Disseminated Leishmaniasis and Rheumatoid Arthritis: Navigating a Clinical Conundrum

Endrit Shahini^1*Donatello Marziliano²Francesco Losito¹Marianna Zappimbulso¹Cavalcanti Elisabetta¹Raffaele Armentano¹Fabio Fucilli¹Raffaele Cozzolongo¹Giuseppe Ingravallo³Fabrizio Pappagallo²Vanessa Desantis⁴Annalisa Saracino⁵Angelo Vacca²Antonio Giovanni Solimando^2*

• ¹National Institute of Gastroenterology S. de Bellis Research Hospital (IRCCS), Bari, Italy
• ²Guido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area-(DiMePRe-J), School of Medicine, Aldo Moro University of Bari, Bari, Italy
• ³Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Pathology Unit, University of Bari "Aldo Moro", Bari, Italy
• ⁴Pharmacology Section, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, Bari, Italy
• ⁵Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Bari, Italy

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 immunemediated mechanisms that increase susceptibility.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 colonystimulating 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.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.