A Challenging Case of Visceral Leishmaniasis

Abstract

The term leishmaniasis includes multiple clinical syndromes: visceral, cutaneous, and mucosal leishmaniasis, resulting from an infection of macrophages throughout the reticuloendothelial system in the dermis and the naso-oropharyngeal mucosa, respectively. The clinical phenotype is mainly driven by the leishmania biologic characteristics and, ultimately, also by the host immune status. The disease is endemic in focal areas in the tropics, subtropics, and southern Europe, transmitted by the bite of female phlebotomine sandflies. Sandflies regurgitate the parasite’s flagellated promastigote stage into the host’s skin; promastigotes bind to receptors on macrophages are phagocytized and transformed within phagolysosomes into non-flagellated amastigotes which replicate and infect additional macrophages. Amastigotes ingested by sandflies transform back into infective promastigotes. Depending on the host’s innate and acquired immune status, systemic and visceral leishmaniasis can be characterized by irregular fever, weight loss, enlargement of the spleen and liver, and anaemia. We present a 42 year-old man with long-lasting type 1 autoimmune hepatitis under immunosuppressive treatment. In January 2017, the patient started to experience low-grade unresponsiveness to empiric antibiotic therapy. The patient developed severe anemia and progressive multilineage cytopenia accompanied by increased levels of inflammatory markers. FDG-PET revealed increased glucose uptake in the liver, spleen, and the whole bone marrow. The subsequently performed bone marrow biopsy evidenced Leishmania amastigotes inside macrophages, confirmed by serological positivity to anti-Leishmania antibody. Immunosuppressive therapy was suspended and replaced by treatment with amphotericin B at 4 mg/kg/day from day 1 to day 5, followed by a single infusion on days 10, 17, 24, 31, and 38. The bone marrow smear after treatment still evidenced few Leishmania amastigotes; in consideration of the patient’s immunosuppression status, two further doses of amphotericin B on days 45 and 52 were employed, leading to infection resolution. In real-life, as exemplified in this case, administering two additional doses of amphotericin B (concerning the guidelines) offered an additional therapeutic opportunity for a patient under long-term immunosuppressive treatment.

Visceral leishmaniasis in Kosovo: A case of misdiagnosis and diagnostic challenges

“…The incubation period for VL can vary from a few weeks to a few years, while the onset is typically insidious and progresses slowly with various signs and symptoms overlapping with the features of other infectious diseases, as described in other case presentations [5] , [6] and VL studies [7] . In our case, the incubation period was probably short because the laboratory results on the patient's hospital admission did not show deviations from the reference values.…”

“…Due to its clinical presentation, the disease can be easily mistaken for other diseases of hematological, malignant, autoimmune, or other etiology. In cases where underlying diseases are present, VL may be misdiagnosed as a progression of an existing condition [5] . Therefore, physicians in endemic regions, such as the Balkans, should be aware of this infection to avoid possible misdiagnosis or diagnostic delays, as was the case with our patient.…”

“…The classical manifestations of advanced disease include irregular and prolonged fever, cachexia (malnutrition being both a risk factor for and a sequela of visceral leishmaniasis), hepatosplenomegaly (with splenomegaly usually predominant and the spleen sometimes massive), anemia, leukopenia, thrombocytopenia, occasionally associated with bleeding, hypergammaglobulinemia (mainly IgG, from polyclonal B cell activation), and hypoalbuminemia [5] .…”

Histological and immunohistochemical evaluations of the bone marrow from femur and sternal manubrium of dogs reactive for leishmaniasis by DPP® and ELISA tests

“…Bone marrow presents high parasitemia in CVL, with no changes in the production of the white and red series at the beginning of the infection, but a reduction in cell production and, consequently, hematological disorders are observed as the disease progress, resulting from changes such as macrophage hyperplasia, erythrocyte hypoplasia, and medullary aplasia 16 . Myelodysplastic alterations have been described in humans with VL, including anemia [16][17] , triggered by the sequestration of red cells in the spleen, pro-inflammatory cytokines that inhibit erythropoietin synthesis, and immunological mechanisms 16 .…”

Avaliações histológica e imunoistoquímica da medula óssea do fêmur e do manúbrio esternal de cães reagentes para leishmaniose aos testes DPP® e ELISA

“…Na LVC, a medula óssea apresenta alta parasitemia, sendo que no início da infecção não há alterações na produção das séries branca e vermelha, mas, com a progressão da doença, ocorre redução da produção celular e, consequentemente, transtornos hematológicos, os quais decorrem de alterações como hiperplasia de macrófagos, hipoplasia de eritrócitos e aplasia medular 16 . Em humanos com LV foram descritas alterações mielodisplásicas, incluindo anemia [16][17] , desencadeada pelo sequestro de hemácias no baço, por citocinas pró-inflamatórias que inibem a síntese de eritropoetina, e por mecanismos imunológicos 16 .…”