What type of hypersensitivity reaction is a past reaction to Iressa (gefitinib)?

Hypersensitivity Reaction to Gefitinib (Iressa)

A past reaction to gefitinib (Iressa) is most likely a Type IV delayed hypersensitivity reaction, specifically a Type IVc reaction involving CD8+ T lymphocytes. 1

Classification of Gefitinib Hypersensitivity

Gefitinib-induced hypersensitivity reactions are typically characterized as Type IV hypersensitivity reactions based on the Gell and Coombs classification system. These reactions are:

• Non-dose related and unpredictable - classified as Type B (Bizarre) adverse drug reactions 1
• T-cell mediated rather than IgE-mediated (which would be Type I immediate hypersensitivity) 1
• Delayed in onset - occurring hours to days after drug exposure, rather than within minutes 1

Clinical Presentation and Mechanism

Gefitinib hypersensitivity typically manifests as:

• Skin reactions (most common) - rash, itching, acne-like eruptions 2
• In severe cases: peeling or blistering of skin 2
• Potential lung inflammation with symptoms similar to those from lung cancer 2

The mechanism involves:

• Activation of specific T-cells (CD4+ and CD8+) 3
• Particularly Type IVc reactions with cytotoxic CD8+ T lymphocytes 4
• Release of perforin, granzyme B, and Fas ligand that can lead to keratinocyte apoptosis 3

Distinguishing from Other Hypersensitivity Types

This reaction differs from:

1. Type I (IgE-mediated) reactions:

   • Type I reactions occur within minutes to hours after exposure 1, 5
   • Involve IgE antibodies and mast cell/basophil degranulation 6
   • Present with urticaria, angioedema, bronchospasm, or anaphylaxis 1

2. Type II (cytotoxic) reactions:

   • Involve antibody-mediated cytotoxicity against cell surface antigens 1
   • Typically cause hemolytic anemia or thrombocytopenia 4

3. Type III (immune complex) reactions:

   • Involve formation and deposition of immune complexes 7
   • Present with serum sickness, vasculitis, or joint pain 1

Management Implications

Understanding that gefitinib reactions are Type IV hypersensitivity has important clinical implications:

• Monitoring: Careful skin and respiratory monitoring during treatment 2
• Intervention: Early recognition and management of skin reactions before they become severe 2
• Discontinuation: Consider stopping treatment for severe reactions (grade 3-4) 1
• Desensitization: Unlike Type I reactions, traditional rapid desensitization protocols are less effective for Type IV reactions 1

Pitfalls and Caveats

• Do not confuse skin reactions with other non-immune adverse effects of gefitinib
• Severe skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis require immediate discontinuation of the drug 2
• Lung symptoms from gefitinib hypersensitivity may mimic progression of underlying lung cancer 2
• Liver function abnormalities may accompany hypersensitivity reactions and should be monitored 2

Understanding the specific type of hypersensitivity reaction helps guide appropriate management strategies and informs decisions about potential rechallenge or alternative treatments in patients with a history of gefitinib reactions.