INTRODUCTION

Background: Treponema pallidum is the microaerophilic spirochete that causes syphilis, a chronic systemic venereal disease with multiple clinical presentations (ie, the great imitator). Syphilis is characterized by episodes of active disease (primary, secondary, tertiary stages) interrupted by periods of latency. Since the diagnosis frequently is suspected after examination of skin lesions, dermatologists are recognized as experts in the diagnosis and treatment of syphilis. Syphilis is transmitted in 2 ways, either from intimate contact with infectious lesions (most common) or blood transfusions (blood collected during early syphilis), or it is transmitted transplacentally from an infected mother to her fetus.

Pathophysiology: In acquired syphilis, the organism rapidly penetrates intact mucous membranes or microscopic dermal abrasions and, within a few hours, enters the lymphatics and blood to produce systemic infection. The central nervous system is invaded early in the infection; during the secondary stage, examinations demonstrate that more than 30% of patients have abnormal findings in the cerebrospinal fluid (CSF). During the first 5-10 years after infection, the disease principally involves the meninges and blood vessels, resulting in meningovascular neurosyphilis. Later, the parenchyma of the brain and spinal cord are damaged, resulting in parenchymatous neurosyphilis.

Regardless of the stage of disease and location of lesions, 2 histopathologic hallmarks of syphilis have been noted including obliterative endarteritis and plasma cell–rich mononuclear infiltrates. Endarteritis is caused by the binding of spirochetes to endothelial cells, mediated by host fibronectin molecules bound to the surface of the spirochetes. The resultant endarteritis heals with scar tissue formation.

The mononuclear infiltrates reflect a delayed-type hypersensitivity response to T pallidum, and in certain individuals with tertiary syphilis, this response by sensitized T lymphocytes and macrophages results in gummatous ulcerations and necrosis. Antigens of T pallidum induce host production of treponemal antibodies and nonspecific reagin antibodies. Immunity to syphilis is incomplete. For example, host humoral and cellular immune responses may prevent the formation of a primary lesion (chancre) on subsequent infections with T pallidum, but they are insufficient to clear the organism. This may be because the outer sheath of the spirochete is lacking immunogenic molecules, or it may be because of down-regulation of helper T cells of the TH1 class.

Frequency:

• In the US: The incidence of syphilis had been declining in recent years, with 53,000 reported cases (11,387 primary and secondary cases) in 1996, compared with 113,000 cases (33,962 primary and secondary cases) reported in 1992. However, the number of cases of primary and secondary syphilis increased yearly from 2000-2003. In 2003, 7177 cases were reported to the US Centers for Disease Control and Prevention. Most of this increase has been noted in men, particularly in men who have sex with other men. The overall cases reported in women decreased. More than 80% of cases were reported in the southern United States. Trends for congenital syphilis cases closely parallel those for acquired syphilis cases in women, namely, a decreased incidence over the past decade.

• Internationally: Syphilis remains prevalent in many developing countries and in some areas of North America, Asia, and Europe, especially Eastern Europe. In some regions of Siberia, as of 1999, prevalence was 1300 cases per 100,000 population.

Mortality/Morbidity:

• Although rarely seen by clinicians since the use of penicillin became widespread in the 1950s, the primary complications of syphilis in adults include neurosyphilis, cardiovascular syphilis, and gumma. Death resulting from syphilis continues to occur. One study found that of 113 recorded deaths resulting from sexually transmitted diseases, 105 were caused by syphilis, with cardiovascular and neurosyphilis accounting for the majority of these deaths.

• These figures have continued to increase since the emergence of the AIDS epidemic, since genital ulcer diseases (including syphilis) are cofactors for the sexual transmission of HIV. Additionally, untreated patients who are HIV seropositive have an increased risk for rapid progression to neurosyphilis and for its complications. In addition, patients with HIV are at greater risk for development or relapse of early symptomatic neurosyphilis for up to 2 years after treatment with intramuscular or intravenous penicillin.

• Congenital syphilis is the most serious outcome of syphilis in women. It has been shown that a higher proportion of infants are affected if the mother has untreated secondary syphilis, compared to untreated early latent syphilis. Since T pallidum does not invade the placental tissue or the fetus until the fifth month of gestation, syphilis causes late abortion, stillbirth, or death soon after delivery in more than 40% of untreated maternal infections. Neonatal mortality usually results from pulmonary hemorrhage, bacterial superinfection, or fulminant hepatitis.

