General Principles and Differential Diagnosis
Drug allergy is fundamentally different from the toxic or cumulative effects of drugs. A true allergic reaction never occurs upon the very first administration of a substance (with the exception of prior hidden sensitization by cross-reacting allergens). The immune system requires time to prepare—the sensitization period, which typically takes 7 to 14 days from the moment of initial contact with the antigen.
It is important to differentiate allergy from other adverse drug reactions:
- Cumulation — the physical accumulation of a drug or its effects. It is impossible upon the first administration and requires repeated doses.
- Idiosyncrasy — a genetically determined aberrant reaction (e.g., due to a congenital enzyme defect). Unlike allergy, it does not require prior immune preparation and can manifest violently upon the very first exposure to the drug.
Immediate Hypersensitivity Reactions (Type I)
The first, anaphylactic type of reaction develops within the first hours (and sometimes minutes) after administration of the triggering dose of the drug into an already sensitized organism. The danger lies in the fact that a microscopic, trace dose of the drug can trigger a violent reaction.
- Mechanism: The process is mediated by immunoglobulin E (IgE). Specific antibodies bind to antigens on the surface of mast cells, triggering their degranulation and a massive release of histamine.
- Clinical presentation: Mild to moderate cases present with pruritic rash (urticaria), local edema, rhinitis, and lacrimation. Severe cases feature bronchospasm, laryngeal edema, and life-threatening anaphylactic shock.
- Typical triggers: Penicillin antibiotics.
Cytolytic (Type II) and Immune Complex (Type III) Types
The second and third types are mediated by other classes of antibodies, predominantly IgG and IgM, and feature a completely different clinical picture.
Cytolytic Type (Type II) This reaction is accompanied by activation of the complement system. Antibodies interact with an antigen fixed to the membranes of blood cells, leading to lysis (destruction) of the cells. Classical examples:
- Methyldopa causes hemolytic anemia.
- Quinidine provokes thrombocytopenic purpura.
- Metamizole sodium can cause agranulocytosis.
Immune Complex Type (Type III) Massive circulating immune complexes of "antigen + antibody + complement" (involving IgG, IgM, IgE) form in the bloodstream. These complexes deposit on the vascular endothelium, causing its damage.
- Manifestation: Development of serum sickness (fever, lymphadenopathy, arthralgia or arthritis, severe pruritus, and urticaria).
- Triggers: Penicillins, sulfonamides.
Delayed-Type Hypersensitivity (Type IV)
The fourth type of reaction is cell-mediated. Antibodies do not participate in its mechanism. The key role here is played by cellular immunity, specifically sensitized T-lymphocytes and macrophages.
Clinically, this type of hypersensitivity most often manifests as contact dermatitis. Such a reaction is characteristic of situations where a drug is applied directly to the skin (ointments, patches, gels).