Journal of Neuro-Ophthalmology, December 1987, Volume 7, Issue 4

Ocular syphilis 1986. Prevalence of FTA-ABS reactivity and cerebrospinal fluid findings.

Serum FTA-ABS tests were obtained for 247 consecutive patients undergoing ambulatory oculoplastic surgery over a 5-month period. The incidence of FTA-ABS reactivity was 52.8%. Cerebrospinal fluid (CSF) from 50 patients with ocular signs of late syphilis and reactive serum FTA-ABS tests was examined. Only 12 (24%) of these patients had reactive serum VDRLs. Thirty patients (60%) had a lymphocytic pleocytosis, elevated protein, or both, in their CSF. No patients had reactive CSF VDRLs. It was concluded that FTA-ABS reactivity is common, serum VDRL tests are inadequate for diagnosing ocular syphilis, and a significant percentage of patients with ocular syphilis have abnormal CSF. More aggressive diagnosis and treatment of ocular syphilis is suggested.

Journal of Clinical Neuro-ophthalmo!ogy 7(4): 191-195, 1987. Ocular Syphilis 1986 Prevalence of FTA-ABS Reactivity and Cerebrospinal Fluid Findings Thomas C. Spoor, M,D" M.S., F.A.C.S., John M. Ramocki, M.D., Frank A. Nesi, M.D., and Michael Sorscher, B.S. '\:J 1987 Raven Press, Ltd., New York Serum FTA-ABS tests were obtained for 247 consecutive patients undergoing ambulatory oculoplastic surgery over a 5-month period. The incidence of FTA-ABS reac­tivity was 52.8%. Cerebrospinal fluid (CSF) from 50 pa­tients with ocular signs of late syphilis and reactive serum FTA-ABS tests was examined. Only 12 (24%) of these patients had reactive serum VDRLs. Thirty pa­tients (60%) had a lymphocytic pleocytosis, elevated protein, or both, in their CSF. No patients had reactive CSF VDRLs. It was concluded that FTA-ABS reactivitv is common, serum VDRL tests are inadequate for diag­nosing ocular syphilis, and a significant percentage of patients with ocular syphilis have abnormal CSF. More aggressive diagnosis and treatment of ocular syphilis is suggested. Key Words: Syphilis-FTA-ABS-Cerebrospinal fluid -Optic atrophy-Chorioretinitis-Neurosyphilis From the Kresge Eye Institute, Detroit, Michigan. Address correspondence and reprint requests to Dr. T. C. Spoor, at Kresge Eye Institute, 3994 John R., Detroit, MI 48201, U.S.A. 191 In 1985, 27,143 cases of infectious syphilis and 40,103 cases of late syphilis were reported in the United States (1). Infectious (primary and sec­ondary) syphilis is followed by latent periods of subclinical infections. Thirty percent of inade­quately treated patients with latent syphilis may develop a tertiary stage characterized by central nervous system disease, aortitis, or progressive destructive gummas (2). Ocular manifestations may be present in pa­tients with infectious or late syphilis. Patients with infectious syphilis may present with iritis, papil­litis, perineuritis, or active chorioretinitis and exu­dative retinal detachments (3,4). Ocular manifes­tations of late syphilis may include chorioretinitis, optic atrophy, abnormal pupillary reactions, recur­rent iritis, and interstitial keratitis. These manifes­tations may represent late ocular syphilis (3). The diagnosis of late ocular syphilis may then be based upon suspicious ocular findings and a reactive serum FTA-ABS test (2-4). Infectious syphilis (1,2,4), tertiary syphilis, and ocular syphilis are clinical diagnoses confirmed se­rologically. Latent syphilis is a serologic diagnosis in an asymptomatic patient. Serologic tests for syphilis may be specific treponemal tests (FTA­ABS or MHA-TP) or nonspecific reaginic tests (VORL or RPR). Once a specific test (FTA-ABS) is reactive, it will remain reactive. A reaginic test (VORL) may convert to nonreactivity with time or after adequate treatment. Subsequently reaginic tests (VORL) are nonreactive in over 30% of pa­tients with late syphilis and are of little help in es­tablishing the diagnosis (2). A specific treponemal test (FTA-ABS or MHA-TP) is necessary to diag­nose late syphilis (2-4). In a previous study (5), a high incidence of FTA-ABS reactivity was found in OCULAR SYPHILIS 1986 193 TABLE 3. Serologic and CSF findings in patients TABLE 4. Ocular, serologic, and CSF findings in with reactive serum FTA-ABS tests (N = 50) patients with reactive serum FTA·ABS tests (N = 50) Positive findings CSF Number Percent Serum Protein Lymphocytes Age Sex VORL (>45 mg/dl) (>5/mm3 ) VORL Serum VORL positive 12 24 Chorioretinitis Cerebrospinal fluid 70 F NR NR VORL positive 0 0 72 F NR 51 NR Pleocytosis (>5 cells/mm3 ) 20 40 75 F NR 52 NR Protein (>45 mg/dl) 18 36 61 F NR NR 74 M 1:2 NR 34 M NR NR 76 M 1:16 NR These patients were considered to have neuro- 67 M NR 78 NR syphilis in spite of their nonreactive CSF VORLs. 