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Year : 2021  |  Volume : 65  |  Issue : 1  |  Page : 85-86  

Scrub typhus with secondary hemophagocytic lymphohistiocytosis in a 3-month-old child from a tertiary care hospital of Odisha

1 Assistant Professor, Department of Pediatrics, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneshwar, Odisha, India
2 Junior Resident, Department of Pediatrics, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneshwar, Odisha, India

Date of Submission24-Jul-2020
Date of Decision08-Oct-2020
Date of Acceptance31-Dec-2020
Date of Web Publication20-Mar-2021

Correspondence Address:
Jyoti Ranjan Behera
Department of Pediatrics, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneshwar - 751 024, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijph.IJPH_565_20

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Scrub typhus is one of the re-emerging infectious diseases in India, whereas hemophagocytic lymphohistiocytosis (HLH) results from an uncontrolled and ineffective hyperinflammatory response to a variety of triggers. HLH is categorized into primary and secondary type with infection being one of the leading causes of secondary HLH. Here, we report a case of 3-month-old girl diagnosed with scrub typhus associated with secondary HLH as both the age of presentation and the association are rarely reported in literature.

Keywords: Hemophagocytic lymphohistiocytosis, infant, scrub typhus

How to cite this article:
Sahu SK, Behera JR, Yadav SK. Scrub typhus with secondary hemophagocytic lymphohistiocytosis in a 3-month-old child from a tertiary care hospital of Odisha. Indian J Public Health 2021;65:85-6

How to cite this URL:
Sahu SK, Behera JR, Yadav SK. Scrub typhus with secondary hemophagocytic lymphohistiocytosis in a 3-month-old child from a tertiary care hospital of Odisha. Indian J Public Health [serial online] 2021 [cited 2021 Dec 8];65:85-6. Available from:

   Introduction Top

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi and transmitted through the bite of the chigger of trombiculid mite.[1] Single painless eschar with an erythematous rim may be found at the bite site. Clinical manifestations are nonspecific including fever, skin rash, myalgia, organomegaly, and lymphadenopathy. Common complications of scrub typhus are meningoencephalitis, pneumonitis, acute renal failure, etc. Hemophagocytic lymphohistiocytosis (HLH) is a rare complication. After extensive literature search, we found the mentioned case to be interesting, as very few cases of HLH associated with scrub typhus in infants have been reported.[2],[3]

   Case Report Top

A 3-month-old female child was referred with high-grade continuous fever and nonbilious, nonprojectile vomiting 3–4 episodes per day for the past 10 days and 8–10 episodes of loose stools for 8 days with no history of cold, cough, increased frequency of urination, rashes, or seizures. On examination, the child was irritable with pallor and bilateral cervical lymphadenopathy with normal vitals. There was hepatomegaly with no other significant systemic finding.

The child was started on intravenous antibiotics after sending necessary investigations with a provisional diagnosis of sepsis. Investigations at admission revealed anemia, leuocytosis with lymphocytic predominance, thrombocytopenia, and high C-reactive protein. Tests for malaria, typhoid, and dengue were negative. Serum electrolytes and renal function tests were within the normal range. Liver function test revealed mild transaminitis and hypoalbuminemia. As the initial investigation parameters pointing toward scrub typhus and considering its high endemicity, a test for scrub typhus was sent which was positive (IgM –0.51).

In view of persistent fever, bicytopenia and splenomegaly possibility of HLH was considered and serum ferritin and triglyceride were sent which were found to be elevated. However, no evidence of hemophagocytosis was there on bone marrow aspiration. Hence, she was diagnosed as a case of scrub typhus with secondary HLH as per the revised HLH-2004 protocol satisfying five of eight diagnostic criteria.[4]

The child was started on oral doxycycline at a dose of 5 mg/kg/day in two divided doses. After 48 h of initiation of doxycycline, the child was afebrile with improvement in clinical and biochemical parameters. She was discharged in a stable condition after 7 days of therapy with doxycycline. On routine follow-up after 2 weeks and 6 months of discharge, the child was healthy and doing fine.

   Discussion Top

Scrub typhus is a reemerging rickettsial disease in India, especially Odisha presenting as an acute febrile illness with manifestation ranging from mild disease to fatal complications.[5] Although the presence of an eschar clinches the diagnosis of scrub typhus, its presence varies from 20% to 87%.[6] Vascuitis involving multiple organ system is the basic underlying pathology of scrub typhus.[6] Due to nonspecific clinical features, a high index of suspicion and correlation with laboratory findings is essential for early initiation of therapy to prevent undue complications and mortality. The delay in diagnosis and management may trigger activation of the immune system.

