Oropharyngeal Condyloma Lata in Secondary Syphilis: Case Report and Literature Review

Introduction

Syphilis is a global health threat and a sexually transmitted infection with rising incidence rates, particularly in urban areas and among men who have sex with men (MSM) [1]. In 2020, the World Health Organization (WHO) reported a resurgence in syphilis cases globally. An estimated 7.1 million adults between 15 and 49 years of age acquired syphilis [2], according to pooled prevalence estimates of syphilis among MSM across the 8 regions of the Sustainable Development Goals and the 6 WHO regions over the past 20 years [3]. Secondary syphilis is a common stage of diagnosis due to its diverse clinical manifestations. Oral syphilis, while accounting for a significant proportion of cases – 35%, 56%, and 9% of primary, secondary, and tertiary syphilis cases, respectively – rarely presents as an isolated manifestation, complicating diagnosis and management [4–6]. The primary lesion of oral syphilis most commonly presents as chancres (58%). Secondary lesions manifest as mucosal patches (42%), isolated or multiple ulcerations (37%), leukoplakia-like plaques (11%), aphthous-like lesions (5%), and pseudomembranous lesions (5%). Although characteristics compatible with condyloma lata were found, these lesions were not identified as condyloma lata [6].

Oropharyngeal condyloma lata (OCL) is a rare manifestation of secondary syphilis. It is characterized by moist, flat, or raised lesions typically found in the anogenital area but occasionally in extragenital locations such as the oral cavity, nasolabial folds, or external auditory meatus [7,8]. Despite anogenital condyloma lata being reported in 4.3–58% of secondary syphilis cases, OCL remains poorly described, with very few documented confirmed cases. Interestingly, among extragenital sites, the oropharynx is the second most common location for these lesions [7].

Given the atypical presentation and rarity of OCL, this case report aims to highlight its clinical features and diagnostic challenges. Recognizing this rare manifestation is critical, as mis-diagnosis can delay appropriate treatment, thereby increasing the risk of transmission and progression. By presenting this case, we hope to contribute to the understanding of oropharyngeal syphilis and underscore the importance of considering secondary syphilis in the differential diagnosis of oropharyngeal lesions.

Case Report

A 43-year-old Thai man, diagnosed with HIV infection 2 years ago, has been receiving antiretroviral therapy with tenofovir alafenamide, emtricitabine, and dolutegravir, achieving virologic suppression for the past 6 months. His CD4 T-cell count was 331 cells/μL. He was also co-infected with chronic hepatitis C.

On 16 February 2023, he developed a sore throat and painful swallowing (odynophagia) without fever, rash, joint pain, or hair loss. He presented to the Infectious Diseases Clinic, Chulabhorn Hospital, Thailand, on 23 February 2023, reporting no recent medication use and infrequent sexual activity with a monogamous heterosexual partner. He could not recall the exact timing of his last sexual encounter but estimated it to be 6 months ago. His history included a diagnosis of secondary syphilis in December 2020 and a non-reactive rapid plasma reagin (RPR) test in May 2022.

On physical examination, a single, non-tender, moist, raised, whitish plaque with an erythematous base was observed on the soft palate mucosa (Figure 1). No lymphadenopathy, hepatosplenomegaly, skin rash (including palms and soles), anogenital lesions, or alopecia were detected. The primary differential diagnoses included OCL, atypical oral candidiasis, and a wart.

A potassium hydroxide (KOH) preparation of the lesion excluded fungal infection, as no yeast or pseudohyphae were observed. Further evaluation with treponemal and non-treponemal tests confirmed the diagnosis of OCL. The RPR test was reactive with a titer of 1: 128, and an electrochemiluminescence immunoassay (ECLIA) for Treponema pallidum antibodies was positive. No imaging studies were deemed necessary, as the diagnosis was based on clinical and laboratory findings.

The patient was promptly treated with a single dose of 2.4 million units of intramuscular benzathine penicillin G. His sore throat resolved completely within 7 days of treatment. Follow-up RPR titers demonstrated a 4-fold reduction, decreasing from 1: 128 at baseline to 1: 64 in May 2023 (3 months post-treatment) and 1: 32 in August 2023 (6 months post-treatment). By November 2023 (9 months post-treatment), the titer had further decreased to 1: 16, and it was 1: 8 in February 2024 (12 months post-treatment), consistent with a serological response to therapy.

Discussion

This case report highlights the rare presentation of secondary syphilis as isolated OCL, emphasizing the diagnostic and therapeutic challenges associated with this atypical manifestation. Isolated OCL is characterized by unique oral lesions, often without systemic features of secondary syphilis, such as lymphadenopathy, rash, or anogenital condyloma lata. The patient presented with a sore throat and odynophagia, accompanied by a distinctive moist, lobulated, grayish-white plaque on the soft palate. These findings, along with positive serological tests for T. pallidum, confirmed the diagnosis. The patient responded rapidly to a single dose of 2.4 million units of intramuscular benzathine penicillin G, with complete resolution of symptoms within 7 days and significant serological improvement over the following months.

Secondary syphilis typically manifests approximately 2–6 weeks after the primary stage, with the rash persisting for 2–12 weeks. Although secondary syphilis is characterized by a wide array of symptoms, including mucocutaneous lesions, rashes (notably on the palms and soles), fever, myalgia, arthralgia, alopecia, and generalized lymphadenopathy, anogenital condyloma lata remains the most recognized and typical presentation. Condyloma lata generally appears 6 weeks to 6 months after the initial infection with T. pallidum, which spreads through the bloodstream. This systemic dissemination leads to mucous membrane lesions and widespread infiltration of spirochetes into these membranes, forming moist papules. These lesions are highly infectious and are commonly found in warm, moist areas of the body, such as the genitalia, perineum, and inner thighs [9,10].

