梅毒吉海反应研究现状

梅毒患者在首次给予抗菌素治疗数小时后可发生发热、头痛、原发皮疹加重和一系列生理学变化为特征的吉海反应。本文对其临床表现、发生机制及预防和治疗的研究现状进行综述。     

A case of Jarisch–Herxheimer reaction in candidiasis treated with systemic fluconazole

Jarisch–Herxheimer reaction (JHR) is an acute and self‐limited condition, which commonly occurs after treatment for spirochetal infections. Probably, it corresponds to a transient immunological reaction to endotoxin‐like products released from the microorganism during the therapy. For this reason, JHR may be associated with many other infectious diseases besides syphilis. Here, we report a case of a patient affected by extended cutaneous candidiasis diagnosed by culture examination; a JHR occurred after an accidental overdose of oral fluconazole.     

Study of FTA-CFS test using monospecific anti-immunoglobulin conjugates IgG, IgM, and IgA

The fluorescent treponemal antibody test for cerebrospinal fluid (FTA-CSF) using monospecific conjugates anti-IgG, IgM, and IgA was used to determine the presence of anti-treponemal antibodies in the spinal fluid of 335 patients with primary, secondary, and latent syphilis and symptomatic and asymptomatic neurosyphilis and of patients with certain neurological disorders. Of these, 230 (68·65%) patients had non-reactive results to this test. Of the remaining 105 patients, 78, 63, and 10 had reactive results with anti-IgG, IgM, and IgA conjugates respectively. Of the 129 cases of known syphilis, 11 were diagnosed as primary, 32 as secondary, and 50 as latent, and 36 patients had neurosyphilis. None of the specimens from the patients with primary syphilis gave reactive results to the test. Specimens from 21 (65·62%) of the 32 patients with secondary syphilis, 30 (60%) of the 50 patients with latent syphilis, and all (97·22%), except one, of the 36 patients with neurosyphilis gave reactive results to one at least of the IgG, IgM, or IgA FTA-CSF tests. Among the specimens from patients with secondary syphilis twice as many gave reactive results with anti-IgG conjugate than with anti-IgM conjugate. However, with specimens from patients with latent syphilis and neurosyphilis this ratio was diminished to 1·5:1. The Kolmer complement-fixation test, although superior in sensitivity and specificity to the Venereal Disease Research Laboratory (VDRL) test, in patients with secondary and latent syphilis and neurosyphilis, was greatly inferior to the FTA-CSF test. Data indicate that anti-treponemal antibodies can be detected in the spinal fluid even in patients with no neurological symptoms in cases of secondary syphilis and that the FTA-CSF test can be a valuable tool in the early detection of an immunological response to treponemal infection in the spinal fluid.     

MALIGNANT SYPHILIS (LUES MALIGNA) AND CONCURRENT INFECTION WITH HIV

Background. During the past 2 1/2 years we observed six patients who had a reactive serology for syphilis, of which four developed widespread noduloulcerative and two vesiculonecrotic lesions. The purpose was to report the occurrence of lues maligna, a rare form of secondary syphilis, in five patients infected with the human immunodeficiency virus (HIV) and in one patient with risk factors for infection. Methods. Tzanck preparations, viral cultures, and skin biopsies were performed to evaluate the etiology of the lesions. Results. Syphilis serology titers ranged from 1:32 to 1:128 and in one instance was as low as 1:8. Such titers can also be found in patients with the latent form of syphilis. Therefore, confirmation of the clinical diagnosis of lues maligna was dependent on skin biopsies that were compatible with secondary syphilis and negative viral studies that excluded varicella, disseminated varicella-zoster or herpes simplex. Lues maligna takes an aggressive course in HIV-infected patients since four of the patients required hospitalization and the two patients who refused to complete treatment, subsequently developed more severe skin and constitutional symptoms. Conclusions. HIV-infected patients are at risk for developing lues maligna. Despite its malignant presentation, lues maligna lesions respond rapidly to treatment with penicillin. Secondary syphilis should be added to the list of diseases known to be more aggressive in HIV-infected patients.     

