Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients.

The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.

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.

The Great Imitator: Atypical Cutaneous Manifestations of Primary Syphilitic Chancre.

Objective To analyze the reasons of misdiagnosis of primary syphilitic chancre and strengthen the understanding of atypical features of this disease. Methods A case series of twenty-seven challenging primary syphilis patients who were not immediately recognized as chancre was included in our study. The clinical data including the patients' age, sex, skin lesions, HIV status, syphilis serologic test results, treatment, and follow-up results were collected. Hematoxylin-eosin and immunohistochemistry staining of skin biopsy sections were reviewed. Results Four female cases with extragenital chancres presenting as erythema or erosive skin lesions on the nipple were misdiagnosed as Paget's disease or eczema. The disorder of missed or misdiagnosed male cases manifested as syphilitic balanitis or multiple chancres on the penis root and adjacent pubis rather than coronal sulcus or frenum. Patients with nonreactive nontreponemal tests at initial presentation were also easily missed or misdiagnosed. Conclusion Primary syphilis presenting as multiple lesions rather than a single chancre, at atypical locations, or with a nonreactive nontreponemal test result, tends to be missed or misdiagnosed.

Effect of syphilis infection on HIV acquisition: a systematic review and meta-analysis.

OBJECTIVES: Co-infection of syphilis and HIV remains hard to manage and its morbidity shows a rising tendency. Syphilis has been associated with increased risk of HIV acquisition in high-risk groups, especially in men who have sex with men (MSM). This systematic review and meta-analysis estimates the effect of syphilis infection on subsequent HIV acquisition, and assesses its difference between MSM and other high-risk populations. METHODS: Five electronic databases were searched for literature published to 21 September 2019 without language restrictions. Longitudinal studies that enrolled key populations to compare the incidence of HIV with and without syphilis exposure were included. We used a random-effects model to estimate the effect of syphilis infection on HIV acquisition among high-risk populations, which include MSM, sex workers, serodiscordant couples, people who inject drugs and attendees of STD clinics. RESULTS: A total of 17 cohorts and 5 case-control studies involving 65 232 participants were included. HIV incidence showed a two-time increase after syphilis exposure, compared with a control group (relative risk (RR) 2.67 (95% CI 2.05 to 3.47); p<0.05 for prevalence; RR 3.21 (95% CI 2.26 to 4.57); p=0.419 for incidence). No significant differences were observed between MSM and other high-risk groups in syphilis infection prevalence (RR 2.60 (95% CI 1.78 to 3.80); p<0.05 vs RR, 2.98 (95% CI 2.15 to 4.14); p<0.05; ratio of relative risk 0.76 (95% CI 0.49 to 1.17)). CONCLUSIONS: Syphilis infection increases the risk of HIV acquisition in high-risk populations. There is no evidence to suggest MSM are at greater risk than other high-risk populations. Prompt diagnosis, timely treatment, preventive interventions against syphilis infection would be a worthwhile investment for reducing HIV incidence. Strategies to combat stigma and discrimination targeted at MSM are pragmatically needed.

Risk Factors for the Co-infection with HIV, Hepatitis B and C Virus in Syphilis Patients.

Syphilis, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) share transmission routes. Syphilis infection can increase the risk of acquiring and transmitting HIV in key populations. The aims of this study were to investigate the risk factors and co-infection patterns for HIV, HBV and HCV in patients with syphilis. A retrospective study was conducted of 2,412 patients with syphilis (1,922 (79.68%) with latent syphilis, 336 (13.93%) with secondary syphilis, 78 (3.23%) with primary syphil-is, 72 (2.99%) with tertiary syphilis, and 4 (0.17%) with congenital syphilis). Positive results were odserved in 8.21% (134/1,620) of patients tested for HIV, 5.75% (82/1,427) for HBV, and 1.02% (14/1,374) for HCV, respectively. Multivariate logistic regression analysis found that male sex (adjusted odds ratio (AOR) 26.03; 95% confidence interval (CI) 10.37-65.36), age <55 years, especially age group 25-34-years (AOR 8.06; 95% CI 4.16-15.61), diagnosed at the Department of Infectious Disease (AOR 19.16; 95% CI 9.74-37.69), patients from Southern China, which is a geographical area south of the Qinling-Huaihe line (AOR 1.86; 95% CI 1.06-3.26) and having a rapid plasma reagin titre ≥1:32 (AOR 1.88; 95% CI 1.12-3.15) were independently associated with HIV infection. Risk factors for HBV co-infection in patients with syphilis, including male sex (AOR 1.78; 95% CI 1.12-2.83) and living in Southern China (AOR 4.66; 95% CI, 2.36-9.17) were also identified.

Clinicopathological characteristics and prognosis of amelanotic acral melanoma: A comparative study with pigmented acral melanoma.

