Distinct Laboratory and Clinical Features of Secondary Hemophagocytic Lymphohistiocytosis in Pediatric Visceral Leishmaniasis

Abstract

Background: Visceral leishmaniasis (VL) is an endemic in Southern Europe. However, details regarding disease burden, clinical presentations, laboratory markers, management and outcome in children are scarce. Methods: Medical records of children (<14 years) admitted with VL to 10 pediatric units in Andalusia (2004–2019) were retrospectively reviewed. VL diagnosis was based on clinical presentation, serology, microscopy and molecular methods. Diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was established using the hemophagocytic lymphohistiocytosis-2004 criteria. Results: A total of 127 patients were identified. Median age was 14.5 months; the main clinical presentations were fever and splenomegaly (95.3% each). Cytopenias were the most common laboratory abnormalities. Diagnostics as well as treatment regimens varied over time and the participating centers. Liposomal amphotericin B was prescribed in 97.6%; relapses as well as adverse events were rarely observed (3.1% each). Thirty-seven patients, diagnosed with sHLH required longer hospital admission (P = 0.001), an increased number of platelet (P < 0.006) and red blood cell (P = 0.0001) transfusions and pediatric intensive care unit admission (P = 0.007). Monocytopenia (P = 0.011) and high C-reactive protein levels (P = 0.031), variables not included in the hemophagocytic lymphohistiocytosis-2004 criteria, were associated with sHLH. One patient deceased in the context of the Leishmania infection. Conclusions: We report data on the largest pediatric VL cohort from Europe, commonly associated with sHLH. Raised C-reactive protein levels and monocytopenia appear to be associated with sHLH. The latter may help to identify these patients and to guide decisions regarding need of additional supportive clinical care and immunomodulatory therapies. The observed high rate of heterogeneity in terms of diagnosis and management warrants the establishment of appropriate guidelines.

Visceral leishmaniasis‐associated haemophagocytic lymphohistiocytosis

“…VL is a chronic infection caused by an intracellular protozoan parasite. It usually spread by sandflies from a domestic or a wild animal 1–4 . It is more common in tropical and subtropical areas and is more common in children <5 years of age 2,4 .…”

“…It usually spread by sandflies from a domestic or a wild animal 1–4 . It is more common in tropical and subtropical areas and is more common in children <5 years of age 2,4 . It is estimated that about 50 000–90 000 new cases of VL occur world‐wide annually, with only <50% reported to World Health Organization (WHO).…”

“…It affects people with low socio‐economic state and is associated with malnutrition and immunodeficiency 5 . The main presenting clinical and biochemical features of VL in children include prolonged fever, weight loss, splenomegaly and pancytopenia 1,2,4 . Delayed diagnosis and inadequate treatment can result in death in almost all cases if left untreated 5 …”

“…HLH is a life‐threatening cytokine storm that can be triggered by infections like VL 1,4 . VL‐associated‐HLH is rare in children but potentially life threatening with about less than 100 cases reported in the literature to date 1,4 . Median age of presentation was about 2 years 1 …”

Takayasu’s arteritis in an adolescent with fever of unknown origin: the contribution of PET–CT in the diagnosis

“…FUO can be a diagnostic challenge due to the many causes involved (table 2). In children, infections are the main aetiology (59% bacterial; 7% viral, especially Ebstein-Barr virus infection; and 10% parasitic, mainly visceral leishmaniosis in low-income countries but also in Spain) 3 4. Certain infections as tuberculosis are important in endemic areas.…”