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Spirochetal disease includes a historical and clinical gamut of infections causing uveitis, including syphilis, endemic syphilis, Lyme disease, relapsing fever, and leptospirosis.
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Ocular findings can occur in primary, secondary, latent, and tertiary syphilis.
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The VDRL test can be falsely negative, especially in later stages of the disease, and a more sensitive and specific test such as the FTA-ABS test should be considered when evaluating patients with possible syphilitic uveitis.
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Lyme serology should be ordered in patients with a history or findings consistent with the disease. False positive results are common when the test is ordered in patients with an extremely low likelihood of Lyme disease.
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Antibiotic regimens for spirochetal disease change frequently. Consulting a physician well versed in treating these diseases is important to ensure the appropriate drug, dose, route, and length of treatment.
Spirochetal infections and the eye
This chapter focuses on uveitis caused by spirochetes. This comprises a variety of infectious diseases with ocular manifestations, including syphilis, bejel, pinta, yaws, Lyme disease, relapsing fever, and leptospirosis. The ocular manifestations of syphilis have been known for well over a century, whereas Lyme disease was first described in the 1970s. The first section of this chapter is devoted to treponemal infections, of which syphilis is by far the most common and important to the practicing ophthalmologist. Syphilis remains an important cause of eye disease and blindness in the United States, and is diagnosed with increasing frequency in patients with acquired immunodeficiency syndrome (AIDS). Sections on endemic syphilis (bejel) and nonvenereal treponemal infections (yaws and pinta) are also included.
The second part of the chapter contains sections on two infections caused by spirochetes of the genus Borrelia and a section on leptospirosis. Although the cause of syphilis was identified at the beginning of the 20th century, the causative agent for Lyme disease was not discovered until 1982. Interestingly, Lyme disease and syphilis share many clinical features and should be considered together in the differential diagnosis of infectious diseases with ophthalmic involvement. The chapter also reviews relapsing fever, an additional infection caused by Borrelia that is often misdiagnosed. Leptospirosis is discussed at the end of the chapter and may be an important cause of uveitis of unknown etiology.
Spirochetes
Definition
Spirochetes are a phylum of bacteria characterized by long, helically coiled cells. These bacteria have lengthwise flagella called axial filaments that allow the spirochetes to move. There are three groups of spirochetes implicated in human disease: Treponema , which cause syphilis and the nonvenereal treponematoses; Borrelia , which cause relapsing fever and Lyme disease; and Leptospira , which cause leptospirosis.
Venereal treponemal diseases
Syphilis
Etiology and Epidemiology
Syphilis was originally called the great pox , but it acquired its current name from the title character of a poem written in 1530 by the Veronese physician and poet Girolamo Fracastoro. Syphilis has also been called the great imitator , because of the myriad symptoms and signs in its repertoire and its ability to mimic numerous other illnesses. Although clinical descriptions of syphilis date back at least half a millennium, it was not until 1905 that Schaudin and Hoffman isolated the spirochete Treponema pallidum from skin lesions of patients with syphilis.
After initial infection there is both a humoral and a cellular immune response. In 1910, Wasserman introduced a complement fixation test to detect nonspecific antibodies that react against cardiolipins, and these antibodies are commonly found in patients with syphilis. The next milestone in the history of syphilis was the use of arsenic derivatives to treat the disease. The coup de grâce in the war against syphilis came in 1943 with the discovery of penicillin, which is still the mainstay of therapy today. In the late 1980s there was a substantial increase in primary and secondary syphilis and an increased incidence of congenital syphilis, especially in the inner cities. In 1986, only 57 cases of congenital syphilis were reported in New York City, but in 1989 more than 1000 cases were documented. With focused efforts to reduce syphilis in the United States, in 2000 the rate of primary and secondary syphilis was 2.1 cases per 100 000 population, the lowest since reporting began in 1941. From 2001 to 2004, rates increased to 2.7 cases per 100 000 population. Approximately 84% of cases occurred in men. Primary and secondary syphilis incidence also varied by race/ethnicity. The incidence of primary and secondary syphilis in 2004 was 9.0 per 100 000 population among blacks, 1.6 among whites, 3.2 among Hispanics, 1.2 among Asian/Pacific Islanders, and 3.2 among American Indian/Alaska Natives. Syphilis is also a problem in patients co-infected with human immunodeficiency virus (HIV). These patients may not mount a serologic response to the treponemal infection and thus elude diagnosis. In addition, standard therapy may be insufficient to eradicate the infection in these immunocompromised patients. ,
T. pallidum is a spirochete that is approximately 0.01–0.02 µm wide and 5–20 µm long. Although it cannot survive long out of the body, it can be cultured and remains viable for several days. Syphilis is transmitted almost exclusively by sexual contact, including sexual intercourse, orogenital and anorectal contact, and occasionally kissing. The disease is most infectious in patients with untreated primary syphilis or secondary syphilis with skin lesions. Disease can also be transmitted by patients with early latent syphilis, especially if they have mucocutaneous involvement; however, disease in patients with late latent syphilis and tertiary syphilis is not infectious. Congenital syphilis occurs with transplacental spread of the spirochete. Interestingly, infection with syphilis does not confer lasting immunity, especially if treatment is received early in the course of the disease.