老年梅毒84例临床分析

目的：明确老年梅毒患者的临床特征。方法：回顾性分析2013年1月至2015年1月在我院初次诊治的84例老年梅毒患者的临床资料。结果：84例患者中男51例,女33例,一期梅毒5例,二期7例,三期3例,潜伏梅毒69例。36例（70.58%）男性和5例（15.15%）女性患者有婚外性行为史。84例老年梅毒患者血清TPPA及RPR检测均为阳性,完成正规驱梅治疗并随访2年的患者有67例,其中30例（44.77%）血清RPR在24个月内转阴。结论：老年梅毒中潜伏梅毒患者比例最大,70%男性患者有婚外性行为史。     

Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study

BACKGROUND: Despite reports of unusual clinical presentations and therapeutic responses among HIV-infected patients with syphilis, syphilis has not been regarded as a serious opportunistic infection that predictably progresses among most HIV-coinfected patients. GOAL: To define and describe differences in the presentation and response to treatment of early syphilis among HIV-infected and HIV-uninfected patients, to describe any differences by gender, and to determine if clinical presentation of central nervous system involvement predicted serologic failure. DESIGN: A prospective, multicenter, randomized, controlled trial of enhanced versus standard therapy to compare the benefit of enhanced therapy, the clinical importance of central nervous system involvement, and the clinical manifestations of early syphilis infection among HIV-infected and HIV-uninfected patients. RESULTS: The median number of ulcers was significantly greater among HIV-infected and HIV-uninfected patients, as was the percent of HIV-infected patients with multiple ulcers. Among patients diagnosed with secondary syphilis, a higher percentage of HIV-infected patients presented with genital ulcers [13/53 (25%)] than did HIV-uninfected patients [27/200 (14%)]. No differences between HIV-infected and HIV-uninfected patients were detected for other secondary syphilis manifestations. Although women presented more frequently with secondary syphilis than did men, no other gender differences in clinical manifestations were noted. Neurologic complaints were reported most frequently among patients with secondary syphilis [103/248 patients (42%)] compared with patients with primary syphilis [32/136 (24%)] and early latent syphilis [48/ 142, (34%)] (P < 0.05), but no differences in neurologic complaints were apparent by HIV status or CSF abnormalities. No neurologic complaints were significantly associated with serologic treatment failures at 6 months. CONCLUSIONS: Overall, HIV infection had a small effect on the clinical manifestations of primary and secondary syphilis. Compared with HIV-uninfected patients, HIV-infected patients with primary syphilis tended to present more frequently with multiple ulcers, and HIV-infected patients with secondary syphilis presented with concomitant genitals ulcers more frequently.     

Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG).

OBJECTIVE: To study syphilis in HIV infection focusing on immunocompromised patients with an atypical or aggressive clinical course of syphilis, inappropriate serological reactions or an unreliable response to therapy. STUDY DESIGN: A multicentre retrospective chart review using a standardised questionnaire for all patients with active syphilis. SETTINGS: Thirteen dermatological and medical centres throughout Germany, all members of the German AIDS Study Group (GASG). PATIENTS: Clinical data of 11,368 HIV infected patients have been analysed for cases of active syphilis requiring treatment. Asymptotic patients with reactive serological parameters indicating latent syphilis without a need for treatment were excluded. RESULTS: Active syphilis was reported in 151 of 11,368 HIV infected patients (1.33%, range per centre 0.3%-5.1%). Most of the 151 syphilis patients were male (93%) and belonged to the homosexual or bisexual exposure category for HIV infection (79%); another 6% were iv drug users. Among the 151 syphilis patients primary syphilis was diagnosed in 17.2%, maculopapular secondary syphilis in 29.1%, ulcerating secondary syphilis in 7.3%, neurosyphilis in 16.6% and latent seropositive syphilis without clinical symptoms but serological abnormalities indicating active syphilis in 25.2%. A history of prior treatments for syphilis was reported in 50%. At the time of syphilis diagnosis 26.5% of the patients were in CDC stage II, 33.8% in stage III and 24.5% in stage IV of HIV disease (CDC classification 1987). CD4 cell count was lowest in those with ulcerating secondary syphilis (mean 307, SD 140/microliters) and neurosyphilis (351, SD 235/ microliters). The highest CD4 count was found in patients with early primary and early secondary syphilis (444, SD 163/microliters and 470, SD 355/microliters). Inappropriate serological response to syphilis infection was found in 81 of 151 patients (54%). Remarkable findings were false negative VDRL titres (11 patients with non primary syphilis), false negative TPHA (1) or 19S-IgM-FTA-ABS-tests (16), and strongly reactive VDRL (> or = 512, 8) or TPHA titres (> or = 10 240, 47). Treatment failures were reported in at least 6 of 151 cases (4%). CONCLUSIONS: Atypical clinical and serological courses of syphilis were observed in HIV infected patients. Ulcerating secondary syphilis with general symptoms ("malignant syphilis") was 60 times more frequent than in historic syphilis series. Neurosyphilis was found in one sixth of those with active syphilis. Therefore lumbar puncture should be considered a routine in coinfections with HIV and syphilis. Treatment efficacy should be monitored carefully.     

