Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study

Abstract

Background Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation. We aimed to describe the clinical and laboratory findings of HLH patients secondary to Visceral leishmaniasis (VL) and their treatment outcome during a 4-year follow-up period compared to primary HLH. Method Forty children with primary HLH confirmed by genetic study and 20 children with HLH secondary to VL confirmed by a blood or bone marrow polymerase chain reaction from 2014 to 2018 in Shiraz, Fars province, Southern Iran, were enrolled. Results The median age at diagnosis was 11.5 months (range 1–170), and 56.7% were male. Fever and splenomegaly were the most frequent clinical presentations. 93.3% of the subjects had an HScore > 169, which had a good correlation with HLH-2004 criteria (r = 0.371, P = 0.004). Patients with primary HLH experienced more thrombocytopenia (P = 0.012) and higher alanine transaminase (P = 0.016), while patients with VL-associated HLH had higher ferritin (P = 0.034) and erythrocyte sedimentation rate (P = 0.011). Central nervous system (CNS) involvement occurred in 38.3% of patients. The mortality rate was higher in patients with CNS disease (61% vs. 35%, P = 0.051). The 3-yr overall survival rate was 35.9%. (24% in primary HLH and 100% in VL-associated HLH, P < 0.001). In Cox regression analysis, platelet count < 100,000/ μ l (hazard ratio 4.472, 95% confidence interval 1.324–15.107, P = 0.016) correlated with increased mortality in patients with primary HLH. Conclusion VL is a potential source of secondary HLH in regions with high endemicity. Treatment of the underlying disease in VL-associated HLH is sufficient in most cases, with no need to start etoposide-based chemotherapy.

Secondary hemophagocytic lymphohistiocytosis in children (Review)

“…Several studies ( 131 , 132 , 134 , 206 ) have reported complete response of Leishmania-associated HLH to amphotericin B therapy +/- steroids, with an excellent prognosis [3 year overall survival rate 24% in pHLH vs. 100% in visceral leishmaniasis-associated HLH; P<0.001; 2021 Iranian cohort of 60 children ( 133 )]. A Chinese retrospective study ( 135 ) reported good results with antiparasitic therapy associated with chemotherapy according to the HLH94 protocol in patients with visceral leishmaniosis-HLH; however, the cohort includes children and adults and it is impossible to discriminate whether treatment intensification depends on age.…”

Síndrome hemofagocítica pós-leishmaniose visceral: revisão de literatura e relato de caso

“…Dentre as parasitoses, a Leishmaniose (Leishmania spp.) é um dos principais desencadeantes (MOTTAGHIPISHEH et al, 2021).…”

“…Em relação à LHH secundária à LV, o tratamento da causa-base com as drogas de escolha pode promover a remissão completa da doença de forma eficaz e segura (SCALZONE et al, 2016;MCCLAIN, 2020;MOTTAGHIPISHEH et al, 2021).…”

Outcome and Prognostic Factors of Hemophagocytic Lymphohistiocytosis in Children: Experience From a Low- and Middle-Income Country

“…Lately, a new analytical score, the H-score, has been used for diagnosis. The Hscore significantly correlates with the HLH-2004 criteria, allowing for an effectual estimation of an individual's risk of having HLH [6][7][8]. In centers where genetic testing is not obtainable, the H-score is a IBM SPSS Statistics for Windows, version 25.0 (released 2017, IBM Corp., Armonk, NY) was used for statistical analysis, and t-test and chi-square tests were used for comparison between continuous and categorical variables.…”