T. pallidum can penetrate intact mucous membranes or abraded skin. The period of incubation varies from 10 to 90 days, but averages 3 weeks. Before primary skin lesions appear, the spirochete spreads via the lymphatics to the bloodstream, from which it then disseminates.
As with many of the spirochetal diseases, the clinical course of syphilis is divided into stages: primary, secondary, and tertiary syphilis ( Box 10-1 ).
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Caused by the spirochete Treponema pallidum
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Transmitted almost exclusively by sexual contact
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Congenital syphilis occurs with transplacental spread of the spirochete
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Disease is divided into stages: primary, secondary, latent, and tertiary
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Tertiary syphilis is subdivided into three subgroups: benign tertiary syphilis, cardiovascular syphilis, and neurosyphilis
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If untreated, syphilis will disseminate
Clinical Manifestations
Primary syphilis
The chancre is the predominant lesion of primary syphilis. It appears about 4 weeks after infection and heals in about 1–2 months in untreated individuals. The lesion begins as an erythematous papule at the inoculation site and later erodes to form a painless ulcer. Multiple chancres can occur, especially in patients coinfected with HIV. Serous fluid from these lesions is teeming with spirochetes. Lesions occur on the penis, anus, and rectum in men and on the cervix, vulva, and perineum in women. Small lesions may also occur on the lips, tongue, buccal mucosa, and skin, and chancres of the eyelids and conjunctiva have also been described.
Secondary syphilis
If untreated, disease in patients with primary syphilis will progress to secondary syphilis 4–10 weeks after the initial manifestations of the disease. One of the unique characteristics of syphilis is that it always disseminates. The skin is involved in about 90% of patients with secondary syphilis. A generalized rash is characteristic of secondary syphilis and may be maculopapular or pustular. The rash commonly occurs on the flexor and volar surfaces of the body, typically the palms and the soles. The rash usually resolves without scarring, but some patients are left with areas of hyper- or hypopigmentation. Mucous membranes become eroded, forming erythematous patches. Condylomata lata is another characteristic dermatologic manifestation of secondary syphilis. The papules develop at the mucocutaneous junctions and in moist areas of the skin, and appear as dull pink or gray hypertrophic lesions. Systemic symptoms of secondary syphilis include fever, malaise, headache, nausea, anorexia, and joint pain. A generalized lymphadenopathy is found in both primary and secondary syphilis. Syphilitic infiltration of the kidneys, liver, and gastrointestinal tract also occurs in secondary syphilis, and about 10% of patients have ocular involvement. Anterior uveitis is the predominant eye finding in early secondary syphilis and may be the most common ocular lesion in syphilis. Some patients may demonstrate a cerebrospinal fluid (CSF) pleocytosis, and a few of these patients experience acute syphilitic meningitis with headache, neck stiffness, cranial nerve palsies, and disc edema.
Latent syphilis
In the first year after initial infection, patients may have recurrences of infectious mucocutaneous lesions. This period of the disease is called early latent syphilis . The late latent phase of syphilis occurs after 1 year of infection, and during this stage of the disease infectious relapses are rare. Most patients who have not been treated remain in this late latent phase of the disease; however, about 30% go on to experience tertiary syphilis.
Tertiary syphilis
Tertiary syphilis is also called late syphilis and is often subdivided into three groups: benign tertiary syphilis, cardiovascular syphilis, and neurosyphilis.
