Syphilis and Nonsyphilitic Treponematoses

The Pathogen

The causative agent of syphilis, T. pallidum subspecies pallidum , is closely related to other pathogenic spirochetes, including those causing yaws ( T. pallidum subspecies pertenue ) and pinta ( Treponema carateum ). T. pallidum is a thin, helical bacterium approximately 0.15 µm wide and 6 to 15 µm long. The organism has 6 to 14 spirals and is tapered on either end. It is too thin to be seen by ordinary Gram stain microscopy but can be visualized in wet mounts by dark-field microscopy or in fixed specimens by silver stain or fluorescent antibody methods.

Unlike most bacteria, which have protein-rich outer membranes, the T. pallidum outer membrane appears to be composed of predominantly phospholipids, with few surface-exposed proteins. This structure may help syphilis progress despite the fact that non–surface-exposed internal antigens elicit a brisk antibody response that is the basis for serologic tests for the diagnosis and management of syphilis. Between the outer membrane and the peptidoglycan cell wall are six axial fibrils; three are attached at each end, and they overlap in the center of the organism. These fibrils are structurally and biochemically similar to flagella and are in part responsible for the organism’s motility. All isolates studied are antigenically similar and susceptible to penicillin.

Primary Syphilis

The incubation period from the time of exposure to the development of the primary lesion averages approximately 21 days (range, 10 to 90 days). Initially, a painless papule develops at the site of inoculation and soon breaks down to form a clean-based ulcer—the chancre—with raised, indurated margins ( Fig. 295-1 ). The borders of the ulcer are raised, firm, and indurated. On occasion, secondary infections change the appearance of the ulcer and can cause the lesion to become painful. Most chancres are single, although multiple ulcers occur in up to 30% of persons. An untreated chancre persists for 2 to 6 weeks, heals spontaneously, and leaves a faint scar. The syphilitic chancre is usually associated with unilateral or bilateral regional lymphadenopathy. Regional lymph nodes are movable, discrete, and rubbery, but they may not be palpable if the chancre occurs in the cervix or rectum.

Chancres can occur at any site of inoculation by direct contact, and most occur in anogenital locations. Chancres can also be seen in the pharynx, on the tongue, around the lips, on the fingers, on the nipples, and other exposed areas. The morphology of the chancre depends in part on the location of the lesion and the host immune response. In previously infected individuals, chancres may be small and remain opular. Chancres of the finger may appear erosive and can be quite painful. Chancres located inside the female genital tract or anal canal are often missed unless clinical suspicion is high and a careful examination is performed.

Secondary Syphilis

If the initial lesion is not effectively treated, the natural history of syphilis infection ( Fig. 295-2 ) is to progress to secondary syphilis between 4 and 8 weeks after the appearance of the primary chancre. Signs and symptoms of secondary syphilis include malaise, fever, headache, sore throat, and other systemic complaints. Most patients have generalized lymphadenopathy, including involvement of the epitrochlear nodes. Approximately 30% of patients have evidence of a healing chancre, although many patients (including a disproportionate number of women and men who have sex with men) give no history of a primary lesion.

At least 80% of patients with secondary syphilis have cutaneous or mucocutaneous lesions at some point in their illness. Usually, the diagnosis is suspected on the basis of the cutaneous eruption. The rash, which is often minimally symptomatic, tends to be faint and can be difficult to visualize, particularly on dark-skinned individuals; as a result, many patients with late syphilis do not recall having a rash. Syphilitic rashes are varied in appearance but have certain characteristic features. Typical lesions are widespread, have symmetrical distribution, and are pink, coppery, or dusky red in color. They are generally nonpruritic and are rarely vesicular or bullous in adults. Lesions usually become indurated after the early macular stage, and they frequently have a superficial scale (i.e., papulosquamous lesions). Skin lesions tend to be polymorphic and rounded and can leave long-term residual pigmentation or depigmentation.