We compared the clinicopathological features and prognosis between 16 amelanotic acral melanomas versus 56 pigmented acral melanomas. Amelanotic acral melanomas showed a thicker Breslow thickness (all had a Breslow thickness > 1 mm), more frequent ulceration (15/16, 93.7%) and lower HMB-45 positive rate than pigmented acral melanomas. However, a significant difference in survival was not observed.

Amelanotic melanoma.

Cutaneous amelanotic melanoma (AM) is a rare amelanotic or a hypomelanotic subtype of melanoma, comprising only 0.4-27.5% of all melanoma cases. The mean age of the patients is over 50 years, and the male/female ratio varies from 0.5 to 4. Patients with red hair, type I skin, freckles, lack of nevi on the back, a sun-sensitive phenotype, or previous AM history are more likely to develop AMs. As AMs lack pigmentation, their appearances vary and can mimic many benign and malignant conditions, thus presenting a diagnostic challenge. AMs are composed of greater proportions of nodular melanoma, acral lentiginous melanoma, and desmoplastic melanoma than pigmented melanomas. They also present with thicker Breslow thickness, higher mitotic rate, more frequent ulceration, higher tumor stage, and lower survival than pigmented melanomas.

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.

[Retrospective analysis of 50 cases of senile syphilis].

OBJECTIVE: To summarize the epidemiological features of senile syphilis. METHOD: The clinical data of 50 elderly (>60 years) patients with syphilis who were treated in the Clinic of Sexually Transmitted Diseases of Peking Union Medical College Hospital were retrospectively analyzed. RESULTS: There were 31 men and 19 women (male to female ratio:1.6:1). Non-marital sexual intercourse was the main route of transmission. The disease was mainly found before surgeries. Among these 50 syphilis cases, 3 were primary syphilis, 13 were secondary syphilis, 10 were early latent syphilis, 12 were late latent syphilis, and 12 were latent syphilis of unknown duration. Co-morbidities with other sexually transmitted diseases were found in 4 patients. The rate of sero-resistance was 40%. CONCLUSIONS: The incidence of syphilis in the senile population is higher than we expected. Routine serological screening for syphilis is required in clinical settings. The underlying diseases, human hosts-related spirochetes, and laboratory testing techniques are important reasons for the false positive findings in senile patients.

Localized pagetoid reticulosis (Woringer-Kolopp disease) completely response to NB-UVB combined with IFN.

A cutaneous lymphoproliferative disorder, localized pagetoid reticulosis (LPR), is rare but distinctive in its clinical and histopathological manifestations. Without an evidence-based medicine treatment guideline because of extremely low incidence, LPR poses a therapeutic challenge. We describe a 67-year-old Chinese woman with LRP who showed complete response to narrow-band ultraviolet B combined with intramuscular interferon alpha-2b.

Early syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin.

INTRODUCTION: Benzathine penicillin G is the treatment of choice for syphilis, but doxycycline and tetracycline are effective second-line treatments. The objective of this study was to assess the serological response to treatment for early syphilis with benzathine penicillin compared with doxycycline or tetracycline. METHODOLOGY: We examined rapid plasma regain (RPR) serological test results of all first-time early syphilis patients in Peking Union Medical College Hospital between 2000 and 2011, comparing treatment with two doses of penicillin to 14-day course of oral doxycycline (100 mg twice daily) or oral tetracycline (500 mg 4 times a day). RESULTS: Of the 641 early syphilis cases with available treatment outcome data, 606 (94.5%) received penicillin and 35 (5.5%) received doxycycline/tetracycline. More than half (52.1%) had secondary syphilis, 13.4% had primary syphilis, and 34.5% had early latent syphilis. A statistically similar serological treatment success rate (p = 0.157) was observed in penicillin-treated patients 91.4% (554/606), when compared with patients treated with doxycycline/tetracycline 82.9% (29/35). CONCLUSION: Doxycycline/tetracycline had a similar serological treatment success rate when compared to penicillin in the treatment of early syphilis.

A new classification of nevus of Ota.

BACKGROUND: The nevus of Ota, is a common benign pigmentary dermatosis, mainly involve innervation area of first and second branch of trigeminal nerve. The classification of nevus of Ota was proposed by Tanino, based on 26 cases of nevus of Ota from 1937 to 1940. Studies about its classification are rarely seen in last 70 years, while it is still practical today. METHODS: Based on the clinical photographs, 1079 consecutive patients with nevus of Ota were verified and reclassified according to the innervation areas of the trigeminal nerve branches. RESULTS: In these 1079 cases, 866 patients were in line with Tanino's classification (80.26%), and 213 patients were not (19.74%). We put forward a new clinical classification (Peking Union Medical College Hospital classification, PUMCH classification) of nevus of Ota based on the innervation area of the trigeminal nerve branches, composed of 5 types and 14 subtypes. The 5 types were as follows: Type I - pigmentation maculeses involving the innervation area of one of the three trigeminal nerve branches, of which there were 424 cases (39.3%), comprising 6 subtypes; Type II - pigmentation macules involving the innervation area of two branches of the three trigeminal nerve branches, of which there were 221 cases (20.48%), comprising 4 subtypes; Type III - pigmentation macules involving the innervation area of all three trigeminal nerve branches, of which there were 361 cases (33.45%), comprising 2 subtypes; Type IV - bilateral type, in which the pigmentation macules involves the bilateral cheek, of which there were 63 cases (5.84%), comprising 2 subtypes; and Type V - complications occurred in the patient, of which there were 10 cases (0.93%). CONCLUSION: The new classification of nevus of Ota is based on the innervation area of the trigeminal nerve branches, and it covers all types of Tanino's classifications; on that basis, some new types and subtypes are brought in and cover almost every clinical condition.