54 F NR 60 16 NR 50 F NR 62 26 NR 51 M NR 9 NR DISCUSSION 79 F NR 14 NR 33 F NR 14 NR The overall incidence of FTA-ABS reactivity was 76 F NR NR 52.8% in this series of predominantly elderly pa- Optic atrophy 71 M NR NR bents not selected for clinical stigmata of late oc- 32 M NR NR ular syphilis. Serologic testing is the mainstay of 68 M NR NR diagnosis of syphilitic ocular disease. Reaginic 85 M 1:8 NR 41 F NR NR tests (VORL or RPR) are insensitive in latent and 61 M 1:2 87 20 NR tertiary syphilis (2,4,7). Specific, treponemal tests 66 F 1:1 NR for syphilis include the FTA-ABS and MHA-TP. 34" M 1:2 36 NR 69 F NR NR In primary syphilis, the sensitivity of serologic 81 F NR 49 NR tests increases with duration of infection. Specific 67 F NR NR treponemal tests are 1000/[ sensitive in infections 33 F NR NR 39" F 1:2 18 62 NR of >40 days' duration (8). Reaginic tests (VORL) 70 M NR 96 55 NR are 96% sensitive. All serologic tests are 100% sen- 68 F NR 12 NR sitive in patients with untreated secondary syph- 70 F 1:2 13 NR 46 M NR 36 NR ilis (2,7). 63 M NR 20 NR In patients with asymptomatic late syphilis, the 68 F NR 12 NR VORL test is 70% sensitive (2,9,10); the MHA-TP 39 M NR 58 NR 43 M NR 69 69 NR test is 93.5-100% sensitive (9,11), and the FTA- 86 M NR 48 50 NR ABS test is 99-100% sensitive (9-11). A reactive Iritis serum FTA-ABS test in the appropriate clinical 28 F 1:4 NR setting should confirm the diagnosis of late syph- 70 F NR NR ilis. The VORL test is insensitive in late syphilis 6209 FM NNRR 50 NNRR and an unreactive VORL may obscure the diag- 42 M NR 69 NR nosis. Of 50 patients with stigmata of ocular syph- 47 M NR 81 NR ilis and reactive FTA-ABS tests, only 12 (24%) had 63 F 1:1 NR reactive VORL tests. Subsequently, VORL reac- Interstitital keratitis 44 F NR 69 NR tivity may be much lower in late syphilis than the 75 M NR 46 NR 70% previously described (2,9,10). Routinely ob- Abnormal pupils taining both VORL and FTA-ABS tests may be dif- 80 F 1:2 48 NR ficult. FTA-ABS testing is often deferred if the Stroke (pontine) VORL is nonreactive. If ocular syphilis is sus- 74 F NR 67 7 NR pected, a serum FTA-ABS test must be specifically Stroke (hemianopia) 79 F NR 214 NR requested, since VORL sensitivity ranges from 6th nerve palsy 28-70% (2,5,9,10) and the serum FTA-ABS test is 59 M 1:1 5 NR 99% sensitive in late syphilis (9-11). Trauma False positive FTA-ABS and MHA-TP results 35 M 1:2 NR occur and are associated with various conditions CSF, cerebrospinal fluid; NR, nonreactive. including autoimmune diseases, genital herpes, " Active papillitis. , (/1Il NClIr"-"l'hthnlll/"I. V"l. - '. J\\l. 4. 1987 194 T. C. SPOOR ET AL. dysproteinemias, narcotic addiction, pregnancy, and nonvenereal treponematosis (2,4). However, an underlying illness cannot be implicated in most false positive FTA-ABS results (12,13). Specificity of both treponemal (FTA-ABS or MHA-TP) sero­logic tests for syphilis is high in healthy persons (99-100%) (7) and decreases to 75-80% in sick pa­tients (7,14,15). None of the present patients had stigmata of active autoimmune disease, were preg­nant, or were sick enough to obviate elective, out­patient surgery. The latter avoids the bias toward false FTA-ABS reactivity in a population of hospi­talized patients. Patients' ages may have contrib­uted to their high incidence of FTA-ABS reactivity (16,17); however, an elderly population, many in­fected in the preantibiotic era, is also more apt to have latent or tertiary syphilis. Technical factors may play an important role in the false reactivity rate of serum FTA-ABS tests (12,18,19). The FTA­ABS tests in this study were performed manually (6) and overseen by a pathologist. This system has been vigorously reviewed by an independent labo­ratory and found to be accurate. Manual FTA-ABS testing is as sensitive as MHA-TP and more sensi­tive than automated FTA-ABS testing (20). This increased sensitivity may account for the high in­cidence of FTA-ABS reactivity. A high prevalence of FTA-ABS reactivity was found in southern Michigan. Similar high preva­lence have been documented in clinics in Miami, Los Angeles, St. Louis, and Atlanta (21). These data indicate that FTA-ABS reactivity is common. As the incidence of infectious syphilis continues to rise and