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Am Fam Physician. 2010;81(8):1029

Background: Fever of unknown origin remains clinically challenging, often requiring weeks to months to secure a diagnosis. Bone marrow biopsy has been shown to be safe and useful in patients with human immunodeficiency virus (HIV) infection who have fever of unknown origin, but its value in immunocompetent patients has not been sufficiently assessed. Hot and colleagues studied patients with fever of unknown origin who had previously received a bone marrow biopsy to determine its usefulness in diagnosis.

The Study: The authors retrospectively reviewed consecutive immunocompetent patients who had undergone a bone marrow biopsy as part of the workup for fever of unknown origin. Eligible patients were required to present a previous inconclusive laboratory and radiologic workup, including testing for tuberculosis and HIV. All biopsies were performed at the posterior iliac crest using a Jamshidi needle. Bone marrow aspirate was evaluated histologically and cultured for mycobacteria. Patient status was monitored for one year after bone marrow biopsy to confirm the diagnosis of febrile illness. Patients were excluded for nosocomial fever, known HIV infection, or for having a history of hematologic malignancy.

Results: Of 130 adult patients with fever of unknown origin, 31 (23.7 percent) were diagnosed as a result of information obtained by bone marrow biopsy. Hematologic malignancies (80.6 percent) and infectious diseases (9.6 percent) were the most common sources of fever of unknown origin. Tuberculosis was identified histologically in two patients, although bone marrow culture failed to identify any cases. The likelihood of diagnosis by bone marrow biopsy was not affected by duration of fever, corticosteroid use, or baseline erythrocyte sedimentation rate or C-reactive protein levels. However, bone marrow biopsy was more likely to yield a diagnosis when anemia (i.e., hemoglobin level less than 11 g per dL [110 g per L]) or thrombocytopenia was present. Bone marrow biopsy was also more useful for patients whose fever of unknown origin was persistent rather than recurrent (diagnostic yield = 32.9 percent versus 8.3 percent, respectively). Only two complications associated with bone marrow biopsy were noted, both involving hematomas that resolved with conservative therapy.

Conclusion: The authors conclude that histologic analysis of bone marrow biopsy is useful for the diagnosis of prolonged fever in cases of fever of unknown origin. Mycobacterial culture of bone marrow aspirate does not appear to be helpful in immunocompetent patients. Bone marrow biopsy is more useful when persistent fever, anemia, or thrombocytopenia is present and less useful with recurrent fever.

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