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

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

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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.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg