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  Table of Contents    
Year : 2017  |  Volume : 60  |  Issue : 1  |  Page : 137-138
Hemophagocytic lymphohistiocytosis secondary to multiple infections: Case report of a rare entity

1 Department of Pathology, Maulana Azad Medical College, New Delhi, India
2 Department of Pediatrics, Maulana Azad Medical College, New Delhi, India

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Date of Web Publication14-Feb-2017

How to cite this article:
Jaiswal A, Mallya V, Singh V, Walia M, Khurana N. Hemophagocytic lymphohistiocytosis secondary to multiple infections: Case report of a rare entity. Indian J Pathol Microbiol 2017;60:137-8

How to cite this URL:
Jaiswal A, Mallya V, Singh V, Walia M, Khurana N. Hemophagocytic lymphohistiocytosis secondary to multiple infections: Case report of a rare entity. Indian J Pathol Microbiol [serial online] 2017 [cited 2020 Jul 9];60:137-8. Available from: http://www.ijpmonline.org/text.asp?2017/60/1/137/200033


Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder of excessive immune activation characterized by uncontrolled proliferation of over reactive lymphocytes and activated macrophages leading to hypercytokinemia, end organ damage, and death.[1] HLH can be secondary to infections. The most common infections associated are viral, however, bacterial and parasitic infections are also known to cause secondary HLH. Only three cases have been reported by far due to multiple infections.[2],[3],[4] To the best of our knowledge, we report the first case of HLH in an 8-year-old boy who had fever for 3 weeks and was subsequently diagnosed to have HLH secondary to Plasmodium falciparum and Mycobacterium tuberculosis.[2],[3],[4] Our patient was an 8-year-old boy presenting with complaints of high-grade fever (103°F), abdominal pain, and vomiting for 6 days. The patient had altered sensorium and hepatosplenomegaly at the time of presentation. On peripheral smear examination, gametocyte of P. falciparum was identified. He did not respond to antimalarials. The hemogram revealed hemoglobin (Hb) of 6.8%, total lymphocyte count of 6400/mm 3, and platelet count of 34,000/mm 3. The erythrocyte sedimentation rate was 90 mm at the end of 1 h, aspartate transaminase - 229 U/L, lactate dehydrogenase - 1384 U/L, triglyceride - 270 mg/dl, and serum ferritin - 5801 ng/ml. Ultrasonography of the abdomen confirmed hepatosplenomegaly. Bone marrow smears showed erythroid hyperplasia with a micronormoblastic reaction, megakaryocytic hyperplasia, increase in lymphocytes, and histiocytes with the evidence of hemophagocytosis in these macrophages [Figure 1]. A solitary epithelioid cell granuloma was also seen, and a possibility of HLH secondary to tuberculosis was suggested [Figure 2]. The bone marrow cultures were positive for M. tuberculosis. The patient was started on antitubercular treatment and responded.
Figure 1: Bone marrow aspirate showing erythrophagocytosis (Giemsa, ×600)

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Figure 2: Bone marrow showing epithelioid cell granuloma (Giemsa, ×600)

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HLH was first reported in 1952 by Farquhar and Claireaux as familial hemophagocyticreticulosis.[5] It commonly occurs in infants with a male to female ratio of 1:1.[5] It is of four types – primary/familial, secondary, sporadic, and macrophage activation syndrome. Primary HLH is mostly associated with a specific genetic mutation at the familial hemophagocytic lymphohistiocytosis loci. Secondary HLH occurs usually secondary to infection, autoimmune disorder, underlying malignancy, or immune suppression/organ transplantation.[5]

A strict diagnostic criteria of HLH was given in 2004 by the Histiocyte Society [5] and is as follows:

  1. A molecular diagnosis consistent with HLH that is the identification of mutations of PRF1, UNC13D, or STX11 (OR)
  2. Five out of the eight criteria below:
    • Fever (>100.4°F)
    • Splenomegaly
    • Cytopenias affecting at least two of three lineages:
      • Hb <9 g/dl (in infants <4 weeks: Hb <10 g/100 ml)
      • Platelets <100 × 109/L
      • Neutrophils <1 × 109/L
    • Hypertriglyceridemia (fasting, ≥265 mg/dl) and/or hypofibrinogenemia (≤150 mg/dl)
    • Ferritin ≥500 ng/ml
    • Hemophagocytosis in the bone marrow, spleen/lymph nodes
    • Low or absent natural killer cell activity
    • Soluble CD25 (soluble IL-2 receptor) >2400 U/ml and in the case of familial HLH, no evidence of malignancy should be present.

Our patient was an 8-year-old boy who met 6 out of 8 criteria.

Malaria and tuberculosis are widespread infectious diseases in India, with high morbidity and mortality. Therefore, we present this case to create awareness about how these common infections can lead to secondary HLH. We reiterate the need to evaluate the patients for common infections to identify the etiology while suspecting HLH.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Janka G. Hemophagocytic lymphohistiocytosis: When the immune system runs amok. Klin Padiatr 2009;221:278-85.  Back to cited text no. 1
DomInguez-Pinilla N, Baro-Fernández M, González-Granado LI. Hemophagocytic lymphohistiocytosis secondary to Epstein Barr virus and leishmania co-infection in a toddler. J Postgrad Med 2015;61:44-5.  Back to cited text no. 2
Halfon P, Retornaz F, Mathieu D, Helbert T, Philibert P, Pégliasco H. Virus-associated hemophagocytic syndrome related to acute CMV and HBV sexual co-infection: A case report. J Clin Virol 2009;46:189-91.  Back to cited text no. 3
Pinto-Patarroyo GP, Rytting ME, Vierling JM, Suarez-Almazor ME. Haemophagocytic lymphohistiocytosis presenting as liver failure following Epstein-Barr and prior hepatitis A infections. BMJ Case Rep 2013;2013. pii: Bcr2013008979.  Back to cited text no. 4
Mehta RS, Smith RE. Hemophagocytic lymphohistiocytosis (HLH): A review of literature. Med Oncol 2013;30:740.  Back to cited text no. 5

Correspondence Address:
Dr. Varuna Mallya
Department of Pathology, Maulana Azad Medical College, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.200033

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