Fever

Fever
An analogue medical thermometer showing the temperature of 38.7 °C

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; M.Umer Tariq [3]

Synonyms and keywords: Pyrexia; febrile response

Mechanism

Temperature is regulated in the hypothalamus, in response to PGE2. PGE2 release, in turn, comes from a trigger, a pyrogen. The hypothalamus generates a response back to the rest of the body, making it increase the temperature set-point.

Hyperthermia: Characterized on the left. Normal body temperature (thermoregulatory set-point) is shown in green, while the hyperthermic temperature is shown in red. As can be seen, hyperthermia can be conceptualized as an increase above the thermoregulatory set-point.
Hypothermia: Characterized in the center: Normal body temperature is shown in green, while the hypothermic temperature is shown in blue. As can be seen, hypothermia can be conceptualized as a decrease below the thermoregulatory set-point.
Fever: Characterized on the right: Normal body temperature is shown in green. It reads "New Normal" because the thermoregulatory set-point has risen. This has caused what was the normal body temperature (in blue) to be considered hypothermic.

Pyrogens

A pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous). The bacterial substance lipopolysaccharide (LPS) is an example of an exogenous pyrogen.

Endogenous

The cytokines (such as interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the hypothalamus. Other examples of endogenous pyrogens are interleukin 6 (IL-6), and the tumor necrosis factor-alpha.

These cytokine factors are released into general circulation where they migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced. The cytokine factors bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, they activate the arachidonic acid pathway.

Exogenous

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.

PGE2 release

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 EP3 subtype of PGE receptors and the 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 of the hypothalamus (PVN). 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.

Hypothalamus response

The brain ultimately orchestrates heat effector mechanisms. These may be;

• Increased heat production by increased muscle tone, shivering and hormones like epinephrine.
• Prevention of heat loss, such as vasoconstriction.

The autonomic nervous system may also activate brown adipose tissue to produce heat (non-exercise-associated thermogenesis, also known as non-shivering thermogenesis), but this seems mostly important for babies. Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.

Types

Pyrexia (fever) can be classed as:

• Low grade: 38–39°C (100.4–102.2°F)
• Moderate: 39–40°C (102.2–104.0°F)
• High-grade: 40–42°C (104.0–107.6°F)
• Hyperpyrexia: over 42°C (107.6°F)

The last is clearly a medical emergency because it approaches the upper limit compatible with human life.

Most of the time, fever types can not be used to find the underlying cause. However, there are specific fever patterns that may occasionally hint the diagnosis:

• 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.
• 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, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.
• Intermittent fever: Temperature is present only for some hours of the day and becomes normal for remaining hours, e.g. malaria, kala-azar, pyaemia, or septicemia. In malaria, there may be a fever with a periodicity of 24 hours (quotidian), 48 hours (tertian fever), or 72 hours (quartan fever, indicating Plasmodium vivax). These patterns may be less clear in travelers.
• Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1°C in 24 hours, e.g. infective endocarditis.

Febricula is a mild fever of short duration, of indefinite origin, and without any distinctive pathology.

Common Causes

Fever is a common symptom of many medical conditions:

• Infectious disease, e.g. influenza, common cold, HIV, malaria, infectious mononucleosis, or gastroenteritis.
• Various skin inflammations, e.g. boils, pimples, acne, or abscess.
• Immunological diseases, e.g. lupus erythematosus, sarcoidosis, inflammatory bowel diseases.
• Tissue destruction, which can occur in hemolysis, surgery, infarction, crush syndrome, rhabdomyolysis, cerebral hemorrhage, etc.
• Drug fever
  • Directly caused by the drug, e.g. lamictal, progesterone, or chemotherapeutics causing tumor necrosis.
  • As an adverse reaction to drugs, e.g. antibiotics or sulfa drugs.
  • After drug discontinuation, e.g. heroin withdrawal.
• Cancers, e.g. Hodgkin disease.
• Metabolic disorders, e.g. gout or porphyria.
• Thrombo-embolic processes, e.g. pulmonary embolism or deep venous thrombosis.

Persistent fever which cannot be explained after repeated routine clinical inquiries, is called fever of unknown origin.

Complete Differential Diagnosis of the Causes of Fever

In Alphabetical Order.

