Fever of unknown origin (FOD)

Specialty: General.

• fever of unclear etiology
• unexplained prolonged febrile syndrome
• pyrexia of dark origin

Why it occurs

• Atypical or deep localized infections (intra-abdominal abscesses, infective endocarditis with negative cultures, extrapulmonary tuberculosis, vertebral osteomyelitis or coccidioidomycosis)
• Malignant neoplasms, especially of hematological origin or solid tumors (Hodgkin and non-Hodgkin lymphoma, hypernephroma, colon cancer or liver metastases, which release direct tumor pyrogens)
• Connective tissue and autoimmune diseases (adult Still's disease, giant cell arteritis, systemic lupus erythematosus or polyarteritis nodosa)
• Prolonged drug reactions (fever due to drugs such as beta-lactams, anticonvulsants, allopurinol or amphotericin B)
• Granulomatous disorders (sarcoidosis, idiopathic granulomatous hepatitis or extrapulmonary Crohn's disease).

Initial workup

Serial blood cultures (minimum three pairs with prolonged incubation), urine culture, chest x-ray, computed tomography (CT) of the chest, abdomen and pelvis with contrast, transthoracic or transesophageal echocardiogram, and biopsy of suspicious tissues (bone marrow or lymph node).

Standard management

• Avoid antipyretics systematically empirically before obtaining cultures so as not to mask the thermal curve, unless specifically indicated
• Paracetamol — 500 to 650 mg orally every 6 hours if hyperthermia compromises hemodynamic stability or causes delirium
• Empirical broad-spectrum antibiotic therapy (only in neutropenic or hemodynamically unstable patients, not routinely indicated in stable FOD).