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RA纤维母细胞样滑膜细胞浸润的机制&&杨麟&
摘要：目的：本研究的目的是探讨在RA患者人群中，细胞因子是否能在纤维母细胞样滑膜细胞内调节双调蛋白和TNF转化酶的表达，并且研究双调蛋白在RA发病机制中所发挥的作用。&
方法：实时定量PCR和westernblot检测了细胞因子对双调蛋白和TNF转化酶的表达的影响。运用IL-1信号通路抑制实验来观察细胞内IL-1的表达是否影响双调蛋白和TNF转化酶的产生。RNA转染用于证实TNF转化酶是否影响IL-1诱导的双调蛋白的分泌。ELISA和western检测了MMP-1和钙粘素11的表达。TRANSWELL实验检测双调蛋白对纤维母细胞样滑膜细胞浸润能力。&
结果：实验结果证明只有白介素1能够增加双调蛋白RNA的表达并呈现出剂量与时间的依赖性。白介素1诱导的双调蛋白的表达主要是通过MAPK, NF-kB, JNK and ERK1/2信号通路。白介素1诱导的TNF转化酶的表达主要是通过PI3K, p38MAPK and NF-kB信号通路。TNF转化酶调节了双调蛋白的表达并上调了表皮生长因子的表达。双调蛋白促进了MMP-1和钙粘素11的表达并且增强了纤维母细胞样滑膜细胞的浸润能力。&结论：白介素1能促进RA患者体内TNF转化酶依赖的双调蛋白的释放，并且通过基质降解从而导致了纤维母细胞样滑膜细胞的浸润。TNF转化酶对于白介素1诱导双调蛋白的分泌是必须的。&
附原文：Abstract Objectives. The aims of
this study were to investigate the expression of amphiregulin (AREG) and
TNF-a-converting enzyme (TACE) in fibroblast-like synoviocytes from humans with
RA (FLS-RA) when stimulated with proinflammatory cytokines and to explore
whether AREG plays a role in RA. Methods. The effects of cytokines on the
expression of AREG and TACE in FLS-RA were measured by quantitative RT-PCR and
western blotting. Blockade of IL-1b-mediated pathways was used to verify the
involvement of intracellular signal pathways in the induction of AREG and TACE.
TAPI-1 and TACE short hairpin RNA (shRNA) infection were used to identify the
role of TACE in IL-1b-induced AREG secretion and shedding. AREG-induced
production of MMP-1 and cadherin-11 in FLS-RA were measured by ELISA or western
blotting. The effect of AREG on FLS-RA invasion was examined using a Transwell
invasion assay. Results. IL-1b, but not other tested cytokines, increased the
expressions of AREG mRNA and protein in a dose-responsive and time-dependent
manner in FLS-RA. IL-1b induced AREG expression via p38 MAPK, NF-kB, JNK and
ERK1/2 signalling pathways and induced TACE expression via PI3K, p38MAPK and
NF-kB signalling pathways in FLS-RA. TACE mediated AREG secretion and shedding.
EGFR (ErbB1) and Her-2 (ErbB2) were expressed in FLS-RA, and AREG increased
MMP-1 and cadherin-11 expression in FLS-RA. AREG promoted the FLS-RA invasion
ability. Conclusion. AREG and TACE expression were up-regulated by IL-1b and
their activations on FLS-RA lead to the matrix degradation by inducing MMP-1
and cadherin-11 production. TACE activity is necessary for IL-1b-induced AREG
release. Our results demonstrate that IL-1b-induced AREG release may be
involved in the pathogenesis of RA.&原文链接：http://www.ncbi.nlm.nih.gov/pubmed/?term=TACE-dependent+amphiregulin+release+is+induced+by+IL-1b+and+promotes+cell+invasion+in+fibroblast-like+synoviocytes+in+rheumatoid+arthritis&
引自：Liu FL1,&Wu CC,&Chang DM. TACE-dependent
amphiregulin release is induced by IL-1β and promotes cell invasion in
fibroblast-like synoviocytes in rheumatoid arthritis. Rheumatology
(Oxford).&2014
F53(2):260-9. doi: 10.1093/rheumatology/ket350. Epub 2013 Nov 6.