2,4-Dinitrophenol Abacavir Abatacept Abrin Acetazolamide Acetohexamide Acute Chest Syndrome Acute Disseminated Encephalomyelitis Acute lymphoblastic leukemia Acute myeloid leukemia Acute posterior multifocal placoid pigment epitheliopathy Acyclovir Adalimumab Adenoviridae Adiposis dolorosa Adjustable gastric band Adrenal hemorrhage African Hemmorhagic Fever African horse sickness African swine fever virus African Trypanosomiasis Albuterol Aldesleukin Alefacept Alemtuzumab Alendronate Alfuzosin Alglucerase Alkhurma virus Allergic bronchopulmonary aspergillosis Allopurinol Alphavirus Altretamine Alveolitis Aminopterin Amitriptyline Amobarbital Amphotericin B Anagrelide Anakinra Anal abscess Anastrozole Ancrod Anisindione Anthrax Aphthovirus Appendicitis Arbovirus Arenavirus Aripiprazole Arterivirus Asparaginase Aspergillosis Astroviridae Atazanavir Atelectasis Atorvastatin Atovaquone Atropine Ophthalmic Auranofin Babanki virus Babesiosis Bacillary angiomatosis Bacillus Calmette-Guerin (BCG) Vaccine Bacterial pneumonia Bartonellosis Benazepril Benztropine Mesylate Bepridil Bevacizumab Bezold's abscess Bisphosphonate BK virus Blackwater fever Blastomycosis Bleomycin Blood transfusion Blue diaper syndrome Bordetella pertussis Bornholm disease Borrelia Bortezomib Boutonneuse fever Brain Abscess Brinzolamide Ophthalmic Bronchitis Brucellosis Bubonic plague Bumetanide Burkitt lymphoma Buruli ulcer Busulfan Butabarbital Butoconazole Vaginal Cream Bwamba Fever Cabin fever Cadmium poisoning Caecitis Calcitriol Campylobacter jejuni Candesartan Capecitabine Captopril Carboplatin Carbuncle Carisoprodol Carmustine Caroli's Disease Carteolol Caspofungin Cat scratch fever Cefaclor Cellulitis Cephalosporin Cetuximab Chagas disease

Chickenpox Childbirth Chlamydia Chlamydophila pneumoniae Chlorambucil Chlordiazepoxide Chlorothiazide Chlorthalidone Cholangitis Cholecystitis Cholesterol Emboli Syndrome Chronic myelogenous leukemia Churg-Strauss Syndrome Ciclosporin Cidofovir Cladribine Clofarabine Clonazepam Clorazepate Clostridium Difficile Clotrimazole CMV Cocaine Coccidioidomycosis Cogan syndrome Colchicine Coley's Toxins Colistimethate Colitis Colorado tick fever virus Community-acquired pneumonia Congenital syphilis Co-trimoxazole Cotton fever Coxiella burnetii infection Coxsackie A virus Craniopharyngioma Crimean Congo Hemorrhagic Fever Crohn's disease Croup Cryptosporidiosis Cyanocobalamin Cyclobenzaprine Cyclosporiasis Cystic Fibrosis Cystitis, infective Cytarabine Cytokine release syndrome Dacarbazine Dacryocystitis Dactinomycin Dalteparin Sodium Dapsone Daptomycin Darbepoetin alfa Darunavir Daunorubicin De Quervain's thyroiditis Deferasirox Delavirdine Dengue Fever Desipramine Dextroamphetamine and Amphetamine Dextromethorphan Diabetes insipidus Diazepam Diclofenac Didanosine Dientamoebiasis Diethylpropion Diflunisal Diltiazem Dimercaprol Dinoprostone Diphtheria Disopyramide Disseminated Intravascular Coagulation Diverticulitis Dobutamine Dolasetron Donepezil Doxorubicin Dressler's syndrome Ebola haemorrhagic fever Echovirus Efalizumab Efavirenz Empyema Emtricitabine Enalapril Enfuvirtide Enoxaparin Entacapone Enterotoxigenic Escherichia coli Epiglottitis Epinastine Ophthalmic Epoetin Alfa Epstein-Barr virus Erlotinib Estazolam Estradiol Topical Etanercept Ethchlorvynol Ethosuximide Etidronate Etodolac Etoposide Exopthalmos Ezetimibe Fabry's Disease Famciclovir Familial Mediterranian Fever Fasciolopsiasis Fasciolosis

