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November 02, 2012

Fever of Unknown Origin and Cancer

A 62-year-old woman presents to the hospital with an almost 2-year history of intermittent fevers of up to 102°F. She reports that over that same time span, she has become progressively weak and has been experiencing darker urine. The family states that occasionally she is “not acting herself”, but they attribute it to old age. The patient is admitted to the hospital with acute kidney injury (AKI), elevated liver function tests (LFTs), and failure to thrive (FTT), presumably due to her decreased oral intake and poor diet. 
During her hospitalization, she continues to spike fevers up to 103°F, and she becomes increasingly altered to the point where she is minimally responsive. Blood cultures remain negative and a CT of her head shows no acute changes or intracranial bleed. Endocarditis, abscesses, and connective tissue diseases are all ruled out as potential causes of her fever. 
At this point, the patient can be described as having a fever of unknown origin (FUO). By definition, FUO is characterized by a temperature >100.9°F on multiple occasions for at least 3 weeks in addition to a negative workup in a hospital for at least one week. The differential diagnosis of FUO is extensive, although one important diagnosis includes cancer. 
Although the data varies between studies, up to 10% of all FUO cases can be attributed to an underlying cancer. The most likely cancers to present with FUO include the hematological malignancies such as lymphoma, leukemia, multiple myeloma, and myelodysplastic syndrome. Additional solid organ tumors that have been associated with FUO include hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The textbook triad of findings in RCC includes hematuria, flank pain, and a palpable abdominal mass, although these occur in less than 10% of all RCC patients. A persistent fever in combination with some of these findings could lead to further investigation into RCC. Metastases to the liver, especially those of adenocarcinoma origin, have also been implicated in FUO.
Depending on the patient presentation, history, and physical, the workup could vary. Further laboratory studies in addition to basic bloodwork include ESR, CRP, tumor markers, chromosomal studies, and bone marrow biopsies. Potentially helpful imaging studies include an abdominal ultrasound; CT of the chest, abdomen, and pelvis; and PET scans. All of these tests are not necessary in every patient with a diagnosis of FUO. Sound clinical judgment is necessary in order to evaluate which tests are the most beneficial to the patient and which will directly impact clinical decision making.
by
Dr.Akshaya Srikanth
Pharm.D, India

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