Biological False Positive Reactions Research Articles

HEPATITIS C VIRUS: ANOTHER CAUSE OF FALSE-POSITIVE SYPHILIS TESTS.

Hepatitis C virus (HCV) infection can now be added to the list of infectious diseases that can cause biologic false-positive reactions for syphilis.

DEEP VENOUS THROMBOSIS OF BOTH LEGS WITH POSITIVE ANTIPHOSPHOLIPID ANTIBODY-A CASE REPORT-

A 49-year-old woman was seen at the hospital because of swelling of the left leg. There was a history of deep venous thrombosis (DVT) of the right leg. The patient was diagnosed as having a DVT in the left leg by color-echography. Thrombectomy was successfully performed. Her symptoms resolved but postoperative venography revealed occlusion of the deep venous system of the left leg. Laboratory data showed thrombocytopenia and prolongation of APTT, but protein C, protein S, antithrombin III, and plasminogen values were normal. Serologic tests for syphilis indicated a biological false-positive reaction, and lupus anticoagulant and anticardiolipin antibody were positive. A diagnosis of antiphospholipid syndrome (APS) was established based on the patient's additional history of three consecutive miscarriages. Despite sustained anticoagulation therapy with warfarin, thrombophlebitis occurred in the left lower leg seven months after the operation. Since it is reported that DVT tends to recur in patients with APS, strict anticoagulation therapy seems to be necessary throughout their lives. Additional antiplatelet therapy may be needed because of possible arterial thrombosis.

Detection of beta-2-glycoprotein-I-dependent antiphospholipid antibodies and anti-beta-2-glycoprotein-I antibody in patients with systemic lupus erythematosus and in patients with syphilis.

We investigated whether or not antiphospholipid antibodies (aPLs; antiphosphadidylserine antibody, aPS; antiphosphatididylinositol antibody, aPI; antiphosphatidic acid antibody, aPA, and antiphosphadidylethanolamine antibody, aPE) were beta 2-glycoprotein-I (GPI)-dependent antibodies like anticardiolipin antibody (aCL) in patients with systemic lupus erythematosus (SLE). None of the patients with syphilis or healthy controls was positive for any GPI-dependent aPL. By contrast, GPI-dependent aCL (40%), aPS (20%), aPI (18%), aPA (12%) and aPE (8%) were detected in patients with SLE. Among these, 4 patients were negative for aCL, but positive for aPS. Those who were positive for more than 2 types of aPL, along with lupus anticoagulant, had a high incidence of arteriovenous thrombosis, fetal loss, thrombocytopenia and biological false-positive reaction to syphilis. From these findings we conclude that GPI-dependent aPLs, other than aCL, are present in patients with SLE, and we should examine more than 2 types of aPL, such as a combination of aCL and aPS, to avoid overlooking aPL. Furthermore, we confirmed that GPI-independent aPL was not rare in SLE patients, but the clinical significance of this type of aPL in this clinical setting is unclear.

Presidential Address to the M.S.S.V.D: Systemic disease and the biological false positive reaction

Presidential Address to the M.S.S.V.D: Systemic disease and the biological false positive reaction

Association of biologic false-positive reactions for syphilis with human immunodeficiency virus infection.

The prevalence of biologic false-positive (BFP) reactions for syphilis (reactive rapid plasma reagin [RPR] test, nonreactive fluorescent treponemal antibody absorption [FTA-ABS] test) among patients attending two sexually transmitted disease (STD) clinics was evaluated to assess relationships between BFP reactions and human immunodeficiency virus (HIV) infection. Among 4863 patients, 357 (7.3%) had serologic evidence of syphilis and 4.9% had HIV infection. Only 40 patients (0.8% of total patients, 11% of those with reactive RPR tests) had BFP serologic tests for syphilis. There were no demographic differences between true syphilis and BFP patients as to sex, age, or intravenous drug use. BFP patients tended to have lower RPR titers (less than or equal to 1:4) than did true syphilis patients. After excluding 317 patients with reactive FTA-ABS tests, BFP RPR tests were seen in 6 (4%) of 159 HIV-seropositive patients and 34 (0.8%) of 4387 HIV-seronegative patients (odds ratio, 5.0; 95% confidence interval, 1.9-12.7). Although more common among HIV-infected than HIV-uninfected patients, BFP reactions are relatively rare among STD clinic patients, and 89% of patients with reactive RPR or VDRL serologic tests for syphilis had current or prior syphilis infection. The RPR test remains useful for guiding decisions regarding therapy for syphilis.

Biological false positive serological tests for syphilis in the Jamaican population.

