Hypersensitivity /Allergy

• It is excessive inflammation occurring in response to the presence of an antigen to

which the patient usually has been previously exposed. The terms hypersensitivity
and allergy are used interchangeably. It is classified into four basic types,
determined by differences in timing, pathophysiology, and manifestations

Four types:
▪ Type I: Immediate
▪ Type II: Cytotoxic
▪ Type III: Immune Complex Reaction
▪ Type IV: Delayed

A. Type I Hypersensitivity: Immediate

➢ It is the most common type of hypersensitivity. These results from the increased
production of the immunoglobulin E (IgE) antibody class. Acute inflammation
occurs when IgE responds to an antigen and causes the release of histamine
and other vasoactive amines from basophils, eosinophils, and mast cells.

➢ It is a immediate reaction beginning within minutes of exposure to an antigen.

Primary chemical mediators are responsible for the symptoms of type I
hypersensitivity because of their effects on the skin, lungs, and gastrointestinal
tract. If chemical mediators continue to be released, a delayed reaction may
occur and may last for up to 24 hours

➢ Clinical symptoms are determined by:

• the amount of the allergen,
• the amount of mediator released
• the sensitivity of the target organ
• the route of allergen entry.

➢ It is characterized by vasodilation, increased capillary permeability, smooth

muscle contraction, and eosinophilia. Systemic reactions may involve laryngeal
stridor, angioedema, hypotension, and bronchial, GI, or uterine spasm. Local
reactions are characterized by hives.

➢ EXAMPLE:
 Anaphylaxis (local or systemic)
 allergic asthma
 atopic allergies such as allergic rhinitis (hay fever)
 allergies to substances such as latex, bee venom, peanuts, iodine,
shellfish, drugs, and thousands of other environmental allergens.
 ➢ Allergens can be contacted in ways:
• Inhaled
• Ingested
• Injected
• Contacted
➢ Some reactions occur just in the areas exposed to the antigen, such as the
mucous membranes of the nose and eyes causing rhinorrhea, sneezing, and
itchy, red, watery eyes.
➢ Other reactions may involve all blood vessels and bronchiolar smooth muscle
causing widespread blood vessel dilation, decreased cardiac output, and
bronchoconstriction.

B. Type II Hypersensitivity: Cytotoxic

➢ The body makes auto-antibodies directed against self-cells that have some
form of foreign protein attached to them. The auto-antibody binds to the self-cell
and forms an immune complex. The self-cell is then destroyed along with the
attached protein.
➢ It involves binding either the IgG or IgM antibody to a cell-bound antigen, may
lead to eventual cell and tissue damage. The reaction is the result of mistaken
identity when the system identifies a normal constituent of the body as foreign
and activates the complement cascade.

➢ Examples:
o Immune hemolytic anemias
o Immune thrombocytopenic purpura
o Hemolytic transfusion reactions
o Goodpasture's syndrome
o Drug-induced hemolytic anemia.

➢ Management:
o It begins with discontinuing the offending drug or blood
product. Plasmapheresis to remove autoantibodies may be
beneficial. Otherwise, treatment is symptomatic.
o Complications such as hemolytic crisis and kidney failure can be life
threatening.

C. Type III Hypersensitivity: Immune Complex Reaction

➢ Excess antigens cause immune complexes to form in the blood. These
circulating complexes usually lodge in small blood vessel walls of the kidneys,
skin, and joints. The complexes trigger inflammation, and tissue or vessel
damage. Many immune complex disorders (mostly connective tissue disorders)
are caused by type III reactions.
 ➢ Examples:
• Manifestations of rheumatoid arthritis caused by immune complexes that
lodge in joint spaces followed by tissue destruction, scarring, and fibrotic
changes.
• Systemic lupus erythematosus (SLE) has immune complexes lodged in the
vessels (vasculitis), the glomeruli (glomerulonephritis), the joints (arthralgia,
arthritis), and other organs and tissues.

D. Type IV Hypersensitivity: Delayed

➢ Also called as “cellular hypersensitivity”
➢ The reactive cell is the T-lymphocyte (T-cell) and antibodies and complement
are not involved. Occurs 24 to 72 hours after exposure to an allergen.
Sensitized T-cells respond to an antigen by releasing chemical mediators and
triggering macrophages to destroy the antigen. It consists of edema, induration,
ischemia, and tissue damage at the site.

