Diagnosing and treating hemophagocytic lymphohistiocytosis in the tropics: Systematic review from the Indian subcontinent

Srinivas Rajagopala; Navneet Singh

Authors

Srinivas Rajagopala
Navneet Singh

Keywords:

Hemophagocytic lymphohistiocytosis, Hemophagocytic syndrome, India, Indian sub-continent

Abstract

Background. Hemophagocytic lymphohistiocytosis (HLH) is a catastrophicsyndrome of unrestrained immune activation. Evaluationand management of HLH in the tropics is challenging. Objectives. Toexamine the reported etiologies and management of HLH reportedfrom the sub-continent. Methods. Systematic review of all publishedcases from the Indian sub-continent. Results. We found only 156 publishedcases of HLH from the sub-continent. HLH was reported fromthe immediate perinatal period to 46 years of age. Infection-associatedHLH (IAHS) constituted 46.8% of all cases of HLH (44% and 51%in children and adults respectively). In adults, tropical infections triggered51% of these cases of IAHS. Steroids were used in 47% of childrenand 10% of adults. Etoposide and/or cyclosporine were used in8% children and 8% of adults only. Intravenous immunoglobulin wasused in another 30% of children and 4% of the adults. HLH-relatedmortality occurred in 31.8% and 28% of children and adults respectively.Conclusions. HLH is under-reported in the sub-continentand has high mortality. Cyclosporine and etoposide are seldom administeredearly despite diagnosis of HLH. Larger cohorts with IAHStriggered by tropical infections are urgently needed to understand itsnatural history and implications of this differing prescription patternon mortality.

Downloads

Download data is not yet available.

References

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.

;48(2):124-31.

Creput C, Galicier L, Buyse S, Azoulay E. Understanding

organ dysfunction in hemophagocytic lymphohistiocytosis. Intensive Care Med. 2008;34(7):1177-87.

Rajagopala S, Singh N, Agarwal R, Gupta D, Dass R. Severe hemophagocytic lymphohistiocytosis in adults-experience from an intensive care unit from North India. Indian J Critical Care Medicine. 2012. in press.

Rajagopala S, Dutta U, Chandra KS, Bhatia P, Varma N, Kochhar R. Visceral leishmaniasis associated hemophagocytic lymphohistiocytosis-case report and systematic review. J Infect.

;56(5):381-8.

Ramachandran B, Balasubramanian S, Abhishek N, Ravikumar KG, Ramanan AV. Profile of hemophagocytic lymphohistiocytosis in children in a tertiary care hospital in India. Indian Pediatr. 2011;48(1):31-5.

Joseph VJ, Sunny AO, Pandit N, Yeshwanth M. Hemophagocytic syndrome. Indian Pediatr. 1992;29(7):897-900.

Biswal N, Shareef S, Nalini P, Sreenisasan S, Basu D. Hemophagocytic lymphohistiocytosis. Ind J Pediatrics. 1999;66:632-5.

Kumar N, Jain S, Singh ZN. Disseminated histoplasmosis with reactive hemophagocytosis: aspiration cytology findings in two cases. Diagn Cytopathol. 2000;23(6):422-4.

Mathew LG, Cherian T, Sudarshanam A, Korah I, Kumar NKS, Raghupathy P. Hemophagocytic Lymphohistiocytosis: A Case Series. Indian Pediatrics. 2000;37:526-31.

Bhutani V, Dutta U, Das R, Singh K. Hemophagocytic syndrome as the presenting manifestation of visceral leishmaniasis. J Assoc Physicians India. 2002;50:838-9.

Kakkar N, Vasishta RK, Banerjee AK, Marwaha RK, Thapa BR. Familial hemophagocytic lymphohistiocytosis: an autopsy study. Pediatr Pathol Mol Med. 2003;22(3):229-42.

Pahwa R, Singh T, Khurana N. Hemophagocytic syndrome in malaria and kala-azar. Indian J Pathol Microbiol. 2004;47(3):348-50.

