HOME

TheInfoList



OR:

Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with
body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...
exceeding the normal range caused by an increase in the body's temperature set point in the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
. There is no single agreed-upon upper limit for normal temperature: sources use values ranging between in humans. The increase in set point triggers increased
muscle contraction Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in musc ...
s and causes a feeling of
cold Cold is the presence of low temperature, especially in the atmosphere. In common usage, cold is often a subjectivity, subjective perception. A lower bound to temperature is absolute zero, defined as 0.00K on the Kelvin scale, an absolute t ...
or chills. 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 Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and Apocrine sweat gland, apocrine glands. The eccrine sweat glands are distribu ...
. Rarely a fever may trigger a febrile seizure, with this being more common in young children. Fevers do not typically go higher than . 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
influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...
, the
common cold The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
,
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
, urinary tract infections,
appendicitis Appendicitis is inflammation of the Appendix (anatomy), appendix. Symptoms commonly include right lower abdominal pain, nausea, vomiting, fever and anorexia (symptom), decreased appetite. However, approximately 40% of people do not have these t ...
,
Lassa fever Lassa fever, also known as Lassa hemorrhagic fever, is a type of viral hemorrhagic fever caused by the Lassa virus. Many of those infected by the virus asymptomatic, do not develop symptoms. When symptoms occur they typically include fever, wea ...
,
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
, and
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
. Non-infectious causes include
vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...
,
deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enl ...
, connective tissue disease, side effects of medication or vaccination, and
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
. It differs from
hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...
, 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 Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...
or
paracetamol Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
(acetaminophen) may help with this as well as lower temperature. 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 Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...
requires 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 evolved as a defense mechanism, treating a fever does not appear to improve or worsen outcomes. Abstract alone is in German and in English. Fever is often viewed with greater concern by parents and healthcare professionals than is usually deserved, a phenomenon known as "fever phobia."


Associated symptoms

A fever is usually accompanied by sickness behavior, which consists of
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness, or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overw ...
, depression, loss of appetite, sleepiness,
hyperalgesia Hyperalgesia ( or ; ''hyper'' from Greek ὑπέρ (''huper'') 'over' + ''-algesia'' from Greek ἄλγος (algos) 'pain') is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and ...
,
dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...
, and the inability to concentrate. Sleeping with a fever can often cause intense or confusing nightmares, commonly called "fever dreams". Mild to severe delirium (which can also cause
hallucinations A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
) may also present itself during high fevers.


Differential diagnosis


Hyperthermia

Hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...
is an elevation of body temperature over the temperature set point, due to either too much heat production or not enough heat loss. Hyperthermia is thus not considered fever. Hyperthermia should not be confused with hyperpyrexia (which is a very high fever). Clinically, it is important to distinguish between fever and hyperthermia as hyperthermia may quickly lead to death and does not respond to antipyretic medications. The distinction may however be difficult to make in an emergency setting, and is often established by identifying possible causes.


Mechanism


Hypothalamus

Temperature is regulated in the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
. The trigger of a fever, called a pyrogen, results in the 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. There are four receptors in which PGE2 can bind (EP1-4), with a previous study showing the EP3 subtype is what mediates the fever response. Hence, the hypothalamus can be seen as working like a
thermostat A thermostat is a regulating device component which senses the temperature of a physical system and performs actions so that the system's temperature is maintained near a desired setpoint. Thermostats are used in any device or system tha ...
. 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 Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
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, the brain orchestrates heat effector mechanisms via the
autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...
or primary motor center for shivering. These may be: * Increased heat production by increased
muscle tone In physiology, medicine, and anatomy, muscle tone (residual muscle tension or tonus) is the continuous and passive partial contraction of the muscles, or the muscle's resistance to passive stretch during resting state.O’Sullivan, S. B. (2007) ...
, shivering (muscle movements to produce heat) and release of hormones like epinephrine; and * Prevention of heat loss, e.g., through vasoconstriction. When the hypothalamic set point moves back to baseline—either spontaneously or via medication—normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting. This contrasts with
hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...
, 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. In infants, the autonomic nervous system may also activate brown adipose tissue to produce heat (non-shivering thermogenesis). Increased heart rate and vasoconstriction contribute to increased
blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
in fever.


Pyrogens

A pyrogen is a substance that induces fever. In the presence of an infectious agent, such as bacteria, viruses, viroids, ''etc''., the immune response of the body is to inhibit their growth and eliminate them. The most common pyrogens are endotoxins, which are lipopolysaccharides (LPS) produced by
Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...
such as '' E. coli.'' But pyrogens include non-endotoxic substances (derived from microorganisms other than gram-negative-bacteria or from chemical substances) as well. The types of pyrogens include internal (endogenous) and external (exogenous) to the body. The "pyrogenicity" of given pyrogens varies: in extreme cases, bacterial pyrogens can act as superantigens and cause rapid and dangerous fevers.


