Haemophagocytic lymphohistiocytosis in kidney transplant recipients
DOI:
https://doi.org/10.17533/udea.iatreia.21Keywords:
hemophagocytic lymphohistiocytosis, histoplasmosis, ferritins, kidney transplantationAbstract
Hemophagocytic lymphohistiocytosis (HLH) in renal transplant recipients is a life-threatening hyper-inflammatory syndrome; associated with uncontrolled activation of cytotoxic T-lymphocytes and macrophages due to infections or immunosuppressive therapy. Histoplasmosis, tuberculosis and herpes virus infection are among the leading infectious causes. It is characterized by fever, organomegaly, cytopenia, hyperferritinemia, hypertrigiceridemia and/or hypofibrinogenemia; which may be accompanied by hemophagocytosis in bone marrow, liver or other organs. HLH can follow a rapidly fatal course, with progression to multisystemic failure and death. The treatment is based on early control of the triggering cause, reducing immunosuppression and stop the inflammatory process. In some cases, is necessary to use other immunosuppressant, chemotherapy and in a very few cases, a bone marrow transplant may be required.
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(1.) Ramachandran S, Zaidi F, Aggarwal A, Gera R. Recent advances in diagnostic and therapeutic guidelines for primary and secondary hemophagocytic lymphohistiocytosis. Blood Cells Mol Dis. 2017;64:53-7. DOI 10.1016/j.bcmd.2016.10.023.
(2.) Karras A. What nephrologists need to know about hemophagocytic syndrome. Nat Rev Nephrol. 2009;5(6):329-36. DOI 10.1038/nrneph.2009.73.
(3.) Otrock ZK, Eby CS. Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis. Am J Hematol. 2015;90(3):220-4. DOI 10.1002/ajh.23911.
(4.) Morimoto A, Nakazawa Y, Ishii E. Hemophagocytic lymphohistiocytosis: Pathogenesis, diagnosis, and management. Pediatr Int. 2016;58(9):817-25. DOI 10.1111/ped.13064.
(5.) Esteban YM, de Jong JLO, Tesher MS. An Overview of Hemophagocytic Lymphohistiocytosis. Pediatr Ann. 2017;46(8):e309-e13. DOI 10.3928/19382359-20170717-01.
(6.) Larroche C. Hemophagocytic lymphohistiocytosis in adults: diagnosis and treatment. Joint Bone Spine. 2012;79(4):356-61. DOI 10.1016/j.jbspin.2011.10.015.
(7.) Wysocki CA. Comparing hemophagocytic lymphohistiocytosis in pediatric and adult patients. Curr Opin Allergy Clin Immunol. 2017;17(6):405-13. DOI 10.1097/ACI.0000000000000405.
(8.) Nieto JF, Gomez SM, Moncada DC, Serna LM, Hidron AI. Successful treatment of hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation secondary to histoplasmosis in a patient with HIV/AIDS. Biomedica. 2016;36(0):9-14. DOI 10.7705/biomedica.v36i2.2797.
(9.) Nieto-Ríos JF, Serna-Higuita LM, Guzman-Luna CE, Ocampo-Kohn C, Aristizabal-Alzate A, Ramírez I, et al. Histoplasmosis in renal transplant patients in an endemic area at a reference hospital in Medellin, Colombia. Transplant Proc. 2014;46(9):3004-9. DOI 10.1016/j.transproceed.2014.06.060.
(10.) Nieto-Ríos JF, Aristizabal-Alzate A, Ocampo C, Serrano-Gayubo AK, Serna-Higuita LM, Zuluaga-Valencia G. Disseminated histoplasmosis and haemophagocytic syndrome in two kidney transplant patients. Nefrologia. 2012;32(5):683-4. DOI 10.3265/Nefrologia.pre2012.Jun.11508.
(11.) Filippone EJ, Singh P, Frank AM, Gupta A, Farber JL. Rapidly Fatal Hemophagocytic Lymphohistiocytosis Developing Within Six Days Following Deceased-Donor Renal Transplantation: Case Report. Transplant Proc. 2016;48(9):3123-7. DOI 10.1016/j.transproceed.2016.03.031.
(12.) Yaich S, Charfeddine K, Hsairi D, Zaghdane S, Kammoun K, Makni S, et al. BK virus-associated hemophagocytic syndrome in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(3):610-4.
(13.) Lehmberg K, Nichols KE, Henter JI, Girschikofsky M, Greenwood T, Jordan M, et al. Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies. Haematologica. 2015;100(8):997-1004. DOI 10.3324/haematol.2015.123562.
