An Overview of Syphilis
Dr Amanda Phoon Nguyen
Syphilis is a systemic infectious disease caused by the filamentous, anaerobic spirochaete Treponema pallidum. The disease can be transmitted sexually (acquired syphilis) or vertically via the placenta (congenital syphilis). Although effective therapy has been available for a long time, the incidence of syphilis has increased worldwide in the past decade. It is endemic in low-income countries and occurs at lower rates in middle-income and high-income countries. The Government of Western Australia has issued an alert due to the increase in syphilis notifications. The rate of syphilis notifications here have doubled between 2016 and 2020.
Communities at risk include:
-People who experience homelessness
-People who use methamphetamine and/or inject drugs
-Culturally and linguistically diverse (CaLD) people
-People who are 16 - 35 years old
-Aboriginal communities in remote areas
-Aboriginal people 16-39 years old, particularly in regions experiencing an ongoing outbreak of infectious syphilis (Goldfields, Kimberley and Pilbara)
-Women of child bearing age (currently represent 30 percent of all infectious syphilis notifications in metropolitan Perth)
-Men who have sex men (MSM) in the Perth metropolitan area.
Clinical Presentation
There are three main stages with different clinical presentations and infectivity. Oral lesions may occur at any of the three main stages of the clinical course, including the primary, secondary, and tertiary phases. Oral manifestations of syphilis are multiple and highly variable, and often detected in secondary stage. Only the 8% of patients and the 25% had, respectively, primary and tertiary lesions. Primary syphilis is detected as ulcer in all patients, while secondary syphilis is detected as ulcer in about 50% of cases. Oral presentation may not be synchronous to cutaneous (Leuci et al. 2013).
Because of the heterogeneity of the oral clinical aspects, the differential diagnosis includes a huge groups of diseases: traumatic or cancerous or non-specific inflammatory ulcers, autoimmune (pemphigus/pemphigoid) or immune-related lesions (lichen planus, erythema multiforme), traumatic (frictional keratosis) or hyperplastic/dysplastic plaques, and other infectious diseases such as tuberculosis, deep fungal, herpes lesions and hairy leucoplakia.
Controversial/rarer presentations include mucosal patches, leukoplakia-like lesions, blistering mucositis, and necrosis of the dorsum of the tongue.
PRIMARY SYPHILIS (adapted from Leao 2006)
The mouth is rarely the site of primary syphilis. A chancre, a painless, indurated ulcer at the site of inoculation, develops within 1 to 3 weeks of acquisition. Primary syphilis is usually the consequence of orogenital or oroanal contact with an infectious lesion. Kissing may, very rarely, cause transmission. Primary syphilis of the mouth manifests as a solitary ulcer usually of the lip or, more rarely, the tongue. Chancres may resolve without treatment.
SECONDARY SYPHILIS (adapted from Leao 2006)
The features of secondary syphilis reflect the hematogenous spread of T. pallidum, and similarly to its other mucocutaneous features, the oral manifestations of secondary syphilis can be more extensive and/or variable than those of the primary disease. Oral lesions arise in at least 30% of patients with secondary syphilis, although very rarely oral ulceration may be the only manifestation of infection. The 2 principal oral features of secondary syphilis are mucous patches and maculopapular lesions, although nodular lesions may rarely arise.
Macular syphilides: Macular lesions tend to arise on the hard palate and manifest as flat-to-slightly raised, firm, red lesions.
Papular syphilides: These are rare. They manifest as red, raised, firm round nodules with a grey center that may ulcerate. The papules usually arise on the anterior dorsal tongue, buccal mucosa or commissures.
Mucous patches: A variety of descriptions of mucous patches have been reported. These may present as oval-to-crescenteric erosions or shallow ulcers of about 1 cm diameter, covered by a grey mucoid exudate and with an erythematous border. Common sites include bilaterally on the mobile surfaces of the mouth. The pharynx, gingivae, tonsils, and very rarely the hard palate can be affected. At the commissures, the mucous patches may appear as split papules. The mucous patches may coalesce to give rise to, or arise de novo as, serpiginous lesions, sometimes termed snail track ulcers.