However, some patients present with variable and nonspecific, isolated oropharyngeal lesions. OCL represents an atypical manifestation, particularly in cases where it occurs without accompanying skin eruptions or other signs commonly associated with secondary syphilis. In HIV-infected patients presenting with secondary syphilis, 85.5% exhibited mucous patches, followed by 10% with ulcers, and 5% with macular lesions [11]. The literature describes 2 distinct features: elevated mucosal plaques covered with a grey or white pseudomembrane and multiple mucous patches that coalesce into serpiginous lesions [12]. Papillomatosis is the only distinguishing feature that differentiates secondary syphilis from the chancre seen in primary syphilis [13]. Constant moisture, friction, heat, and maceration facilitate the coalescence and growth of syphilitic nodules, eventually leading to the formation of plaque-like condyloma [14].

Our comprehensive literature review revealed publications with documented oral and OCL, as well as publications that included syphilis with oral manifestations such as pharyngitis, nodules, plaques, and tonsillitis, which provided figures that were carefully reviewed and found to be potentially compatible with OCL.

A literature review revealed similar cases of OCL with diverse clinical presentations and outcomes (Table 1). Most documented cases have involved males, with ages ranging from 19 to 58 years, and a significant proportion reported risk factors such as unprotected oral or anogenital sexual contact. The risk factors are primarily linked to sexual behavior, including unprotected intercourse – both heterosexual and homosexual – and encounters with sex workers. In line with previous studies, oral sexual practices were identified in only a minority of OCL cases and remain a controversial factor among the sexual behaviors associated with OCL [15].

Patients with OCL typically present with various symptoms, including syphilitic angina (sore throat), a sensation of a foreign body, and painless oral lesions. These lesions exhibit diverse appearances, ranging from hypertrophic, verrucous, or mucous plaques to patches within the oral cavity, often leading to initial misdiagnoses, such as lymphoma, oral candidiasis, or condyloma acuminata.

Our review indicates that OCL lesions may persist for 1 week to 5 months. The most common sites for these lesions are the palate, lips, tonsils, and tongue, where they manifest as firm, moist, smooth, or papillate hypertrophic plaques. Additionally, mucous patches may coalesce into serpiginous lesions, described as snail track ulcers, verrucous plaques, cauliflower-like growths, leukoplakia-like plaques, and non-ulcerated white plaques covered with a pale grayish pellicle-like exudate (plaque opaline) [16], which can emit a sweet odor [5]. Notably, our review found no reports of ulceration or ulceronodular forms (Lues maligna), which have also been described as OCL.

Intriguingly, isolated OCL can manifest independently of anogenital condyloma lata and may occur without accompanying corymbiform syphilids or the involvement of other organs. However, some cases have reported generalized lymphadenopathy or cervical adenitis. Unlike a chancre, which is typically reported as a solitary lesion, isolated OCL can present as either solitary or multiple lesions [17]. The serological profiles of these cases often showed high titers on non-treponemal tests, with VDRL titers ranging from 1: 8 to 1: 128, with 71% of cases exhibiting titers of 1: 32 or higher and reactive treponemal tests, confirming the diagnosis [7]. Histopathological examination, performed in select cases, typically reveals plasma cell-rich infiltration and the presence of T. pallidum, consistent with syphilitic lesions. The pathological manifestation of OCL is plasma cell-rich mononuclear infiltration with the presence of T. pallidum. These should be distinguished from granulomatous nodules in gumma [17]. While biopsy is not routinely performed, it may be necessary in cases where malignancy or other conditions are suspected.

Treatment with benzathine penicillin G was consistently effective, with most patients achieving complete recovery within 1 to 2 weeks of therapy. The majority showed a fourfold reduction in non-treponemal titers within 3 to 6 months, similar to the outcomes in our case. This reinforces the importance of early diagnosis and prompt treatment to ensure favorable outcomes and prevent further transmission (Table 1).

The clinical implications of this case are significant. The increasing incidence of syphilis, particularly among individuals with HIV and those engaging in high-risk sexual behaviors, underscores the need for heightened clinical vigilance. OCL often mimics other oral conditions, posing a diagnostic challenge for healthcare providers, including dentists and otolaryngologists. As our review demonstrates, serological testing remains a cornerstone for diagnosing OCL and should be considered in all cases of unexplained oral lesions, especially when risk factors for syphilis are present.

This case, along with a review of similar reports, highlights the importance of including OCL in the differential diagnosis of oropharyngeal lesions, even in the absence of classic signs of secondary syphilis. Delayed or missed diagnoses can result in silent transmission, disease progression, and severe complications. Additionally, inadequate adherence to contact precautions and high-risk behaviors, such as oral sex, mouth-to-mouth kissing, and sharing toothbrushes, play a critical role in disease transmission. These factors can lead to significant consequences, including the progression of secondary syphilis to its latent or tertiary stages [11,18]. Future research should aim to better elucidate the epidemiology and clinical spectrum of OCL, particularly its association with HIV and other risk factors, to enhance diagnostic accuracy and improve patient outcomes.

Conclusions

Isolated OCL is an under-reported and deceptive manifestation of secondary syphilis, often mimicking other oral conditions and complicating diagnosis. Treponemal serological testing is essential for its definitive identification, particularly in patients with a history of unprotected sexual encounters. The varied presentation of OCL highlights the importance of a thorough differential diagnosis to avoid misdiagnosis and delayed care. Early recognition and timely treatment with benzathine penicillin G are crucial to preventing disease progression and reducing transmission risk.