Visceral leishmaniasis masquerading as autoimmune disease flare in a non-endemic area: diagnostic challenges and the role of targeted next-generation sequencing

Visceral leishmaniasis (VL) can present atypically in patients receiving immunosuppressive therapy, closely overlapping with autoimmune disease flares and posing a particular diagnostic challenge in non-endemic settings. We report a 57-year-old woman from Beijing, China, with a 2-year history of systemic lupus erythematosus (SLE) and Sjögren syndrome on long-term hydroxychloroquine and methylprednisolone. She had no known travel to leishmaniasis-endemic regions and no recognized sandfly exposure. She presented with anorexia, vomiting, and intermittent fever, and was found to have splenomegaly, marked hypergammaglobulinaemia (IgG 30.28 g/L), reduced complement C3, and patchy brown hyperpigmentation of all four limbs. Initial blood counts showed progressive pancytopenia (white blood cell count nadir 1.02 × 10⁹/L; haemoglobin 7.9 g/dl; platelets 64 × 10⁹/L). On hospital day 3, blood targeted next-generation sequencing (tNGS, 500+ pathogen panel) detected Leishmania genus at 425,566 specific reads (estimated concentration 10⁵ copies/mL); a second tNGS platform identified the species as Leishmania donovani, a positive rK39 test provided serological support, and bone marrow smear subsequently demonstrated Leishmania amastigotes. Following antileishmanial therapy with sodium stibogluconate, systemic symptoms resolved, blood counts recovered, and the limb hyperpigmentation faded substantially. In immunosuppressed patients living in non-endemic areas, VL should be considered when fever, splenomegaly, and cytopenias cannot be fully explained by autoimmune activity. tNGS can deliver rapid pathogen identification when epidemiological clues are absent.