Brief Introduction on Hypersensitivity with an overview on Anaphylaxis

2. OBJECTIVES
 BRIEF INTRODUCTION ON HYPERSENSIVITY
 DEFINITION
 CLASSIFICATION
 OVERVIEW ON ALL TYPES
 ANAPHYLAXIS

3. BACKGROUND
 It was coined by Von Pirquet in 1906.
 Hypersensitivity reactions – ‘over reaction’ of the
immune system to harmless environmental antigens or
agents like pollens.
 It occurs when an already sensitized individual is re-
exposed to the same foreign substance.
 Terms hypersensitivity and allergy are used
interchangeably

4. DEFINITION
HYPERSENSITIVITY REACTION
 A state of altered reactivity in which the body reacts
with an exaggerated immune response to a foreign
agent.
 These reactions may be damaging, uncomfortable, or
occasionally fatal.
 Coombs and Gell classified hypersensitivity into 4
types.

5. Coombs and Gell’s Classification

6. TYPE 1 HYPERSENSITIVITY
 Commonly called as allergy and can occur within
minutes
 Mediated by IgE antibodies in response to stimulation of
Th2 cells by an antigen.
 The antigens that stimulate it are called allergens
(i.e. House dust, Pollens, Cosmetics, Insects, Clothing and Drug)
 Exposure may be ingested, inhalation, injection or direct
contact.
 Type I hypersensitivity reactions can be systemic (e.g.,
systemic anaphylaxis) or localized to a specific target
tissue or organ (e.g., allergic rhinitis, asthma, Allergic
conjunctivitis, urticarial,eczema).

7. TYPE II: CYTOTOXIC REACTIONS
 Body makes special IgG autoantibodies directed
against self cells that have some form of foreign
protein attached . Hence IgG mediated
 Antigen: 1. may be intrinsic to the cell membrane
2. may take the form of an exogenous antigen
adsorbed on the cell surface.
 Hypersensitivity results from the binding of antibodies
to normal or altered cell-surface antigen
 Clinical examples include hemolytic anemias,
thrombocytopenic purpura, hemolytic
transfusion reactions, Goodpasture’s syn drome,
and drug-induced hemolytic anemia

8. TYPE III: IMMUNE COMPLEX REACTIONS
 Excess antigens cause immune complexes to form
in blood; these circulating complexes usually lodge
in small blood vessels
 Usual sites include kidneys, skin, joints & small
blood vessels
 Lodge in the small vessel walls, trigger
inflammation & cause tissue or vessel damage
 Examples: rheumatoid arthritis, systemic lupus
erythematosus & serum sickness

9. TYPE IV: DELAYED HYPERSENSITIVITY
REACTIONS
 Reactive cell T-lymphocyte (T-cell)
 Antibodies & complement not involved
 Local collection of lymphocytes & macrophages causes
edema, induration, ischemia & tissue damage at site
within hours to days after exposure
 Examples: Tb test (positive purified protein
derivative), contact dermatitis, poison ivy skin rashes,
insect stings, tissue transplant rejection & sarcoidosis

11. WHAT IS ANAPHYLAXIS
 Ana (without), phylaxis (protection).
 Acute multi-systemic allergic reaction involving the
skin, airway, vascular system, and GI.
 Anaphylaxis is defined as a serious allergic or
hypersensitivity reaction (type 1) that is rapid in onset
and may cause death.

12. HISTORY SPEAKS
1st recorded 2640 BC in
hieroglyphics
The story of sudden
death of a pharaoh after
a bee sting
Richet & Portier coined
term anaphylaxis to
describe the unexpected
effect during
immunization of the dogs.

13. The prevalence of anaphylaxis in the general population is at
least 1.6% and probably higher - Robert A. Wood, journal of
allergy and clinical immunology, 2013.
The incidence rate is from 1.21% to 15. 5 % in general
population. Neugut, 2001-Arch Int Med
Mortality rate -2.4 per million in US.
INCEDENCE AND PREVALANCE

14. ETIOLOGY
Pharmlogic agents
• Antibiotics (penicillin)
• Nonsteroidal anti-inflammatory drugs (Asprin)
• intravenous (IV) contrast agents
Stinging insects Physiological
• Ants, bees, hornets, wasps. Cold and Exercise induced
Food
• Peanuts, seafood, and wheat
Latex
• Rare
• No latex-associated deaths

15. U.S. TOP “8”
•Fish
•Crustacean
Shellfish
•Egg
•Milk
•Peanuts
•Tree-nuts
•Soy
•Wheat
•Gluten ?
+Sesame
+Molluscs
+Sulfites
+Gluten
Canada
Top 8 Plus + Sesame
+ Molluscs
+ Sulfites
+ Gluten
+ Celery
+ Mustard
+ Lupin
E.U.
Top 8 Plus
+Buckwheat
+ Another 20
allergens are
recommended
Japan
4 of Top 8
*Milk
*Egg
*Peanuts
*Wheat
Plus
+ Buckwheat
+Sesame
+Molluscs
+Sulfites
+Gluten
Australia/NZ
Top 8 Plus+ Gluten (in
place of
wheat)
+ Sulfites
Codex
Top 7 Plus
+Sulfites
+Gluten (in
place of
wheat)
Hong Kong
Top 7 Plus
International Food Allergen List
INTERNATIONAL FOOD ALLERGEN LIST

16. ETIOLOGY
34%
37%
20%
7%
2%
Causes of anaphylaxis in a study of 266 patients (Data
from Kemp et al)
Food
Idiopathic
Drugs
Exercise
Latex, hormones,
insect bites

