Syphilis Clinical Presentation

Because the manifestations of syphilis (particularly advanced syphilis) are nonspecific and may masquerade as many other diseases, the physician must keep a high index of suspicion regarding the possible diagnosis of syphilis. Rigorous attention to the time course of symptoms is required for proper staging.

Obtain a thorough sexual and social history, including the number of sexual partners, condom use, history of sexually transmitted diseases (STDs) in the patient and their partners, intravenous (IV) drug use, and exposure to blood products.

In children and infants, seek a maternal history, history of exposure to individuals with syphilis or blood products, and a history of sexual abuse.

Primary syphilis

Primary syphilis occurs within 3 weeks of contact with an infected individual. It manifests mainly on the glans penis in males and on the vulva or cervix in females. Ten percent of syphilitic lesions are found on the anus, fingers, oropharynx, tongue, nipples, fingers, or other extragenital sites. Regional nontender lymphadenopathy follows invasion.

Lesions (chancres) are usually solitary, raised, firm, red papules that can be several centimeters in diameter. The chancre erodes to create an ulcerative crater within the papule, with slightly elevated edges around the central ulcer (see the images below). It usually heals within 4-8 weeks, with or without therapy.

Although genital chancres are frequently solitary, they may be multiple in some patients. Sometimes they appear as “kissing” lesions on opposing skin surfaces—for example, the labia (see the image below).

Secondary syphilis

Secondary syphilis manifests in various ways. It usually presents with a cutaneous eruption within 2-10 weeks after the primary chancre and is most florid 3-4 months after infection. The eruption may be subtle; 25% of patients may be unaware of skin changes. A localized or diffuse mucocutaneous rash (generally nonpruritic and bilaterally symmetrical) with generalized nontender lymphadenopathy is typical (see the image below). Patchy alopecia and condylomata lata may also be observed.

Mild constitutional symptoms of malaise, headache, anorexia, nausea, aching pains in the bones, and fatigue often are present, as well as fever and neck stiffness. A small number of patients develop acute syphilitic meningitis and present with headache, neck stiffness, facial numbness or weakness, and deafness.

Other less-common manifestations include GI involvement, hepatitis, nephropathy, proctitis, arthritis, and optic neuritis.

Latent syphilis

Latency may last from a few years to as many as 25 years before the destructive lesions of tertiary syphilis manifest. Affected patients may recall symptoms of primary and secondary syphilis. They are asymptomatic during the latent phase, and the disease is detected only by serologic tests.

Latent syphilis is divided into early latent and late latent. The distinction is important because treatment for each is different. The early latent period is the first year after the resolution of primary or secondary syphilis. Asymptomatic patients who have a newly active serologic test after having a serologically negative test result within 1 year are also considered to be in the early latent period. Late latency syphilis is not infectious; however, women in this stage can spread the disease in utero.

A small percentage of infants infected in utero may have a latent form of infection that becomes apparent during childhood and, in some cases, during adult life. The earliest symptom that occurs prior to age 2 years is rhinitis (snuffles), soon followed by cutaneous lesions. After age 2 years, parents may note problems with the child’s hearing and language development and with vision. Facial and dental abnormalities may be noted.

Tertiary syphilis

Tertiary (late) syphilis is slowly progressive and may affect any organ. The disease is generally not thought to be infectious at this stage. Manifestations may include the following:

• Altered mental status
• Focal neurologic findings, including sensorineural hearing and vision loss
• Dementia
• Symptoms related to the cardiovascular system or the central nervous system (CNS)

The lesions of benign tertiary syphilis usually develop within 3-10 years of infection. The typical lesion is a gumma, and patient complaints usually are secondary to bone pain, which is described as a deep boring pain characteristically worse at night. Trauma may predispose a specific site to gumma involvement.

CNS involvement may occur, with presenting symptoms representative of the area affected (ie, brain involvement [headache, dizziness, mood disturbance, neck stiffness, blurred vision] and spinal cord involvement [bulbar symptoms, weakness and wasting of shoulder girdle and arm muscles, incontinence, impotence]).

Some patients may present up to 20 years after infection with behavioral changes and other signs of dementia, which is indicative of neurosyphilis.

Congenital syphilis

Early congenital syphilis occurs within the first 2 years of life. Late congenital syphilis emerges in children older than 2 years.

Conduct the physical examination with the manifestations of primary, secondary, and tertiary syphilis in mind. The lesions and exanthem of primary and secondary syphilis are infectious; thus, gloves and other relevant personal protective equipment must be worn.

Primary syphilis

The patient is typically afebrile. Symmetric rash is typical; however, the presence of overlying superinfection, scratching, or scaling may make the presentation atypical.

