Hemophagocytic lymphohistiocytosis: an unusual complication in Orientia tsutsugamushi disease (scrub typhus).

Abstract

BackgroundHemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of Orientia tsutsugamushi disease (scrub typhus).MethodsHere 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.ResultsAll 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.ConclusionWe 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.

Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry

“…Cases with no evidence of familial recurrence have been called “secondary,” but we prefer to call them “sporadic.” For instance, HLH can develop as a complication of juvenile idiopathic arthritis (these cases have been called macrophage activation syndrome [MAS]) or during immunosuppressive therapies for cancer or autoimmune disorders, 4 , 16 although it can occur also in the course of protozoal (leishmaniasis and malaria), rickettsial, 17 or mycobacterial infection. In a proportion of cases of sporadic HLH, one finds cytocidal defects similar (although less profound) to those seen in patients with FHL.…”

Hemophagocytic Syndrome Associated with Scrub Typhus: A Case Report from North East India

“…This hypothesis has been further substantiated by the observation of increased serum levels of IFN-γ, M-CSF and TNF-α in patient with scrub typhus in several studies [13]. In a review by Basheer et al [9] 21 cases of haemophagocytic syndrome associated with scrub typhus was described out of which 14 were of mild to moderate nature.…”

“…However, it can also invade underlying tissues such as smooth muscle cells, perivascular macrophages, and monocytes. Consequently, widespread vasculitis or perivasculitis is the hallmark pathophysiologic mechanism implicated in Multiorgan Dysfunction Syndrome (MODS) in patients with severe infection [9]. Our patient was diagnosed to have scrub typhus by the positivity in the immunochromatographic card test for detection of IgM antibodies to Orientia tsutsugamushi.…”

Hemophagocytic Lymphohistiocytosis in Adults: Low Incidence of Primary Neoplasm as a Trigger in a Case Series From Turkey

“… 1 Its primary form generally occurs due to an underlying genetic immune dysfunction and primarily affects infants and young children, whereas the secondary form occurs due to various underlying conditions ranging from viral infections to autoimmune diseases and cancers in adults. 2 , 3 …”