Approach to Pyrexia / Fever of Unknown Origin (FUO) in Older Adults

Classical FUO (Petersdorf and Beeson, 1961) means fever above 38.3°C on several occasions, lasting more than 3 weeks, with no diagnosis after 1 week of hospital investigation.

Durack and Street (1991) revision is the version used today: fever above 38.3°C for more than 3 weeks, undiagnosed after 3 days of inpatient work-up or 3 outpatient visits. Four subtypes exist: classical, nosocomial, neutropenic and HIV-associated.

Inflammation of unknown origin (IUO) is a related entity — prolonged raised acute-phase reactants without fever. It is common in older people and is investigated the same way as FUO.

In the elderly the definition of fever itself must be lowered. Textbook criteria for long-term care residents are a single oral temperature above 100°F (37.8°C), repeated oral temperature above 99°F, or a rise of more than 2°F above the patient's own baseline.

Older people have a lower baseline body temperature and may show no diurnal rise, so a "normal" reading can conceal significant infection.

Fever is blunted or absent in roughly one-third of elderly patients with serious bacterial infection, and typically defined fever is absent in more than half of long-term care residents with serious infection.

Conversely, when fever is present in a very old patient it is more likely to indicate bacterial rather than viral illness — it carries greater diagnostic weight, not less.

Hypothermia is an ominous sign and predicts higher mortality than fever in elderly sepsis. Absence of leucocytosis also does not exclude bacterial infection.

Infections: tuberculosis (miliary and extrapulmonary), infective endocarditis, occult abscess (hepatic, subphrenic, perinephric, dental, prostatic), urinary sepsis, osteomyelitis, infected prosthesis or pacemaker lead. Nearly 50% of infective endocarditis occurs in older adults, usually on degenerative or prosthetic valves.

Non-infectious inflammatory disease: in the elderly this group is proportionally larger than in the young. Giant cell arteritis and polymyalgia rheumatica are the single most important treatable causes; also adult-onset Still's disease, vasculitis and sarcoidosis.

Malignancy: lymphoma (especially non-Hodgkin), renal cell carcinoma, hepatic metastases, atrial myxoma, myelodysplastic syndrome.

Miscellaneous: drug fever (antibiotics, allopurinol, phenytoin, methyldopa), venous thromboembolism, subacute thyroiditis, haematoma, and factitious fever. In India also consider malaria, enteric fever, visceral leishmaniasis, amoebic liver abscess, brucellosis, scrub typhus and dengue.

Key geriatric principle: FUO in an older person is usually an atypical presentation of a common disease, not a rare disease. In elderly series, TB, endocarditis, GCA/PMR and lymphoma account for the majority.

Repeated history and repeated full examination are the highest-yield "investigations." Undress the patient fully: examine the sacrum and heels for pressure sores, temporal arteries, oral cavity and dentition, joints, and do a rectal and genital examination.

Suspect infection in any older person with functional decline, new confusion, falls, incontinence, reduced oral intake or failure to cooperate with staff, even without fever. Also review the drug chart at every step — steroids, paracetamol and NSAIDs mask fever.

First-line tests: complete blood count with differential, ESR and CRP, renal and liver function, urinalysis and urine culture, three sets of blood cultures off antibiotics, chest radiograph, sputum for AFB/CBNAAT, HIV serology, and abdominal ultrasound. A WBC above 14,000/mm³ or left shift above 6% warrants careful assessment for bacterial infection.

Second-line tests: contrast CT chest/abdomen/pelvis, echocardiography (transthoracic then transoesophageal), temporal artery ultrasound or biopsy in anyone above 50 with raised ESR, autoantibodies, protein electrophoresis, and bone marrow examination if cytopenias are present.

Avoid blind antibiotics — they sterilise cultures and obscure the diagnosis. Exceptions are haemodynamic instability, neutropenia and strong suspicion of endocarditis. Do not give an empirical steroid trial before excluding TB and malignancy. Choose empirical cover with gram-negative organisms in mind, adjust all doses to renal function, and monitor aminoglycoside levels. When repeated evaluation is unrevealing, "suspect tuberculosis when an older patient is inexplicably failing."

"In older adults, FUO is usually an atypical presentation of a common disease, not a rare disease."

"Fever in the elderly is defined as a single oral temperature above 100°F, a repeated temperature above 99°F, or a rise of more than 2°F above baseline."

"Giant cell arteritis is the most important treatable cause of FUO in patients over 50 and must be actively excluded."

"Hypothermia in an infected older patient carries a worse prognosis than fever."

"I would not start blind antibiotics or an empirical steroid trial before excluding tuberculosis and malignancy."

Draw a simple algorithm: History and repeated examination → first-line tests → CT and echocardiography → FDG PET-CT → targeted biopsy.