title: Hemophagocytic Lymphohistiocytosis: an Unusual Complication of Orientia tsutsugamushi Disease (Scrub Typhus).
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of Orientia tsutsugamushi disease (scrub typhus).
  
  
  METHODS
  Here we describe the clinicopathological features, laboratory parameters, management, and outcome of three adult patients (1 female, 2 males) with scrub typhus associated HLH from a tertiary center. A brief and concise review of international literature on the topic was also added.
  
  
  RESULTS
  All three patients satisfied the HLH-2004 diagnostic criteria; one had multi-organ dysfunction with very high ferritin level (>30,000 ng/ml), and all had a dramatic recovery following doxycyclin therapy. Literature review from January 1990 to March 2014 revealed that scrub typhus associated HLH were reported in 21 patients, mostly from the scrub endemic countries of the world. These included 11 females and 10 males with a mean age of 35 years (range; 8 months to 81 years). Fifteen of 17 patients (where data were available) had a favorable outcome following early serological diagnosis and initiation of definitive antibiotic therapy with (N=6) or without (N=9) immunosuppressive/immunomodulator therapy. Mutation analysis for primary HLH was performed in one patient only, and HLH-2004 protocol was used in two patients.
  
  
  CONCLUSIONS
  We suggest that HLH should be considered in severe cases of scrub typhus especially if associated with cytopenia (s), liver dysfunction, and coagulation abnormalities. Further studies are required to understand whether an immunosuppressive and/or immunomodulator therapy could be beneficial in those patients who remain unresponsive to definitive antibiotic therapy.
authors.affiliation: Department of General Medicine, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Aneesh
authors.initials: A
authors.lastname: Basheer
authors.affiliation: Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Somanath
authors.initials: S
authors.lastname: Padhi
authors.affiliation: Department of Gastroenterology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Vinoth
authors.initials: V
authors.lastname: Boopathy
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Saumyaranjan
authors.initials: S
authors.lastname: Mallick
authors.affiliation: Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Shashikala
authors.initials: S
authors.lastname: Nair
authors.affiliation: Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Renu G'Boy
authors.initials: RG
authors.lastname: Varghese
authors.affiliation: Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Reba
authors.initials: R
authors.lastname: Kanungo