(14.) Vega J, Rodriguez M, Goecke H, Santamaria H. Síndrome hemofagocítico en un trasplantado renal con síndrome de Alport. Rev Med Chile. 2013;141:519-24. DOI 10.4067/S0034-8872013000400014.
(15.) Karras A, Thervet E, Legendre C, Groupe Cooperatif de transplantation d’Ile de F. Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature. Transplantation. 2004;77(2):238-43. DOI 10.1097/01.TP.0000107285.86939.37.
(16.) Marinella MA. Hematologic abnormalities following renal transplantation. Int Urol Nephrol. 2010;42(1):151-64. DOI 10.1007/s11255-009-9558-5.
(17.) Nusshag C, Morath C, Zeier M, Weigand MA, Merle U, Brenner T. Hemophagocytic lymphohistiocytosis in an adult kidney transplant recipient successfully treated by plasmapheresis: A case report and review of the literature. Medicine (Baltimore). 2017;96(50):e9283. DOI 0.1097/MD.0000000000009283.
(18.) Segall L, Moal MC, Doucet L, Kergoat N, Bourbigot B. Toxoplasmosis-associated hemophagocytic syndrome in renal transplantation. Transpl Int. 2006;19(1):78-80. DOI 10.1111/j.1432-2277.2005.00179.x.
(19.) Ardalan MR, Shoja MM, Tubbs RS, Esmaili H, Keyvani H. Postrenal transplant hemophagocytic lymphohistiocytosis and thrombotic microangiopathy associated with parvovirus b19 infection. Am J Transplant. 2008;8(6):1340-4. DOI 10.1111/j.1600-6143.2008.02244.x.
(20.) Lo MM, Mo JQ, Dixon BP, Czech KA. Disseminated histoplasmosis associated with hemophagocytic lymphohistiocytosis in kidney transplant recipients. Am J Transplant. 2010;10(3):687-91. DOI 10.1111/j.1600-6143.2009.02969.x.
(21.) Ponticelli C, Alberighi OD. Haemophagocytic syndrome--a life-threatening complication of renal transplantation. Nephrol Dial Transplant. 2009;24(9):2623-7. DOI 10.1093/ndt/gfp282.
(22.) Daver N, McClain K, Allen CE, Parikh SA, Otrock Z, Rojas-Hernandez C, et al. A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults. Cancer. 2017;123(17):3229-40. DOI 10.1002/cncr.30826.
(23.) Nieto-Rios JF, Gómez de Los Ríos SM, Serna-Higuita LM, Ocampo-Kohn C, Aristizabal-Alzate A, Gálvez-Cárdenas KM, et al. Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor. Colomb Med. 2016;47(4):196-202.
(24.) Nieto-Rios JF, Gómez de Los Ríos SM, Serna-Higuita LM, Ocampo-Kohn C, Aristizabal-Alzate A, Gálvez-Cárdenas KM, et al. Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor. Colomb Med. 2016;47(4):196-202.
(25.) Nieto-Ríos JF, Gómez de Los Ríos SM, Serna-Higuita LM, Gálvez-Cardenas KM. Enfermedad linfoproliferativa postrasplante de órgano sólido. Iatreia. 2016;29(3):312-22.
(26.) Hust MA, Blechacz BRA, Bonilla DL, Daver N, Rojas-Hernandez CM. Adult cancer-related hemophagocytic lymphohistiocytosis - a challenging diagnosis: a case report. J Med Case Rep. 2017;11(1):172. DOI 10.1186/s13256-017-1344-x.
(27.) Wakefield C, Mehta PA, Corathers S, Geller J, Gelfand M, Olowokure O, et al. A First Report of Secondary Hemophagocytic Lymphohistiocytosis Associated With Papillary Thyroid Carcinoma. J Pediatr Hematol Oncol. 2018;40(2):e97-e8. DOI 10.1097/MPH.0000000000000991.
(28.) Satzger I, Ivanyi P, Langer F, Kreipe HH, Schaper-Gerhardt K, Beutel G, et al. Treatment-related hemophagocytic lymphohistiocytosis secondary to checkpoint inhibition with nivolumab plus ipilimumab. Eur J Cancer. 2018;93:150-3. DOI 10.1016/j.ejca.2018.01.063.
(29.) Janka GE, Lehmberg K. Hemophagocytic syndromes--an update. Blood Rev. 2014;28(4):135-42. DOI 10.1016/j.blre.2014.03.002.
(30.) Voskoboinik I, Smyth MJ, Trapani JA. Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol. 2006;6(12):940-52. DOI 10.1038/nri1983.
