title: Hemophagocytic lymphohistiocytosis: An unusual complication in disseminated Mycobacterium tuberculosis.
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of disseminated Mycobacterium tuberculosis (MTB). The clinical course of tuberculosis-associated HLH (TB-HLH) has been reported to be unpredictable.
  
  
  METHODS
  Here we describe the clinicopathological features, laboratory parameters, management, and outcome data of a patient who satisfied the 2004 diagnostic criteria for HLH secondary to disseminated MTB; we also do a systematic review of the international literature on TB-HLH. The literature review (January 1975-March 2014) found that HLH complicated the clinical course of 63 tuberculosis patients (41 males, 22 females, mean age = 45 ± 23.5 years) with a high mortality rate of 49% (31/63 died). The mean serum ferritin level (n = 44/63) was 5963 ng/mL (range 500-38,539 ng/mL); and a higher proportion (54.2%) of patients had pancytopenia at presentation. On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03-7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08-19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16-6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51-7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis. Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66-3.22, P = 0.35) did not alter the outcome in these patients.
  
  
  CONCLUSIONS
  HLH should be considered as a differential diagnosis in patients with tuberculosis who present with cytopenias, organomegaly, and coagulopathy. Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality. The utility of immunosuppressive/immunomodulator therapy lacks general concensus among treating physicians, and warrants further studies.
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 Biostatistics, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Ravichandran
authors.affiliation: Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Sahoo
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 General Medicine, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Aneesh
authors.initials: A
authors.lastname: Basheer
keywords: Antitubercular therapy; hemophagocytic lymphohistiocytosis; survival; tuberculosis