Drug allergy

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 (the exception being the presence of latent sensitization by cross-allergens). The immune system requires time to prepare — the sensitization period, which usually takes from 7 to 14 days from the moment of initial contact with the antigen.

It is important to distinguish allergy from other adverse reactions:

• Cumulation — physical accumulation of a drug or its effects. Impossible upon first administration, requires repeated doses.
• Idiosyncrasy — a genetically determined aberrant reaction (for example, due to an innate enzyme defect). Unlike allergy, it does not require prior immunological preparation and can manifest violently upon the very first exposure to the drug.

Immediate-type reactions (Type I)

The first, anaphylactic type of reactions develops in the first hours (and sometimes minutes) after the administration of a resolving dose of the drug into an already sensitized body. The danger lies in the fact that a microscopic, trace dose of the drug can act as a trigger for a violent reaction.

• Mechanism: The process is mediated by immunoglobulins E (IgE). Specific antibodies bind to antigens on the surface of mast cells, provoking their degranulation and a massive release of histamine.
• Clinical presentation: In mild or moderate cases, itchy rash (urticaria), local edema, rhinitis, and lacrimation occur. In severe cases — 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 have a completely different clinical presentation.

Cytolytic type (Type II) The reaction is accompanied by the activation of the complement system. Antibodies interact with an antigen fixed on the membranes of formed blood elements, 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 complexes of "antigen + antibody + complement" (involving IgG, IgM, IgE) are formed in the bloodstream. These complexes deposit on the vascular endothelium, causing its damage.

• Manifestation: Development of serum sickness (fever, lymphadenopathy, arthralgia or arthritis, severe itching and urticaria).
• Triggers: Penicillins, sulfonamides.

Delayed-type (Type IV)

The fourth type of reaction is cell-mediated. Antibodies are not involved in its mechanism. The key role here is played by cellular immunity, namely sensitized T-lymphocytes and macrophages.

Clinically, this type of hypersensitivity most often manifests as contact dermatitis. This reaction is characteristic of situations where a medicinal product is applied directly to the skin (ointments, patches, gels).

Class and exam questions

What else to study on this topic

• Sensitization and the cross-allergy phenomenon
• Pathogenesis of serum sickness and endothelial damage
• Genetic enzyme defects as the basis of idiosyncrasy
• The role of mast cells and histamine in immediate-type reactions

Other topics in "General Pharmacology"

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