(31.) Filippone EJ, Farber JL. Hemophagocytic lymphohistiocytosis: an update for nephrologists. Int Urol Nephrol. 2016;48(8):1291-304. DOI 10.1007/s11255-016-1294-z.
(32.) Weaver LK, Behrens EM. Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Curr Opin Rheumatol. 2014;26(5):562-9. DOI 10.1097/BOR.0000000000000093.
(33.) Weaver LK, Behrens EM. Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis. Curr Treatm Opt Rheumatol. 2017;3(1):33-48. DOI 10.1007/s40674-017-0059-x.
(34.) Canna SW, Behrens EM. Making sense of the cytokine storm: a conceptual framework for understanding, diagnosing, and treating hemophagocytic syndromes. Pediatr Clin North Am. 2012;59(2):329-44. DOI 10.1016/j.pcl.2012.03.002.
(35.) De Saint Basile G, Menasche G, Fischer A. Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules. Nat Rev Immunol. 2010;10(8):568-79. DOI 10.1038/nri2803.
(36.) Thiery J, Keefe D, Boulant S, Boucrot E, Walch M, Martinvalet D, et al. Perforin pores in the endosomal membrane trigger the release
f endocytosed granzyme B into the cytosol of target cells. Nat Immunol. 2011;12(8):770-7. DOI 10.1038/ni.2050.
(37.) Marsh RA. Epstein-Barr Virus and Hemophagocytic Lymphohistiocytosis. Front Immunol. 2017;8:1902. DOI 10.3389/fimmu.2017.01902.
(38.) Arlet JB, Le TH, Marinho A, Amoura Z, Wechsler B, Papo T, et al. Reactive haemophagocytic syndrome in adult-onset Still’s disease: a report of six patients and a review of the literature. Ann Rheum Dis. 2006;65(12):1596-601. DOI 10.1136/ard.2005.046904.
(39.) Esmaili H, Mostafidi E, Mehramuz B, Ardalan M, Mohajel-Shoja M. An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome). J Nephropathol. 2016;5(1):8-4. DOI 10.15171/jnp.2016.02.
(40.) Thaunat O, Delahousse M, Fakhouri F, Martinez F, Stephan JL, Noel LH, et al. Nephrotic syndrome associated with hemophagocytic syndrome. Kidney Int. 2006;69(10):1892-8. DOI 10.1038/sj.ki.5000352.
(41.) Al-Lamki RS, Mayadas TN. TNF receptors: signaling pathways and contribution to renal dysfunction. Kidney Int. 2015;87(2):281-6. DOI 10.1038/sj.ki.5000352.
(42.) Allen CE, Yu X, Kozinetz CA, McClain KL. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;50(6):1227-35. DOI 10.1002/pbc.21423.
(43.) Lehmberg K, McClain KL, Janka GE, Allen CE. Determination of an appropriate cut-off value for ferritin in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2014;61(11):2101-3. DOI 10.1002/pbc.25058.
(44.) Otrock ZK, Daver N, Kantarjian HM, Eby CS. Diagnostic Challenges of Hemophagocytic Lymphohistiocytosis. Clin Lymphoma Myeloma Leuk. 2017;17S:S105-S10. DOI 10.1016/j.clml.2017.02.017.
(45.) George MR. Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med. 2014;5:69-86. DOI 10.2147/JBM.S46255.
(46.) Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-31. DOI 10.1002/pbc.21039.
(47.) Asci G, Toz H, Ozkahya M, Cagirgan S, Duman S, Sezis M, et al. High-dose immunoglobulin therapy in renal transplant recipients with hemophagocytic histiocytic syndrome. J Nephrol. 2006;19(3):322-6.
(48.) Caselli D, Arico M, Party EPW. The role of BMT in childhood histiocytoses. Bone Marrow Transplant. 2008;41 Suppl 2:S8-S13. DOI 10.1038/bmt.2008.46.
(49.) Lin S, Li Y, Long J, Liu Q, Yang F, He Y. Acute liver failure caused by hemophagocytic lymphohistiocytosis in adults: A case report and review of the literature. Medicine (Baltimore). 2016;95(47):e5431. DOI 10.1097/MD.0000000000005431.
(50.) Pastula DM, Burish M, Reis GF, Bollen A, Cha S, Ralph J, et al. Adult-onset central nervous system hemophagocytic lymphohistiocytosis: a case report. BMC Neurol. 2015;15:203. DOI 10.1186/s12883-015-0470-6
(51.) Machaczka M, Vaktnas J, Chiang SC, Bryceson YT. Alemtuzumab treatment for hemophagocytic lymphohistiocytosis. Nat Rev Clin Oncol. 2010;7(10). DOI 10.1038/nrclinonc.2010.40-c1.
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