1.4
Ref: ASCIA 20101.7
Signs and symptoms of allergy and anaphylaxis
Some individuals experience anaphylaxis without prior mild or
moderate symptoms
Testing for Specific IgE
• Skin prick testing
• Intradermal testing
• Serum fluoroenzymeimmunoassay (AKA
ImmunoCap, “RAST”)
• Basophil activation assays (whole blood)
Detection of specific IgE in serum
Principle
• Allergen in solid phase
• Patient serum containing
specific IgE
• Detection
ALLERGEN
Detection Ab
IgE
Skin Prick Testing
t = 1 minute
t = 4 min
t = 8 min
t = 10 min
t = 15 min
Rye grass 8mm
Bermuda grass 7mm
Johnson grass 9mm
Bahia grass 9mm
Ragweed 6mm
D. pteronyssinus 10mm
D. farinae 8mm
Cat dander 6mm
Dog dander 5mm
Mould mix 4mm
Positive control 6mm
Negative control
Serum tryptase
Ref: Simons, Camargo. 2010; Yunginger, Squillace et al. 1989; Sampson, Menderson et al. 1992.
• Serum tryptase should be measured within 4 hours after anaphylaxis
• Serum tryptase is often normal after food anaphylaxis
3.9
Food allergy can be IgE mediated
and/or non-IgE mediated
IgE mediated food allergy
• Acute urticaria/angioedema
• Contact urticaria
• Anaphylaxis
• Immediate gastrointestinal hypersensitivity
• Food-dependent exercise induced anaphylaxis
• Oral allergy syndrome (food-pollen allergy
syndrome)
Food allergy or food intolerance?
Food intolerance:
• does not involve the immune system
• does not result in IgE mediated reactions including anaphylaxis
• symptoms can sometimes resemble those of mild or moderate
food allergy
There is no reliable skin or blood test to diagnose food intolerances
Diagnosis of food allergy and risk of anaphylaxis should always be
medically confirmed
1.2
Food allergy
Whilst 90% of food allergic reactions are caused by allergic reactions to
these foods, any food can cause an allergic reaction
1.11
Food allergy is common
2.3
In Australia:
• Children < 1yr: 10%
• Children < 5 yrs: 4-8%
• Adults: up to 2%
Natural history of food allergy
• Peanut, tree nut, fish, sesame and shellfish allergies
usually persist
• Milk, egg, soy and wheat allergy commonly resolve
• 85% of young children in population based studies
outgrow their allergy to milk or egg by age 3-5 years
2.4ref: http://foodallergens.ifr.ac.uk Skripak, JACI 2007, Savage, JACI 2007.
Cause of Allergic ReactionPercent
Peanut 60% 0.190968 37
Tree nut 27% 0.087742 17
Fish 2% 0.005161 1
Milk 8% 0.025806 5
Shrimp 3% 2
62
0% 10% 20% 30% 40% 50% 60% 70%
Peanut
Tree nut
Fish
Milk
Shrimp
Percent of Cases
Cause of Fatal Anaphylaxis
Common causes of fatal food anaphylaxis
Ref: Pumphrey, Garland. 2007 2.8
Shrimp (prawn)
AATHP 28 August 2011
• Majority of food-allergic individuals need to eat >500 mg
• Significant minority reacts to lower amounts
*Lowest Observed Adverse Effect Levels (LOEALs)
• Touching or smelling the allergen may cause mild/moderate
reaction but unlikely to cause anaphylaxis
Ref: Pumphrey. 2004, http://foodallergens.ifr.ac.uk, VITAL, 2007. 2.9
Small amounts of food can trigger anaphylaxis in
some very sensitive individuals
Oral allergy syndrome
1.3
Aero-
allergen
Homologous
food allergen
• Mild oral
symptoms
• ≈ 7%
anaphylaxis
Oral allergy syndrome
• Occurs in response to physical exertion
• Symptoms only occur if exercise within few hours of eating
specific food/s
• Most common foods:
– Wheat, other grains and nuts in Western populations
– Wheat and shellfish in Asian populations
– Fruits, vegetables, seeds, legumes, various meats, cow’s milk
and egg
• Symptoms include extreme fatigue, warmth, flushing, pruritus
and urticaria progressing to anaphylaxis