Endogenous

Endogenous pyrogens are
cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s released from
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s (which are part of the
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
). In general, they stimulate chemical responses, often in the presence of an
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
, leading to a fever. Whilst they can be a product of external factors like exogenous pyrogens, they can also be induced by internal factors like damage associated molecular patterns such as cases like
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
or lupus. 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 (TNF) also acts as a pyrogen, mediated by interleukin 1 (IL-1) release. These cytokine factors are released into general circulation, where they migrate to the brain's circumventricular organs where they are more easily absorbed than in areas protected by the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
. The cytokines then bind to endothelial receptors on vessel walls to receptors on microglial cells, resulting in activation of the arachidonic acid pathway. Of these, IL-1β, TNF, and IL-6 are able to raise the temperature setpoint of an organism and cause fever. These proteins produce a
cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such a ...
which induces the hypothalamic production of PGE2 which then stimulates the release of neurotransmitters such as cyclic adenosine monophosphate and increases body temperature.


Exogenous

Exogenous pyrogens are external to the body and are of microbial origin. In general, these pyrogens, including bacterial cell wall products, may act on Toll-like receptors in the hypothalamus and elevate the thermoregulatory setpoint. An example of a class of exogenous pyrogens are bacterial lipopolysaccharides (LPS) present in the cell wall of
gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...
. According to one mechanism of pyrogen action, an immune system protein, lipopolysaccharide-binding protein (LBP), binds to LPS, and the LBP–LPS complex then binds to a
CD14 CD14 ( cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP). ...
receptor on a
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
. The LBP-LPS binding to CD14 results in cellular synthesis and release of various endogenous
cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s, e.g., interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNFα). A further downstream event is activation of the arachidonic acid pathway.


Neural circuit mechanism with PGE2 action

PGE2 release comes from the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s 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 setpoint 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 The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
. Under normal conditions, EP3-expressing neurons in the POA are important thermoregulatory neurons, which provide continuous inhibitory signals with the transmitter GABA to control sympathetic output neurons in the DMH and rRPa, thereby performing bidirectional regulation of basal body temperature. During infection, PGE2 produced in the brain inhibits the activity of EP3-expressing neurons in the POA to attenuate the inhibition of sympathetic output, and thereby activates the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface, leading to fever. It is presumed that the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving
pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
and various endocrine organs.


Diagnosis

A 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 . An ear (tympanic) or
forehead In human anatomy, the forehead is an area of the head bounded by three features, two of the skull and one of the scalp. The top of the forehead is marked by the hairline, the edge of the area where hair on the scalp grows. The bottom of the fo ...
(temporal) temperature may also be used. * Temperature in the mouth (oral) is at or over in the morning or over in the afternoon * Temperature under the arm (axillary) is usually about below core body temperature. In adults, the normal range of temperatures in healthy individuals is (rectal), ( ear), (urine), (oral), and (axillary), with no significant gender differences. Normal body temperatures vary depending on many factors, including age, sex, time of day, ambient temperature, activity level, and more. Normal daily temperature variation has been described as 0.5 °C (0.9 °F). A raised temperature is not always a fever. For example, the temperature rises in healthy people when they exercise, 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 may represent a clinically significant fever.


Associated conditions

Fever is a common
symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...
of many medical conditions: *
Infectious disease An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
, e.g.,
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
, dengue,
Ebola Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after in ...
,
gastroenteritis Gastroenteritis, also known as infectious diarrhea, is an inflammation of the Human gastrointestinal tract, gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of ...
, HIV,
influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...
,
Lyme disease Lyme disease, also known as Lyme borreliosis, is a tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...
, rocky mountain spotted fever, secondary syphilis,
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
, mononucleosis, as well as infections of the skin, e.g., abscesses and boils. * Immunological diseases, e.g., relapsing polychondritis, autoimmune hepatitis,
granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), after Nazi German physician Friedrich Wegener, is a rare, long-term, systemic disorder that involves the formation of granulomas and vasculitis, inflammatio ...
, Horton disease,
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...
s, Kawasaki disease, lupus erythematosus, sarcoidosis, Still's disease,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
, lymphoproliferative disorders and
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...
; * Tissue destruction, as a result of cerebral bleeding, crush syndrome,
hemolysis Hemolysis or haemolysis (), also known by #Nomenclature, several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may ...
,
infarction Infarction is tissue death (necrosis) due to Ischemia, inadequate blood supply to the affected area. It may be caused by Thrombosis, artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as a ...
, rhabdomyolysis,
surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
, etc.; *
Cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
s, particularly blood cancers such as leukemia and lymphomas; *
Metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the ...
s, e.g.,
gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...
, and porphyria; and * Inherited metabolic disorder, e.g., Fabry disease. Adult and pediatric manifestations for the same disease may differ; for instance, in
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
, one metastudy describes 92.8% of adults versus 43.9% of children presenting with fever. In addition, fever can result from a reaction to an incompatible blood product.