Erythroderma: a clinical and prognostic study.

BACKGROUND: Erythroderma is a rare skin disorder and studies on its causes and prognosis are rare in the literature. OBJECTIVES: We reviewed the clinical, laboratory and biopsy materials of 260 patients diagnosed with erythroderma who were treated in our department over an 11-year period. Patients were followed up to better understand the evolution of erythroderma. METHODS: This study was performed at our hospital between January 2001 and 2012 and included 260 patients with erythroderma. We recorded epidemio-clinical, biological and histological data, treatments and outcomes. Clinical-histological correlation was analyzed. Overall survival and relapse-free survival for a limited number of etiologies were described using Kaplan-Meier estimates. RESULTS: The mean age at onset in this study was 52.57 ± 17.94 (SD) years (range 13-87), with a male-to-female ratio of 3:1. Acute onset was present in 15.38% of patients. Clinical findings were dominated by pruritus (87.69%), fever (40%), edema (37.69%), chills (31.15%), nail changes (29.62%), weakness (19.23%), lymphadenopathy (19.23%), weight loss (14.62%) and islands of normal skin (13.46%). Skin biopsies revealed the cause in 55.56% (65/117) of the patients. The most common causative factors were pre-existing dermatoses (70.77%), followed by idiopathic causes (14.23%), drug reactions (12.69%) and malignancies (2.31%). Among the pre-existing dermatoses, psoriasis was the most common etiology (143/260, 55%). In the drug-induced group, carbamazepine was the most frequently implicated drug in our study (33.33%). Chinese traditional herbal medicines are among the causes of drug-induced erythroderma as well. We also found that Langerhans cell histiocytosis, tongue cancer, hypereosinophilic syndrome, bullous pemphigoid and dermatomyositis could be causes of erythroderma. From our follow-up study, 39 (31.2%) of the 125 patients from whom information was available had relapsed. The patients with idiopathic erythroderma had a higher relapse rate. Of the 5 patients who died, 4 deaths were directly related to erythroderma. CONCLUSION: Most of the clinical features of erythroderma are unspecific with few cause-orienting clues. Although numerous laboratory values were abnormal, most findings were nondiagnostic and were related to the inflammatory process, except for skin biopsy. Our study had a high percentage of erythroderma secondary to pre-existing dermatoses and a low percentage of malignancy patients. Repeated evaluations, close follow-up and biopsy are recommended.

[Advances in syphilis detection].

Syphilis, a chronic bacterial infection caused by the spirochete Treponema pallidum subsp. pallidum, remains a public health concern worldwide. Syphilis control is largely dependent upon early identification and prompt treatment. The diagnosis of syphilis is mainly based on laboratory tests, especially serology and dark-field microscopy. In recent years, recombinant Treponema pallidum antigen-based rapid tests, polymerase chain reaction, and immunoglobulin M antibody detection have also shown certain sensitivities and specificities for syphilitic patients at different stages.

[Lupus erythematosus panniculitis: clinical and histopathological analysis of 22 cases].

OBJECTIVE: To explore the clinical and histopathological manifestations, therapy and prognosis of lupus erythematosus panniculitis (LEP). METHOD: We retrospectively reviewed the clinical data and histopathological features of 22 cases of LEP diagnosed at Peking Union Medical College Hospital from January 2008 to February 2010. RESULTS: The lesions appeared as atrophy, erythema, subcutaneous nodules, infiltrated erythema, and ulceration over the scalp, face, upper limbs, and buttock. Histopathological features were lobular panniculitis in the subcutaneous fat; sometimes septal panniculitis could be seen. Hydroxychloroquine sulfate and corticosteroid were effective treatment; most patients responded well to the treatment, while a few experienced recurrence when the treatment tapped or discontinued. CONCLUSIONS: LEP is a rare cutaneous variant of lupus erythematosus. The diagnosis of LEP is mainly based on clinical findings and pathological features. Hydroxychloroquine and low- and middle-dose corticosteroid are effective for the treatment of LEP.