kjh The Korean Journal of Hematology Korean J Hematol 1738-7949 2092-9129 Korean Society of Hematology 10.5045/kjh.2007.42.1.62 kjh-42-62 Case Report A Case of Hemophagocytic Lymphohistiocytosis Accompanied by Acute Hepatitis A: Review of the Literature LeeHye-JeongM.D. ChungJoo SeopM.D. ShinHo-JinM.D. ChoiYoung JinM.D. ParkYoung-EunM.D. KimPyo-JunM.D. KimIl-DooM.D. LeeEun-YupM.D. 1 ChoGoon JaeM.D. Departments of Internal Medicine, Busan, Korea Pathology, College of Medicine, Pusan National University Hospital, Busan, Korea Correspondence to：Ho-Jin Shin, M.D. Department of Internal Medicine, College of Medicine, Pusan National University Hospital 10, Ami-dong 1-ga, Seo-gu, Busan 602-739, Korea Tel: +82-51-240-7673, Fax: +82-51-254-3127 E-mail: hojinja@hanmail.net 032007 19032007 42162 66 01122007 19122007 02012007 Copyright © 2007 Korean Society of Hematology 2007 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A previously healthy 26-year-old female was referred to our hospital because of fever and abnormalities of her blood biochemistry. Her laboratory results displayed leukopenia (1.79×103/μL), thrombocytopenia (85×103/μL), the serum aspartate aminotransferase and alanine aminotransferase levels were elevated to more than 2,000 IU/L, and the serum levels of lactate dehydrogenase and ferritin were markedly increased. Mild hepatosplenomegaly was reported on the abdomen-pelvis computed tomography. The bone marrow smears revealed proliferation of mature histiocytes that were ingesting platelets and erythrocytes, which is consistent with hemophagocytic lymphohistiocytosis. Although the other viral markers were all negative, the anti-hepatitis A IgM was positive and the anti-hepatitis A IgG was negative. Therefore, the patient was diagnosed as hepatitis A-associated hemophagocytic lymphohistiocytosis. Since a fulminant clinical course was suspected, 2 cycles of cyclosporine (3mg/kg iv from day 1 to day 5), dexamethasone (30mg iv qd from day1 to day 4) and immunoglobulin (500mg/kg iv day 1) therapy was started from the seventh day after onset and a favorable clinical outcome resulted.

 Hemophagocytic lymphohistiocytosis Acute hepatitis A Thrombocytopenia REFERENCESWatanabe M Shibuya A Okuno J Maeda T Tamama S Saigenji K Hepatitis A virus infection associated with heamophagocytic syndrome: report of two cases Intern Med 200241 118892 Ezdinli EZ Kucuk O Chedid A Hypogammaglobulinemia and hemophagocytic syndrome associated with lymphoproliferative disorders Cancer 198657 102437 Shimazaki C Inaba T Nakagawa M B-cell lymphoma-associated hemophagocytic syndrome Leuk Lymphoma 200038 12130 Imashuku S Differential diagnosis of hemophagocytic syndrome: underlying disorders and selection of the most effective treatment Int J Hematol 199766 13551 Risdall RJ McKenna RW Nesbit ME Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis Cancer 197944 9931002 Mckenna RW Risdall RJ Brunning RD Virus associated hemophagocytic syndrome Hum Pathol 198112 3958 Domenech P Palomeque A Martinez-Gutierrez A Vinolas N Vela E Jimenez R Severe aplastic anaemia following hepatitis A Acta Haematol 198676 2279 Onaga M Hayashi K Nishimagi T A cause of acute hepatitis A with marked hemophagocytosis in bone marrow Hepatol Res 200017 20511 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 200241 118892 McPeake JR Hirst WJ Brind AM Williams R Hepatitis A causing a second episode of virus-associated haemophagocytic lymphohistiocytosis in a patient with Still's disease J Med Virol 199339 1735 Kondo H Date Y Effects of simultaneous rhG-CSF and methylprednisolone “pulse” therapy on hepatitis A virus-associated haemophagocytic syndrome Eur J Haematol 199554 2713 Wu CS Chang KY Dunn P Lo TH Acute hepatitis A with coexistent hepatitis C virus infection presenting as a virus-associated hemophagocytic syndrome: a case report Am J Gastroenterol 199590 10025 Kyoda K Nakamura S Machi T Kitagawa S Ohtake S Matsuda T Acute hepatitis A virus infection-associated hemophagocytic syndrome Am J Gastroenterol 199893 11878 Ishii E Ohga S Aoki T Prognosis of children with virus-associated hemophagocytic syndrome and malignant histiocytosis: correlation with levels of serum interleukin-1 and tumor necrosis factor Acta Haematol 199185 939 Imashuku S Hibi S Sako M Soluble interleukin-2 receptor: a useful prognostic factor for patients with hemophagocytic lymphohistiocytosis Blood 199586 47067 Figures and Tables