唾液腺超声能使2012
ACR干燥综合症分类标准的诊断性能显著提高&&杨麟&&摘要：目的：本研究的目的是评估唾液腺超声（sGUS）是否能提高干燥综合症2012
ACR分类标准。&
方法：本研究共纳入了法国的101名可疑的干燥综合症患者。超声结构分数大于等于2分被认为是反常的。诊断的参考标准是由一组医学专家根据结果双盲分析得到并进行评判。&结果:45例患者被诊断为干燥综合症。在101名可疑患者中，干燥综合症患者和非干燥综合症患者眼部染色分数&3的比率是相近的。在血清学检查方面，抗SSA
/ SSB抗体阳性再加上RF阳性以及ANA滴度&1:320相比于单纯的抗SSA
/ SSB阳性能更好增加诊断的敏感性。唾液腺超声对于诊断干燥综合症的敏感性为60%，特异性为87.5%，并且使ACR标准的敏感性增加从64.4%增加到到84.4%，而特异性仅略有下降，从91.1%到89.3%。&
结论: 唾液腺超声能使干燥综合症的ACR分类标准的诊断性显著提高。唾液腺超声应包括在未来的干燥综合症诊断标准中。&
附原文：Abstract
Objective. The aim of this study was to
evaluate whether salivary gland ultrasonography (SGUS) improves the diagnostic
performance of the 2012 ACR classification criteria for SS. Methods. We studied
a cohort of 101 patients with suspected SS seen at a single center in Brittany,
France. An SGUS echo structure score &2 was considered abnormal. The
reference standard was a clinical diagnosis of SS made by a group of experts
blinded to SGUS findings. Results. SS was diagnosed in 45 patients. Similar
proportions of patients with and without SS had an ocular staining score &3.
Adding RF positivity and ANA titre &1:320 as an alternative to anti-SSA/SSB positivity
increased the sensitivity of the serological item without modifying specificity
compared with using anti-SSA/SSB alone. SGUS was 60.0% sensitive and 87.5%
specific for SS. Adding the SGUS score to the ACR criteria increased
sensitivity from 64.4% to 84.4% and only slightly decreased specificity, from
91.1% to 89.3%. Conclusion. The diagnostic performance of the ACR classification
criteria for SS is notably improved by adding the SGUS score. SGUS should be
included in future classification criteria for SS.&
原文链接：http://www.ncbi.nlm.nih.gov/pubmed/?term=Salivary+gland+ultrasonography+improves+the+diagnostic+performance+of+the+2012+American+College+of+Rheumatology+classification+criteria+for+Sjo%C2%A8+gren%E2%80%99s+syndrome&
引自：Cornec D1,&Jousse-Joulin S,&Marhadour T,&Pers JO,&Boisramé-Gastrin S,&Renaudineau Y,&Saraux A,&Devauchelle-Pensec
V. Salivary&gland&ultrasonography&improves&the&diagnostic&performance&of the&2012&American&College&ofRheumatology&classification&criteria&for&Sjogren's&syndrome. Rheumatology&(Oxford).&2014 Apr 4. [Epub ahead of print]
血清阴性的抗磷脂综合征犹如马赛克
摘要：临床实践中有许多提示抗磷脂综合症表现,但是抗心磷脂抗体、抗β 2-GPI抗体和狼疮抗凝物持续阴性，因此把这些人称作抗体阴性的APS。本研究用不同的方法学验证24例血清阴性的抗磷脂综合征患者血清中的抗体，通过薄层色谱-免疫染色的方法检测抗磷脂抗体，通过ELISA检测抗膜联蛋白/心磷脂复合物抗体，通过ELISA和斑点杂交检测抗膜联蛋白抗体和抗凝血酶抗体。对照组包括了25例抗磷脂综合征、18例狼疮和32例正常对照组。结果：24例血清阴性抗磷脂综合征患者中，13例通过薄层色谱-免疫染色的方法检测抗磷脂抗体阳性，11例抗膜联蛋白/心磷脂复合物抗体阳性，3例患者抗凝血酶抗体阳性，1例患者抗膜联蛋白V抗体阳性。在血清阴性的抗磷脂综合征患者的血清中，应该检测针对新的抗原（主要是膜联蛋白V/心磷脂）的抗体及通过新的检测方法（薄层色谱-免疫染色）来检测抗体。因此，血清阴性的抗磷脂综合征实际上就是一个马赛克，在里面针对不同抗原的抗体能被检测到。
附原文：In the clinical practice it is possible to find
patients with clinical signs suggestive of antiphospholipid syndrome (APS), who are persistently negative for the
laboratory criteria of APS, that is, anti-cardiolipin antibodies (aCL), anti- β
2-GPI antibodies and lupus anticoagulant. Therefore, it was proposed for these
