Resolution of syphilis-related rapidly progressive glomerulonephritis with penicillin therapy: Case report
.

Renal manifestations of syphilis are variable, with membranous nephropathy being the most commonly described lesion. Rapidly progressive glomerulonephritis (RPGN) is rare and there is only one case report in the literature describing syphilis-associated crescentic glomerulonephritis. We report a rare case of RPGN secondary to latent syphilis, which resolved with penicillin treatment in the absence of immunosuppressive therapy. A 28-year-old Black male with a history of HIV was evaluated for severe acute kidney injury, nephrotic-range proteinuria, and active urine sediment. Serologies for glomerulonephritis were negative. Rapid plasma reagin and treponema pallidum particle agglutination assay were reactive, confirming syphilis diagnosis. Kidney biopsy revealed focal and segmental necrotizing and crescentic lesion. Patient received weekly benzathine penicillin (PCN) for 3 weeks, and renal function improved to baseline. This dramatic improvement happened with PCN alone, a finding which has not been previously reported. We recommend that syphilis be considered in the differential diagnosis of all patients with proteinuria or suspected glomerulonephritis.

The Jarisch-Herxheimer reaction in syphilis: could molecular typing help to understand it better?

OBJECTIVES: The Jarisch-Herxheimer reaction (JHR) is a febrile inflammatory reaction that may occur in patients after treatment of syphilis. The overall rate is estimated to be 10-25% with broad variations over time. It appears to be related to factors like stage of the disease or reagin titres. In this study, we aimed to describe the incidence of and risk factors including strain typing for JHR among patients with syphilis. METHODS: From January through October 2015, 224 consecutive patients (82 of them with HIV) who were diagnosed with early syphilis were enrolled in this prospective observational study in a referral STI clinic in Barcelona. An appointment was offered to them after 10-14 days of treatment to inquire about the reaction with the use of a standardized form. Treponema pallidum molecular typing was made to detect a possible strain related to reaction. RESULTS: Overall, 28% of patients developed JHR. This varied from 56% in secondary, 37% in primary to 7% in early latent syphilis. The most frequent types of reaction were fever (57.5%) and worsening of the lesions (31%). The median time to development of JHR was 6 h [IQR 4-10 h] and lasted a median of 9 h [IQR 4-24 h]. The JHR was less probable in early latent compared to primary/secondary syphilis (P = 0.04) and in patients treated with doxycycline compared to those treated with penicillin (P = 0.01). No differences were seen regarding reagin titres or HIV status, and no association with a specific strain was found. CONCLUSIONS: In this study, JHR occurred in a similar frequency as in other contemporary studies. Symptomatic syphilis and treatment with penicillin were associated with an increased risk of JHR, whereas the previous episode of syphilis was associated with a low risk of it. We could not find associations with specific strains of T. pallidum.

Molecular Subtyping and Surveillance of Resistance Genes In Treponema pallidum DNA From Patients With Secondary and Latent Syphilis in Hunan, China.

BACKGROUND: Over the past decade, the incidence of syphilis and widespread macrolide resistance in its etiological agent, Treponema pallidum subsp. pallidum, have become a major health concern across countries, including China. Regional trends in subtypes and antibiotic resistance can be monitored effectively by molecular surveillance programs. In this study, whole blood samples were used to assess circulating T. pallidum strains collected from various regions of Hunan, China, between 2013 and 2015. METHODS: Traditional polymerase chain reaction, targeting polA, tpp47, bmp, and tp0319 genes, was used as preliminary screening assay. About 455 polymerase chain reaction-positive specimens were obtained from 2253 whole blood samples of patients with secondary or latent syphilis. Molecular subtyping was performed using a Centers for Disease Control and Prevention-based typing method combined with an analysis of the variable region of tp0548 gene. Resistance to macrolides was analyzed by examining point mutations in 23S rRNA, and the presence of the G1058C point mutation within 16S rRNA associated with decreased susceptibility to doxycycline was assessed. RESULTS: Circulating T. pallidum strains were resolved into 32 subtypes, among which subtype 14d/f was predominant. A2059G mutation in 23S rRNA, and the G1058C mutation in 16S rRNA was absent, but the prevalence of A2058G mutation in 23S rRNA was 97.5%. CONCLUSIONS: We found that it is possible to use whole blood to evaluate molecular subtypes and monitor antibiotic resistance in circulating T. pallidum strains, especially when chancres are absent. High frequency of macrolide-resistant T. pallidum indicates that macrolide antibiotics, such as azithromycin, should be avoided as a treatment option for syphilis in Hunan, China.