HLH is a severe, potentially life-threatening entity manifesting due to uncontrolled proliferation and activation of T-lymphocytes leading to cytokine storm. It is categorized into two types: primary or familial and secondary. Common presentations are unremitting fever, hepatosplenomegaly, cytopenias, and hemophagocytosis by activated macrophages along with hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia.[7] Histiocytes with ingested blood elements (Hamophagocytes) are one of the hallmarks of HLH found on bone marrow aspiration but may not be always present as in our case.

The cytokine storm associated with the immune response to O. tsutsugamushi is the basic pathology in the development of HLH as a complication of scrub typhus.[8] On activation of the cytokine cascade, the immune system loses its regulatory function leading to HLH. The rare primary form usually presents in infancy requiring multiple immunosuppressants and having high fatality with homologous stem cell transplantation being the definitive treatment. Unlike the primary type which is genetic in origin, secondary HLH is usually associated with several underlying diseases (infectious, rheumatological, malignancy, etc.,) and has a better prognosis.[8] Infections can also unmask familial HLH; however, its recurrent nature and fulminant course distinguish it from the secondary form. As per a systematic review published in 2018, only 13 pediatric cases of HLH associated with scrub typhus were reported in literature, of which only three were infants:[9] one was 2-month-old from India[2] and the other two were 8 months' old from China and South Korea, respectively. The infant from China succumbed due to intracranial hemorrhage, while the other two recovered. Another case from India published in 2019 was 8 month old who expired due to hepatic dysfunction and disseminated intravascular coagulation.[3] Apart from our case, only two cases of HLH associated with infant scrub typhus mentioned above are reported from India.

   Conclusion Top

Unremitting fever with clinical deterioration even in a case of diagnosed infectious etiology when associated with splenomegaly and bicytopenia should always raise a suspicion of HLH and relevant investigation should be done for its diagnosis. Although it usually gets resolved on treating the underlying disease as described in our case, sometimes, it may become life-threatening requiring treatment with steroid, cyclosporine, etoposide, etc.[10] Hence, awareness of HLH as a complication of infectious disease is of immense prognostic importance.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Rathi N, Rathi A. Rickettsial infections: Indian perspective. Indian Pediatr 2010;47:157-64.  Back to cited text no. 1
Pazhaniyandi S, Lenin R, Sivathanu S. Hemophagocytic lymphohistiocytosis with a leukemoid reaction in an infant with scrub typhus. J Infect Public Health 2015;8:626-9.  Back to cited text no. 2
Agrwal S, Dabas A, Mantan M, Yadav S. Hemophagocytic lymphohistiocytosis with neurological manifestations in an infant with scrub typhus: A rare fatal occurrence. Trop Doct 2019;49:52-3.  Back to cited text no. 3
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-31.  Back to cited text no. 4
Bal M, Mohanta MP, Sahu S, Dwibedi B, Pati S, Ranjit M. Profile of pediatric scrub typhus in Odisha, India. Indian Pediatr 2019;56:304-6.  Back to cited text no. 5
Ogawa M, Hagiwara T, Kishimoto T, Shiga S, Yoshida Y, Furuya Y, et al. Scrub typhus in Japan: Epidemiology and clinical features of cases reported in 1998. Am J Trop Med Hyg 2002;67:162-5.  Back to cited text no. 6
Chi WC, Huang JJ, Sung JM, Lan RR, Ko WC, Chen FF. Scrub typhus associated with multiorgan failure: A case report. Scand J Infect Dis 1997;29:634-5.  Back to cited text no. 7
Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med 2012;63:233-46.  Back to cited text no. 8
Naoi T, Morita M, Kawakami T, Fujimoto S. Hemophagocytic Lymphohistiocytosis Associated with Scrub Typhus: Systematic Review and Comparison between Pediatric and Adult Cases. Trop Med Infect Dis 2018;3:19.  Back to cited text no. 9
Kwon HJ, Yoo IH, Lee JW, Chung NG, Cho B, Kim HK, et al. Life-threatening scrub typhus with hemophagocytosis and acute respiratory distress syndrome in an infant. J Trop Pediatr 2013;59:67-9.  Back to cited text no. 10


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