Oral Syphilis Research Articles

Oral syphilis - the great imitator: a series of six cases

Syphilis is an infectious disease which can present with multitudinous mucocutaneous manifestations. Often referred to as the ‘great mimicker', syphilis can present with non-specific symptoms and has a tropism for various organ systems. The oral cavity has been identified as a site commonly affected in the early stages of syphilis infection. Identification of the diverse presentations seen across the different stages of syphilis infection can assist in early diagnosis and treatment for this cohort of patients. Despite accurate diagnostic tools and the susceptibility of the infection to standard antimicrobial therapy, syphilis infections continue to rise worldwide.We present the clinical features and management of six cases of oral syphilis who presented to our unit. One case presented in 2008, but the other five cases presented between 2016 and 2023, reflecting the increasing incidence of syphilis infection. Five cases presented in the secondary stage of the infection while one presented with a primary infection in the form of a single chancre.The documented cases demonstrate the non-specific and variable clinical features of oral syphilis and highlight the importance of awareness in the dental profession of these manifestations. Dentists have an important role to play in recognising the disease and arranging appropriate testing for early intervention. This will not only reduce the incidence of the devastating consequences of tertiary infections but will also result in reduced spread of the disease.

Immunohistochemistry and RT-PCR as ancillary tools in the diagnosis of acquired oral syphilis.

To investigate Treponema pallidum detection using immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) assays in acquired oral syphilis (AOS). Thirty-seven paraffin-embedded tissue specimens of AOS (32 secondary and five primary) were analyzed, integrating double-positive serological results with clinicodemographic and histopathological data. T. pallidum presence was semiquantitatively assessed by IHC, while RT-PCR targeted T. pallidum DNA. Sensitivity, specificity, and the area under the curve (AUC) were calculated with 95% confidence intervals (CI). The study included mostly females (62.2%) with a mean age of 27.1 years. T. pallidum was detected in all samples by IHC, predominantly in the epithelium across all layers (43.2%). RT-PCR identified T. pallidum DNA in 32 cases, with negative results observed in cases of secondary AOS. The AUC for IHC versus disease stage was 62.5% (95% CI: 45.1-77.8), and for RT-PCR, it was 57.8% (95% CI: 40.5-73.8). The AUC comparing IHC to RT-PCR was 83.8% (95% CI: 67.9-93.8). This study represents the first attempt to evaluate the proposed direct detection algorithm for AOS. IHC and RT-PCR serve as ancillary tools for detecting T. pallidum in both primary and secondary stages of AOS.

Syphilis: a re-emerging disease. An update for the dental practitioner

Syphilis is a primarily sexually transmitted chronic infection caused by the spirochete, Treponema pallidum. There has been a dramatic increase in cases of syphilis in the Western world, with cases tripling in England between 2010 and 2019. Syphilis can present in a dental setting and dentists should enquire about sexual history if suspicious of syphilis to ensure early diagnosis and treatment. We present five cases seen with variable presentations of oral syphilis between 2016 and 2021 in a dental hospital. CPD/Clinical Relevance: Increased awareness of syphilis among the dental team is essential to ensure early referral, diagnosis and treatment.

Bilateral chancre of the tongue: An unusual presentation of primary syphilis.

Syphilis is a sexually transmitted infectious disease caused by the spirochete bacterium Treponema pallidum. A characteristic lesion of primary syphilis is chancre. It can develop over genital or extra genital sites, depending on the site of contact with the infectious agent. Cases of oral syphilis have been on the rise in the previous two decades, probably because of the involvement of the oral cavity in sexual practices. We here report an unusual case of primary syphilis who presented with a painless indurated oral ulcer over the lateral borders of the tongue.

The oral presentation of secondary syphilis among men: the evolving interplay between syphilis, HIV and prophylactic strategies

Syphilis has been intricately linked with HIV because of shared transmission pathways and because these infections promote each other’s transmission. In addition, HIV infection may change the clinical presentation and management of syphilis lesions. Initially, the HIV epidemic had improved safe sex practices among men who have sex with men (MSM), but subsequent effective treatment and prophylaxis strategies, have resulted in behavioural disinhibition and a resurgence of syphilis. Here, we report on three cases of oral secondary syphilis and explore the relationship between oral syphilis and sexual practices, HIV and prophylactic measures that MSM employ. Three men, who presented to the University of Pretoria Oral Health Centre (UPOHC), complaining of oral lesions, were diagnosed by histopathology with secondary syphilis. The clinical appearance of the lesions, HIV status, treatment and prophylaxis employed by the men were documented. The clinical presentation, sexual practices, HIV status and prophylactic measures among these men differed and demonstrate the complexity of oral secondary syphilisdiagnosis and management.Syphilis presents variably in the oral cavity, and this may be linked to the sexual practices and HIV status of the patient.