• Diagnosis usually based on clinical history
• Avoid culprit food/s for at least 4-6 hours before exercise
Food dependent exercise induced anaphylaxis
1.11
Insect stings are a common trigger of
anaphylaxis
7.1
Common triggers:
• Honey Bees (most common)
• Paper wasps
• European Wasps (becoming more common)
• Australian Jack Jumper Ant stings
7.2
Bites less commonly trigger anaphylaxis than
insect stings
Although bites are common in endemic areas, anaphylaxis
is rarely triggered by:
• Ticks
• Mosquitoes
• March Flies
Reactions
• Typical local reactions:
– Erythema and painful swelling (up to 5cm) that
develops within minutes and resolves within hours
• Large local reactions
– 10%
– 10cm
– Peak at 48 hours and resolve over 5 – 10 days
– Risk of systemic reactions 5 – 15%
– May be IgE mediated
• Anaphylaxis
• Systemic toxic reactions
– Dose dependent
• Unusual reactions
– Toxic or non-IgE immune mediated
– Serum sickness like syndromes
– Hypersensitivity vasculitis
• Anyone with insect venom
anaphylaxis should be referred to a
clinical immunology/allergy
specialist, even if no immunotherapy
to allergen currently exists
• Adrenaline autoinjector should be
prescribed for all patients with
anaphylaxis to insect venom;
consider alert bracelet
When to refer for immunotherapy – insect venom
allergy
36
Drug allergy allergy
Adverse reactions to drugs is a significant problem, however allergic reactions (IgE
mediated) are rare:
• Antibiotics
– Uncommon
– Testing is only available for a limited range of antibiotics
• General anaesthetics
– Rare
– Specialised testing required
• Local anaesthetics
– Rare
– Vasovagal reactions are common
• Vaccination
– Rare, occurs in approximately 1/250,000 doses
• NSAIDS
– The majority of reactions are not IgE mediated
– IgE mediated reactions to NSAID are characterised by urticaria, angioedema or
anaphylaxis
1.13Ref: Up-to-date, 2010
Anaphylaxis
• Anaphylaxis is a severe potentially life-
threatening systemic allergic reaction
characterised by rapid onset of life-
threatening airway breathing of circulatory
problems, and is usually but not always
associated with skin or mucosal changes
Triggers of anaphylaxis
Common
• Foods
• Insects
• Medications
Uncommon
• Latex
• Exercise (with or without food)
• Cold temperature
• Immunisation (rare)
• Unidentified (idiopathic)
1.6
112 anaphylaxis deaths in Australia between
1997 and 2005
Anaphylaxis deaths by
cause and age group
Fatal anaphylaxis - associations
• Asthma
• Delayed or no administration of adrenaline
• Age:
– Teenagers and young adults (food allergy)
– Adults (insect and drug allergy)
• Upright posture during anaphylaxis
• Food allergic individuals eating away from home
• Initial misdiagnosis
• Systemic mastocytosis
Previous mild/moderate reactions may not rule out subsequent
severe or fatal reactions
Ref: Bock. 2010; Liew, Williamson, Tang. 2008; Bock. 2007; Pumphrey. 2003; Bock. 2001
2.7
Signs of anaphylaxis
• Difficult/noisy breathing
• Swelling of the tongue
• Swelling or tightness in throat
• Difficulty talking and/or hoarse voice
• Wheeze or persistent cough
• Persistent dizziness or collapse
• Pale and floppy (young children)
Mild or moderate signs and symptoms may not
always precede anaphylaxis
All individuals at risk of anaphylaxis should:
• Know what to do in an emergency
• Have an ASCIA Action Plan for Anaphylaxis completed by their
medical practitioner
• Carry an adrenaline autoinjector and know how to use it
Management of anaphylaxis anaphylaxis
1.5
Why is adrenaline effective?
