Nonreactive Rapid Plasma Reagin Research Articles

Perianal warty dyskeratoma

Warty dyskeratoma is a rare keratinization disorder marked by acantholytic dyskeratosis and belongs to the spectrum of acantholytic dyskeratosis in dermatology. It was first documented in 1954 and typically manifests in the head, neck, oral mucosa, and trunk, with several cases reported since its discovery. A 35-year-old unmarried gentleman presented in April 2022 with a 5-year history of perineal itching and discomfort. His physical examination revealed a 7-8 centimeter perianal grouped papular plaque. His medical history was unremarkable, and he has no family history of similar conditions or other dermatological disorders. Lab results showed non-reactive rapid plasma reagin and human immunodeficiency antigen/antibody combo. Liver and renal function tests were within normal range as well. The microscopic findings revealed features including prominent hyperkeratosis, invagination filled with keratin, and the surrounding area exhibiting acantholysis and intercellular edema. In conjunction with the patient’s clinical presentation, this histological profile led to the diagnosis of warty dyskeratoma. After treatment with calcipotriene and other topical agents, the last presentation showed very good improvement; the physical examination indicated remarkable thin, flat, soft, grayish plaque in the perianal area. This case report presents a unique instance of warty dyskeratoma affecting the perianal area, shedding light on differential diagnosis and clinical management in this atypical context, which significantly broadens the understanding and emphasizing that the Warty dyskeratoma can manifest in diverse body regions, urging its consideration in the differential diagnosis of perianal papular lesions.

1618. Assessing and Improving Accurate Diagnosis and Reporting of Congenital Syphilis in a Tertiary Care Children's Hospital

Abstract Background Congenital syphilis (CS) occurs due to transplacental passage of active infection to the fetus during pregnancy. Clinical presentation ranges from asymptomatic to severe permanent disability. Nationally, the incidence and prevalence of syphilis among cisgender females ages 15-44 have increased, with proportional increases in rates of CS. In 2020, 19 cases of CS were reported to the Chicago Department of Public Health (CDPH), a 138% increase from 2019 (8 cases). There are circumstances where infants with a non-reactive rapid plasma reagin (RPR-) may potentially contract syphilis in the context of inadequate maternal treatment per national guidelines. (Figure 1) Currently, only infants with RPR reactivity (RPR+) are reported to CDPH, potentially underestimating the true incidence. Our project sought to identify RPR- infants who received treatment to improve reporting to CDPH, more accurately reflect the prevalence of CS in Chicago, and ultimately guide interventions to reduce and eliminate CS.Figure 1:2021 Center for Disease Control (CDC) Possible Congenital Syphilis Definition Methods Data was collected via electronic medical record (EMR) review for infants born at Comer Children’s Hospital in Chicago, IL between 2012 and 2022, filtered using ICD-9 code (090) and ICD-10 code (A50.9) for CS. Infants were excluded if diagnosis code was used in error, there was no RPR result, or diagnosis occurred at an outside institution. (Figure 2) Infants were stratified as having CS with RPR+ or RPR-. Retrospectively, each infant was also classified with a diagnosis of less likely CS, possible CS, and proven CS per national guidelines.Figure 2:Patient Stratification by ICD-9 and ICD-10 Code for Congenital Syphilis and RPR Reactivity. RPR = Rapid Plasma Reagin Results 68 infants with CS were identified. 57 infants received IV PCN with diagnoses of proven or possible CS (84%). 51 (75%) patients were RPR+ and 17 (25%) were RPR-. (Figure 3) Of the 17 RPR-, 11 had a diagnosis of possible CS (65%) and received IV PCN while 6 (35%) had less likely CS and received one dose of intramuscular (IM) PCN (Table 1). None of the RPR- infants were reported to CDPH.Figure 3:Total Number of Congenital Syphilis Cases Based on CDC Definition. CS = Congenital Syphilis, CDC = Center for Disease ControlTable 1:Total Number of Days of Intravenous or Intramuscular Penicillin Administration per RPR reactivity.. Aq PCN = Aqueous Penicillin G, Ben PCN = Benzathine Penicillin G, IM = Intramuscular, IV = Intravenous Conclusion In this retrospective analysis, reporting CS based solely on a reactive infant RPR leads to underreporting. As we confront the rising incidence of CS, (Figure 4) it is critical that we have a complete understanding of the epidemiology which may lead to increased support for public health initiatives focused on decreasing and eliminating CS.Figure 4:Timeline of Total CS and RPR- CS Cases at Hospital per Year. CS = Congenital Syphilis Disclosures Allison H. Bartlett, MD, MS, CVS/Caremark: Honoraria Jessica Ridgway, MD, Gilead Sciences: Expert Testimony