Early macular lesions are typically seen on the trunk, followed by spread to the rest of the body. The face is often spared, except for the perioral area. Next, a papular rash appears that is usually generalized and characteristically marked on the palms and soles ( Fig. 295-1B ). These rashes are often associated with a superficial scale and may be hyperpigmented. Facial rashes may be pustular and can resemble acne vulgaris. On occasion, the scaling may be so prominent that it resembles psoriasis. Ulceration may occur and produce lesions resembling ecthyma. In malnourished or debilitated patients, extensive and destructive ulcerative lesions with a heaped-up crust may occur, the so-called rupial lesions. Lesions around the hair follicles may result in patchy alopecia of the beard or scalp.

Ringed or annular lesions may occur, especially around the face and particularly on dark-skinned individuals. A lesion at the angle of the mouth or the corner of the nose may have a central linear erosion, the so-called split papule.

In approximately 30% of secondary syphilis patients, so-called mucous patches ( Fig. 295-1C ) develop. These slightly raised, oval areas are covered by a grayish white membrane that, when raised, reveals a pink base that does not bleed. These lesions may be seen on the genitalia, mouth, tongue, palate, and pharynx.

In warm, moist areas such as the perineum, large, pale, flat-topped papules may coalesce to form condylomata lata ( Fig. 295-1D ). Papules may also be seen in the axilla and rarely occur in a generalized form. These papules are not to be confused with the common venereal warts (i.e., condylomata acuminata), which tend to be smaller, multiple, verrucous in appearance, and more sharply raised than condylomata lata. Like mucous patches, condylomata lata are highly infectious.

Other systemic manifestations of secondary syphilis include hepatitis, which has been reported in up to 10% of patients, and symptomatic gastritis. Jaundice is rare, but an elevated alkaline phosphatase level is common. Liver biopsy reveals small areas of focal necrosis and mononuclear infiltrate or periportal vasculitis. Spirochetes can often be visualized with silver stains. Periostitis with widespread lytic lesions of bone has been reported. An immune complex nephropathy with transient nephrotic syndrome ( Chapter 107 ) has been documented. Between 10 and 30% of patients have cerebrospinal fluid (CSF) pleocytosis, but symptomatic meningitis is uncommon (<1%). Ocular involvement with iritis and anterior uveitis can also occur during the secondary stage (see Ocular Syphilis section). Secondary manifestations heal spontaneously within 2 to 6 weeks, and the infection then becomes latent.

Relapsing Syphilis

After resolution of the primary or secondary skin lesions, 20 to 30% of patients experience cutaneous recurrences. Rarely, the relapse takes the form of recurrence of the primary chancre. Recurrent lesions may be fewer or more firmly indurated than the initial lesions. Like the typical lesions of primary or secondary syphilis, relapsing infection can be transmitted to exposed sexual partners.

Latent Syphilis

By definition, latent syphilis is the stage at which there are no clinical signs of syphilis. Latency, which may last for a lifetime, is usually detected by reactive serologic tests for syphilis (see Diagnosis). Congenital syphilis must also be excluded before the diagnosis of latent syphilis can be made. Patients may or may not have a clinical history of earlier primary or secondary syphilis manifestations.

Latency has been divided into two stages: early and late. Most infectious relapses occur in the first year, and epidemiologic evidence shows that the most infectious period is during the first year after infection. Early latency is therefore defined as occurring within the first year after infection or as a newly reactive serologic test response for syphilis in an otherwise asymptomatic individual who has had a negative serologic test result within the preceding year. With the exception of vertical transmission (which can occur during any stage of syphilis in a pregnant woman), late latent syphilis and latent syphilis of unknown duration are considered noninfectious to sexual contacts.

Late (Tertiary) Syphilis

Without antibiotics, about one third of infected patients develop the destructive lesions of tertiary syphilis, involving the eyes, the central nervous system, the heart, and other organs, including the skin, years to decades after primary infection. In developed countries, however, tertiary syphilis is now very rare.

Late or tertiary syphilis ( Table 295-1 ) is usually slowly progressive, although certain neurologic syndromes may have a sudden onset because of endarteritis and central nervous system thrombosis. Although any organ of the body may be involved, three main types of disease can be distinguished: late benign (gummatous), cardiovascular, and neurosyphilis.