|Other names||Pyrexia, febrile response|
|An analog medical thermometer showing a temperature of 38.7 °C or 101.7 °F|
|Specialty||Infectious disease, pediatrics|
|Symptoms||Initially: shivering, feeling cold|
Later: flushed, sweating
|Causes||Increase in the body's temperature set point|
|Diagnostic method||Temperature > between 37.5 and 38.3 °C (99.5 and 100.9 °F)|
|Treatment||Based on underlying cause, not required for fever itself|
|Medication||Ibuprofen, paracetamol (acetaminophen)|
Fever, also known as pyrexia and febrile response, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using values between 37.5 and 38.3 °C (99.5 and 100.9 °F). The increase in set point triggers increased muscle contractions and causes a feeling of cold. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. Rarely a fever may trigger a febrile seizure. This is more common in young children. Fevers do not typically go higher than 41 to 42 °C (105.8 to 107.6 °F).
A fever can be caused by many medical conditions ranging from non-serious to life-threatening. This includes viral, bacterial and parasitic infections such as the common cold, urinary tract infections, meningitis, malaria and appendicitis among others. Non-infectious causes include vasculitis, deep vein thrombosis, side effects of medication, and cancer among others. It differs from hyperthermia, in that hyperthermia is an increase in body temperature over the temperature set point, due to either too much heat production or not enough heat loss.
Treatment to reduce fever is generally not required. Treatment of associated pain and inflammation, however, may be useful and help a person rest. Medications such as ibuprofen or paracetamol (acetaminophen) may help with this as well as lower temperature. Measures such as putting a cool damp cloth on the forehead and having a slightly warm bath are not useful and may simply make a person more uncomfortable. Children younger than three months require medical attention, as might people with serious medical problems such as a compromised immune system or people with other symptoms. Hyperthermia does require treatment.
Fever is one of the most common medical signs. It is part of about 30% of healthcare visits by children and occurs in up to 75% of adults who are seriously sick. While fever is a useful defense mechanism, treating fever does not appear to worsen outcomes. Fever is viewed with greater concern by parents and healthcare professionals than it usually deserves, a phenomenon known as fever phobia.
- 1 Signs and symptoms
- 2 Diagnosis
- 3 Pathophysiology
- 4 Management
- 5 Epidemiology
- 6 History
- 7 Society and culture
- 8 Other animals
- 9 References
- 10 Further reading
- 11 External links
Signs and symptoms
|Note: The difference between fever and hyperthermia is the underlying mechanism. Different sources have different cut-offs for fever, hyperthermia and hyperpyrexia.|
A wide range for normal temperatures has been found. Central temperatures, such as rectal temperatures, are more accurate than peripheral temperatures. Fever is generally agreed to be present if the elevated temperature is caused by a raised set point and:
- Temperature in the anus (rectum/rectal) is at or over 37.5–38.3 °C (99.5–100.9 °F) An ear (tympanic) or forehead (temporal) temperature may also be used.
- Temperature in the mouth (oral) is at or over 37.7 °C (99.9 °F)
- Temperature under the arm (axillary) is at or over 37.2 °C (99.0 °F)
In healthy adults, the range of normal, healthy temperatures for oral temperature is 33.2–38.2 °C (91.8–100.8 °F), for rectal it is 34.4–37.8 °C (93.9–100.0 °F), for tympanic membrane (the ear drum) it is 35.4–37.8 °C (95.7–100.0 °F), and for axillary (the armpit) it is 35.5–37.0 °C (95.9–98.6 °F). Harrison's Principles of Internal Medicine defines a fever as a morning oral temperature of >37.2 °C (>98.9 °F) or an afternoon oral temperature of >37.7 °C (>99.9 °F) while the normal daily temperature variation is typically 0.5 °C (0.9 °F).
Normal body temperatures vary depending on many factors, including age, sex, time of day, ambient temperature, activity level, and more. A raised temperature is not always a fever. For example, the temperature of a healthy person rises when he or she exercises, but this is not considered a fever, as the set point is normal. On the other hand, a "normal" temperature may be a fever, if it is unusually high for that person. For example, medically frail elderly people have a decreased ability to generate body heat, so a "normal" temperature of 37.3 °C (99.1 °F) may represent a clinically significant fever.