Treponema pallidum infection rate in patients attending the general hospital of Benguela, Angola

The objectives of this study were to estimate the rate of infection by Treponema pallidum and co-infection with Human Immunodeficiency Virus (HIV) in individuals attending the General Hospital of Benguela (GHB), Angola, to verify the Rapid Plasma Reagin (RPR) test performance for its diagnosis when compared with other RPR tests, and to compare a rapid treponemal test with the Treponema pallidum hemagglutination assay (TPHA). This is a cross-sectional study carried out between August 2016 and January 2017, at the GHB, 546 individuals attending the emergency room, the outpatient service or hospitalized at the GHB were included. All the samples were tested at the GHB with the routine hospital RPR test and a rapid treponemal test. The samples were then transported to the Institute of Hygiene and Tropical Medicine (IHMT) where RPR testing and TPHA testing were performed. The rate of T. pallidum active infection, demonstrated by a reactive RPR and TPHA result, was 2.9%, of which 81.2% corresponded to indeterminate latent syphilis and 18.8% to secondary syphilis. HIV co-infection was detected in 62.5% of individuals diagnosed with syphilis. Past infection, defined as a non-reactive RPR and reactive TPHA test, was diagnosed in 4.1% of individuals. The high rate of syphilis/HIV co-infection emphasizes the urgent requirement for adequate sexually transmitted infections (STIs) screening, prevention and treatment programs. In addition, implementation of quality control measures within RPR testing protocols at GHB are needed, including training for laboratory personnel, adequate equipment and introduction of other rapid testing.

Gaps in the elimination of congenital syphilis in a tertiary care center in Thailand.

The World Health Organization has set a goal to eliminate mother-to-child transmission of syphilis to a target of <50 cases per 100000 live births. This study aimed to determine the rate of congenital syphilis and identify gaps in prevention. A retrospective chart review was conducted in a tertiary care center in Bangkok, Thailand. The study included all pregnant women with positive syphilis serology and their infants. All congenital syphilis cases were categorized according to Centers for Disease Control criteria. From 2013 to 2017, 69 syphilis-infected pregnant women were included, with 30 congenital syphilis cases. The rate of congenital syphilis was 115 cases (95% CI 78-164) per 100000 live births. The median (interquartile range) maternal age was 21 (18-32)years and 12 (17%) women had human immunodeficiency virus co-infection. Regarding maternal treatment, 28 (41%) women had inadequate treatment due to 13 cases (19%) of late or no antenatal care, six cases (8%) of recent infection near delivery, five cases (7%) of failure of treatment provision, and four (6%) others. There were three syphilitic stillbirths who were prematurely born to untreated pregnant women and 67 live births (one set of twins) of which 27 met definitions of probable congenital syphilis. They received complete treatment with penicillin and had non-reactive rapid plasma reagin within the first 6months of life, with the exception of one who had non-reactive rapid plasma reagin at the age of 7months. Congenital syphilis remains a problem in our setting. Nearly half of pregnant women who had syphilis had inadequate treatment. There is an urgent need to strengthen diagnosis and the treatment cascade of syphilis during antenatal care.

