e.g., COVID-19, dengue, Ebola, gastroenteritis, HIV, influenza, Lyme disease, rocky mountain spotted fever, secondary syphilis, malaria, mononucleosis, as well as infections of the skin, e.g., abscesses and boils. Immunological diseases, e.g., relapsing polychondritis, autoimmune hepatitis, granulomatosis with polyangiitis, Horton disease, inflammatory bowel diseases, Kawasaki disease, lupus erythematosus, sarcoidosis, and Still's disease; Tissue destruction, as a result of cerebral bleeding, crush syndrome, hemolysis, infarction, rhabdomyolysis, surgery, etc.; Cancers, particularly blood cancers such as leukemia and lymphomas; Metabolic disorders, e.g., gout, 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, 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. Teething is not a cause of fever. Function Immune function Fever is thought to contribute to host defense, as the reproduction of pathogens 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; decreased endotoxin effects; and increased proliferation of T cells. Advantages and disadvantages Having a fever response in 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 vertebrates suggest that they recover more rapidly from infections or critical illness due to fever. In sepsis, fever is associated with reduced mortality. Pathophysiology of fever induction Hypothalamus Temperature is regulated in the hypothalamus. 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. 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