Types

Various patterns of measured patient temperatures have been observed, some of which may be indicative of a particular
medical diagnosis Medical diagnosis (abbreviated Dx, Dx, or Ds) is the process of determining which disease or condition explains a person's symptoms and signs. It is most often referred to as a diagnosis with the medical context being implicit. The information ...
: * Continuous fever, where temperature remains above normal and does not fluctuate more than in 24 hours (e.g. in bacterial pneumonia, typhoid fever, infective endocarditis,
tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
, or
typhus Typhus, also known as typhus fever, is a group of infectious diseases that include epidemic typhus, scrub typhus, and murine typhus. Common symptoms include fever, headache, and a rash. Typically these begin one to two weeks after exposu ...
). * Intermittent fever is present only for a certain period, later cycling back to normal (e.g., in
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
,
leishmaniasis Leishmaniasis is a wide array of clinical manifestations caused by protozoal parasites of the Trypanosomatida genus ''Leishmania''. It is generally spread through the bite of Phlebotominae, phlebotomine Sandfly, sandflies, ''Phlebotomus'' an ...
, pyemia,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, or
African trypanosomiasis African trypanosomiasis is an insect-borne parasitic infection of humans and other animals. Human African trypanosomiasis (HAT), also known as African sleeping sickness or simply sleeping sickness, is caused by the species ''Trypanosoma bru ...
). * Remittent fever, where the temperature remains above normal throughout the day and fluctuates more than in 24 hours (e.g., in infective endocarditis or
brucellosis Brucellosis is a zoonosis spread primarily via ingestion of raw milk, unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever. The bacteria causing this disease, ''Brucella'', are small ...
). * Pel–Ebstein fever is a cyclic fever that is rarely seen in patients with Hodgkin's lymphoma. * Undulant fever, seen in
brucellosis Brucellosis is a zoonosis spread primarily via ingestion of raw milk, unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever. The bacteria causing this disease, ''Brucella'', are small ...
. * Typhoid fever is a continuous fever showing a characteristic ''step-ladder pattern,'' a step-wise increase in temperature with a high plateau. Among the types of intermittent fever are ones specific to cases of malaria caused by different pathogens. These are: * Quotidian fever, with a 24-hour periodicity, typical of
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
caused by '' Plasmodium knowlesi'' (''P. knowlesi''); * Tertian fever, with a 48-hour periodicity, typical of later course
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
caused by '' P. falciparum'', '' P. vivax'', or '' P. ovale''; * Quartan fever, with a 72-hour periodicity, typical of later course
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
caused by '' P. malariae''. In addition, there is disagreement regarding whether a specific fever pattern is associated with Hodgkin's lymphoma—the Pel–Ebstein fever, with patients argued to present high temperature for one week, followed by low for the next week, and so on, where the generality of this pattern is debated. Persistent fever that cannot be explained after repeated routine clinical inquiries is called fever of unknown origin. 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
neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
s, 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 Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
than in apparently healthy people.


Hyperpyrexia

Hyperpyrexia is an extreme elevation of
body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...
which, depending upon the source, is classified as a core body temperature greater than or equal to ; the range of hyperpyrexia includes cases considered severe (≥ 40 °C) and extreme (≥ 42 °C). It differs from
hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...
in that one's thermoregulatory system's set point for body temperature is set above normal, then heat is generated to achieve it. In contrast, hyperthermia involves body temperature rising above its set point due to outside factors. The high temperatures of hyperpyrexia are considered medical emergencies, as they may indicate a serious underlying condition or lead to severe morbidity (including permanent
brain damage Brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating trauma-induced damage. A common ...
), or to death. A common cause of hyperpyrexia is an
intracranial hemorrhage Intracranial hemorrhage (ICH) refers to any form of Hemorrhage, bleeding Internal bleeding, within the Human skull, skull. It can result from trauma, vascular abnormalities, hypertension, or other medical conditions. ICH is broadly categorized ...
. Other causes in emergency room settings include Malignant Catatonia,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, Kawasaki syndrome,Marx (2006), p. 2506. neuroleptic malignant syndrome,
drug overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.
,
serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...
, and thyroid storm.


Function


Immune function

Fever is thought to contribute to host defense, as the reproduction of
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
s with strict temperature requirements can be hindered, and the rates of some important immunological reactions are increased by temperature. Fever has been described in teaching texts as assisting the healing process in various ways, including: :* increased mobility of leukocytes; :* enhanced leukocyte
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
; :* decreased endotoxin effects; and :* increased proliferation of T cells.


