Negative Venereal Disease Research Laboratory Research Articles

Exposing the Great Imitator: Proposal for a Holistic Diagnosis of Oral Secondary Syphilis in People Living with HIV.

Oral secondary syphilis may mimic various infectious, neoplastic, or immune-mediated processes; hence, its diagnosis may represent a challenge. Early diagnosis of syphilis, a disease that has increased in recent decades, is essential for adequate management, particularly in people living with HIV (PLWH). This study aimed to comprehensively characterize oral secondary syphilis in a group of 47 PLWH. A group of PLWH with oral secondary syphilis attending four HIV-referral centers in Mexico City was included (2004-2021). Clinical and laboratory data were retrieved, and an exhaustive oral examination was performed following the established criteria. Demographic, clinicopathological, immunohistochemical, and serological features of the patients were analyzed. Approximately 11% of PLWH with oral secondary syphilis demonstrated negative Venereal Disease Research Laboratory tests. A noticeable feature was the absence of symptoms in 95.7% of cases, despite the clinically evident appearance of the lesions. In contrast to previous results, 18% of ulcerations were detected to be deep, crateriform, and infiltrative, and 22% of the mucous patches were highly keratotic lesions. Most samples (77.3%) showed superficial lymphoplasmacytic infiltrates in the superficial lamina propria, with perivascular and perineural patterns, and immunohistochemistry was positive in 66.7% of the cases. The "great imitator" appears not only clinically but also histopathologically and immunohistochemically, where features may be comparable with those of chronic inflammatory processes, deep infections, or malignant processes. Although not recommended as a routine assay, IHC could be a critical tool, particularly in PLWH with atypical clinical features or with negative and/or dubious serology.

A case of ocular neurosyphilis in a patient with HIV

A case of ocular neurosyphilis in a patient with HIV

Lues Maligna in an Immune-Reconstituted Patient with Retroviral Infection: A Case Report

Lues Maligna in an Immune-Reconstituted Patient with Retroviral Infection: A Case Report

Congenital syphilis: a revision of the cases over the last 18 years in a referral hospital in Lisbon

Introduction: Congenital syphilis is a preventable disease and its persistence reflects a failure in prenatal care delivery systems. Objectives: To identify demographic maternal characteristics, risk factors and clinical features of congenital syphilis. The secondary outcome was to describe the symptomatic cases of congenital syphilis. Methods: Retrospective study of all the children born, between 1997-2015, to syphilis seropositive women. We collected data regarding sociodemographic characteristics, maternal VDRL (Venereal Disease Research Laboratory) titers, co-infections and treatment during pregnancy, clinical features, treatment and follow-up. Results: From a total of 80,639 newborns, 310 mothers and 225 babies had positive VDRL titers. The prevalence risk for congenital syphilis was 0.27%, higher between 2003-2008. Observed maternal characteristics were: 3.9% young mothers (< 20 y), 45.2% African origin, 12.5% basic educational levels, 14.5% unemployed, 6.5% co-infected with human immunodeficiency virus (HIV), 4.7% drug abuse. Prenatal care coverage was provided in 82.9% of the mothers, with only 52.9% adequately treated. Maternal syphilis was classified in: 21.6% early, 21.6% late, 56.8% undetermined. The newborns were classified in: 13.2% highly probable, 41.6% possible and 45.2% less likely. There were four cases of symptomatic congenital syphilis, 3 of them with neurosyphilis. 96% were treated with penicillin. 165/310 (53%) had an adequate follow-up, and the mean age for a negative VDRL titer was at 5.6 months of age. Conclusions: The high percentage of women inadequately treated alerts to the importance of improving prenatal care. Neurosyphilis is a rare and severe presentation of congenital syphilis; screening is essential to avoid late cases or sequels.

Predictors of serological cure after treatment in patients with early syphilis: A retrospective observational study in Thailand.

Some patients with early syphilis who receive appropriate treatment do not reach a serological cure and have a persistent titer which does not meet the criteria for treatment failure (serofast state). This retrospective study aimed to determine the prevalence of serological cure and the serofast state as well as the factors associated with serological cure after treatment of patients with early syphilis. A serological cure was defined as occurring when there was a ≥4-fold decrease in nontreponemal titer, whereas patients with a ≥4-fold increase were considered as having either a treatment failure or reinfection. Nontreponemal titers that neither increased nor decreased ≥4-fold after treatment were considered to be in a serofast state. Seroreversion was defined as occurring when there was a negative test within 12 months of treatment. There were 179 patients with a mean age of 31.9 years; 174 (97.2%) were men, and 125 (70%) were HIV patients. Of the total, 174 (98%; 95% confidence interval 94.82-99.42%) patients achieved a serological cure, whereas five were in a serofast state 12 months after treatment. Those five serofast patients were all HIV-positive men, of which 4 (80%) had secondary-stage syphilis, a CD4 count ≤200 cells/μl and a titer <1:8. In a bivariate analysis, a serological cure was associated with a baseline Venereal Disease Research Laboratory >1:16 titers (P = 0.018), and a CD4 cell count >200 cells/μl in 6 months preceding treatment (P = 0.016). The median time to a serological cure was 96 days. Only 22 (12.3%) of the patients achieved seroreversion at 12 months after treatment. A retrospective medical record review is likely to have a selection bias, and in our study, 196 (52%) patients were excluded due to missing information. Most patients with early syphilis who achieved a serological cure at 12 months after treatment had high baseline Venereal Disease Research Laboratory titers and CD4 cell counts. However, only 22 (12.3%) had a negative Venereal Disease Research Laboratory titer after 1 year of treatment.

Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV+ patients with syphilis.

Lumbar puncture in neurologically asymptomatic HIV+ patients is still under debate. There are different criteria for detecting neurosyphilis through cerebrospinal fluid (CSF), especially in cases that are negative through the Venereal Disease Research Laboratory (VDRL), regarding cellularity and protein content. However, a diagnosis of neurosyphilis can still exist despite negative VDRL. Treponema pallidum hemagglutination assay (TPHA) titers and application of the TPHA index in albumin and IgG improve the sensitivity, with a high degree of specificity. Thirty-two patients were selected for this study. VDRL was positive in five of them. The number of diagnoses reached 14 when the other techniques were added. It was not determined whether cellularity and increased protein levels were auxiliary tools in the diagnosis. According to our investigation, CSF analysis using the abovementioned techniques may be useful in diagnosing neurosyphilis in these patients.

False-Positive Venereal Disease Research Laboratory Tests in the Cerebrospinal Fluid With Meningeal Carcinomatosis

There are many causes of false-positive Venereal Disease Research Laboratory (VDRL) tests in serum, for example, systemic lupus erythematosus, pregnancy, liver disease, intravenous drug abuse. Such patients have a negative serum fluorescent treponemal antibody absorption test. False-positive VDRLs in the cerebrospinal fluid (CSF) are extremely rare. We present a case of suspected neurosyphilis in a patient with a negative serum VDRL and fluorescent treponemal antibody absorption test but with a positive CSF VDRL. This is only the third reported case of a false-positive CSF VDRL, which, in this case, was caused by meningeal carcinomatosis.

FENÓMENO PROZONA EM PACIENTE HIV NEGATIVO

O fenómeno prozona resulta de altos títulos de anticorpos em pacientes com sífilis, provocando uma resposta falso negativa do “Venereal Disease Research Laboratory“ (VDRL). Relatamos um caso de uma paciente feminina, 50 anos, com lesões eritematosas, assintomáticas disseminadas e hiperemia em conjuntiva ocular esquerda. Ao exame, múltiplas placas eritemato infiltradas, entremeadas por pele sã, em tronco, dorso, abdome e face. Linfonodo epitrocleano palpável à direita. Trazia exames gerais normais e VDRL negativo. Solicitado FTA-ABS IgG reagente e VDRL em soro diluído: 1:512. Confirmando, portanto, a ocorrência do fenómeno prozona.

Serological Response to Treatment of Syphilis According to Disease Stage and HIV Status

Serology is the mainstay for syphilis diagnosis and treatment monitoring. We investigated serological response to treatment of syphilis according to disease stage and HIV status. A retrospective cohort study of 264 patients with syphilis was conducted, including 90 primary, 133 secondary, 33 latent, and 8 tertiary syphilis cases. Response to treatment as measured by the Venereal Disease Research Laboratory (VDRL) test and a specific IgM (immunoglobulin M) capture enzyme-linked immunosorbent assay (ELISA; Pathozyme-IgM) was assessed by Cox regression analysis. Forty-two percent of primary syphilis patients had a negative VDRL test at their diagnosis. Three months after treatment, 85%-100% of primary syphilis patients had reached the VDRL endpoint, compared with 76%-89% of patients with secondary syphilis and 44%-79% with latent syphilis. In the overall multivariate Cox regression analysis, serological response to treatment was not influenced by human immunodeficiency virus (HIV) infection and reinfection. However, within primary syphilis, HIV patients with a CD4 count of <500 cells/μL had a slower treatment response (P = .012). Compared with primary syphilis, secondary and latent syphilis showed a slower serological response of VDRL (P = .092 and P < .001) and Pathozyme-IgM tests (P < .001 and P = .012). The VDRL should not be recommended as a screening test owing to lack of sensitivity. The syphilis disease stage significantly influences treatment response whereas HIV coinfection only within primary syphilis has an impact. VDRL test titers should decline at least 4-fold within 3-6 months after therapy for primary or secondary syphilis, and within 12-24 months for latent syphilis. IgM ELISA might be a supplement for diagnosis and treatment monitoring.

Prevalence of syphilis among HIV-seroreactive patients

Presence of genital ulcer disease facilitates human immunodeficiency virus (HIV) transmission and their ­diagnosis is essential for the proper management. Venereal Disease Research Laboratory (VDRL) test is used as a screening test for the diagnosis of syphilis. However, unusual VDRL test results have been reported in HIV-infected persons with syphilis. There are reports showing higher than expected VDRL titers as well as biological false positive in most of the studies. A negative Rapid Plasma Reagin (RPR) test or VDRL test result may not rule out syphilis in patients with HIV infection. For laboratory confirmation of syphilis, one specific Treponemal test, namely, Fluroscent Treponemal Antibody Absorption (FTA-ABS) test or Treponema Pallidum Haemagglutination Assay (TPHA) should be done along with VDRL.<br>In the present study, 88 HIV-seropositive patients with history of high-risk behaviour were screened for syphilis by VDRL test. Out of these 88 cases, 42 (47.7%) patients were positive for TPHA and eight (9.1%) patients were reactive for VDRL in various titers. All the eight patients who were reactive for VDRL test were also positive for TPHA test.<br>Persons with HIV infection acquired through sexual route should be screened for sexually transmitted infections (STIs), and all patients with STIs should be counselled for HIV testing. This will help in proper management of patients having STIs and HIV coinfection.