Viral infections and drug hypersensitivity

Abstract Virus infections and T‐cell‐mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus‐induced second signals: certain drugs like β‐lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo‐antigens do not induce an immune reaction, probably because co‐stimulation is missing. During a virus infection, the hapten‐modified peptides are presented in an immune‐stimulatory environment with co‐stimulation. A drug‐specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p‐i) : drugs tend to bind to proteins and may even bind to immune receptors. Without viral infections, this low affine binding may be insufficient to elicit T‐cell activation. During a viral infection, immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p‐i reactions and may even be sufficient for T‐cell activation and symptoms. There is a situation where the virus‐DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p‐i mediated immune stimulation during acute DRESS, which coincidentally activates many herpes virus‐specific T cells. Through p‐i stimulation, they develop a cytotoxic activity by killing herpes peptide‐expressing cells and releasing herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes‐virus viraemia after DRESS.