Benign tertiary syphilis
The gumma is the typical lesion of benign tertiary syphilis and is a chronic granulomatous lesion that heals with scarring and fibrosis. It is a rare finding in the penicillin era and responds rapidly to treatment. Gummas tend to develop in the skin and mucous membranes, but can occur in almost any tissue and have even been found in the choroid of the eye.
Cardiovascular syphilis
The lesions of cardiovascular syphilis include aortitis and aortic aneurysms, aortic valvular insufficiency, and narrowing of the coronary ostia. Disease starts about 5–10 years after infection, but symptoms of cardiovascular syphilis may not be clinically evident for more than 20 years.
Neurosyphilis
This condition is said to occur in 5–10% of untreated patients with syphilis. Asymptomatic neurosyphilis is found in some patients who have a positive CSF Venereal Disease Research Laboratory (VDRL) test result but no symptoms of central nervous system (CNS) disease. In addition, invasion of the CNS by T. pallidum may be more common in early syphilis than once thought. Lukehart and colleagues isolated T. pallidum from the CSF in 12 of 40 (30%) patients with untreated primary and secondary syphilis, and an additional four patients, in whom no T. pallidum was isolated, had reactive CSF on the VDRL test. Neurosyphilis can occur at any time in the course of the disease. Uveitis and hearing loss are more common in the earlier stages.
One type of neurosyphilis, meningovascular syphilis, presents as an aseptic meningitis that can occur at any time after primary syphilis. Unilateral or bilateral cranial nerve palsies are common, and headache, neck stiffness, dizziness, lassitude, and blurred vision occur. The classic neuro-ophthalmic finding of neurosyphilis is the Argyll Robertson pupil. This is a small, irregular pupil that is unreactive to light but normally reactive to accommodation; it is commonly seen in cases of meningovascular syphilis in which the base of the brain is involved. If the spinal cord is involved patients may experience bulbar symptoms, muscle weakness and wasting, and slowly progressive spastic paraplegia with bladder incontinence.
T. pallidum may also invade the substance of the brain. Parenchymatous neurosyphilis is a meningoencephalitis with progressive loss of cortical function. Patients can experience altered mental status and even syphilitic psychosis, with irritability, reduced memory, poor judgment, confusion, and delusions. Seizures may occur. On neurologic examination patients demonstrate tremors of the mouth and tongue, hyperreflexia, and in some cases extensor plantar responses. Pathologically, the brain parenchyma is infiltrated with spirochetes, and the meninges are inflamed and thickened. The CSF is hypercellular and has a positive VDRL test result. Cranial nerve palsies, however, are uncommon, and optic atrophy is rare. Although pupillary abnormalities may be seen, a complete Argyll Robertson pupil is not characteristic. Neurosyphilis should still be considered in the differential diagnosis of advanced neurologic disease with generalized paresis, although this finding is rare in the United States.
Tabes dorsalis is a form of neurosyphilis with involvement of the posterior columns and the posterior roots of the spinal cord, resulting in pain, ataxia, sensory changes, reduced tendon reflexes, and ocular findings. Severe stabbing pain in the lower extremities heralds this form of neurosyphilis. Unsteadiness and a wide-based gait develop later, followed by hyperesthesia and paresthesia. Incontinence and impotence are other common sequelae. Charcot’s arthropathy occurs in large joints devoid of sensation that are prone to destructive changes. Argyll Robertson pupils are frequent in this form of neurosyphilis, and optic atrophy is commonly found.
Congenital syphilis
Congenital syphilis results from the transplacental transmission of T. pallidum from the mother to the fetus. Untreated primary or secondary syphilis is almost invariably transmitted to the fetus, whereas transmission in later stages of the disease occurs less frequently. Congenital syphilis is preventable with proper treatment of the mother; therefore, all expectant mothers should have a VDRL test at the beginning and near the end of pregnancy. In fact, screening at the time of delivery is now mandatory in the State of New York.
Signs and symptoms of early congenital syphilis may not appear until several days after birth, and Dorfman and Glaser stated that the diagnosis of congenital syphilis may be missed if serologic tests are not performed for both the mother and her infant at the time of delivery. A generalized rash develops and resembles the rash of secondary syphilis, except that in the infant the rash may be vesicular or bullous. Rhinitis (also called the snuffles), jaundice, hepatosplenomegaly, anorexia, and pseudoparalysis may also be found. Osteochondritis and pathologic fractures are common, and radiographic changes on bone films are present in more than 90% of patients. Chorioretinitis is often evident in the first few months of life.