The pattern of temperature changes may occasionally hint at the diagnosis:
- Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1 °C in 24 hours, e.g. lobar pneumonia, typhoid, meningitis, urinary tract infection, or typhus. Typhoid fever may show a specific fever pattern (Wunderlich curve of typhoid fever), with a slow stepwise increase and a high plateau. (Drops due to fever-reducing drugs are excluded.)
- Intermittent fever: The temperature elevation is present only for a certain period, later cycling back to normal, e.g. malaria, kala-azar, pyaemia, or sepsis. Following are its types:
- Quotidian fever, with a periodicity of 24 hours, typical of Plasmodium knowlesi malaria
- Tertian fever (48-hour periodicity), typical of later in the course of Plasmodium falciparum, Plasmodium vivax, or Plasmodium ovale malaria
- Quartan fever (72-hour periodicity), typical of later in the course of Plasmodium malariae malaria.
- Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1 °C in 24 hours, e.g., infective endocarditis, brucellosis.
- Pel–Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists.
A neutropenic fever, also called febrile neutropenia, is a fever in the absence of normal immune system function. Because of the lack of infection-fighting neutrophils, a bacterial infection can spread rapidly; this fever is, therefore, usually considered to require urgent medical attention. This kind of fever is more commonly seen in people receiving immune-suppressing chemotherapy than in apparently healthy people.
Febricula is an old term for a low-grade fever, especially if the cause is unknown, no other symptoms are present, and the patient recovers fully in less than a week.
Hyperpyrexia is an extreme elevation of body temperature which, depending upon the source, is classified as a core body temperature greater than or equal to 40.0 or 41.5 °C (104.0 or 106.7 °F). Such a high temperature is considered a medical emergency, as it may indicate a serious underlying condition or lead to problems including permanent brain damage, or death. The most common cause of hyperpyrexia is an intracranial hemorrhage. Other possible causes include sepsis, Kawasaki syndrome, neuroleptic malignant syndrome, drug overdose, serotonin syndrome, and thyroid storm.
Infections are the most common cause of fevers, but as the temperature rises other causes become more common. Infections commonly associated with hyperpyrexia include roseola, measles and enteroviral infections. Immediate aggressive cooling to less than 38.9 °C (102.0 °F) has been found to improve survival. Hyperpyrexia differs from hyperthermia in that in hyperpyrexia the body's temperature regulation mechanism sets the body temperature above the normal temperature, then generates heat to achieve this temperature, while in hyperthermia the body temperature rises above its set point due to an outside source.
Hyperthermia is an example of a high temperature that is not a fever. It occurs from a number of causes including heatstroke, neuroleptic malignant syndrome, malignant hyperthermia, stimulants such as substituted amphetamines and cocaine, idiosyncratic drug reactions, and serotonin syndrome.
Fever is a common symptom of many medical conditions:
- Infectious disease, e.g., influenza, primary HIV infection, malaria, Ebola, infectious mononucleosis, gastroenteritis, Lyme disease, Dengue
- Various skin inflammations, e.g., boils, abscess
- Immunological diseases, e.g., lupus erythematosus, sarcoidosis, inflammatory bowel diseases, Kawasaki disease, Still disease, Horton disease, granulomatosis with polyangiitis, autoimmune hepatitis, relapsing polychondritis
- Tissue destruction, which can occur in hemolysis, surgery, infarction, crush syndrome, rhabdomyolysis, cerebral bleeding, etc.
- Reaction to incompatible blood products
- Cancers, most commonly kidney cancer and leukemia and lymphomas
- Metabolic disorders: gout, porphyria
- Inherited metabolic disorder: Fabry disease
Persistent fever that cannot be explained after repeated routine clinical inquiries is called fever of unknown origin.
Temperature is ultimately regulated in the hypothalamus. A trigger of the fever, called a pyrogen, causes release of prostaglandin E2 (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point.
In many respects, the hypothalamus works like a thermostat. When the set point is raised, the body increases its temperature through both active generation of heat and retention of heat. Peripheral vasoconstriction both reduces heat loss through the skin and causes the person to feel cold. Norepinephrine increases thermogenesis in brown adipose tissue, and muscle contraction through shivering raises the metabolic rate. If these measures are insufficient to make the blood temperature in the brain match the new set point in the hypothalamus, then shivering begins in order to use muscle movements to produce more heat. When the hypothalamic set point moves back to baseline either spontaneously or with medication, the reverse of these processes (vasodilation, end of shivering and nonshivering heat production) and sweating are used to cool the body to the new, lower setting.
