Allergies and Hypersensitivity

Question 1

Explain the difference between drug allergies and drug hypersensitivity reactions

Answer 1

Drug allergies: IgE mediated [involve innate + adaptive immune systems]

DHR: release of mast cell and basophil derived mediators by pharmacologic or physical effect [involve chemical mediators]

E.g., histamine => red man syndrome (Vancomycin)
inhibition of breakdown of bradykinin => Angioedema (ACEi/ARB)
alter metabolism of PG => NSAIDs induced asthma (NSAIDs)

Question 2

What are the 4 classifications of allergic reactions?

Answer 2

Type 1 immediate hypersensitivity
- IgE mediated, mast cell derived mediators + cytokines

Type 2 antibody-mediated diseases
- IgM or IgG mediated, bind to cell surface Ag, complement and Fc receptor-mediated

Type 3 immune complex mediated diseases
- Ag-Ab complex in vascular basement membrane or tissues, complement and Fc receptor-mediated

Type 4 T cell mediated diseases
- Delayed reaction mediated by T cells

Question 3

What is anaphylaxis?

Answer 3

Acute, life-threatening reaction that involves multiple organ systems (e.g., skin, airway, cardio, GIT, CNS)

Greatest risk within first few hours

Question 4

What are the clinical manifestations of allergic/hypersensitivity reactions?

Answer 4

1. Anaphylaxis
2. Serum sickness/drug fever - drug-Ab complex cause systemic symptoms
3. Drug induced autoimmunity - SLE
4. Vasculitis - inflammation and necrosis of bleed vessel walls, can be limited to skin or involve multiple organs
5. Respiratory - acute inflitrative, chronic fibrotic pulmonary reactions
6. Hematologic - eosinophilia, hemolytic anemia, thrombocytopenia, agranulocytosis

Question 5

What are the 3 serious cutaneous adverse reactions (SCAR)?

Answer 5

1. DRESS - drug rash with eosinophilia and systemic symptoms
2. SJS - stevens-johnson syndrome
3. TEN - toxic epidermal necrolysis

Question 6

What are the key characteristics of DRESS?

Answer 6

1. Rash
2. Eosinophilia
3. Internal organ involvement - e.g., hepatitis, nephritis, adenopathy, pneumonia

10% mortality

Question 7

SJS and TEN are mucocutaneous disorders. Describe their clinical presentation.

Answer 7

Progressive bullous or blistering disorders - dermatologic emergencies
Progress to include mucous membrane erosion and epidermal detachment

Question 8

Between SJS and TEN, which is characterized by greater detachment of body surface area and greater mortality?

Answer 8

TEN >30% detachment of BSA, 10-70% mortality

SJS <10% detachment of BSA, 1-5% mortality

*SJS-TEN overlap gives a 10-30% detachment of BSA

Question 9

What can increase susceptibility to drug hypersensitivity syndromes?

Answer 9

Human leukocyte antigen (HLA) alleles

Genetic variation can also affect metabolic deactivation of drugs