The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis.

PURPOSE: This study was designed to investigate whether the antiinflammatory and antiproliferative activity of oral and intravitreal methotrexate (MTX) suppresses intraocular inflammation in patients with presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis. METHODS: Interventional prospective study including three cases with presumed latent syphilitic uveitis treated with intravenous penicillin and oral MTX, and two cases with presumed tuberculosis-related uveitis treated with standard antituberculosis therapy and intravitreal MTX injections. Treatment efficacy of all cases was assessed by best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography. RESULTS: Four eyes of 3 patients with presumed latent syphilitic uveitis had improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema in 6 months with oral MTX therapy. No recurrence of intraocular inflammation was observed in 6 months to 18 months of follow-up period after cessation of MTX. Two eyes of two patients with presumed tuberculosis-related uveitis showed improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema after intravitreal injections of MTX. No recurrence of intraocular inflammation was observed in 6 months to 8 months of follow-up period after cessation of antituberculous therapy. CONCLUSION: For the first time in the treatment of presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis, we believe that MTX might have an adjunctive role to suppress intraocular inflammation, reduce uveitic macular edema, and prevent the recurrences of the diseases.

The treatment outcome and predictors of serological response in syphilis in a sexually transmitted infections center, China.

Serology is the mainstay for syphilis treatment monitoring. Baseline rapid plasma reagin (RPR) titre, HIV status, and syphilis stage have been found to be associated with the time to serological response among syphilis patients. This study mainly aims to evaluate the time to serological response, and to identify factors affecting the serological outcome. Medical records of syphilis cases diagnosed in Peking Union Medical College Hospital (PUMCH) between 2008 and 2018 were retrospectively reviewed. Kaplan-Meier analysis was performed to evaluate the median time to serologic response and cumulative probability of serologic response over time according to different variables. Cox regression model was conducted to find factors associated with serological response. There were 984 patients diagnosed with primary, secondary, or latent syphilis cases and receiving injections of benzathine penicillin G (BPG) as initial treatment at the Peking Union Medical College Hospital (PUMCH) between 2008 and 2018. Finally, data on 571 patients, including 49 (8.6%) primary syphilis, 261 (45.7%) secondary syphilis, and 261 (45.7%) latent syphilis, were used for analysis. It took longer time to achieve serological response for subjects aged ≥45 years than younger individuals (89 days versus 58 days; p=0.008). Males achieved serological response more quickly than females (71 days versus 83 days; p = 0.011). There was a significant difference in the time to serological response according to different syphilis stages (p < 0.001), with 55 days (95% CI, 43-67 days) for primary, 57 days (95% CI, 51-63 days) for secondary, and 117 days for latent syphilis. In addition, patients with lower baseline RPR titre had longer period to achieve serological response (252 days [95% CI, 129-375 days] for RPR titre ≤1:8, 78 days [95% CI, 63-93 days] for RPR titres from 1:16 to 1:32, and 53 days [95% CI, 49-57 days] for RPR titres ≥1:64, respectively; p<0.001). However, no significant difference in time to serological response to treatment was found according to HIV coinfection status. The result of multivariate Cox regression analysis showed that being older than 45 years with latent syphilis, HIV coinfection, or with baseline RPR titre ≤1:8 was associated with slow response. Among patients followed for at least 1 year or seroreverted, 128 (36.9%) had seroreverted within a year, and 219 (63.1%) still had a positive RPR after 1 year. For multiple logistical regression, being female and HIV coinfection were significantly associated with the failure of seroreversion (OR, 0.42 [95% CI, 0.26-0.68]; p <0.001). This study revealed that younger age, higher initial RPR titre, early syphilis stage, and HIV-negative status were associated with faster serological cure. Female sex, individuals with HIV coinfection, and latent syphilis were significantly associated with the failure of seroreversion.

Membranous Glomerulonephritis as an Uncommon Presentation of Secondary Syphilis: A Reminder on Therapeutic Decision-Making in Clinical Practice.

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

Pre-treatment syphilis titers: distribution and evaluation of their use to distinguish early from late latent syphilis and to prioritize contact investigations.