This contrasts with hyperthermia, in which the normal setting remains, and the body overheats through undesirable retention of excess heat or over-production of heat. Hyperthermia is usually the result of an excessively hot environment (heat stroke) or an adverse reaction to drugs. Fever can be differentiated from hyperthermia by the circumstances surrounding it and its response to anti-pyretic medications.
A pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous) to the body. The bacterial substance lipopolysaccharide (LPS), present in the cell wall of gram-negative bacteria, is an example of an exogenous pyrogen. Pyrogenicity can vary: In extreme examples, some bacterial pyrogens known as superantigens can cause rapid and dangerous fevers. Depyrogenation may be achieved through filtration, distillation, chromatography, or inactivation.
In essence, all endogenous pyrogens are cytokines, molecules that are a part of the immune system. They are produced by activated immune cells and cause the increase in the thermoregulatory set point in the hypothalamus. Major endogenous pyrogens are interleukin 1 (α and β) and interleukin 6 (IL-6). Minor endogenous pyrogens include interleukin-8, tumor necrosis factor-β, macrophage inflammatory protein-α and macrophage inflammatory protein-β as well as interferon-α, interferon-β, and interferon-γ. Tumor necrosis factor-α also acts as a pyrogen. It is mediated by interleukin 1 (IL-1) release.
These cytokine factors are released into general circulation, where they migrate to the circumventricular organs of the brain due to easier absorption caused by the blood–brain barrier's reduced filtration action there. The cytokine factors then bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, the arachidonic acid pathway is then activated.
One model for the mechanism of fever caused by exogenous pyrogens includes LPS, which is a cell wall component of gram-negative bacteria. An immunological protein called lipopolysaccharide-binding protein (LBP) binds to LPS. The LBP–LPS complex then binds to the CD14 receptor of a nearby macrophage. This binding results in the synthesis and release of various endogenous cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. In other words, exogenous factors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway. The highly toxic metabolism-boosting supplement 2,4-dinitrophenol induces high body temperature via the inhibition of ATP production by mitochondria, resulting in impairment of cellular respiration. Instead of producing ATP, the energy of the proton gradient is lost as heat.
PGE2 release comes from the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase. These enzymes ultimately mediate the synthesis and release of PGE2.
PGE2 is the ultimate mediator of the febrile response. The set point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate the dorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa), and the paraventricular nucleus (PVN) of the hypothalamus . Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.
The brain ultimately orchestrates heat effector mechanisms via the autonomic nervous system or primary motor center for shivering. These may be:
- Increased heat production by increased muscle tone, shivering and hormones like epinephrine (adrenaline)
- Prevention of heat loss, such as vasoconstriction.
In infants, the autonomic nervous system may also activate brown adipose tissue to produce heat (non-exercise-associated thermogenesis, also known as non-shivering thermogenesis). Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.
There are arguments for and against the usefulness of fever, and the issue is controversial. There are studies using warm-blooded vertebrates with some suggesting that they recover more rapidly from infections or critical illness due to fever. Studies suggest reduced mortality in bacterial infections when fever was present.
In theory, fever can aid in host defense. There are certainly some important immunological reactions that are sped up by temperature, and some pathogens with strict temperature preferences could be hindered.
Research has demonstrated that fever assists the healing process in several important ways:
- Increased mobility of leukocytes
- Enhanced leukocyte phagocytosis
- Endotoxin effects decreased
- Increased proliferation of T cells
Fever should not necessarily be treated. Most people recover without specific medical attention. Although it is unpleasant, fever rarely rises to a dangerous level even if untreated. Damage to the brain generally does not occur until temperatures reach 42 °C (107.6 °F), and it is rare for an untreated fever to exceed 40.6 °C (105 °F). Treating fever in people with sepsis does not affect outcomes.
Some limited evidence supports sponging or bathing feverish children with tepid water. The use of a fan or air conditioning may somewhat reduce the temperature and increase comfort. If the temperature reaches the extremely high level of hyperpyrexia, aggressive cooling is required (generally produced mechanically via conduction by applying numerous ice packs across most of the body or direct submersion in ice water). In general, people are advised to keep adequately hydrated. Whether increased fluid intake improves symptoms or shortens respiratory illnesses such as the common cold is not known.