Acquired Oral Syphilis Guidelines for Dental Practitioners: Two Case Studies and A Literature Review

The clinical features of syphilitic lesions in the oral mucosa are variable, and there are no specific guidelines in the scientific English literature for dental practitioners regarding oral signs and symptoms that mandate serological tests for syphilis. We performed an updated review of reports on protocols for managing acquired oral syphilis (AOS) and offer recommendations with an emphasis on clinical features. We also add two new cases from our own files. Our analyses of global reports revealed that males are significantly more often affected than females, and their mean age is higher. Young adults are most affected, with a peak in the third and fourth decades of life. Ulcers and mucous patches as manifestations of AOS are the most prevalent clinical features in the oral mucosa. Mucous patches are significantly more prevalent in females as compared to males and tend to present as multiple rather than isolated lesions, while ulcers frequently appear as a sole lesion. The tongue, lip, and palate are the most affected anatomical sites. New oral lesions in the context of unprotected sexual intercourse warrant serological testing for syphilis.

ORAL MANIFESTATIONS OF SYPHILIS: A WARNING TO ORAL HEALTH PROFESSIONALS

<h3>Objectives</h3> The aim of the present study was to review the literature about the role of oral health professionals in syphilis diagnosis, highlighting its oral manifestations. <h3>Study Design</h3> A detailed literature search was conducted in 5 databases (Embase, Lilacs, PubMed, Scopus, and Web of Science) from January 2010 to April 2021 using the search strategy "Syphilis AND Oral." <h3>Results</h3> The literature showed that oral lesions can appear in any infection stage, although they were more common at the second one. Oral syphilis presented a nonspecific clinical aspect, mimicking other conditions. Usually, the oral manifestations of secondary syphilis were multiple asymptomatic whitish and slightly elevated lesions called mucous plaque. Also, the characteristic chancre of the primary stage due to oral sex must also be listed, as well as syphilitic gumma and luetic glossitis in the third stage. Special attention should be paid to pregnant women because vertical transmission of the disease can occur, causing congenital syphilis. <h3>Conclusions</h3> Oral lesions are frequently present in syphilitic patients; therefore, capacitated oral health professionals are important in syphilis diagnosis to work as a high-value resource against the rising number of notifications of this disease.

ORAL SYPHILIS IN AN ADULT PATIENT WITH AN INITIALLY VDRL NEGATIVE TEST

We report an uncommon presentation of oral syphilis in a male patient, 29 years old with a 2-month mouth ulcer. Clinical examination showed right submandibular lymphadenopathy and a painless ulcer located on the right labial commissure. Serology was requested for syphilis (VDRL) and HIV—both nonreactive—and a complete blood count that showed no changes. An incisional biopsy was performed with a diagnosis of an inflammatory process. Histochemical stains, such as Ziehl Nielsen and PAS, were requested, in addition to serology for toxoplasmosis and histoplasmosis, which were all nonreactive. Two months later, due to the persistence of the lesion, FTA-ABS and VDRL were requested again, and both were positive, characterizing syphilis. Afterward, treatment with benzathine penicillin 1,200,000 UI (2 applications/3 weeks) was proposed, and the patient remains in follow-up.

Secondary Syphilis Occurring on the Tongue: Report of a Case

<h3>Objective</h3> According to the Centers for Disease Control the rate of syphilis has steadily increased nearly every year since 2001. Tertiary syphilis is associated with serious complications that can be avoided by early diagnosis and treatment. Although primary and secondary syphilis typically involve the genitals, the oral cavity may be the initial site of disease. Given the recent increase in incidence, it is critical to recognize this disease to aid in prevention of life-threatening complications. Here, we report a case of oral syphilis and present the clinical, histopathological and immunohistochemical features. <h3>Clinical Presentation</h3> A 21-year-old female presented to an oral and maxillofacial pathologist for evaluation of a lesion on the tongue of one-month duration. Her medical diagnoses included bipolar disorder and genital herpes. Her social history included smoking and cocaine abuse. Upon examination, a mildly erythematous elevated plaque of the posterior dorsal tongue measuring 2.0 × 1.5 cm was identified. <h3>Intervention and Outcome</h3> An incisional biopsy was performed under intravenous sedation by an oral and max- illofacial surgeon. Microscopic review showed oral mucosa demonstrating papillary hyperparakeratosis, neu- trophilic microabscesses and a moderateto-intense chronic inflammatory infiltrate possessing an abundance of plasma cells in the underlying connective tissues. These features were suspicious for a diagnosis of secondary syphilis. Tissue was sent to the Mayo Clinic for <i>Treponema pallidum</i> study by immunohistochemistry. Review of the stained slides showed numerous spirochetal organisms throughout the epithelium, confirming the diagnosis. The patient's primary care provider was contacted to initiate therapy. The NYC Department of Health and Mental Hygiene was notified of this diagnosis fulfilling mandatory reporting requirements. <h3>Conclusion</h3> The rate of syphilis diagnosis is on the rise. Presentation in the oral cavity, while rare, is important for oral healthcare providers to be familiar with as early diagnosis and treatment are likely to prevent serious complications.

