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 Table of Contents  
Year : 2013  |  Volume : 4  |  Issue : 4  |  Page : 153-155

Hemophagocytic lymphohistiocytosis with hepatitis A

1 Department of Hematology, Medical Oncology and Transplant, Bangalore, Karnataka, India
2 Department of Pediatrics, Manipal Hospital, Bangalore, Karnataka, India

Date of Web Publication26-Feb-2014

Correspondence Address:
Ashish Dixit
Comprehensive Cancer Center, Manipal Hospital, 98, Rustam Bagh, Airport Road, Bangalore - 560 017, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1658-5127.127903

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Hemophagocytic lymphohistiocytosis (HLH) is a rare condition of unregulated immune function. Prompt clinical detection and treatment of the condition is important for survival. Its association with hepatitis A is rare and only limited to case reports. We present a 4-year-old boy with hepatitis A associated HLH and treated successfully with steroid monotherapy. A review of literature has been done for hepatitis A associated secondary HLH.

Keywords: Hemophagocytic lymphohistiocytosis, hemophagocytosis, hepatitis

How to cite this article:
Das K, Ramakrishnan M, Agrawal N, Pai S, Dixit A. Hemophagocytic lymphohistiocytosis with hepatitis A. J Appl Hematol 2013;4:153-5

How to cite this URL:
Das K, Ramakrishnan M, Agrawal N, Pai S, Dixit A. Hemophagocytic lymphohistiocytosis with hepatitis A. J Appl Hematol [serial online] 2013 [cited 2023 Feb 4];4:153-5. Available from: https://www.jahjournal.org/text.asp?2013/4/4/153/127903

  Introduction Top

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition. It can present as primary (familial) or secondary condition after immunological insult. Its association with hepatitis A is extremely rare and the treatment strategy is not well defined.

  Case Report Top

A 4-year-old male child presented with pallor, breathlessness, and fever for 3 days. There was no history of bleeding or previous blood transfusion. He had fever and icterus 1 month back and was diagnosed to have acute hepatitis A (hepatitis A IgM+) infection. That episode was managed with supportive care, and he recovered well although mild icterus persisted. There was a history of exposure to antimalarial (cloroquine) 2 days back which was prescribed by the primary pediatrician, and no other significant drug exposure was noted. He was born out of non-consanguineous marriage. Family history was noncontributory. Clinical examination revealed pallor, icterus, hepatomegaly (3 cm below costal margin), and splenomegaly (2 cm below costal margin), but no lymphadenopathy. Laboratory workup revealed severe anemia (normocytic) with low leukocyte and platelet counts. Reticulocyte count was low and lactate dehydrogenase (LDH) was increased. Liver enzymes were deranged with high cholestatic hyperbilirubinemia [Table 1]. Glucose-6-phosphate dehydrogenase (G6PD) enzyme activity was reduced. Enzyme-linked immunosorbent assay (ELISA) tests for HIV, hepatitis B, and hepatitis C were negative. Cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) was negative as well. Ultrasonography of abdomen revealed hepatosplenomegaly along with gall bladder sludge. His clinical condition improved with supportive care and packed red blood cells (PRBC) transfusion, although he remained symptomatic with fever, persistent pancytopenia, and deranged liver function test. Blood cultures were sterile. Bone marrow examination revealed hypercellular marrow with myeloid hyperplasia, increased histiocytes with foci of hemophagocytosis, and absent erythroid precursors [Figure 1]. Triglyceride and ferritin levels were high [Table 1]. He was diagnosed to have HLH and was started on dexamethasone 10 mg/m2. Etoposide was not considered in view of high icterus and preceding hepatitis A. He responded dramatically and became afebrile with complete recovery of cytopenias within 72 h. Liver functions also improved gradually to normal. His steroid was tapered off over the next 4 weeks. On follow-up after 3 months, he was quite asymptomatic with normalization of blood parameters.
Table 1: Laboratory parameters at presentation

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Figure 1: Bone marrow aspiration showing hemophagocytosis

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  Discussion Top

HLH is a consequence of unregulated macrophage proliferation with immune dysfunction and cytokine overexpression. Abnormally proliferated macrophages engulf hematopoietic cells and cause pancytopenia along with infiltration of reticuloendothelial systems, while the cytokines cause constellation of symptoms including high-grade fever and multiorgan dysfunction often described with HLH and are used as the diagnostic criteria. HLH may be primary (familial) or secondary (acquired). Although the distinction is hard to make in children, presence of family history supports the diagnosis of primary HLH. Secondary HLH often occurs after infectious, rheumatological, or malignancy insult. Epstein-Barr virus (EBV) is more commonly associated with HLH, although it has been reported with CMV, HIV, hepatitis, and influenza too. [1],[2] Association of hepatitis A with HLH is limited to case reports only and it has been found to have good prognosis. [3],[4],[5],[6],[7] Majority of the case reports are from Japan and Taiwan, and there is a paucity of reports from the Indian subcontinent. [8] Diagnosis of HLH is made as per the criteria laid by the Histiocytic Society in 2004. [9] It is often under considered as differential and underdiagnosed too. A study has revealed it as one of the important causes of multiorgan dysfunction in patients admitted in the pediatric intensive care unit (PICU) setting. [10]

The index case presented with acute onset of pallor pertaining to his G6PD status. Persistent fever with direct hyperbilirubinemia, splenomegaly, and pancytopenia after 1 month of viral hepatitis episode prompted us to look for HLH. The time lag from hepatitis A to HLH is quite variable in the literature, ranging from 3 to 21 days. [7] Absence of family history supports its secondary nature.

