A 55-year-old man resident in Barcelona was evaluated for a 2-week history of unexplained fever despite antipyretic treatment. Medical record was positive only for hypertension controlled with enalapril. He was born in Barcelona and he always lived there. 2 years ago he had traveled to China and Israel, and 10 years ago to several countries of South America, with no other relevant epidemiological risk. The patient denied alcohol intake previous to admission At admission he was 39.1 °C, the heart rate was 89 bpm, and the blood pressure was 123/66 mmHg. Physical examination was unremarkable. Initial blood test revealed increased C-reactive protein levels to 10.55 mg/dL, elevated aspartate aminotransferase (88 U/L), alanine aminotransferase (76 U/L), alkaline phosphatase (202 U/L) and gamma glutamyl transferase (269 U/L). Bilirubin and prothrombin time were within normal range. The hemoglobin was 12.7 g/dl and laboratory test showed leukopenia (2.83 × 109/L) and thrombopenia (115 × 109). Blood and urine cultures were taken on admission. Chest radiography was normal. Due to fever and analytical results it was decided to perform an abdominal ultrasonography revealing a hypoechoic lesion suggestive of a subcapsular splenic infarction. Infective endocarditis was suspected, starting an antibiotic combination of intravenous ampicillin 2 g/ 4 hs, cloxacillin 2 g/4 hs and ceftriaxone 2 g/12 hs. Transthoracic echocardiography was unremarkable and blood cultures were negative, discontinuing ampicillin and cloxacillin.
The patient continued having febrile peaks over 2 weeks, treated mainly by physical measures to avoid hepatotoxic drugs. A computed tomography revealed 15 cm-splenomegaly and several splenic infarctions, with no other abnormalities. Repeated blood analysis showed worsening of liver tests (AST 1649 U/L, ALT 911 U/L, gamma GT 447 U/L, total bilirubin 4.20 mg/dl, ammonium 82 μmol/L, albumin 2.4 mg/dl, prothrombin time of 40%), pancytopenia (hemoglobin 8 g/L, platelets 48 × 109), high levels of triglycerides 222 mg/dl, elevated ferritin 12.886 ng/mL, lactic dehydrogenase 915 U/L, total proteins 55 g/l, normal kidney function test and normal blood smear.
Microbiology investigations (including serologies and molecular biology) were negative for tuberculosis, Coxiella, Brucella, Human immunodeficiency virus, viral hepatitis (A to E), Cytomegalovirus, Epstein-Barr virus and parvovirus B19. IgG for Leishmania was positive, with a title of 1:200 by IIFT technique and IgM was negative. He had low titers of antinuclear and anti-smooth muscle antibodies (1:80). Given these findings it was decided to perform a bone marrow aspiration and a 18F-fluorodeoxyglucose-positron emission tomography in combination with computed tomography scanning (FDG-PET/TC). There were no signs of haematologic malignancy in the bone marrow and there were no hemophagocytosis. Aspirated material inoculated into parasitic growth media and a Giemsa-stained smear was made, both were negative. FDG-PET/TC revealed a diffuse high uptake in the spleen, liver, and bone marrow but without involvement of lymph nodes or other organs (Fig. 1).
Given the worsening of liver tests, a diagnostic liver biopsy was performed and histopathology showed an acute hepatitis with confluent necrosis and mixed inflammatory infiltrates with abundant plasmatic and histiocytic cells. Isolated macrophages with intracytoplasmic Leishmania amastigotes were observed (Fig. 2). Polymerase chain reaction in tissue was positive for Leishmania infantum. The patient started treatment with liposomal amphotericin B 3 mg/kg/day for 5 days and two additional single weekly doses, at day 14th and 21st, showing slow but continuous analytical and clinical involvement. He was completely recovered 1 month later.
