Journal of Infection and Public Health (2011) 4, 108—124 REVIEW Fever, fever patterns and diseases called ‘fever’ — A review Dimie Ogoina ∗ Immunology and Infectious Disease Unit, Department of Medicine, Bingham University Teaching Hospital, Jos Plateau State, Nigeria Received 19 February 2011; received in revised form 21 April 2011; accepted 8 May 2011 KEYWORDS Summary Fever is a prominent feature of disease since antiquity. The febrile Fever; response is orchestrated by the central nervous system through endocrine, neuro- Body temperature; logical, immunological and behavioural mechanisms. Other than a regulated rise Pyrogens; in body temperature, fever is often accompanied by various sickness behaviours, Pathogenesis; changes in metabolic and physiological characteristics of body systems and alter- ations in immune responses. Fever and the febrile response, therefore, remain Fever patterns; significant contributors to the pathogenesis, clinical presentation and outcome of Disease many illnesses and diseases. This review highlights the pathophysiology of the febrile response and describes the fever types and patterns, including their clinical significance. The various med- ical illnesses called ‘‘fever’’ are also listed and the origins of their appellations discussed. © 2011 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved. Contents Introduction ................................................................................................ 109 Thermoregulation........................................................................................... 109 Defining normal and febrile body temperatures ........................................................ 110 Pathophysiology of the febrile response..................................................................... 110 Fever: the role pyrogens and cryogens ................................................................. 110 Pryogens ......................................................................................... 110 Cryogens......................................................................................... 111 The fever pathways .................................................................................... 111 The humoral pathway ............................................................................ 111 The neural pathway.............................................................................. 112 ∗ Correspondence address: PMB 005, Karu, Nasarawa State, Nigeria. Mobile: +234 8034510717. E-mail address: [email protected] 1876-0341/$ — see front matter © 2011 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jiph.2011.05.002 Fever, fever patterns and diseases called ‘fever’ — A review 109 Symptoms of fever.......................................................................................... 112 Classification, types and patterns of fever .................................................................. 112 Mechanisms underlying fever patterns.................................................................. 114 Significance of fever patterns .......................................................................... 115 Diseases called ‘fever’ ...................................................................................... 115 Concluding remarks......................................................................................... 122 Funding ..................................................................................................... 122 Competing interests ........................................................................................ 122 Ethical approval ............................................................................................ 122 Acknowledgment.......................................................................................... 122 References ................................................................................................ 122 Introduction This review gives an overview of the pathophys- iology of the febrile response and describes the Fever is one of the oldest clinical indicators of fever types and patterns, including their clinical disease in the mammalian host as well as one of significance. The various medical illnesses called the most common reasons for medical consultations ‘‘fever’’ are also listed and the origins of their worldwide [1,2]. Fever often occurs in response to appellations discussed. infection, inflammation and trauma. However, this view of fever is merely an oversimplification as a growing body of evidence now suggests that fever Thermoregulation represents a complex adaptive response of the host to various immune challenges whether infec- In healthy individuals, body temperature varies in tious or non-infectious. Although elevated body relation to several environmental and biological temperature is an indispensable component of factors such as time of day, site of temperature the febrile response, it is not synonymous with measurements, level of physical activity, age, sex fever. It is generally agreed that fever is a reg- and race, among others [2,7]. In spite of this vari- ulated rise in body temperature above normal ability, body temperature is tightly regulated within daily fluctuations occurring in conjunction with a fairly constant range-a thermal set point (recently an elevated thermoregulatory set point [1—5]. renamed thermal balance point [8]) through the To highlight the adaptive nature of the febrile process of thermoregulation. response, the International Union of Physiological The old view that temperature regulation func- Sciences Commission for Thermal Physiology in 2001 tions as a unified control system with a single defined fever as a state of elevated core temper- thermoregulatory centre has been rejected. Based ature, which is often, but not necessarily, part of on recent evidence, core temperature is regulated the defensive responses of multicellular organisms by various relatively independent thermoeffector (host) to the invasion of live (micro-organisms) or loops, each having its own afferent and efferent inanimate matter recognised as pathogenic or alien branches [7—9]. Hence, the regulation of body by the host [6]. temperature is dependent on a thermoregulatory The complexity of the febrile response may circuitry. However, the preoptic region of the ante- be attributable to its multi-systemic effects rior hypothalamus is still considered the major orchestrated by endocrine, neurological, immuno- thermoregulatory centre in the CNS where periph- logical and behavioural mechanisms. Apart from eral and centrally generated temperature signals a regulated rise in body temperature, fever is are received and integrated [7—9]. also accompanied by various sickness behaviours, The preoptic region consists of heat sensitive changes in metabolic and physiological character- neurons, namely warm and cold sensitive neu- istics of body systems and alterations in immune rons, which are activated or inhibited in response responses [2,3]. The febrile response, therefore, to temperature changes. In cold environments, remains a significant contributor to the pathogen- decrease firing of warm sensitive neurons and esis, clinical presentation and outcome of many increase firing of cold sensitive neurons leads to illnesses and diseases. Consequently, understanding activation of heat gain mechanisms and preven- fever and febrile response is vital in the diagnosis, tion of heat loss (i.e. by skin vasoconstriction, treatment and follow-up of various ailments and piloerection, decrease sweating, increased mus- diseases. cle contraction, non-shivering thermogenesis, and 110 D. Ogoina seeking warm clothing or environments). In hot temperatures [2,8]. Although, axillary tempera- environments, increase firing of warm sensitive tures are convenient to undertake, they are the neurons and decrease firing of cold sensitive neu- least accurate method of temperature measure- rons leads to activation of heat loss mechanisms ment, especially in adults. Axillary thermometers and inhibition of heat gain mechanisms (i.e. by take longer time to reach equilibrium and they are sweating, removal of clothing or seeking cold envi- altered by various factors such as by ambient tem- ronments). Ultimately, body temperature is kept perature, sweat, humidity and the density of hair within a normal regulated limit by a delicate bal- in the axilla [2,8]. ance between heat loss and heat gain. Pathophysiology of the febrile response Defining normal and febrile body temperatures The development of the febrile response is akin to the normal thermoregulatory processes that fol- Due to wide variability of body temperature in low exposure to cold temperatures. However, in relation to several factors, defining febrile body fever the thermal balance point is reset to a higher temperatures remain a subject of controversy with level such that normal peripheral and central body varied definitions by different authors. However, temperatures are now sensed as cold temperature most authors [2—4] are in agreement with a study signals by the thermoregulatory circuitry [2—5]. in which modern calibrated thermometers were Consequently, fever is different from heat stroke used to measure 700 baseline-oral temperatures of and hyperthermia where body temperature is ele- 148 middle aged healthy adults of different races vated without a corresponding elevation of the [10]. In this study, the mean