Drug Allergy Reaction Classification – Immune Reactions
Drug allergy reactions may be classified, at least theoretically, according to one of four implicated immunologic mechanisms, according to the scheme of Gell and Coombs:
Type I Drug Allergy Reactions
Type I reactions are the result of an IgE antibody reaction, which induces immediate-type hypersensitivity reactions. With subsequent drug exposure following sensitization, the multivalent antigen–hapten complex cross-links IgE bound to mast cells and basophils, leading to the release of preformed mediators (such as histamine) and the production of newly generated mediators (such as the leukotrienes). Systemic anaphylaxis, angioedema, bronchospasm, or urticaria due to penicillin allergy are the best understood responses in this category.
Type II Drug Allergy Reactions
Type II drug allergy reactions are mediated by IgG, or possibly IgM, antibodies directed against drug-modified cell surface antigens, which elicit complement-mediated cytotoxicity. Such responses induce cytopenias, such as Coombs’ positive hemolytic anemia where the drug or its metabolite binds to the erythrocyte membrane. Antibody, directed against the drug or altered cell membrane antigens, binds to its target, resulting in complement fixation and subsequent cell lysis. Similar reactions may occur in many tissues including the skin. Alternatively, drug–antibody immune response complexes may form and adhere to cell membranes, again leading to complement fixation and cell lysis.
Type III Drug Allergy Reactions
Type III reactions occur via immune complex formation. The size of the immune complex determines its site of tissue deposition and the resultant immune injury. The classic example is serum sickness, with involvement of the skin, joints, and lymphoid system, though drug fever is also commonly seen.
Type IV Drug Allergy Reactions
Type IV reactions, also known as delayed-type hypersensitivity, are cell mediated through T- lymphocyte responses to drug antigens. These may occur either as contact dermatitis associated with topically applied medications or as one of a variety of reaction patterns with systemic drug exposure. In contact sensitization, the drug forms a hapten and combines with self proteins to form an antigenic complex. Langerhans’ cells internalize the complex and travel via the lymphatics to regional lymph nodes where the ‘antigen’ is presented to T lymphocytes. After clonal T-cell expansion, the T cells are redistributed in the skin.
Once antigen is re-encountered, the T cells are activated, resulting in cytokine release and mononuclear cell recruitment, vesicle formation, and edema. Systemic drug exposure may generate maculopapular skin eruptions, eczematous or exfoliative dermatoses or erythema multiforme with or without mucosal involvement (Stevens–Johnson syndrome) or toxic epidermal necrolysis (TEN). While type IV contact hypersensitivity reactions to topical medications are relatively infrequent, nurses, pharmacists, and other personnel in the pharmaceutical industry are at the greatest risk of developing such an occupational asthma allergy.