Syphilis

Syphilis is caused by the spirochete Treponema pallidum, ssp. pallidum, which belongs to the order Spirochaetales. T. pallidum ssp. endemicum is a subspecies that causes bejel, or endemic syphilis. Other pathogenic treponemes for humans include T. pallidum ssp. pertenue, the cause of yaws, and T. carateum, the cause of pinta. There are other Treponema species that infect other animals or are free-living. Since 2000, there has been an increase in the number of reported cases in the United States, with 11,466 cases of primary and secondary syphilis being reported in 2007, which is a 15.7% increase when compared to the figures from 2006.

Centers for Disease Control and Prevention: Sexually transmitted disease surveillance 2007 supplement: syphilis surveillance report, Atlanta, March 2009, US Department of Health and Human Services, Centers for Disease Control and Prevention.

T. pallidum is a delicate spiral bacterium that measures 6 to 20 mm in length and 0.10 to 0.18 mm in width (Fig. 28-1). Because of the narrow width, it is not visible by normal light microscopy and must be visualized by darkfield microscopy, by silver stains (i.e., Warthin-Starry or modified Steiner stains), or by immunoperoxidase stains (Treponema). The spiral coils are regularly spaced at a distance of about 1 mm. The typical spirochete has 6 to 14 coils. The organism reproduces by transverse fission.

The origin of syphilis had been a point of great debate among experts, with some authorities favoring a New World origin because of an epidemic of syphilis that ravaged Europe in the last decade of the 15th century, when it was referred to as the “Great Pox” (as opposed to smallpox). Because this epidemic coincided with the return of Columbus from America in 1493, this suggested that it was imported from the West Indies. Of interest, Columbus himself is thought to have died from syphilitic aortitis. Other authorities maintained that it had always been present in the Old World. Studies on skeletal remains clearly demonstrate that while treponemal disease was present in the Old World, epidemic syphilis was imported from the New World.

Tognotti E: The rise and fall of syphilis in Renaissance Europe, J Med Humanit 30:99–113, 2009.

Syphilis is most commonly acquired as a sexually transmitted disease but also may be acquired congenitally (see Chapter 57) or, rarely, by blood transfusions. The organism is very fragile and easily killed by heat, cold, drying, soap, and disinfectants. Since the spirochete is so fragile, the possibility that an infection could be acquired from a toilet seat is statistically very remote.

The classic Hunterian chancre develops at the site of inoculation as a painless ulcer with a firm, indurated border (Fig. 28-2). The size may vary from a few millimeters to several centimeters in diameter. Associated unilateral or bilateral, painless, regional, nonsuppurative lymphadenopathy develops in 50% to 85% of patients approximately 1 week after the appearance of the primary ulcer. It is important to realize that up to 50% of all chancres are atypical. Painful ulcers, multiple ulcers (Fig. 28-3), secondarily infected ulcers, and nonindurated ulcers are variations on the classic chancre.

Lee V, Kinghorn G: Syphilis: an update, Clin Med 8:330–333, 2008.

Extragenital chancres occur in 5% of all cases of primary syphilis, although the incidence may be as high as 10%. The most common extragenital sites are the lip, which is associated with oral sex, and anus, which is associated with anal intercourse. Anal intercourse may also produce rectal or colonic chancres as high as 20 cm into the bowel. Other reported sites include the tongue, tonsil, finger, thumb (Fig. 28-4), eyelid, chin, nipple, umbilicus, axilla, and even the lower limb. A high index of suspicion is required to diagnose extragenital chancres.

Scott CM, Flint SR: Oral syphilis—reemergence of an old disease with oral manifestations, Int J Oral Maxillofac Surg 34:58–63, 2005.

