Abstract
Immunophenotyping by flow cytometry has revolutinized the diagnosis of blood cell disorders such as leukemias and lymphomas and is now commonly used in diagnosis and prognosis of such patients. We describe a case of human ehrlichiosis mimicking T-cell lymphoma/leukemia based on flow cytometry of bone marrow cells and confirmed by T-cell receptor gene rearrangement (TCR) by polymerase chain reaction (PCR). Treatment with doxycycline reversed these findings. A 20-year-old, Amish female presented with fatigue, fever, chills, sweating, low back pain, and lower abdominal pain for 2 days. She admitted to multiple bites from ticks 2 weeks prior to presentation and also reported having numerous animals such as cats, dogs, cows, goats, horses at her farm where she lived. Clinical exam was significant for fever of 101.4 F, heart rate of 118/min, BP of 80/60 mm Hg and a distended urinary bladder which was treated by catheter drainage. Relevant laboratory tests are shown in table 1.
| Hemoglobin | 9.7 | 12–16 gm/dl |
| WBC | 0.8 | 4–10.8 k/mm3 |
| Platelets | 16 | 150–400 k/mm3 |
| Segments | 62% | 50–75% |
| Lymphocytes | 15% | 20–40% |
| Sodium | 140 | 125–135 mmol/L |
| AST | 126 | 0–37 IU/L |
| ALT | 71 | 0–65 IU/L |
| Alk. Phos. | 49 | 50–136 IU/L |
| LDH | 691 | 91–190 IU/L |
| Hemoglobin | 9.7 | 12–16 gm/dl |
| WBC | 0.8 | 4–10.8 k/mm3 |
| Platelets | 16 | 150–400 k/mm3 |
| Segments | 62% | 50–75% |
| Lymphocytes | 15% | 20–40% |
| Sodium | 140 | 125–135 mmol/L |
| AST | 126 | 0–37 IU/L |
| ALT | 71 | 0–65 IU/L |
| Alk. Phos. | 49 | 50–136 IU/L |
| LDH | 691 | 91–190 IU/L |
Chest radiograph, Ultrasound and Computed tomography scan of the abdomen were within normal limits. With a provisional diagnosis of septic shock and suspicion for Ehrlichiosis, therapy with intravenous(IV) fluids, vasopressors and doxycycline was initiated. Blood was cultured and a sample was forwarded to CDC for analysis of tick borne infections.
In order to evaluate and exclude blood disorders like leukemia and lymphoma in a patient with fever and pancytopenia, a bone marrow aspiration and biopsy was performed. It showed cytologically abnormal-appearing, large sized lymphocyte population with irregular nuclear membranes. Flow cytometry of the bone marrow cells revealed 8–10% of phenotypically abnormal T-cells with abnormally weak intensity of membrane surface CD3, CD5, and CD7 expression and negativeCD4 and CD8 expression. These cells also expressed HLA-DR and CD38 at uncommonly bright intensity and there were no CD34 benign immature B-cells. Cytogenetics however was normal. Interestingly, PCR analysis was positive for clonal TCR gamma gene rearrangement. These results were reported as consistent with involvement of marrow by a peripheral T-cell lymphoma/leukemia
T-Cell receptor PCR analysis
Since the patient was steadily improving with IV Doxycycline, we decided to wait and repeated the bone marrow aspiration a week later. This time the bone marrow exam was found to be normal morphologically, on flow cytometry and TCR gamma gene rearrangement by PCR.
Patient was discharged on oral doxycycline after a stay of 13 days in the hospital. The blood test for ehrlichiosis from CDC was reported 3 weeks later as positive for Ehrlichia chaffeensis by PCR. Patient is doing well 6 months after the illness. This case illustrates that Ehrlichiosis can transiently cause T cell abnormalities resulting in false positive analysis on flow cytometry and TCR gamma gene rearrangement, thereby leading to false positive diagnosis of Ehrlichiosis. Reconfirmation with repeat studies need to be done before considering active treatment for lymphoma/leukemia.
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