BACKGROUND: Treatment, contact investigation, and reporting decisions for syphilis cases are based on the stage of disease. Because of limitations of current staging protocols, the rapid plasma reagin (RPR) titer has been proposed as an alternative priority marker for contact investigation. METHODS: We describe the RPR titers and stages for 10,021 syphilis cases reported between 1997 and 1999 in Columbia, South Carolina; Houston, Texas; and Jackson, Mississippi. We constructed receiver operating characteristic curves (ROC curves) to compare titer and stage. We calculated the number of infected contacts to evaluate the use of titer to prioritize contact investigation. RESULTS: RPR titers differed by stage, with 67% of primary, 95% of secondary, 78% of early latent, and 41% of late latent and unknown duration having titers >1:8; however, there was considerable overlap in titer distributions. The ROC curve based on titer values demonstrated good agreement between titer and latent stage. Prioritization by titer (> or =1:8) of latent cases would result in a similar number of cases interviewed and contacts located as stage prioritization, although different cases are prioritized. CONCLUSION: Titer distributions meaningfully but imperfectly distinguish populations with different stages. Recent analyses and anecdotal reports indicate the difficulty and inconsistency of staging latent syphilis. Over time, titer could provide a more objective and reliable historical record of syphilis trends. Titer may be a useful alternative or adjunct to stage in prioritizing latent syphilis cases for investigation.

B safe, B sorted: results of a hepatitis B vaccination outreach programme.

The risk of hepatitis B among men having sex with men (MSM) is high, with core antibody rates ranging from 5% to 81%. We describe an outreach, hepatitis B vaccination programme aiming to raise awareness of hepatitis B and increase vaccination uptake. The 13-week programme used an ultra rapid vaccination schedule. Follow-up was defined as complete if the client was core antibody positive, had adequate surface antibody levels following prior vaccination or received three vaccine doses. One hundred and fifty clients were screened for hepatitis B and syphilis. Three cases of untreated syphilis (early latent) and one case of e-antigen-positive hepatitis B were detected. With the aid of text-message reminders, a vaccination completion rate of 76.6% was achieved, with 82.5% completing follow-up. In conclusion, this programme succeeded in reaching MSM not routinely accessing services. Text messaging was an acceptable and effective method of follow-up, resulting in high vaccination completion rates.

Test Not Talk screening for asymptomatic men.

This audit reviews the first year's experience within a rapid comprehensive sexually transmitted infection (STI) and HIV screening for asymptomatic men in a small-integrated sexual health clinic in outer London. Men requesting STI/HIV screening only were offered symptom self-assessment, blood tests for syphilis and HIV, and first void urine tests for chlamydia and gonorrhoea. Of 468 available appointments, 337 were made (72%) and 303 were kept (80%). Of the 303 attendances, 264 (87%) were first-ever attendances. Of the 303 men seen, 295 (97.4%) underwent chlamydia and gonorrhoea testing, while 246 (80.9%) were tested for syphilis and HIV. No new HIV diagnoses were made. One patient was diagnosed with late latent syphilis and one had asymptomatic gonorrhoea, while 20 (6.6%) diagnoses of chlamydia were made. We believe that Test Not Talk clinics offer a good approach to rapid screening of asymptomatic men and to meet their sexual health needs.

The outcome of treatment of early latent syphilis and syphilis with undetermined duration in HIV-infected and HIV-uninfected patients.

The aim of the study was to compare the outcome of syphilis treatment in HIV-infected and -uninfected patients. An observational study on patients diagnosed with early syphilis in three genitourinary clinics in the UK between January 2003 and June 2005 was conducted. Failure of the initial Venereal Disease Research Laboratory (test) (VDRL) titre to decrease four-fold within 12 months in the absence of history of re-infection was considered as treatment failure. During the study period, 190 HIV-uninfected and 129 HIV-infected patients were diagnosed, and 161 (84%) HIV-uninfected and 100 (77.5%) HIV-positive patients with diagnosis of syphilis who had 24 months follow-up syphilis serology results were included in the study (P = 0.10). There were 381 and 508 follow-up episodes for HIV-infected and -uninfected patients, respectively, within 24 months. One HIV-infected patient was diagnosed with neuro-syphilis. After 12 months, 102 (63%) HIV-uninfected and 76 (70%) HIV-infected patients were treated (P = 0.04). On Cox proportional hazard model, successful treatment after 12 months was associated with having VDRL titre more than 1:6 (hazard ratio [HR] 1.011; 95% confidence interval [CI], 1.004-1.019; P = 0.002). Those with negative immunoglobulin M enzyme immunoassay were less likely to have been successfully treated after 12 months (HR 0.676 [95% CI 0.518-0.883]; P = 0.004). HIV sero-status, age, sex group and treatment regimen were not associated with success of treatment. In conclusion, HIV sero-status did not play a role in the outcome of syphilis treatment. Treatment failure in a proportion of HIV-infected patients is due to a slower decline in VDRL titre rather than lack of response to treatment.

No improvement in serological response among serofast latent patients retreated with benzathine penicillin.

