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Year : 2010  |  Volume : 56  |  Issue : 4  |  Page : 301-302

Hemophagocytosis in scrub typhus

1 Division of Medicine, Lyell McEwin Hospital, South Australia, Australia
2 Department of Microbiology, Kasturba Medical College, Manipal University, Manipal, India
3 Department of Microbiology, P.D. Hinduja National Hospital & Medical Research Centre, Mumbai, India
4 Department of Critical Care, Bombay Institute of Medical Sciences, Mumbai, India

Date of Submission03-Feb-2010
Date of Decision24-Apr-2010
Date of Acceptance16-Jun-2010
Date of Web Publication7-Oct-2010

Correspondence Address:
R Valsalan
Division of Medicine, Lyell McEwin Hospital, South Australia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0022-3859.70949

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How to cite this article:
Valsalan R, Kosaraju K, Sohanlal T, Prem Kumar P S. Hemophagocytosis in scrub typhus. J Postgrad Med 2010;56:301-2

How to cite this URL:
Valsalan R, Kosaraju K, Sohanlal T, Prem Kumar P S. Hemophagocytosis in scrub typhus. J Postgrad Med [serial online] 2010 [cited 2023 Jun 5];56:301-2. Available from:

Hemophagocytosis syndrome or hemophagocytic lymphohistiocytosis (HLH) is a rare hematological disorder characterized by febrile illness, cytopenia, lymphadenopathy and hepatosplenomegaly and hyperferritinemia. [1] Phagocytosis of blood cells and their precursors is a hallmark of hemophagocytic syndromes (HPS). Hemophagocytosis is achieved mostly by monocytes and macrophages, and nitro-blue tetrazolium reduction by monocytes from patients with HLH is approximately six times that of control monocytes. Excessive activation of monocytes in HLH may be due to stimulation by high levels of activating cytokines. High levels of interferon-γ (IFN-γ), soluble interleukin-2 receptor, tumor necrosis factor-α (TNF-α), interleukin-1, and interleukin-6 have been demonstrated, suggesting the elaboration of activating cytokines by T-helper cells or it can also result from poorly regulated or inappropriate Th1 responses to intracellular pathogens. The details of immunological protective mechanisms against rickettsial infections, including activation of cytokines, are not fully understood, but macrophages and T-cells are believed to play an important role in protection against rickettsial infections and appearance of HPS. HPS is caused by a number of viruses, including Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus-6 as well as collagen-vascular diseases and malignancies, particularly T-cell lymphomas [2] . Hemophagocytosis causing pancytopenia is a medical emergency and is fatal despite aggressive treatment. We report a 22-year-old barber who came with acute febrile illness of 10 days duration. On examination he was pale and febrile (104Ί F). Non-tender small discrete lymph nodes were seen in the cervical region. Hepatosplenomegaly was present on abdominal examination. Cardiovascular, respiratory and central nervous system examinations were unremarkable. Complete blood picture revealed hemoglobin- 8.5 gm%, reticulocyte count 0.16%, WBC count 700 cells/mm 3 , shift to left with neutrophils 34%, lymphocytes 62%, monocytes 4%, platelet count 12,000 cells/mm 3 and ESRErythrocyte sedimentation rate) 120 mm/h. Renal, liver functions, X-ray and computed tomography reports of thorax were within normal limits. Bactec blood cultures were sterile. Widal test, Standard agglutination test for  Brucella More Details, ANA global and profile, HIV (Human Immunodeficiency Virus) ELISA (Enzyme Linked Immunosorbent Assay), ELISA for Hepatitis B surface antigen and antibodies to Hepatitis-C virus were negative. Serum ferritin was >2000 microgram/L. Patient was empirically started on Piperacillin-Tazobactum and Teicoplanin for febrile neutropenia. Bone marrow aspiration showed hypercellular marrow with marked suppression of erythropoeisis and megakaryopoeisis with increased leucopoiesis, toxic vacoulation and hemophagocytosis [Figure 1] and [Figure 2]. The fever continued to spike despite therapy. Three days after the antibiotics, patient developed maculo--papular rash involving the extremities, palms and soles but sparing facial region [Figure 3]. The antibiotics were stopped suspecting drug-induced rash. He was empirically started on Doxycycline 100 mg twice daily. Meanwhile, Weil-Felix test showed titers: OX-19: 40, OX-2: 160, OX-K: 320. After 48 h of starting Doxycycline, patient showed a striking response with fever touching the baseline. He became afebrile and the rash started disappearing. Ten days following anti-rickettsial therapy, a repeat Weil Felix test demonstrated increasing titers: OX-2 and OX-19- negative OX K 1: 320 and blood picture showed hemoglobin- 9.8 gm%, reticulocyte count 9%, WBC count 10,500 cells/mm 3 , platelet count1,74,000 cells/mm 3 and ESR 60 mm/h. IgM(Enzyme Linked Immunosorbent Serum Assay) ELISA for scrub typhus was positive with OD value (optical density) - 3.022 and cut-off OD - 0.225 (Scrub Typhus IgM ELISA-Inbios International). Scrub typhus is usually endemic in South East Asia, northern Australia and pacific islands. In India it has been reported from Himalayan regions, Haryana and southern India. [3] Scrub typhus presents as acute febrile illness which generally causes nonspecific symptoms and signs. The necrotic eschar is the pathognomonic feature, but is quite rare in the South East Asian population. [4] Thrombocytopenia has been reported in a few cases and is the result of consumption of platelets due to disseminated intravascular coagulation. [5] Our patient had all the features favoring HPS. The classical eschar noted in scrub typhus was not seen and could probably be due to the bite by the larval stage of mite. [6] Indirect immunofluorescence (IFA) is the gold standard test for scrub typhus, but ELISA is equally specific as IFA and more sensitive in the early phase of infection. [7] Our patient had high titers initially and the titers remained high even after one week which confirms scrub typhus infection. Mortality rates of untreated patients have ranged from 0-30%. [6] The prognosis of scrub typhus associated with HPS is unknown. In our patient, there was a clear association between scrub typhus and hemophagocytosis as was shown by the correct diagnosis of scrub typhus and the disappearance of the hemophagocytic phenomenon after successful treatment with specific chemotherapy. Pancytopenia associated with scrub typhus has been rarely reported in the medical literature;. [8] We believe it is important to consider scrub typhus as an important cause of bone marrow HPS in endemic areas like India. It is always beneficial to start anti-rickettsial chemotherapy empirically in these patients as the diagnostic facilities in most places are not readily available.
Figure 1: Bone marrow aspirate film showing myeloid precursors with dyspoiesis and toxic vacuolation (Leishman stain, ×1000)