Congenital syphilis may mimic other congenital infections, such as rubella, cytomegalovirus infection, and toxoplasmosis. A positive serologic test result for syphilis may be caused by passive transfer of antibody from the mother; therefore, diagnosis of congenital syphilis is based on a positive fluorescent treponemal antibody absorption (FTA-ABS) test and a rising VDRL titer. Results of serologic tests performed in infants and their mothers may be negative at the time of delivery if syphilis is acquired toward the end of the pregnancy.
After 2 years the child is described as having late congenital syphilis. Like syphilis in adults, late congenital syphilis may remain latent with few sequelae, although cardiovascular involvement does occur, and meningovascular syphilis with neurologic manifestations, including eighth cranial nerve deafness, is common. Acute syphilitic meningitis, generalized paresis, and tabes dorsalis are less common. Interstitial keratitis is the classic ophthalmic sign of congenital syphilis, occurring in 10% of patients.
Deformities of the permanent teeth occur after early syphilitic infection. The characteristic Hutchinson teeth are notched, thin, upper incisors with abnormal spacing. Hutchinson’s triad is the occurrence of Hutchinson’s teeth, interstitial keratitis, and deafness, but the occurrence of all three in the same patient is unusual. The bone lesions of early congenital syphilis tend to progress in late congenital syphilis, with the development of syphilitic arthritis. Finally, gummas may develop in the subcutaneous tissue and produce ulcerative skin lesions.
Ocular Manifestations
Table 10-1 lists some of the more common eye manifestations of the different stages of syphilis. Ophthalmic manifestations of primary syphilis are limited to chancres of the eyelid and the conjunctiva. A primary syphilitic lesion in the lacrimal gland is extremely rare but has been reported.
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The eyelids are commonly involved in the rash of secondary syphilis, and blepharitis and loss of lashes and eyebrows are common. Conjunctivitis mimicking trachoma has also been seen in secondary syphilis, but dacryocystitis and dacryoadenitis are rare. Keratitis, iris nodules ( Fig. 10-1 ), iridocyclitis, episcleritis, and scleritis have all been reported in secondary syphilis. Late in the secondary stage, chorioretinitis and vitritis may develop ( Fig. 10-2A ). A diffuse neuroretinitis may occur and is often localized to the peripapillary area. This is followed by a pigmentary retinopathy similar in appearance to retinitis pigmentosa. Disc edema ( Fig. 10-3 ), exudative retinal detachment, and perivasculitis are less common findings.
The gummas of tertiary syphilis can involve the eyelids, and if extensive can cause destructive ulceration, but gummatous dacryoadenitis and infiltration of the lacrimal sac have only rarely been reported. Conjunctival vascular changes occur, but gummas of the conjunctiva almost never occur. As seen in secondary syphilis, syphilitic blepharitis with madarosis is common. A diffuse bilateral periostitis is the most common orbital finding of tertiary syphilis. Uniocular interstitial keratitis is the most common corneal finding in tertiary syphilis, but punctate stromal keratitis can occur with iritis. Episcleritis and scleritis occur, but discrete gummas of the sclera are rare. Uveitis is a common finding in late tertiary syphilis. Halperin and colleagues stated that the main posterior segment complications of acquired syphilis include chorioretinitis, vasculitis, venous and arterial occlusive disease, retinal detachment with choroidal effusion, macular edema, neuroretinitis, optic neuritis, vitritis ( Fig. 10-2A ), and pseudoretinitis pigmentosa ( Fig. 10-2B ). Choroidal neovascular membranes and subretinal fibrosis ( Fig. 10-4 ) can also occur. A posterior placoid chorioretinitis has been described in late latent syphilis. Vitreous opacities are common, and lens dislocation has been reported in many patients.
The most typical manifestation of congenital syphilis is bilateral interstitial keratitis, which appears later in life. A pigmentary retinitis and glaucoma can also occur as a result of congenital syphilitic keratouveitis.
The Argyll Robertson pupil and disc edema are most commonly seen in meningovascular syphilis, along with oculomotor palsies and other pupillary abnormalities. Later in the course of meningovascular syphilis, optic atrophy occurs. A complete Argyll Robertson pupil is rare in cases of general paresis, but, as with optic atrophy, is more common in cases of tabes dorsalis.
