Distinct Laboratory and Clinical Features of Secondary Hemophagocytic Lymphohistiocytosis in Pediatric Visceral Leishmaniasis: A Retrospective Analysis of 127 Children in Andalusia, Spain (2004-2019).

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.

Calprotectina fecal como apoyo al diagnóstico en la alergia a las proteínas de leche de vaca no IgE mediada / Faecal calprotectin as an aid to the diagnosis of non-IgE mediated cow's milk protein allergy

INTRODUCCIÓN: El objetivo del estudio es evaluar la utilidad de la calprotectina fecal (CPF) en lactantes con sospecha de alergia a las proteínas de leche de vaca (APLV) no IgE mediada tanto para el diagnóstico como para predecir la respuesta clínica a la supresión láctea. PACIENTES Y MÉTODOS: Estudio prospectivo, de un año de duración, incluyendo 82 lactantes entre 1-12 meses en el Área Este de Málaga-Axarquía. De ellos: 40 se diagnostican de APLV no IgE mediada (síntomas compatibles y respuesta positiva a la supresión láctea), 12 no se confirma APLV y además 30 como grupo control. Se determina CPF al diagnóstico, al mes y a los 3 meses. El análisis estadístico realizado fue ANOVA para medidas repetidas, regresión logística nominal y curvas ROC utilizando los programas SPSS 20 y Medcalc. RESULTADOS: Se analizan diferencias entre los grupos y se objetiva relación estadísticamente significativa entre cifras elevadas de CPF y padecer APLV (p <0,0001). También se constata relación estadísticamente significativa entre cifras de CPF al diagnóstico, al mes y a los 3 meses (p < 0,001). Finalmente se realiza una curva ROC entre cifras de CPF y diagnóstico de APLV resultando una área bajo la curva de 0,89 y siendo 138μg/g el mejor nivel de corte. Sin embargo, para predecir respuesta clínica este valor es únicamente de 0,68. CONCLUSIONES: Cifras de CPF inferiores a 138μg/g podrían ser útiles para descartar el diagnóstico de APLV no IgE mediada. La CPF no es un buen test para predecir respuesta clínica a la exclusión láctea

INTRODUCTION: The aim of the study was to assess the use of faecal calprotectin (FCP) in infants with signs and symptoms of non-IgE-mediated cow's milk protein allergy (CMA) for both diagnosis and prediction of clinical response at the time of withdrawal of milk proteins. PATIENTS AND METHODS: A one year prospective study was conducted on 82 infants between 1 and 12 months of age in the Eastern area of Málaga-Axarquía, of whom 40 of them had been diagnosed with non-IgE-mediated CMA (with suggestive symptoms and positive response to milk withdrawal), 12 not diagnosed with CMA, and 30 of them were the control group. FCP was measured at three different times: time of diagnosis, and one and three months later. ANOVA for repeated measures, nominal logistic regression and ROC curves were prepared using the SPSS.20 package and Medcalc. RESULTS: Differences between diagnostic and control groups were assessed: there was a statistically significant relationship (p<.0001) between high FCP levels and infants suffering CMA, as well as the levels at time of diagnosis, 1 and 3 months (p <.001). A ROC curve was constructed between FCP levels and diagnosis of CMA, with 138 ug/g, with the best cut-off being with an area under the curve of 0.89. However, it is only 0.68 to predict a clinical response. CONCLUSIONS: FCP levels lower than 138ug/g could be useful to rule out non-IgE-mediated CMA diagnosis. Calprotectin is not a good test to predict clinical response to milk withdrawal

[Faecal calprotectin as an aid to the diagnosis of non-IgE mediated cow's milk protein allergy]. / Calprotectina fecal como apoyo al diagnóstico en la alergia a las proteínas de leche de vaca no IgE mediada.

INTRODUCTION: The aim of the study was to assess the use of faecal calprotectin (FCP) in infants with signs and symptoms of non-IgE-mediated cow's milk protein allergy (CMA) for both diagnosis and prediction of clinical response at the time of withdrawal of milk proteins. PATIENTS AND METHODS: A one year prospective study was conducted on 82 infants between 1 and 12 months of age in the Eastern area of Málaga-Axarquía, of whom 40 of them had been diagnosed with non-IgE-mediated CMA (with suggestive symptoms and positive response to milk withdrawal), 12 not diagnosed with CMA, and 30 of them were the control group. FCP was measured at three different times: time of diagnosis, and one and three months later. ANOVA for repeated measures, nominal logistic regression and ROC curves were prepared using the SPSS.20 package and Medcalc. RESULTS: Differences between diagnostic and control groups were assessed: there was a statistically significant relationship (p<.0001) between high FCP levels and infants suffering CMA, as well as the levels at time of diagnosis, 1 and 3 months (p <.001). A ROC curve was constructed between FCP levels and diagnosis of CMA, with 138 ug/g, with the best cut-off being with an area under the curve of 0.89. However, it is only 0.68 to predict a clinical response. CONCLUSIONS: FCP levels lower than 138ug/g could be useful to rule out non-IgE-mediated CMA diagnosis. Calprotectin is not a good test to predict clinical response to milk withdrawal.