Fat Embolism Syndrome Fenoprofen Fetal alcohol syndrome Filgrastim Filoviridae Fipexide Flavivirus Flavoxate Floxuridine Flucytosine Fludarabine Phosphate Fluorouracil Fluphenazine Fluticasone and Salmeterol Inhalation Fluvastatin Fluvoxamine Fosamprenavir Foscarnet Sodium Fosinopril Free-living amebic infection Furosemide Furunculosis Fusarium Gabapentin Gallbladder empyema Ganciclovir Gastritis Gastroenteritis Gastrointestinal perforation Gatifloxacin Gefitinib Gemcitabine Hydrochloride Giardiasis Glatiramer acetate Glipizide Glyburide Gonorrhea Goserelin Gout Gradenigo's syndrome Granisetron Grifulvin V Group A streptococcal infection Guanethidine Haemophilus influenzae serotype B infection Haloperidol Hamman-Rich Syndrome Hand-foot-mouth syndrome Hantavirus Pulmonary Syndrome Haverhill fever Hay fever Hemophagocytic lymphohistiocytosis Heparin Hepatitis A Hepatitis B Hepatitis E Hepato-biliary diseases Heroin withdrawl Herpangina Herpes zoster Herpesviridae Herxheimer reaction Hidradenitis suppurativa Histrelin HIV/AIDS Hodgkin's lymphoma Hookworm Human monocytotropic ehrlichiosis Hydralazine Hydrochlorothiazide Hyperimmunoglobulinemia D with recurrent fever Ibandronate Idarubicin Idiopathic pulmonary haemosiderosis Ifosfamide Ileitis Imatinib Imiglucerase Imiquimod Immune Globulin Intravenous Immune reconstitution inflammatory syndrome Impetigo herpetiformis Indomethacin Infectious mononucleosis Infective Endocarditis Influenza virus Interstitial nephritis Intra-abdominal abscess Ipratropium and Albuterol Inhalation Ischemic colitis Isocarboxazid Itraconazole Juvenile Myelomonocytic Leukemia (JMML) Kaposi's sarcoma Kawasaki disease Kikuchi disease Krabbe disease La Crosse encephalitis Lamivudine Langerhans cell histiocytosis Laryngitis Lassa Fever Legionellosis Leishmaniasis Lemierre's Syndrome Leptospirosis

Levalbuterol Inhalation Levetiracetam Levomepromazine Linezolid Liothyronine Lisinopril Listeriosis Lithraea molleoides Lorazepam Lovastatin Loxapine Ludwig's angina Lung abscess Lung cancer Lupoid hepatitis Lyme disease Lymphocytopenia Lymphogranuloma venereum Macrophage activation syndrome Malakoplakia Malaria Malignant hyperthermia Marburg hemorrhagic fever Mastitis Mastocytosis Mastoiditis Measles Mechlorethamine Meclofenamate Mediastinitis Mefenamic acid Melarsoprol Melioidosis Melphalan Meningitis Meprobamate Mercaptopurine Mesothelioma Metal fume fever Methadone withdrawl Methimazole Methocarbamol Methotrexate Methsuximide Methyclothiazide Methyldopa and Hydrochlorothiazide Methylphenidate Metolazone Metoprolol Metronidazole Micafungin Miconazole Mifepristone Miliary tuberculosis Minocycline Mitomycin Modafinil Moexipril Moricizine Moxifloxacin ophthalmic Muckle-Wells syndrome Mumps Murray Valley encephalitis virus Mycobacterium avium complex Mycophenolate Mycoplasma pneumoniae Myxoma Nabumetone Naegleria infection Nafcillin Sodium Nalmefene Natalizumab Necrotizing fasciitis Nefazodone Nephroblastoma Neuroleptic malignant syndrome Neutropenia Nevirapine Nilutamide Nitrofurantoin Nocardiosis Noma (disease) Norovirus infection Nortriptyline Occult abscess Olanzapine Omphalitis Omsk hemorrhagic fever Ondansetron O'nyong'nyong virus Opisthorchis infection Oprelvekin Orbital cellulitis Oropouche virus Oseltamivir Otitis media Oxacillin Sodium Oxaliplatin Oxamniquine Oxazepam Oxcarbazepine Oxybutynin Oxycodone and aspirin Paclitaxel Palifermin Paliperidone Pamidronate Pancreatitis Paracoccidioidomycosis Paragonimus Infection Paratyphoid fever Pegaspargase Peginterferon alfa-2a Pel-Ebstein fever Pelvic inflammatory disease Pemetrexed Penicilliosis Penicillamine Pentetic acid

