DOI: https://doi.org/10.21203/rs.3.rs-2801635/v1
Background
Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis endemic with atypical early clinical manifestations, and it is very easy to be misdiagnosed. Up to now, there has been no report on plasmacytosis caused by HFRS. Here we report a case of HFRS complicated by plasmacytosis mimicking multiple myeloma.
Case presentation:
We present an atypical case of HFRS, with the patient exhibiting both bone marrow and peripheral blood plasmacytosis during the course of illness. Besides, the patient presented with lymphadenopathy and was diagnosed with AITL and died soon due to cardiogenic shock.
Conclusions
HFRS should be one of differential diagnosis of plasmacytosis in certain endemic area.
Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China [1]. The main pathological characteristics are increased vascular permeability and acute thrombocytopenia with marked permeability of microvascular beds [2]. The main clinical manifestations are renal damage, bleeding, fever and shock. This disease is of an urgent and rapid progress, and if not timely diagnosis and effective treatment, it can lead to serious consequences and even death. However, the early clinical manifestations are often atypical, and it is very easy to be misdiagnosed. Here we report a case of HFRS complicated by plasmacytosis mimicking multiple myeloma. Up to now, there has been no report on plasmacytosis caused by HFRS.
A 75-year-old women had a sudden onset of fever on February 7, 2019, with a maximal temperature of 37.9℃, accompanied by runny nose, headache, fatigue, dry mouth, decreased appetite and mild drowsiness. The patient lived in Liaoning Province and newly came to Hainan Province one week ago. Except a history of hypertension for 20 years, she had no other specific diseases or familial medical history. She visited a local clinic in Hainan Province on February 9, 2019. Blood tests showed WBC 18.76 × 109/L, Hb 108 g/L, PLT 35 × 109/L, IgA 1290 mg/dl, IgM 71 mg/dl, IgG 2690 mg/dl, IgE 873 IU/ml. Bone marrow cytology and peripheral blood smear showed plasmacytosis, with proplasmacytes accounting for 26% and 23% of all nucleated cells respectively. With a preliminary diagnosis of plasma cell leukemia, she was admitted to Beijing Hospital on February 14, 2019. The vital signs were body temperature 36℃, heart rate 80/min, respiratory rate 18/min, and blood pressure 120/80 mmHg. Physical examination revealed palpable lymph nodes in the neck, and no tenderness in the sternum. Upon admission, hematologic tests revealed gradually increased WBC with progressively decreased Hb and PLT, which is summarized in Table 1. On February 27, the patient presented diffuse bleeding points of both lower limbs with nasal bleeding. Blood biochemistry showed Cr 76 µmol/L, LDH 364 U/L, Fer 597 ng/ml, β2-MG 12.33 mg/L, ESR 102 mm/hr, CPR 1.5 mg/dl, PCT 0.07 ng/ml, PT 18.7 s, D-Dimer 542 ng/ml. Immunofixation by electrophoresis revealed increased immunoglobulin: IgA 1210mg/dl, IgM 209 mg/dl, IgG 4990 mg/dl, IgE 429 IU/ml. Proteinuria was observed including albumin, α1-MG, β2-MG, and immunoglobulin light chains without Bence Jones protein. Besides, Hainan flow cytometric immunophenotyping of bone marrow revealed that the increased plasma cells were not monoclonal——the intracellular kappa/lambda light chain was expressed in a non-restrictive way. Since admission, several cytological examinations had been performed, and certain amounts of abnormal plasma cells were found in both bone marrow and peripheral blood, which is shown in Table 2. Combined with above factors, the primary diagnosis was reactive plasma cell disease. To figure out the behind reason, screening tests of infectious diseases, such as CMV and EBV, autoantibody profile and tumor markers had been done, and there were no positive findings. PET/CT revealed multiple lymphadenopathies with partial interfusion and SUVmax of 29.8. On February 28, the patient underwent left supraclavicular lymph node biopsy, after which, chest symptoms such as short of breath and moist rales began to appear. Blood tests showed WBC 17.87 × 109/L, Hb 71g/L, PLT 26 × 109/L, Fbg 0.94 g/L, PT 24.1 s, APTT 32.1 s, D-Dimer 847 ng/ml, and increased myocardial enzyme with maximal cTnI of 1.87 µg/L. ECG revealed inverted T wave of V2 and V3. Echo demonstrated SWMA of the anterior wall and interventricular septum. Thus, NSTEMI accompanied with ALHF was considered with or without DIC. Vasodilators, diuretic, plasma transfusion and other supportive medications were administered to the patient. On March 1, the patient presented with atrial fibrillation and recovered after treatment with sildenafil, atenolol and amiodarone. Soon afterwards, she got conscious disturbance, acute renal failure with transient oliguria and polyuria, hypernatremia, kaliopenia and metabolic acidosis with gradually decreased peripheral blood oxygen saturation. Non-invasive ventilator-assisted ventilation was administered on March 3. On March 5, return of lymph node biopsy results demonstrated a hint of AITL with plasmacytosis (Fig. 1). On March 6, the results of IgM and IgG antibodies for HTNV with ELISAs returned positive. Eventually, a diagnosis of HFRS was reached. However, the patients died of cardiogenic shock caused by reoccurrence of myocardial infarction at midnight on March 6, 2019.