Medications that lower fevers are called antipyretics. The antipyretic ibuprofen is effective in reducing fevers in children. It is more effective than acetaminophen (paracetamol) in children. Ibuprofen and acetaminophen may be safely used together in children with fevers. The efficacy of acetaminophen by itself in children with fevers has been questioned. Ibuprofen is also superior to aspirin in children with fevers. Additionally, aspirin is not recommended in children and young adults (those under the age of 16 or 19 depending on the country) due to the risk of Reye's syndrome.
Using both paracetamol and ibuprofen at the same time or alternating between the two is more effective at decreasing fever than using only paracetamol or ibuprofen. It is not clear if it increases child comfort. Response or nonresponse to medications does not predict whether or not a child has a serious illness.
With respect to the effect of antipyretics on the risk of death in those with infection, studies have found mixed results as of 2019. Animals models have found worsened outcomes with the use of antipyretics in influenza as of 2010 but they have not been studied for this use in humans.
About 5% of people who go to an emergency room have a fever.
A number of types of fever were known as early as 460 BC to 370 BC when Hippocrates was practicing medicine including that due to malaria (tertian or every 2 days and quartan or every 3 days). It also became clear around this time that fever was a symptom of disease rather than a disease in and of itself.
Society and culture
Fever phobia is the name given by medical experts to parents' misconceptions about fever in their children. Among them, many parents incorrectly believe that fever is a disease rather than a medical sign, that even low fevers are harmful, and that any temperature even briefly or slightly above the oversimplified "normal" number marked on a thermometer is a clinically significant fever. They are also afraid of harmless side effects like febrile seizures and dramatically overestimate the likelihood of permanent damage from typical fevers. The underlying problem, according to professor of pediatrics Barton D. Schmitt, is "as parents we tend to suspect that our children’s brains may melt."
As a result of these misconceptions parents are anxious, give the child fever-reducing medicine when the temperature is technically normal or only slightly elevated, and interfere with the child's sleep to give the child more medicine.
Fever is an important feature for the diagnosis of disease in domestic animals. The body temperature of animals, which is taken rectally, is different from one species to another. For example, a horse is said to have a fever above 101 °F (38.3 °C). In species that allow the body to have a wide range of "normal" temperatures, such as camels, it is sometimes difficult to determine a febrile stage.
Fever can also be behaviorally induced by invertebrates that do not have immune-system based fever. For instance, some species of grasshopper will thermoregulate to achieve body temperatures that are 2–5 °C higher than normal in order to inhibit the growth of fungal pathogens such as Beauveria bassiana and Metarhizium acridum. Honeybee colonies are also able to induce a fever in response to a fungal parasite Ascosphaera apis. 
- Sullivan JE, Farrar HC (March 2011). "Fever and antipyretic use in children". Pediatrics. 127 (3): 580–7. doi:10.1542/peds.2010-3852. PMID 21357332.
- Sue E. Huether (2014). Pathophysiology: The Biologic Basis for Disease in Adults and Children (7 ed.). Elsevier Health Sciences. p. 498. ISBN 9780323293754.
- "Taking Care of Someone Who is Sick". 13 August 2010. Archived from the original on 24 March 2015. Retrieved 8 May 2015.
- Kluger MJ (2015). Fever: Its Biology, Evolution, and Function. Princeton University Press. p. 57. ISBN 9781400869831.
- Garmel GM, Mahadevan SV, eds. (2012). "Fever in adults". An introduction to clinical emergency medicine (2nd ed.). Cambridge: Cambridge University Press. p. 375. ISBN 978-0521747769.
- Axelrod, Yekaterina K.; Diringer, Michael N. (May 2008). "Temperature management in acute neurologic disorders". Neurologic Clinics. 26 (2): 585–603, xi. doi:10.1016/j.ncl.2008.02.005. PMID 18514828.
- Laupland, Kevin B. (July 2009). "Fever in the critically ill medical patient". Critical Care Medicine. 37 (7 Suppl): S273–8. doi:10.1097/CCM.0b013e3181aa6117. PMID 19535958.
- Richardson M, Purssell E (September 2015). "Who's afraid of fever?". Archives of Disease in Childhood. 100 (9): 818–20. doi:10.1136/archdischild-2014-307483. PMID 25977564.
- Garmel GM, Mahadevan SV, eds. (2012). An introduction to clinical emergency medicine (2nd ed.). Cambridge: Cambridge University Press. p. 401. ISBN 9780521747769.