Diagnosis cannot be based on clinical presentation alone, and, unfortunately, T. pallidum cannot be cultured. The most specific and rapid method of diagnosing primary syphilis is the demonstration of the spirochete utilizing darkfield examination by a trained observer. This test is not readily available to most community physicians and usually requires sending the patient to a sexually transmitted disease (STD) clinic or medical center. The material for examination can be obtained from either the ulcer or an aspirate from an enlarged lymph node. A single negative darkfield examination does not rule out the possibility of syphilis, and it should not be regarded as negative until there are negative examinations on 3 consecutive days. Primary syphilis can also be diagnosed by biopsying the primary ulcer and demonstrating the organism by special stain.

In lieu of these procedures, a presumptive diagnosis can be made by serologic tests (see Chapter 3). The Venereal Disease Research Laboratory (VDRL) test and rapid plasma reagin (RPR) test are negative in early primary syphilis and should be repeated weekly for 1 month to be considered as negative. The diagnosis is more likely if a rising titer can be demonstrated. The fluorescent treponemal antibody-absorption (FTA-ABS) test turns positive earlier and is more sensitive.

The recommended treatment for primary syphilis is benzathine penicillin G, 2.4 million units in a single intramuscular (IM) dose or procaine penicillin, 600,000 units IM daily for 10 to 14 days. Nonpregnant patients who are allergic to penicillin can be treated with either doxycycline (100 mg orally two times per day for 14 days), tetracycline (500 mg orally four times per day for 14 days), or ceftriaxone (125 mg IM every day for 10 days, 250 mg IM every other day, or 1000 mg IM for 8 to 10 days).

Treatment failures have been reported with all regimens, and patients should have follow-up serologic titers at 3, 6, 12, and 24 months to ensure a fourfold decline in titers. Failure of non-treponemal antibody titers to fall fourfold within 6 months of treatment can be considered a probable treatment failure. Patients need to be reported to the proper public health agency to ensure tracking of known sexual partners.

Centers for Disease Control and Prevention: Sexually transmitted disease guidelines 2006, MMWR 55:22–33, 2006.

Secondary syphilis usually begins about 6 weeks after the onset of the primary chancre. In approximately 25% of cases, the primary ulcer will still be present. In one study, 25% of patients with secondary syphilis did not recall a primary chancre.

Baughn RE, Musher DM: Secondary syphilitic lesions, Clin Microbiol Rev 18:205–216, 2005.

The syphiloderm of secondary syphilis is most commonly a maculopapular dermatitis (Fig. 28-5A, B) with variable scaly (70%), papular (12%), or macular (10%) lesions. Less common morphologic appearances include annular (Fig. 28-5C, D), pustular, and psoriasiform lesions. The rash typically demonstrates a widespread symmetrical distribution, although in some patients, lesions may be localized to a single anatomic region, such as the palms and soles. In a large study done in the United States, the most common sites of involvement, in descending order, were the soles, trunk, arms, genitals, palms, legs, face, neck, and scalp.

Dave S, Gopinath DV, Thappa DM: Nodular secondary syphilis, Dermatol Online J 9:9, 2003. (Readers can go to this journal online and see clinical photographs.)

Condylomata lata are whitish or grayish, elevated, broad, flat papular lesions of secondary syphilis that primarily occur in moist areas, such as the penis (Fig. 28-6A), labia, inner thighs, and anal region. These papular lesions may coalesce to form verrucous plaques that are easily confused with condylomata acuminata, which are genital warts caused by human papillomavirus. Condylomata lata are more common in women than men.

Begovac J, Lukas D: Images in clinical medicine. Condylomata lata of secondary syphilis, N Engl J Med 352:708, 2005.

Shallow, usually painless erosions of the mucous membranes (Fig. 28-6B). Some mucous patches demonstrate linear shapes and have been described as resembling “snail tracks.”

The hair loss primarily affects the scalp but may also involve the eyebrows and eyelashes. It presents as a nonscarring, patchy alopecia that is described as a “moth-eaten” pattern (see Figure 20-8). This classic pattern appears to be uncommon in the 20th century. The most common pattern of hair loss in secondary syphilis today is a nonspecific diffuse hair loss due to a telogen effluvium (see Chapter 20).

