LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 7738
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size
IJPM is coming out with a Special issue on "Genitourinary & Gynecological pathology including Breast". Please submit your articles for these issues


 
  Table of Contents    
BRIEF COMMUNICATION  
Year : 2012  |  Volume : 55  |  Issue : 2  |  Page : 215-217
Viral markers in patients with hemophagocytosis: A prospective study in a tertiary care hospital


1 Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
2 Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India
3 Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab, India

Click here for correspondence address and email

Date of Web Publication3-Jul-2012
 

   Abstract 

Background : Hemophagocytic syndrome (HPS) is a rare clinicopathological condition characterized by the activation of macrophages with prominent hemophagocytosis in bone marrow and other reticulo-endothelial systems. HPS can be familial or secondary to infections including viruses. Aim : To study the viral markers in patients with HPS. Materials and Methods : Serum samples of patients with HPS and control group were screened for anti EBV VCA IgM, and IgG, anti-Parvo B19 IgM, and anti-CMV IgM antibodies using commercially available ELISA kits and CMV and ParvoB19 DNA by polymerase chain reaction (PCR). Results and Discussion : The present prospective study reports the profile of viral markers in HPS cases from north India. Among the 14 HPS cases 43% (6/14) were positive for at least one viral marker tested, of which EBV was found to be the most prevalent (3/6: 50%) followed by parvovirus B19(2/6: 33%) and cytomegalovirus (1/6: 17%). Mortality was noted in 33% of virus associated HPS patients. Our study highlights the higher association of Epstein-Barr virus (EBV) with HPS as compared to other viruses along with higher rate of mortality in both parvovirus B 19 and EBV associated HPS.

Keywords: Cytomegalovirus, Epstein-Barr virus, hemophagocytosis, Parvovirus B19

How to cite this article:
Mishra B, Varma N, Appannanavar S, Malhotra P, Sharma M, Bhatnagar A, Ratho RK, Varma S. Viral markers in patients with hemophagocytosis: A prospective study in a tertiary care hospital. Indian J Pathol Microbiol 2012;55:215-7

How to cite this URL:
Mishra B, Varma N, Appannanavar S, Malhotra P, Sharma M, Bhatnagar A, Ratho RK, Varma S. Viral markers in patients with hemophagocytosis: A prospective study in a tertiary care hospital. Indian J Pathol Microbiol [serial online] 2012 [cited 2019 Oct 23];55:215-7. Available from: http://www.ijpmonline.org/text.asp?2012/55/2/215/97876



   Introduction Top


Hemophagocytic syndrome (HPS) is a clinicopathological condition characterized by the activation of histiocytic macrophages with prominent hemophagocytosis in bone marrow and other reticulo-endothelial systems. [1] Clinically, the disease is characterized by fever, pancytopenia, splenomegaly, and features of hemophagocytosis in reticulo endothelial cells. Besides familial etiology, various infectious agents have been reported in HPS. Among the viruses, agents like Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6) and parvovirus B19 (PVB19) have been implicated. [2],[3],[4] The present study was planned to find out the profile of viral markers in patients with HPS in a well controlled prospective case series.

The study was carried out over a period of three years in a tertiary care hospital that caters mostly to the Northern and North Western states of India. Fourteen consecutive patients with clinical and biochemical markers suggestive of HPS were recruited in the study group following the criteria of Henter et al.[5] Nineteen patients with aplastic anemia with no evidence of hemophagocytosis in bone marrow were included as controls. Serum samples of both the groups were screened for anti EBV VCA IgM, and IgG, anti-Parvo B19 IgM and anti CMV IgM antibodies using commercially available ELISA kits (Novatec, Germany). Further CMV and ParvoB19 DNA PCR were done in serum samples following the protocol as described earlier. [6],[7]

Fourteen HPS patients who fulfilled the inclusion criteria were enrolled in the study. All patients were immunocompetent males with a median age of 29 years (range 9-35 years). Of the 14 HPS patients six were positive for one of the viral markers tested as compared to none in controls (43% Vs 0%). EBV infection was found to be the most prevalent one (3/6: 50%), followed by parvovirus B19 (2/6:33%) and CMV (1/6: 17%) [Figure 1]. The detail of viral markers positivity by serology and DNA detection is shown in [Table 1].
Figure 1: Viral IgM in patients with hemophagocytic syindrome (n = 14)

Click here to view
Table 1: Viral IgM and IgG in patients with HPS (n = 14) and control (n = 19) population

Click here to view


All these patients were managed with supportive care with blood or platelet transfusion. Some of the patients had received antibiotics, steroids and intravenous immunoglobulins. Two of the six virus infected HPS patients died during the course of the disease.