Diagnosis
The diagnosis of syphilis is based on the clinical history, physical examination, and laboratory tests. Although darkfield examination or immunofluorescent staining of mucocutaneous lesions can lead to the prompt diagnosis of primary, secondary, and early congenital syphilis, most physicians order serologic tests to make or confirm a diagnosis. There are both nontreponemal and treponemal tests. Confusion often arises in determining whether a VDRL test should be ordered rather than an FTA-ABS test, and in the interpretation of the results. In this section the various diagnostic tests for syphilis are explained, and a strategy for ordering tests is outlined ( Box 10-2 ).
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Diagnosis is based on clinical history, physical examination, and laboratory tests
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There are both nontreponemal and treponemal tests for syphilis
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Nontreponemal tests are often used to screen for syphilis. The two most common screening tests are the Venereal Disease Research Laboratory (VDRL) test and the rapid plasma reagin (RPR) test
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Treponemal tests are more sensitive in diagnosing patients with latent or late syphilis and more specific than the VDRL. The most commonly used treponemal test is the fluorescent treponemal antibody absorption (FTA-ABS) test
Darkfield microscopy can be used to identify spirochetes present in tissue fluids. T. pallidum is difficult to distinguish from other spirochetes, and so darkfield examination requires expertise. In clinical practice, greater reliance is placed on the serologic test for syphilis.
The two most commonly used screening tests for syphilis are the VDRL test and the rapid plasma reagin (RPR) test. Both of these are nontreponemal reaginic tests. Infection with T. pallidum stimulates nonspecific antibodies against cardiolipin. The VDRL test quantitates these antibodies by use of slide flocculation. The VDRL test is well standardized, and the result is reported as reactive, weakly reactive, borderline, or nonreactive. The rapid plasma reagin test is a similar assay for detecting anticardiolipin antibody.
The sensitivity and the specificity of the VDRL test vary, depending on the stage of disease ( Table 10-2 ). The VDRL test starts to become positive about 1–2 weeks after the appearance of the primary chancre and is positive in 99% of patients with secondary syphilis. In later stages of the disease, however, the VDRL test reactivity decreases, and only about 70% of patients with cardiovascular syphilis or neurosyphilis have a positive VDRL test result. In addition, the VDRL test often becomes nonreactive after treatment for syphilis.
| Percentage of patients with positive results | ||||
| Late or latent syphilis | ||||
| Test | ||||
| Primary syphilis | Secondary syphilis | Treated disease | Untreated disease | |
| VDRL | 70 | 99 | 1 | 70 |
| FTA-ABS | 85 | 100 | 98 | 98 |
The serologic tests for syphilis are not 100% specific, and false-positive results can occur, especially in patients with other spirochetal diseases and connective tissue diseases ( Table 10-3 ). Any weakly reactive or reactive VDRL test needs to be confirmed with a more specific test. The tests used for this purpose are the treponemal tests for syphilis, such as the T. pallidum agglutination tests (TPHA and MHA-TP) or the more commonly used FTA-ABS test. The T. pallidum immobilization test is almost completely specific for syphilis, but is expensive and difficult to perform and therefore rarely used. The microhemagglutination– T. pallidum (MHA-TP) assay for antibodies to T. pallidum is another specific test for syphilis but is also used less frequently than the FTA-ABS test. In the FTA-ABS test, the patient’s serum is absorbed with extracts of nonpathogenic treponemes to remove possible cross-reacting antitreponemal antibody that is not specific for T. pallidum . The absorbed serum is then made to react against T. pallidum , and specific antibodies are detected by the addition of fluorescein-labeled antihuman γ-globulin. Results are reported as nonreactive or as 1+ to 4+ positive, based on the intensity of the fluorescence.
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A weakly reactive FTA-ABS test may not be reproducible. The FTA-ABS test is more sensitive than the VDRL test at all stages of syphilis, but it is more expensive and difficult to perform. The FTA-ABS test is also not entirely specific for syphilis, because false-positive results are seen in patients with systemic lupus erythematosus, biliary cirrhosis, and some connective tissue diseases, such as rheumatoid arthritis (see Table 10-3 ).
Because serologic tests for syphilis may take several weeks to become reactive, immediate diagnosis requires demonstration of treponemes in tissue fluid by darkfield microscopy. The VDRL test is an excellent screening test for patients with later primary syphilis and secondary syphilis. The sensitivity of the VDRL test is 99% for patients with secondary syphilis; however, all positive results should be confirmed with an FTA-ABS test.