• Inhibits the release of inflammatory mediators
• Reverses the physiological effect of mediators by:
– Reducing airway mucosal oedema
– Inducing bronchodilatation
– Inducing vasoconstriction (thus increasing HR & BP)
– Increasing strength of cardiac contraction
Lasts ~ 15-20 minutes; repeated doses may be needed
after 5 minutes if no response
Ref: Tole, Lieberman. 20074.4
There are two brands of adrenaline autoinjectors –
EpiPen® and Anapen®
• Junior devices (150µg) recommended for
children 10 to 20 kg (aged ~1-5 years)
• Higher dose devices (300µg) recommended for
children over 20 kg (aged over ~5 years) and
adults
EpiPen Jr Anapen Jr
Anapen
5.2
EpiPen
Orange needle end
Blue safety
release
Viewing window
EpiPen with orange needle end and blue safety release
Expiry date
Instructions on
how to use
(on other side)
5.5
• Available in Australia mid 2011
How to give EpiPen with orange needle end and blue safety
release
5.6
Patient’s
photo and
personal
details
Confirmed
allergens
Contact details
for family and
doctor
Adrenaline
autoinjector
brand name
Signs, symptoms,
action for mild or
moderate
allergic reactions
Instructions
on how to
use the
device
Signs, symptoms,
action for
anaphylaxis
Additional
information
6.3
PBS supply of adrenaline autoinjectors in Australia
• Maximum of 2 (EpiPen or Anapen) for both children and adults
• Initial supply:
– When risk and clinical need has been assessed by, or in
consultation with a clinical immunologist, allergist,
paediatrician or respiratory physician
– After hospital or emergency department discharge for acute
allergic anaphylaxis treated by adrenaline
• Continuing supply for anticipated emergency treatment of acute
allergic reactions with anaphylaxis, where the patient has
previously been issued with an authority prescription for this
drug
5.14
Guidelines for prescribing an adrenaline autoinjector
Always recommended if…
•History of anaphylaxis (and continued risk)
•These patients should be referred to a clinical immunology/allergy
specialist
May be recommended if…
•History of a generalised allergic reaction and one or more risk
factors:
– Asthma
– Age (children >5 yrs, adolescents, young adults)
– Specific allergic triggers
– Co-morbidity (e.g. ischaemic heart disease)
– Geographical remoteness from emergency medical care
•These patients should be referred to a clinical immunology/allergy
specialist
5.15
Guidelines for prescribing an adrenaline autoinjector
Not normally recommended...
• Asthma with no history of anaphylaxis nor generalised allergic
reactions
• Positive allergy test without a history of clinical reactions
• Family history of anaphylaxis or allergy
• Bee stings
− local reactions only (children and adults)
− generalised rash only (children)
• These patients generally do not need referral to a clinical
immunology/allergy specialist
5.16

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Allergy and Anaphlaxis

  • 2. • Definitions • Basic immunology of allergy • Testing for specific IgE • Food allergy • Insect allergy • Drug allergy • Anaphylaxis • Management of anaphylaxis
  • 3. Definitions (EAACI/WAO) • Hypersensitivity is objective reproducible symptoms or signs, initiated by exposure to a defined stimulus that is tolerated by normal subjects • Allergy is immune mediated hypersensitivity • Allergens are antigens, usually proteins, that cause allergy • Atopy is a personal and/or familial tendency to become sensitised (ie. produce IgE) in response to normal exposure to allergens, with development of asthma, rhinoconjunctivitis and eczema
  • 4. • Anaphylaxis is a severe potentially life-threatening systemic allergic reaction characterised by rapid onset of life-threatening airway breathing of circulatory problems, and is usually but not always associated with skin or mucosal changes
  • 5. Allergy Nomenclature Hypersensitivity Allergic hypersensitivity (immunological mechanism defined or strongly suspected) Non-allergic hypersensitivity (immunological mechanism excluded) IgE-mediated Non IgE-mediated
  • 6. IgE
  • 10. Allergy = allergen specific IgE and symptoms upon exposure to allergen 1.4
  • 11. Ref: ASCIA 20101.7 Signs and symptoms of allergy and anaphylaxis Some individuals experience anaphylaxis without prior mild or moderate symptoms
  • 12. Testing for Specific IgE • Skin prick testing • Intradermal testing • Serum fluoroenzymeimmunoassay (AKA ImmunoCap, “RAST”) • Basophil activation assays (whole blood)
  • 13. Detection of specific IgE in serum Principle • Allergen in solid phase • Patient serum containing specific IgE • Detection ALLERGEN Detection Ab IgE
  • 15. t = 1 minute
  • 16. t = 4 min
  • 17. t = 8 min
  • 18. t = 10 min
  • 19. t = 15 min Rye grass 8mm Bermuda grass 7mm Johnson grass 9mm Bahia grass 9mm Ragweed 6mm D. pteronyssinus 10mm D. farinae 8mm Cat dander 6mm Dog dander 5mm Mould mix 4mm Positive control 6mm Negative control
  • 20. Serum tryptase Ref: Simons, Camargo. 2010; Yunginger, Squillace et al. 1989; Sampson, Menderson et al. 1992. • Serum tryptase should be measured within 4 hours after anaphylaxis • Serum tryptase is often normal after food anaphylaxis 3.9
  • 21. Food allergy can be IgE mediated and/or non-IgE mediated
  • 22. IgE mediated food allergy • Acute urticaria/angioedema • Contact urticaria • Anaphylaxis • Immediate gastrointestinal hypersensitivity • Food-dependent exercise induced anaphylaxis • Oral allergy syndrome (food-pollen allergy syndrome)
  • 23. Food allergy or food intolerance? Food intolerance: • does not involve the immune system • does not result in IgE mediated reactions including anaphylaxis • symptoms can sometimes resemble those of mild or moderate food allergy There is no reliable skin or blood test to diagnose food intolerances Diagnosis of food allergy and risk of anaphylaxis should always be medically confirmed 1.2
  • 24. Food allergy Whilst 90% of food allergic reactions are caused by allergic reactions to these foods, any food can cause an allergic reaction 1.11
  • 25. Food allergy is common 2.3 In Australia: • Children < 1yr: 10% • Children < 5 yrs: 4-8% • Adults: up to 2%
  • 26. Natural history of food allergy • Peanut, tree nut, fish, sesame and shellfish allergies usually persist • Milk, egg, soy and wheat allergy commonly resolve • 85% of young children in population based studies outgrow their allergy to milk or egg by age 3-5 years 2.4ref: http://foodallergens.ifr.ac.uk Skripak, JACI 2007, Savage, JACI 2007.