cases the term of seronegative APS (SN-APS). In order to detect autoantibodies
with different methodological approaches, sera from 24 patients with SN-APS
were analysed for anti-phospholipid antibodies using TLC immunostaining, for
anti-vimentin/cardiolipin antibodies by enzyme-linked immunosorbent assay
(ELISA), and for anti-annexin V and anti-prothrombin antibodies by ELISA and
dot blot. Control groups of our study were 25 patients with APS, 18 with
systemic lupus erythematosus (SLE), and 32 healthy controls. Results revealed
that 13/24 (54.2%) SN-APS sera were positive for aCL (9 of whom were also
positive for lysobisphosphatidic acid) by TLC immunostaining, 11/24 (45.8%) for
anti-vimentin/cardiolipin antibodies, 3/24 (12.5%) for anti-prothrombin
antibodies, and 1/24 (4.2%) for anti-annexin V antibodies. These findings
suggest that in sera from patients with SN-APS, antibodies may be detected
using "new" antigenic targets (mainly vimentin/cardiolipin) or
methodological approaches different from traditional techniques (mainly TLC
immunostaining). Thus, SN-APS represents a mosaic, in which antibodies against
different antigenic targets may be detected.
引自：Conti F1, Capozzi A2, Truglia S1, et al.The mosaic of
"seronegative" antiphospholipid syndrome. J Immunol Res. 9601. doi:
10.9601. Epub 2014 Mar 17.
抗磷脂综合征的靶向治疗
摘要：目的：为将来能制定出更加安全的靶向治疗，本文综述近期正在进行的治疗抗磷脂综合征的新的治疗策略。近期发现：新的治疗策略包括了CD20的单抗和新的抗凝物（包括直接抗凝血酶和抗X因子的拮抗剂）。研究侧重于干扰抗磷脂抗体介导的细胞的激活，针对补体成分和用定制的肽段阻断抗磷脂抗体的致病部分等。总结：抗磷脂综合征是以血栓形成和病态妊娠为主要表现，同时伴有抗磷脂抗体持续的中高滴度阳性的疾病。目前主要的治疗方案是长期使用维生素K的拮抗剂，将来将侧重于发现一些新的治疗靶点，目前一些针对新的靶点的治疗正在进行。挑战在于设计出前瞻性的、随机的、双盲的实验来足以验证这些新的治疗方案，有利于他们应用与临床实践。
附原文：PURPOSE OF REVIEW: To review novel therapeutic targets that are currently
under investigation to develop safer, targeted therapies for antiphsopholipid antibody (aPL)-mediated clinical manifestations.RECENT FINDINGS: Novel therapeutic options
potentially available include anti-CD20 monoclonal antibodies and
new-generation anticoagulants (such as direct thrombin and anti-Xa inhibitors).
Research focusing on interfering with aPL-mediated cell activation, targeting
complement components and the innovative concept of blocking the pathogenic
subpopulation of aPL with tailored peptides are currently being explored.SUMMARY: Antiphospholipid syndrome is an autoimmune disease characterized by thrombosis
and pregnancy morbidity occurring in
patients persistently positive for aPL. Current therapeutic options remain
confined to long-term anticoagulation with vitamin K antagonists. The future
holds much promise with the identification of novel potential targets, many of
which are currently under investigation. The challenge will be to design
prospective randomized controlled clinical trials to provide the evidence
necessary to support integration of these therapies into clinical practice.
引自: Sciascia S1, Khamashta MA, D'Cruz DP.Targeted therapy in antiphospholipid
syndrome. Curr Opin Rheumatol. ):269-75. doi:
10.1097/BOR.0051.