Pentostatin Peplomycin Perianal abscess Pericoronitis Perindopril Peritonitis Peritonsillar abscess Puerperal pyrexia Pharyngitis Pharyngoconjunctival fever Phenazopyridine Phenelzine Phenobarbital Phentermine Phenytoin Pimecrolimus topical Pimozide Pindolol Piroxicam Pityriasis rosea Pleurisy Plicamycin Pneumocystis jirovecii pneumonia POEMS syndrome Poliomyelitis Polyarteritis nodosa Polytetrafluoroethylene Pontiac fever Posaconazole Pravastatin Prazepam Praziquantel Prazosin and polythiazide Pregabalin Primaquine Primidone Procainamide Procarbazine Prochlorperazine Procyclidine Propafenone Propiomazine Propylthiouracil Prostatitis Protriptyline Pseudomembranous colitis/C.difficile Psittacosis Pulmonary alveolar proteinosis Pyelonephritis Pyrazinamide Pyrexia of unknown origin Q fever Quetiapine Quinapril Rabies vaccine Ramipril Ranitidine bismuth citrate Rasagiline Rat-bite fever Reactive Polyarticular Arthritis Renal Cell Carcinoma Retinoic acid syndrome Rheumatic fever Rheumatoid arthritis Rhinovirus Ribavirin Rickettsial infections Rifampicin Rift Valley fever virus Riluzole Risedronate Risperidone Rituximab Rocky Mountain Spotted Fever Roseola Ross River Fever Rosuvastatin Rotavirus Rubella Salmonella enteritidis Salmonella typhi infection/ Typhoid fever Salsalate Saquinavir Sarcoidosis Sargramostim Scarlet fever Schistosomiasis Scopolamine Scrofula Secobarbital Selegiline Sennetsu fever Sepsis Septic arthritis Serotonin syndrome Serum sickness Severe acute respiratory syndrome Shigellosis Sibutramine Sickle-cell disease Silicosis Silver sulfadiazine Simvastatin Sindbis virus Sinusitis Sirolimus Sleeping sickness Smallpox Sodium oxybate Solanine Solifenacin Spironolactone Spotted Fever Staphylococcal toxic shock syndrome Staphylococcal enteritis Still's disease Stool softeners

Strep throat Streptococcus pyogenes Streptokinase Streptozocin Strontium-89 chloride Stuve-Wiedemann syndrome Subacute thyroiditis Subdural hygroma Succimer Sulfadiazine Sulfasalazine Sulfinpyrazone Sulfisoxazole Sulindac Sulprostone Sunitinib Swine flu Synovial sarcoma Syphillis Systemic lupus erythematosus Takayasu's Arteritis Tamoxifen Tamsulosin Tanapox Temazepam Temozolomide Temporal arteritis Teniposide Terbinafine Teriparatide (rDNA origin) Testosterone Transdermal Thiabendazole Thioamide Thioguanine Thiotepa Thrombophlebitis Thyroid Medication Ticarcillin Disodium Ticlopidine Tiludronate Tiotropium Inhalation Tipranavir Tirofiban Tocainide Tolazamide Tolbutamide Tolosa-Hunt syndrome Topotecan Hydrochloride TORCH infections Toxic epidermal necrolysis Toxic megacolon Toxic Shock Syndrome Toxocara infection Tracheitis Trandolapril Transfusion reaction Transfusion-associated graft versus host disease Tranylcypromine Trastuzumab Traveler's diarrhea Trazodone Trench Fever Triamterene Triazolam Trichinosis Trichothecene Trihexyphenidyl Trimethadione Trimetrexate Glucuronate Trimipramine Troleandomycin Tropical pulmonary eosinophilia Tuberculosis Tularemia Ulcerative colitis Urate crystal arthropathy Urinary tract infection Valacyclovir Valganciclovir Valproate semisodium Valproic Acid Varicella (Chickenpox) Vaccine Varicella-zoster virus Vasculitis Verapamil Vibrio parahaemolyticus Vibrio vulnificus Vinblastine Vinorelbine Tartrate Viral Hepatitis A Viral Hepatitis C Viral infections Visceral leishmaniasis Vitamin A Voriconazole Vorinostat Weber-Christian disease Wegener Granulomatosis West Nile Virus Whipple's disease Yellow Fever Vaccine Yellow Fever Virus Yersinia enterocolitica Infection (Yersiniosis) Yersinia Pestis Infection Yersinia pseudotuberculosis Zalcitabine Zika fever Zinc oxide Ziprasidone Zoledronate Zonisamide