1493. Effect of HIV Status on Early Syphilis Treatment Response in the Era of Combination Antiretroviral Therapy

BackgroundRates of incident early syphilis are increasing and HIV-coinfection is common. Syphilis treatment for HIV-positive individuals does not differ from that of the general population, although data published prior to combination antiretroviral therapy (cART) suggest that HIV-infected persons may be less likely to achieve expected serologic responses to treatment (SRT).MethodsWe conducted a cohort study of early syphilis diagnosed in a large HIV clinic and a public sexually transmitted diseases (STD) clinic in San Diego. SRT was defined as a fourfold or greater decline in rapid plasma reagin (RPR) titer following syphilis treatment. We compared SRT at 6 and 12 months post-treatment between HIV-infected and HIV-uninfected persons.ResultsOf 1,239 early syphilis cases reviewed, 742 (61%) were included in the analysis. Reasons for exclusion included lack of follow-up RPR (n = 454), nonreactive RPR at syphilis diagnosis (n = 33), and incomplete data (n = 10). Of those analyzed, 533 (72%) were HIV-positive; 168 (23%) HIV-negative; HIV status was unknown for 41 (5%). Overall, 449 (60%) and 657 (89%) of analyzed cases achieved SRT 6 and 12 months after treatment, respectively. HIV-positive cases were less likely to achieve SRT at 12 months than HIV-negative cases (464/533 [87%] vs. 160/168 [95%], P = 0.003, Figure 1), as were early latent syphilis cases (285/348 [82%]) vs. primary (102/117 [92%]) and secondary syphilis (264/277 [94%]) (Table 1).Table 1.Serologic Response to Treatment by Syphilis Clinical StageSyphilis StageRPR Titer ResponsePrimary N = 117Secondary N = 277Early Latent N = 348 P-Value6 months post-treatment ≥4-fold decline70 (60%)177 (64%)202 (58%) <4-fold decline47 (40%)100 (36%)146 (42%)0.32312 months post-treatment ≥4-fold decline108 (92%)264 (95%)285 (82%) <4-fold decline9 (8%)13 (5%)63 (18%)<0.001 ConclusionIn this cohort of early syphilis cases, most achieved SRT within 12 months of treatment, but only 60% achieved SRT within 6 months. Significantly lower 12-month SRT responses were seen in HIV-positive compared with HIV-negative persons and in early latent compared with primary and secondary syphilis. The impact of cART use, viral suppression, and treatment choice on outcomes is being analyzed.Disclosures All authors: No reported disclosures.

Transient aortitis documented by positron emission tomography in a case series of men and transgender women infected with syphilis

ObjectivesSyphilis infection persists globally contributing to preventable and treatable morbidity and mortality. How extensive early syphilis disseminates is unknown. To better understand the relationship between early syphilis infection and inflammation...

The Impact of Combined Antiretroviral Therapy on Biologic False-Positive Rapid Plasma Reagin Serologies in a Longitudinal Cohort of HIV-Infected Persons

Our objective was to determine the impact of combination antiretroviral therapy (cART) and the degree of immunosuppression on biologic false-positive (BFP) rapid plasma reagin (RPR) tests among persons infected with human immunodeficiency virus (HIV). This was a nested retrospective study of HIV-infected patients enrolled in the Johns Hopkins HIV Clinical Cohort. BFP RPR was defined as a reactive RPR and a nonreactive fluorescent treponemal antibody-absorption (FTA-ABS) test. Patients with BFP tests were compared to 2 control groups: HIV-infected patients (1) with active syphilis (reactive RPR and FTA-ABS) and (2) without current syphilis (nonreactive RPR). A persistent BFP test was defined by having at least 2 visits with consistent BFP at all visits. Of 711 patients with HIV, 96 (13.5%) had BFP tests and 342 (48.1%) had syphilis. Twenty-two of 96 (23%) had persistent BFP tests. cART use was associated with decreased odds of BFP tests compared to having syphilis (adjusted odds ratio [AOR], 0.31; 95% CI, .15-.63) and those with nonreactive RPR (AOR, 0.42; 95% CI, .22-.81). cART use was also associated with decreased odds of BFP persistence (AOR, 0.07; 95% CI, .01-.33). Neither CD4 count nor HIV RNA was significantly associated with BFP test results. Lower RPR titers, younger age, and injection drug use were associated with increased odds of BFP. The use of cART appears to decrease the odds of BFP RPR tests. This finding suggests that nontreponemal titer fluctuations in persons with HIV may reflect the influence of factors unrelated to syphilis disease activity.

