Medicines in the human body have a direct therapeutic effect, but can also lead to adverse immune and non-immune reactions. Immune one is quite rare and covers up to 10-15% but can be life-threatening.
Drug hypersensitivity reactions (DHR) are heterogeneous. Drugs can activate the immune system in different ways, leading to a large variety of clinical reactions. Different subclassifications based on timing of symptom appearance or type of immune mechanism have been proposed. Mechanisms of action of drugs leading to immune/inflammatory cell stimulation is a further decisive factor in understanding and managing DHR. There are three ways in which they can be distinguished: 1) some drugs have or gain the ability to bind covalently to proteins, with formation of new antigens, and thus elicit immune reactions to hapten-carrier complexes (allergic/immune reaction); 2) a substantial part of immune-mediated DHR is due to a typical off-target activity of drugs on immune receptors like HLA and TCR (pharmacological interaction with immune receptors, p-i reactions); such p-i reactions are linked to severe DHR as SJS, DRESS; and (c) symptoms of DHR can also appear if the drug stimulates or inhibits receptors or enzymes of inflammatory cells (pseudo-allergy). These three distinct ways of stimulations of immune or inflammatory cells differ substantially in time of appearance, dose dependence, predictability, and cross-reactivity, and thus need to be differentiated. Knowledge of potential DHR mechanisms is essential way for the right diagnostic, treatmend and also of choice of alternative drugs.
Laboratory diagnosis of DHR is appropriate in order to avoid potentially dangerous provocation tests in vivo. To this day, it is taking the first steps and, in clinical practice, is advantageous for few types of drug-induced reactions.
