How can bone marrow examination help in diagnosing Pyrexia of Unknown Origin (PUO)?

Role of Bone Marrow Examination in Diagnosing Pyrexia of Unknown Origin (PUO)

Bone marrow examination is a valuable diagnostic tool in pyrexia of unknown origin (PUO) with a diagnostic yield of approximately 24%, particularly when patients present with hematological abnormalities such as anemia or thrombocytopenia. 1

Diagnostic Yield and Utility

• Bone marrow examination can identify the underlying cause in 8-24% of PUO cases, making it an important component of the diagnostic workup when initial investigations are inconclusive 2, 1
• The diagnostic yield is highest in patients with hematological abnormalities, with thrombocytopenia (odds ratio 4.9) and anemia (odds ratio 3.24) being the most reliable predictive factors for a positive bone marrow finding 1
• Bone marrow aspiration and biopsy can detect both hematological and non-hematological diseases that cause PUO, including infections, malignancies, and inflammatory conditions 2

Specific Conditions Diagnosed Through Bone Marrow Examination

• Hematological malignancies represent the most common diagnoses obtained through bone marrow examination in PUO cases, including:

  • Malignant lymphomas (most frequent finding) 1
  • Acute leukemias 1
  • Hairy cell leukemia 1
  • Multiple myeloma 1

• Infectious causes identifiable through bone marrow examination include:

  • Bacterial infections (42.8% of positive bone marrow findings) 2
  • Mycobacterial infections, particularly tuberculosis (42.8% of positive findings) 2
  • Fungal infections (10.7% of positive findings) 2
  • Viral infections (3.5% of positive findings) 2

Patient Selection for Bone Marrow Examination

• Bone marrow examination should not be performed based solely on prolonged fever; specific clinical or hematological indications should be present 3, 4

• Indications that increase the diagnostic yield include:

  • Presence of cytopenia (especially anemia and thrombocytopenia) 4, 1
  • Splenomegaly or other evidence of reticuloendothelial system involvement 4
  • Immunocompromised status (HIV, post-transplant, autoimmune conditions on immunosuppression) 2, 4
  • Advanced age 4
  • Abnormal peripheral blood smear 1

• Blind bone marrow biopsy (without specific indications) has limited utility in immunocompetent patients but may be more useful in immunocompromised individuals 5

Technical Considerations

• Both bone marrow aspiration and biopsy should be performed for optimal diagnostic yield 2
• Samples should be collected for:
  • Cytological examination 2, 3
  • Histological examination 2, 3
  • Microbiological cultures (though these have limited value in some studies) 2, 1

Timing in the Diagnostic Algorithm

• Bone marrow examination should be considered after initial investigations fail to identify the cause of fever 4
• It should be performed before initiating empiric antimicrobial therapy when infection is suspected, as prior antibiotic use may reduce the diagnostic yield 2
• In the diagnostic algorithm, bone marrow examination typically follows basic laboratory testing and imaging studies such as FDG-PET/CT, which has higher sensitivity (80-100%) for identifying the source of fever in PUO cases 6, 7

Limitations and Pitfalls

• The diagnostic yield varies significantly based on patient selection criteria and the thoroughness of prior investigations 3, 1
• Fever alone, even when prolonged and undiagnosed, is not sufficient indication for bone marrow biopsy 3
• False negatives may occur due to sampling error, especially in focal infections or infiltrations 2
• Corticosteroid use prior to bone marrow examination does not appear to significantly affect the diagnostic yield 1

In summary, bone marrow examination should be considered in the diagnostic workup of PUO when patients present with hematological abnormalities or specific risk factors, but should not be performed indiscriminately in all patients with unexplained fever.