Because the sensitivity of the VDRL test may be only 70% in patients with latent or late syphilis, both VDRL and FTA-ABS tests should be ordered if a later stage of disease is suspected. From the ophthalmic standpoint, many patients with uveitis or disc edema are suspected of having late syphilis, and many uveitis specialists and neuro-ophthalmologists routinely order both VDRL and FTA-ABS tests in the evaluation of these patients. As stated above, in the United States, testing for syphilis has consisted of initial screening with an inexpensive nontreponemal test, with subsequent testing of reactive specimens with a treponemal test. Some clinical laboratories have started using automated treponemal tests and then retest reactive results with a nontreponemal test. It is not clear what the recommendations are for patients who test positive with the treponemal test and then negative for the nontreponemal test. If not previously treated, these patients should probably be treated for late latent syphilis.
In addition, all patients who may have had syphilis for more than a year should have a lumbar puncture for CSF examination. A cell count, differential count, protein determination, and VDRL test should be performed on the CSF to look for evidence of neurosyphilis. As stated previously, CNS invasion by T. pallidum may be common in early syphilis. The finding of CNS involvement is important because the recommended therapy is different from that for patients without CNS involvement. Serologic tests for neurosyphilis can also be confusing. The CSF-VDRL is insensitive but highly specific. A CSF serologic diagnosis is usually based on production of local antitreponemal antibodies, and an intrathecal T. pallidum antibody index can be calculated.
Infants born with congenital syphilis have positive VDRL and FTA-ABS test results from the passive transfer of immunoglobulin (Ig) G antibodies across the placenta; therefore, an IgM FTA-ABS test is used to diagnose congenital syphilis because IgM antibodies do not cross the placenta, and a positive test result would indicate actual infection in the infant.
Patients with undiagnosed interstitial keratitis should be suspected of having late congenital syphilis. A thorough history of previous therapy should be elicited, and patients should then undergo VDRL and FTA-ABS tests and a CSF examination. If the CSF VDRL test result is positive, some experts recommend that the patient be treated as for latent syphilis ( Table 10-4 ). Patients with a positive serum VDRL or FTA-ABS result but negative CSF findings are treated as for primary or secondary syphilis.
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Finally, newer diagnostic techniques may be helpful in diagnosing syphilis in patients with ocular manifestations of syphilis. The polymerase chain reaction (PCR) may be used to detect T. pallidum in ocular specimens such as aqueous humor.
Prognosis
Most patients recover without long-term sequelae if syphilis is recognized and treated early. If untreated, about 25% of these patients have one or more relapses with mucocutaneous lesions. Eventually, most untreated patients remain in a latent stage of the disease; however, about one-third go on to experience tertiary syphilis. Benign tertiary syphilis occurs in about 15% of untreated patients. Cardiovascular syphilis occurs in 10% of these, and CNS involvement is seen in about 8% of untreated patients.
Treatment
General recommendations
Although guidelines for the treatment of syphilis exist, controversy persists. Before treating a patient with syphilis one should refer to the most current recommendations for therapy, and consultation with an infectious disease specialist may be helpful. Coinfection with HIV should be ruled out because standard therapy may be insufficient to eradicate disease in these patients. Recommendations for therapy are based on the stage of disease and are presented in Table 10-4 . Riedner and colleagues evaluated the efficacy of treating primary or latent syphilis with a single oral dose of 2 g azithromycin or a single intramuscular dose of 2.4 million units of penicillin G benzathine. Cure rates were 97.7% for patients in the azithromycin group and 95.0% in the penicillin G benzathine group, achieving the prescribed criteria for equivalence.
Unfortunately, the ideal therapy for patients with uveitic syphilis has not been determined. Virulent T. pallidum infection has been reported to persist in the eye despite treatment with penicillin; therefore, many experts suggest that patients with any ocular inflammation secondary to syphilis be treated as for neurosyphilis, even if the CSF findings are normal.
In addition to treating the patient, the physician has a responsibility to report the disease to the local health department to ensure that all sexual contacts over at least the past 3 months are contacted, examined, and treated as necessary.
Patients with syphilis should have the VDRL test repeated at 3, 6, and 12 months after treatment because titers should become nonreactive within a year after successful therapy. In addition, patients with CSF involvement should have repeated CSF examinations at 6-month intervals for at least 3 years. Patients should be re-treated if clinical evidence of syphilis occurs, if a previously nonreactive VDRL test again becomes reactive, or if an initially high-titer VDRL test does not decrease fourfold within a year.