  • 27. Cause of Allergic ReactionPercent Peanut 60% 0.190968 37 Tree nut 27% 0.087742 17 Fish 2% 0.005161 1 Milk 8% 0.025806 5 Shrimp 3% 2 62 0% 10% 20% 30% 40% 50% 60% 70% Peanut Tree nut Fish Milk Shrimp Percent of Cases Cause of Fatal Anaphylaxis Common causes of fatal food anaphylaxis Ref: Pumphrey, Garland. 2007 2.8 Shrimp (prawn)
  • 28. AATHP 28 August 2011 • Majority of food-allergic individuals need to eat >500 mg • Significant minority reacts to lower amounts *Lowest Observed Adverse Effect Levels (LOEALs) • Touching or smelling the allergen may cause mild/moderate reaction but unlikely to cause anaphylaxis Ref: Pumphrey. 2004, http://foodallergens.ifr.ac.uk, VITAL, 2007. 2.9 Small amounts of food can trigger anaphylaxis in some very sensitive individuals
  • 29. Oral allergy syndrome 1.3 Aero- allergen Homologous food allergen • Mild oral symptoms • ≈ 7% anaphylaxis
  • 31. • Occurs in response to physical exertion • Symptoms only occur if exercise within few hours of eating specific food/s • Most common foods: – Wheat, other grains and nuts in Western populations – Wheat and shellfish in Asian populations – Fruits, vegetables, seeds, legumes, various meats, cow’s milk and egg • Symptoms include extreme fatigue, warmth, flushing, pruritus and urticaria progressing to anaphylaxis • Diagnosis usually based on clinical history • Avoid culprit food/s for at least 4-6 hours before exercise Food dependent exercise induced anaphylaxis 1.11
  • 32. Insect stings are a common trigger of anaphylaxis 7.1 Common triggers: • Honey Bees (most common) • Paper wasps • European Wasps (becoming more common) • Australian Jack Jumper Ant stings
  • 33. 7.2 Bites less commonly trigger anaphylaxis than insect stings Although bites are common in endemic areas, anaphylaxis is rarely triggered by: • Ticks • Mosquitoes • March Flies
  • 34. Reactions • Typical local reactions: – Erythema and painful swelling (up to 5cm) that develops within minutes and resolves within hours • Large local reactions – 10% – 10cm – Peak at 48 hours and resolve over 5 – 10 days – Risk of systemic reactions 5 – 15% – May be IgE mediated • Anaphylaxis
  • 35. • Systemic toxic reactions – Dose dependent • Unusual reactions – Toxic or non-IgE immune mediated – Serum sickness like syndromes – Hypersensitivity vasculitis
  • 36. • Anyone with insect venom anaphylaxis should be referred to a clinical immunology/allergy specialist, even if no immunotherapy to allergen currently exists • Adrenaline autoinjector should be prescribed for all patients with anaphylaxis to insect venom; consider alert bracelet When to refer for immunotherapy – insect venom allergy 36
  • 37. Drug allergy allergy Adverse reactions to drugs is a significant problem, however allergic reactions (IgE mediated) are rare: • Antibiotics – Uncommon – Testing is only available for a limited range of antibiotics • General anaesthetics – Rare – Specialised testing required • Local anaesthetics – Rare – Vasovagal reactions are common • Vaccination – Rare, occurs in approximately 1/250,000 doses • NSAIDS – The majority of reactions are not IgE mediated – IgE mediated reactions to NSAID are characterised by urticaria, angioedema or anaphylaxis 1.13Ref: Up-to-date, 2010
  • 38. Anaphylaxis • Anaphylaxis is a severe potentially life- threatening systemic allergic reaction characterised by rapid onset of life- threatening airway breathing of circulatory problems, and is usually but not always associated with skin or mucosal changes
  • 39. Triggers of anaphylaxis Common • Foods • Insects • Medications Uncommon • Latex • Exercise (with or without food) • Cold temperature • Immunisation (rare) • Unidentified (idiopathic) 1.6
  • 40. 112 anaphylaxis deaths in Australia between 1997 and 2005
