High Incidence of Peripheral Blood Plasmacytosis In Patients with Dengue Virus Infection: a Prospective Study

One of the characteristic features of dengue virus (DENV) infection is the occurrence of leukopenia and thrombocytopenia, probably resulting from virus induced bone marrow suppression. Despite the general bone marrow suppression, polyclonal peripheral blood plasmacytosis has occasionally been described in DENV infected patients. The frequency of peripheral blood (PB) plasmacytosis in patients with dengue infection, the origin of these plasma cells (PCs) and the mechanisms by which they appear in the blood are not known. We initiated this prospective observational study to quantify and describe the kinetics and phenotype of PB plasmacells (PCs) in these patients.

Morphological examination of the peripheral blood smear was performed in 35 sequential returned travelers suspected of DENV infection, with a history of less than 14 days of fever. Flow cytometric (FC) analysis for the characterization and immunophenotyping of lymphocyte subsets and PCs was performed in 31 patients. Follow-up samples were available for 8 patients.

Our results show that PB plasmacytosis is a very common hematological finding in DENV infection, with extreme values of up to 36% of total white blood cells in some patients. Depending on the number of days since the onset of fever at presentation, PB plasmacytosis was observed in 64% to 73% of 28 patients with confirmed DENV infection, and in none of 7 patients with other febrile illnesses. PB plasmacytosis was the most pronounced before 7 days after onset of illness and declined rapidly thereafter, to completely disappear after 14 days of illness. The median percentage of PCs at day 7 was 2.5% (range 0–36%; 25–75 interquartile range: 0–8%). The median percentage of PCs was significantly higher in patients with secondary DENV infection than in patients with primary infection (4.5% versus 1.0%; p=0.05). Viral RNA was detectable in 18 of 28 DENV infected patients with a highly variable viral load, but there was no correlation between viral load and percentage of PCs. We found an excellent correlation between percentage of PCs as assessed by morphology and by flow cytometry (r²= 0.85). The majority of CD138⁺ PCs (89%) had a shared immunophenotype (CD45⁺/CD19⁻/CD56⁻), which differed from normal plasmacells which are generally CD19⁺. In all cases the PCs were polyclonal.

PB plasmacytosis, characterized by a transient presence of polyclonal PCs in the circulation, is a common event in DENV infection and is probably the result of a vigorous humoral immune response to dengue. With an increasing number of travelers to areas where dengue virus is endemic, it is important also for hematologists to recognize this benign cause of sometimes extreme plasmacytosis, for which no invasive procedures such as bone marrow examinations are needed.

No relevant conflicts of interest to declare.