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Year : 2015  |  Volume : 8  |  Issue : 4  |  Page : 511-512  

Hemophagocytic lymphohistiocytosis and fever of unknown origin

Hainan Medical University, China; Faculty of Medicine, University of Nis, Serbia; Public Health, Joseph Ayobabalola University, Nigeria; Surin Rajabhat University, Thailand

Date of Web Publication14-Jul-2015

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Viroj Wiwanitkit
Wiwanitkit House, Bangkhae, Bangkok

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Wiwanitkit V. Hemophagocytic lymphohistiocytosis and fever of unknown origin. Med J DY Patil Univ 2015;8:511-2

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Wiwanitkit V. Hemophagocytic lymphohistiocytosis and fever of unknown origin. Med J DY Patil Univ [serial online] 2015 [cited 2021 Mar 7];8:511-2. Available from:

The present publication on "A case of hemophagocytic lymphohistiocytosis presenting as pyrexia of unknown [1]" is very interesting. [1] The difficulty in diagnosis of a rare syndrome is the interesting point in the commented clinical report. [1] In fact, hemophagocytic lymphohistiocytosis is an important hemophagocytic syndrome (HPS). [2] It can be seen in both adults and children. [3] The syndrome can be described as "systemic proliferation of benign hemophagocytic cells of the monocyte-macrophage-histiocyte lineage, associated with fever, cytopenias, hepatosplenomegaly, lymphadenopathy, and coagulopathy." [2],[3] There are two forms of hemophagocytic lymphohistiocytosis; (a) the common form in infants, known as "familial hemophagocytic lymphohistiocytosis" and (b) the form that can be seen at any age group, known as "reactive HPS". [3] Since it is not a common problem, diagnosis is sometimes very difficult. As noted by Favara, "diagnostic criteria include idiopathic fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and the presence of hemophagocytosis. The surgical and autopsy pathology features infiltrates composed of lymphocytes and ordinary, but activated, histiocytes and hemophagocytosis." [2] The important differential diagnoses of hemophagocytic lymphohistiocytosis included other conditions that can present with a HPS (such as "malignant histiocytosis, X-linked lymphoproliferative disorder, congenital immunodeficiency states, the accelerated phase of Chediak-Higashi syndrome, and cytophagic histiocytic panniculitis"). [2]

As noted, fever is an important presentation of hemophagocytic lymphohistiocytosis. Sometimes, it might be the only one chief complaint of the patient. In that case, the diagnosis can be delayed. The situation of fever of unknown origin can be expected (as seen in the present commented publication). [1] As noted by Antoon et al., hemophagocytic lymphohistiocytosis has to be included in differential diagnosis for coping with the problem of fever of unknown origin. [4] An interesting similar case study was published from Malaysia by Fadilah et al. [5] Fadilah et al. reported "a patient with unexplained fever in which a final diagnosis of HPS was established in a bone marrow study." [5] Fadilah et al. noted that "the hallmark of HPS is the accumulation of activated macrophages that engulf hematopoietic cells in the reticuloendothelial system" and concluded that "HPS should be included in the differential diagnosis of pyrexia of unknown origin." [5] Another interesting case is from Australia. [6] This case is the syndrome detected in a children. [6] Gilchrist et al. reported "a 5-month-old infant presented with a short history of fever of unknown origin [6] " In this case, the boy had only "a resting tachycardia during periods of normal temperature, and pancytopenia." [6] Gilchrist et al. concluded that the syndrome should be considered in any patients "with fever, splenomegaly and cytopenia of at least two cell lines." [6]

It is no doubt that the concern on the problem is the key point for getting the final diagnosis. It seems that the early diagnosis is needed and the diagnosis is mainly by bone marrow examination. However, since the bone marrow examination required invasive specimen collection procedure, it is the controversial issue to make an invasive approach for management of case with fever of unknown origin versus the basic medical concept, "first do no harm." The bone marrow study should be selected in case of fever of unknown origin accompanied with unexplained cytopenia. [7] The use of new less invasive laboratory tests such as ferritin and soluble interleukin-2-receptor should be used if available. [7]

  References Top

Madhavan I, Nair M, Krishnankutty PK, Andrews MA. A case of hemophagocytic lymphohistiocytosis presenting as pyrexia of unknown origin. Med J DY Patil Univ 2015;8:508-12.  Back to cited text no. 1
  Medknow Journal  
Favara BE. Hemophagocytic lymphohistiocytosis: A hemophagocytic syndrome. Semin Diagn Pathol 1992;9:63-74.  Back to cited text no. 2
Tsuda H. Hemophagocytic syndrome (HPS) in children and adults. Int J Hematol 1997;65:215-26.  Back to cited text no. 3
Antoon JW, Knudson-Johnson M, Lister WM. Diagnostic approach to fever of unknown origin. Clin Pediatr (Phila) 2012;51:1091-4.  Back to cited text no. 4
Fadilah SA, Raymond AA, Leong CF, Cheong SK. Haemophagocytic syndrome presenting as pyrexia of unknown origin. Med J Malaysia 2006;61:91-3.  Back to cited text no. 5
Gilchrist M, Wong M, Mansour A, Isaacs D. An unusual cause of fever. J Paediatr Child Health 2012;48:1039-42.  Back to cited text no. 6
Rademacher C, Hartmann D, Spiethoff A, Jakobs R. Ferritin and soluble interleukin-2-receptor in the diagnosis of fever of unknown origin. Dtsch Med Wochenschr 2014;139:23-7.  Back to cited text no. 7


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