- Kiekkas P, Aretha D, Bakalis N, Karpouhtsi I, Marneras C, Baltopoulos GI (August 2013). "Fever effects and treatment in critical care: literature review". Australian Critical Care. 26 (3): 130–5. doi:10.1016/j.aucc.2012.10.004. PMID 23199670.
- Garmel GM, Mahadevan SV, eds. (2012). An introduction to clinical emergency medicine (2nd ed.). Cambridge: Cambridge University Press. p. 5. ISBN 9780521747769.
- "Fever". MedlinePlus. 30 August 2014. Archived from the original on 11 May 2009.
- Schaffner A (March 2006). "[Fever--useful or noxious symptom that should be treated?]". Therapeutische Umschau. 63 (3): 185–8. doi:10.1024/0040-5922.214.171.124. PMID 16613288.
- Niven DJ, Stelfox HT, Laupland KB (June 2013). "Antipyretic therapy in febrile critically ill adults: A systematic review and meta-analysis". Journal of Critical Care. 28 (3): 303–10. doi:10.1016/j.jcrc.2012.09.009. PMID 23159136.
- Hart BL (1988). "Biological basis of the behavior of sick animals". Neuroscience and Biobehavioral Reviews. 12 (2): 123–37. doi:10.1016/S0149-7634(88)80004-6. PMID 3050629.
- Johnson RW (September 2002). "The concept of sickness behavior: a brief chronological account of four key discoveries". Veterinary Immunology and Immunopathology. 87 (3–4): 443–50. doi:10.1016/S0165-2427(02)00069-7. PMID 12072271.
- Kelley KW, Bluthé RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, Broussard SR (February 2003). "Cytokine-induced sickness behavior". Brain, Behavior, and Immunity. 17 Suppl 1 (1): S112-8. doi:10.1016/S0889-1591(02)00077-6. PMID 12615196.
- Marx, John (2006). Rosen's emergency medicine: concepts and clinical practice. Mosby/Elsevier. p. 2239. ISBN 978-0-323-02845-5.
- Hutchison, James S.; et al. (June 2008). "Hypothermia therapy after traumatic brain injury in children". New England Journal of Medicine. 358 (23): 2447–2456. doi:10.1056/NEJMoa0706930. PMID 18525042.
- Pryor, Jennifer A.; Prasad, Ammani S. (2008). Physiotherapy for Respiratory and Cardiac Problems: Adults and Paediatrics. Elsevier Health Sciences. p. 8. ISBN 0702039748.
- Grunau, Brian E.; Wiens, Matthew O.; Brubacher, Jeffrey R. (September 2010). "Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review". Canadian Journal of Emergency Medicine. 12 (5): 435–442. doi:10.1017/s1481803500012598. PMID 20880437.
Dantrolene may also be associated with improved survival and reduced complications, especially in patients with extreme (≥ 42 °C) or severe (≥ 40 °C) hyperpyrexia
- Sharma, Hari Shanker, ed. (2007). Neurobiology of Hyperthermia (1st ed.). Elsevier. pp. 175–177, 485. ISBN 9780080549996. Retrieved 19 November 2016.
Despite the myriad of complications associated with heat illness, an elevation of core temperature above 41.0 °C (often referred to as fever or hyperpyrexia) is the most widely recognized symptom of this syndrome.
- Niven DJ, Gaudet JE, Laupland KB, Mrklas KJ, Roberts DJ, Stelfox HT (November 2015). "Accuracy of peripheral thermometers for estimating temperature: a systematic review and meta-analysis". Annals of Internal Medicine. 163 (10): 768–77. doi:10.7326/M15-1150. PMID 26571241.
- "Measuring a Baby's Temperature". www.hopkinsmedicine.org. Archived from the original on 3 November 2019. Retrieved 10 September 2019.
- "Tips for taking your child's temperature". Mayo Clinic. Retrieved 10 September 2019.
- Barone JE (August 2009). "Fever: Fact and fiction". The Journal of Trauma. 67 (2): 406–9. doi:10.1097/TA.0b013e3181a5f335. PMID 19667898.
- Sund-Levander M, Forsberg C, Wahren LK (June 2002). "Normal oral, rectal, tympanic and axillary body temperature in adult men and women: a systematic literature review". Scandinavian Journal of Caring Sciences. 16 (2): 122–8. doi:10.1046/j.1471-6712.2002.00069.x. PMID 12000664.
