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| Year : 2021 | Volume
: 64
| Issue : 1 | Page : 192-194 |
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| Hemophagocytic lymphohistiocytosis secondary to Candida albicans and reactivated EBV infections: A case report and review of the literature |
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Wenyan Yang1, Keyu Liu2, Fengling Zou3, Xueqin Wang2, Junping Yin2, Yifeng Wu4, Xiaolei Chai5, Liheng Zheng6
1 Department of Nursing, The Thrid Affiliated Hospital of Jinzhou Medical University, Liaoning Province, China
2 Department of Clinical Laboratory, Affiliated Hospital of Engineering, University of Hebei, Handan, China
3 Department of Hematology, Affiliated Hospital of Engineering, University of Hebei, Handan, China
4 Department of Medical Imaging, Affiliated Hospital of Engineering, University of Hebei, Handan, China
5 Department of Blood Transfusion, Affiliated Hospital of Engineering, University of Hebei, Handan, China
6 Department of Clinical Laboratory, Chest Hospital of Hebei Province, Hebei Province, China
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| Date of Submission | 28-Apr-2020 |
| Date of Decision | 17-May-2020 |
| Date of Acceptance | 27-Jul-2020 |
| Date of Web Publication | 8-Jan-2021 |
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 Abstract | | |
Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a potentially life-threatening syndrome. This is the first case of acquired HLH caused by dual infections with Candida albicans and reactivated EBV infections, which focuses on the importance of morphological awareness of peripheral blood and bone marrow because sometimes they are the only locations that HLH and fungal microorganisms can be diagnosed. A 29-year-old woman with a history of abdominal distension and 9 months of intermittent fevers ($38.8°C) was admitted to the hematology department with treatment for leukopenia and thrombocytopenia. Severe infection of bilateral pulmonary and marked hepatosplenomegaly were detected by computed tomography. EB virus-CA IgG, EB virus-NA IgG and EB virus-CA IgM were positive. Scattered yeast-like fungi were found on peripheral blood and bone marrow (BM) smears. BM smears indicated prominent hemophagocytosis. Cultures of bronchoalveolar lavage and BM confirmed the growth of C. albicans. A diagnosis of HLH caused by dual infections with Candida albicans and reactivated EBV infections was established based on the clinical features of the patient because 7 of the 8 diagnostic criteria were met. She was treated with etoposide, dexamethasone for HLH, as well as highly active antifungal and antiviral therapies for the underlying etiology of dual infections. The patient eventually recovered following the effective treatment. A timely and accurate diagnosis is crucial to the prognosis of the dangerous disease.
Keywords: Candida albicans, dual infections, EB-virus, hemophagocytic lymphohistiocytosis, morphology
How to cite this article:
Yang W, Liu K, Zou F, Wang X, Yin J, Wu Y, Chai X, Zheng L. Hemophagocytic lymphohistiocytosis secondary to Candida albicans and reactivated EBV infections: A case report and review of the literature. Indian J Pathol Microbiol 2021;64:192-4 |
How to cite this URL:
Yang W, Liu K, Zou F, Wang X, Yin J, Wu Y, Chai X, Zheng L. Hemophagocytic lymphohistiocytosis secondary to Candida albicans and reactivated EBV infections: A case report and review of the literature. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Apr 22];64:192-4. Available from: https://www.ijpmonline.org/text.asp?2021/64/1/192/306519 |
| Introduction | |  |
Hemophagocytic lymphohistiocytosis (HLH) has been known as a potentially fatal syndrome due to activation and proliferation of histiocytes with hypercytokinemia, which is characterized by fever, hepatosplenomegaly, and pancytopenia. The etiology of HLH can be either primary or secondary. Primary HLH usually occurs in children with molecular biological abnormalities connected with the cytotoxic function of NK and T cells, whereas secondary HLH caused by infections, immunodeficiency syndromes and malignancies generally manifests in elder patients. The diagnosis of HLH is based on clinical features of hemophagocytosis in bone marrow, cytopenias, fever, splenomegaly, elevated ferritin and soluble CD25, reduced activity of NK cells, hypertriglyceridemia or hypofibrinogenemia.[1] Here, we present a rare case of HLH associated with dual infections of Candida albicans and reactivated EBV infections.