Abdomen-pelvis computed tomography shows splenomegaly, mild hepatomegaly and periportal low density in liver. Collapsed gallbladder with wall thickening and fluid collection in pelvic cavity are also detected.

Bone marrow aspiration showing hemophagocytosis of megakaryocyte (A), and red blood cells (B) (Wright-Giemsa stain, ×400).

Laboratory data

  Normal ranges and units      
Hematology     Serology  
WBC 4.0～11.0 103/μL 1.79 HBsAg －
RBC 3.75～5.20 106/μL 4.31 HBsAb +
Hb 12.5～15.0g/dL 12.2 HBeAg －
PLT 140～400 103/μL 85 HBeAb －
Coagulation     HBcAb IgM －
PT 11.0～14.1 sec 14.9 HCV Ab －
aPTT 30～44 sec 38.4 HAV Ab IgM +
Fibrinogen 200～400mg/dL 160 HAV Ab IgG －
D-dimer 0.06～0.5μg/mL 1.04 EBV DNA －
Serum chemistry     EBV DNA in BM －
Total bilirubin 0.3～1.3mg/dL 2.02 EBV anti-EA-DR IgA －
Direct bilirubin 0.05～0.4mg/dL 1.37 EBV anti-EA-DR IgG +
AST 10～40IU/L 3,119 EBV anti-EA-DR IgM －
ALT 6～40IU/L 2,456 EBV anti-EBNA IgG +
LDH 218～472IU/L 3,260 EBV anti-EBNA IgM －
ALP 95～280IU/L 375 EBV anti-VCA IgA －
GTP 11～73IU/L 167 EBV anti-VCA IgG +
Total cholesterol 180～210mg/dL 142 EBV anti-VCA IgM －
TG 37～144mg/dL 74 HSV IgG +
HDL 35～72mg/dL 30 HSV IgM －
Ferritin 6～282ng/mL 1,209 CMV PCR －
CRP 0～0.5mg/dL 0.27 Anti-HIV Ab －

Abbreviations: WBC, white blood cell; Hb, hemoglobin; PLT, platelet; PT, prothrombin time; aPTT, activated partial thromboplatin time; AST, aspartate aminotransferase; ALT, alanine aminotranferase; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; GTP, glutamyl transpeptidase; TG, triglyceride; HDL, high-density lipoprotein; CRP, C-reactive protein; HCV, hepatitis C virus; HAV, hepatitis A virus; EBV, Ebstein-barr virus; HSV, herpes simplex virus; CMV, cytomegalovirus; HIV, human immunodeficiency virus.

Case reports of hepatitis A virus associated hemophagocytic lymphohistiocytosis

Case Year Age/Sex Treatment sIL-2R (U/mL) Outcome Underlying diseas
Watanabe et al (9) 1988 24/F None Unknown Recovered  
McPeake et al (10) 1993 20/F Steroid pulse Unknown Recovered Still's disease
Kondo and Date et al (11) 1995 49/F Steroid pulse, rhG-CSF 2,080 Recovered  
Wu et al (12) 1995 23/M Steroid pulse Unknown Died HCV carrier
Kyoda et al (13) 1998 40/M None Unknown Recovered  
Watanabe et al (9) 2000 36/M HDF, steroid pulse, combination chemotherapy∗ Unknown Died  
Onaga et al (8) 2000 19/F Steoid pulse 1,920 Recovered  
Watanabe et al (9) 2002 45/M None 4,870 Recovered  
  2002 41/M None 2,590 Recovered HCV carrier
Present patient 2005 26/F Combination chemotherapy† Unknown Recovered  

Abbreviations: rhG-CSF, recombinant human granulocyte colony stimulating factor; HDF, hemo-diafiltration; HCV, hepatitis C virus; sIL-2R, soluble interleukine-2-receptor.

∗Combination chemotherapy, cyclophosphamide, vincristine and predni-olone;

Combination chemotherapy, cyclophosphamide, prednisolone and immunoglobulin.