| Laboratory tests | Day 1 | Day 10 | Day 15 | Normal range |
|---|---|---|---|---|
| WBC (109/L) | 7.75 | 11.04 | 60.55 | 3.5–9.5 |
| Hb (g/L) | 100 | 87 | 63 | 110–150 |
| PLT (109/L) | 88 | 35 | 7 | 125–350 |
| Cytological examinations | Beijing Hospital | Clinical Consultancy |
|---|---|---|
| BM cytology | Proplasmacytes accounting for 34%. | Myeloma cells accounting for 16.5%. |
| PB cytology | Plasma cells accounting for 11%. | Myeloma cells accounting for 24%. |
| FCI of BM | Polyclonal plasma cells accounting for 20.32%, mainly expressing CD38, CD138, CD19, CD27, HLA-DR, not expressing CD56. | Polyclonal plasma cells accounting for 12.92%, mainly expressing CD38, CD138, CD19, CD27, not expressing CD20, CD56, CD117. |
| FCI of PB | Polyclonal plasma cells accounting for 3.22%, mainly expressing CD38, CD138, CD19, CD27, CD81, HLA-DR, not expressing CD56, CD20, CD117. |
HFRS is zoonosis endemic in eastern Asia, especially in China, whose main manifestations include fever, increased vascular permeability, coagulation abnormalities and acute kidney injury [1]. The diagnosis of HFRS is based on exposure history, typical manifestations and serum test results, such as the detection of IgM or IgG antibodies against Hantavirus [2]. The pathogenesis of HFRS has not been fully elucidated. Recent studies prompted that the infection of HTNV induced endothelial cell permeability injury and subsequently, triggered the immune response and cytokine storm [3–5]. The prognosis of HFRS is related to the severity of the disease and whether the treatment is timely. The main cause of death in severe patients is refractory shock. Therefore, early diagnosis and early treatment are the key to the treatment of HFRS.
Herein, we present an atypical case of HFRS, with the patient exhibiting both bone marrow and peripheral blood plasmacytosis during the course of illness. Although the cytology of plasma cells mimicked multiple myeloma, BM cell immunophenotyping revealed benign, polyclonal plasma cell infiltration, compatible with reactive plasmacytosis. In addition, the immune globulins were polyclonal as assessed by immunofixation. Besides, the patient presented with lymphadenopathy and was diagnosed with AITL and died soon due to cardiogenic shock. The question that whether there is relationship or not between AITL with HFRS remains to be answered. Although previous research revealed increased risk for lymphoma following HFRS [6], we could not rule out whether lymphoma existed earlier than infection.
Reactive plasmacytosis is an uncommon event found in a variety of diseases such as infectious diseases, autoimmune disorders and tumors, which is associated with the elevated IL-6 level in the hematopoietic microenvironment of BM. Reactive plasmacytosis has been reported in several types of virus infections including Hepatitis A virus, Epstein-Barr virus, Dengue virus and parvovirus B19 infection [7–10]. However, to our knowledge, no HFRS-associated reactive plasmacytosis cases have been reported in the literature. In this report, we describe an unusual case of HFRS presenting with reactive plasmacytosis both in peripheral blood and bone marrow. Similar to the effects of many other pathogenic viruses, HFRS is mainly medicated by the efforts of the immune system to clear the infection. Therefore, it has been widely accepted that HFRS pathogenesis is largely immune mediated, including immune complexes, complement activation, T cell response, B cell response, and HTNV-induced cytokine production, including IL-6, which might account for reactive plasmacytosis in our case [4–5]. Meanwhile, our patient was also diagnosed of AITL, in which one of the rare immunologic abnormalities is exuberant polyclonal plasmacytosis. Therefore, whether the event of plasmacytosis was caused by infection itself or tumor remains to be explored.
Unfortunately, the patient died of cardiogenic shock caused by reoccurrence of myocardial infarction before administration of antivirus treatment. Anderson’s study identified an increased risk for AMI in the first weeks after HFRS [11]. HFRS patients have abnormal coagulation with elevated thrombosis and fibrinolysis and DIC. Additionally, HTNV infection may have a negative impact on heart functions. Consequently, HTNV infection induces an enhanced state of inflammation and coagulation, which might contribute to the increased risk for acute myocardial infarction during acute HFRS reported here.
In summary, although this case reported an unusual event that occurs in HFRS, the mechanism of HFRS in reactive plasmacytosis remains unknown. Further research should be carried out to address this question. In addition, it is critical to make an early and correct diagnosis of HFRS, based on detailed epidemiological data and clinical characteristics and laboratory findings. The clinicians should be aware that HFRS can be associated with reactive plasmacytosis.
white blood cell
hemoglobin
platelet count
creatinine
immune globulin
lactic dehydrogenase
ferritin
cardiac troponin I
Electrocardiograph
non-ST segment elevated myocardial infarction
acute left sided heart failure
segmental wall motionabnormalities
prothrombin time
activated partial thromboplastin time
fibrinogen
disseminated intravascular coagulation
EB virus
cytomegalovirus
Positron Emission Tomography-Computed Tomography
standard uptake value
Angioimmunoblastic T-Cell Lymphoma
bone marrow
peripheral blood
flow cytometric immunophenotyping.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Written informed consent was obtained from the patient’s next of kin for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Availability of data and materials
Not applicable.
Competing interests:
The authors declare that they have no competing interests.
Funding:
Not applicable.
Authors' contributions:
Qian Long, Bai Jiefei and Liu Hui wrote the main manuscript text. Feng Ru and Wang Ting prepared Figure1 and Table 1-2. All authors reviewed the manuscript.
Acknowledgements
The authors are grateful to Ms. Tang Hao for revising the English text.