A total of 19,067 sera were screened for biological false positive (BFP) reactivity by the Venereal Disease Research Laboratory (VDRL) test. Sera which were reactive in the VDRL test were confirmed by the fluorescent treponemal antibody absorption (FTA-ABS) test. BFP reactions were detected in 0.59% of the general population, 0.72% of pregnant women and 11.8% of patients with systemic lupus erythematosus (SLE). The rate of BFP reactors among pregnant women did not differ significantly from the general population. The female to male ratio of BFP in the general population was 2:1 whilst that in the group of patients with SLE was 8:1. The overall seroprevalence of syphilis was 2.2%.

Biological True and False Serological Tests for Syphilis: Their Relationship with Anticardiolipin Antibodies

Anticardiolipin antibodies (ACA) were determined by an ELISA assay in 142 VDRL-positive patients who were classified in two groups: group I consisted of 77 patients with syphilis and group II of 65 patients with biological false-positive reaction in the standard test for syphilis. In group I 10% had ACA versus 52% in group II (p less than 0.0001). Isotype distribution in group II showed a predominance of IgG. These results suggest that antiphospholipid antibodies in VDRL and ACA tests have different specificities.

The anticardiolipin syndrome. A new way to slice an old pie, or a new pie to slice?

Students of systemic lupus erythematosus have long been confused by the paradoxical association of atypical clinical features such as recurrent thrombosis and spontaneous abortion with the lupus anticoagulant and biologic false-positive VDRL reaction. The recent development of sensitive, solid-phase immunoassays for quantitating the autoantibody response to phospholipids holds the promise of illuminating the basis for this seeming enigma. It is now apparent that antiphospholipids antibodies such as anticardiolipin might well play a role in mediating the elements of this paradox. In addition, other cutaneous vascular conditions as diverse as livedo reticularis and Degos' disease might also be related to this type of autoimmune response.

Evaluation of VDRL test in Sudanese blood donors.

2201 blood donors and 199 patients with sexually transmitted diseases (STD) were tested with the Venereal Disease Research Laboratory (VDRL) and the fluorescent treponemal antibody-absorption (FTA-ABS) tests. The VDRL test was found positive in 30 (1.36%) of the blood donors and 11 (5.5%) of the patients. Syphilis was confirmed by FTA-ABS test in one patient (0.5%) but not in blood donors. The biological false positive (BFP) reactions were 1.36% in blood donors and 5.0% in control patients. The place of VDRL test as a screening test for syphilis and the low rate of its seroreactivity among blood donors was discussed. The BFP reactions were reviewed to assist in the interpretation of the VDRL test which was evaluated on the basis of the control specimens. It was concluded that syphilis should be excluded before blood is transfused and the VDRL test should remain the screening test of choice in the blood transfusion service.

Posttreatment Serological Response of Biologic False-Positive Reactors

IN 1980, there were 27,204 reported cases of primary and secondary syphilis in the United States, an increase of 33.4% during the last three years. 1 It is well known that certain diseases, immunizations, and febrile states may produce a reaction to a reagin blood test for syphilis in the absence of this disease. In the United States, approximately 45 million persons are tested for syphilis and about 1.4 million have a reaction to reagin test. 2 How many have biologic false-positive reactions is unknown. However, in Massachusetts, slightly more than 160,000 blood samples were sent to the state laboratory for the rapid plasma reagin circle-card test (RPR-CT) for syphilis. Approximately 7% were found to be reactive. Further testing of the reactive blood tests with the fluorescent treponemal antibody absorption (FTA-ABS) test disclosed that about 25% had a nonreactive FTA-ABS test, indicating that the patient has a biologic falsepositive reaction.

Serological Tests for Syphilis in Rape Cases

To the Editor.— In a recent issue (226:1577, 1973), Dr. Haymann comments on emergency department protocol for the management of rape cases. He advises that a serological test for syphilis be done at that time. Another consultant, Dr. Garcia, advises that management include prevention of venereal disease. If the patient appears at the emergency department within hours of the alleged rape, a serological test for syphilis would be useless, as the assay is dependent upon the systemic response of the individual's immune system. This may not be manifest for up to several weeks. Immediate serological tests can further complicate the situation in the event of biological false-positive reactions. An efficient follow-up at monthly intervals including serological testing might be more informative for the physician and more beneficial to the patient.

Biologic false-positive reactions in serologic tests for syphilis in narcotic addiction. Reduced incidence during methadone maintenance treatment.

Biologic false-positive (BFP) tests for syphilis was found in 23% of 69 New York heroin addicts. After 23 ± 7 months of methadone maintenance treatment, BFP decreased to 5.8%. No correlation between abnormalities in SGOT, alkaline phosphatase, albumin, total protein, and the presence or loss of BFP reactions was observed. Similarly, no correlation between serum IgM or IgG levels or latex-fixation titers and the presence or loss of BFP reactions was found. BFP is a nonspecific serologic abnormality seen in urban narcotic addicts, which is alleviated by methadone treatment, presumably as a result of reduced exposure to unknown antigens.

