Epstein-Barr virus associated secondary hemophagocytic lymphohistiocytosis with an unusual presentation of abdominal compartment syndrome

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm syndrome caused by an overactive but ineffective immune reaction. Without prompt diagnosis and treatment, HLH is life-threatening. However, presenting symptoms are often nonspecific, with fatigue and fever being the most common. A high index of suspicion is therefore critical for early diagnosis and timely management. A previously healthy, 65-year-old female who initially presented with fever and abdominal pain developed abdominal compartment syndrome (ACS) requiring decompressive laparotomy on hospital day 6. Intraoperative frozen sections of biopsied liver showed intense portal lymphohistiocytic infiltrates. Epstein-Barr virus DNA copy numbers escalated from 600 copies/ mL after admission to 134,000 copies/mL before death. The diagnostic criteria of HLH-2004 were met. Patient expired on hospital day 12. It is important to raise awareness of ACS being an unusual presentation of HLH. Recent changes in diagnostic criteria tailored to adult HLH cases are reviewed.

Keywords

Hemophagocytic lymphohistiocytosis / abdominal compartment syndrome / liver biopsy / Epstein-Barr virus

References

[1] Parikh SA,Letendre L,Wolanskyj AP.Prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis..Mayo Clin Proc2014;89:484-92

[2] Tesi B,Chiang SC,Abboud M,Devecioglu O,Yeoh AE,Möttönen M,Hästbacka J,Nunes S,Sabel M,Tvedt TH,Unal S,Meeths M,Nordenskjöld M.Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis..Genome Med2015;7:130 PMCID:PMC4684627

[3] Nikiforow S.The unique aspects of presentation and diagnosis of hemophagocytic lymphohistiocytosis in adults..Hematology Am Soc Hematol Educ Program2015;2015:183-9

[4] Brisse E,Put K,Mitera T,Rutgeerts O,Ninivaggi M,Boon L,Wouters CH,Matthys P.Mouse cytomegalovirus infection in BALB/c mice resembles virus-associated secondary hemophagocytic lymphohistiocytosis and shows a pathogenesis distinct from primary hemophagocytic lymphohistiocytosis..J Immunol2016;196:3124-34

[5] Lee JH,Lee YJ,Lee JW.Acalculous diffuse gallbladder wall thickening in children..Pediatr Gastroenterol Hepatol Nutr2014;17:98-103 PMCID:PMC4107227

[6] Henter JI,Aricó M,Filipovich AH,Ladisch S,Webb D,Janka G.HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis..Pediatr Blood Cancer2007;48:124-31

[7] Schram AM.How I treat hemophagocytic lymphohistiocytosis in the adult patient..Blood2015;125:2908-14

[8] Rivière S,Coppo P,Aumont C,Fardet L.Reactive hemophagocytic syndrome in adults: a retrospective analysis of 162 patients..Am J Med2014;127:1118-25

[9] Hejblum G,Galicier L,Marzac C,Fardet L.A web-based delphi study for eliciting helpful criteria in the positive diagnosis of hemophagocytic syndrome in adult patients..PLoS One2014;9:e94024 PMCID:PMC3977971

[10] Fardet L,Lambotte O,Aumont C,Coppo P.Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome..Arthritis Rheumatol2014;66:2613-20

[11] Barba T,Iwaz J,Ninet J,Lega JC,Argaud L,Jamilloux Y,Sève P.Hemophagocytic lymphohistiocytosis in intensive care unit: a 71-case strobe-compliant retrospective study..Medicine (Baltimore)2015;94:e2318 PMCID:PMC4697985

[12] Gupta A,Valani R,Weitzman S.The role of the initial bone marrow aspirate in the diagnosis of hemophagocytic lymphohistiocytosis..Pediatr Blood Cancer2008;51:402-4

[13] Strauss R,Westenburger B,Kirchner T.Multifactorial risk analysis of bone marrow histiocytic hyperplasia with hemophagocytosis in critically ill medical patients--a postmortem clinicopathologic analysis..Crit Care Med2004;32:1316-21