Neurocognitive impairment in HIV-infected individuals with previous syphilis

Cognitive impairment is common in HIV-infected individuals, as is syphilis. Treponema pallidum, the bacterium that causes syphilis, invades the central nervous system early in disease. We hypothesized that HIV-infected patients with a history of syphilis or neurosyphilis would have more cognitive impairment than HIV-infected individuals without these infections. Eighty-two of 1574 enrollees in CHARTER, a prospective, observational study, had reactive serum rapid plasma reagin (RPR) tests. They were matched to 84 controls with non-reactive RPR by age, gender, ethnicity and HIV risk factor. Participants underwent comprehensive neuropsychological (NP) evaluations. RPR results were confirmed and serum fluorescent treponemal antibody absorption (FTA-ABS) test reactivity determined at a central laboratory. Sera from 101 of 166 participants were FTA-ABS reactive, indicating past or current syphilis. Among the 136 individuals without confounding conditions, compared with patients who had never had syphilis, those with prior syphilis had a greater number of impaired NP test domains (1.90 SD [1.77] versus 1.25 [1.52], P = 0.03), a higher global deficit score (0.47 [0.46] versus 0.31 [0.33], P = 0.03), and more were impaired in the NP learning domain (36 [42.9%] of 84 versus 13 [25.0%] of 52, P = 0.04). These effects of prior syphilis remained after controlling for education and premorbid intelligence.

Characteristics of Patients with Primary and Late Latent Syphilis Patients Who Were Initially Non-Reactive to the Rapid Plasma Reagin Test

We aimed at determining the characteristics of patients with primary and late latent syphilis who were non-reactive on initial screening by rapid plasma reagin (RPR) but reactive by treponemal tests. We collected the RPR test results of all primary and late latent syphilis patients in our hospital from December 2000 to March 2012. The characteristics of syphilis patients who were non-reactive by RPR testing were compared to those of reactive patients. Multiple logistic regression was used to identify factors associated with non-reactive RPR results. Among primary syphilis patients, 37 (16.5%) were non-reactive on initial RPR and were compared with the 187 reactive cases. Age >35 years was an independent factor associated with a non-reactive result in primary cases (odds ratio [OR], 95% confidence intervals [CI] = 3.55 [1.39-9.07]). Of the late latent patients, 61 (8.8%) were non-reactive by RPR and 636 were reactive. Age >34 years was also an independent factor associated with a non-reactive result in late latent cases (OR [95% CI] = 4.30 [2.28-8.12]). This study suggests that RPR testing alone is insufficient to diagnose primary and late latent infections, especially in middle-aged and elderly individuals. Syphilis detection was lower for patients with primary syphilis than for those with late latent syphilis based on the results of the RPR.

Case report and evaluation of the frequency of the prozone phenomenon in syphilis serology - an infrequent but important laboratory phenomenon

Treponema pallidum specific serology generally remains reactive for life. Therefore, the diagnosis of syphilis reinfection relies on clinical assessment and nontreponemal (reagin) serologic testing. The prozone phenomenon can lead to a falsely nonreactive rapid plasma reagin (RPR) assay result. We report a case of secondary syphilis in a HIV infected patient with a previous history of syphilis infection, where a falsely nonreactive RPR assay was associated with a delayed diagnosis of reinfection and infectious syphilis. The prozone phenomenon was detected in several of the patient's serum samples collected around this time. We subsequently undertook a prospective evaluation for the prozone phenomenon in 3222 consecutive sera, which were assayed using the RPR assay for clinical purposes over a 10-month period. The overall rate of the prozone phenomenon was 2 out of 3222 samples (0.06%; 95% confidence interval (CI): 0.02-0.22%) and the rate per reactive sample was 2 out of 397 (0.5%; 95% CI: 0.14-1.81%). Clinicians should request RPR testing at dilutions of sera when syphilis is suspected clinically and the RPR assay is nonreactive.

Evidence-based Care Management of the Late Preterm Infant

A 2-week-old male infant born at 35 weeks' gestational age (GA) to a 36-year-old multi-gravida woman presents to the pediatric office for the first primary care office visit after discharge from the hospital. The GA of 35 weeks was confirmed by the Dubowitz assessment performed 4 hours after birth. A review of the hospital discharge record revealed a positive maternal history for hepatitis B antigen (HBsAg+); non-reactive rapid plasma reagin; and an emergency Caesarean section after 6 hours of labor because of fetal heart rate decelerations.