The diagnosis of secondary syphilis requires a health care provider with a strong index of suspicion. The cutaneous manifestations of secondary syphilis may mimic other skin diseases, including pityriasis rosea, psoriasis, erythema multiforme, pityriasis lichenoides et varioliformis acuta, and some drug reactions. It is a good rule of thumb to consider secondary syphilis in any patient having a generalized dermatitis with associated lymphadenopathy.

As with primary syphilis, the most specific tests are the demonstration of the spirochete either in a skin biopsy or on darkfield examination, which can be performed on either the secondary skin lesions or on aspirates from lymph nodes. In contrast to primary syphilis, serologic tests are almost invariably positive. The only exception is when there is a false-negative reaction due to a prozone phenomenon, which occurs in 1% to 2% of patients with secondary syphilis. The prozone phenomenon occurs when the titers are very high and can be eliminated by diluting the serum.

Hoang MP, High WA, Molberg KH: Secondary syphilis: a histologic and immunohistochemical evaluation, J Cutan Pathol 31:595–599, 2004.

For the purpose of treatment, the Centers for Disease Control and Prevention defines infections of <1 year as early latent syphilis and infections of >1 year as late latent. The World Health Organization considers early latent syphilis to extend up to 2 years.

Like primary and secondary syphilis, early latent syphilis is treated with 2.4 million units (mu) of benzathine penicillin G intramuscularly in a single dose. Late latent syphilis or latent syphilis of unknown duration is treated with a total of 7.2 mu of benzathine penicillin G administered as three doses of 2.4 mu intramuscularly at 1-week intervals. Penicillin-allergic patients are treated with doxycycline or tetracycline for 2 weeks in early latent syphilis and for 4 weeks in late latent syphilis.

Lumbar punctures to rule out neurosyphilis are recommended for patients with late latent syphilis of more than 1-year duration or unknown duration who demonstrate neurologic symptoms, treatment failure, serum nontreponemal antibody titer equal to or greater than 1:32, other evidence of active syphilis (iritis, aortitis, gumma), nonpenicillin treatment, or positive HIV test. Syphilis frequently attacks the central nervous system, as demonstrated by the fact that 40% of patients with primary or secondary syphilis demonstrate cerebrospinal fluid pleocytosis, and 24% of patients with secondary syphilis demonstrate a reactive VDRL. In patients with syphilis/HIV coinfection there is evidence to suggest that lumbar puncture may be indicated in all coinfected patients since the disease is more aggressive; however, this is also controversial.

Chan DJ: Syphilis and HIV co-infection: when is lumbar puncture indicated? Curr HIV Res 3:95–98, 2005.

• Neurosyphilis (general paresis or tabes dorsalis)

Marra CM: Update on neurosyphilis, Curr Infect Dis Rep 11:127–134, 2009.

Late benign syphilis usually occurs 1 to 46 years after resolution of the secondary skin lesions. Although almost any organ may be involved, the most common organ is the skin (70%) followed by the mucous membranes (10%) and bones (10%). The primary lesion of late benign syphilis is the gumma. A gumma is a granulomatous lesion that contains treponemes only rarely; it probably represents a hypersensitivity reaction.

The skin lesions of late benign syphilis present as nodules and plaques that demonstrate a tendency for central healing and peripheral extension. The central healed areas characteristically demonstrate scarring and atrophy (Fig. 28-7). The mucosal lesions may involve any mucosal surface but demonstrate a tendency to extend to and destroy the nasal cartilage, producing a “saddle nose” deformity. Involvement of the mucosa over the hard palate may produce a perforation.

Rocha N, Horta M, Sanches M, et al: Syphilitic gumma—cutaneous tertiary syphilis, J Eur Acad Dermatol Venereol 18:517–518, 2004.