Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition

Somanath Padhi, Renu G’ Boy Varghese, Anita Ramdas, Manjiri Dilip Phansalkar, RajLaxmi Sarangi

PDF(245 KB)
PDF(245 KB)
Front. Med. ›› 2013, Vol. 7 ›› Issue (4) : 492-498. DOI: 10.1007/s11684-013-0292-0
RESEARCH ARTICLE

Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition

Author information +
History +

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially life threatening, hyper inflammatory syndrome of diverse etiologies. Cardinal signs include prolonged fever, organomegaly, and persistent unexplained cytopenias. In spite of the well known diagnostic criteria put forth by HLH society, this continues to pose great diagnostic challenge in both pediatric and adult intensive care settings. We describe 4 adult (2 males, 2 females, aged 19, 29, 40, and 17 years) and 3 pediatric (2 males, 1female, aged 1 month, 6 months, and 12 years) patients with secondary HLH who satisfied the HLH-2004 diagnostic criteria. Definite evidence of hemophagocytosis was noted in 4 patients on initial bone marrow examination. The underlying etiologies were as follows: Rickettsia tsutsugamushi (case 1), autoimmune disorder (case 2), systemic onset juvenile idiopathic arthritis (sJIA) (case 3), unknown bite (possibly a venomous snake) (case 4), Plasmodium vivax (case 5), Cytomegalo virus (case 6), and Mycobacterium tuberculosis (case 7). In one patient, hemophagocytosis was presumed to have been exacerbated by administration of granulocyte monocyte colony stimulating factor (GM-CSF) for severe neutropenia. Two patients died with disseminated intravascular coagulation (DIC) and multi organ failure within few days of HLH diagnosis. Immunosuppressive therapy was started in 3 patients, and etoposide was started in one patient only. Due to lack of specificity of diagnostic criteria, diagnosing and differentiating HLH from its closest mimickers like sepsis/septic shock may be quite challenging in critically ill patients. Therefore, increasing awareness among physicians is essential for early diagnosis and effective therapy to reduce the mortality.

Keywords

hemophagocytic lymphohistiocytosis / diagnosis / therapy / GM-CSF / bone marrow

Cite this article

Download citation ▾
Somanath Padhi, Renu G’ Boy Varghese, Anita Ramdas, Manjiri Dilip Phansalkar, RajLaxmi Sarangi. Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition. Front Med, 2013, 7(4): 492‒498 https://doi.org/10.1007/s11684-013-0292-0