➢ Example type IV reaction:

• Positive purified protein derivative (PPD) test for tuberculosis (TB)
• Contact dermatitis
• Poison ivy skin rashes
• Local response to insect stings
• Tissue transplant rejections
• Graft-versus-host disease
• Hashimoto's thyroiditis
• Sarcoidosis

➢ Patch testing for type IV hypersensitivity involves applying test chemicals that
contain the allergen. The patches remain in place for 48 hours. After removal,
the skin areas in contact with the chemical are examined for localized redness,
swelling, and blisters

➢ Major focus of management:

• Removal of the offending antigen.
• The reaction is self-limiting in 5 to 7 days, and the patient is treated
symptomatically.
• Monitor the reaction site and sites distal to the reaction for circulation
adequacy.
• Diphenhydramine (Benadryl) is not useful for type IV reactions.
• Corticosteroids can reduce the discomfort and help resolve the reaction
more quickly.
Assessment:
❖ Physical Examination
➢ Presentation of symptoms
▪ disease - specific symptoms
➢ Comprehensive Allergy History
➢ Diagnostic Evaluation
• Blood test
• Skin test
• Skin test
• Radioallergosorbent test (RAST)

1. Complete Blood Count with Differential

• WBC : Normal (without infection)
• Eosinophil: 5-15% - nonspecific
15-40% - eosinophilia
2. Eosinophil Count
o Obtained from blood samples
o Or smears from:
• Nasal secretions
• Conjunctival secretions
• sputum
3. Total Serum Immunoglobulin E Levels
o Normal IgE levels
o High IgE levels

Skin Tests
• Intradermal injection or superficial application (epicutaneous) of
solutions at several sites.
• Precautions before skin test:
a. Testing is not performed during bronchospasm
b. Epicutaneous tests are performed before other testing
methods
c. Emergency equipment must be ready to treat anaphylaxis
• Types of Skin test:
a. Prick Skin Test
b. Intradermal skin testing
c. Patch Testing
• Interpretation:
a. (+) positive reaction :
• urticarial wheal (round, reddened skin elevation)
• localized erythema (diffuse redness) in the area of
inoculation or contact
 • Pseudopodia (irregular projection at the end of a
wheal)
b. = sensitivity to the corresponding antigen

***False positive result - improper preparation or administration of

allergens
• Guidelines for interpretation:
a. Skin tests are more reliable for diagnosing atopic sensitivity in
patients with allergic rhinoconjunctivitis than in patients with
asthma.
b. Positive skin tests correlate highly with food allergy.
c. The use of skin tests to diagnose immediate hypersensitivity
to medications is limited, because metabolites of medications,
not the medications themselves, are usually responsible for
causing hypersensitivity

4. Provocative Testing
o Direct administration of the suspected allergen to the sensitive tissue
o Identifying clinically significant allergens in patients who have a large
number of positive tests
o Limitation of one antigen per session and the risk of producing
severe symptoms, particularly bronchospasm, in patients with
asthma.
5. Radioallergosorbent Test
o Radioimmunoassay that measures allergen specific IgE
o Sample of the patient’s serum is exposed to a variety of suspected
allergen particle complexes. If antibodies are present, they will
combine with radiolabeled allergens. Test results are then compared
with control values.

Management:
1. Avoidance Therapy
2. Pharmacologic Therapy
➢ Antihistamines
• Diphenhydramine
• Chlorpheniramine
• Hydroxyzine
•
❖ Side effects:
 ✓ Sedation
✓ Nervousness
✓ Tremors
✓ Dizziness
✓ Dryness
✓ Palpitations
✓ Anorexia
✓ Nausea
✓ Vomiting
❖
➢ Andrenergic agents

-Side effects:
✓ Hypertension
✓ Dysrhythmias
✓ Palpitations
✓ Central nervous system stimulation
✓ Irritability
✓ Tremors
✓ Tachyphylaxis
➢ Mast-cell stabilizers
 ➢ Corticosteroids

➢ Leukotrine modifiers

- Leukotriene-Receptor Antagonists (LTRAs)

- Leukotriene-Receptor Inhibitors (LTRIs)

3. Immunotherapy