Characteristics of primary and late latent syphilis cases which were initially non-reactive with the rapid plasma reagin as the screening test

The aim of the study was to determine the characteristics of primary and late latent syphilis cases that were non-reactive on initial screening by rapid plasma reagin (RPR) but reactive by treponemal tests. RPR test results of all primary and late latent syphilis cases in the province of Alberta, Canada during 1980-2001 were compiled. The proportion of syphilis cases that were non-reactive by RPR testing was compared with reactive cases. Multiple logistic regression was used to identify factors associated with non-reactive RPR results. Among primary syphilis cases, 224 (26%) were non-reactive on initial RPR and were compared with 639 reactive primary cases. Independent factors associated with a non-reactive result were male gender (odds ratio, [OR] = 1.99 [1.22-3.26]), Caucasian ethnicity (OR = 1.77 [1.20-2.61]) and diagnosis during the 1980-1986 syphilis outbreak period in Alberta (OR = 3.13 [1.45-6.74]). Of the late latent cases, 512 (39%) were non-reactive by RPR and 791 were reactive. A non-reactive test for late latent cases was associated with male gender (OR = 2.91 [2.15-3.94]), Canadian Aboriginal (OR = 2.91 [1.59-5.32]), Caucasian (OR = 1.87 [1.35-2.58]), black ethnicity (OR = 1.76 [1.28-2.42]) and diagnosis during the 1980-1986 Alberta syphilis outbreak (OR = 1.67 [1.29-2.16]). RPR testing alone is insufficient to diagnose primary and late latent infections under certain conditions and patient characteristics. Case detection was lower for late latent syphilis when compared with primary syphilis based on the properties of the RPR. Further studies are needed to inform the optimal use of the RPR test in laboratory testing algorithms for the diagnosis of syphilis and to determine the cost effectiveness of better screening tests for syphilis.

An Interaction Between Aspirin and Valproate: The Relevance of Plasma Protein Displacement Drug-Drug Interactions

An Interaction Between Aspirin and Valproate: The Relevance of Plasma Protein Displacement Drug-Drug Interactions

38-Year-Old Man With Priapism and a History of Paranoid Schizophrenia

38-Year-Old Man With Priapism and a History of Paranoid Schizophrenia

Cases from the Osler Medical Service at Johns Hopkins University

Presenting featuresA 26-year-old man with human immunodeficiency virus infection (CD4 count, 3/μL) was admitted for evaluation of a 2-month history of fevers and fatigue and a 1-week history of nausea and abdominal pain. He had no previous history of opportunistic infections. His physical examination was notable for a temperature of 39°C and mild hepatomegaly without significant tenderness. There were no heart murmurs, and he did not have splenomegaly, lymphadenopathy, skin rash, or neurological changes. His white blood cell count was 2.9/μL, his platelet count was 132,000/μL, and his hematocrit was 22.4%. His alkaline phosphatase level was slightly elevated at 152 U/L, but his aminotransferase and bilirubin levels were normal. Evaluation included negative hepatitis serologies, negative blood and mycobacterial cultures, negative toxoplasmosis immunoglobulin (Ig) M and IgG, a nonreactive rapid plasma reagin, a negative purified protein derivative skin test, and negative serum cryptococcal and urine histoplasmosis antigens. A computed tomographic scan of the abdomen (Figure 1) revealed hepatomegaly with a patchy enhancing pattern, periportal edema, and multiple small lesions in the spleen.Upon further questioning, the patient reported that he had traveled extensively in Italy, France, and Spain while in the military, during which had he consumed unpasteurized milk products. He was currently working as a drill sergeant at a prison. He also had a pet cat and had recent contact with a friend’s kitten.What is the diagnosis?

Posterior uveitis in patients with positive serology for syphilis.

The clinical features and ophthalmologic findings of 20 patients with syphilitic posterior uveitis seen at the Detroit Medical Center from November 1993 through February 1996 were reviewed. The mean age was 58 years; 8 patients were male and 12 were female; and all patients were black. Three of 9 patients tested were HIV positive. Patients were divided into 2 groups: those with acute (8) and those with chronic (12) syphilitic posterior uveitis. Chorioretinitis was the predominant uveitic pattern (15/20). Eighteen patients presented with blurred vision. All patients had reactive serum fluorescent treponemal antibody, absorbed (FTA-ABS); 3 had nonreactive rapid plasma reagin (RPR). Mean RPR titer in the chronic uveitis group and in the acute uveitis group was 1:27.3 and 1:209.8, respectively. Seven patients had abnormal cerebrospinal fluid (CSF); CSF VDRL was reactive in 2 patients. All patients were treated with intravenous penicillin G. Eight of 14 patients seen at follow-up showed improvement of ophthalmologic findings. Syphilis should be considered in the differential diagnosis of posterior uveitis.