Hemophagocytic Lymphohistiocytosis

  • Kyung-Nam KohEmail author


A previously healthy 11-month-old girl was transferred to the emergency room (ER) with a 7-day history of high fever and progressive lethargy. Her parents reported that she had developed mild cough and rhinorrhea 1 week before presentation. These symptoms were followed by severe illness with high fever, distended abdomen, skin rash, and poor oral intake. She was empirically started on broad-spectrum antibiotics at the referring hospital before transfer.


Hemophagocytic lymphohistiocytosis (HLH) Perforin/granzyme pathway Familial hemophagocytic lymphohistiocytosis (FHL) Secondary hemophagocytic lymphohistiocytosis (secondary HLH) Hyperinflammation 


  1. Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Franco JL, Gaspar HB, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Picard C, Puck JM, Sullivan K, Tang MLK (2014) Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol 5:162PubMedPubMedCentralGoogle Scholar
  2. Filipovich AH, Chandrakasan S (2015) Pathogenesis of hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am 29:895–902CrossRefGoogle Scholar
  3. George MR (2014) Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med 5:69–86CrossRefGoogle Scholar
  4. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124–131CrossRefGoogle Scholar
  5. Horne A, Trottestam H, Aricò M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI (2008) Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol 140:327–335CrossRefGoogle Scholar
  6. Ishii E (2016) Hemophagocytic lymphohistiocytosis in children: pathogenesis and treatment. Front Pediatr 4:1–9CrossRefGoogle Scholar
  7. Jordan MB, Allen CE, Weitzman S, Filipovich AH, Mcclain KL (2011) How I treat hemophagocytic lymphohistiocytosis. Blood 11815(118):4041–4052CrossRefGoogle Scholar
  8. Koh KN, Im HJ, Chung NG, Cho B, Kang HJ, Shin HY, Lyu CJ, Yoo KH, Koo HH, Kim HJ, Baek HJ, Kook H, Yoon HS, Lim YT, Kim HS, Ryu KH, Seo JJ (2015) Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party. Eur J Haematol 94:51–59CrossRefGoogle Scholar
  9. Lehmberg K, Mcclain KL, Janka GE, Allen CE (2014) Determination of an appropriate cut-off value for ferritin in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 61:2101–2103CrossRefGoogle Scholar
  10. Mahlaoui N, Ouachee-Chardin M, de Saint Basile G, Neven B, Picard C, Blanche S, Fischer A (2007) Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients. Pediatrics 120:e622–e628CrossRefGoogle Scholar
  11. Marsh RA, Vaughn G, Kim M, Li D, Jodele S, Joshi S, Mehta PA, Davies SM, Jordan MB, Bleesing JJ, Filipovich AH (2010) Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood 116:5824–5831CrossRefGoogle Scholar
  12. Marsh RA, Jordan MB, Talano J-A, Nichols KE, Kumar A, Naqvi A, Vaiselbuh SR (2016) Salvage therapy for refractory hemophagocytic lymphohistiocytosis: a review of the published experience. Pediatr Blood Cancer 64:1–7Google Scholar
  13. Morimoto A, Nakazawa Y, Ishii E (2016) Hemophagocytic lymphohistiocytosis: pathogenesis, diagnosis, and management. Pediatr Int 58:817–825CrossRefGoogle Scholar
  14. Risma K, Jordan M (2012) Hemophagocytic lymphohistiocytosis: updates and evolving concepts. Curr Opin Pediatr 24:9–15CrossRefGoogle Scholar
  15. Rosado FGN, Kim AS (2013) Hemophagocytic lymphohistiocytosis. Am J Clin Pathol 139:713–727CrossRefGoogle Scholar
  16. Ryu J-M, Kim KM, Oh SH, Koh KN, Im HJ, Park C-J, Chi H-S, Seo JJ (2013) Differential clinical characteristics of acute liver failure caused by hemophagocytic lymphohistiocytosis in children. Pediatr Int Off J Jpn Pediatr Soc 55:748–752CrossRefGoogle Scholar
  17. Seo JJ (2015) Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: recent advances and controversies. Blood Res 50:131–139CrossRefGoogle Scholar
  18. Sieni E, Cetica V, Hackmann Y, Coniglio ML, Da Ros M, Ciambotti B, Pende D, Griffiths G, Arico M (2014) Familial hemophagocytic lymphohistiocytosis: when rare diseases shed light on immune system functioning. Front Immunol 5:1–19CrossRefGoogle Scholar
  19. Trottestam H, Horne AC, Arico M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI (2011) Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 118:4577–4584CrossRefGoogle Scholar
  20. Zhang L, Zhou J, Soko L (2014) Hereditary and acquired hemophagocytic lymphohistiocytosis. Cancer Control 21:301–312CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s HospitalUniversity of Ulsan College of MedicineSeoulSouth Korea

Personalised recommendations