[14] Jung SY.Hemophagocytic syndrome diagnosed by liver biopsy in a female patient with systemic lupus erythematosus..J Clin Rheumatol2013;19:449-51

[15] Ju HY,Kim SJ,Kim H,Park KD,Chae JH,Cheon JE,Ahn HS.Hemophagocytic lymphohistiocytosis diagnosed by brain biopsy..Korean J Pediatr2015;58:358-61 PMCID:PMC4623456

[16] Ferry JA.Hematolymphoid tumors of the gastrointestinal tract, hepatobiliary tract, and pancreas.Odze and Goldblum's Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. 3rd ed.2015;Amsterdam, The NetherlandsElsevier879

[17] Favara BE.Histopathology of the liver in histiocytosis syndromes..Pediatr Pathol Lab Med1996;16:413-33

[18] Kapelari K,Heitger A,Margreiter R,Offner FA.Loss of intrahepatic bile ducts: an important feature of familial hemophagocytic lymphohistiocytosis..Virchows Arch2005;446:619-25

[19] Billiau AD,Van Damme-Lombaerts R,Wouters C.Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages..Blood2005;105:1648-51

[20] Teramura T,Yagi T,Hibi S.Quantitative analysis of cell-free Epstein-Barr virus genome copy number in patients with EBV-associated hemophagocytic lymphohistiocytosis..Leuk Lymphoma2002;43:173-9

[21] Smith MC,Greig B,Vnencak-Jones C,Kim AS.The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder..Int J Clin Exp Pathol2014;7:5738-49 PMCID:PMC4203186

[22] Li J,Zheng W,Zhang W,Tian X.Hemophagocytic lymphohistiocytosis: clinical analysis of 103 adult patients..Medicine (Baltimore)2014;93:100-5 PMCID:PMC4616310

[23] Tsuji T,Yamasaki H,Tsuda H.A high sIL-2R/ferritin ratio is a useful marker for the diagnosis of lymphoma-associated hemophagocytic syndrome..Ann Hematol2014;93:821-6 PMCID:PMC3976506

[24] Tabata C.Possible prediction of underlying lymphoma by high sIL-2R/ferritin ratio in hemophagocytic syndrome..Ann Hematol2012;91:63-71

[25] Jiang T,Lu W.The prognostic significance of beta2 microglobulin in patients with hemophagocytic lymphohistiocytosis..Dis Markers2016;2016:1523959 PMCID:PMC4826701

[26] Imashuku S,Tabata Y,Hashida T,Ishimoto K.Outcome of clonal hemophagocytic lymphohistiocytosis: analysis of 32 cases..Leuk Lymphoma2000;37:577-84

[27] Ahn JS,Shin MG,Yang DH,Kim SH,Lee SR,Kim HJ.Clinical significance of clonality and Epstein-Barr virus infection in adult patients with hemophagocytic lymphohistiocytosis..Am J Hematol2010;85:719-22

[28] Matsuda K,Yanagisawa R,Ishii E.Detection of T-cell receptor gene rearrangement in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis using the BIOMED-2 multiplex polymerase chain reaction combined with GeneScan analysis..Clin Chim Acta2011;412:1554-8

[29] Kawaguchi H,Herbst H,Asada M,Hanada R,Sakurai M.Epstein-Barr virus-infected T lymphocytes in Epstein-Barr virus-associated hemophagocytic syndrome..J Clin Invest1993;92:1444-50 PMCID:PMC288289

[30] Trottestam H,Aricò M,Filipovich AH,Imashuku S,Webb D,Henter JI.Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol..Blood2011;118:4577-84 PMCID:PMC3208276

[31] Otrock ZK.Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis..Am J Hematol2015;90:220-4

[32] Oto M,Uneda S,Yoshida M.Prognostic factors and outcomes of adult-onset hemophagocytic lymphohistiocytosis: a retrospective analysis of 34 cases..Hematol Rep2015;7:5841 PMCID:PMC4508551