Complete Differential Diagnosis of the Causes of Fever

(By Organ System)

Cardiovascular	Vasculitis, Infective Endocarditis, Dressler's syndrome, Cholesterol Emboli Syndrome,
Chemical / poisoning	2,4-Dinitrophenol, Abrin, Cadmium poisoning, Colchicine, Lithraea molleoides,
Dermatologic	Weber-Christian disease, Toxic epidermal necrolysis, Scrofula, Necrotizing fasciitis, Furunculosis, Cellulitis, Carbuncle,
Drug Side Effect	Abacavir , Abatacept , Acetazolamide , Acetohexamide , Acyclovir , Adalimumab , Albuterol , Aldesleukin , Alefacept , Alemtuzumab, Alendronate , Alfuzosin , Alglucerase , Allopurinol, Altretamine , Aminopterin, Amitriptyline , Amobarbital, Amphotericin B, Anagrelide , Anakinra , Anastrozole , Ancrod, Anisindione , Aripiprazole , Asparaginase , Atazanavir , Atorvastatin , Atovaquone , Atropine Ophthalmic , Auranofin , Benazepril , Benztropine Mesylate , Bepridil , Bevacizumab , Bisphosphonate, Bleomycin, Bortezomib , Brinzolamide Ophthalmic , Bumetanide , Busulfan , Butabarbital , Butoconazole Vaginal Cream , Calcitriol , Candesartan , Capecitabine , Captopril , Carboplatin , Carisoprodol , Carmustine , Carteolol , Caspofungin, Cefaclor, Cephalosporin, Cetuximab , Chlorambucil , Chlordiazepoxide , Chlorothiazide , Chlorthalidone , Ciclosporin, Cidofovir , Cladribine , Clofarabine, Clonazepam , Clorazepate , Clotrimazole , Cocaine, Colchicine, Colistimethate , Co-trimoxazole , Cyanocobalamin , Cyclobenzaprine , Cytarabine , Dacarbazine , Dactinomycin , Dalteparin Sodium , Dapsone, Daptomycin, Darbepoetin alfa, Darunavir , Daunorubicin , Deferasirox , Delavirdine , Desipramine , Dextroamphetamine and Amphetamine , Dextromethorphan, Diazepam , Diclofenac, Diethylpropion , Diflunisal , Diltiazem , Disopyramide , Dobutamine , Dolasetron , Donepezil , Doxorubicin , Efalizumab , Efavirenz , Emtricitabine , Enalapril , Enfuvirtide, Enoxaparin , Entacapone , Epinastine Ophthalmic , Epoetin Alfa , Erlotinib , Estazolam , Estradiol Topical , Etanercept , Ethosuximide , Etidronate , Etodolac , Etoposide, Ezetimibe , Famciclovir, Fenoprofen , Fipexide, Filgrastim , Flavoxate , Floxuridine , Flucytosine, Fludarabine Phosphate , Fluorouracil , Fluphenazine , Fluticasone and Salmeterol Inhalation , Fluvastatin , Fluvoxamine, Fosamprenavir , Foscarnet Sodium , Fosinopril , Furosemide , Gabapentin , Gatifloxacin , Gefitinib , Gemcitabine Hydrochloride , Glatiramer acetate, Glipizide , Glyburide , Goserelin , Granisetron , Grifulvin V, Guanethidine , Haloperidol, Heparin , Histrelin , Hydralazine , Hydrochlorothiazide , Ibandronate , Idarubicin , Ifosfamide , Imatinib , Imiglucerase , Imiquimod , Immune Globulin Intravenous , Indomethacin , Ipratropium and Albuterol Inhalation , Isocarboxazid , Itraconazole , Lamivudine , Levalbuterol Inhalation , Levetiracetam , Levomepromazine, Linezolid, Liothyronine , Lisinopril , Lorazepam , Lovastatin , Loxapine , Mechlorethamine , Meclofenamate , Mefenamic acid, Melphalan , Meprobamate , Mercaptopurine, Methadone withdrawl, Methimazole , Methocarbamol , Methsuximide , Methyclothiazide , Methyldopa and Hydrochlorothiazide , Methylphenidate, Metolazone , Metoprolol, Metronidazole, Miconazole , Mifepristone, Minocycline, Mitomycin , Modafinil , Moexipril , Moricizine , Moxifloxacin ophthalmic , Nabumetone , Nafcillin Sodium , Nalmefene, Natalizumab , Nefazodone , Nilutamide , Nitrofurantoin , Nortriptyline , Olanzapine , Ondansetron , Oprelvekin, Oseltamivir , Oxacillin Sodium , Oxaliplatin , Oxamniquine, Oxazepam , Oxcarbazepine , Paclitaxel, Palifermin , Paliperidone , Pamidronate , Pegaspargase , Pemetrexed , Pentetic acid, Pentostatin , Perindopril , Phenazopyridine , Phenobarbital , Phenytoin , Pimecrolimus topical , Pimozide , Pindolol , Piroxicam , Plicamycin , Posaconazole , Pravastatin , Prazepam , Praziquantel, Prazosin and polythiazide , Pregabalin , Primaquine , Primidone , Procainamide, Procarbazine , Prochlorperazine , Procyclidine , Propafenone , Propiomazine, Propylthiouracil , Protriptyline , Pyrazinamide, Quetiapine , Quinapril , Ramipril , Ranitidine bismuth citrate , Rasagiline , Ribavirin , Rifampicin, Riluzole , Risedronate , Risperidone , Rituximab , Rosuvastatin , Salsalate , Saquinavir , Sargramostim , Scopolamine, Secobarbital , Sibutramine, Silver sulfadiazine , Simvastatin , Sirolimus , Sodium oxybate , Solanine, Spironolactone , Stool softeners , Streptozocin , Strontium-89 chloride , Sulfadiazine , Sulfasalazine , Sulfinpyrazone , Sulfisoxazole , Sulindac , Sunitinib , Tamoxifen , Tamsulosin , Tanapox, Temazepam , Temozolomide , Teniposide , Terbinafine , Teriparatide (rDNA origin) , Testosterone Transdermal , Thiabendazole, Thioamide, Thioguanine , Thiotepa , Thyroid Medication , Ticarcillin Disodium , Ticlopidine , Tiludronate , Tiotropium Inhalation , Tipranavir , Tirofiban, Tocainide , Tolazamide , Tolbutamide , Topotecan Hydrochloride , Trandolapril , Tranylcypromine , Trastuzumab , Trazodone , Triamterene, Triazolam , Trichothecene, Trihexyphenidyl , Trimethadione , Trimetrexate Glucuronate , Trimipramine , Troleandomycin , Valacyclovir , Valproate semisodium, Valproic Acid , Verapamil , Vinblastine , Vinorelbine Tartrate , Voriconazole, Vorinostat , Zalcitabine , Ziprasidone , Zoledronate, Zonisamide ,
Ear Nose Throat	Sinusitis, Pharyngoconjunctival fever, Pharyngitis, Peritonsillar abscess, Otitis media, Orbital cellulitis, Mastoiditis, Ludwig's angina, Laryngitis, Gradenigo's syndrome, Dacryocystitis, Croup, Bezold's abscess,
Endocrine	Subacute thyroiditis, Exopthalmos, Diabetes insipidus, De Quervain's thyroiditis, Adrenal hemorrhage,
Environmental	Zinc oxide, Silicosis, Polytetrafluoroethylene, Metal fume fever,
Gastroenterologic	Ulcerative colitis, Toxic megacolon, Pseudomembranous colitis/C.difficile, Peritonitis, Perianal abscess, Pancreatitis, Ischemic colitis, Intra-abdominal abscess, Ileitis, Hepato-biliary diseases, Gastritis, Gastroenteritis, Gastrointestinal perforation, Diverticulitis, Crohn's disease, Colitis, Cholangitis, Cholecystitis, Caroli's Disease, Caecitis, Appendicitis, Anal abscess,
Genetic	Muckle-Wells syndrome, Sickle-cell disease, Krabbe disease, Hyperimmunoglobulinemia D with recurrent fever, Fabry's Disease, Cystic Fibrosis, Familial Mediterranian Fever, Blue diaper syndrome,
Hematologic	Disseminated Intravascular Coagulation, Blood Transfusion, Acute lymphoblastic leukemia, Acute myeloid leukemia,
Iatrogenic	Transfusion reaction, Transfusion-associated graft versus host disease, Serotonin syndrome, Malignant hyperthermia, Adjustable gastric band,
Infectious Disease	Adenoviridae, African Hemmorhagic Fever, African horse sickness, African swine fever virus, African Trypanosomiasis, Alkhurma virus, Allergic bronchopulmonary aspergillosis, Alphavirus, Anthrax, Aphthovirus, Arbovirus, Arenavirus, Aripiprazole , Arterivirus, Aspergillosis, Astroviridae, Babanki virus, Bacillary angiomatosis, Bartonellosis, BK virus, Blackwater fever, Blastomycosis, Bordetella pertussis, Bornholm disease, Borrelia, Boutonneuse fever, Brucellosis, Bubonic plague, Buruli ulcer, Bwamba Fever, Cabin fever, Campylobacter jejuni, Cat scratch fever, Chagas disease, Chickenpox, Chlamydia, Chlamydophila pneumoniae, Clostridium Difficile, CMV , Coccidioidomycosis, Colorado tick fever virus, Cotton fever, Coxiella burnetii infection, Coxsackie A virus, Crimean Congo Hemorrhagic Fever, Cryptosporidiosis, Cyclosporiasis, Dengue Fever, Dientamoebiasis, Diphtheria, Ebola haemorrhagic fever, Echovirus, Enterotoxigenic Escherichia coli, Epstein-Barr virus, Fasciolosis, Fasciolopsiasis, Filoviridae, Flavivirus, Fusarium, Giardiasis, Gonorrhea, Group A streptococcal infection, Haemophilus influenzae, Haverhill fever, Hantavirus Pulmonary Syndrome, Herpangina, Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis E, Herpes zoster, Herpesviridae, HIV/AIDS, Hookworm, Infectious mononucleosis, Influenza virus , Lassa Fever, Legionellosis, Leishmaniasis, Leptospirosis, Lemierre's Syndrome, Listeriosis, Lyme disease, Malaria, Measles, Melioidosis, Miliary tuberculosis, Mumps, Murray Valley encephalitis virus, Mycobacterium avium complex, Mycoplasma pneumoniae, Naegleria infection, Nocardiosis, Noma (disease), Norovirus infection, Omsk hemorrhagic fever, O'nyong'nyong virus, Opisthorchis infection, Oropouche virus, Paracoccidioidomycosis, Paragonimus Infection, Paratyphoid fever, Penicilliosis, Pityriasis rosea, Pneumocystis jirovecii pneumonia, Poliomyelitis, Pontiac fever, Psittacosis, Q fever, Rat-bite fever, Rhinovirus, Rheumatic fever, Rickettsial infections, Rift Valley fever virus, Rocky Mountain Spotted Fever, Roseola, Ross River Fever, Rotavirus, Rubella, Salmonella enteritidis, Salmonella typhi infection/ Typhoid fever, Scarlet fever, Schistosomiasis, Septic arthritis, Shigellosis, Severe acute respiratory syndrome, Sindbis virus, Sleeping sickness, Smallpox, Marburg hemorrhagic fever, Mediterranean spotted fever, Staphylococcal enteritis, Streptococcus pyogenes, Swine flu, Syphillis, TORCH infections, Toxic Shock Syndrome, Toxocara infection, Traveler's diarrhea, Trench Fever, Trichinosis, Tularemia, Varicella-zoster virus, Vibrio parahaemolyticus, Vibrio vulnificus, Visceral leishmaniasis, West Nile Virus, Whipple's disease, Yellow Fever Virus, Yersinia enterocolitica Infection (Yersiniosis), Yersinia Pestis Infection, Yersinia pseudotuberculosis, Zika fever,
Musculoskeletal / Ortho	Septic arthritis, Reactive Polyarticular Arthritis,
Neurologic	Subdural hygroma, Neuroleptic malignant syndrome, Meningitis, La Crosse encephalitis, Krabbe disease, Craniopharyngioma, Brain Abscess, Acute Disseminated Encephalomyelitis,
Nutritional / Metabolic	Blue diaper syndrome, Gout, Porphyria
Obstetric/Gynecologic	Pelvic inflammatory disease, Childbirth,
Oncologic	Acute lymphoblastic leukemia, Acute myeloid leukemia, Pel-Ebstein fever, Synovial sarcoma, Renal Cell Carcinoma, Myxoma, Mesothelioma, Lung cancer, Juvenile Myelomonocytic Leukemia (JMML), Kaposi's sarcoma, Hodgkin's lymphoma, Craniopharyngioma, Chronic myelogenous leukemia,
Opthalmologic	Tolosa-Hunt syndrome, Temporal arteritis, Cogan syndrome, Acute posterior multifocal placoid pigment epitheliopathy,
Overdose / Toxicity	Vitamin A, Coley's Toxins, Didanosine , Ethchlorvynol, Ganciclovir , Melarsoprol, Methotrexate , Mycophenolate , Nevirapine , Oxybutynin , Oxycodone and aspirin , Peginterferon alfa-2a , Phenelzine , Phentermine, Selegiline , Solifenacin , Valganciclovir ,
Psychiatric	No underlying causes
Pulmonary	Tuberculosis, Tracheitis, Pulmonary alveolar proteinosis, Pleurisy, Lung cancer, Lung abscess, Empyema, Community-acquired pneumonia, Bronchitis, Atelectasis, Alveolitis, Allergic bronchopulmonary aspergillosis, Acute Chest Syndrome,
Renal / Electrolyte	Urinary tract infection, Pyelonephritis, Interstitial nephritis,
Rheum / Immune / Allergy	Wegener Granulomatosis, Varicella (Chickenpox) Vaccine , Yellow Fever Vaccine , Takayasu's Arteritis, Systemic lupus erythematosus, Still's disease, Serum sickness, Sarcoidosis, Rheumatoid arthritis, Rabies vaccine , Polyarteritis nodosa, Lupoid hepatitis, Langerhans cell histiocytosis, Kawasaki disease, Hay fever, Churg-Strauss Syndrome, Bacillus Calmette-Guerin (BCG) Vaccine ,
Sexual	Syphillis, Lymphogranuloma venereum,
Trauma	No underlying causes
Urologic	Prostatitis,
Miscellaneous	Retinoic acid syndrome, POEMS syndrome, Omphalitis, Occult abscess, Neutropenia, Mastitis, Lymphocytopenia, Kikuchi disease, Immune reconstitution inflammatory syndrome, Herxheimer reaction, Heroin withdrawl, Hemophagocytic lymphohistiocytosis, Fetal alcohol syndrome, Fat Embolism Syndrome, Cytokine release syndrome, Congenital syphilis, Cocaine, Adiposis dolorosa,