Bakhshi S, Pautu JL. EBV-associated Hemophagocytic Lymphohistiocytosis with Spontaneous Regression Indian Pediatrics. 2005;42:1253-5.

Dutta U, Mittal S, Ratho RK, Das A. Acute liver failure and severe hemophagocytosis secondary to parvovirus B19 infection. Indian J Gastroenterol. 2005;24(3):118-9.

Saluja S, Sunita, S Bhasin, D K Gupta, B Gupta, S P Kataria, et al. Disseminated Histoplasmosis with Reactive Haemophagocytosis Presenting as PUO in an Immunocompetent Host. J Assoc Physicians India. 2005;53:906-8.

Agarwal S, Narayan S, Sharma S, Kahkashan E, Patwari AK. Hemophagocytic syndrome associated with visceral leishmaniasis. Indian J Pediatr. 2006;73(5):445-6.

Malhotra AK, Bhaskar G, Nanda M, Kabra M, Singh MK, Ramam M. Griscelli syndrome. J Am Acad Dermatol. 2006;55(2):337-40.

Karthik R. Infectious Causes of Macrophage Activation Syndrome. J Assoc Physicians India. 2007;55:877.

Mathur P, Samantaray JC, Samanta P. Fatal haemophagocytic syndrome and hepatitis associated with visceral leishmaniasis. Indian J Med Microbiol. 2007;25:416-8.

Pinto L, Kagalwala F, Singh S, Balakrishnan C, Prabhu S, Khodaiji S. Macrophage Activation Syndrome: Experience from a Tertiary Referral Centre. J Assoc Physicians India. 2007;55:185-7.

Das S, Kalyani R. Hemophagocytic syndrome. Ind J Pathol Microbiol. 2008;51(1):125-6.

Jain D, Singh T. Dengue virus related hemophagocytosis: a rare case report. Hematology. 2008;13(5):286-8.

Medhi K, Kumar R, Rishi A, Kumar L, Bakhshi S. Subcutaneous panniculitis like T-cell lymphoma with hemophagocytosis: complete remission with BFM-90 protocol. J Pediatr Hematol Oncol. 2008;30(7):558-61.

Rajam L, Prasad V, Yatheesha BL. Reactive hemophagocytic syndrome. Indian J Pediatr. 2008;75(12):1261-3.

Raka S, Nayar P, Godbole R, Manchanda R. Familial hemophagocytic Iymphohistiocytosis. Indian J Hematol Blood Transfus. 2008;25(2):78-80.

Balasubramanian S, Kaarthigeyan K, Aparna V, Srinivas S. Tuberculosis associated hemophagocytic syndrome in infancy. Indian Pediatr. 2008;45:593-5.

Singh S, Samant R, Joshi VR. Adult onset Still’s disease: a study of 14 cases. Clin Rheumatol. 2008;27(1):35-9.

Gosh JB, Roy M, Bala A. Infection Associated with Hemophagocytic Lymphohisticytosis triggered by nosocomial Infection. OMJ. 2009;24:223-5.

Gupta AP, Parate SN, Bobhate SK, Anupriya. Hemophagocytic syndrome: A cause for fatal outcome in tuberculosis. Ind J Pathol Microbiol. 2009;52(2):260-2.

Juneja M, Jain R, Mishra D. Macrophage activation syndrome in an inadequately treated patient with systemic onset juvenile idiopathic arthritis. Kathmandu Univ Med J (KUMJ). 2009;7(28):411-3.

Patel KK, Patel AK, Sarda P, Shah BA, Ranjan R. Immune reconstitution visceral leishmaniasis presented as hemophagocytic syndrome in a patient with AIDS from a nonendemic area: a case report. J Int Assoc Physicians AIDS Care (Chic). 2009;8(4):217-20.

Pramanik S, Pal P, Das PK, Chakrabarty S, Bhattacharya A, Banerjee S. Reactive Haemophagocytic Lymphohistiocytosis. Indian Journal of Pediatrics. 2009;76:643-5.

