The prevalence of disabling foot pain in patients with early rheumatoid arthritis

BackgroundFoot pain occurs up to 94% in patients with longstanding rheumatoid arthritis (RA) causing ambulation problems and disability. It was thought that these problems occur already early during the disease process but no data are available. The Manchester Foot Pain and Disability Questionnaire (MFPDQ) is a valid tool to assess disabling foot pain which is easy to complete and analyse.ObjectiveTo gather data about the prevalence of foot pain with its consequence on disability in early diagnosed patients with rheumatoid arthritis.MethodA questionnaire asking about foot pain and the MFPDQ were given to 200 patients with RA diagnosed within the last 4 years. The results of the MFPDQ were divided into categories of disability.ResultsOne-hundred and eighty-five participants completed the pain questionnaire and 126 the MFPDQ. Foot pain was reported by 74% of the participants with 64% experiencing pain in the last month and 60% at the time of completing the questionnaires. Results of the MFPDQ showed that 53% of the participants scored moderate disability and 30% severe disability caused by foot pain.ConclusionFoot pain occurs early in patients with RA resulting in moderate to severe disability in the majority of participants.     

类风湿性关节炎继发寰枢椎脱位的手术治疗

目的:总结手术治疗类风湿性关节炎(rheumatoid arthritis,RA)继发寰枢椎脱位的临床疗效。方法:2010年1月~2018年12月收治57例RA继发寰枢椎脱位的患者,男14例,女43例;年龄46~79岁(61.8±12.4岁)。类风湿性关节炎病史2.5~36.8年(17.5±3.7年),诊断RA后出现上颈椎相关症状时间为1.5~19.4年(8.9±2.4年)。患者均有不同程度的枕颈部疼痛、颈部姿势异常和活动受限。术前神经功能ASIA分级:B级3例,C级12例,D级20例,E级22例;JOA评分4~14分(8.7±1.8分),VAS 4~10分(7.4±1.5分)。寰椎前向脱位44例,其中寰齿前间距(anterior atlantodental interval,AADI)>10mm者8例;寰椎后向脱位9例;寰椎前后向脱位4例。6例合并下颈椎不稳,10例合并枕颈部其他畸形。13例枕寰关节先天性融合及骨性融合无枕寰关节活动度者采用枕颈固定融合术治疗(A组);44例有枕寰关节活动度的患者采用寰枢椎融合固定融合术治疗,其中16例寰枢椎脱位牵引不能复位的患者先行前路经下颌下寰枢椎关节松解术再一期后路行寰枢椎融合术治疗(B组),28例寰枢椎脱位牵引能复位的患者直接采用后路寰枢椎融合内固定术治疗(C组)。定期随访患者的临床症状和神经功能改善情况,影像学观察寰枢椎复位和植骨融合情况。结果:患者均顺利完成手术,A组手术时间100~130min(118.2±13.5min),术中出血量100~300ml(190.5±42.8ml);B组手术时间180~240min(221.4±20.3min),术中出血量100~260ml(157.3±36.1ml);C组手术时间100~130min(109.4±12.1min),术中出血量100~200ml(124.1±32.7ml)。术中均未发生椎动脉和脊髓损伤。所有患者随访期间复查颈椎CT及MRI显示寰枢椎序列重建满意,齿状突区域脑脊液线清晰,脊髓无压迫,术后AADI为2~3mm(2.4±0.4mm)。患者均获随访,随访时间12~84个月(34.4±10.3个月),术后12个月随访时,2例ASIA分级B级患者恢复至C级,C级患者6例恢复至D级、3例恢复至E级,9例D级患者恢复至E级,其余患者无变化;JOA评分改善至10~17分(14.6±3.5分),VAS评分降至1~5分(3.6±1.4分),与术前比较均有显著性差异(P<0.05)。1例患者植骨块发生自发性部分吸收,随访1年半时植骨块吸收停止并部分融合,未再次行植骨术;其余患者植骨均融合。随访期间均未发现螺钉松动、移位、断裂和寰枢椎再脱位、失稳现象。结论:RA累及上颈椎时会造成寰枢椎脱位导致脊髓受压,依据枕寰关节活动度情况采用寰枢椎融合术或枕颈融合术治疗可获得良好的临床效果。     

Immunogenicity of tocilizumab in patients with rheumatoid arthritis

Objective

The immunogenicity of tocilizumab (TCZ) has been poorly studied. We assessed the immunogenicity of TCZ and serum TCZ trough levels in rheumatoid arthritis (RA) patients and the preexisting TCZ-specific CD4+ T cell repertoire in healthy controls.