Virus associated HPS is the most common form of reactive hemophagocytic syndrome characterized by generalized proliferation of histiocytes and features of phagocytosis in the presence of systemic viral infection. [1] In untreated cases, virus associated HPS has invariably been fatal. Secondary hemophagocytic syndrome of infectious etiology especially of virus origin found to have better outcome. [8] It warrants early diagnosis and supported by aggressive treatment. Due to lack of proper studies this entity failed to draw attention and as yet the exact role of many viruses in HPS is not known. The present prospective study reports a series of adult HPS in India with the association of a viral etiology in 43% patients with a predominance of EBV in 21% (3/14) cases followed by ParvoB19 (2/14: 14%) and CMV (1/14:7%). Various studies have implicated EBV in 30-60% cases. [9] A study in pediatric population indicated 44% (8/18) association of EBV in HPS. Imashuku et al. have shown a higher rate of association with EBV positivity in up to 66% (8/10) of the cases. [10] The mortality in general is high with virus associated HPS and it can increase up to 80% in EBV associated HPS. The case fatality rate of 56% has been reported by Ying Kang et al. where 30% of cases died within 2 months of diagnosis. [11] The present study based on the Indian patients in a tertiary care hospital, observed the similar rate of mortality.

Virus-infected T cell activation further leading to stimulation of macrophages initiating hemophagocytosis is the hallmark in the pathogenesis of HPS. Thus activation CD8+ and CD4+ cells trigger marked cytokine release producing tumor necrosis factor α, a key factor in histiocytic activation. [12]

Parvo B19-associated hemophagocytic syndrome is seen both in healthy individuals and in patients with underlying diseases like hematological malignancies. [13] Keith et al. have reported fatal Parvo B19 associated HPS in two patients with hereditary spherocytosis. [14] In our study, Parvovirus B 19 infection in one immunocompetent patient was fatal due to associated myocarditis and myositis. [15] HPS due to CMV is a rare but fatal complication seen in resultant CMV infection following immunosuppression. [2] In the present study one HPS case had associated CMV infection who showed recovery following supportive management.

Treatment of HPS is an open challenge. Cases with viral origin (V-HPS) have been tried with antiviral agents (acyclovir/ganciclovir), immunoglobulins and immunoregulatory molecules (IL2, INF alpha) and steroids. Additionally drugs like etoposide that acts by modulating monocyte and macrophages and cyclosporine A have been tried with varying results. [16] From the available reports in patients with secondary HPS, supportive care and treatment of underlying infection is associated with recovery in 60%-70%. [4] In recent times therapeutic advances in immunochemical regimes and bone marrow transplantation have greatly improved the outcome of patients with HPS. [16]

In conclusion, this is one of the prospective series of hemophagocytic syndrome cases worked up for virological markers in Indian patients. Our study highlights the higher prevalence of EBV associated HPS as compared to other viruses along with higher rate of mortality in both parvovirus B19 and EBV associated HPS. Virus associated HPS is fatal in untreated patients and special therapeutic measures are required to control the disease progression. High index of suspicion is required for recognition of infection associated HPS in general and virus associated HPS in particular, as overwhelming HPS can obscure the typical clinical picture of primary infections. Early diagnosis using viral serology along with Viral DNA detection can serve as a useful tool in the work up of patients with clinical hemophagocytic syndrome.

 
   References Top

1.Fisman DN. Hemophagocytic Syndromes and Infection. Emerg Infect Dis 2000;6:601-8.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Hoang MP, Dawson DB, Rogers ZR, Scheuermann RH, Rogers BB. Polymerase chain reaction amplification of archival material for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis. Hum Pathol 1998;29:1074-7.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Dharancy S, Crombe V, Copin MC, Boleslawski E, Bocket L, Declerck N, et al. Fatal Hemophagocytic Syndrome Related to Human Herpesvirus-6 Reinfection Following Liver Transplantation: A Case Report. Transplant Proc 2008;40:3791-3.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Reiner AP, Spivak JL. Hemophagocytic histiocytosis: A report of 23 new patients and a review of the literature. Medicine 1988;67:369-88.  Back to cited text no. 4
[PUBMED]    
5.Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol 1991;18:29-33.  Back to cited text no. 5
[PUBMED]    
6.Mewara A, Mishra B, Ratho RK, Kumar P. Cytomegalovirus glycoprotein B gene polymorphism and its association with clinical presentations in infants. Southeast Asian J Trop Med Public Health 2009;40:759-64.  Back to cited text no. 6
[PUBMED]    
7.Mishra B, Malhotra P, Ratho RK, Singh MP, Varma S, Varma N. Human parvovirus B19 in patients with aplastic anemia. Am J Hematol 2005;79:166-7.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007;166:95-109.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Reisman RP, Greco M. Virus-associated hemophagocytic syndrome due to Epstein-Barr virus. Hum Pathol 1984;15:290-3.  Back to cited text no. 9
    