Prasad R, Muthusami S, Pandey N, Tilak V, Shukla J, Mishra OP. Unusual presentations of Visceral leishmaniasis. Indian J Pediatr. 2009;76(8):843-5.

Premaratna R, Williams HS, Chandrasena TG, Rajapakse RP, Kularatna SA, de Silva HJ. Unusual pancytopenia secondary to haemophagocytosis syndrome in rickettsioses. Trans R Soc Trop Med Hyg. 2009;103(9):961-3.

Puliyel MM, Rose W, Kumar S, Moses PD, Gibikote S. Prolonged neurologic course of familial hemophagocytic lymphohistiocytosis. Pediatr Neurol. 2009;41(3):207-10.

Aggarwal D, Gupta R, Singh S, Gupta K, Kudesia M. Hemophagocytic Lymphohistiocytosis in BCell Lymphoproliferative Disorder: Report of a Rare Association. Indian Journal of Hematology and Blood Transfusion. 2010;26(2):74-6.

Dass R, Barman H, Duwarah SG, Choudhury V, Jain P, Deka NM, et al. Macrophage activation syndrome in malaria. Rheumatol Int. 2010;30(8):1099-101.

Deshpande A, Nayar PS, Pradhan AM, Manchanda RV. Miliary tuberculosis with hemophagocytosis in a two months old infant. Indian J Hematol Blood Transfus. 2010;26(3):115-7.

Gopal GK, Anugrah C, Boorugu H. Scrub typhus associated macrophage activation syndrome. Trop Doct. 2010;40(4):249-50.

Koul PA, Khan U, Shah S, Jan MR, Wani DA, Abdul D, et al. Hemophagocytic Lymphohistiocytosis: A 25-Year Experience at a Tertiary Care Hospital. WebmedCentral INFECTIOUS DISEASES [serial on the Internet]. 2010;1(9):Available from: http://www.webmedcentral.com/wmcpdf/Article_

WMC00674.pdf.

Kumar S, Vaidyanathan B, Gayathri S, Rajam L. Systemic onset juvenile idiopathic arthritis with macrophage activation syndrome misdiagnosed as Kawasaki disease: case report and

literature review. Rheumatol Int. 2010. Available from: https://springerlink3.metapress.com/

content/84213931j616105v/resource-secured/

?target=fulltext.pdf&sid=ceyydymehif4ssuffc14q

o3&sh=www.springerlink.com

Mondal N, Suresh R, Acharya NS, Praharaj I, Harish BN, Mahadevan S. Hemophagocytic syndrome in a child with brucellosis. Indian J Pediatr. 2010;77(12):1434-6.

Ramesh M, Singh V, Ghuliani R, Kapur BN, Singh J, Shankar S. Histiocytosis Syndromes of Childhood: A report of four cases. J Nepal Paediatr Soc. 2010;30(3):171-4.

Suresh N, Sankar J. Macrophage activation syndrome: a rare complication of incomplete Kawasaki disease. Ann Trop Paediatr. 2010;30(1):61-4.

Valsalan R, Kosaraju K, Sohanlal T, Kumar PSP. Hemophagocytosis in scrub typhus. J Postgrad Med. 2010;56:301-2.

Ali N, Fadoo Z, Masood N, Adil SN. Successful Engraftment and Survival Following Allogeneic Hematopoietic Stem Cell Transplant in a Child with Familial Hemophagocytic Lymphohistiocytosis. Indian J Pediatr. 2011. Available from: http://www.

springerlink.com/content/9272744w8016562t/

Gupta A, Sen R, Batra C, Banerjee D, Jain M. Hemophagocytic syndrome secondary to cytomegalovirus infection in an infant. J Cytol. 2011;28(1):36-8.

Jayakrishnan MP, Veny J, Feroze M. Rickettsial infection with hemophagocytosis. Trop Doct. 2011;41(2):111-2.