Relationship between the morphology of the atlanto-occipital joint and the radiographic results in patients with atlanto-axial subluxation due to rheumatoid arthritis

The upper cervical spine is a common focus of destruction from rheumatoid arthritis (RA). Atlanto-axial subluxation (AAS) presents with marked frequency among patients with instability. However, there are occasional patients who show no motion between the occipital bone and atlas on a dynamic cervical radiograph in AAS patients. This study investigated the morphology of the atlanto-occipital joint (AOJ) in AAS patients due to RA using computed tomography, and examined the relationship between its morphology and other radiographic results. Twenty-six consecutive patients with AAS due to RA treated by surgery were reviewed. The subjects included 18 females and 8 males. The average patient age was 59.3 years. The mean duration of RA was 14.3 years. In all the patients, the AOJ was morphologically evaluated using sagittal reconstruction view on computed tomography before surgery. Moreover, the ADI value was investigated at the neutral and maximal flexion position, and atlanto-axial angle (AAA) at the neutral position in preoperative lateral cervical radiographs. The morphology of the AOJ on a CT sagittal reconstruction view was classified into three types as follows: a normal type which showed a maintenance of the joint space, a narrow type which showed a disappearance of the joint space and a fused type which showed the fusion of the AOJ. The pre-operative CT sagittal reconstruction image of the AOJ demonstrated a normal type bilaterally in six cases (Group A). In 15 cases (Group B), CT image demonstrated narrowing on at least one side of the AOJ. In five cases (Group C), CT images demonstrated fusion on at least one side of the AOJ. The average ADI value at the flexion position was 10.7 mm in Group A, 11.7 mm in Group B, and 12.6 mm in Group C. There was no significant difference among those groups. The average ADI value at the neutral position before surgery was 2.8 mm in Group A, 5.9 mm in Group B, and 10.4 mm in Group C. There was no significant difference between Group A and B (P > 0.105), and Groups B and C (P > 0.032), however, there was a significant difference between Groups A and C (P < 0.004). The average AAA value was 25.3° in Group A, 19.3° in Group B and 3.4° in Group C. There was no significant difference between Groups A and B (P > 0.230), however, there was a significant difference between Groups A and C (P < 0.002), and Groups B and C (P < 0.007). This study showed that fusion or ankylosis of the AOJ induced an enlargement of the ADI and anterior inclination of the atlas in the neutral position, despite the fact that normal findings of AOJ showed a slight displacement of the atlas to axis in RA patients showing AAS involvement. This morphology may progress to SAS and VS due to AOJ after atlanto-axial arthrodesis. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.     

Intubation difficulties in patients with rheumatoid arthritis

Background : Fibreoptic intubation has been suggested to be the best method to manage a compromised airway. This retrospective study was designed to compare endotracheal intubation with the help of a rigid laryngoscope or a fibrescope in patients with rheumatoid arthritis.
Methods : Intubation difficulties with the laryngoscope and the fibrescope in patients with rheumatoid arthritis were investigated during a period of five and a half years. The anaesthesia records were used for analysis. The patients were divided into two groups (group I with 41 patients and group II with 37 patients) reflecting the change in the routine airway management in patients with rheumatoid arthritis in our hospital from the beginning of 1993. Before that time the patients were usually intubated orotracheally under general anaesthesia, but since 1993 rheumatoid patients with anticipated difficulties in endotracheal intubation have been preferably intubated fibreoptically awake under sedation and topical anaesthesia with a fibrescope.
Results : Major difficulties in endotracheal intubations were encountered in 13% of patients in group I and in 8% in group II. On two occasions in group I tracheostomy was needed. In one of these patients, emergency tracheostomy was performed. In the latter group, the main reason for prolonged fibreoptic intubations was lack of experience.
Conclusion : The introduction of fibreoptic intubation technique has had a favourable influence on the safety in the airway management of surgical patients with rheumatoid arthritis.     

