Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 3118  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Article Submission Resources Sections Etcetera Contact
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (240 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
 :: Introduction
 :: Discussion
 :: Case Report
 ::  References

 Article Access Statistics
    PDF Downloaded16    
    Comments [Add]    
    Cited by others 2    

Recommend this journal


  Table of Contents     
Year : 2015  |  Volume : 61  |  Issue : 1  |  Page : 44-45

Hemophagocytic lymphohistiocytosis secondary to Epstein Barr virus and Leishmania co-infection in a toddler

Department of Pediatrics, Hematology and Oncology Unit. Hospital Universitario "12 de Octubre", Carretera Andalucia km 5,400, Postal code 28041, Madrid, Spain

Date of Submission27-Jan-2014
Date of Decision13-Feb-2014
Date of Acceptance07-Apr-2014
Date of Web Publication15-Dec-2014

Correspondence Address:
Dr. L I González-Granado
Department of Pediatrics, Primary Immunodeficiencies and Pediatric Infectious Diseases Unit. Hematology and Oncology Unit Hospital 12 de Octubre, Carretera Andalucia km 5,400, Postal code 28041, Madrid
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0022-3859.147052

Rights and Permissions

 :: Abstract 

This is the report of an EBV + Leishmanial co-infection. The patient developed hemophagocytic syndrome (HLH) and was treated with the standard HLH-2004 protocol. However, PCR in bone marrow discovered this secondary cause for HLH. In endemic countries, visceral leishmaniasis should be considered in the differential diagnosis even in EBV-related HLH, as chemotherapy toxicity may be avoided.

Keywords: Epstein-barr virus, hemophagocytic syndrome, visceral leishmaniasis

How to cite this article:
Domínguez-Pinilla N, Baro-Fernández M, González-Granado L I. Hemophagocytic lymphohistiocytosis secondary to Epstein Barr virus and Leishmania co-infection in a toddler. J Postgrad Med 2015;61:44-5

How to cite this URL:
Domínguez-Pinilla N, Baro-Fernández M, González-Granado L I. Hemophagocytic lymphohistiocytosis secondary to Epstein Barr virus and Leishmania co-infection in a toddler. J Postgrad Med [serial online] 2015 [cited 2020 Aug 12];61:44-5. Available from:

 :: Introduction Top

Hemophagocytic lymphohistiocytosis (HLH) is a rare but lethal disease, which may be due to genetic defects, as in familial HLH caused by mutations in FHL1 - HPLH1, FHL2 - PRF1 (Perforin), FHL3 - UNC13D (Munc13-4), FHL4 - STX11 (Syntaxin 11), FHL5 - STXBP2 (Syntaxin binding protein 2)/UNC18-2, or immunodeficiency syndromes as Chediak-Higashi, Hermansky Pudlak, Griscelli or X-linked Lymphoproliferative syndrome. On the other hand, acquired HLH is associated with malignancies, autoimmune diseases, and infections with the Epstein Barr Virus (EBV) being the main trigger. [1]

 :: Case Report Top

A 22-month-old girl presented to us with 8-day fever (40°C), and mild cough. On examination, she had hepatosplenomegaly. Past medical history included failure to thrive, but normal neurological development. She was the first child of a non-consanguineous marriage. She had normal brown hair and normal skin. There was no family history of albinism. On physical examination, she was stunted, pale, and had non-tender hepatomegaly of 5-6 cm; the spleen was palpable 4 cm below the left costal margin as confirmed by abdominal ultrasound. The WBC count was 5100/mm 3 (ANC 1200/mm 3 ), Hb 9.1 g/dl, and platelets 47.000/mm 3 . She had mild hypertransaminasemia and hypoalbuminemia. Ferritin was 1134 ng/ml. Soluble IL-2 receptor (sCD25) was 3183 UI/ml. Blood cultures were negative. Serum immunoglobulins and lymphocyte subsets were normal.