Usefulness of Fever

There are arguments for and against the usefulness of fever, and the issue is controversial. There are studies using warm-blooded vertebrates and humans in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever.

Theoretically, fever has been conserved during evolution because of its advantage for 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. The overall conclusion seems to be that both aggressive treatment of fever and too little fever control can be detrimental. This depends on the clinical situation, so careful assessment is needed.

Fevers may be useful to some extent since they allow the body to reach high temperatures. This causes an unbearable environment for some pathogens. White blood cells also rapidly proliferate due to the suitable environment and can also help fight off the harmful pathogens and microbes that invaded the body.

Treatment

Fever should not necessarily be treated. Fever is an important signal that there's something wrong in the body, and it can be used for follow-up. Moreover, not all fevers are of infectious origin.

Even when treatment is not indicated, however, febrile patients are generally advised to keep themselves adequately hydrated, as the dehydration produced by a mild fever can be more dangerous than the fever itself. Water is generally used for this purpose, but there is always a small risk of hyponatremia if the patient drinks too much water. For this reason, some patients drink sports drinks or products designed specifically for this purpose.

Most people take medication against fever because the symptoms cause discomfort. Fever increases heart rate and metabolism, thus potentially putting an additional strain on elderly patients, patients with heart disease, etc. This may even cause delirium. Therefore, potential benefits must be weighed against risks in these patients. In any case, fever must be brought under control in instances when fever escalates to hyperpyrexia and tissue damage is imminent.

Treatment of fever should be based primarily on lowering the set-point, but facilitating heat loss may also contribute. The former is accomplished with antipyretics. Wet cloth or pads are also used for treatment, and applied to the forehead. Heat loss may be an effect of (possibly a combination of) heat conduction, convection, radiation, or evaporation (sweating, perspiration). This may be particularly important in babies, where drugs should be avoided. However, if water that is too cold is used, it induces vasoconstriction and prevents adequate heat loss.

References

Articles

Books

• 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
• Kasper, D.L.; Braunwald, E.; Fauci, A.S.; Hauser, S.L.; Longo, D.L.; Jameson, J.L. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2005. ISBN 0-07-139140-1.

External Links

• What to do if your child has a fever from Seattle Children's Hospital
• Fever and Taking Your Child's Temperature
• US National Institute of Health factsheet
• BUPA factsheet