Title: Fever of Unknown Etiology
Authors: Suk Zhou, OMS III; Palvinder Garcha, OMS III; Nell Shonnard, PA-C; Mihret Asressahegn, MD
Abstract
In adults, fever ≥ 100.4°F with altered mental status is usually concerning for infection. This case is unique in that a patient, who presented with a one day fever of 101.2°F and altered mental status, had an unremarkable extensive workup during her 12 day hospitalization.
A 68-year-old Caucasian female with a history of HTN, DM II, COPD, and GERD presented to the ER after she was found stabbing the carpet with scissors by her spouse. Per family, she had worsening mentation for a “few weeks” with generalized weakness. In the ER, the patient had a fever of 101.2 F; other vitals included HR of 100 bpm, BP of 140/P, and 88% O2 Sat on RA. On exam, she had latency of speech. NIH Stroke Scale was 0 and CTA Head w/out contrast was unremarkable. Brain MRI had no acute abnormality. Sepsis workup was initiated and blood cultures were drawn. WBC, lactic acid, COVID, inflammatory markers, UA, CXR, and urine toxicology were unremarkable. Due to suspicion of meningoencephalitis, LP was performed and dexamethasone with broad antimicrobial therapy (IV acyclovir, ampicillin, ceftriaxone, and vancomycin) were started. The patient was admitted to PCU. CSF returned negative for WBC, protein, or glucose abnormality; antimicrobial therapy was discontinued. Her blood, UA, and CSF cultures showed no growth. Day 3 to 7 of hospitalization, the patient’s BP was elevated despite multiple antihypertensive agents. Subsequent renal doppler did not show stenosis. Tele-psychiatry was consulted for depression and anxiety. The patient’s mentation and BP did improve on day 7 of hospitalization. Aside from the one episode of fever, the patient remained afebrile during her stay. The patient was discharged to an assisted living facility. Final diagnoses included:
- Fever resolved, source unclear
- Acute metabolic encephalopathy, possibly due to delirium
- Watery diarrhea, possibly secondary to antibiotic treatment
- HTN
- Hyperlipidemia
- Hypothyroidism
- COPD
- OSA
- Depression/Anxiety
There is no adequate explanation for the patient’s initial fever and altered mental status. Recent searches for similar case presentations yielded limited results. While this case demonstrates the standard of care for patients presenting with similar symptoms, it also illuminates a category of patients with fever of unclear etiology who do not fit the accepted clinical definition for fever of unknown etiology (FUO) proposed by Petersdorf and Beeson in 1961. There is room for discussion regarding follow up care for this patient population after discharge from the hospital.
I am one of the judges for your interesting case study. Based on what you know about FUO and the inconsistent diagnostic criteria, if the hospital asked you to provide the 3 to 5 most important criteria to make this diagnosis, what would you suggest?
Hi Dr. Callan,
Thank you for watching our presentation.
I would suggest the following as the most important criteria to make the diagnosis of FUO:
1) Fever higher than 38.3°C (taken from Petersdorf and Beeson 1961 definition)
2) Absence of an identified cause of fever despite workup in either inpatient or outpatient setting
(taken from Haidar and Singh 2022)
3) Fever for sufficient time to rule out self-limiting fevers, based on clinical judgement (taken from Haidar and Singh 2022)
Thank you
Thank you for your presentation. The case appears to fit recent criteria for FUO, what do you think about having a time requirement for FUO? Do you agree with the recent suggestions of no time requirement, or should there be a time requirement?
Hi Dr. Walser,
Thank you for watching our presentation.
I do believe there should be a time component to the diagnosis. However, I do NOT think it should be as rigid as the one proposed by Petersdorf and Beeson. I think the time component should be based on clinical judgement for the specific patient case. Ultimately, the quality, duration, and result of the patient’s diagnostic workup should have more weight in the consideration of FUO.
Thank you
Judge: Can you do a differential diagnosis including the possible causes of the acute metabolic encephalopathy and why delirium was ultimately proposed as a possible cause?
Hi Jennifer,
Thank you for watching our presentation.
Our differential diagnoses:
– Meningoencephalitis
– Drug induced cognitive impairment
– Dementia with behavioral disturbance
– Acute metabolic encephalopathy in the setting of underlying cognitive impairment
– Stroke
The causes of acute metabolic encephalopathy can be the following:
– Hepatic or renal failure
– Uncontrolled diabetic states such as diabetic ketoacidosis
– Hyperthyroidism
– Hypothyroidism
– Vitamin or electrolyte deficiencies and abnormalities
The mechanism of delirium is unclear and therefore often used as a diagnosis of exclusion. Such as in the case of this patient who had an overwhelmingly unremarkable workup despite her initial presentation. This is why the rigid time component in the standard definition of FUO, proposed by Petersdorf and Beeson 1961, is sometimes problematic.
Thank you