Recurrent constrictive pericarditis associated with seropositive rheumatoid arthritis: A case report

IntroductionConstrictive pericarditis is an uncommon disease characterized by impaired diastolic filling of the ventricles, encased in a fibrotic pericardium resulting from an inflammatory process.Rheumatoid arthritis is a rare cause of constrictive pericarditis, usually due to a concomitant acute or chronic serositis.Presentation of caseThis paper presents a unique case of recurrent constrictive pericarditis associated with seropositive rheumatoid arthritis, requiring pericardiectomy and complicated three years later by recurrent fibrosis, demanding a second pericardiectomy.DiscussionDefining this entity as recurrent constrictive “pericarditis” might be a mistake, given that a total pericardiectomy was performed in first instance.No risk factors for recurrent fibrosis have been identified in the current medical literature, apart from partial pericardiectomy. We cannot demonstrate exclusively that rheumatoid arthritis is a risk factor for recurrent pericardial/epicardial fibrosis due to the rare nature of the disease.ConclusionFurther large scale studies are necessary to identify the risk factors for recurrence.     

Repair of radiographic hip joint in juvenile rheumatoid arthritis patients treated with etanercept plus methotrexate

For patients suffering from rheumatoid arthritis (RA), structural damage, i.e. bone erosion and joint space narrowing, is a major factor leading to functional disability. Negative radiographic progression has been shown in joints, especially in RA patients treated with tumor necrosis factor alpha (TNFα) inhibitors in combination with methotrexate. Bone erosion repair in small joints have been observed but only one study selected large weight-bearing joints. We reported 2 cases of patients with severe seropositive juvenile RA who shown improvement of joint space narrowing and subchondral erosion in hip joint when treated with etanercept in combination with methotrexate for at least 1 year. Two Japanese cases were also published but with different TNF inhibitors. The mechanisms of bone erosion or joint space narrowing repair are unclear. One study investigated whether bone erosions in rheumatoid arthritis patients show evidence of repair in metacarpophalangeal joints when treated with TNF inhibitors and MTX. These results suggested that repair in RA emerged from the bone marrow and the endosteal lining rather than the periosteal compartment. No study investigated joint space narrowing repair in hip joint in rheumatoid arthritis patients. Larger studies needed to confirm joint space narrowing improvement in hip joint in patients treated with TNF inhibitors and to explain the mechanisms of repair.     

Clinical significance of tocilizumab-related neutropenia in patients with rheumatoid arthritis

ObjectiveTo determine the risks and clinical significance of tocilizumab (TCZ)-related neutropenia, in real-world settings, for patients with rheumatoid arthritis (RA).MethodsMedical records of RA patients treated with TCZ at a tertiary referral hospital in South Korea were collected. Infectious complications were defined as cases confirmed by clinical diagnosis and treated with antibiotics.ResultsA total of 277 RA patients with TCZ treatment (intravenous: 152 [54.9%], subcutaneous: 125 [45.1%]) were included in our study. During the observational period, 22 (7%) patients experienced grade 3 neutropenia. No patients discontinued TCZ due to neutropenia, while the dosage of conventional synthetic DMARD (csDMARD) was either reduced or discontinued for 8 patients. Patients, who experienced neutropenia while using csDMARD, had a higher risk for grade 3/4 neutropenia during TCZ treatment (hazard ratio [HR]: 3.120, 95% CI: 1.189–8.189, P = 0.021). Among infections, pulmonary infections were the most common (10.35 per 100 patient-years). Age over 60 years (HR: 2.133, 95% CI: 1.118–4.071, P = 0.022) and the presence of extra-articular manifestations (adjusted HR: 11.096, 95% CI: 5.353–22.999, P < 0.001), but not neutropenia (adjusted HR: 1.263, 95% CI: 0.269–5.945, P = 0.77), were risk factors for infections during TCZ treatment.ConclusionApproximately 7% of RA patients treated with TCZ developed grade 3 neutropenia. The previous history of neutropenia during csDMARD was a risk factor for TCZ-related neutropenia. Age and extra-articular manifestations, but not neutropenia, were risk factors for infection during TCZ treatment, suggesting that TCZ treatment can be maintained in the presence of neutropenia unless infection occurs.     

