Low-grade Fever: How to Distinguish Organic from Non-organic Forms

From International Journal of Clinical Practice
M. Affronti; P. Mansueto; M. Soresi; A. M. Abbene; A. Affronti; M. Valenti; L. Giannitrapani; G. Montalto

Posted: 02/18/2010; Int J Clin Pract. 2010;64(3):316-321. © 2010

Abstract
Background and aim: Low-grade fever (LGF) is defined as a body temperature between 37.5 and 38.3 °C, which is below the classical value reported for fever of unknown origin (FUO). We attempted to characterise its epidemiology, aetiology and clinical aspects to improve the methodological approach to diagnosis.

Design and Methods: We reviewed and evaluated a survey of patients with LGF, followed as outpatients of our Department, a tertiary referral centre from 1997 to 2008. The same classifications were applied for classical FUO, and in the patients diagnosed with LGF, we also investigated for habitual hyperthermia (HH).
Results: Seventy-three patients were selected and divided into two groups: group A included 32 patients classified with organic fever and group B included 41 patients with HH. Aetiology of organic LGF was: infectious disease 59%; neoplasm 3.1%; inflammatory non-infectious disease 6.2%; miscellaneous 18.7%; undiagnosed 12.5%. Mean age was significantly higher in the organic fever than in the HH group (p < 0.02). Splenomegaly and loss of weight were significantly associated with organic fever (p < 0.05), while dizziness and general malaise were associated with HH. Lack of any pathological signs at physical examination was significantly more frequent in HH (p < 0.0001). Among the biochemical tests, white blood cells and C-reactive protein were more frequently above normal limits in group A than in group B (p < 0.05).

Conclusions: In our experience, LGF requires the same methodological diagnostic approach as FUO, because there is no relationship between body temperature values and the severity of the underlying diseases, and the aetiological spectrum is also the same.

Introduction
Fever is one of the most common clinical manifestations referred by patients to their physicians.[1] The challenge is to distinguish between fevers caused by the more or less serious pathologies, requiring a specific therapy, and those caused by the vast majority of other ailments, which instead often present a self-limited pathology.
Fever is defined as an increase in body temperature mediated by a functional alteration of the regulatory centre of the hypothalamus, causing a rise in temperature towards the upper values of the set-point, the activation of the peripheral mechanisms of thermogenesis and the inhibition of those of thermodispersion.[2,3]
Hyperthermia, on the contrary, is an increase in body temperature independent of the physiological homeostatic control mechanisms, which do not, however, raise the hypothalamus set-point. In other words, it arises from a 'peripheral' alteration of the mechanisms of thermoproduction and thermodispersion.

Another important condition is the fever of unknown origin (FUO), which poses considerable problems for physicians, because although most diseases underlying FUO are treatable, they can be difficult to diagnose in a particular patient and for reasons which are not always clear.[4–11]

Low-grade fever (LGF) commonly refers to a condition with a body temperature continually or intermittently between 37.5 and 38.3 °C. As in the case of fever, it is absolutely a symptom accompanying very many infectious, and autoimmune and neoplastic diseases. Sometimes, however, there is no particular organic pathology, as in the case of habitual hyperthermia (HH), which, rather than a disease, should be considered a paraphysiological variant of normal body temperature.[6]

Habitual hyperthermia is a clinical condition characterised by a body temperature never higher than 38.3 °C, with an erratic circadian rhythm. It may persist for years and for rather complex reasons, and the normal body temperature of an otherwise perfectly healthy subject remains elevated. It is typical of young asthenic women prone to headaches and with vasomotor liability. Its diagnosis today is still possible, but only after an adequately prolonged period of observation and measurement of body temperature.[6] Although FUO is widely recognised and is frequently reported, in our opinion, LGF has not received adequate attention in the literature. This work, therefore, reviews our clinical experience of patients with LGF, with the aim of shedding further light on its frequency, causes, management, work-up, prognosis and possible links with the much better-known forms of FUO.