Pathophysiology, Etiology, and Clinical Manifestations of Fever of Unknown Origin (FUO)

Fever of unknown origin (FUO) is a prolonged fever exceeding three weeks without an obvious etiology despite thorough investigation. It manifests across different patient populations including immunocompetent individuals, neutropenic patients, nosocomial cases, and those with HIV.

Pathophysiology and Etiology

FUO is often attributed to infectious diseases, malignancies, autoimmune disorders, and undiagnosed conditions. Each patient population experiences different underlying causes:

• Immunocompetent patients: Often associated with bacterial, viral, or fungal infections, or inflammatory diseases.
• Neutropenic patients: Frequently caused by opportunistic infections due to compromised immunity.
• Nosocomial cases: Post-surgical infections, drug fever, and central line-associated infections.
• HIV-positive individuals: Opportunistic infections such as tuberculosis and cytomegalovirus, or neoplastic diseases.

Clinical Manifestations

FUO presents with a persistent fever exceeding 38.3°C (101°F) accompanied by systemic symptoms such as malaise, weight loss, and night sweats.

Diagnostic Approach

Laboratory Investigations

Extensive laboratory testing, including complete blood count, inflammatory markers (CRP, ESR), serology, and cultures, is essential to determine the underlying cause.

Imaging Techniques

CT scans, MRI, and PET scans play crucial roles in detecting occult infections, malignancies, and autoimmune disorders.

Clinical Criteria

Diagnosis is established by fulfilling criteria such as prolonged fever, negative routine diagnostics, and the exclusion of common causes.

Conclusion

FUO remains a diagnostic challenge requiring a multidisciplinary approach. Advances in imaging and molecular diagnostics are aiding clinicians in identifying elusive etiologies.