This review summarizes the molecular mechanisms linking viral infections, particularly HFMD, to onychomadesis, highlighting the role of viral receptors and signaling pathways in nail stem cell differentiation.
Onychomadesis, characterized by proximal detachment of the nail plate due to temporary arrest of matrix proliferation, has been increasingly recognized as a complication following viral infections. Enterovirus-associated hand-foot-and-mouth disease (HFMD) is the most frequently reported cause. Recent studies demonstrate that some enteroviruses, including Coxsackievirus A10, utilize the host receptor KREMEN1 (KRM1) to impair Wnt/β-catenin signaling and suppress nail stem cell differentiation, thereby providing a molecular basis for infection-induced nail shedding. Additionally, cases of onychomadesis linked to other viral infections, including KRM1-independent enteroviruses, influenza virus, SARS-CoV-2, varicella-zoster virus, and co-infections involving HIV and mpox, have also been documented. Despite growing recognition of the virus-induced onychomadesis, in most cases the exact pathogeneses are yet elusive, thereof lack of approved treatments. Understanding the molecular mechanisms of onychomadesis and other sequelae can enhance diagnostics and therapies, guiding future drug development for virus-induced nail disorders and related complications. A comprehensive literature search was conducted using PubMed up to Dec 2025, including the search terms: onychomadesis, Beau's line, infection or virus, and follow-up. This review aims to explore the molecular pathophysiology of virus-induced onychomadesis and to examine the underlying molecular mechanisms, including the roles of viral receptors and signaling pathways in nail stem cell differentiation. It scrutinizes the currently available literatures of link between viral infections, particularly HFMD, and onychomadesis, focusing on the molecular mechanisms involved, and explores potential therapeutic insights.
Cui et al. (Tue,) studied this question.