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Figure 2: Bone marrow aspirate film showing hemophagocytosis (Leishman stain ×1000)

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Figure 3: Photograph showing maculopapular rash on the lower extremeties

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 :: References Top

1.Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C. Infections associated with haemophagocytic syndrome. Lancet Infect Dis 2007;7:814-22.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Iwasaki H, Hashimoto K, Takada N, Nakayama T, Ueda T, Nakamura T. Fulminant Rickettsiatsutsugamushi infection associated with haemophagocytic syndrome. Lancet 1994;343:1236.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Mathai E, Lloyd G, Cherian T, Abraham OC, Cherian AM. Serological evidence for the continued presence of human rickettsioses in southern India. Ann Trop Med Parasitol 2001;95:395-8.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Mahajan SK. Scrub typhus. J Assoc Physicians India 2005;53:954-8.  Back to cited text no. 4  [PUBMED]    
5.Rickettsial Diseases. In: Kas per DL, Fauci AS, LongoDL, Braunwald E, Hauser SL, Jameson JL, Editors. Harrison's Principles of Internal medicine 17th ed. New York: Mc Graw Hill; 2008. p. 1059-67.  Back to cited text no. 5      
6.Chaudhry D, Garg A, Singh I, Tandon C, Saini R. Rickettsial diseases in Haryana: not an uncommon entity. J Assoc Physicians India 2009;57:334-7.  Back to cited text no. 6  [PUBMED]    
7.Varghese GM, Abraham OC, Mathai D, Thomas K, Aaron R, Kavitha ML, et al. Scrub typhus among hospitalised patients with febrile illness in South India: magnitude and clinical predictors. J Infect 2006;52:56-60.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Premaratna R, Williams HS, Chandrasena TG, Rajapakse RP, Kularatna SA, de Silva HJ. Unusual pancytopenia secondary to haemophagocytosis syndrome in rickettsioses.Trans R Soc Trop Med Hyg 2009;103:961-3.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  


  [Figure 1], [Figure 2], [Figure 3]

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