Which lab findings suggest a specific cause for fever of unknown origin (FUO)?

Updated: May 17, 2021
  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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Anemia is an important finding and suggests a serious underlying disease.

Suspect herpesvirus infection if the patient has lymphocytosis with atypical cells.

Leukocytosis with an increase in bands suggests an occult bacterial infection, as well as occult hemorrhage, hematoma, or thromboembolic process.

Diagnose malaria and spirochetal diseases with the aid of direct examination of the peripheral blood smear; however, repeated examinations by an experienced technologist are often necessary. With Relapsing Fever/spirochetal diseases, it is best to obtain blood sample during febrile period for highest probablity of spirochetemia and direct observation. Preleukemic states may not manifest in the peripheral blood smear, and bone marrow aspirate may not reveal the correct diagnosis; bone marrow biopsy may be necessary for diagnosis. 

Adult-onset Still disease is often difficult to diagnose. Laboratory abnormalities include pronounced leukocytosis, an elevated erythrocyte sedimentation rate (ESR), anemia, and abnormal liver function test results.

Among solid tumors, renal cell carcinoma is most commonly associated with FUO, with fever being the only presenting symptom in 10% of cases. Hematuria may be absent in approximately 40% of cases, whereas anemia and a highly elevated sedimentation rate are common.

Laboratory findings in giant cell arteritis (GCA) include an elevated ESR, mild to moderate normochromic normocytic anemia, elevated platelet counts, and abnormal liver function test results (25% of cases). Perform a biopsy of a temporal artery to obtain a definitive diagnosis. Pathologic review shows vasculitis and a mononuclear cell infiltrate.

At least one liver function test result is usually abnormal in an underlying disease that originates in the liver or a disease that causes nonspecific alterations of the liver (eg, granulomatous hepatitis).

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