The chancre of primary syphilis usually begins as a single, painless papule that rapidly becomes eroded and indurated, with a surrounding red areola. The edge and base of the ulcer have a cartilaginous (buttonlike) consistency on palpation. Although classic chancres are not painful, they can become so if suprainfected with bacteria. Atypical primary lesions are common and may manifest as a papular lesion without subsequent ulceration or induration.

The primary lesion usually is associated with regional lymphadenopathy that may be unilateral or bilateral. Inguinal adenitis is usually discrete, firm, mobile, and painless, without overlying skin changes.

Chancres usually are located on the penis in heterosexual men, but in homosexual men, they may be found in the anal canal, mouth, or external genitalia. Common primary sites in women include the cervix and labia. Extragenital chancres occur most commonly above the neck, typically affecting the lips or oral cavity.

The lesion is highly infectious; when abraded, it exudes a clear serum containing numerous T pallidum organisms.

The healing primary chancre may remain present in 15-25% of patients.

Secondary syphilis

Secondary syphilis may present in many different ways but usually includes a localized or diffuse mucocutaneous rash and generalized nontender lymphadenopathy. The exanthem may be macular, papular, pustular, or mixed (see the images below).

Initial lesions are bilaterally symmetric, pale red to pink (in light-skinned persons) or pigmented (in dark-skinned persons), discrete, round, nonpruritic macules that measure 5-10 mm in diameter and are distributed on the trunk and proximal extremities. After several days or weeks, red papular lesions 3-10 mm in diameter appear. These lesions often become necrotic and are distributed widely with frequent involvement of the palms and soles (see the image below).

Tiny papular follicular syphilids involving hair follicles may result in patchy alopecia. In addition to the classic moth-eaten alopecia, a diffuse alopecia also has been reported.

Reddish-brown papular lesions on the penis or anogenital area can coalesce into large elevated plaques up to 2-3 cm in diameter, known as condylomata lata (see the images below). Lesions usually progress from red, painful, and vesicular to “gun metal grey” as the rash resolves. Condylomata lata are highly infectious. They are sometimes confused with condylomata acuminata or venereal warts.

From 10-15% of patients with secondary syphilis develop superficial mucosal erosions, usually painless, on the palate, pharynx, larynx, glans penis, vulva, or in the anal canal and rectum. These mucous patches are circular silver-gray erosions with a red areola. The erosions harbor treponemes and can transmit disease.

Ocular abnormalities, such as iritis, are a rare clinical finding, although anterior uveitis has been reported in 5-10% of patients with secondary syphilis. Less common findings include periostitis, arthralgias, meningitis, nephritis, hepatitis, proctitis, and ulcerative colitis. Go to Interstitial Keratitis for complete information on this topic.

Thirty percent of patients experience recurring symptoms after the primary or secondary stage of syphilis. Lesions are less numerous but are still infectious.

Tertiary syphilis

Symptomatic tertiary syphilis is the result of a chronic, progressive inflammatory process that eventually produces clinical symptoms years to decades after the initial infection. The liver and skeleton are commonly affected. Fever, jaundice, anemia, and nighttime skeletal pain are characteristic.

Gummatous syphilis is characterized by coalescent granulomatous lesions, called gummas, that usually affect skin, bone, and mucous membranes but may involve any organ system, often causing local destruction of the affected organ system (see the image below). Cutaneous gummas are indurated, nodular, papulosquamous or ulcerative lesions that form characteristic circles or arcs with peripheral hyperpigmentation. They may mimic other granulomatous ulcerative lesions and may be histologically indistinguishable from them.

Although gummas may be identified on the skin, in the mouth, and in the upper respiratory tract, they appear most commonly on the leg just below the knee. Gummas may be multiple or diffuse but usually are solitary lesions that range from less than 1 cm to several centimeters in diameter. They are generally asymmetric and grouped together.

Cardiovascular syphilis usually involves the aorta, though other large arteries may be affected as well. Invading treponemes cause scarring of the tunica media. Over many years, the inflammatory scarring weakens the aortic wall, leading to aneurysm formation, which causes incompetence of the aortic valve and narrowing of the coronary ostia.

The most common clinical finding on cardiovascular examination is a diastolic murmur with a tambour quality, secondary to aortic dilation with valvular insufficiency.

Neurosyphilis is caused by invasion of T pallidum into the CNS. It manifests as an insidious but progressive loss of mental and physical functions and is accompanied by mood alterations.

Neurosyphilis may be either asymptomatic or symptomatic. In asymptomatic neurosyphilis, no signs or symptoms are present, but CSF abnormalities are demonstrable, including possible pleocytosis, elevated protein, decreased glucose, or a reactive CSF Venereal Disease Research Laboratory (VDRL) test.