- Longo DL, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J (2011). Harrison's Principles of Internal Medicine (18 ed.). New York: McGraw-Hill. p. 4012. ISBN 978-0-07-174889-6.
- Muhammad I, Shabbir Ahmad Nasir (May 2009). Bedside Techniques: Methods of clinical examination. Saira Publishers and Salamat Iqbal Press, Multan.
- Ferri FF (2009). "Chapter 332. Protozoal infections". Ferri's Color Atlas and Text of Clinical Medicine. Elsevier Health Sciences. p. 1159. ISBN 978-1-4160-4919-7. Archived from the original on 3 June 2016.
- Hilson AJ (July 1995). "Pel-Ebstein fever". The New England Journal of Medicine. 333 (1): 66–7. doi:10.1056/NEJM199507063330118. PMID 7777006.. They cite Richard Asher's lecture Making Sense (Lancet, 1959, 2, 359)
- Rolla L. Thomas (1906) . The eclectic practice of medicine. The Scudder Brothers Company. p. 261. Archived from the original on 11 May 2015.
- Grunau BE, Wiens MO, Brubacher JR (September 2010). "Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review". Canadian Journal of Emergency Medicine. 12 (5): 435–42. doi:10.1017/s1481803500012598. PMID 20880437.
Dantrolene may also be associated with improved survival and reduced complications, especially in patients with extreme (≥ 42°C) or severe (≥ 40°C) hyperpyrexia
- Sharma HS, ed. (2007). Neurobiology of Hyperthermia (1st ed.). Elsevier. pp. 175–177, 485. ISBN 9780080549996. Archived from the original on 8 September 2017. Retrieved 19 November 2016.
Despite the myriad of complications associated with heat illness, an elevation of core temperature above 41.0°C (often referred to as fever or hyperpyrexia) is the most widely recognized symptom of this syndrome.
- "Fever". Harrison's Principles of Internal Medicine 19/E (Vol.1 & Vol.2) (19 ed.). McGraw Hill Professional. 2015. p. Chapter 23. ISBN 9780071802161.
- McGugan EA (March 2001). "Hyperpyrexia in the emergency department". Emergency Medicine. 13 (1): 116–20. doi:10.1046/j.1442-2026.2001.00189.x. PMID 11476402.
- Loscalzo, Joseph; Fauci, Anthony S.; Braunwald, Eugene; Dennis L. Kasper; Hauser, Stephen L; Longo, Dan L. (2008). "Chapter 17, Fever versus hyperthermia". Harrison's principles of internal medicine. McGraw-Hill Medical. ISBN 978-0-07-146633-2.
- Marx 2006, p. 2506
- Tintinalli J (2004). Emergency Medicine: A Comprehensive Study Guide, Sixth edition. McGraw-Hill Professional. p. 1187. ISBN 978-0-07-138875-7.
- Fauci A, et al. (2008). Harrison's Principles of Internal Medicine (17th ed.). McGraw-Hill Professional. pp. 117–121. ISBN 978-0-07-146633-2.
- Puéchal X, Terrier B, Mouthon L, Costedoat-Chalumeau N, Guillevin L, Le Jeunne C (March 2014). "Relapsing polychondritis". Joint, Bone, Spine. 81 (2): 118–24. doi:10.1016/j.jbspin.2014.01.001. PMID 24556284.
- Longo DL (2012). Harrison's principles of internal medicine (18th ed.). New York: McGraw-Hill. ISBN 978-0071748896.
- Massignan C, Cardoso M, Porporatti AL, Aydinoz S, Canto G, Mezzomo LA, Bolan M (March 2016). "Signs and Symptoms of Primary Tooth Eruption: A Meta-analysis". Pediatrics. 137 (3): e20153501. doi:10.1542/peds.2015-3501. PMID 26908659. Archived from the original on 21 February 2016.
- Fauci, Anthony (2008). Harrison's Principles of Internal Medicine (17 ed.). McGraw-Hill Professional. pp. 117–121. ISBN 978-0-07-146633-2.
- Evans SS, Repasky EA, Fisher DT (June 2015). "Fever and the thermal regulation of immunity: the immune system feels the heat". Nature Reviews. Immunology. 15 (6): 335–49. doi:10.1038/nri3843. PMC 4786079. PMID 25976513.