The Histiocytic Society has proposed the treatment guidelines with which the survival of patients with HLH, an earlier fatal disease, has improved. [9] Treatment of HLH associated with hepatitis A is not clear. Intravenous immunoglobulin (IVIG) has been found to be effective. [11],[12] The index case was started on steroid as per the protocol and showed remarkable improvement in his general condition as well as laboratory parameters. Etoposide was withheld due to his deranged liver function and with the experience that spontaneous regression is possible in virus-related HLH. [3],[13]

  Conclusion Top

HLH should be considered as a differential diagnosis for patient with non-responsive fever and multiorgan involvement. Our case supports an association of hepatitis A with HLH. These can easily be treated with steroid or IVIG monotherapy; however, use of Etoposide may be required in non-responsive cases.

  References Top

1.Domachowske JB. Infectious triggers of Hemophagocytic Syndrome in children. Pediatr Infect Dis J 2006;25:1067-8.  Back to cited text no. 1
2.Tsenga YT, Shenga WH, Linb BH, Lin CW, Wang JT, Chen YC, et al. Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults. J Microbiol Immunol Infect 2011;44:191-7.  Back to cited text no. 2
3.Watanabe M, Shibuya A, Okuno J, Maeda T, Tamama S, Saigenji K. Hepatitis A Virus Infection Associated with Hemophagocytic Syndrome: Report of Two Cases. Intern Med 2002;41:1188-92.  Back to cited text no. 3
4.Bay A, Bosnak V, Lebisatan G, Yavuz S, Yilmaz F, Hizli S. Hemophagocytic lymphohistiocytosis in two pediatric patients secondary to Hepatitis A viral infection. Pediatr Hematol Oncol 2012;29:211-4.  Back to cited text no. 4
5.Canoz PY, Afat E, Temiz F, Azizoglu NO, Citilcioglu HB, Tumgor G, et al. Reactive hemophagocytic lymphohistiocytosis after Hepatitis A infection. Indian J Hematol Blood Transfus 2013; doi :10. 1007/s12288-013-0241-8. [Epub ahead of print].  Back to cited text no. 5
6.Seo JY, Seo DD, Jeon TJ, Oh TH, Shin WC, Choi WC, et al. A case of hemophagocytic syndrome complicated by acute viral Hepatitis A infection. Korean J Hepatol 2010;16:79-82.  Back to cited text no. 6
7.Tuon FF, Gomes VS, Amato VS, Graf ME, Fonseca GH, Lazari C, et al. Hemophagocytic syndrome associated with hepatitis A: Case report and literature review. Rev Inst Med Trop Sao Paulo 2008;50:123-7.  Back to cited text no. 7
8.Kaur S, Kulkarni KP, Mahajan A, Sibal A. Hemophagocytosis associated with Hepatitis A And E coinfection in a young child. Indian J Hematol Blood Transfus 2011;27:117-8.  Back to cited text no. 8
9.Henter JI, Horne AC, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-31.  Back to cited text no. 9
10.Nahum E, Ben-Ari J, Stain J, Schonfeld T. Hemophagocytic lymphohistiocytic syndrome: Unrecognized cause of multiple organ failure. Pediatr Crit Care Med 2000;1:51-4.  Back to cited text no. 10
11.Larroche C, Bruneel F, André MH, Bader-Meunier B, Baruchel A, Tribout B, et al. Intravenously administered gamma-globulins in reactive hemaphagocytic syndrome. Multicenter study to assess their importance, by the immunoglobulins group of experts of CEDIT of the AP-HP. Ann Med Interne 2000;151:533-9.  Back to cited text no. 11
12.Tai CM, Liu CJ, Yao M. Successful treatment of acute hepatitis A-associated hemophagocytic syndrome by intravenous immunoglobulin. J Formos Med Assoc 2005;104:507-10.  Back to cited text no. 12
13.Bakhshi S, Pautu JL. EBV associated hemophagocytic lymphohistiocytosis with spontaneous regression. Indian Pediatr 2005;42:1253-5.  Back to cited text no. 13


  [Figure 1]

  [Table 1]

This article has been cited by
1 Hepatitis A infection related haemophagocytic syndrome: a case report and systematic review
Bipadabhanjan Mallick,Philip Daniel,Usha Dutta
Tropical Doctor. 2019; 49(3): 234
[Pubmed] | [DOI]


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