Symptomatic neurosyphilis produces various clinical syndromes that develop in approximately 5% of patients with syphilis who remain untreated. It may manifest in the following three forms:

• Syphilitic meningitis
• Meningovascular neurosyphilis
• Parenchymatous neurosyphilis

Syphilitic meningitis usually develops within 6 months to several years of initial infection, and patients present with typical symptoms of meningitis, including headache, nausea and vomiting, and photophobia, but are typically afebrile. Patients may exhibit cranial nerve abnormalities.

Meningovascular syphilis manifests 5-10 years after infection and is the result of endarteritis, which affects small blood vessels of the meninges, brain, and spinal cord. Patients may present with CNS vascular insufficiency or outright stroke. The most common presentation of meningovascular syphilis (diffuse inflammation of the pia and arachnoid along with widespread arterial involvement) is an indolent stroke syndrome involving the middle cerebral artery.

Cranial nerve palsies and pupillary abnormalities occur with basilar meningitis.

Parenchymatous neurosyphilis results from direct parenchymal CNS invasion by T pallidum and is usually a late development (15-20 years after primary infection). It includes general paresis and tabes dorsalis. Paretic syphilis is the result of widespread parenchymal invasion that causes individual cell death and brain atrophy. Tabes dorsalis is the result of damage to the sensory nerves in dorsal roots, producing ataxia and loss of pain sensation, proprioception, and deep tendon reflexes in joints.

Patients with parenchymatous neurosyphilis present with ataxia; incontinence; paresthesias; and loss of position, vibratory, pain, and temperature sensations. Paresis and dementia, with changes in personality and intellect, may develop.

Tabes dorsalis presents with signs of demyelination of the posterior columns, dorsal roots, and dorsal root ganglia (eg, ataxic wide-based gait and foot slap, areflexia and loss of position, deep pain and temperature sensations). Deep ulcers of the feet can result from loss of pain sensation.

Argyll Robertson pupil, which occurs almost exclusively in neurosyphilis, is a small irregular pupil that reacts normally to accommodation but not to light.

Rare findings include iritis, with possible adhesion of the iris to the anterior lens, producing a fixed pupil (not to be confused with Argyll Robertson pupil).

Go to Neurosyphilis for complete information on this topic.

Congenital syphilis

The manifestations of untreated congenital syphilis can be divided into those that are expressed prior to age 2 years (early) or after age 2 years (late).

Clinical evidence of early congenital syphilis is similar to that of secondary syphilis in adults.^[16] Early signs and symptoms include development of a diffuse rash, characterized by extensive sloughing of the epithelium, particularly on the palms, soles, and skin around the mouth and anus. The rash has a higher probability of being atypical and can be vesicular or bullous instead of the characteristic reddish brown macular rash.

A compilation of early clinical presentations of congenital syphilis in 9 studies involving a total of 212 infants included abnormal bone radiographs (61%); hepatomegaly (51%); splenomegaly (49%); petechiae (41%); other skin rashes (35%); anemia (34%); lymphadenopathy (32%); jaundice (30%); pseudoparalysis, often due to pain secondary to osteochondritis (28%); and snuffles (23%).

A classic mucocutaneous sign is depressed linear scars radiating from the orifice of the mouth (perioral fissures), termed rhagades (Parrot lines).

Additional symptoms of early congenital syphilis include the following:

• Hemorrhagic rhinitis
• Periostitis
• Mucous patches
• Hydrops
• Glomerulonephritis
• Thrombocytopenia
• Neurologic involvement
• Ocular involvement (see the image below.)Syphilis. This photograph illustrates chorioretinitis of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

The clinical manifestations of untreated congenital neurosyphilis present in 25% of patients older than age 6 years and correspond to those of adult neurosyphilis. Late congenital syphilis mainly manifests as neurologic symptoms. Cardiovascular abnormalities are rare. Findings include the following^[17] :

• Bony abnormalities, including prominent frontal bones, depression of nasal bridge, abnormal maxilla development, anterior tibial bowing, frontal bossing of Parrot, and Higoumenakia sign (unilateral irregular enlargement of the sternoclavicular portion of the clavicle secondary to periostitis)
• Clutton joints (arthritis of both knees)
• Interstitial keratitis
• Hutchinson incisors (centrally notched and widely spaced, peg-shaped, upper central incisors; see the image below)
• Mulberry molars (sixth-year molars with multiple poorly developed cusps)
• Cranial nerve VIII deafness
• Paroxysmal cold hemoglobinuria
• Gummatous involvement - Gummatous periostitis occurs in patients aged 5-20 years and tends to cause destructive lesions of the palate and nasal septum (saddle nose).
• Corneal opacitiesSyphilis. This photograph shows an example of Hutchinson teeth in congenital syphilis. Note notching. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

Go to Pediatric Syphilis for complete information on this topic.

Complications of syphilis may include the following:

• Cardiovascular disease
• CNS disease
• Membranous glomerulonephritis
• Paroxysmal cold hemoglobinemia
• Irreversible end-organ damage
• Disfigurement by gummas