女性类风湿关节炎患者骨密度的研究

目的探讨女性类风湿关节炎(RA)患者骨密度(BMD)的变化和骨质疏松(OP)的发生情况及其与临床指标的相关性.方法采用双能X线骨密度仪,测量了45例女性RA患者和45例女性正常人的前臂、腰椎2～4以及股骨颈、Ward区和大转子的骨矿含量,并同时测定握力、关节功能、X线分期、关节压痛数和肿胀数、日常生活能力评估(以健康评估表HAQ积分表示)和血沉、血清类风湿因子、C反应蛋白、钙、磷、碱性磷酸酶等指标.结果女性RA患者中除股骨Ward区骨量丢失较对照组差异有显著性(P＜0.05)外,其余各测定部位的BMD与对照组间差异无显著性(P＞0.05).45例女性RA患者中发生骨质疏松较非骨质疏松组年龄更大(P＜0.005),关节功能更差(P＜0.01),HAQ积分更高(P＜0.05),握力更低(P＜0.05),CRP更高(P＜0.05).女性RA患者中服用糖皮质激素组与未服用糖皮质激素组间BMD及OP发生情况的差异无显著性(P＞0.05).绝经后女性RA患者的骨量丢失较绝经前明显(P＜0.05);除桡骨远端外,绝经后患者各测定部位BMD均低于绝经前患者(P＜0.05).Logistic Regression分析显示年龄:OR=1.085[(1.019-1.156),P=0.011]和关节功能:OR=4.828[(1.368-17.039),P=0.014]为RA患者骨质疏松发生的相关因素.结论女性RA患者的总体骨量变化与正常人相近,但股骨Ward区的骨量丢失明显高于正常人.其BMD的降低和OP的发生与年龄、绝经和关节炎的严重程度有关.     

骨质疏松与类风湿关节炎

类风湿关节炎和骨质疏松在我国都属于常见病和多发病,而二者之间又有着非常重要的联系。但是目前临床上还没有一个广泛应用的药物可以同时对两者都产生很好的治疗效果。为了进一步了解骨质疏松和类风湿关节炎的关系,将来能够找到更好的治疗药物,笔者从流行病学、发病机制以及治疗方法等方面分别进行了论述。     

Efficacy of baricitinib on periodontal inflammation in patients with rheumatoid arthritis

ObjectiveDespite a widely recognized bidirectional pathobiologic relationship between rheumatoid arthritis (RA) and periodontal disease, the impact of innovative anti-rheumatic drugs in modulating not only inflammatory and immune articular damage, but also periodontal microenvironment remains debatable. We aimed to evaluate the periodontal status in RA with and without baricitinib, a Janus kinase (JAK) inhibitor, and to better describe association between these entities.MethodsWe performed a prospective longitudinal 24-weeks study in 21 active RA initiating baricitinib. Standard assessments included a dual rheumatologic (RA activity, disability, serological, inflammatory profile) and dental evaluation comprising plaque index, gingival index, bleeding on probing, probing depth, clinical attachment level.ResultsMore than half of RA presented at baseline with chronic periodontitis, as suggested by high prevalence of sites with dental plaque, abnormal bleeding on probing, probing depth and clinical attachment level. Aggressive periodontal disease was reported particularly in disease subsets with excessive inflammatory (serum C reactive protein level) and serologic biomarkers (anti-citrullinated peptide antibodies). Furthermore, significant correlations between dental pathology, disease activity and ACPA levels were also reported (P < 0.05). Consistent improvement was noticed in both rheumatoid arthritis characteristics and periodontal status after 24 weeks of baricitinib (P < 0.05).ConclusionRA, particularly severe active ACPA-positive disease, is basically associated with altered periodontal health. JAK blockade through oral baricitinib may be efficient in patients with active RA and potentially able to modulate the inflammatory process in the periodontal tissue.     