17. PATHOPHYSIOLOGY
 First exposure
 Activation of TH2 cell → Stimulate IgE switiching
Allergen
TH2 Cell
B Cell

18. Pathophysiology
 First exposure
 IgE production
IgE secreting B cell
IgE

19. PATHOPHYSIOLOGY
 First exposure
 IgE bind to mast cell
Mast cell
FcɛRI
IgE

20. PATHOPHYSIOLOGY
 Second exposure
 Recognition Allergen
Mast cell
FcɛRI
IgE

21. PATHOPHYSIOLOGY
 Second exposure
 Activation of mast cell to release histamine and other
mediators
Allergen
Mediators
Mast cell
FcɛRI
IgE

22. PATHOPHYSIOLOGY

23. SIGNS & SYMPTOMS
Itching flushing
hives (urticaria) swelling
Skin

24. SIGNS & SYMPTOMS
Itching tearing
redness
swelling around the
eyes
Eyes

25. SIGNS & SYMPTOMS
Sneezing
runny nose nasal congestion
swelling of the tongue metallic taste
Nose &
mouth

26. SIGNS & SYMPTOMS
Difficulty breathing coughing chest tightness
wheezing or other
sounds
increased mucus
production
throat swelling or
itching
change in voice
or a sensation of
choking
Lungs and throat

27. SIGNS & SYMPTOMS
Dizziness weakness fainting
rapid, slow, or irregular
heart rate
low blood pressure
Heart and circulation

28. SIGNS & SYMPTOMS
Nausea vomiting
cramps diarrhea
Digestive system

29. SIGNS & SYMPTOMS
Anxiety confusion
sense of impending
doom
Nervous system

30. DIFFERENTIAL DIAGNOSIS
PRESENTATION DIFFERENTIAL DIAGNOSIS
Hypotension Septic shock
Vasovagal reaction
Cardiogenic shock
Hypovolemic shock
Respiratory distress with wheezing or stridor Airway foreign body
Asthma and chronic obstructive pulmonary disease
exacerbation
Vocal chord dysfunction syndrome
Postprandial collapse
Airway foreign body
Monosodium glutamate ingestion
Sulfite ingestion
Scombroid fish poisoning
Flush syndrome
Carcinoid
Postmenopausal hot flushes
Red man syndrome (vancomycin [Vancocin])
Miscellaneous Panic attacks
Systemic mastocytosis
Hereditary angioedema
Leukemia with excess histamine production

31.  An increased amount of tryptase protein can be
measured in a blood sample collected during the first
three hours after anaphylaxis symptoms have begun.
 Plasma histamine levels also rises as soon as five to 10
minutes after onset but remain elevated for only 30 to 60
minutes.
DIAGNOSTIC CRITERIA
 naphylaxis network symposium:
J Allergy Clin Immunol 2006 ;117 : 391-7
LAB INVESTIGATION

33. PREVENTION
Avoid the responsible allergen (e.g. food,
drug, latex, etc.).
Keep an adrenaline kit (e.g. Epipen) and
Benadryl on hand at all times.
Wear medic Alert bracelets .
Venom immunotherapy is highly effective in
protecting insect-allergic individuals.

34. TREATMENT-FIRST AID
Place patient in
Trendelenburg
position.
Establish and maintain
airway.
Give oxygen via nasal
cannula as needed.
Place a tourniquet
above the reaction site.
Epinephrine at the site
of antigen injection.
Start IV to rise BP.

35. TREATMENT OF ANAPHYLAXIS
 EPINEPHRINE (1:1000) SC or IM- 0.01 mg/kg (maximal
dose 0.3-0.5 ml)- administer in a proximal extremity-
may repeat every 10-15 min, p.r.n.
 EPINEPHRINE intravenously (IV)- used for
anaphylactic shock not responding to therapy- monitor
for cardiac arrhythmias
 EPINEPHRINE via endotracheal tube
 Epi-pen shold be kept at work, home
 Incase of children,it should be kept in
school as well.

36. TREATMENT OF ANAPHYLAXIS
 Benadryl (diphenhydramine)- H1 antagonist
 Tagamet (cimetidine)- H2 antagonist
 Corticosteroid therapy: hydrocortisone IV or
prednisone po

37. TREATMENT OF ANAPHYLAXIS
 Biphasic courses in some cases of anaphylaxis:
Recurrence of symptoms: 1-8 hrs later
In those with severe anaphylaxis, observe for 6 hours
or longer.
In milder cases, treat with prednisone; Benadryl every
4 to 6 hours; advise to return immediately for
recurrent symptoms

38. TREATMENT OF ANAPHYLAXIS IN
BETA BLOCKED PATIENTS
 Give epinephrine initially.
 If patient does not respond to epinephrine and other
usual therapy
Glucagon 1 mg IV over 2 minutes

39. USE OF EPINEPHRINE IN
FOOD ALLERGY
 Epinephrine should be used immediately after
accidental ingestion of foods that have caused
anaphylactic reactions in the past.
 An individual who is allergic to peanut, nuts**,
shellfish, and fish should immediately take
epinephrine if they consume one of these foods.
 A mild allergic reaction to other foods (e.g. minor
hives,vomiting) may be treated with an
antihistamine

40. References
 Abbas & Lichtman, Basic Immunology 3E, Chapter 11
 http://www.authorstream.com/Presentation/Moiloa-898248-
anaphylaxis/
 http://med.mui.ac.ir/clinical/orjanc/Anaphylaxis.ppt
 http://www.uptodate.com/contents/anaphylaxis-symptoms-and-
diagnosis-beyond-the-basics
 http://www.oregonems.org/Downloads/Anaphylaxis.ppt
 Anaphylaxis network symposium: J Allergy Clin Immunol 2006 ;117 :
391-7