Fever and cancer
Fever is an elevation in core body temperature often seen in cancer patients, often as a response to pyrogens — substances that induce fever. It can arise from infections, particularly in patients undergoing cancer treatments that compromise the immune system, such as chemotherapy. Common cancers associated with fever include lymphomas and leukemias, with the condition sometimes being more a result of the treatment rather than the cancer itself. The body's response to fever involves complex mechanisms involving cytokines, which are proteins that signal the brain to increase temperature, ultimately enhancing the immune response.
While fever can be beneficial in fighting infections, prolonged or high fever can lead to complications, including organ damage. Diagnosing the cause of fever in cancer patients requires thorough medical history, physical examination, and various tests, as it can indicate life-threatening infections or specific cancer-related conditions. Treatment typically focuses on addressing the underlying cause rather than the fever itself, and in some cases, antipyretic medications may be used for comfort. Preventative measures, such as managing potential sources of infection and careful monitoring during treatment, are crucial for reducing the incidence of fever in this vulnerable population.
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Fever and cancer
ALSO KNOWN AS: Hyperpyrexia
RELATED CONDITIONS: Infection and sepsis in cancer treatment, myelosuppression, neutropenia
DEFINITION: Fever is a pyrogen-mediated elevation of the core body temperature. This is in distinction to hyperthermia, which is an unregulated rise in core temperature, as occurs in heat stroke. Pyrogens may originate outside the body (exogenous) or be produced within the body (endogenous). Exogenous pyrogens are typically microorganisms or their toxins and products but also include drugs, antigen-antibody complexes, and other substances. Endogenous pyrogens are various chemicals produced by host cells and are called cytokines.
Risk factors: Although many types of malignant neoplasms may cause fever, some of the most common are lymphomas, leukemias, preleukemia, and renal cell carcinoma. However, fever in cancer patients is more often a consequence of treatment than of the cancer. The protective barrier provided by the skin and mucous membranes may be breached by surgery or vascular catheter placement, providing entrance points for invading microbes, which produce infection and fever. A similar phenomenon may result from chemotherapeutic cancer drugs that destroy not only the cancer cells but also oral and mucous membrane lining cells, inducing mucositis. Drugs may also kill bone marrow cells (myelosuppression and neutropenia), which impairs bodily defense mechanisms against infectious agents. The vascular catheters used to administer medicines, intravenous fluids, and blood components are risks for infection, and the risk increases the longer the catheter stays in place. Administration of blood components can produce fever through several mechanisms.
The antibiotics Antibiotics used to treat infection may produce fever, complicating therapy. Some antibiotics, such as sulfonamides and chloramphenicol, can cause neutropenia and fever. Finally, antibiotics may alter the patient's normal flora, allowing overgrowth of problem organisms. Fungi, such as those of the Candida species, may overgrow on the skin and in the gastrointestinal tract, causing infection. An anaerobic toxin-producing bacterium called Clostridium difficile can overgrow in the colon, causing fever and diarrhea.
Venous thrombosis can also cause fever. Some cancers, especially adenocarcinomas, are associated with a hypercoagulable state. Venous stasis may result from an obstructing tumor mass or lymphadenopathy, immobility (bedrest or surgery), and dehydration. Some antineoplastic drugs can result in endothelial injury. All these factors can contribute to the formation of fever-associated thrombi.
Etiology and the disease process: Fever is a complex and incomplete process initiated by producing endogenous pyrogens or cytokines. Cytokines are polypeptide proteins produced by host cells, probably mononuclear macrophages. Cytokines, including interleukin-1, tumor-necrosis factor, and interleukin-6, make the rapid onset of fever by acting directly on the brain (hypothalamus). The exogenous pyrogens or some endogenous molecules induce the release of cytokines. Exogenous pyrogens are usually microbes and their products (including toxins). An example of an endogenous molecule is a complement-binding antigen-antibody complex. Finally, the hypothalamus produces prostaglandin E2, which orchestrates physiologic changes that increase core temperature.
