Introduction: Leprosy, caused by Mycobacterium leprae, is primarily characterized by cutaneous and peripheral nerve involvement. Nonetheless, musculoskeletal manifestations are also frequently observed and are commonly misdiagnosed as rheumatic diseases. Case Presentation: We report a case of lepromatous leprosy presenting with chronic arthritis and HLA-B27 positivity, which was misdiagnosed as peripheral spondyloarthritis in the early stage due to the absence of typical clinical manifestations. Conclusion: Lepromatous leprosy may mimic peripheral spondyloarthritis, especially with HLA-B27 positivity. Clinicians should consider leprosy in refractory arthritis or neuropathy, even in non-endemic areas, to prevent disability and transmission.