10.Imashuku S, Hlbi S, Todo S. Hemophagocytic lymphohistiocytosis in infancy and childhood. J Pediatr 1997;130:352-7.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Jin YK, Xie ZD, Yang S, Lu G, Shen KL. Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A retrospective study of 78 pediatric cases in mainland of China. Chin Med J 2010;123:1426-30.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Su IJ, Wang CH, Cheng AL, Chen RL. Hemophagocytic syndrome in Epstein-Barr virus-associated T-lymphoproliferative disorders: Disease spectrum, pathogenesis, and management. Leukemia Lymphoma 1995;19:401-6.  Back to cited text no. 12
[PUBMED]  [FULLTEXT]  
13.Shirono K, Tsuda H. Parvovirus B19-associated haemophagocytic syndrome in healthy adults. Br J Haematol 1995;89:923-6.  Back to cited text no. 13
[PUBMED]    
14.Muir K, Todd WT, Watson WH, Fitzsimons E. Viral-associated haemophagocytosis with parvovirus-B19-related pancytopenia. Lancet 1992;339:1139-40.  Back to cited text no. 14
[PUBMED]  [FULLTEXT]  
15.Bal A, Mishra B, Singh N, Das A, Jindal SK. Fulminant parvovirus B19-associated pancarditis with haemophagocytic lympho-histiocytosis in an immunocompetent adult. APMIS 2009;117:773-7.  Back to cited text no. 15
[PUBMED]  [FULLTEXT]  
16.Imashuku S. Advances in the Management of Hemophagocytic Lymphohistiocytosis. Int J Hematol 2000;72:1-11.  Back to cited text no. 16
[PUBMED]    

Top
Correspondence Address:
Baijayantimala Mishra
MD, MAMS, Additional Professor, Department of Virology, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.97876

Rights and Permissions


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]

This article has been cited by
1 Children as Biomarker Orphans: Progress in the Field of Pediatric Biomarkers
Darla R. Shores,Allen D. Everett
The Journal of Pediatrics. 2018; 193: 14
[Pubmed] | [DOI]
2 Parvovirus B19-associated Hemophagocytic Lymphohistiocytosis in a Patient With Glucose-6-phosphate Dehydrogenase Deficiency
Aida Zeckanovic,Matej Perovnik,Janez Jazbec,Miroslav Petrovec,Marko Pokorn,Marko Kavcic
Journal of Pediatric Hematology/Oncology. 2018; 40(8): e550
[Pubmed] | [DOI]
3 Hemophagocytic syndrome suspected to be caused by herpes simplex virus complicated with severe hepatitis during the immunosuppressive therapy for dermatomyositis
Norihiro Nagamura,Tomoko Ishitobi
Modern Rheumatology Case Reports. 2017; 1(2): 113
[Pubmed] | [DOI]
4 Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: response to HLH-04 treatment protocol
Elva Jiménez-Hernández,Octavio Martínez-Villegas,Berenice Sánchez-Jara,María Angélica Martínez-Martell,Beatriz Hernández-Sánchez,Paloma del Rocío Loza-Santiaguillo,Eduardo Pedro-Matías,José Arellano-Galindo
Boletín Médico Del Hospital Infantil de México (English Edition). 2016; 73(1): 26
[Pubmed] | [DOI]
5 Usefulness of protein analysis for detecting pathologies in bone remains
Cristina Pérez-Martínez,Gemma Prieto-Bonete,María D. Pérez-Cárceles,Aurelio Luna
Forensic Science International. 2016; 258: 68
[Pubmed] | [DOI]
6 Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: response to HLH-04 treatment protocol
Elva Jiménez-Hernández,Octavio Martínez-Villegas,Berenice Sánchez-Jara,María Angélica Martínez-Martell,Beatriz Hernández-Sánchez,Paloma del Rocío Loza-Santiaguillo,Eduardo Pedro-Matías,José Arellano-Galindo
Boletín Médico del Hospital Infantil de México. 2016; 73(1): 26
[Pubmed] | [DOI]
7 Disseminated coxsackievirus B fulminant myocarditis in an immunocompetent adult: a case report
Uma Nahar Saikia,Baijayantimala Mishra,Mirnalini Sharma,Ritambara Nada,BD Radotra
Diagnostic Microbiology and Infectious Disease. 2014; 78(1): 98-100
[Pubmed] | [DOI]
8 Ce qu’il faut savoir sur le syndrome d’activation macrophagique en soins intensifs
L. Galicier
Réanimation. 2013; 23(2): S482-S490
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed12870    
    Printed128    
    Emailed4    
    PDF Downloaded172    
    Comments [Add]    
    Cited by others 8    

Recommend this journal