123例早期梅毒临床分析

目的观察早期梅毒的临床特点及疗效,为提高早期诊治水平提供科学依据。方法对123例早期梅毒患者的临床资料进行综合分析。结果本组病例中男性76例,女性47例。Ⅰ期梅毒53例,以外生殖器硬下疳为主;Ⅱ期梅毒67例,以掌跖暗红斑、扁平湿疣及玫瑰疹为主;潜伏梅毒3例,无皮疹。123例患者USR、Trust、TI'PA试验均为阳性(100%):使用苄星青霉素治疗梅毒血清试验阴转率达95.9%。结论早期梅毒临床表现多样性,易误诊。苄星青霉素是治疗早期梅毒的首选药物。     

儿童获得性梅毒14例分析

目的 分析儿童获得性梅毒的临床表现及其治疗方法。方法 回顾分析2007年7月至2010年12月诊治的14例儿童获得性梅毒患者的临床资料。结果 14例患者中10例为二期梅毒,早、晚期潜伏梅毒各2例。14例患者均有与现症梅毒患者密切接触史或被成人梅毒患者口内咀嚼食物后喂养史。所有患者血清快速血浆反应素环状卡片试验（RPR）及梅毒螺旋体血凝试验（TPHA）均阳性。其皮损主要发生于口腔黏膜,躯干少见,表现为黏膜白斑和黏膜湿丘疹、皮肤脓疱等。7例患者被误诊为其他皮肤病。结论 儿童获得性梅毒临床常被误诊或忽视。有不典型皮疹、尤其是与活动性梅毒患者有密切接触者,应考虑儿童获得梅毒可能。     

Toll样受体2 mRNA在梅毒患者外周血单一核细胞的表达

目的研究一期梅毒、二期梅毒、早期潜伏梅毒患者驱梅治疗前、后外周血单一核细胞(PBMCs)Toll样受体2(TLR2)mRNA的表达情况。方法采用实时定量PCR方法检测一期梅毒、二期梅毒、早期潜伏梅毒患者各15例驱梅治疗前和驱梅治疗结束后3个月PBMCs中TLR2mRNA的表达水平,并与20例正常人作对照。结果驱梅治疗前一期梅毒、二期梅毒及早期潜伏梅毒患者与正常对照组TLR2mRNA表达水平比较差异有统计学意义(P<0.001);一期梅毒、二期梅毒及早期潜伏梅毒组之间比较,差异无统计学意义(P>0.05);经驱梅治疗后,一期梅毒、二期梅毒及早期潜伏梅毒患者PBMCs中TLR2mRNA的表达水平显著下降,与驱梅治疗前比较,差异有统计学意义(P<0.001);与正常对照组比较,差异无统计学意义(P>0.05);TLR2mRNA的表达水平与血清RPR滴度不存在相关关系(P>0.05)。结论TLR2可能参与了免疫细胞对梅毒螺旋体的识别和信号转导,并在梅毒的发生、发展过程中可能起重要作用。     

Auditory brain-stem responses in syphilis.

Analysis of auditory brain-stem electrical responses (BSER) provides an effective means of detecting lesions in the auditory pathways. In the present study the wave patterns were analysed in 11 patients with secondary or latent syphilis with no clinical symptoms referrable to the central nervous system and in two patients with congenital syphilis and general paralysis. Decreased amplitudes and prolonged latencies occurred frequently in patients with secondary and with advanced syphilis. This technique is a notable diagnostic advance in detecting syphilitic damage of the brain stem.     