Unexpected Reason for Non-healing Oral Ulcers: Syphilis.

Syphilis is a sexually transmitted infectious disease caused by Treponema pallidum and characterized by a complex and variable clinical presentation. Cases of unexpected oral syphilis presenting as non-healing ulcers are uncommonly reported. We report 3 cases (one female and two males, aged 35, 35, and 56 years, respectively) in which patients presented with non-healing oral ulcers. Biopsies revealed surface ulceration and a significant neutrophilic infiltrate rather than the more conventional plasma cell infiltrate seen with most reported syphilis infections, potentially leading to an inaccurate diagnosis. Treponema pallidum immunohistochemistry highlighted spirochetes within the epithelium, with additional diagnostic confirmation by serum T. pallidum particle agglutination assay. Sexual history documentation by the clinician with nonspecific oral ulcers is paramount to aiding diagnosis and leading to proper management. Further, it is important to perform immunohistochemistry for T. pallidum in oral biopsies from non-healing ulcers, especially when clinical history raises the differential diagnosis or when other clinical manifestations may support this consideration.

Acquired oral syphilis: A multicenter study of 339 patients from South America.

To report the clinicopathologic features of acquired oral syphilis cases in South American countries. Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3years. Individuals aged 20-29years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.

ORAL SECONDARY SYPHILIS IN PEOPLE LIVING WITH HIV: A 16-YEAR EXPERIENCE IN MEXICO CITY

Background The increase in syphilis rates worldwide, particularly in people living with HIV (PLWH), as well as the challenging diagnosis that secondary syphilis represents, make essential the accurate recognition of its manifestations, particularly in easy-access sites like the oral mucosa. Objective To describe the clinicopathologic spectrum of oral secondary syphilis (OSS) in PLWH. Methods A cross-sectional and descriptive study that included PLWH with OSS from 3 HIV referral centers in Mexico City (2004-2020). Demographic and clinical data were obtained. A comprehensive oral examination was done. OSS was diagnosed following established criteria. Histopathologic/cytological procedures were performed to rule out specific oral lesions. In all patients, Venereal Disease Research Laboratory tests were assessed and, if possible, a confirmatory fluorescent treponemal antibody test or biopsy was performed. Statistical analysis was performed using SPSS v25. Results Forty-seven PLWH with OSS (97.8% male, median age: 32 years, 63.8% with acquired immunodeficiency syndrome) were included. Thirty-five were receiving combination antiretroviral therapy (74.5%; median of 1146 [Q1-Q3: 337.5-1971] days) with a median CD4+ count of 385 (Q1-Q3: 223-664) cells/mm3 and a Log10 HIV viral load of 4.1 (Q1-Q3: 3.7-5.3) copies/mL. Forty had a complete clinical-serological diagnosis (85.1%; 17 had histopathologic confirmation) and 7 had a clinical-histopathologic diagnosis. Twenty-nine individuals presented 1 lesion (61.7%), and mucous patch was the most common type mainly on oropharyngeal mucosa, followed by ulcers and macular lesions. Ten patients presented maculopapular dermatosis (21.3%). Conclusions In PLWH, oral lesions, particularly mucous patch and/or ulcers on the oral and oropharyngeal mucosa, must alert specialists to consider a diagnosis of syphilis and perform a comprehensive panel of confirmatory tests.

