Case Report: Disseminated leishmaniasis and rheumatoid arthritis: navigating a clinical conundrum

Abstract

Background: Leishmaniasis is a potentially life-threatening protozoan infection that presents with many clinical manifestations, including cutaneous, mucocutaneus and visceral forms. In patients with rheumatoid arthritis (RA), cutaneous leishmaniasis can persist or re-emerge due to treatment-induced immunosuppression. However, it remains unclear whether this severe opportunistic infection is primarily driven by medication-induced immunosuppression or other poorly understood immune-mediated mechanisms that increase susceptibility.

Case presentation: We describe an unusual case of disseminated leishmaniasis in a 50-year-old Italian man from Apulia, diagnosed with RA two years earlier. Following 15 months of unsuccessful immunosuppressive therapies, he developed severe multilineage pancytopenia, moderate hypertransaminasemia, elevated inflammatory markers, monoclonal gammopathy, clinically significant hepatosplenomegaly, and an ulcerated skin lesion. Initial diagnostic efforts excluded common infectious agents, primary hematological disorders, Felty syndrome, and amyloidosis. The non-specific histopathological findings from the pyoderma gangrenosum-like lesion and the transient clinical response to empirical steroids, broad-spectrum antibiotics, and granulocyte colony-stimulating factors further complicated the diagnostic process. The breakthrough came when a liver biopsy, performed to investigate persistent hypertransaminasemia, revealed Leishmania amastigotes within macrophages. This finding triggered a re-evaluation of the ulcerated skin lesion, and histological analysis confirmed concurrent cutaneous leishmaniasis. Subsequent bone marrow biopsy also identified Leishmania amastigotes, clinching the diagnosis of disseminated leishmaniasis. A holistic re-assessment of the patient's clinical presentation, developmental history, and laboratory, radiologic, and pathological data led to the definitive diagnosis. Treatment with standard intravenous amphotericin B resulted in clinical resolution. A follow-up bone marrow biopsy a few weeks later confirmed the infection had been completely eradicated.

Conclusions: In patients with rheumatological conditions, the overlapping symptoms of systemic diseases and infections like leishmaniasis can lead to significant diagnostic delays. This case underscores the importance of comprehensive and meticulous diagnostic evaluations in immunosuppressed individuals to prevent potentially fatal outcomes.

Keywords: anti-CCP antibodies; immunosuppression; leishmaniasis; rheumatoid arthritis; zoonosis.

Figure 1

Hepatosplenomegaly was seen in the CT-scan (coronal section) in the (a) arterial phase; (b) venous phase, and (c) portal phase (d) portal (up), venous (down) phases; (e) arterial (left), portal (right) and venous (down) phases (sagittal sections).

Figure 2

Ulcerated skin lesion on the left leg that resembles pyoderma gangrenosum, at the time of diagnosis and during the healing process.

Figure 3

Three echotomography-assisted lunges were performed at the 7^th intercostal space using a semiautomatic needle (16 Gauge, 150 mm in length) to remove a whitish hepatic parenchyma frustule measuring about 10 mm; (a) Hepatic section stained with H&E (magnification x200). Nodular pattern of human visceral leishmaniasis (VL). Inflammatory nodule with mononuclear cells, consisting of lymphocytes, macrophages and plasma cells; (b) Hepatic section stained with H&E (magnification x600). Immature granulomas formed by macrophages harboring a high number of amastigotes (arrow); (c) Immunohistochemistry (magnification x 200). Macrophages stained with CD68 (arrowhead).

Figure 4

Material taken from a crusted skin lesion in the absence of the healthy structures of the epidermal lining. A 1.5 mm skin biopsy was taken from the edge of the lesions with a sterile surgical blade using 2% xylocaine as an anesthetic. The sample was fixed in 10% neutral buffered formalin (pH 7.2) for at least 78 hours, then routinely processed and sectioned at 3-4 µm and stained with hematoxylin and eosin (HE). Ulcerated and crusted parts of the skin lesion were excluded. Histological examination revealed the presence of amastigotes in the tissues colored by Giemsa, confirming the diagnosis of Leishmaniasis. (a) ulcerated surface of the skin with eschar and hyalurosis of the reticular dermis (HE 10X magnification); (b) in the subcutaneous tissue was highlighted necrotic phlogistic material with foamy histiocytes and haematoxylyphotic debris (HE 10X magnification); (c) HE Staining of skin biopsy revealed numerous intracellular amastigotes (4 µm) of Leishmania species (arrowheads) (HE stains, 60X magnification).