近10年梅毒血清固定患者临床分析

目的：研究梅毒血清固定现象及其相关影响因素。方法：回顾过去10年的梅毒患者资料,所有患者均采用苄星青霉素240万U（每周1次,连续3次）肌内注射治疗,统计梅毒血清固定的发生率和形成时间,用多因素逐步回归方法分析梅毒血清固定与患者年龄、性别、梅毒分期、血清快速血浆反应素（RPR）试验初始滴度等因素的关系,并作前、后5年的比较。结果：423例梅毒患者2年内RPR试验阴转率为82．5％,有74例（17．5％）出现血清固定,其中一期梅毒血清固定发生率为3．8％,二期梅毒为17．5％,潜伏梅毒为40．5％;多因素逐步回归分析结果表明,梅毒分期是与血清固定发生有显著性意义的相关因素,在过去10年中,后5年各期梅毒患者的血清固定发生率都有不同程度增加,特别是潜伏梅毒患者的血清固定发生率显著增高（P＜0．01）。结论：病期不明的潜伏梅毒增多是后5年潜伏梅毒患者血清固定发生率显著增高的主要原因,加强对潜伏梅毒的筛查和及时治疗是减少梅毒血清固定形成的关键。     

19S-IgM-梅毒螺旋体明胶凝集试验对梅毒患者的诊断和评价

目的评价19S-IgM-梅毒螺旋体明胶凝集试验(19S-IgM TPPA)法检测梅毒患者血清中特异性TP-IgM抗体的临床意义.方法采用经IgG/RF免疫吸附剂处理后的93例梅毒患者血清和3例梅毒妇女所生新生儿血清,用TPPA法检测TP-IgM抗体.结果73例未经正规驱梅治疗的梅毒患者血清中,一期梅毒的TP-IgM抗体阳性率78.26%(18/23),二期梅毒的阳性率100%(32/32),隐性梅毒的阳性率47.06%(8/17),3例梅毒妇女所生新生儿血清TP-IgM抗体1例阳性.经正规驱梅治疗RPR转阴的21例梅毒患者血清中TP-IgM抗体阳性率4.76%(1/21).结论采用19S-IgM-TPPA法检测先天梅毒和二期梅毒具有较高的价值,但不宜单独应用诊断一期和隐性梅毒,对梅毒疗效的观察有待进一步研究.     

Micro-TPHA test in the routine serodiagnosis of syphilis

Sera from untreated primary, secondary and latent syphilis and treated syphilis were tested with a new micro-Treponema pallidum haemagglutination assay (micro-TPHA, Syfhatect, Wellcome Diagnostics, U.K) compared with the standard VDRL slide test. Serum titers of 1:8 and above were considered positive on the VDRL, and those 1:20 and above were taken as positive on the micro-TPHA. All patients with secondary syphilis were positive with both tests. 65.5% of cases of primary syphilis were positive with VDRL, compared to 78.8% with micro-TPHA. For latent syphilis, 87.5% were positive with VDRL, and 100% were positive with micro-TPHA. Of 25 patients with treated syphilis and reactive VDRL sera, all were also positive with micro-TPHA. Of 76 persons with treated syphilis who were no longer reactive on VDRL, 91% had positive micro-TPHA tests. The micro-TPHA test is so sensitive that it cannot be used to evaluate response to treatment in the sense that a VDRL test will become negative.     

Primary and secondary syphilis, 20 years'' experience. 3: Diagnosis, treatment, and follow up.

The methods of diagnosis (dark ground microscopy and serology), treatment, and follow up of 946 patients with primary and 854 with secondary syphilis who presented to a London STD clinic between 1965 and 1984 were reviewed retrospectively. On dark ground microscopy spirochaetes typical of Treponema pallidum were seen in 673 (78%) of 884 patients with primary syphilitic chancres. Of the patients with primary syphilis, 137 (14.5%) had negative serology results at presentation. Eight (0.9%) of the patients with secondary syphilis had negative results at presentation, but seven of these gave positive results one month later. Procaine penicillin was the treatment used most, and erythromycin the commonest alternative. The Jarisch-Herxheimer reaction occurred more often after treatment with penicillin than with erythromycin or tetracycline (p less than 0.005). In most patients the Venereal Diseases Research Laboratory (VDRL) test showed a consistent fall in titre after treatment; a small proportion, however, continued to give positive results (some at a high titre) with no other evidence of reinfection or treatment failure.     

