SAT-265 - Fever of Unknown Origin: A Diagnostic Challenge with Current Lipid Lowering Therapies

Introduction:
Evolocumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), is one of the most effective lipid-lowering agents available. Common side effects include injection site reactions, flu-like symptoms (nasopharyngitis, fever, chills), and myalgia. We present a case of a 69-year-old female who was admitted to the hospital for fever of unknown origin, which was likely related to evolocumab use.

Case Description:
Patient had a past medical history of type 2 diabetes, dyslipidemia, and coronary artery disease. She was admitted in August 2024 for coronary artery bypass grafting. At discharge, evolocumab 140 mg every two weeks subcutaneously and ezetimibe 10mg daily were added to atorvastatin 80 mg daily. One week after discharge, she developed intermittent fevers (101–103°F), occurring 2–3 times per month, associated with myalgias, chills, rigors, and malaise. The patient denied sore throat, skin changes, abdominal pain, chest pain, palpitations, nausea, vomiting, headache, or other symptoms. Timing of episodes did not correlate with evolocumab dose; and they continued even when the patient decided to skip 1-2 doses. She received two courses of cefdinir, in October 2024 and January 2025, without resolution of fevers. She was hospitalized in April 2025 for persistent fevers up to 103°F. Laboratory evaluation showed mild leukocytosis, while CMP, ESR, CRP, urinalysis, ANA, and RF were within normal limits. Blood cultures, HIV testing, and hepatitis panel were negative. Transthoracic echocardiogram showed no vegetations. CT imaging of the chest, abdomen, and pelvis with contrast was unremarkable for infectious or acute pathology. Evolocumab was discontinued at discharge due to concern for drug-induced fever. The last evolocumab dose was administered in April 2025. At follow-up in May 2025, the patient reported persisting episodes, even 4 weeks after the last injection. The patient finally reported resolution of fevers around July 2025, 2-3 months after the last dose. No more episodes have been reported since then.

Discussion:
While flu-like symptoms and fever are well-reported with evolocumab, they tend to be mild and resolve over time. To our knowledge, no prior case of evolocumab induced prolonged fever of unknown origin (>3 months) has been reported. Recognizing this potential association may help prevent invasive diagnostic workups and reduce healthcare costs in patients receiving evolocumab who present with fever of unknown origin. Given the long half-life of evolocumab (11-17 days), and lack of correlation in timing of fever episodes with evolocumab dosing, the association may be hard to identify as symptoms can persist even after not taking medication for >1 month. High degree of suspicion is needed to arrive to this diagnosis.

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