  • 42. Fatal anaphylaxis - associations • Asthma • Delayed or no administration of adrenaline • Age: – Teenagers and young adults (food allergy) – Adults (insect and drug allergy) • Upright posture during anaphylaxis • Food allergic individuals eating away from home • Initial misdiagnosis • Systemic mastocytosis Previous mild/moderate reactions may not rule out subsequent severe or fatal reactions Ref: Bock. 2010; Liew, Williamson, Tang. 2008; Bock. 2007; Pumphrey. 2003; Bock. 2001 2.7
  • 43. Signs of anaphylaxis • Difficult/noisy breathing • Swelling of the tongue • Swelling or tightness in throat • Difficulty talking and/or hoarse voice • Wheeze or persistent cough • Persistent dizziness or collapse • Pale and floppy (young children) Mild or moderate signs and symptoms may not always precede anaphylaxis
  • 44. All individuals at risk of anaphylaxis should: • Know what to do in an emergency • Have an ASCIA Action Plan for Anaphylaxis completed by their medical practitioner • Carry an adrenaline autoinjector and know how to use it Management of anaphylaxis anaphylaxis 1.5
  • 45. Why is adrenaline effective? • Inhibits the release of inflammatory mediators • Reverses the physiological effect of mediators by: – Reducing airway mucosal oedema – Inducing bronchodilatation – Inducing vasoconstriction (thus increasing HR & BP) – Increasing strength of cardiac contraction Lasts ~ 15-20 minutes; repeated doses may be needed after 5 minutes if no response Ref: Tole, Lieberman. 20074.4
  • 46. There are two brands of adrenaline autoinjectors – EpiPen® and Anapen® • Junior devices (150µg) recommended for children 10 to 20 kg (aged ~1-5 years) • Higher dose devices (300µg) recommended for children over 20 kg (aged over ~5 years) and adults EpiPen Jr Anapen Jr Anapen 5.2 EpiPen
  • 47. Orange needle end Blue safety release Viewing window EpiPen with orange needle end and blue safety release Expiry date Instructions on how to use (on other side) 5.5 • Available in Australia mid 2011
  • 48. How to give EpiPen with orange needle end and blue safety release 5.6
  • 49. Patient’s photo and personal details Confirmed allergens Contact details for family and doctor Adrenaline autoinjector brand name Signs, symptoms, action for mild or moderate allergic reactions Instructions on how to use the device Signs, symptoms, action for anaphylaxis Additional information 6.3
  • 50. PBS supply of adrenaline autoinjectors in Australia • Maximum of 2 (EpiPen or Anapen) for both children and adults • Initial supply: – When risk and clinical need has been assessed by, or in consultation with a clinical immunologist, allergist, paediatrician or respiratory physician – After hospital or emergency department discharge for acute allergic anaphylaxis treated by adrenaline • Continuing supply for anticipated emergency treatment of acute allergic reactions with anaphylaxis, where the patient has previously been issued with an authority prescription for this drug 5.14
  • 51. Guidelines for prescribing an adrenaline autoinjector Always recommended if… •History of anaphylaxis (and continued risk) •These patients should be referred to a clinical immunology/allergy specialist May be recommended if… •History of a generalised allergic reaction and one or more risk factors: – Asthma – Age (children >5 yrs, adolescents, young adults) – Specific allergic triggers – Co-morbidity (e.g. ischaemic heart disease) – Geographical remoteness from emergency medical care •These patients should be referred to a clinical immunology/allergy specialist 5.15
  • 52. Guidelines for prescribing an adrenaline autoinjector Not normally recommended... • Asthma with no history of anaphylaxis nor generalised allergic reactions • Positive allergy test without a history of clinical reactions • Family history of anaphylaxis or allergy • Bee stings − local reactions only (children and adults) − generalised rash only (children) • These patients generally do not need referral to a clinical immunology/allergy specialist 5.16