Haemophagocytic lymphohistiocytosis complicating visceral leishmaniasis in the UK: a case for detailed travel history, a high index of suspicion and timely diagnostics

Abstract

A 4-month-old male infant presented acutely unwell with fever. He was initially treated for sepsis but failed to improve with IV broad spectrum antibiotics. Haemophagocytic lymphohistiocytosis (HLH) was diagnosed due to his fever, pancytopenia, splenomegaly, hypertriglyceridaemia, hypofibrinogenaemia and significant hyperferritinaemia. An array of differentials for HLH including both immunological and infectious causes were considered and excluded. He had travelled to Madrid, and hence visceral leishmaniasis (VL) was suspected, but was not confirmed on the initial bone marrow aspirate (BMA) microscopy or culture. He improved with empirical treatment with dexamethasone and liposomal amphotericin B. VL was later confirmed on BMA PCR. He made a good recovery and remained well at 12 month follow-up. Non-endemic countries need rapid and sensitive VL diagnostics. A thorough travel history and high clinical index of suspicion are necessary to avoid the pitfall of treatment with intense immunosuppression recommended in treatment guidelines for HLH.

Clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis induced by Leishmania infantum infection

“…Leishmania infection is a well-known cause of infection associated HLH [4,[8][9][10][11]. It was reported that about 25.77% of patients with adult hemophagocytic syndrome were induced by Leishmania infection [12].…”

Non-Endemic Leishmaniases Reported Globally in Humans between 2000 and 2021—A Comprehensive Review

“…Outside the European region, cases were diagnosed in Australia (n = 10, [28,36,45,57,64,211,251]), Kenya (n = 16, [16]), Kuwait (n = 36, [19]), Saudi Arabia (n = 35, [259]) and the USA (n = 8, [21,43,49,51,55,60,215]). The predominance of cases from the Mediterranean region likely reflects more intensive travel to southern Europe, especially in people from countries where most cases were diagnosed such as France (n = 107, [6,18,61,68]), the UK (n = 80, [22,38,50,52,58,201,204,207,210,214,219,252,253,261]) and Germany (n = 68, [8,20,25,27,33,35,37,40,44,46,47,53,56,…”

“…Similarly, laboratory findings of 125 patients translated the natural history of the disease well known in endemic countries [286]: most patients had single or multiple lineage cytopenias, while elevation of liver enzymes and renal failure were less commonly described (Table 2). In 22 patients, laboratory findings were consistent with hemophagocytic lymphohistiocytosis (HLH) [17,26,44,49,50,52,59,68,206,214]. Although the association between leishmaniasis and HLH seems to be a rare finding in the pediatric population of endemic areas [288], cases occurring in infants have been reported in imported cases [44], so in children under 2 years of age traveling to endemic areas, leishmaniasis should be included in the differential diagnosis of secondary HLH.…”