Case Study: Drug-Induced Anaphylaxis

Patient Profile:
• Name: John
• Age: 35
• Gender: Male
• Medical History: No known allergies
 Case Presentation
John, a 35-year-old male, presented to the emergency
department (casuality) with symptoms of anaphylaxis. He had
undergone dental treatment and was given a local anesthetic
injection of lidocaine for a dental procedure. Shortly after the
injection, John experienced the sudden onset of symptoms,
including difficulty breathing, swelling of the face and lips,
hives, and a feeling of impending doom and dizziness
 Assessment and Diagnosis

The medical team assessed John's vital signs, which revealed

a rapid pulse rate of 120 beats per minute, a blood
pressure of 90/60 mmHg, and a decreased oxygen
saturation of 82%. Based on his clinical presentation and the
rapid onset of symptoms following the lidocaine injection, a
diagnosis of drug-induced anaphylaxis was made.
 Immediate Treatment

• The medical team administered intramuscular

epinephrine (0.5 mg) to John to alleviate his symptoms
and improve his airway and blood pressure. They also
started him on supplemental oxygen through a face
mask to improve his oxygen saturation levels
 Stabilization and Monitoring

• John was placed on continuous cardiac monitoring, and

his blood pressure and oxygen saturation were
closely monitored. Intravenous access was established
for further medication administration and fluid
resuscitation if necessary.
 Additional Medications

• To further manage his symptoms, John received

intravenous corticosteroids (such as
methylprednisolone) to reduce inflammation and
histamine release. He was also given antihistamines
(such as diphenhydramine) to block histamine
receptors and reduce allergic responses.
 Observation and Follow-up

Following the initial treatment, John's symptoms started to

improve. His breathing became less labored, and his blood
pressure stabilized. He was observed in the emergency
department for several hours to ensure that his symptoms
did not recur. The medical team advised John to follow up
with an allergist for further evaluation and identification of the
specific allergen responsible for his anaphylactic reaction.
HYPERSENSITIVITY

Dr K Ravi Kiran
 Learning objectives
By the end of this class you should be able to
• Define hypersensitivity
• Overview of different types of Hypersensitivity
• Understand the
– Mechanism
– Testing & Treatment
of Type I hypersensitivity reaction
Normal vs Exaggerated response
 Definition of Hypersensitivity

Exaggerated and Inappropriate immune response

in a Sensitised Host on subsequent contact

with Specific Antigen

CLASSIFICATION
 Classification
Traditional Gell & Coombs
Time Pathogenesis
Immediate & Type I, II, III, IV
Delayed
 Gell and Coombs Classification

  Type- I Type- II Type- III Type- IV

Immune Humoral Humoral Humoral Cell mediated
response altered

Immediate or Immediate Immediate Immediate Delayed

delayed

Duration 2min to 30 5-8 hrs 2-8 hrs 24 to 72 hrs

between min
appearance of
symptoms &
antigen contact
 Gell and Coombs Classification

  Type- I Type- II Type- III Type- IV

Antigen Soluble Cell surface Soluble Soluble or bound
bound
Mediator IgE IgG Ag-Ab complex TDTH cell
Effector Mast cell 1. ADCC Complement Macrophage
mechanism degranulation 2. Complement activation and activation leads to
mediated inflammatory phagocytosis or
cytolysis response cell cytotoxicity

Desensitization Easy, but short Easy, but short Easy, but short Difficult but
to the allergen lasting lasting lasting sustained
 Gell and Coombs Classification

  Type- I Type- II Type- III Type- IV

Typical 1.Anaphylaxis 1.Transfusion 1.Arthus reaction 1.Tuberculin test
manifestations 2.Asthma reactions 2.Serum sickness 2.Granuloma
3.Atopic 2.Rh 3.Glomerulonephtiritis formation in
dermatitis incompatibility 4.Rheumatoid arthritis tuberculosis,
3.Hemolytic leprosy, etc
anemia 3.Contact
dermatitis
Allergens that induce type- I hypersensitivity reaction

Food Nuts, egg, peas, sea food, beans, milk

Plants & pollens Rye grass, rag weed, timothy grass
Proteins Foreign serum Vaccines
Drugs Penicillin, sulphonamides, local anesthetics
and salicylates
Insect bite products Venom of Bee, Wasp, Ant and Dust mites
Others Mold spores, animal hair and dander
 Mechanism of type I hypersensitivity

