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Fever of unknown origin

FUO is defined as the presence of fever of 38.3ºC (>101ºF) or more recorded on several occasions, evolving for at least 3 weeks with no diagnosis reached even after one week of relevant and intelligent investigations. FUO is usually an uncommon presentation of common diseases. FUO are classified into four main categories along with common causes in each of these categories.

1. Classic FUO—corresponds to the previous definition except that instead of one week of investigations, it requires up to 3 outpatient visits or 3 days in the hospital, viz. tuberculosis, abscesses, bacterial endocarditis, visceral leishmaniasis, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, acute leukaemia, and systemic lupus erythematosus.

2. HIV-related FUO—the duration of fever is >4 weeks for inpatients or >3 days for hospitalized patients with HIV infections, viz. tuberculosis, cryptococcosis, Pneumocystis jiroveci pneumonia, and bacterial pneumonia.

3. Nosocomial FUO—fever of >38.3°C on several occasions lasting for more than 72 hours, developing after admission in a hospitalized patient and remains undiagnosed after 3 days of investigation including 2 days incubation of cutures, viz. postoperative (abscess, haematoma, foreign bodies), infected prostheses, infected catheters, Clostridium difficile colitis, deep vein thrombosis, pulmonary embolism, and drug fever.

4. Neutropenic FUO—similar to the previous definition, except that it occurs in a patient who has neutrophil count of less than 500/mm3 or expected to fall to this level in 1-2 days, viz. Gram-negative bacterial, staphylococcal, central venous catheter infections, invasive fungal infections, dental abscesses, perianal infections, cytomegalovirus, and herpes simplex virus infections.

If patient does not fit into any of the above definition, the patient should be referred to a specialist for investigations and management.

SALIENT FEATURES Prolonged unexplained fever, often with no localizing clue on history, physical examination and basic laboratory investigations. Diagnostic evaluation

A detailed clinical history and repeated and meticulous physical examination are valuable in providing potentially diagnostic clues (PDC) to the cause of fever in these patients. No single algorithmic approach to diagnosis can be recommended for all patients of FUO and diagnostic approach needs to be individualized.

A complete haemogram including peripheral blood smear for malarial parasite, serum biochemistry particularly liver function tests, a tuberculin test and an X-ray of chest should be done in every patient with prolonged fever. Other investigations which are often helpful include tests related to collagen vascular disease; an ultrasonography of abdomen to localize intra-abdominal foci of infections and a contrast enhanced computed tomography (CECT) of chest and abdomen in detecting mediastinal lymph nodes and parenchymal lung abnormalities not seen on conventional chest X-ray. Further, diagnostic approach should take into consideration the PDCs from the evaluation of history, results of repeated physical examination, basic investigations and any investigation done prior to this episode. If any abnormal or doubtful lesion is detected FNAC/biopsy should be obtained. Treatment

Treatment will be based on the specific cause of fever. Thorough investigations generally yield a specific cause of fever in about 90% of patients. Sometimes evaluation may need discontinuation of all drugs being taken by the patient to rule out drug fever as the cause of FUO.

Symptomatic treatment for fever (for details see section on fever). Sponging with lukewarm water may be done, if fever produces discomfort. The emphasis in patients with classic FUO is on continued observation and examination.

(Caution: Avoid ‘shotgun’ trials. Empirical therapies consisting of therapeutic trials commonly used in patients with FUO are: Antibiotics, antitubercular treatment (ATT) and corticosteroids).

If on the basis of clinical evaluation and inability to reach a definitive diagnosis, a therapeutic trial is started, the following principles must be kept in mind:

Give only one set of trial at a given time. The doses of drugs and period of therapeutic trial must be

adequate. The patient must be followed closely for response.

The ability of glucocorticoids and NSAIDs to mask fever while permitting the spread of infection dictates that their use should be avoided unless infection has been largely ruled out. Follow-up

In about 10% of cases, no cause may be diagnosed despite thorough evaluation. In such cases, if patient is well preserved, just a close clinical and investigative follow-up may be enough to look for any PDCs which may be evolving or appear later in the course of disease. However, if the patient is sick or is deteriorating and no diagnosis is reached, an appropriate empirical therapeutic trial is justified. Patient education

Self-medication should be avoided. Antibiotics should be taken only on advice of a physician. Avoid covering the patient with high fever with a blanket, etc. Plenty of fluids should be taken. Stay in a cool environment. Washing/sponging of face and limbs should be done repeatedly.



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