Finally, patients receiving therapy for syphilis, especially intravenous therapy, should be monitored for a Jarisch–Herxheimer reaction. This is a hypersensitivity response to treponemal antigens. The reaction may exacerbate pre-existing ocular inflammation, such as uveitis and interstitial keratitis; prophylaxis with corticosteroids may help in some cases.
Approach to Syphilis in Patients with AIDS
Recognition of concurrent infection with HIV in patients with syphilis is important to the clinician because the diagnostic and therapeutic approach to syphilis may differ in these patients. Numerous reports suggest that uncharacteristic clinical manifestations of syphilis may occur in patients with concomitant HIV infection. , Unusual cases of ocular syphilis in HIV-infected patients with findings of panuveitis and retinal detachment have been reported, and some authors have stated that the incidence of ocular complications of syphilis may be increased in HIV-infected patients. In addition, acute retinal necrosis and acute retinitis have been associated with syphilis in patients coinfected with HIV. , Despite some unique symptoms and signs, these patients usually also experience the characteristic clinical manifestations of syphilis. Patients with both HIV infection and syphilis may have an accelerated course with a greater likelihood of uveitis and progression to neurosyphilis. In the study by Berry and colleagues there was no difference in the detection of T. pallidum in the CSF in patients with or without concurrent HIV infection; nevertheless, it appears that treatment failures are more common in HIV-infected patients. In addition, serologic evidence of syphilis may be delayed. Hicks and colleagues reported on a patient with AIDS and skin manifestations consistent with secondary syphilis in whom the VDRL and FTA-ABS results were negative on two separate occasions. A skin biopsy demonstrated spirochetes with Warthin–Starry staining of the tissue, and the patient’s VDRL and FTA-ABS test results later became positive, suggesting a delayed immunologic response.
Although patients with HIV infection and syphilis have more symptoms of CNS involvement, such as acute syphilitic meningitis and hearing loss, many of them do not have positive CSF VDRL test results and may manifest only CSF leukocytosis or elevated CSF protein concentration, findings that are seen in HIV patients without syphilis. These findings have prompted some clinicians to treat all patients with concurrent HIV infection and syphilis with high-dose antibiotic therapy to cover the possibility of CNS involvement. The Centers for Disease Control and Prevention in Atlanta is currently studying the question of appropriate antibiotic therapy for patients with syphilis and concurrent HIV infection. For now, recommendations include the careful evaluation of all patients with syphilis for underlying HIV infection. Patients with AIDS should also be monitored for clinical signs of syphilis, and the diagnosis should be pursued despite negative serologic results early in the course of the disease.
Patients with syphilis and HIV infection should have a lumbar puncture to look for evidence of neurosyphilis. Because treatment failures are common, some infectious disease consultants suggest that all patients be treated with a regimen adequate for neurosyphilis. After treatment, a VDRL test is suggested every month for at least 3 months, with close observation for evidence of recurrence.
Nonvenereal treponematoses
Endemic syphilis
Etiology and Epidemiology
Endemic syphilis, yaws, and pinta are three nonvenereal treponemal infections that are spread by body contact and are endemic in certain geographic areas. Endemic syphilis, also known as bejel, is caused by T. pallidum II, a spirochete that is morphologically and serologically indistinguishable from the T. pallidum that causes syphilis. Bejel is endemic in many arid countries, mostly in the Middle East and Africa.
Clinical Manifestations
The onset of bejel usually occurs in childhood and typically presents with a mucous patch on the buccal mucosa. Mucosal lesions are followed by papulosquamous and erosive papular lesions of the trunk and extremities. Latency can occur if the early stages of the disease are not treated. Periostitis of the bones of the legs and gummatous lesions of the nose and soft palate are seen in later stages. Neurologic and cardiovascular involvement and congenital transmission of endemic syphilis are uncharacteristic. Similarly, chancres, which are typical of primary syphilis, are not found as early signs of endemic syphilis.
Ocular Manifestations
Although neurologic involvement is uncharacteristic of endemic syphilis, ocular manifestations have been reported. Tabbara and colleagues studied 17 patients with clinical and serologic findings that were consistent with endemic syphilis who also had ocular complaints. Ocular findings included uveitis in nine patients, optic atrophy in six, and chorioretinal scars in six. Additional findings are presented in Table 10-5 .
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