Leishmaniose visceral associada à linfo-histiocitose hemofagocítica em pacientes pediátricos: uma condição pouco conhecida e com risco de vida

Abstract

Visceral leishmaniasis (VL) is a neglected disease, endemic in several regions of Brazil, which can often be complicated by hemophagocytic lymphohistiocytosis (HLH), a potentially fatal disorder resulting from the excessive, non-malignant activation/proliferation of T lymphocytes and macrophages. We describe clinical, laboratory and therapeutic response differences in the course of the disease between patients with VL who met the HLH criteria and those who did not, admitted to a referral hospital in an endemic area in the northern region of the state of Minas Gerais. Series of six (35.2%) cases from a historical cohort of 17 children hospitalized between September 2019 and September 2024. 11/17 (64.7%) came from urban areas. Mean age of 3.7 ± 3.1 years, 12/17 (70.5%) were male. Mean weight of 16.8 ± 7.9 kg. Main signs and symptoms were fever (100%), hepatosplenomegaly (100%), mucous-cutaneous pallor (88.2%), bleeding (17.6%) and edema (5.8%). Transfusions were performed in 3/17 (17.6%) patients. All used packed red blood cells. Laboratory findings showed low levels of hemoglobin 7.82 ± 1.23 g/dL, leukocytes 3,997.64 ± 1,709.92/mm3, platelets 81,235.29 ± 31,942.38/mm3, INR 1.18 ± 0.20. Elevated levels of ferritin 786.12 ± 1,193.55 µg/dL, triglycerides 279.00 ± 169.14 mg/dL, CRP 115.04 ± 113.72 mg/L and LDH 972.52 ± 625.68. Fibrinogen 185.73 ± 109.97mg/dL, AST 149.29 ± 185.18 UI/L, AST 80.35 ± 93.80 UI/L, total bilirubin 0.69 ± 0.57 mg/dL, direct 0.48 ± 0.51/dL. Total proteins 6.89 ± 1.35 g/dL, albumin 3.44 ± 0.44 g/dL, globulins 3.44 ± 1.22 g/dL, creatinine 0.51 ± 0.17 mg/dL, urea 22.58 ± 8.30 mg/d. Rapid test for VL, positive 16/17 (94.0%). Hemophagocytosis not investigated since the rapid test, more sensitive and less invasive, was chosen. Soluble receptor dosage for IL-2, in 10/17 (58.0%). Antibiotic therapy in 10/17 (58.8%) patients, empirical 8/10 (80%) specific 2/10 (20%). All were negative for HIV and received first treatment for VL. The therapeutic options for VL were liposomal amphotericin B and N-methylglucamine antimoniate, following the guidelines of the Ministry of Health protocol. All patients were cured. However, corticosteroid therapy was administered to 33% (2/6) of the patients who did not respond to specific therapy for leishmaniasis, and dexamethasone was prescribed in anti-inflammatory doses, with prompt response. The mean time between onset of symptoms and admission was 39.18 ± 56.30 days. Fever was reported by all caregivers as the initial sign of the disease. The mean hospital stay was 16.88 ± 6.99 days. All patients were followed for 12 months without recurrence. There were no significant differences between the clinical variables of the groups. Triglyceride and ferritin levels showed significance. All six HLH patients presented five positive criteria, which authorized the diagnosis, based on the HLH-2004 protocol. These were fever, splenomegaly, bicytopenia or pancytopenia, and elevated ferritin and triglyceride levels. Therefore, HLH is not a rare complication in VL-endemic areas, and a diagnosis of HLH should be considered due to the overlap of clinical features and cytopenias. Despite the small number of cases in this study, we suggest triglyceride and ferritin levels among the tests to be requested in suspected kala-azar, and liposomal amphotericin B as a therapeutic option.