Abstract
Objective
To describe the epidemiology, clinical features, laboratory findings, outcome and the difficulties in diagnosis and management of children with Hemophagocytic Lymphohistiocytosis (HLH) in a tertiary children’s hospital in India.
Study Design
Retrospective analysis of case records of all the children with a diagnosis of HLH from December 2006 to December 2008.
Setting
Tertiary care children’s teaching hospital in Chennai, India.
Results
43 children had a diagnosis of hemophagocytosis, of who only 33 (19 male, mean age 46 months, range 50 days-14 years) met the inclusion criteria based on the HLH-2004 protocol of the Histiocyte Society. The predominant presenting features included prolonged fever and hepatosplenomegaly. CNS symptoms were present in 36%. Anemia (Hb <9gm/dL), and thrombocytopenia (platelets <1,00,000/mm3) were present in 97% and 72%, respectively. Among the biochemical markers, hyperferritinemia was present in 97%, and hypofibrinogenemia and high LDH in 92%. Bone marrow examination showed hemophagocytosis in 84%. Infectious agents were identified in 42% children, with viruses accounting for 2/3 of them (5 Dengue virus, 3 EBV, 1 CMV, 1 TB and 5 bacterial agents). The mean duration between the onset of symptoms and the diagnosis was 16 days. Corticosteroids were the most commonly used immunomodulatory agents (67%), followed by IVIg (64%). Cyclosporine was used in 33% and Etoposide in 15%. Improvement of laboratory parameters was noticed within 5–7 days of starting treatment. Overall survival rate was 76%.
Conclusion
HLH should be considered in the differential diagnosis of children with prolonged fever, hepatosplenomegaly and cytopenia. Prompt recognition and appropriate therapy may result in good outcome, particularly in Infection associated HLH.
Similar content being viewed by others
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. 2007;48:124–131.
Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000;6:601–608.
Janka GE. Hemophagocytic syndromes. Blood Rev. 2007;21:245–253.
Balasubramanian S, Kaarthigeyan K, Aparna V, Srinivas S. Tuberculosis associated hemophagocytic syndrome in infancy. Indian Pediatr. 2008;45:593–595.
Palazzi DL, McClain KL, Kaplan SL. Hemophagocytic syndrome in children: An important diagnostic consideration in fever of unknown origin. Clin Infect Dis. 2003;36:306–312.
Ariffin H, Lum SH, Cheok SA, Sekhar K, Ariffin WA, Chan LL, et al. Hemophagocytic lymphohistiocytosis in Malaysian children. J Paediatr Child Health 2005;4:136–139.
Mathew LG, Cherian T, Sudarshanam A, Korah I, Kumar NK, Raghupathy P. Hemophagocytic lymphohistiocytosis: A case series. Indian Pediatr. 2000;37:526–537.
Chen CJ, Huang YC, Jaing TH, Hung IJ, Yang CP, Chang LY, et al. Hemophagocytic Syndrome: a review of 18 pediatric cases. J Microbiol Immunol Infect. 2004;37:157–163.
Arico M, Janka G, Fisher A, Henter JI, Blanche S, Elinder G, et al. Hemophagocytic lymphohistiocytosis: report of 122 children from the International Registry. Leukemia. 1996;10:197–203.
Veerakul G, Sanpakit K, Tanphaichitr VS, Mahasandana C, Jirarattanasopa N. Secondary hemophagocytic lymphohistiocytosis in children: an analysis of etiology and outcome. J Med Assoc Thai. 2002;85:S530–S541.
Filipovich AH. Hemophagocytic lymphohistio-cytosis and other hemophagocytic disorders. Immunol Allergy Clin North Am. 2008;28:293–313.
Kogawa K, Lee SM, Villanueva J, Marmer D, Sumegi J, Fillipovich AH. Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members. Blood. 2002;99:61–66.
Arico M, Allen M, Brusa S, Clementi R, Pende D, Maccario R, et al. Haemophagocytic lymphohistiocytosis: proposal of a diagnostic algorithm based on perforin expression. Br J Haematol. 2002;119:180–188.
Imashuku S, Hlbi S, Todo S. Hemophagocytic Lymphohistiocytosis in infancy and children. J Pediatr. 1997;130:352–357.
Gupta A, Tyrell P, Valani R, Benseler S, Weitzman S, Abdelhaleem M. The role of the initial bone marrow aspirate in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008:51:402–404.
Lee JS, Kang JH, Lee GK, Park HJ. Successful treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with HLH-94 Protocol. J Korean Med Sci. 2005;20:209–214.
Imashuku S, Kuriyama K, Teramura T, Ishii E, Kinugawa N, Koto M, et al. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001;19:2665–2673.
Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I. Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol. 2007;86:58–65.
Larroche C, Bruneel F, Andre MH, Bader-Meurier B, Baruchel A, Tribout B, et al. Intravenously administered gamma-globulins in reactive hemophagocytic syndrome. Multicenter study to assess their importance, by the immunoglobulins group of experts of CEDIT of the AP-HP. Ann Med Interne. (Paris) 2000;151:533–539.
Emmenegger U, Frey U, Reimers A, Fux C, Semela D, Cottagnoud P, et al. Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes. Am J Hematol. 2001;68:4–10.
Henter JI, Arico M, Samuelsson-Horne A, Egeler RM, Elinder G, Filipovich AH, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002;100:2367–2373.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ramachandran, B., Balasubramanian, S., Abhishek, N. et al. Profile of hemophagocytic lymphohistiocytosis in children in a tertiary care hospital in India. Indian Pediatr 48, 31–35 (2011). https://doi.org/10.1007/s13312-011-0020-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13312-011-0020-2