The Multisystemic Nature of Syphilis: Challenges in Diagnosis

Syphilis, a chronic systemic infection caused by Treponema pallidum, reemerges as a major global health concern due to its rising incidence and wide-ranging clinical presentations. While often regarded as a sexually transmitted infection confined to the genital tract, syphilis frequently involves multiple organ systems, particularly in its secondary and tertiary stages. This review highlights the key organ-specific manifestations of syphilis, focusing on cardiovascular, pulmonary, hepatic, renal, and neurological complications. Cardiovascular involvement may include aortitis, aortic regurgitation, and coronary ostial stenosis. Pulmonary syphilis, though rare, can mimic malignancies or granulomatous diseases. Hepatic syphilis often presents as cholestatic hepatitis and, in severe cases, may progress to fulminant liver failure. Renal complications range from mild proteinuria to nephrotic syndrome and glomerulonephritis. Neurosyphilis, previously considered a late-stage and uncommon outcome, is now increasingly recognized earlier in the disease course, with a wide rage of clinical symptoms. Effective diagnosis relies on a combination of serologic testing, imaging, histopathological evaluation and, in special cases, advanced molecular techniques such as metagenomic sequencing. Timely recognition and treatment with penicillin remain critical in preventing long-term organ damage. Given syphilis’s ability to imitate various conditions and affect diverse populations, increased clinical vigilance and a multidisciplinary approach are essential for effective management.