The document defines anaphylaxis as an IgE-mediated, systemic allergic reaction and anaphylactoid reaction as a similar reaction that is non-allergic. It describes the epidemiology, etiology, pathophysiology, clinical features, diagnosis, and treatment of anaphylaxis. Common causes include antibiotics, hymenoptera stings, and foods. Diagnosis involves history and physical exam. Epinephrine is the first-line treatment to reverse symptoms. Prevention strategies include skin testing for IgE-mediated reactions and avoiding triggers for those with a history of allergic reactions.

1. ANAPHYLAXIS

2. Definition
Hypersensitivity – inappropriate immune
response to generally harmless antigen,
anaphylaxis is most severe form of immediate
hypersensitivity reaction.
Anaphylaxis – is an IgE mediated, rapidly
developing systemic allergic reaction.
Anaphylactoid reaction (non – allergic
anaphylaxis) – mimics anaphylaxis but is due
to direct degranulation of Mast cells by the
offending agent.
Clinical features of both are same

3. Differences
Anaphylaxis Anaphylactoid
Exposure to Ag –
sensitization –
reexposure
No sensitization
IgE mediated Mast cell
degranulation
Non IgE mediated Mast
cell degranulation
Skin prick tests useful -
Serum tryptase level >
25ug/L
negative

4. Epidemiology
Risk factors
– Atopic individuals are at no greater risk
– Poorly controlled asthma – fatal outcome
– Previous anaphylaxis – recurrence risk 40 – 60% for
stings, 20 – 40 % for radio contrast & 10 – 20% for
penicillin.
Prevalence data limited – ranges from 5/1000 to
2/10000 ED visits. Less severe reactions never
reported.
Commonest causes
– Antibiotics
– Hymenoptera stings
– Food

5. Etiology – anaphylaxis/anaphylactoid reactions
1. Drugs
1. B lactam antibiotics - Penicillin and other antibiotics
2. ASA
3. Trimethoprim – sulphamethoxazole
4. Vancomycin
5. NSAID/ Opiates
6. IV anesthetics - suxamethonium, propofol
2. Food and additives
1. Nuts
2. Sea food - shellfish
3. Eggs/ milk
4. Soybeans
5. Seeds
6. Sulfites
3. Others
1. Hymenoptera stings
2. Ionic Radiocontrast
3. Physical – exercise/cold
4. Idiopathic – 30%
5. Latex

6. Pathophysiology
Basic event is Mast/basophil degranulation
due to
1. IgE cross linking
2. Complement activation
3. Direct activation
4. Modulation of arachidonic acid metabolism
5. Exercise or temperature dependent effects
6. Idiopathic

7. Classic anaphylaxis
Requires two separate exposures to Ag/ hapten
protein complex (penicillin)
First exposure Ag/ hapten protein complex – APC –
cell surface bound to MHC 2 complex – T helper
cell – IL 4 – Th 2 response- IgE synthesis.
IgE constant region binds to IgE receptors on Mast
cells & basophils, COVERS the cells with Ag
specific IgE.
After a latent period reexposure IgE bridging –
deregulation occurs- Antibiotics/foods/stings

8. Complement mediated
Blood products/mismatch – immune
complexes involving IgG/IgM antibodies
leading to complement pathway activation
and formation of anaphylatoxins C3a/ C5a
which directly lead to degranulation.

9. Non immunologic mechanisms
By
– Direct stimulation
– Unknown mechanisms
Agents which cause such reactions
– Radio contrast – high osmolarity ionic contrasts
– activates complement system
– Muscular depolarizing drugs - direct
– Opiates - direct
– Dextrans

10. Modulation of Cyclooxygenase pathway
Aspirin /NSAID cause anaphylaxis by non
Mast cell process.
Precise mechanism unknown. Alteration in
PG & LT synthesis (COX 1 )
5 – 10% of asthmatics – rarely full syndrome

11. Pathophysiology
Anaphylactic Reaction
antigen
Mast cell
IgE
Drug
Anaphylactoid reaction
Complement activation
Kinin system
Fibrinolytic system
Coagulation system
Histamine
SRSA
Leukotrines
Kinins
Prostaglandins
Target organs
Respiratory
CVS
Skin

12. Effects of mediators
Histamine has all the following effects
1. Decrease in systemic vascular
resistance
2. Leakage of fluid from capillaries and
post capillary venules - Kinins
3. Bronchoconstriction – PAF, SRS-A(LT
C4/D4/E4), prostaglandins
4. Cutaneous and mucosal inflammation
– Leukotrines, prostaglandins