1. Sensitization phase
2. Effector phase
o Both occurring with an interval of 2-3
weeks.
Explanation
Break
Identify him
 Primary mediators
Preformed Chemical that are Released Immediately
Primary Mediators Action
Histamine and ↑Vascular permeability
Serotonin ↑Smooth-muscle contraction
Eosinophil chemotactic Eosinophil chemotaxis
factor (ECF-A)
Neutrophil chemotactic Neutrophil chemotaxis
factor (NCF-A)
Proteases Bronchial mucus secretion; Degradation of
blood-vessel basement membrane
 Secondary mediators
Synthesized and Released
Secondary Mediators Action
Platelet-activating factor Platelet aggregation and degranulation;
Contraction of pulmonary smooth muscles
Leukotrienes (slow reactive ↑ Vascular permeability; Contraction of pulmonary
substance of anaphylaxis, SRS-A) smooth muscles

Prostaglandins ↑Vasodilation; Contraction of pulmonary smooth

muscles; Platelet aggregation

Bradykinin ↑Vascular permeability; Smooth-muscle contraction

Cytokines Systemic anaphylaxis; ↑ Expression of cell adhesion
(IL-1 and TNF-α) molecules (CAMs) on venular endothelial cells
 TYPE- I HYPERSENSITIVITY REACTION

Hallmark –

• Production of IgE by sensitized B cells

• Re-contact with an allergen induces mast cell

degranulation
 TYPE- I HYPERSENSITIVITY REACTION

oLocalized - ATOPY

oSystemic - ANAPHYLAXIS
 ANAPHYLAXIS
• Acute medical emergency condition, characterized by
severe dyspnoea, hypotension, and vascular collapse
leading to death.
• Occurs within minutes of exposure to allergen and
unless treated promptly, may lead to fatality.
• Epinephrine (adrenalin) is the drug of choice for
systemic anaphylactic reactions.
 ATOPY
• Reaction is limited to a specific target tissue or organ, mostly the
epithelial surfaces at the entry sites of allergen.
• These allergies afflict more than 20% of people.
• Almost always run in families (i.e. inherited)
• Examples include:
o Allergic rhinitis (or hay fever)
o Asthma
Allergic rhinitis (or hay fever)
• Most common atopic disorder.

• Affects 10% of the population.

• Results from exposure to airborne allergens with the conjunctiva

and nasal mucosa leading to appearance of various symptoms
such as ↑watery secretions of the conjunctiva, nasal mucosa, and
upper respiratory tract, as well as sneezing and coughing.
 Asthma
• The stimulus may or may not be an allergen.

• Accordingly asthma can be classified as-

– Allergic asthma: Induced by airborne or blood-borne allergens,
such as pollens, dust, fumes, insect products, or viral antigens.
– Intrinsic asthma: It is independent of allergen stimulation,
induced by exercise or cold.
 Asthma
• Second most common atopic manifestation.
– Differs from hay fever in involvement of lower
respiratory mucosa, resulting in contraction of the
bronchial smooth muscles and airway edema, ↑mucus
secretion; all together leading to bronchoconstriction
and dyspnoea.
 Factors influencing type I hypersensitivity

• Genetic makeup
• Allergen dose:
o Dose of the allergen has a definite impact on the type of
immune response produced.
• TH1 vs TH2 response
Detection of type I hypersensitivity
 Non- Specific Tests
Radioimmunosorbent test (RIST)

• Quantitatively detects the total serum IgE antibody up to nanogram.

• Highly sensitive technique, based on the radioimmunoassay.
 Specific tests
• Skin prick test
 Radioallergosorbent test (RAST)

• Quantitatively detects the serum level of allergen specific IgE.

• Allergen itself is coated to beads or disks, so that when the patient’s
serum is added, only the allergen specific IgE would bind to the
beads or disks.
 Other specific tests
• Multiplex immunoblot assay
• Fluoro-enzyme immunoassay (FEIA)
 Treatment
Drugs Mechanism of action
Antihistamines Block H1 receptors on target cells; hence
antagonise the effects of histamine released
Epinephrine Stimulates cAMP production in mast cells;
(adrenaline) thereby prevents mast cell degranulation
Cortisone Blocks conversion of histidine to histamine and
stimulates cAMP levels in mast cells
Theophylline Prolongs high cAMP levels in mast cells
Cromolyn sodium Blocks Ca2+ influx into mast cells
 Prevention
• Avoidance of contact with known allergens
• Hyposensitization/Desensitization
• Monoclonal anti-IgE
 Review
• Define hypersensitivity
• Overview of different types of Hypersensitivity
• Type I hypersensitivity
– Mechanism
– Examples
– Testing & Treatment
Thank you!