· Others: macroglossia, painful fissuring and/or papular lesions on the anterior 2/3 dorsum tongue.
ULCERONODULAR DISEASE (LUES MALIGNA) (adapted from Leao 2006)
Ulceronodular disease is an explosive generalized form of secondary syphilis characterized by fever, headache, and myalgia, followed by a papulopustular eruption that rapidly transforms into necrotic, sharply demarcated ulcers with hemorrhagic brown crusts, organized in rupioid layers commonly on the face and scalp. The mucosa is involved in about one third of affected patients. Lues maligna gives rise to crateriform or shallow ulcers on the gingivae, palate or buccal mucosa, with multiple erosions on the hard and soft palates, tongue and lower lip.
NODULAR DISEASE
Rarely, secondary syphilis can manifest as nodules alone. This nodular eruption of syphilis has a predilection for the face, mucous membranes, palms of the hands and soles of the feet. Lesions may occur on the vermillion, mimicking squamous cell carcinoma or keratoacanthoma.
LATENT SYPHILIS
In early latent syphilis, usually the first 12 months after secondary disease, affected patients are infectious. In late latent syphilis the infectivity falls.
TERTIARY SYPHILIS
Clinical disease arises in about one third of patients with untreated secondary syphilis. The oral complications of tertiary syphilis center upon gumma formation, and much more rarely, syphilitic leukoplakia (and controversial risk of oral squamous cell carcinoma) and neurosyphilis.
Gummas tend to arise on the hard palate and tongue, although very rarely they may occur on the soft palate, lower alveolus, and parotid gland. Gumma manifests radiologically as ill-defined radiolucencies that may resemble malignancy. The areas of ulceration eventually heal, although the resultant scarring can, at least on the tongue, cause fissuring.
NEUROSYPHILIS
Argyll Robertson pupil, both unilateral and bilateral trigeminal neuropathy and facial nerve palsy. Potentially, syphilitic osteomyelitis may give rise to trigeminal neuropathy.
CONGENITAL SYPHILIS
Early features include diffuse maculopapular rash, periostitis (frontal bossing), and rhinitis. Late features, manifesting at least 24 months after birth, comprise the Hutchinsonian triad of interstitial keratitis of the cornea, sensorineural hearing loss, and dental anomalies.
Diagnosis
The diagnosis of syphilis may require a knowledge of the patient’s sexual history, physical examination, and an interpretation of serological and microbiological findings. The diagnosis is often made on clinical and serological grounds without recourse to biopsy. Histopathology is not always helpful, as there are no specific histopathological features, though some histological features may be indicative. An immunohistochemical reaction using an anti-treponemal antibody is highly specific, with specificity ranging from 74% to 94%.
If you suspect your patient has oral lesion due to a syphilis infection, the following steps can be taken:
-Swab for polymerase chain reaction (PCR) testing by rotating a DRY swab near the centre of the ulcer for 5 seconds. Apply pressure to express tissue fluid from the wound bed. Send the swab without transport medium to a pathology provider and request a syphilis PCR.
-Alternatively, refer the patient
-Ensure the patient’s GP/primary health care provider (e.g. Aboriginal health service, Homeless Healthcare) receives a copy of the SYPHILIS PCR test result.
For serological testing, the non-treponemal tests become positive 1–4 weeks after the appearance of the primary lesion, and 6 weeks after exposure. The most commonly used is the VDRL (Venereal Disease Research Laboratory) test which is the method of choice for follow-up testing during and after treatment. The treponemal tests are used mainly as confirmatory tests to verify reactivity in non-treponemal tests. The most common is the FTA-ABS test.
Management includes benzathine penicillin G, tetracycline, azithromycin, or doxycycline. However, resistance to azithromycin has emerged rapidly.
References and further reading:
Leao et al. 2006
Minicucci et al. 2013
Leuci et al. 2013