Kumar S, Rajam L. Posterior reversible encephalopathy syndrome (PRES/RPLS) during pulse steroid therapy in macrophage activation syndrome. Indian J Pediatr. 2011;78(8):1002-4.

Ray S, Kundu S, Saha M, Chakrabarti P. Hemophagocytic Syndrome in Classic Dengue Fever. J Glob Infect Dis. 2011;3(4):399-401.

Roy A, Kar R, Basu D, Srivani S, Badhe BA. Clinico-hematological profile of Chediak-Higashi syndrome: Experience from a tertiary care center in south India. Ind J Pathol Microbiol. 2011;54(3):547-9.

Vinoth PN, Thomas KA, Selvan SM, Suman DF, Scott JX. Hemophagocytic syndrome associated with Plasmodium falciparum infection. Indian J Pathol Microbiol. 2011;54(3):594-6.

Chandra H, Chandra S, Sharma A. Histoplasmosis on bone marrow aspirate cytological examination associated with hemophagocytosis and pancytopenia in an AIDS patient. Korean J Hematol. 2012;47(1):77-9.

John TM, Jacob CN, Ittycheria CC, George AM, Jacob AG, Subramaniyam S, et al. Macrophage activation syndrome following Acinetobacter baumannii sepsis. Int J Infect Dis. 2012;16(3):e223-4.

Maheshwari P, Chhabra R, Yadav P. Perinatal Tuberculosis associated Hemophagocytic Lymphohistiocytosis. Indian J Pediatr. 2012:;79(9):1228-9.

Mishra B, Varma N, Appannanavar S, Malhotra P, Sharma M, Bhatnagar A, et al. Viral markers in patients with hemophagocytosis: A prospective study in a tertiary care hospital. Indian J Pathol Microbiol. 2012;55:215-7.

Nayan D, Bhagyalakshmi S, Nitin K, Farah J, Chandrakala S. Hemophagocytic Lymphohistiocytosis in a 19 Year Old Critically Ill Patient. Indian Journal of Hematology and Blood Transfusion.

;28(2):117-20.

Singh S, Chandrakasan S, Ahluwalia J, Suri D, Rawat A, Ahmed N, et al. Macrophage activation syndrome in children with systemic onset juvenile idiopathic arthritis: clinical experience from northwest India. Rheumatol Int. 2012;32(4):881-6.

Sood N, Yadav P. Hemophagocytic syndrome associated with concomitant Klebsiella and Parvovirus B-19 infection. Indian J Pathol Microbiol 2012;55:124-5.

Currimbhoy Z. An outbreak of an infection associated with circulating activated monocytes and hemophagocytes in children in Bombay, India. Am J Pediatr Hematol Oncol. 1991;13(3):274-9.

Vijayalakshmi AM, Ganesh VRR. Hemophagocytic Syndrome Associated with Dengue Hemorrhagic Fever. Indian Pediatrics. 2009;46:545.

Sharma M, Dass J, Tyagi S. ATRA Induced Reactive Hemophagocytosis: a Case Report. Mediterr J Hematol Infect Dis. 2011;3(1):e2011034.

Gupta A, Modi CJ, Gujral S. Hemophagocytosis by leukemic cells in biphenotypic acute leukaemia: a rare case. Indian J Pathol Microbiol. 2010;53(2):370-1.

Avasthi R, Mohanty D, Chaudhary S, Mishra K. Disseminated Tuberculosis: Interesting Hematological Observations. J Assoc Physicians India. 2010;58:243-4.

Bhattacharyya M, Ghosh MK. Hemophagoctic lymphohistiocytosis--recent concept. J Assoc Physicians India. 2008;56:453-7.

Henter JI. Biology and treatment of familial hemophagocytic lymphohistiocytosis: importance of perforin in lymphocyte-mediated cytotoxicity and triggering of apoptosis. Med Pediatr Oncol. 2002;38(5):305-9.

Imashuku S, Tabata Y, Teramura T, Hibi S. Treatment strategies for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Leuk Lymphoma. 2000;39(1-2):37-49.