Race: In the United States, syphilis is more prevalent among persons of minority race and ethnicity. The reported prevalence of syphilis is somewhat higher among blacks than other ethnic groups. However, this rate has declined significantly in the past few years. From 2000-2003, the primary and secondary syphilis rate declined from 12 cases per 100,000 population to 7.8 cases per 100,000 population in this ethnic group. In 2002, 49.8% of all reported cases were in blacks, compared with 39.2% of cases in 2003.

Sex: The male-to-female ratio has increased over the past 3 years, largely due to the increased rate of disease among men who have sex with other men. In 2003, it was approximately 5:1.

Age: The incidence of syphilis peaks at age 15-34 years.

CLINICAL

History:

• Primary syphilis occurs within 3 weeks of contact with an infected individual. Patients usually present with a solitary red papule that rapidly forms a painless nonbleeding ulcer or chancre (see Image 1). The chancre usually heals within 4-8 weeks, with or without therapy.

• Secondary syphilis 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.

• 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.

• 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.

• 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.

Physical:

• Primary syphilis
  • The primary lesion (chancre) occurs on the penis or scrotum of 70% of men with syphilis and on the vulva, cervix, or perineum of more than 50% of women with syphilis.

  • The primary lesion usually is a single ulcerated lesion with a surrounding red areola. The edge and base of the ulcer have a cartilaginous (buttonlike) consistency on palpation.

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

  • Extragenital chancres occur most commonly above the neck, typically affecting the lips or oral cavity.

  • The regional lymph nodes usually enlarge painlessly and are firm, discrete, and nontender.

• Secondary syphilis
  • The protean manifestations of the secondary stage usually include localized or diffuse symmetric mucocutaneous lesions and generalized nontender lymphadenopathy (see Images 3-4).

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

• Initial lesions are bilaterally symmetric, pale red to pink (in light-skinned persons) or pigmented (in dark-skinned persons), discrete, round 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.

• 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.

• In 10% of patients, highly infectious papules develop at the mucocutaneous junctions and, in moist intertriginous skin, become hypertrophic and dull pink or gray (condyloma lata; see Image 2).

• From 10-15% of patients with secondary syphilis develop superficial mucosal erosions 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.

• 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, and ulcerative colitis.

• Tertiary syphilis
  • 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.

  • Cutaneous gummas are indurated, nodular, papulosquamous or ulcerative lesions that form characteristic circles or arcs with peripheral hyperpigmentation.

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

• Symptomatic neurosyphilis produces various clinical syndromes that develop in approximately 5% of patients with syphilis who remain untreated. 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.

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

• 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.

• 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).

• 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).

• Early manifestations
  • 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.

  • 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 (28%), and snuffles (23%).

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

• Late manifestations
  • Late signs and symptoms are rare and, if encountered, usually involve complications including interstitial keratitis, cranial nerve VIII deafness, corneal opacities, and/or recurrent arthropathy.

  • The clinical manifestations of untreated congenital neurosyphilis present in 25% of patients older than age 6 years and correspond to those of adult neurosyphilis.

  • Gummatous periostitis occurs in patients aged 5-20 years and tends to cause destructive lesions of the palate and nasal septum (saddle nose).

  • Dental abnormalities may be evident, such as centrally notched and widely spaced, peg-shaped, upper central incisors (Hutchinson teeth) and sixth-year molars with multiple poorly developed cusps (mulberry molars).

  • Peculiar bone findings include frontal bossing of Parrot and Higoumenakia sign, which is unilateral irregular enlargement of the sternoclavicular portion of the clavicle secondary to periostitis.

DIFFERENTIALS

Amyloidosis, Lichen
Chancroid
Drug Eruptions
Erythema Multiforme
Herpes Simplex
Leprosy
Lymphogranuloma Venereum
Pityriasis Rosea
Pityriasis Rubra Pilaris
Rubella
Sarcoidosis
Scabies
Tinea Corporis

Other Problems to be Considered:

Erosive balanitis
Traumatic superinfected lesions