Abstract Introduction Parkinsonism-Hyperpyrexia Syndrome (PHS) is a rare, potentially fatal complication of Parkinson’s disease characterized by hyperthermia, rigidity, altered mental status, and autonomic instability following withdrawal or reduction of dopaminergic therapy. Recognition is critical yet challenging, particularly when clinical presentation overlaps with neuroleptic malignant syndrome (NMS) in patients with concurrent antipsychotic exposure. Case Presentation A 77-year-old male with Parkinson’s disease and dementia presented to the emergency department with respiratory distress and decreased responsiveness. His recent history included multiple behavioral health admissions with medication non-compliance, specifically refusing his carbidopa-levodopa. At a psychiatric facility, he received multiple doses of haloperidol for agitation before being transferred. On presentation, he exhibited fever (102.2 °F), tachycardia (HR 154), hypoxia requiring intubation, and rigid extremities without tremors. He developed wide-complex ventricular tachycardia requiring cardioversion and demonstrated persistent hyperpyrexia reaching 104.7 °F despite broad-spectrum antibiotics. Laboratory findings revealed elevated creatine kinase (254 U/L), troponin elevation, and lactic acidosis. Infectious work-up identified polymicrobial pneumonia and UTI; however, fever persisted despite appropriate antimicrobial therapy and negative repeat cultures. Temperature patterns showed persistent elevation unresponsive to antipyretics, requiring external cooling measures. Despite aggressive treatment including therapeutic cooling, antibiotics for concurrent aspiration pneumonia, and cardiovascular support, he demonstrated persistent hyperthermia, recurrent ventricular arrhythmias, hemodynamic instability, and rigidity throughout his seven-day hospitalization. Discussion This case illustrates the diagnostic complexity of PHS in patients with multiple confounding factors. The patient’s medication timeline revealed dopaminergic withdrawal approximately seven days before presentation, consistent with PHS onset patterns. Concurrent haloperidol administration created diagnostic uncertainty between PHS and NMS, though the temporal relationship with carbidopa-levodopa withdrawal favored PHS. The presence of infection further complicated diagnosis, as sepsis initially appeared to explain the clinical presentation. However, persistence of hyperpyrexia and autonomic instability despite infection control suggested an underlying hyperthermia syndrome. Conclusion PHS remains underrecognized, particularly in complex patients with multiple comorbidities. This case emphasizes the importance of detailed medication reconciliation in Parkinson’s patients presenting with unexplained fever and rigidity. Early recognition and prompt reinstitution of dopaminergic therapy are essential for improving outcomes. Clinicians should maintain high suspicion for PHS in Parkinson’s patients with recent medication changes, even when alternative explanations exist. This abstract is funded by: None
Reyles et al. (Fri,) studied this question.