Oral and Maxillofacial Pathology Case of the Month Diagnosis and Management

ORALand maxillofacial pathology diagnosis and management—from page 234

Diagnosis: Mucous Patch-secondary Syphilis

Discussion

Based on the clinical findings, location of the lesions and the patient’s medical history, a differential diagnosis should include mucous patch as a manifestation of secondary syphilis; chronic hyperplastic candidiasis, leukoplakia, and pseudomembranous pharyngitis are also considered.

Syphilis:

Syphilis, caused by the Spirochete Treponema pallidum, is one of the common sexually transmitted diseases noted in the United States.1,2 Mucous patch is the classic oral manifestation of secondary syphilis which develops 2-12 weeks after the initial infection and 8-weeks after the resolution of primary syphilis. Since reaching a historic low in 2000 and 2001, there has been a resurgence in syphilis incidence in the United States, especially among males who have sex with men (MSM).1,2 Multiple sexual partners, decreasing use of barrier protection (i.e., condom), illicit drug use, alcohol abuse, and HIV coinfection are the major risk factors for contracting syphilis.1,2

The transmission of T. pallidum usually occurs via sexual contact.3,4 These organisms penetrate the skin and mucosal barriers via oral or genital mucosal breeches during sexual activity. Once entered through the skin or mucosa, T. pallidum disseminates rapidly to the regional lymph nodes.2,4 If left untreated, it undergoes systemic dissemination via the bloodstream and progresses to secondary syphilis.2,4 Untreated syphilis can progress over years through a series of clinical stages and have serious potentially lifealtering and irreversible health consequences such as neurological complications, hearing loss, blindness, and an increased likelihood of contracting other sexually transmitted diseases.2 Pregnant females with syphilis infection can give birth to babies with congenital syphilis, as well as suffer from an increased risk of miscarriage, stillbirth, birth defects, and/ or infant death.2 Although deaths from syphilis in the adult population are rare, a 6.5% case-fatality rate has been reported for babies born with congenital syphilis.

Primary Syphilis:

Primary syphilis, which presents as a chancre, develops the site of the bacterial organism’s entry and presents as a painless, red, indurated ulcer. Primary syphilis usually appears on the genitalia, but may be present on other sites such as the anus or oral cavity. The chancre heals on its own in a few days to weeks, even without treatment. The lips are the most common site of primary syphilis of the oral cavity, followed by the tongue and tonsillar area.

Secondary Syphilis:

Secondary syphilis demonstrates the most recognized clinical manifestations of syphilis, particularly among women or MSM, presumably because the painless anogenital chancre of primary syphilis is often overlooked. The classic presentation of secondary syphilis consists of nonspecific generalized symptoms (e.g., fever, malaise, lymphadenopathy) and variable mucocutaneous manifestations, including a maculopapular skin rash. When mucous membranes are involved, lesions can appear as highly infectious mucous patches and in moist areas might have an exuberant, verrucous appearance resembling warts (referred to as condylomata lata). These manifestations usually present 3 to 10 weeks after initial exposure. Primary syphilis and secondary syphilis are the sexually transmissible stages of infection.

Latent Syphilis:

The latent stage of syphilis is a period when there are no visible signs or symptoms of syphilis. It can occur between the primary and secondary stages and can also occur after the resolution of secondarystage lesions, potentially lasting for years.

Tertiary Syphilis:

Tertiary syphilis is a rare form of syphilis that can appear 10–30 years after infection was first acquired and it can be fatal. It can affect multiple organ systems, including the brain, nerves, eyes, heart, blood vessels, liver, bones, and joints. Tertiary syphilis is rarely encountered in developed countries owing to advancement of disease diagnosis and treatment.

Congenital Syphilis:

While the major increase in syphilis has been attributed to MSM, an increase in infection rates among females has also been reported. Pregnant females with syphilis infection are at risk of giving birth to babies with congenital syphilis due to vertical transmission. Contracting syphilis during pregnancy increases the risk of risk of miscarriage, stillbirth, premature labor, low birth weight, birth defects, and/ or infant death. Early intervention with penicillin therapy can successfully treat congenital syphilis in newborns. While the timely diagnosis of the disease remains the most prominent prognostic marker for congenital syphilis, blanket antenatal screening may prove an effective tool in disease prevention.2

Diagnosis of syphilis:

Treponema pallidum has a slender, coiled morphology and when examined by dark-field microscopy it moves with a drifting rotary motion (corkscrew). However, most clinical settings do not have the facility to directly detect T. pallidum with darkfield microscopy when lesions are present.6 Moreover, the darkfield microscopy cannot distinguish T-pallidum from other morphologically similar spirochetes of oral microbiome. Serologic tests consisting of both non-treponemal tests and treponemal-specific tests are used for screening and diagnostic confirmation of syphilis, respectively. Commonly used nontreponemal tests are rapid plasma reagin [RPR] and Venereal Disease Research Laboratory [VDRL]. The screening tests detect anticardiolipin antibodies present in syphilitic patients’ sera,

ORALand maxillofacial pathology, continued

using antigen substrate composed of cardiolipin, cholesterol and lecithin. These non-treponemal tests are inexpensive, rapid, and convenient for initial screening of patients suspected of having syphilis. These tests are also useful for monitoring the efficacy of treatment. However, these tests have less sensitivity for detecting syphilis during its early and late stages. Moreover, these tests tend to give false positivity among older patients, pregnant women, patients with autoimmune diseases such as systemic lupus erythematosus, malignancy, viral and mycoplasma infection. The treponemal tests (e.g., the T. pallidum particle-agglutination test or an automated enzyme or chemiluminescence immunoassay) are sensitive and specific for diagnostic confirmation of syphilis. If the nontreponemal test is non-reactive, further testing is necessary with a confirmatory treponemal test. The standard of care for treating syphilis is penicillin, and the patient’s response to treatment is assessed via serological test titers over a period of several months.

Hyperplastic candidiasis

HIV-positive patients are at high-risk for developing oropharyngeal candidiasis. Candidiasis is the most common opportunistic infection among HIV positive patients.5 Soft palate, tonsils, and oropharynx are the favored slides for candidiasis. Oropharyngeal candidiasis is considered a cardinal sign of immune suppression secondary to HIV infection.6 Although most of the oropharyngeal candidiasis among HIV patients is caused by Candida albicans, oral infections caused by nonalbicans Candida species are in the rise among HIV positive patients, especially among patients who are undergoing nucleosidebased HAART therapy.7 There are 3 clinical forms of oropharyngeal candidiasis: 1. Pseudomembranous candidiasis (also known as thrush) 2. Erythematous (atrophic) candidiasis 3. Hyperplastic candidiasis

Among HIV patients with immunosuppression, pseudomembranous candidiasis is the most common form and presents as painless, creamy white plaques. These white plaques can be partially wiped away with a tongue blade leaving an erythematous and eroded mucosal surface. Hyperplastic candidiasis presenting as thick white plaque resembling leukoplakia is a chronic form of candidal infection seen among HIV positive patients. Occurrence of chronic and/or recalcitrant oropharyngeal candidiasis among HIV-positive patients is an indicator of immune suppression. Oropharyngeal candidiasis typically occurs among HIV positive patients with CD4 T-lymphocytes counts <200 cells/mm.3 With the advent of “Combination Antiretroviral Therapy (cART)” oral candidiasis among HIV patients has declined dramatically. The current patient was on cART and his CD4 count was 527/mm.3 Therefore, it is highly unlikely the white plaques noted in his oropharynx and tonsillar area represent hyperplastic candidiasis.

Multifocal leukoplakias:

Oral leukoplakia is the most common type of oral potentially malignant disorder.8 It presents as a non-wipeable white patch/ plaque that cannot be characterized clinically or histopathologically to any specific disease.8 Leukoplakias most frequently occur at a single site and rarely present as multiple white patches/ plaques. The only exception for this rule is proliferative verrucous leukoplakia (PVL). PVL is a high-risk premalignancy presenting as multifocal and progressive leukoplakias. PVL is more common among elderly females and frequently involves the gingivae. PVL rarely begins in the oropharynx and only involves the oropharynx and its advanced stage. HIV patients have increased risk for developing both HPV-related and HPVunrelated oropharyngeal squamous cell carcinomas designated as nonAIDS defining cancers. However, multifocal white plaques are not the clinical presentations of these cancers involving the oropharynx and tonsil.

Pseudomembranous pharyngitis:

Pseudomembranous pharyngitis is bacterial infection caused by toxin-producing strains of Corynebacterium diphtheriae. 9 C. diphtheria is a non-encapsulated, nonmotile, gram positive bacillus causes upper respiratory tract and cutaneous infections.9 Pseudomembranous pharyngitis clinically presents with thick gray to white pseudomembrane overlying uvula, tonsils, and pharynx.9 It is preventable by vaccination, hence people most at risk of catching this infection on exposure to carrier or diseased individuals are those who are unvaccinated or have low antitoxin antibody levels. Pseudomembranous pharyngitis frequently occurs among children and is symptomatic, which effectively rules out this diagnosis in the current case.9

Patient’s follow-up:

This patient was tested for syphilis with reactive rapid plasma reagin (RPR) and RPR Reactive with 1:128. Subsequently, the patient was treated with three doses of 2.4 million penicillin G benzathine, resulting in successful resolution of the infection. References

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