- Silhavy TJ, Kahne D, Walker S (May 2010). "The bacterial cell envelope". Cold Spring Harbor Perspectives in Biology. 2 (5): a000414. doi:10.1101/cshperspect.a000414. PMC 2857177. PMID 20452953.
- Chapter 58 in: Walter F. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 978-1-4160-2328-9.
- Stefferl A, Hopkins SJ, Rothwell NJ, Luheshi GN (August 1996). "The role of TNF-alpha in fever: opposing actions of human and murine TNF-alpha and interactions with IL-beta in the rat". British Journal of Pharmacology. 118 (8): 1919–24. doi:10.1111/j.1476-5381.1996.tb15625.x. PMC 1909906. PMID 8864524.
- Roth J, Blatteis CM (October 2014). "Mechanisms of fever production and lysis: lessons from experimental LPS fever". Comprehensive Physiology. 4 (4): 1563–604. doi:10.1002/cphy.c130033. ISBN 9780470650714. PMID 25428854.
- Yen M, Ewald MB (June 2012). "Toxicity of weight loss agents". Journal of Medical Toxicology. 8 (2): 145–52. doi:10.1007/s13181-012-0213-7. PMC 3550246. PMID 22351299.
- Soszyński D (2003). "[The pathogenesis and the adaptive value of fever]". Postepy Higieny I Medycyny Doswiadczalnej (in Polish). 57 (5): 531–54. PMID 14737969.
- Kluger MJ, Kozak W, Conn CA, Leon LR, Soszynski D (September 1998). "Role of fever in disease". Annals of the New York Academy of Sciences. 856 (1): 224–33. Bibcode:1998NYASA.856..224K. doi:10.1111/j.1749-6632.1998.tb08329.x. PMID 9917881.
- Su F, Nguyen ND, Wang Z, Cai Y, Rogiers P, Vincent JL (June 2005). "Fever control in septic shock: beneficial or harmful?". Shock. 23 (6): 516–20. PMID 15897803.
- Rantala S, Vuopio-Varkila J, Vuento R, Huhtala H, Syrjänen J (April 2009). "Predictors of mortality in beta-hemolytic streptococcal bacteremia: a population-based study". The Journal of Infection. 58 (4): 266–72. doi:10.1016/j.jinf.2009.01.015. PMID 19261333.
- Fischler MP, Reinhart WH (May 1997). "[Fever: friend or enemy?]". Schweizerische Medizinische Wochenschrift (in German). 127 (20): 864–70. PMID 9289813.
- Craven, R and Hirnle, C. (2006). Fundamentals of nursing: Human health and function. Fourth edition. p. 1044
- Lewis, SM, Heitkemper, MM, and Dirksen, SR. (2007). Medical-surgical nursing: Assessment and management of clinical problems. sixth edition. p. 212
- "Fever". Medline Plus Medical Encyclopedia. U.S. National Library of Medicine. Archived from the original on 11 May 2009. Retrieved 20 May 2009.
- "What To Do If You Get Sick: 2009 H1N1 and Seasonal Flu". Centers for Disease Control and Prevention. 7 May 2009. Archived from the original on 3 November 2009. Retrieved 1 November 2009.
- Drewry AM, Ablordeppey EA, Murray ET, Stoll CR, Izadi SR, Dalton CM, Hardi AC, Fowler SA, Fuller BM, Colditz GA (May 2017). "Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis". Critical Care Medicine. 45 (5): 806–813. doi:10.1097/CCM.0000000000002285. PMC 5389594. PMID 28221185.
- Meremikwu M, Oyo-Ita A (2003). Meremikwu MM (ed.). "Physical methods for treating fever in children". The Cochrane Database of Systematic Reviews (2): CD004264. doi:10.1002/14651858.CD004264. PMC 6532675. PMID 12804512.
- "Fever". National Institute of Health. Archived from the original on 30 April 2016.
- Guppy MP, Mickan SM, Del Mar CB, Thorning S, Rack A (February 2011). "Advising patients to increase fluid intake for treating acute respiratory infections". The Cochrane Database of Systematic Reviews (2): CD004419. doi:10.1002/14651858.CD004419.pub3. PMID 21328268.
- Perrott DA, Piira T, Goodenough B, Champion GD (June 2004). "Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever: a meta-analysis". Archives of Pediatrics & Adolescent Medicine. 158 (6): 521–6. doi:10.1001/archpedi.158.6.521. PMID 15184213.