| Case Report | | |
A 29-year-old woman with a history of abdominal distension and 9 months of intermittent fevers ($38.8°C) was admitted to the hematology department with treatment for leukopenia and thrombocytopenia. (white blood cells, 2.84 × 109/L; platelets, 10 × 109/L; hemoglobin, 108 g/L). Besides, the patient presented with severe pneumonia, multiple organ injury, respiratory failure and abnormal coagulation. She had no history of hepatic diseases, and tests for hepatitis B surface antigen, e antigen, core antibody, and hepatitis C virus antibody were negative. Severe infection of bilateral pulmonary and marked hepatosplenomegaly were detected by computed tomography. EB virus-CA IgG, EB virus-NA IgG and EB virus-CA IgM were positive, and an EBV load of 1,800 copies/mL was detected in whole blood of the patient (DNA). Serum autoantibodies were all negative, and human immunodeficiency virus was negative. The result of liver function test was abnormal (ALT 130 U/L, AST 81 U/L). Hypersensitive C - reactive protein (54.4 mg/l), triglyceride (4.02 mmol/L), ferritin (2268 ng/mL) and soluble CD25 (9914.95 pg/mL) levels were markly elevated; fibrinogen level was decreased (0.86 g/L). A small amount of scattered yeast-like fungi was found on peripheral blood smears. BM smears indicated prominent hemophagocytosis, which showed multiple nucleated red cells, numerous mature red blood cells, granulocytes, platelets were engulfed by histiocytes [Figure 1]a and [Figure 1]b. Numerous yeast-like fungi were seen disseminated throughout the BM smears, some of which were even in the histiocytes. [Figure 1]a and [Figure 2]a, [Figure 2]b, d black arrow]. Prussian blue staining on bone marrow smears was positive for histiocytes [Figure 2]e. Gram staining on bone marrow smears revealed large amounts of yeast-like fungi [Figure 2]c, and the level of 1,3-beta-D dextran was markly increased (G test, 299.7 pg/ml), by which the presence of deep fungal infection was confirmed. Cultures of bronchoalveolar lavage and bone marrow confirmed the growth of C. albicans. Flow cytometry immunophenotyping showed nucleated cells with normal phenotypes. Cytogenetic analysis of the BM cells indicated a 46, XY (20) karyotype, and primary HLH related genes were negative. A diagnosis of HLH caused by dual infections with Candida albicans and reactivated EBV infections was established based on the clinical features of the patient because 7 of the 8 diagnostic criteria were met. She was treated with intravenous etoposide (100mg/time, 2 times a week, dexamethasone (15mg/day, orally) for HLH as well as biapenem, linezolid, caspofungin and acyclovir for the underlying etiology of infections. The dosage of etoposide and dexamethasone was reduced gradually, and the duration of the drugs was 8 weeks. Additional symptomatic treatments included relieving asthma and spasmolysis, and intravenous infusion of albumin when hypoalbuminemia occurred etc. The patient eventually recovered following the effective treatment, which proved our accurate diagnosis for the patient. In view of the young patient with hepatosplenomegaly, we considered the investigation of underlying etiology of her acquired HLH should be aggressive, including liver biopsy for ruling out hepatosplenic T-cell lymphoma, which may be caused by EBV infection. However, the patient refused to do the invasive test. Several BM immunophenotypic analyses and biopsies were performed for the sake of detecting an underlying disease without success. At the latest follow-up, our patient was in good condition, with normalized routine blood count, plasma ferritin and liver function, and no signs of HLH. | Figure 1: Bone marrow (BM) smears indicated prominent hemophagocytosis, which showed multiple nucleated red cells, numerous mature red blood cells, granulocytes, platelets were engulfed by histiocytes. (a and b) Wright-Giemsa staining ×1000)
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 | Figure 2: Numerous yeast-like fungi were seen disseminated throughout BM smears, some of which were even in the histiocytes. (a, b and d) black arrow, Wright-Giemsa staining ×1000). Prussian blue staining on BM smears was positive for histiocytes (e), Prussian blue staining ×1000), Gram staining on BM smears revealed large amounts of yeast-like fungi. (c), black arrow, Gram staining ×1000)
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| Discussion | | |
Hemophagocytic lymphohistiocytosis (HLH) has been known as a potentially fatal syndrome caused by genetic and acquired factors, which results in an acute inflammatory reaction. Due to the acute and life-threatening course of the disease, severe acquired cases generally lead to death. Doctors and laboratory staff should grasp the clinical features and diagnostic criteria of the disease, since a timely diagnosis and accurate treatment are crucial to the prognosis of the dangerous disease.
