Mapping the spectrum of cutaneous adverse reactions associated with systemic acyclovir and valacyclovir: a scoping review

Cutaneous adverse drug reactions (CADRs) associated with systemic antiviral agents such as acyclovir and valacyclovir are generally considered uncommon but may present with a wide range of clinical and histopathological patterns, from mild exanthems to severe and potentially life-threatening reactions. Although these medications are widely used in the management of herpesvirus infections across diverse patient populations, the full spectrum, frequency, and characteristics of their associated cutaneous reactions have not been comprehensively mapped. Existing evidence is scattered across case reports and small observational studies, which limits clinicians’ ability to recognize atypical presentations and assess potential risk factors. The purpose of this scoping review is to systematically identify, map, and categorize all reported cutaneous adverse reactions associated with systemic acyclovir and valacyclovir in human patients. The review will summarize clinical morphologies, histopathological findings, timing of onset, dosing relationships, management strategies, and patient outcomes. Particular attention will be given to uncommon, severe, or poorly characterized reaction patterns, including biphasic or papulovesicular eruptions observed at higher drug doses. This scoping review will follow established methodological frameworks for scoping reviews and will include primary studies such as observational studies, case series, and case reports published in English or Spanish. Multiple bibliographic databases will be systematically searched to ensure comprehensive coverage of the literature. The expected outcomes of this project include: (1) a comprehensive map of the spectrum of cutaneous adverse reactions to systemic acyclovir and valacyclovir; (2) improved characterization of clinical and histopathological patterns; (3) identification of knowledge gaps and research priorities; and (4) generation of clinically relevant information that may support earlier recognition, risk stratification, and safer prescribing practices. Ultimately, this review aims to strengthen pharmacovigilance knowledge regarding these widely used antiviral agents and to inform future research and clinical decision-making.