Pyrexia of Unknown Origin

One of the most challenging problem a physician used to face in day to day practice is the evaluation of patients with prolonged pyrexia—a truly significant test of his clinical skills. Causes of PUO vary according to geographical area, health care setup, investigations facilities, and physicians’ attitude. Because of socioeconomic and other factors, infectious diseases are still very common in developing countries. Amongst the infectious causes tuberculosis usually extra pulmonary or miliary is the single most common infection in most PUO series. Mycobacterium tuberculosis is a genius organism which can affect any and every organ system of the body. It can virtually produce any known clinical syndrome except true pregnancy. So it is reasonable to think of tuberculosis as a cause of fever in a PUO setting when no cause is obvious. The most important investigation in a case of PUO is to evaluate the patient by a physician who has not seen the patient previously. The tests already done should be reviewed attentively. There might have some clue to diagnosis in those. Some investigations may have to be repeated; new investigations may have to be ordered. Definitive diagnosis of tuberculosis requires isolation of the tubercle bacillus from the body fluid or any tissue obtained by FNA or biopsy, which is often difficult. Institution of empirical anti tuberculous therapy may be justified in any patient of PUO where no specific diagnosis is evident after a reasonable diagnostic workup and tuberculosis is a strong possibility and the patient is rapidly deteriorating. “Humanity has three great enemies: fever, famine and wars. Of these by far the greatest, by far the most terrible is fever” – Sir William Osler (1849-1919). Terrible for the patient because of not curing within expected period and terrible for the physician for not reaching a diagnosis even after exhaustive investigation. There are 3 types of fever usually the physicians encounter: acute onset fever usually producing no diagnostic or therapeutic problem; Recurrent fever; and third group having prolonged fever amongst which a group remains undiagnosed even after logical extensive investigations termed as pyrexia or fever of unknown or undetermined origin (PUO or FUO). One of the most challenging problems a physician faces in his daily practice is the evaluation of a patient with prolonged pyrexia—a truly significant test of his clinical skills. PYREXIA OF UNKNOWN ORIGIN In 1961, Petersdorf and Beeson first defined PUO as “fever lasting for more than 3 weeks, more than 38.3°C on several occasions and no diagnosis after 1 week of indoor investigations”.1 Three weeks duration eliminated short lived infections; mainly viral fevers and 1 week of indoor investigations allow sufficient time for appropriate initial investigations to be completed. Cost of hospitalization is increasing day by day. Now a days most of the patients of PUO can be managed as outdoor patients and incidence of HIV (human immunodeficiency virus), nosocomial infections and neutropenic patients are increasing day by day. Considering this, Durack and Street (1991) proposed a new classification of PUO (Table 1).2 Major changes in new classification were that it didn’t require 3 weeks duration to satisfy diagnosis of PUO and blood culture negative at 48 hours was a must. WHEN A FEVER CASE DOES BECOMES PUO? Unawareness of atypical presentations of common diseases (most important), lack of detailed initial clinical work up, delay in advising appropriate investigation, misinterpretation of either clinical feature or investigation result, false negative or positive test results and multiple pathologies in the same patient are the few factors responsible for a fever case to be labeled as PUO. Repeated basic clinical evaluation is probably most important factor in reaching a diagnosis. But in some cases of PUO, the cause remains undiagnosed even after exhaustive investigations. Explanation for such fevers could be pathologies which are yet unidentified or diagnostic tests for them are not available widely or not advised. Often a patient who complains of fever does not have fever when checked by thermometer. So ‘I feel feverish, ‘fever is inside the body...does not come in thermometer’ should not be considered as PUO. According to one study (PUO of >1 year duration on average) 28% patients did not have fever when oral temperatures were taken for several weeks. 3 They are the most anxious people and do doctor shopping. By this time they have done so many investigations failing to find any clue or solving their problem. They may be asked to record the temperature C H A P T E R 7 Approach to patients with Pyrexia of Unknown Origin Suspected to have Tuberculosis