Clinical and Immunological Overlap Between Visceral Leishmaniasis and Rheumatic Disorders: A Comparative Review on Diagnostic Challenges

Rheumatic diseases are complex systemic disorders characterized by multi-organ involvement and diverse laboratory abnormalities. The diagnostic approach involves a comprehensive evaluation of clinical and serological markers and the exclusion of conditions with overlapping presentations, such as other rheumatic diseases and systemic infections. Visceral leishmaniasis (VL) is a protozoan infection that primarily affects the reticuloendothelial system. Direct effects of parasite infiltration of the reticuloendothelial system, combined with the subsequent host immune response, produce clinical and laboratory findings that mimic those of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Furthermore, the exaggerated immune response observed in a subset of VL patients overlaps clinically with primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). VL can mimic SLE and Felty's syndrome and may trigger secondary HLH. Furthermore, in endemic regions, VL can present as a coexisting condition in patients with SLE and RA, often mimicking disease flares. In these vulnerable patient groups who are receiving immunosuppressive therapies, delayed diagnosis can significantly worsen the clinical course and prognosis of VL. This review explores the clinical and immunological manifestations of VL, providing a detailed comparative evaluation of its diagnostic overlap with HLH, MAS, SLE, and Felty's syndrome.