|Year : 2013 | Volume
| Issue : 4 | Page : 153-155
Hemophagocytic lymphohistiocytosis with hepatitis A
Kunal Das1, Meera Ramakrishnan2, Nitika Agrawal2, Swati Pai1, Ashish Dixit1
1 Department of Hematology, Medical Oncology and Transplant, Bangalore, Karnataka, India
2 Department of Pediatrics, Manipal Hospital, Bangalore, Karnataka, India
|Date of Web Publication||26-Feb-2014|
Comprehensive Cancer Center, Manipal Hospital, 98, Rustam Bagh, Airport Road, Bangalore - 560 017, Karnataka
Source of Support: None, Conflict of Interest: None
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
| Introduction|| |
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|| |
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.
| Discussion|| |
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. , Association of hepatitis A with HLH is limited to case reports only and it has been found to have good prognosis. ,,,, Majority of the case reports are from Japan and Taiwan, and there is a paucity of reports from the Indian subcontinent.  Diagnosis of HLH is made as per the criteria laid by the Histiocytic Society in 2004.  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. 
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.  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.  Treatment of HLH associated with hepatitis A is not clear. Intravenous immunoglobulin (IVIG) has been found to be effective. , 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. ,
| Conclusion|| |
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.
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