Waldenström's macroglobulinemia in a patient with a chronic biologic false-positive serologic test for syphilis

Acute and chronic biologic false-positive serologie reactions for syphilis (VDRL) have been associated with a variety of diseases. Several investigators emphasize that false-positive VDRL titers are usually very low. This report describes a 73 year old man with Waldenström's macroglobulinemia. The biologic false-positive serologic test for syphilis was recognized 33 years before the diagnosis of Waldenström's macroglobulinemia was made. VDRL titers were as high as 1:8192 and 1:32,000 during exacerbations of the macroglobulinemia. A biologic false-positive serologic test for syphilis is frequently associated with an elevated immunoglobulin M (IgM) level. It would be interesting to search for a relation between biologic false-positive serologic tests for syphilis and diseases characterized by monoclonal gammopathies.

Diagnostic Significance of Positive Syphilis Tests

To the Editor.— Dr. Nicholas J. Fiumara's reply (223:1167, 1973) to a question regarding VDRL tests in a 20-year-old virgin woman does not appear to me to be entirely consistent with the information provided in the query. The repeated VDRL tests in low titer are as consistent with latent syphilis as with a biological false-positive reaction. The FTA-ABS tests were on two occasions and negative on two others. If truly positive, the FTA-ABS test would confirm a diagnosis of syphilis indicating lumbar puncture and adequate treatment. If truly negative, the FTA-ABS test would rule out syphilis and indicate further investigation, especially in terms of autoimmune disease as Dr. Fiumara suggests. Aside from the unique and recognizable beaded pattern false positive found in lupus erythematosus, 1 the FTA-ABS test is highly specific for syphilis. Confirmation of the status of the FTA-ABS test and possible use of a second specific

THE RAPID PLASMA REAGIN (CIRCLE) CARD TEST: A SCREENING TEST FOR SYPHILIS

The results of the Rapid Plasma Reagin circle card and VDRL slide tests on 820 problem sera are compared. TPI and FTA-ABS tests were also carried out on each specimen of serum. The RPR circle card test was found to be more sensitive, but less specific, than the VDRL slide test. The RPR circle card test detected 32 more cases of syphilis than the VDRL slide test. However, it showed more biological false positive reactions than the VDRL test. The RPR circle card test is simple and quick to perform, and compares favourably with the VDRL test. It appears to be an acceptable screening test for syphilis.

The Treponema pallidum haemagglutination (TPHA) test in biological false positive and leprosy sera.

The Treponema pallidum haemagglutination (TPHA) test was carried out on 274 sera known to show biological false positive reactions to reagin tests for syphilis. The Treponema pallidum immunization (TPI) and fluorescent treponemal antibody absorption (FTA-ABS) tests were non-reactive on all these sera. Thirty-one or 11.3% showed reactive results in the TPHA test. Sera from 267 people who had lepromatous leprosy were also tested in the TPHA test. Fourteen sera were reactive in the TPHA, TPI, and FTA-ABS tests and were from people who had both syphilis and leprosy. Biological false positive reactions were shown by 26 of the leprosy sera, of which three or 11.5% were also reactive in the TPHA test. A further four sera in the leprosy group were reactive only in the TPHA test. The possible cause of false reactive TPHA test results is discussed. It was concluded that where reagin and TPHA tests are reactive in a person who has no history or clinical signs of syphilis, the serum should be referred for TPI and FTA-ABS testing.

The rapid plasma reagin (circle) card test in biological false positive and leprosy sera

The rapid plasma reagin (RPR) circle card and the Venereal Disease Reference Laboratory (VDRL) slide test results were compared on a group of sera known to show biological false positive (BFP) reactions to reagin detection tests for syphilis. The RPR test was more specific than the VDRL test on the sera selected, ie, it gave fewer false positive results than the VDRL test. However, in a group of presumed normal sera, the RPR test gave BFP reactions while the VDRL test gave none. The RPR test gave fewer BFP reactions than the VDRL test in 269 sera from patients with lepromatous leprosy.

Occurrence of antinuclear factors and immunoglobulins bound to the dermo-epidermal junction in patients with chronic biological false positive (CBFP) reactions for syphilis

No abstract available

Presidential Address to the M.S.S.V.D. Systemic disease and the biological false positive reaction.

Presidential Address to the M.S.S.V.D. Systemic disease and the biological false positive reaction.

Familial Chronic Biologic False-Positive Seroreactions for Syphilis

Two families manifested hereditary chronic biologic false-positive (BFP) seroreactions for syphilis. In one family, this trait was demonstrated in four of seven members, affecting three generations, grandfather, son, daughter, and granddaughter. Grandfather and son manifested increasing reagin titers over a period of 11 to 17 years. Positive Coombs' tests indicating autoantibodies were demonstrated in two seroreactors. In the second family, three of five members were affected, father, son, and daughter. The chronic BFP reaction appears to be a genetically transmissible trait associated with humoral autoantibodies with the potential for autoimmune disease.