Advantages and disadvantages

A fever response to an infectious disease is generally regarded as protective, whereas fever in non-infections may be maladaptive. Studies have not been consistent on whether treating fever generally worsens or improves mortality risk. Benefits or harms may depend on the type of infection, health status of the patient and other factors. Studies using
warm-blooded Warm-blooded is a term referring to animal species whose bodies maintain a temperature higher than that of their environment. In particular, homeothermic species (including birds and mammals) maintain a stable body temperature by regulating ...
vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
suggest that they recover more rapidly from infections or critical illness due to fever. In
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, fever is associated with reduced mortality.


Management

Fever does not necessarily need to be treated, and most people with a fever 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 , and it is rare for an untreated fever to exceed . Treating fever in people with
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
does not affect outcomes. Small trials have shown no benefit of treating fevers of or higher of critically ill patients in ICUs, and one trial was terminated early because patients receiving aggressive fever treatment were dying more often. According to the NIH, the two assumptions which are generally used to argue in favor of treating fevers have not been experimentally validated. These are that (1) a fever is noxious, and (2) suppression of a fever will reduce its noxious effect. Most of the other studies supporting the association of fever with poorer outcomes have been observational in nature. In theory, these critically ill patients and those faced with additional physiologic stress may benefit from fever reduction, but the evidence on both sides of the argument appears to be mostly equivocal.


Conservative measures

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 The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
is not known.


Medications

Medications that lower fevers are called '' antipyretics''. The antipyretic
ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...
is effective in reducing fevers in children. It is more effective than acetaminophen (paracetamol) in children. Ibuprofen and acetaminophen may safely be 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 Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
in children with fevers. Additionally,
aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
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.


Epidemiology

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. About 5% of people who go to an emergency room have a fever.


History

A number of types of fever were known as early as 460 BC to 370 BC when
Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
was practicing medicine including that due to
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
(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. Infections presenting with fever were a major source of mortality in humans for about 200,000 years. Until the late nineteenth century, approximately half of all humans died from infections before the age of fifteen. An older term, febricula (a
diminutive A diminutive is a word obtained by modifying a root word to convey a slighter degree of its root meaning, either to convey the smallness of the object or quality named, or to convey a sense of intimacy or endearment, and sometimes to belittle s ...
form of the
Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
word for fever), was once used to refer to a low-grade fever lasting only a few days. This term fell out of use in the early 20th century, and the symptoms it referred to are now thought to have been caused mainly by various minor viral respiratory infections.


Society and culture


Mythology

* Febris (''fever'' in
Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
) is the goddess of fever in
Roman mythology Roman mythology is the body of myths of ancient Rome as represented in the literature and visual arts of the Romans, and is a form of Roman folklore. "Roman mythology" may also refer to the modern study of these representations, and to th ...
. People with fevers would visit her temples. *Tertiana and Quartana are the goddesses of tertian and quartan fevers of malaria in Roman mythology. * Jvarasura (''fever-demon'' in
Hindi Modern Standard Hindi (, ), commonly referred to as Hindi, is the Standard language, standardised variety of the Hindustani language written in the Devanagari script. It is an official language of India, official language of the Government ...
) is the personification of fever and disease in
Hindu Hindus (; ; also known as Sanātanīs) are people who religiously adhere to Hinduism, also known by its endonym Sanātana Dharma. Jeffery D. Long (2007), A Vision for Hinduism, IB Tauris, , pp. 35–37 Historically, the term has also be ...
and Buddhist mythology.


Pediatrics

Fever is often viewed with greater concern by parents and healthcare professionals than might be deserved, a phenomenon known as fever phobia, which is based in both caregiver's and parents' misconceptions about fever in children. Among them, many parents incorrectly believe that fever is a
disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
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 that "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.


Other animals

Fever is an important metric for the
diagnosis Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...
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 The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 mi ...
is said to have a fever above (). In species that allow the body to have a wide range of "normal" temperatures, such as
camel A camel (from and () from Ancient Semitic: ''gāmāl'') is an even-toed ungulate in the genus ''Camelus'' that bears distinctive fatty deposits known as "humps" on its back. Camels have long been domesticated and, as livestock, they provid ...
s, whose body temperature varies as the environmental temperature varies, the body temperature which constitutes a febrile state differs depending on the environmental temperature. 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''.


References


Further reading

*


External links


Fever and Taking Your Child's Temperature



Drugs most commonly associated with the adverse event Pyrexia (Fever) as reported the FDA


at MedlinePlus

at ''The New York Times'' {{Authority control Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate Symptoms and signs Thermoregulation