Role of bone marrow examination in pyrexia of unknown origin

The report by Akhtar et al. reminds us of the importance of a stepwise approach to evaluating pyrexia of unknown origin (PUO) in low-middle-income countries.^1,2 We wish also to highlight the role of bone marrow (BM) examination as a valuable diagnostic tool in PUO when other investigations are negative. It is particularly helpful in cases involving reticuloendothelial organs, manifesting as cytopenia involving one or more cell lineages, splenomegaly, or lymphadenopathy such as haematological malignancy (viz. lymphoma or leukaemia), infections (viz. histoplasmosis, kala-azar, disseminated tuberculosis, cytomegalovirus), or haemophagocytic syndrome.^2–4 It may also be required in diagnosing various auto-inflammatory conditions (e.g., adult-onset Still's disease), which require a mandatory exclusion of alternate differentials such as malignancy and infection. ⁵

BM examination includes aspirate or biopsy, culture and flow cytometry where indicated. A diagnostic utility of 24% was demonstrated in an immunocompetent French cohort, where thrombocytopenia or anaemia predicated a diagnosis by BM. ⁶ An Indian study on PUO in older adults found a high diagnostic yield of 47%. ⁷ Its role is even more important in immunodeficiency states, where an early diagnosis is often required.^8,9 A scoring system based on haemoglobin, absolute neutrophil count, platelet count, a leucoerythroblastic picture on peripheral smear, splenomegaly, ferritin and lactate dehydrogenase, has been proposed to predict a yield of BM examination in PUO. ¹⁰