类风湿性关节炎全膝关节置换的临床疗效观察

目的:观察人工全膝关节置换术治疗严重类风湿性关节炎的临床疗效.方法:我院2003年3月-2005年12月对11例严重类风湿关节炎患者行人工全膝关节置换术,平均随访13个月,按美国特种外科医院膝关节评分系统(HSS)进行疗效评定.结果:所有患者没有一例行翻修手术,X线显示所有置换假体植入位置满意,没有假体松动、移位现象出现.11个膝关节的术后情况比较满意.HSS评分平均指数从术前的41分提高到术后的90分.结论:人工全膝关节置换术可作为类风湿性关节炎患者保存关节功能,改善疼痛的一种有价值的治疗方法.     

Serum retinol-binding protein 4 is associated with insulin resistance in patients with early and untreated rheumatoid arthritis

ObjectiveRetinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA.MethodsIn this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40.ResultsIn those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36–52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05–1.11, P < 0.001) and 5% (1.05; 1.02–1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02).ConclusionElevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients     

Lumbar fusion outcomes in patients with rheumatoid arthritis

Although outcomes after cervical fusion in rheumatoid arthritis (RA) patients are widely published, outcomes of lumbar fusion in RA patients has not been reported. Ninteen patients with RA, identified using ICD-9 and CPT codes, who underwent instrumented posterolateral lumbar fusion were matched for age, gender, smoking status, date, and level of surgery to a contemporaneous non-RA group. Medical records and radiographs were reviewed by the primary author who had no role in the treatment of these patients. The average age was 64 years in the RA group and 65 years in the non-RA group. The male to female ratio was 2:17 and 1:18, respectively. There were three smokers and two diabetics in each group. An average of 1.5 levels was fused in each group. Average follow-up was 24 and 27 months, respectively. In the RA group, 15 patients were taking DMARDs with 7 of those also taking oral steroids; 4 patients were taking NSAIDs only. There were seven complications (37%) in the RA group versus four (21%) in the non-RA group; wound infections in three patients (16%) in the RA group versus one (5%) in the non-RA group; and non-union in two patients (11%) in the RA group versus three (16%) in the non-RA group. Clinical outcomes were similar between the two groups with 74% of patients achieving good to excellent results in the RA group compared to 63% in the non-RA group (p = 0.692). Surgeons and their RA patients who undergo an instrumented lumbar fusion can expect a slightly higher complication rate than patients without RA which may be related to osteopenia and immunosuppression.     

类风湿关节炎指骨关节超声改变与骨质疏松的相关性

目的 探讨类风湿性关节炎（RA）指骨关节病变超声改变与骨量变化的相关性。方法应用高频超声 对100例RA患者的手指关节进行扫查, 观察其滑膜厚度、关节腔、骨面、关节周围软组织及血流供应情况 ,并采用双能X线吸收法测定腰椎和股骨颈的骨密度。结果 高频超声可清晰显示手部指骨关节腔积液、关 节滑膜增生、关节侵蚀及骨质疏松情况,伴随着骨质疏松危险因素的RA患者,骨密度与RA的性别、年龄、 病程呈负相关,年龄越大、病程越长, 其骨密度越低(P＜0.05)。RA女性患者发生骨质疏松症明显高于男 性。结论 骨量变化及超声表现与患者性别、年龄、病程具有明显相关性。骨密度检测结合超声检查更能 够实时的反映RA的骨量变化。     