the infected population ages, the preva­lence of late syphilis will increase, as may ocular manifestations. Attempting to determine the ap­propriate treatment for patients with reactive serum FTA-ABS test and ocular manifestations of late syphilis, the CSF from 50 patients was exam­ined. Patients with late syphilis may have a reac­tive serum FTA-ABS test with normal neurologic and CSF examinations (latent syphilis), normal neurologic but abnormal CSF examinations (asymptomatic neurosyphilis), or abnormal neuro­logic and CSF examinations (neurosyphilis) (2). The diagnosis of neurosyphilis is based on a reactive serum FTA-ABS test coupled with a reac­tive CSF VORL and/or lymphocytic pleocytosis (2,7). Some consider sole reliance on these tests in­adequate (22). A reactive CSF VORL is a highly specific indicator of neurosyphilis (7). False posi­tive results have been reported (23), often attrib­uted to contamination of CSF by blood or break- , "I' ,11 tj,f' blond --CSF h,Hrier (7). However, it is 1l.lll! ,\"1'" "I insensitive, being reactive in only 22-69% of pa­tients with active neurosyphilis (7,24). None of the present 50 patients with ocular and neuro-oph­thalmologic signs of late syphilis had reactive VORLs in their CSF. Additionally, all patients with reactive serum VORLs had (12) nonreactive VORLs in their CSF. The diagnostic value of nonreactive VORLs in the CSF of these patients is questionable. A CSF FTA-ABS may be more sensitive than a VORL (22,25,26), but it is nonspecific. False posi­tive reactions may occur (27,28), and the antibody is thought to diffuse into the CSF from the serum (29). Since the results are nonspecific and its inter­pretation is uncertain, FTA-ABS tests on CSF are not recommended for use in the United States (30). Since the CSF VORL may remain reactive for an extended period after adequate treatment (3), the CSF cell count is used to determine the extent of inflammatory activity and the response to therapy after treatment of neurosyphilis (7). The CSF pro­tein level may also be elevated in patients with neurosyphilis; but, this level may also stay ele­vated long after adequate treatment and is less useful as an indicator of response to treatment. The value of routine lumbar puncture in pa­tients with asymptomatic, late syphilis (latent) has recently been questioned (31). Some have sug­gested that lumbar puncture offers little benefit over appropriate treatment with penicillin (32) and may increase morbidity. Hart (7) suggests that CSF examination be limited to four situations: pa­tients with syphilis and neurologic abnormalities, before retreatment of patients who have had re­lapses after any forms of therapy, as a baseline in patients treated with nonpenicillin regimens, and in all infants suspected of having congenital syph­ilis. If ocular abnormalities are considered neuro­logic abnormalities, patients with ocular or neuro­ophthalmologic stigmata of late syphilis should undergo lumbar puncture. The current data indi­cate that CSF abnormalities will be found in many patients with neuro-ophthalmologic signs or evi­dence for neurologic disease. Additionally, many patients with optic atrophy and inactive chorio­retinitis had mildly abnormal CSF. All patients, however, had nonreactive CSF VORL tests. Lumbar puncture prior to treatment in patients with neurologic or neuro-ophthalmic abnormali­ties and patients with evidence for active chorio­retinitis or papillitis is suggested. Patients with inactive chorioretinitis or stable optic atrophy may OCULAR SYPHILIS 1986 195 be treated with intramuscular benzathine peni­cillin (2.4 million U/week for 3 weeks) in lieu of lumbar puncture. Any evidence for active ocular inflammation or progressive deterioration of vi­sual acuity or field should prompt baseline lumbar puncture. Abnormal CSF should prompt subse­quent treatment with high-dose, intravenous aqueous penicillin (12-24 million U/day i.v. for 10-14 days). Any patients treated with a nonpeni­cillin regimen should undergo a baseline lumbar puncture. REFERENCES 1. U.S. Department of Health and Human Services: Sexually transmitted diseases (STD) statistical letters lfmrs 1957-1986. Centers for Disease ControL Atlanta (1986) 2. Holmes KK. Syphilis. In: Thorn GW. Adams RD, Braun­wald E, Isselbacker, Kj, Petersdord RG, eds. Harrison's prillciples of illtemal medicine. New York: McGraw-Hill. 1981:716-26. 3. Spoor TC, Wynn Pj, Hartel WC, Bryan CS. 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