Extreme plasmacytosis in peripheral blood is a rare finding most often associated with plasma cell leukemia but rarely with other malignancies, infectious diseases, or drug reactions. We report the case of a 40-year-old man who was a US expatriate working and traveling in East Asia. He presented with complaints of fever, myalgia, headache, vomiting, and diarrhea of 3 days' duration. An initial evaluation revealed elevated liver function tests, thrombocytopenia (68 × 103/μL), and a white blood cell count of 5.8 × 103/μL with 19% plasma cells (1100/μL), 9% abnormal plasmacytoid lymphocytes (520/μL), 37% polymorphonuclear leukocytes, 3% band forms, 27% lymphocytes, 4% monocytes, and 1% eosinophils. An extensive evaluation was performed, including infectious disease serologies, a bone marrow biopsy, and flow cytometry. During the course of 3 days, his symptoms and hematologic findings improved dramatically. Serologic results were reactive for dengue (immunoglobulin M [IgM] positive, reciprocal IgG titer, 655 360), consistent with a secondary infection of unknown serotype. He remains well 4 years later. To our knowledge, plasmacytosis to this degree has not been described in dengue fever, but atypical lymphocytosis is common. In patients from dengue-endemic areas, even extreme plasmacytosis should be assessed to determine whether it is transient and related to an acute illness before proceeding to an extensive evaluation.

Peripheral blood plasmacytosis of more than 1% to 2% is rare. Plasmacytosis of 20% or more suggests plasma cell leukemia or myeloma,1 both of which have a poor prognosis. Reactive plasmacytosis has been reported in association with infection, inflammation, certain medications, and intoxications, but plasmacytosis of this extreme degree is rare. Reactive lymphocytosis with increased circulating B lymphocytes, including cells containing immunoglobulin, is characteristic of dengue fever,2 but, to our knowledge, plasmacytosis as such has not been described. We report a case of extreme, transient plasmacytosis in a patient with a secondary dengue fever infection.

A 40-year-old white man who was a US-born engineer and who had lived for 3 years in Tokyo presented for evaluation of fever and diarrhea on May 29, 1998. Prior to his residence in Japan, he had lived and worked for 2 to 6 years each in South Africa, Kuwait, and Zimbabwe.

The patient left Tokyo 2 weeks prior to presentation and had spent a week at a resort in Borakai, Philippines, where he mainly relaxed on the beach and went on day treks on horseback into the forested area nearby. The patient ate freely, including salads. He did not take any antimalarial prophylaxis. He was bitten on the wrist at some point by an unknown insect and developed a small nodule. He had developed vomiting and loose stools on May 21 when he left the Philippines for Bangkok, where on May 23 he had a fever of 39.4°C and chills. He was seen at a local clinic and given norfloxacin for 3 days with resolution of his diarrhea and a decrease in temperature. On May 26, he developed severe myalgia, headache, and mild, persistent photophobia, all of which persisted.

On physical examination, he was a flushed-looking man, with a temperature of 37.5°C, a pulse rate of 88 beats/min, and normal blood pressure. His conjunctivae were injected. There was a soft mobile nontender node in the right posterior cervical chain and bilateral shotty inguinal nodes. His cardiopulmonary examination was unremarkable. No hepatosplenomegaly was appreciated. Other positive findings included diffuse erythroderma uniformly involving his face, trunk, and extremities, and a small red papule on his right wrist. His initial malaria smear was negative, and a presumptive diagnosis of acute dengue fever was made.

Laboratory results on presentation were remarkable for a strikingly increased population of plasma cells, plasmacytoid lymphocytes, and thrombocytopenia (68 × 103/μL). With a total white blood cell count of 5.8 × 103/μL (reference range, 4.1–10.9), the differential was 19% plasma cells (1100/μL), 9% abnormal plasmacytoid lymphocytes (520/μL), 37% polymorphonuclear leukocytes, 3% band forms, 27% lymphocytes, 4% monocytes, and 1% eosinophils. The hemoglobin level was 16.7 g/dL (13.5–17.0). Alanine aminotransferase at 125 U/L (7–40) and aspartate aminotransferase at 135 U/L (11–40) were both elevated, but tests of coagulation were within reference ranges. Because the patient needed to return to work overseas, an expedited evaluation was requested and performed.

