How to investigate a 56-year-old female with recurring episodes of fever, loss of appetite, and a history of upper respiratory tract (URT) infection and allergic bronchitis, despite treatment with antibiotics and inhalers?

Systematic Investigation of Recurrent Fever in a 56-Year-Old Woman

The most appropriate approach to investigate recurrent fever episodes in this 56-year-old woman with a history of upper respiratory tract infection and allergic bronchitis is to follow a systematic diagnostic algorithm focusing first on infectious causes, then non-infectious etiologies including autoinflammatory conditions.

Initial Assessment

• Evaluate the pattern of fever episodes - timing, duration, associated symptoms, and response to previous treatments 1
• Review the complete medication history, including antibiotics and inhalers previously used, to assess for potential drug fever 1
• Document the exact temperature measurements during fever episodes and any associated symptoms (chills, sweats, etc.) 1
• Assess for specific symptoms during fever episodes that might localize the source of infection 1

First-Line Investigations

• Complete blood count with differential to evaluate for leukocytosis, leukopenia, or other hematologic abnormalities 1
• Comprehensive metabolic panel to assess liver and kidney function 1
• Blood cultures (at least two sets) obtained during or just before fever episodes 1
• Urinalysis and urine culture to rule out occult urinary tract infection 1
• Chest radiography to evaluate for persistent pneumonia, bronchiectasis, or other pulmonary pathology 1
• C-reactive protein and erythrocyte sedimentation rate to assess the degree of inflammation 1

Second-Line Investigations

• If respiratory symptoms persist:

  • High-resolution CT scan of the chest to evaluate for bronchiectasis, interstitial lung disease, or occult infection 1
  • Sputum culture for bacterial pathogens, including acid-fast bacilli to rule out tuberculosis 2
  • Consider bronchoscopy with bronchoalveolar lavage if pulmonary infiltrates are present 1

• For persistent fever without obvious source:

  • CT scan of sinuses to evaluate for chronic sinusitis 1
  • Abdominal ultrasound or CT to evaluate for occult intra-abdominal infection, abscess, or malignancy 1
  • Echocardiogram to rule out endocarditis if blood cultures are positive or there are cardiac murmurs 1

Specific Considerations for This Patient

• Evaluate for inadequate treatment of the initial respiratory infection:

  • Review the antibiotic choice, dosage, and duration for the initial upper respiratory tract infection 1
  • Consider resistant organisms if the patient received multiple courses of antibiotics 1
  • Assess for post-viral bronchial hyperreactivity that may be misdiagnosed as allergic bronchitis 1

• Consider non-infectious causes of recurrent fever:

  • Drug fever from antibiotics or other medications 1
  • Autoimmune conditions such as temporal arteritis (especially relevant in this age group) 2
  • Autoinflammatory syndromes that can present with periodic fever 3
  • Occult malignancy, particularly lymphoma 2

Management Algorithm

1. First visit: Complete history, physical examination, and first-line laboratory tests

   • If a clear source is identified, treat accordingly
   • If no source is identified, proceed to second-line investigations 1

2. Within 3-5 days: Reassess response to any initiated treatments

   • If fever persists without identified etiology, expand diagnostic workup 1
   • Consider empiric antibiotic discontinuation if drug fever is suspected 1

3. Within 1-2 weeks: If fever persists despite negative initial workup:

   • Perform CT scans of chest, abdomen, and sinuses 1
   • Consider specialist consultation (infectious disease, rheumatology) 2
   • Evaluate for temporal arteritis with ESR, CRP, and consider temporal artery biopsy if indicated 2

4. Beyond 2 weeks of investigation: If fever remains unexplained:

   • Consider bone marrow biopsy to rule out hematologic malignancy 2
   • Gallium scintigraphy or PET-CT scan to identify occult inflammation or malignancy 2
   • Consider trial of NSAIDs or steroids based on clinical suspicion of inflammatory condition 2

Common Pitfalls to Avoid

• Continuing antibiotics without clear evidence of bacterial infection can lead to resistance and mask the underlying cause 1, 4
• Attributing fever to "viral syndrome" without adequate investigation in an older adult with prolonged symptoms 2
• Failing to consider non-infectious causes early in the diagnostic process 3, 2
• Not recognizing drug fever as a potential cause of recurrent fever episodes 1
• Overlooking tuberculosis, which remains an important cause of fever of unknown origin, especially in older adults 2

By following this systematic approach, the underlying cause of the patient's recurrent fever episodes can be identified and appropriately treated, improving morbidity and mortality outcomes.