Epstein-Barr virus (EBV) serology yielded seroreactivity (positive IgM and IgG anti-VCA) with negative IgG anti-EBNA. EBV viral load was 637 copies/ml. Leishmania serology showed both negative immunochromatography and indirect immunofluorescence. Conversely, serum ELISA was slightly positive. Leishmanial antigen in the urine was negative. Bone marrow aspiration revealed hemophagocytosis. The patient worsened clinically, with persistent malaise, progressive splenomegaly, and petechial rash on her chest and legs. Subsequent investigations were WBC 4800/mm 3 (ANC 800/mm3), Hb 6.8 g/dl and platelets 27000/mm 3 , triglycerides 686 mg/dl, ferritin 3849 ng/ml, and sCD25 3596 UI/ml with normal clotting tests as well as perforin expression by flow-cytometry. Hair microscopy was not performed because clinical features of albinism were not present neither in our patient nor in her family. HLH-2004 protocol was started. The following day, Leishmania Polymerase Chain Reaction was done where Leishmanial DNA was detected by nested PCR. [2] ) This was confirmed on a bone marrow aspirate as well. Standard therapy with liposomal amphotericin B (3 mg/kg/day IV on days 1, 2, 3, 4, 5, 14, and 21) was given. The patient completed HLH-2004 protocol, except for 2 doses of etoposide due to clinical and laboratory improvement without evidence of underlying primary HLH. At 30 month follow up, there is no evidence of relapse. As CD107a degranulation assay was not performed (just normal intracytoplasmic pattern of perforin staining), primary HLH is not absolutely discarded as a differential diagnosis.

 :: Discussion Top

HLH comprises a rare group of disorders caused by activation of CD8 + T cells and macrophages and high-level secretion of pro-inflammatory cytokines, [3] characterized by persistent fever, cytopenia, hepatosplenomegaly, and hemophagocytosis in bone marrow, lymph nodes, liver or spleen. [4] Primary HLH as well as secondary HLH not controlled by treatment of underlying condition must be treated with HLH-2004 protocol, which includes dexamethasone, cyclosporine A, and etoposide. In EBV-HLH, it has been proposed a multi-step treatment, [5] in an attempt to reduce long-term toxicity of etoposide.

A case of EBV-Leishmania co-infection in a 9-month old girl as a trigger for HLH has been reported. [6] However, EBV viral load was not reported. Transient low-level viremia has been reported without significance in immunocompromised and non-immunocompromised host.

In our patient, we found EBV and Leishmania co-infection, an extremely rare association. Both are well-known causes of secondary HLH. In addition, EBV is the main trigger of primary HLH, what makes it difficult to distinguish between primary and secondary HLH. This is the main reason why investigation of Leishmania by PCR should be done on bone marrow of patients with HLH and EBV infection (specially in endemic areas), to rule out Leishmania infection because its sensitivity and specificity are greater than microscopy or other microbiological test, [5] in order to avoid toxicity derived from drugs contained in HLH-2004 protocol.

 :: References Top

Purtilo DT. Epstein-Barr virus: The spectrum of its manifestations in human beings. South Med J 1987;80:943-7.  Back to cited text no. 1
Cruz I1, Cañavate C, Rubio JM, Morales MA, Chicharro C, Laguna F, et al. A nested polymerase chain reaction (Ln-PCR) for diagnosing and monitoring Leishmania infantum infection in patients co-infected with human immunodeficiency virus Original Research Article. Trans R Soc Trop Med Hyg 2002;96:S185-9.   Back to cited text no. 2
Chandrakasan S, Filipovich AH. Hemophagocytic Lymphohistiocytosis: Advances in Pathophysiology, Diagnosis, and Treatment. J Pediatr 2013;163:1253-9.  Back to cited text no. 3
Henter JI, Aricò M, Egeler RM, Elinder G, Favara BE, Filipovich AH, et al. HLH-94: A treatment protocol for hemophagocytic lymphohistiocytosis. HLH study Group of the Histiocyte Society. Med Pediatr Oncol 1997;28:342-7.  Back to cited text no. 4
Shirashi A, Ohga S, Doi T. Treatment choice of immunotherapy or further chemotherapy for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2012;59:256-70.   Back to cited text no. 5
Koliou MG, Soteriades ES, Ephros M, Mazeris A, Antoniou M, Elia A, et al. Hemophagocytic lymphohistiocytosis associated with epstein barr virus and Leishmania donovani Coinfection in a Child From Cyprus. J Pediatr Hematol Oncol 2008;30:704-7.  Back to cited text no. 6

This article has been cited by
1 Medley of infections-a diagnostic challenge
Raghavendra Bhat,Parul Kodan,Meenakshi A Shetty
Asian Pacific Journal of Tropical Biomedicine. 2015; 5(5): 418
[Pubmed] | [DOI]
2 Hemophagocytic Syndrome in Children With Visceral Leishmaniasis
Elizabeth F. Daher,Laio L. L. Lima,Ana Patrícia F. Vieira,Lucas S. Nascimento,Douglas S. Soares,Krasnalhia Lívia S. Abreu,Kathia L. C. R. Zuntini,Geraldo B. Silva Junior
The Pediatric Infectious Disease Journal. 2015; 34(12): 1311
[Pubmed] | [DOI]


Print this article  Email this article
Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow