{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:38:01Z","timestamp":1790379481923,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Syphilis can present with diverse clinical manifestations, earning the name \u201cgreat imitator.\u201d Malignant syphilis (MS) is a rare, severe form of secondary syphilis, typically reported in immunocompromised patients, particularly those living with HIV. However, MS can occasionally occur in immunocompetent individuals, posing diagnostic challenges due to its atypical presentation. Methods: A case report is presented alongside a PubMed literature search using the terms \u201c(malignant syphilis OR lues maligna) AND (immunocompetent) AND (case report OR case series).\u201d No language or temporal restrictions were applied, yielding 18 relevant publications. Results: A 60-year-old HIV-negative man presented with fever, weight loss, papular lesions, and a single ulcer on the sternum. Serology was positive for syphilis, and PCR confirmed T. pallidum DNA in the lesion. Treatment with a single intramuscular dose of benzathine penicillin G led to prompt clinical and serological improvement. Literature review (n = 18) showed that MS in immunocompetent patients affects both sexes (55% male; mean age 37.1 years), often presents with ulceronodular or rupioid crusted lesions, and frequently involves systemic symptoms. Molecular diagnostics were rarely reported, with most diagnoses relying on histopathology and serology. Treatment with benzathine penicillin G was effective in all cases, and full recovery was achieved. Conclusions: MS can occur in immunocompetent, HIV-negative individuals without obvious risk factors. Clinicians should maintain a high index of suspicion in cases of systemic, cutaneous, or ocular manifestations suggestive of MS. Molecular assays can facilitate diagnosis and prevent unnecessary invasive procedures. Benzathine penicillin G remains the treatment of choice, demonstrating high therapeutic effectiveness. MS should be considered in the differential diagnosis of ulcerative or nodular dermatoses, regardless of immune status.<\/jats:p>","DOI":"10.3390\/jcm14248839","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:57:24Z","timestamp":1765879044000},"page":"8839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Malignant Syphilis in an Immunocompetent Patient: A Case Report and Review of the Literature"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8975-4916","authenticated-orcid":false,"given":"Chiara Vincenza","family":"Mazzola","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties \u201cG D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"},{"name":"Infectious and Tropical Diseases Unit and Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Bono","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties \u201cG D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"},{"name":"Infectious and Tropical Diseases Unit and Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenia","family":"Giacchino","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties \u201cG D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"},{"name":"Microbiology and Virology Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Cal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties \u201cG D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"},{"name":"Microbiology and Virology Unit, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-4285","authenticated-orcid":false,"given":"Luca","family":"Pipit\u00f2","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties \u201cG D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"},{"name":"Infectious and Tropical Diseases Unit and Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-1796","authenticated-orcid":false,"given":"Antonio","family":"Cascio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties \u201cG D\u2019Alessandro\u201d, University of Palermo, 90133 Palermo, Italy"},{"name":"Infectious and Tropical Diseases Unit and Sicilian Regional Reference Center for the Fight Against AIDS, AOU Policlinico \u201cP. Giaccone\u201d, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/S0140-6736(22)02348-0","article-title":"Syphilis","volume":"402","author":"Peeling","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1136\/sextrans-2024-056367","article-title":"Interesting case of syphilis with atypical vegetative lesions","volume":"101","author":"Gaudiano","year":"2025","journal-title":"Sex. Transm. 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