Atypical Presentation of Lamotrigine Induced DRESS Syndrome: A Case Report and Review of the Literature

Abstract

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal hypersensitivity reaction associated with a range of medications, including aromatic anticonvulsants such as lamotrigine. This syndrome is characterized by delayed onset, fever, rash, hematologic abnormalities, and multi-organ involvement. Although eosinophilia is often considered a hallmark, its absence does not rule out the diagnosis. Case Presentation: We present the case of a 40-year-old man with intellectual disability and chronic polypharmacy who developed DRESS syndrome three weeks after the initiation of lamotrigine. His clinical course was marked by fever, diffuse skin rash, hepatic dysfunction, and acute anuric renal failure requiring dialysis. Laboratory evaluation revealed markedly elevated liver enzymes, high inflammatory markers, and atypical lymphocytosis without eosinophilia. Despite initial improvement following high-dose intravenous corticosteroids, the patient experienced sudden pancytopenia, respiratory failure, and ultimately died from suspected sepsis. Conclusions: A comprehensive review of 34 reported cases of lamotrigine-induced DRESS showed significant heterogeneity in clinical presentation, with 18% lacking eosinophilia and only limited viral reactivation testing reported. Notably, severe renal involvement such as seen in this case was rare, emphasizing the spectrum of disease severity. This report highlights the diagnostic challenges of DRESS syndrome, particularly in atypical presentations and vulnerable populations. It underscores the importance of early recognition, comprehensive diagnostic workup — including consideration of viral reactivation — and prompt withdrawal of the offending agent. Clinician awareness of atypical features, such as the absence of eosinophilia and fulminant organ failure, is critical for timely diagnosis and intervention.