- Hay AD, Redmond NM, Costelloe C, Montgomery AA, Fletcher M, Hollinghurst S, Peters TJ (May 2009). "Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial". Health Technology Assessment. 13 (27): iii–iv, ix–x, 1–163. doi:10.3310/hta13270. PMID 19454182.
- Southey ER, Soares-Weiser K, Kleijnen J (September 2009). "Systematic review and meta-analysis of the clinical safety and tolerability of ibuprofen compared with paracetamol in paediatric pain and fever". Current Medical Research and Opinion. 25 (9): 2207–22. doi:10.1185/03007990903116255. PMID 19606950.
- Meremikwu M, Oyo-Ita A (2002). "Paracetamol for treating fever in children". The Cochrane Database of Systematic Reviews (2): CD003676. doi:10.1002/14651858.CD003676. PMC 6532671. PMID 12076499.
- Autret E, Reboul-Marty J, Henry-Launois B, Laborde C, Courcier S, Goehrs JM, Languillat G, Launois R (1997). "Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever". European Journal of Clinical Pharmacology. 51 (5): 367–71. doi:10.1007/s002280050215. PMID 9049576.
- "2.9 Antiplatelet drugs". British National Formulary for Children. British Medical Association and Royal Pharmaceutical Society of Great Britain. 2007. p. 151.
- Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW (October 2013). "Combined and alternating paracetamol and ibuprofen therapy for febrile children". The Cochrane Database of Systematic Reviews (10): CD009572. doi:10.1002/14651858.CD009572.pub2. PMC 6532735. PMID 24174375.
- King D (August 2013). "Question 2: does a failure to respond to antipyretics predict serious illness in children with a fever?". Archives of Disease in Childhood. 98 (8): 644–6. doi:10.1136/archdischild-2013-304497. PMID 23846358.
- Ludwig, J; McWhinnie, H (23 May 2019). "Antipyretic drugs in patients with fever and infection: literature review". British Journal of Nursing. 28 (10): 610–618. doi:10.12968/bjon.2019.28.10.610. PMID 31116598.
- Eyers, S; Weatherall, M; Shirtcliffe, P; Perrin, K; Beasley, R (October 2010). "The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis". Journal of the Royal Society of Medicine. 103 (10): 403–11. doi:10.1258/jrsm.2010.090441. PMC 2951171. PMID 20929891.
- Nassisi D, Oishi ML (January 2012). "Evidence-based guidelines for evaluation and antimicrobial therapy for common emergency department infections". Emergency Medicine Practice. 14 (1): 1–28, quiz 28–9. PMID 22292348.
- Sajadi MM, Bonabi R, Sajadi MR, Mackowiak PA (October 2012). "Akhawayni and the first fever curve". Clinical Infectious Diseases. 55 (7): 976–80. doi:10.1093/cid/cis596. PMID 22820543.
- Crocetti M, Moghbeli N, Serwint J (June 2001). "Fever phobia revisited: have parental misconceptions about fever changed in 20 years?". Pediatrics. 107 (6): 1241–6. doi:10.1542/peds.107.6.1241. PMID 11389237.
- Klass, Perri (10 January 2011). "Lifting a Veil of Fear to See a Few Benefits of Fever". The New York Times. Archived from the original on 29 September 2015.
- "Equusite Vital Signs". www.equusite.com. Archived from the original on 26 March 2010. Retrieved 22 March 2010.
- Schmidt-Nielsen K, Schmidt-Nielsen B, Jarnum SA, Houpt TR (January 1957). "Body temperature of the camel and its relation to water economy". The American Journal of Physiology. 188 (1): 103–12. doi:10.1152/ajplegacy.19126.96.36.199. PMID 13402948.
- Thomas MB, Blanford S (July 2003). "Thermal biology in insect-parasite interactions". Trends in Ecology & Evolution. 18 (7): 344–350. doi:10.1016/S0169-5347(03)00069-7.
- Rhoades, R. and Pflanzer, R. Human physiology, third edition, chapter 27 Regulation of body temperature, p. 820 Clinical focus: pathogenesis of fever. ISBN 0-03-005159-2
|Wikimedia Commons has media related to Fever.|
- Fever and Taking Your Child's Temperature
- US National Institute of Health factsheet
- Drugs most commonly associated with the adverse event Pyrexia (Fever) as reported the FDA