10年前后RA患者骨质疏松发生情况的横断面对比研究

目的横断面对比10年前后类风湿关节炎(RA)患者骨密度(BMD)的变化和骨质疏松(OP)的发生情况,分析其发生的原因。方法采用DEXA法测定2011年确诊的120例RA患者和120例正常人股骨和腰椎部位BMD,详细记录RA患者各临床及实验室资料。同时与2001年53例RA患者的BMD等资料进行横断面对比。结果①正常人、2001年RA及2011年RA患者3组间OP发生率有明显差别(15.0%、22.6%、34.2%;x2=17.218,P=0.002)。②2001年53例RA患者中,非OP患者的年龄(43.73±15.06 vs 59.25±14.75,t=3.154,P=0.003)、CRP(35.35±31.91 vs 58.74±31.81,t=2.235,P=0.030)明显低于OP组。③2011年120例RA患者中,非OP患者的年龄(48.94±11.98 vs 56.66±14.26,t=3.135,P=0.002)、HAQ(1.39±0.67 vs 1.66±0.73,t=2.067,P=0.041)明显低于OP组。④2001年发生OP与非OP的RA患者中,服用糖皮质激素的患者比例无差别(P>0.05)。2011年发生OP的RA患者中服用糖皮质激素的患者比例为73.2%(30/41),明显高于非OP患者中的53.2%(42/79)(x2=4.501,P=0.034)。⑤与2001年RA相比,2011年RA患者的DAS28更低(6.77±1.38 vs 5.97±1.30,t=3.613,P<0.0001)、关节功能更好(1:18:22:12 vs 9:57:50:3,x2=20.690,P<0.0001),但关节X线分期更差(7:26:12:8 vs 13:27:53:23,x2=13.302,P=0.004)。⑥Logistic Regression分析发现:年龄(OR=1.093,P=0.010,95%CI:1.022～1.169)和CRP(OR=1.025,P=0.037,95%CI:1.002～1.48)为2001年RA患者发生OP的危险因素;年龄(OR=1.047,P=0.012,95%CI:1.010～1.085)和HAQ评分(OR=2.040,P=0.046,95%CI:1.013～4.111)为2011年RA患者发生OP的危险因素。结论 10年前后的横断面对比研究提示,RA患者OP发生率明显高于正常人,且呈上升趋势;高龄和RA疾病活动性是两个不同年度的横断面资料中RA患者发生OP的相同的危险因素。RA患者中糖皮质激素的使用比例的增高,可能是其关节炎症表现好转,但关节X线分期更差及OP发生率更高的原因之一。     

Clinical course of bucillamine-induced nephropathy in patients with rheumatoid arthritis

Background Bucillamine, a disease-modifying antirheumatic drug widely prescribed in Japan, is reported to be a cause of proteinuria. However, to date, the clinical course of the nephropathy associated with the use of bucillamine has not been described in detail.Methods We analyzed renal biopsy findings from 10 patients with rheumatoid arthritis and concomitant bucillamine-induced nephropathy. Each patient was followed up until proteinuria had resolved.Results Proteinuria appeared 2–11 months after the initiation of the treatment with bucillamine. Nine patients, who stopped bucillamine treatment immediately (within 3 months) after the onset of proteinuria, were diagnosed as having stage I membranous nephropathy. Only one patient, who used bucillamine for 9.5 months after the onset of proteinuria, was diagnosed as having stage II membranous nephropathy. In all patients with stage I membranous nephropathy, the proteinuria disappeared within 7 months after they stopped bucillamine treatment. On the other hand, in the patient with stage II membranous nephropathy, the proteinuria persisted for 14 months after the use of bucillamine was stopped. In all the patients, the proteinuria resolved completely without deterioration of renal function. None of the patients has experienced recurrence of proteinuria.Conclusions In patients with proteinuria induced by treatment with bucillamine, membranous nephropathy is the most common disorder. Immediate withdrawal of bucillamine results in prompt and complete resolution of proteinuria without deterioration of renal function.     

Epstein-Barr virus and rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, with a 0.5% worldwide prevalence. The cause of RA remains unknown, however both genetic and environmental factors may contribute to its development. Among these is the Epstein-Barr virus (EBV). Here, we discuss several aspects of the close relationship between EBV and RA. Patients with RA have impaired control of EBV infection. Indeed, they have high titres of antibodies against EBV antigens. Their peripheral blood T lymphocytes are less efficient at controlling the outgrowth of EBV-infected B cells. RA patients have more EBV-infected B cells than normal controls, leading to a 10-fold systemic EBV overload. Post-transplant lymphoproliferative disorder (PTLPD) is a polyclonal EBV-positive B lymphocyte proliferation, which can evolve into an EBV-positive B cell lymphoma. RA patients also have an increased risk of developing EBV-associated lymphoproliferative disorder (LPD). Hence the need to monitor EBV load when treating RA patients with immunosuppressors. EBV, a widespread virus, highly recognized by antibodies but never eliminated, is an ideal candidate to trigger chronic immune complex disease. Anti-EBV antibody responses should be considered as one of the chronic autoantibody responses linked to the development of RA, in the same way as anti-citrullinated protein antibodies.