Fever is an adaptive response that, for the most part, is beneficial. Increased temperature is associated with increased production of antibacterial substances (superoxides and interferon), increased neutrophil migration, and increased T-cell proliferation, all of which are beneficial in the fight against invading microbes. Nonetheless, fever is metabolically demanding, and prolonged fever can be deleterious to the patient. High fever can damage organs and contribute to circulatory collapse or failure.
Incidence: The relationship between fever and cancer may be examined by looking first at fever in patients who are not diagnosed with cancer or any other causative disease process and second at fever in patients with specific cancer that has already been diagnosed.
An underlying malignancy is causative in 9 to 30 percent of patients with an undiagnosed fever of undetermined origin. Lymphoreticular neoplasms, such as Hodgkin disease and non-Hodgkin lymphoma, are the most common. The age of patients with fever of unknown origin influences the percentage of neoplasms. Children usually have fewer cancers and more infections, while older adults have higher percentages of cancers.
The incidence of fever in patients in whom cancer is already diagnosed varies widely, as it depends on many variables, including the type and severity of the cancer, treatments employed, and comorbid illnesses. Fever is a common problem in cancer patients.
Symptoms: At the onset of a fever, body heat is conserved by vasoconstriction, and the patient initially feels cool, especially in the hands and feet. Shivering occurs when muscles act to produce heat. Finally, the patient feels warm as the higher setpoint for core temperature is reached. Sweating and vasodilatation (flushing) occur only with heat loss and the subsequent falling temperature.
Screening and diagnosis: A detailed history and careful physical examination are essential for patients with fever of undetermined origin and can provide critical information. Sometimes, fever patterns themselves can be revealing. A sudden onset of fever, particularly if preceded by rigors or chills, indicates bacteremia or fungemia. Pel-Epstein fever is associated with Hodgkin disease and is characterized by three to ten days of fever followed by three to ten days without a fever. An initial battery of laboratory and radiologic tests is followed by an ordering sequence of more tests depending on the results of previous tests. Ultimately, a biopsy of an abnormal mass, lymph node, or bone marrow is usually required for the diagnosis of a specific cancer as a cause of a fever with an undetermined origin.
Patients with previously diagnosed cancer present equally challenging problems in determining fever etiology. The most pressing issue is determining if the patient has a life-threatening infection. Empiric antibiotic therapy is commonly administered as a safeguard. After taking a thorough history and performing a physical examination, the patient undergoes blood and urine tests, radiologic studies, blood cultures, and other tests to determine the source of infection. If there are no indications of infection and empiric antibiotic therapy has no beneficial effect, noninfectious causes must be sought. Drugs, venous thrombosis, and neoplastic fever are all possible. When other causes of fever have failed to be detected by any means and neoplastic fever appears likely, treating the patient with the nonsteroidal anti-inflammatory agent naproxen can aid in the diagnosis. Naproxen has a unique ability to suppress tumor fever but does not significantly affect fevers of non-neoplastic origin.
Treatment and therapy: Antipyretic therapy is generally provided only when the patient is uncomfortable or the fever is causing problems such as cardiovascular failure due to fever-induced tachycardia. The fever is not routinely treated because it is a continuing clue to the underlying diagnosis; treatment of the cause of the fever leads to final resolution.
Complicating infections are treated with antibiotics, and associated catheters and other foreign bodies are removed whenever possible. If infection is associated with neutropenia, a granulocyte colony-stimulating factor is administered to restore the neutrophil numbers. Drugs are discontinued when necessary, and blood clots are removed or treated. Neoplastic fever can be treated with naproxen while the cancer is being removed or treated with other measures.
Prognosis, prevention, and outcomes: The prognosis depends on many factors but is often related to the ability to successfully control infection in the feverish patient. Correspondingly, unresolved immunosuppression or uncontrolled neoplastic growth can render infections difficult or impossible to resolve. Successful treatment is possible for most patients after a specific etiology for the fever is established.
Prevention is mainly directed at infections complicating cancers and antineoplastic therapies. Careful management of vascular catheters, minimization of immunosuppressive periods, and prophylactic antibiotics during critical times can all help prevent infections and fever.
Bibliography
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