THE CHALLENGING DIAGNOSIS OF SERONEGATIVE ORAL SYPHILIS IN AN HIV-INFECTED PATIENT

<h3>Background</h3> In people living with HIV/syphilis-coinfection, overlapping of clinical stages and misleading anti-treponemal serologic tests have been described. This is the report of serological (false-negative) non-reactive, polymerase chain reaction (PCR)-confirmed syphilis in an HIV-infected patient. <h3>Case Description</h3> An HIV-infected male patient, 28-years-old, receiving antiretrovirals (TDF/FTC/DTG) with therapeutic success (CD4: 667 cells/mm³, undetectable HIV-plasma viral load), was referred to our Oral Pathology & Medicine Service in Mexico City. A 3-month asymptomatic ulcerated lesion on the right side of the soft palate and anterior pillar, with granular appearance, irregular borders, and measuring 2 to 3 cm in diameter, was observed. A painless, right cervical lymph node was present. A quantitative serum Venereal Disease Research Laboratory (VDRL) assay was nonreactive (serum was diluted 6-fold to rule out a prozone phenomenon and remained negative). Histopathologic analysis revealed an intense mixed inflammatory infiltrate; differential diagnosis included secondary syphilis, lymphoproliferative disorder, and deep mycotic infection. The immunohistochemistry (IHC) for <i>T. pallidum</i> was negative. DNA extraction was performed, and the <i>T. pallidum</i> gene polA was amplified by PCR; as a consequence, the patient received benzathine-penicillin G (2.4 million units) single dose. VDRL and treponemal FTA-abs were done twice, with negative results. A new biopsy revealed positive IHC<i>-T. pallidum</i>. Two months later, a mucous patch appeared on the tonsillar pillar, with histopathologic features of secondary syphilis and positivity for IHC-<i>T. pallidum</i>. VDRL and FTA-abs assays remained non-reactive. Oral lesions resolved after 3 doses of benzathine-penicillin G. <h3>Conclusions</h3> In absence of serological evidence, the diagnosis of oral syphilis is a challenge. PCR and IHC may represent supplementary helpful diagnostic tools.

Rare Infections of the Oral Mucosa

(1) Background: Oral mucosal infections are a commonly encountered clinical pathology in patients who consult dentists, mainly for dental diseases. Currently, the involvement of oral and dental infections in cardiovascular and neurological diseases, among others, is widely discussed in the literature. In the present research, we elaborated a comprehensive report on rare oral mucosal infections, including oral syphilis and head and neck tuberculosis. (2) Methods: The research was performed by the authors using three databases (PubMed, Wiley, and ScienceDirect). Scientific articles published from January 2000 to January 2020 were selected and reviewed to assess the epidemiology, symptoms, and diagnosis of oral syphilis and head and neck tuberculosis. (3) Results: Oral syphilis was mainly noticed as ulcers and secondary types of disease. Tuberculosis of the head and neck was most frequently encountered as cervical lymphadenopathy. (4) Conclusions: Rare oral infections diagnosis may be challenging due to their evolving polymorphic clinical appearance and their ability to mimic various diseases in the oral cavity and head and neck area.

Oral Manifestations of Syphilis: a Review of the Clinical and Histopathologic Characteristics of a Reemerging Entity with Report of 19 New Cases.

Syphilis is a sexually-transmitted infectious disease caused by Treponema pallidum. Cases of primary and secondary syphilis are on the rise in the United States, with a 14.4% increase in new cases noted from 2017 to 2018 and an escalation of 71% between the years 2014 and 2018. Fulfilling its nickname of "the great imitator," oral manifestations of syphilis may mimic a variety of infectious, neoplastic, or immune-mediated processes, both clinically and histopathologically. This large spectrum of appearances can create a diagnostic challenge to the clinician and/or pathologist, leading to delay in diagnosis or misdiagnosis. A database of oral syphilis cases was created from archives at the University of Kentucky, University of Pittsburgh, LIJMC, Columbia University MC, and University of Tennessee. The age, sex, race, location, duration, and clinical description were recorded. Cases without positive reaction upon immunohistochemistry or serologic tests were excluded. We identified 19 new cases of oral syphilis (17 males, one female, and one case unknown sex) and described the clinical and histopathological features of this re-emerging and potentially fatal disease. All cases demonstrated dense lymphoplasmacytic inflammation, often with inflammatory exocytosis or ulceration at the surface, and perivascular inflammation. Early recognition of the histopathologic and clinical manifestations of oral syphilis is imperative for prompt diagnosis, improved patient outcomes, and disease prevention.