血清可溶性白介素2受体检测及其在梅毒中的临床意义

目的：探讨SIL－2R在梅毒血清中的临床意义。方法：采用ELISA抗体夹心法检测75例梅毒患者治疗前后SIL－2R水平、RPR滴度变化及其与各期梅毒临床之间关系。结果：所有梅素血清中SIL－2水平明显高于正常人（P＜0.001）、二期和潜伏期都高于一期（P＜0.01）,二期与潜伏期相比无明显差异（P＞0.01）。治疗后各期梅RPR滴度下降,SIL－2R水平也显著下降（P＜0.001）,二期,潜伏期梅毒血SIL－2R仍高于对照组（P＜0.05。结论：对同一病例作连续SIL－2R水平检测有助于了解疾病活动性和治疗效果。     

87例妊娠梅毒患者临床特征和妊娠结局的回顾性分析

对我院2015年1月1日至2018年12月31日诊治的87例妊娠梅毒患者的临床资料进行回顾性分析,结果示潜伏梅毒80例,一期梅毒和二期梅毒患者分别为4例和3例。潜伏梅毒患者中RPR滴度≤1:4者59例,≥1:8者21例。一期梅毒和二期梅毒患者中RPR滴度≤1:4者1例,≥1:8者6例;87例患者中,72例（82.76%）在孕期进行了抗梅毒治疗。妊娠梅毒患者的不良妊娠结局发生率为23.53%,其中先天梅毒的发生率为3.80%。RPR滴度、梅毒诊断孕周及治疗情况与不良妊娠结局的发生相关(均P＜0.05)。     

梅毒患者外周血单核细胞亚群的研究

目的 探讨未经治疗的一期、二期和隐性梅毒患者外周血单核细胞亚群的变化.方法 流式细胞仪检测58例未经治疗的梅毒患者(包括隐性梅毒36例,一期梅毒8例,二期梅毒14例)的外周血单核细胞CD14highSCD16-亚群和CD14+CD16+亚群.结果 与正常人对照组相比.梅毒患者CD14+CD16+单核细胞所占比例明显升高,所占总单核细胞比例为12.0%±5.0%,而CD14highCD16-Mo亚群明显降低.为88.0%±5.1%,二者差异均有统计学意义.隐性梅毒、一期梅毒、二期梅毒之间CD14highCD16-亚群和CD14+CD16+亚群差异无统计学意义.结论 未经治疗的梅毒患者外周血单核细胞亚群的变化可能与梅毒螺旋体的持续感染有关,与各临床分期相关性不明显.     

452例梅毒患者的临床分析

目的:了解梅毒的发病及临床特点,以探求及早控制本病的措施。方法:对本院1997年1月-2002 年12月间的452例梅毒患者的临床资料进行整理和临床分析。结果:452例梅毒中一期梅毒174例,占38.5%, 二期梅毒198例,占43.8%,一、二期梅毒共存者6例,占1.3%。潜伏期(隐性)梅毒74例,占16.4%。结论:正规足量的驱梅药物治疗,一期梅毒治愈恢复明显快于二期梅毒。     

Short-time, high-dosage penicillin infusion therapy of syphilis: an alternative to recommended regimens?

The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intravenously every 6 h up to a total dose of 90 MIU within 48 h. No adverse reactions were registered but 9 patients showed a Herxheimer reaction. Four patients were lost to follow-up and the remaining 16 were serologically and clinically followed for mean 18.5 months (range 3-36). During this period, the Wassermann reaction turned negative for 12 patients and was reduced more than fourfold for the rest, with one exception. None of the patients showed clinical signs of active syphilis following treatment. The cerebrospinal fluid penicillin concentration was measured in one patient during treatment and found to be much higher than the minimally treponemacidal concentration generally recommended. The treatment modality is reviewed and discussed and it may provide an alternative to conventional treatment regimens of early syphilis.