Persistent non-treponemal titres after treatment are common among patients with latent syphilis. Although retreatment is often done in clinical practice, optimal management remains uncertain due to the paucity of data regarding serological response to retreatment and long-term outcomes. We compared the serological responses of serofast latent syphilis patients retreated with 7.2 million units of benzathine penicillin with the responses of patients who did not receive retreatment (control group). We retrospectively analysed the serological response to therapy following retreatment of 35 serofast latent syphilis patients at 12 months with benzathine penicillin 2.4 million units weekly for 3 weeks. In all, 74.3% (26/35) of the cases with latent syphilis who failed to achieve serological cure at 12 months after initial therapy achieved serological cure after retreatment and after an additional 12 months of follow-up. However, statistically similar serological cure rate was observed in 80.0% (28/35) of the control group (p > .05). Our findings illustrate no improvement in serological response among serofast latent patients retreated with three doses of benzathine penicillin.

Syphilis: uncommon presentations in adults.

The clinical manifestations of syphilis are variable in appearance and have been described for centuries. The disease has been arbitrarily divided mainly into three stages. Uncommon presentations of syphilis in adults include (a) primary syphilis-atypical forms of chancre vary in size, shape, morphology, and color. Small ulcus durum is single or multiple, grouped, or herpetiform. Giant necrotic and phagedenic chancres are resolved with scar formation. In intratriginous areas, ulcus durum is rhagadiform, linear, "rocket type," or bilateral. (b) Secondary syphilids include macular (roseolas, leukomelanoderma), papular (small miliar or lichenoid, or with large size-lenticular or nummular), papulosquamous, syphilis cornee, psoriasiform, annular en cockade, nodular, condylomata lata, malignant syphilis, and others; there are also mucosal lesions, loss of the hairs, and alteration of the nails. (c) Tertiary syphilis occurs decades after infection in three main forms: gummatous, cardiovascular, and neurosyphilis (asymptomatic, meningeal, meningovascular, and parenchymatous-such as general paresis or tabes dorsalis). Early recognition of the clinical manifestations of syphilis is important for the start of treatment, recovery of patients, and the prevention of the spread of disease.

Lumbar puncture in asymptomatic late syphilis. An analysis of the benefits and risks.

We evaluated the treatment of asymptomatic patients with untreated syphilis of more than one year's duration (asymptomatic late syphilis) using a decision-analysis model. Two strategies were compared: treatment with 7.2 million units of penicillin G benzathine, or performing a lumbar puncture to test for asymptomatic neurosyphilis followed by penicillin and management based on cerebrospinal fluid analysis. Estimates of probabilities of disease prevalence, test sensitivity, and cure and complication rates were derived from published studies. Both strategies resulted in a cure rate of at least 99.7% using the best estimates. Although the strategy using lumbar puncture results in a 0.2% higher cure rate, its rate of complications (0.3%) exceeds its marginal benefit. We conclude that a lumbar puncture offers little additional benefit and may increase morbidity in patients with asymptomatic late syphilis.

Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). DESIGN: Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. PATIENTS: Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. RESULTS: Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. CONCLUSIONS: Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost-effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients.

Auditory function in early syphilis. A follow up study.

Twenty-six patients with secondary or early latent syphilis were examined by auditory brainstem response (ABR) audiometry and by pure tone audiometry before and after treatment. Normalization was registered in four of seven patients with pathological ABR before treatment. while in three patients the ABR abnormalities remained after treatment. Thirteen patients exhibited a sensorineural hearing-loss before treatment. In two patients this hearing-loss improved after treatment and a syphilitic etiology seems plausible. The reversible lesions in the auditory system may be related to asymptomatic syphilitic meningitis. Permanent ABR abnormalities might reflect syphilitic vascular involvement in the brainstem.

[Paroxysmal cold hemoglobinuria: only in the textbooks?]. / Hemoglobinuria paroxística a frigore: sólo en los libros de texto?

Although it was common in the preantibiotic era, paroxysmal cold hemoglobinuria (PCH) is now an exceptional condition. A 34-year-old female with anemia and episodic hemoglobinuria provoked by cold is reported. The laboratory studies suggested intravascular hemolytic anemia, and the Donath-Landsteiner test showed a biphasic IgG hemolysin with anti-P specificity. This finding and the evidence of latent syphilis were diagnostic of PCH. Penicillin therapy suppressed the hemolytic episodes, although the Donath-Landsteiner test is still positive. It is concluded that PCH is still an exisiting disease which should be considered in the differential diagnosis of episodic hemoglobinuria.