References

[1]
Janka G. Hemophagocytic lymphohistiocytosis: when the immune system runs amok. Klin Padiatr 2009; 221(5): 278–285
CrossRef Pubmed Google scholar
[2]
Machaczka M. Genetic and acquired hemophagocytic lymphohistiocytosis. Int Rev Allergol Clin Immunol 2011; 17(3–4): 63–69
[3]
Tseng YT, Sheng WH, Lin BH, Lin CW, Wang JT, Chen YC, Chang SC. Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults. J Microbiol Immunol Infect 2011; 44(3): 191–197
CrossRef Pubmed Google scholar
[4]
Glasser L, Legolvan M, Horwitz HM. Florid histiocytic hemophagocytosis following therapy with long acting G-CSF (pegfilgrastim). Am J Hematol 2007; 82(8): 753–757
CrossRef Pubmed Google scholar
[5]
Wang S, Degar BA, Zieske A, Shafi NQ, Rose MG. Hemophagocytosis exacerbated by G-CSF/GM-CSF treatment in a patient with myelodysplasia. Am J Hematol 2004; 77(4): 391–396
CrossRef Pubmed Google scholar
[6]
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48(2): 124–131
CrossRef Pubmed Google scholar
[7]
Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology (Am Soc Hematol Educ Program) 2009; 2009(1): 127–131
CrossRef Pubmed Google scholar
[8]
Créput C, Galicier L, Buyse S, Azoulay E. Understanding organ dysfunction in hemophagocytic lymphohistiocytosis. Intensive Care Med 2008; 34(7): 1177–1187
CrossRef Pubmed Google scholar
[9]
Raschke RA, Garcia-Orr R. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest 2011; 140(4): 933–938
CrossRef Pubmed Google scholar
[10]
Gurion R, Lehman TJ, Moorthy LN. Systemic arthritis in children: a review of clinical presentation and treatment. Int J Inflam 2012; 2012:271569
[11]
Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy. Expert Rev Clin Immunol 2010; 6(1): 137–154
CrossRef Pubmed Google scholar
[12]
Buyse S, Teixeira L, Galicier L, Mariotte E, Lemiale V, Seguin A, Bertheau P, Canet E, de Labarthe A, Darmon M, Rybojad M, Schlemmer B, Azoulay E. Critical care management of patients with hemophagocytic lymphohistiocytosis. Intensive Care Med 2010; 36(10): 1695–1702
CrossRef Pubmed Google scholar
[13]
Kuwata K, Yamada S, Kinuwaki E, Naito M, Mitsuya H. Peripheral hemophagocytosis: An early indicator of advanced systemic inflammatory response syndrome/hemophagocytic syndrome. Shock 2006; 25(4): 344–350
CrossRef Pubmed Google scholar
[14]
To KK, Hung IF, Li IW, Lee KL, Koo CK, Yan WW, Liu R, Ho KY, Chu KH, Watt CL, Luk WK, Lai KY, Chow FL, Mok T, Buckley T, Chan JF, Wong SS, Zheng B, Chen H, Lau CC, Tse H, Cheng VC, Chan KH, Yuen KY. Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis 2010; 50(6): 850–859
CrossRef Pubmed Google scholar
[15]
Takahashi N, Chubachi A, Kume M, Hatano Y, Komatsuda A, Kawabata Y, Yanagiya N, Ichikawa Y, Miura AB, Miura I. A clinical analysis of 52 adult patients with hemophagocytic syndrome: the prognostic significance of the underlying diseases. Int J Hematol 2001; 74(2): 209–213
CrossRef Pubmed Google scholar
[16]
Dhote R, Simon J, Papo T, Detournay B, Sailler L, Andre MH, Dupond JL, Larroche C, Piette AM, Mechenstock D, Ziza JM, Arlaud J, Labussiere AS, Desvaux A, Baty V, Blanche P, Schaeffer A, Piette JC, Guillevin L, Boissonnas A, Christoforov B. Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review. Arthritis Rheum 2003; 49(5): 633–639
CrossRef Pubmed Google scholar
[17]
Kaito K, Kobayashi M, Katayama T, Otsubo H, Ogasawara Y, Sekita T, Saeki A, Sakamoto M, Nishiwaki K, Masuoka H, Shimada T, Yoshida M, Hosoya T. Prognostic factors of hemophagocytic syndrome in adults: analysis of 34 cases. Eur J Haematol 1997; 59(4): 247–253
CrossRef Pubmed Google scholar
[18]
Shea YF, Chan JFW, Kwok WC, Hwang YY, Chan TC, Ni MYX, Li IWS, Chiu PKC, Luk JKH, Chu LW. Haemophagocytic lymphohistiocytosis: an uncommon clinical presentation of tuberculosis. Hong Kong Med J 2012; 18(6): 517–525
Pubmed
[19]
Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/ systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med 2009; 10(3): 387–392
CrossRef Pubmed Google scholar
[20]
Castillo L. High elevated ferritin levels and the diagnosis of HLH/Sepsis/SIRS/MODS/MAS. Pediatr Blood Cancer 2008; 51(5): 710–711, author reply 710–711
CrossRef Pubmed Google scholar
[21]
Allen CE, Yu X, Kozinetz CA, McClain KL. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2008; 50(6): 1227–1235
CrossRef Pubmed Google scholar
[22]
Hahn YS, Kim JG. Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis. Korean J Pediatr 2010; 53(11): 921–930
CrossRef Pubmed Google scholar

Acknowledgements

The authors are grateful to Dr. Jayaprakash Sahoo, M.D., D.M (Endocrinology), Assistant Professor, Department of Endocrinology, JIPMER, Puducherry, India for the article on tuberculosis associated secondary HLH (Reference No.18).
Compliance with ethics guidelines
Somanath Padhi1, Renu G’ Boy Varghese1, Anita Ramdas1, Manjiri Dilip Phansalkar1 and RajLaxmi Sarangi declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from next of kin of all patients for being included in the study.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
AI Summary AI Mindmap
PDF(245 KB)

Accesses

Citations

Detail

Sections
Recommended

/