Pathophysiology and clinical outcomes of pancytopenia in disseminated histoplasmosis: a scoping review

Purpose: Pancytopenia in the setting of disseminated histoplasmosis is sparsely described in the literature. We investigated the underlying mechanisms of pancytopenia in disseminated histoplasmosis and highlighted clinical outcomes.

Methods: We conducted a scoping review of cases and series on disseminated histoplasmosis presenting with pancytopenia published between 2001 and 2024. PubMed database was used for the search. The search terms were (disseminated histoplasmosis) AND (pancytopenia OR haemophagocytic syndrome OR lymphohistiocytosis).

Results: We identified 72 cases. Forty-four (61.1%) cases were from the Americas, 18 (25.5%) from Asia, 8 (11.1%) from Europe, and 1(1.4%) each from Africa and Australia. Of the 72 cases, five cases (6.9%) were reported in children. The mean age was 41.9 ± 16.7 years with a range of 3 months to 78 years. Seven cases (9.7%) were immunocompetent, 27 (37.5%) had an underlying HIV infection and 45 (62.5%) were complicated with haemophagocytic lymphohistiocytosis syndrome. Histoplasma antigen assay (n = 29, 40.2%) was the major diagnostic method followed by bone marrow biopsy (n = 28, 38.9%). Fifty-three cases (73.6%) recovered, 15 (20.8%) died and outcomes were not stated in 4 cases (5.65%). The relationship between haemophagocytic lymphohistiocytosis and fatal outcomes was not statistically significant (P = 0.5). Likewise, HIV infection was not significantly associated with fatal outcomes (P = 0.6). Fatal outcomes were predominantly due to difficulty or delayed diagnosis of disseminated histoplasmosis and/or haemophagocytic lymphohistiocytosis (n = 5, 6.9%), multiple organ failure (n = 4, 5.6%) and late presentation (n = 2, 2.8%).

Conclusion: Pancytopenia in disseminated histoplasmosis is associated with poor outcomes. Such a hematologic finding should arouse the index of suspicion in the attending clinician for an invasive mycosis like disseminated histoplasmosis to avert fatal outcomes. Besides haemophagocytic lymphohistiocytosis, other factors associated with pancytopenia in disseminated histoplasmosis were the cooccurrence of viral and bacterial infections.