13. Classification of severity
1. Mild (skin and subcutaneous tissue only)
erythema, urticaria, periorbital oedema or
angioedema
2. Moderate (features of Respiratory, CVS or
GI involvement) – dyspnea, stridor, wheeze,
nausea, vomiting, dizziness, diaphoresis, chest
tightness or abdominal pain.
3. Severe (hypoxia, hypotension, CNS
compromise) cyanosis, BP < 90 mm Hg,
confusion, unconsciousness
MILD FORMS CAN CHANGE TO SEVERE ANY
TIME.

14. Clinical features
Most serious reactions occur within minutes
of exposure
May be delayed for hours – 2.5 hours after
parenteral exposure.
Oral exposure manifestations unpredictable
Some have Biphasic reaction – recurrence
after 4 to 8 hrs ( 3- 20% patient) - SRSA
Some have protracted course – require
treatment for several hours

15. Classic presentation
Begins with pruritus, cutaneous flushing, urticaria
Sense of fullness in throat, anxiety, chest
tightness, SOB & lightheadedness
Level of consciousness, resp distress circulatory
collapse
Loss of consciousness & cardio respiratory arrest
‘LUMP in throat & hoarseness heralds life
threatening laryngeal oedema’.

16. Clinical features
1. Skin/mucosa
1. Pruritus
2. Urticaria
3. Angioedema
2. Respiratory distress (laryngeal oedema,
laryngospasm, bronchospasm)
3. CVS – hypotension
4. Abdomen
1. Abdominal cramping
2. Diarrhea
5. Feeling of impending doom before
CVS/respiratory symptoms

17. Diagnosis
History & examination
If onset delayed & if related to food diagnosis may
not be easy
D/D
– Vasovagal - MI
– Arrhythmia - asthma
– Seizure - H.angiooedema
– Epiglottitis - F body
Lab
– Histamine levels elevated for 5- 30 min post reaction
– Tryptase – neutral protease found only in mast cell
granules. Elevated for several hours.

18. Treatment
The most common cause of death
is airway obstruction followed by
shock
May vary from mild to severe but if
left untreated all reactions have the
potential to become severe rapidly
Previous mild reaction does not
predict the severity on reexposure

19. Primary Treatment
1. Discontinue suspected allergen – prevents
further mast cell recruitment
2. Maintain airway and give 100% oxygen
3. Discontinue all sedatives/vasodepressors
4. Epinephrine
1. 0.1 mg IV bolus (1 ml of 1: 10,000) repeat 1 to 5
minutes. (3 ml via central line/ 15 minutes)
2. 0.3 to 0.5 mg (1:1,000) IM every 15 minutes
3. 3- 5 ml 1;10,000 in 10 ml endotracheally
4. Repeated doses may be required
5. Volume expansion – 0.5 to 1 litre bolus and
than titrate with BP and urinary output

20. Secondary Treatment
1. Antihistaminics
1. Relieve skin symptoms. No effect on
cardiopulmonary responses once Histamine has
been released.
2. Both H1 and H2 blockers
3. Diphenhydramine 1mg/kg, Ranitidine
2. Inhaled Salbutamol 2.5 to 5 mg
3. Steroids
1. Severe reactions. No immediate effect
2. May prevent relapse of severe reactions
3. Methyl Prednisolone 125 mg/hydrocortisone 250 –
500 mg

21. Prevention
Skin testing – for IgE mediated reactions
– Prick puncture/intradermal small dose
– Negative Control on other hand
– 20 minutes
– Wheal 3 mm larger than control
– No case of penicillin induced anaphylaxis has
been reported if skin test was negative
History of allergic reactions
I Card

22. Drug reactions
Penicillins
1. Reactive bicyclic lactam ring covalently
binds to tissues – major determinant –
responsible for anaphylaxis
2. If skin test is negative a delayed non IgE
mediated reaction may still occur
3. 75% patient who report penicillin allergy
have negative skin test and are not at risk
for anaphylaxis
4. 4% have positive skin test and are at risk
for anaphylaxis

23. Cephalosporins
1. Cross reactivity to penicillin – 4
fold risk of hypersensitivity
reactions if patient is allergic to
penicillin
2. Most common with first
generation cephalosporins
3. Can use third and fourth
generation with occasional mild
reactions

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