Several cases of acquired HLH due to rare causes have been reported so far, in which the disease was secondary to marrow anaplastic large cell lymphoma (ALCL), acute myelocytic leukemia (AML), metastatic adenocarcinoma, chronic lymphocytic leukemia (CLL), disseminated histoplasmosis, malaria infection, and Wegener's granulomatosis [Table 1].[2],[3],[4],[5],[6],[7],[8],[9] Dao et al.[6] and Alina[7] reported respectively a patient presented with HLH due to disseminated histoplasmosis, and both patients had good outcomes on account of prompt diagnosis and appropriate treatment. Klein et al.[8] showed a patient with HLH secondary to malaria infection recovered rapidly after receiving intravenous quinine. Xu et al.,[2] Takahashi et al.,[3] and Yiu et al.[4] described patients with HLH due to progressive malignant tumors all had poor outcomes. Kamangar et al.[5] reported HLH caused by inert lymphoma, in which the patient obtained clinical improvement following treatment. Aparna et al.[9] reported a patient presenting with HLH secondary to Wegener's granulomatosis died within 4 days after treatment.
These rare cases showed that the prognosis of acquired HLH was closely related to etiology, which led to hemophagocytosis. HLH due to progressive malignancies predicted poor outcomes; on the contrary, the patient with HLH secondary to inert tumor owned a relatively good prognosis. Besides, attributing to timely diagnosis and appropriate treatment, the patients who presented with HLH due to the underlying etiology of infections all had good outcomes.
Based on our extensive review of the literature, we did not discover another case of a patient diagnosed with HLH secondary to Candida albicans and reactivated EBV infections. The presence of the microorganism on peripheral blood and bone marrow smears reminded us of the possibility of fungal infection. Cultures of bronchoalveolar lavage and BM recommended subsequently were positive, which ruled out the possibility of sample contamination, and the presence of deep fungal infection was also confirmed by G test. The presence of EB virus-NA IgG indicated that the patient had signs of previous infection of EBV, and polymerase chain reaction (PCR) revealed that our patient reactivated a previous infection of EBV, which was positive for EBV at the acute phase of the disease. In addition to young age of the patient, a timely diagnosis and subsequent effective treatment resulted in a rapid recovery of the patient.
| Conclusion | | |
We herein report the first case of HLH caused by dual infections with Candida albicans and reactivated EBV infections, which focuses on the importance of morphological awareness of peripheral blood and bone marrow because sometimes they are the only locations that fungal microorganisms can be diagnosed. A timely and accurate diagnosis is crucial to the prognosis of the dangerous disease.
Ethical approval
Informed consent has been obtained by the authors.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Kleynberg RL, Schiller GJ. Hemophagocytic lymphohistiocytosis in adults: Updates in diagnosis and treatment. Blood 2011;118:5037-5037.  |
| 2. | Xu Z, Burns BF. Hemophagocytosis due to bone marrow, ALCL, ALK. Blood 2014;124:478. |
| 3. | Takahashi T, Matsugama M. Refractory hemophagocytic syndrome in a patient with acute myelocytic leukemia. Blood 2013;121:2820. |
| 4. | Yiu RC, Lau LC. Hemophagocytosis and complex marrow karyotype in metastatic adenocarcinoma. Blood 2013;122:3402. |
| 5. | Kamangar E, Zhao W. Hemophagocytosis in a patient with persistent chronic lymphocytic leukemia. Blood 2013;122:2149. |
| 6. | Dao LN, He R. Hemophagocytic lymphohistiocytosis secondary to iatrogenic disseminated histoplasmosis. Blood 2016;127:2775. |
| 7. | Alina M. Huang. Hemophagocytic lymphohistiocytosis and disseminated histoplasmosis. Blood 2014;123:2449. |
| 8. | Klein E, Ronez E. Peripheral hemophagocytosis in malaria infection. Blood 2012;119:910. |
| 9. | Harbhajanka A, Mahon B. Hemophagocytic lymphohistiocytosis in a patient with granulomatosis with polyangiitis (Wegener's granulomatosis) [J]. Blood 2015;126:2892-2. |
Correspondence Address:
Xiaolei Chai
Department of Blood Transfusion, Affiliated Hospital of Engineering, University of Hebei, Handan, Hebei Province
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/IJPM.IJPM_457_20
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