What is the recommended diagnostic work‑up and initial management for fever of unknown origin in an elderly patient?

Fever of Unknown Origin in Elderly Patients

Diagnostic Work-Up

In elderly patients with FUO, multisystem diseases—particularly temporal arteritis—are the most common cause, requiring routine temporal artery biopsy as a standard component of the diagnostic evaluation. 1

Initial Clinical Assessment

Perform a focused physical examination targeting high-yield areas specific to elderly patients 2:

• Respiratory rate, hydration status, and mental status (altered mental status may be the only sign of infection in elderly) 2
• Temporal arteries (palpate for tenderness, nodularity, or absent pulse—temporal arteritis is the most frequent specific diagnosis in elderly FUO) 1
• Oropharynx, conjunctiva, and skin (including sacral, perineal, and perirectal areas for occult abscesses) 2
• Chest, heart, and abdomen (intra-abdominal infections account for significant morbidity in elderly) 2
• All indwelling devices (catheters, pacemakers—potential infection sources) 2

Mandatory Initial Laboratory Testing

Within 12-24 hours of symptom onset, obtain 2, 3:

• Complete blood count with manual differential to assess bands and immature forms 2
  • Leukocytosis (WBC ≥14,000 cells/mm³) or left shift (bands ≥6% or total band count ≥1,500 cells/mm³) warrants careful assessment for bacterial infection even without fever 2
• Inflammatory markers: ESR and CRP 3, 4
• Blood cultures: Minimum 2 sets from different sites (ideally 60 mL total) before any antibiotics 3
• Urinalysis with dipstick for leukocyte esterase and nitrite 2
  • Critical caveat: Do NOT culture urine in asymptomatic elderly patients—15-50% have asymptomatic bacteriuria that should not be treated 2

Initial Imaging

• Chest radiography as baseline 3, 4
• Abdominal/pelvic CT or ultrasound if no diagnosis emerges, as intra-abdominal abscesses (diverticulitis, cholecystitis, appendicitis) are leading causes in elderly and may present atypically without focal findings 2

Disease-Specific Diagnostic Priorities in Elderly

The diagnostic approach must prioritize the three most common categories in elderly FUO 1:

1. Multisystem Diseases (31% of cases) 1:

• Temporal artery biopsy should be performed routinely if standard tests are unrevealing 1
• Giant cell arteritis often presents with FUO before classic symptoms emerge 5
• Consider rheumatoid factor and antinuclear antibodies 4

2. Infections (25% of cases) 1:

• Tuberculosis requires extensive search including sputum cultures, interferon-gamma release assays, and consideration of extrapulmonary sites 1
• Intra-abdominal abscesses are a leading diagnosis—maintain high suspicion even without localizing signs 2
• Microbiologic investigations yield diagnosis in 16% of elderly FUO cases 1

3. Malignancies (12% of cases) 1:

• Higher percentage than in younger patients but still less common than multisystem diseases 1

Advanced Imaging When Initial Work-Up Unrevealing

[18F]FDG PET/CT is the highest-yield advanced diagnostic tool with 84-86% sensitivity and 56% diagnostic yield 6, 3:

• Perform within 3 days of starting oral glucocorticoids to avoid false negatives 6, 3
• Has 79% clinical impact, prompting specialist referrals or treatment changes 7
• Gallium scintigraphy had diagnostic contribution in 36% of elderly FUO cases and should be considered before last-resort procedures 1

Tissue Diagnosis

Biopsies yielded final diagnosis in 38% of elderly FUO cases 1:

• Temporal artery biopsy (routine if unrevealing work-up) 1
• CT-guided biopsy of identified lesions 7
• Bone marrow biopsy if hematologic abnormalities present 4

Initial Management

When to Withhold Empiric Therapy

Avoid empiric antibiotics or steroids in stable elderly patients with FUO, as they obscure diagnosis and may be harmful if malignancy or certain infections are present 6, 3:

• Allow self-limiting viral illnesses to resolve without treatment 6
• Steroids mask inflammatory findings on subsequent PET/CT imaging 6
• High-dose steroids increase hospital-acquired infection risk, hyperglycemia, GI bleeding, and delirium without improving mortality 6

Exceptions Requiring Empiric Therapy

Initiate empiric treatment immediately in 6, 3:

• Suspected urosepsis: Obtain urine and blood cultures, change indwelling catheter before specimen collection, then start antibiotics 2
• Critically ill or hemodynamically unstable patients: Obtain 3 blood cultures over 1-2 hours, then start broad-spectrum antibiotics 3
• Intra-abdominal infection suspected: This is a medical emergency requiring admission to acute care facility 2

Special Considerations for Long-Term Care Facility Residents

• Review advance directives before any intervention 2
• If resources available, initial diagnostic tests can be performed in facility if done in timely manner 2
• Transfer to acute care if intra-abdominal infection, urosepsis, or severe pneumonia suspected 2

Critical Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria—it is present in 15-50% of elderly and treatment does not improve outcomes 2
• Do not delay evaluation of intra-abdominal infections—they present atypically in elderly with increased mortality if treatment delayed 2
• Do not skip temporal artery biopsy—temporal arteritis is the most frequent specific diagnosis and may not present with classic symptoms initially 1, 5
• Do not use empiric steroids—they obscure diagnosis and worsen outcomes unless giant cell arteritis is confirmed 6
• Undiagnosed cases are significantly lower in elderly (12%) than younger patients—persistent evaluation usually yields diagnosis 1