Malignancy
Malignancies of all varieties have been reported to be associated with fever. In most series, hematologic malignancies account for a high percentage of cases of FUO (Fever of Unknown Origin). The most common causes are Hodgkin’s and non-Hodgkin’s lymphoma as well as leukemia. Of the solid tumors, renal cell carcinoma and hepatocellular carcinoma are well established causes of fever. Any patient with a prior history of malignancy should be investigated fully for recurrence of the malignancy or a secondary malignancy in the context of prior chemotherapy or radiation. A prior history of radiation therapy is also known to be associated with pneumonitis and pericarditis as a cause of fever.
Collagen Vascular Diseases
Collagen vascular diseases are an important cause of FUO. Once life-threatening infectious and malignant causes of fever are ruled out, prolonged observation may be necessary before the diagnosis of one of these diseases becomes apparent. Still’s disease is an important consideration and is characterized by the presence of lymphadenopathy, polyarthritis, myalgias, splenomegaly, and serositis. An evanescent salmon-colored rash and a sore throat are usual findings. Fever can precede other symptoms by as long as 1 year, thus making the diagnosis difficult. Laboratory abnormalities include highly elevated ferritin levels, leukocytosis, an elevated erythrocyte sedimentation rate, and mild abnormalities in liver-associated enzymes. Serologic markers for other rheumatologic diseases are negative. In elderly patients, polymyalgia rheumatica is another important consideration, particularly when stiffness or pain is present in the shoulder or hip girdles.
Drug Fever
All potential offending drugs should be stopped. Although some drugs are common causes of FUO, the list of etiologic agents causing drug fever is extensive. The drug may have been started many weeks before the fever began. There may be an associated rash or eosinophilia present. Typically, drug fever resolves within 48 hours of stopping the agent.
Factitious Fever
Factitious fever describes a fever that is simulated or induced. Although some patients with factitious fever may be malingering, a factitious fever is often a sign of very serious mental illness. The classic patient is a young woman with some experience in health care, although this is certainly not always the case. Clues that a fever is factitious can be gleaned from a constellation of symptoms that do not correlate with any known disease. Once the diagnosis is suspected, the patient should be handled with empathy, bearing in mind that this may be a presentation of major psychiatric pathology and instability. Given patient variability, it is difficult to formulate a standardized approach, and psychiatric consultation is recommended.
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