Diagnosis of oral syphilis remains a challenge – A case report

Diagnosis of oral syphilis remains a challenge – A case report

ORAL SYPHILIS CLINICOPATHOLOGIC FEATURES OF 19 NEW CASES

Objective To report the clinicopathologic features of 19 new cases of oral syphilis in a population from Brazil. Study Design Oral syphilis cases diagnosed in the last 4 years were retrieved and a descriptive analysis was performed. Results There were 11 men and eight women, with age ranging from 16 to 60 years (mean of 27.2 years). The most common clinical appearance of oral syphilis was of white plaques or ulcers usually affecting the tongue, buccal mucosa, palate, and lower lip. Two patients showed cervical lymphadenopathy, with skin involvement of the hands and abdominal region. Fourteen patients were subjected to biopsy and microscopically, all cases revealed perivascular and subepithelial lymphoplasmacytic infiltrate in a vascularized connective tissue, which was covered by stratified squamous epithelium with acanthosis, hyperkeratosis, and microabscesses. The diagnosis of oral syphilis in all patients was confirmed by serologic positivity for Venereal Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS). Eighteen patients showed oral manifestations of secondary syphilis and 1 patient of primary syphilis. Conclusions Patients with oral syphilis from Brazil showed similar clinicopathologic features compared with other countries. Oral manifestations may be the first sign of syphilis.

SECONDARY ORAL SYPHILIS IN A YOUNG PATIENT WITH NO PREVIOUS HISTORY OF RISK EXPOSURE

An 18-year-old female patient who had a 1-year-old daughter came to us presenting a 2-week lesion that has begun as a bubble. Examination showed an asymptomatic smooth white lesion without ulcerations in lower lip mucosa and minor lesions on tongue. She was a healthy patient, had no previous lesion, and had a normal pregnancy demonstrated by her health card. Blood count had normal parameters. She reports not to have a sexually active life, and denies habits of smoking and alcoholism. After examination, autoimmune lesions were suspected. A cytopathologic scraping was performed with diagnosis of a mononuclear inflammatory process with atypical squamous cells and intense epithelial dysplasia. Incisional biopsy was performed in lower lip with histopathologic report of oral syphilis. Requested Venereal Disease Research Laboratory with reagent report and HIV-1 and -2 were both negative. She was referred to an infectious diseases sector for treatment of secondary syphilis. The lesions suffered remission in 10 days.

ORAL SYPHILIS: A CASE SERIES WITH ORAL INVOLVEMENT OF A REEMERGING DISEASE

The current literature reported an increase in cases of syphilis in different regions of Latin America. The aim of this study is to present a series of 19 cases from the Oral Medicine Department, Dentistry College, National University of Cordoba in Argentina with secondary syphilis diagnosed by oral lesions and serologic antibody studies from 2010 to 2018. A wide range of variable clinical presentations and Venereal Disease Research Laboratory (VDRL) titers were recorded in order to establish an association between antibody tests and clinical progression of oral lesions. A high increase of the disease diagnosed at our institution in the last decade was also reported worldwide. This phenomenon suggests the reemergence of a sexually transmitted infection that was believed to have been controlled. Oral syphilis mimics many other diseases becoming a diagnostic challenge for the clinician. Early diagnosis of the disease could avoid the spread of the infection.

A RETROSPECTIVE ANALYSIS OF 12 CASES OF ORAL SYPHILIS RECENTLY DIAGNOSED AT A SOLE INSITITUTION

Syphilis is an infectious disease caused by the bacterium Treponema pallidum and has 3 classically clinical stages. This disease may mimic several other more common oral mucosa lesions. This study aimed to describe the different oral manifestations of 12 patients diagnosed as having syphilis in the last few years at our institution. Eleven of the 12 syphilis cases presented lesions of secondary syphilis and 1 of primary syphilis. The diagnosis was made through biopsies or/and laboratory tests, and the treatment was conducted by intramuscular injections of benzathine penicillin G with good results. The patients' group examination confirmed the theory that syphilis may resemble several other diseases. Dental surgeons should be aware of the manifestations of oral syphilis, which might be very different from the classical description of mucous patches, to play a desirable key role on the diagnosis and control of this disease. Syphilis is an infectious disease caused by the bacterium Treponema pallidum and has 3 classically clinical stages. This disease may mimic several other more common oral mucosa lesions. This study aimed to describe the different oral manifestations of 12 patients diagnosed as having syphilis in the last few years at our institution. Eleven of the 12 syphilis cases presented lesions of secondary syphilis and 1 of primary syphilis. The diagnosis was made through biopsies or/and laboratory tests, and the treatment was conducted by intramuscular injections of benzathine penicillin G with good results. The patients' group examination confirmed the theory that syphilis may resemble several other diseases. Dental surgeons should be aware of the manifestations of oral syphilis, which might be very different from the classical description of mucous patches, to play a desirable key role on the diagnosis and control of this disease.