The bone marrow biopsy and aspirate were unremarkable. Flow cytometry of the bone marrow lymphocytes showed normal T cells and polyclonal B cells; abnormal cells were not identified. Modest polyclonal increases of IgG and IgA, but no monoclonal protein, were demonstrable in the serum. Polyclonal immunoglobulins and other serum proteins were present in his urine.

Serologic tests for syphilis, hepatitis B surface antigen and antibody, antibody to hepatitis B core antigen, antibody to hepatitis C, human immunodeficiency virus p24 antigen and antibody to human immunodeficiency virus, antibody to cytomegalovirus, and Rocky Mountain spotted fever and scrub typhus antibodies were negative. Three sequential smears for malaria were negative. Blood (3×), urine, and stool cultures were unremarkable. Stool samples tested for ova and parasites and for Clostridium difficile toxin were negative. Serologic tests for Epstein-Barr virus, rubeola, and rubella were consistent with prior exposure. Serologic tests for dengue virus performed at the US Centers for Disease Control, San Juan, Puerto Rico, were positive for IgM and IgG (reciprocal IgG titer, 655 360) and were consistent with a secondary dengue infection of unknown serotype.3 

The patient's fever and diarrhea resolved 3 days later, as did his plasmacytosis and thrombocytopenia. Liver function tests remained mildly elevated. This patient remains well 4 years later. His most recent laboratory results were unremarkable.

Extreme plasmacytosis in peripheral blood is rare but striking when seen. A retrospective review of 98 261 complete blood cell counts with differential performed at the Lahey Clinic (Burlington, Mass) yielded only 6 instances in which relative plasmacytosis was 10% or greater. These were obtained from 2 patients, both with hematologic malignancies. This is the most frequent explanation for this finding, but transient plasmacytosis secondary to other causes has also been reported occasionally. Conditions for which plasmacytosis or the combination of plasma cells and plasmacytoid lymphocytes exceeded 10% of the peripheral white blood cell count are summarized in the Table. Additionally, other authors have reported conditions in which plasmacytosis occurred to a lesser degree (eg, varicella zoster infection, rubeola) or was reported but not quantified (eg, mumps, malaria). Most of these associations are sporadic, but plasmacytosis is seen in rubella reliably enough to have been proposed as a diagnostic criterion for that infection at a time when serologic testing was both less developed and less available.

Peripheral Blood Plasmacytosis Not Associated With Hematologic Malignancy in Which Plasmactyosis or Combined Plasma Cells and Plasmacytoid Cells Exceeded 10% of Circulating White Blood Cells*

Peripheral Blood Plasmacytosis Not Associated With Hematologic Malignancy in Which Plasmactyosis or Combined Plasma Cells and Plasmacytoid Cells Exceeded 10% of Circulating White Blood Cells*
Peripheral Blood Plasmacytosis Not Associated With Hematologic Malignancy in Which Plasmactyosis or Combined Plasma Cells and Plasmacytoid Cells Exceeded 10% of Circulating White Blood Cells*

This patient, presenting with plasma cells and plasmacytoid lymphocytes comprising 28% of his white cell differential, thrombocytopenia, and constitutional symptoms, was thought clinically to have dengue fever, but he underwent an extensive evaluation to rule out the possibility of concomitant hematologic malignancy. Plasmacytosis has not been reported as a feature of dengue fever; however, given the known proliferation of B cells in this condition, it is not a surprising finding. It is perhaps significant that this was a secondary infection: among the historic cases listed in the Table, 3 were associated with serum sickness or hyperimmunization, implying prior exposure to antigens. Epidemic dengue fever has recently reemerged worldwide. In this context, an associated plasmacytosis may be seen more frequently. In dengue-endemic regions, peripheral blood smears performed for malaria diagnosis or other reasons may demonstrate extreme plasmacytosis. If due to dengue fever, it should resolve with resolution of the primary illness. Recognition that it is a self-limited phenomenon could obviate extensive clinical evaluation.

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A portion of this material was presented at Oxford 2000: New Challenges in Tropical Medicine and Parasitology, Oxford, United Kingdom, on September 21, 2000.

Author notes

Reprints: John M. Gawoski, MD, Department of Laboratory Medicine, Lahey Clinic, 41 Mall Rd, Burlington, MA 01805 ([email protected])