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Viral infections and drug hypersensitivity
  • Marie-Charlotte Brüggen,
  • Werner Pichler
Marie-Charlotte Brüggen
UniversitatsSpital Zurich Dermatologische Klinik

Corresponding Author:marie-charlotte.brueggen@usz.ch

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Werner Pichler
ADR-AC GmbH Holligenstr 91 3008 Bern
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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. In the absence of 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 acvitates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity with killing of herpes peptide-expressing cells and release of 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.
03 Jul 2022Submitted to Allergy
08 Jul 2022Submission Checks Completed
08 Jul 2022Assigned to Editor
11 Jul 2022Reviewer(s) Assigned
06 Aug 2022Review(s) Completed, Editorial Evaluation Pending
08 Aug 2022Editorial Decision: Revise Minor
26 Sep 20221st Revision Received
26 Sep 2022Submission Checks Completed
26 Sep 2022Assigned to Editor
29 Sep 2022Reviewer(s) Assigned
12 Oct 2022Review(s) Completed, Editorial Evaluation Pending
14 Oct 2022Editorial Decision: Accept