Nodular Secondary Syphilis: Systematic Review of an Underrecognized Clinical Phenotype

Area of Science:

• Dermatology
• Infectious Diseases
• Syphilology

Background:

• Secondary syphilis exhibits diverse skin lesions mimicking other conditions.
• Nodular syphilis presents a diagnostic challenge, often mistaken for lymphomas or fungal infections.
• Malignant syphilis, a severe subset, includes nodulo-ulcerative necrotic lesions, particularly in immunosuppressed individuals.

Purpose of the Study:

• To establish a nosological framework and clinical description for nodular secondary syphilis.
• To investigate the association of nodular syphilis with immunosuppression and human immunodeficiency virus (HIV) infection.
• To clarify whether all nodular syphilis presentations constitute the malignant variant.

Main Methods:

• A systematic review of published cases of nodular syphilis.
• Searches conducted in PubMed and Embase databases.
• Analysis of 144 collected case reports.

Main Results:

• Nodular secondary syphilis occurs in immunocompetent patients, not solely in those with immunosuppression or HIV.
• Nodular lesions alone do not automatically classify syphilis as malignant.
• Extended antibiotic regimens showed no clear benefit without documented late-stage disease or neurosyphilis.

Conclusions:

• Nodular secondary syphilis is not exclusive to immunocompromised individuals.
• Timely recognition and appropriate antibiotic therapy are crucial for effective management.
• Treatment efficacy is consistent across different clinical severities and HIV statuses.