血清阴性与阳性APS的临床表现无明显差异&李常虹&
摘要（英国）目的：尽管医学文献中有关临床诊断为抗磷脂综合征（APS）且抗磷脂抗体（aPL）谱持续阴性患者的个案报道越来越多，但至今仍没有一项研究能够纳入一系列类似的患者并总结其相应的临床特点。&
方法：作者评估了154例APS患者的临床表现，其中87例患者为血清阳性的APS患者，67例为aPL持续阴性但有血栓和/或死胎的病史，同时也具备至少2项APS诊断标准外的临床表现的患者（即所谓的血清阴性APS患者，SN-APS）。患者在招募入组时针对病史进行了回顾性问诊。&
结果：血清阳性的APS患者与SN-APS患者相比，血栓事件或产科死亡率方面无显著性差异，包括深静脉血栓（31.4% vs 31%）、肺栓塞（23.8% vs 28.7%）、中风（14.9% vs 17.2%）、短暂性缺血发作（11.9% vs 10.3%）、孕早期自发流产（67.1% vs 52.1%）、死产率（62.5% vs 59.4%）、早产率（28.1% vs 21.7%）或先兆子痫（28.1% vs 23.1%）。&
结论：经典的APS与SN-APS患者具备相似的临床表现谱。这一结果提示临床上对于APS患者的处理不应当仅仅依赖于常规抗磷脂抗体的出现。&
附原文：Abstract
OBJECTIVES: Although the medical literature currently provides a
growing number of isolated case reports of patients with clinically well-defined
antiphospholipid syndrome (APS) and persistently negative antiphospholipid
antibodies (aPL), there are no studies including a series of patients
addressing the clinical features of this condition.METHODS: The authors assessed clinical manifestations of APS in
154 patients: 87 patients with seropositive APS and 67 patients with thrombosis
and/or pregnancy morbidity persistently negative for aPL and presenting with at
least two additional non-criteria manifestations of APS (the so-called 'seronegative
APS', SN-APS). Patients were interviewed at the time of recruitment, and a
retrospective file review was carried out. RESULTS: There were no significant differences in the frequency
of thrombotic events or obstetric morbidity in patients with SN-APS versus
patients with seropositive APS: deep vein thrombosis (31.4% vs 31.0%),
pulmonary embolism (23.8% vs 28.7%), stroke (14.9% vs 17.2%), transient
ischaemic attack (11.9% vs 10.3%), early spontaneous abortions (67.1% vs
52.1%), stillbirths (62.5% vs 59.4%), prematurity (28.1% vs 21.7%) or
pre-eclampsia (28.1% vs 23.1%). CONCLUSIONS:
Classic and SN-APS patients show similar clinical profiles. The results
suggest that clinical management in patients with APS should not be based only
on the presence of conventional aPL.&引自：Rodriguez-Garcia JL, Bertolaccini ML, Cuadrado MJ, Sanna G, Ateka-Barrutia O, Khamashta MA. Clinical manifestations of antiphospholipid syndrome (APS) with and
without antiphospholipid antibodies (the so-called 'seronegative APS'). Ann Rheum Dis. ):242-4.
超声能预测RA患者临床缓解停药后的复发情况
摘要：目的：本前瞻性研究的目的是明确超声评估滑膜炎能否预测达到临床缓解后停止使用生物制剂的患者的复发。
方法：本研究纳入使用生物制剂达到临床缓解（DAS28 & 2.6）后同意停用生物制剂的患者。缓解接受40个关节、134个滑膜位点的超声检查并随访6个月。随访期间对患者进行评价的医生不知道其基线时超声检查的结果。
结果：本研究纳入42例接受TNF拮抗剂或妥珠单抗的患者。利用ROC曲线确定最优的cut-off值，结果显示整体超声评分高的患者复发率显著高于整体超声评分低的患者(灰阶评分和能量多普勒评分均P& 0.001)。以DAS28分组，DAS28高和低两组无显著差异(P = 0.158) (log-rank test)。灰阶评分的阳性和阴性预测价值为80.0%和73.3%，能量多普勒评分的阳性和阴性预测价值为88.9 % and 74.2 %。
结论：在接受生物制剂治疗达到临床缓解的RA患者中，如果超声检测到残存的滑膜炎将预示其停药后短期内复发。我们的研究结果为进一步进行大规模的研究制定以超声指导优化生物制剂治疗提供了基础。
附原文：Abstract Objective: This prospective study
aimed to determine whether the comprehensive ultrasonographic assessment of
synovial inflammation predicts relapse after discontinuation of biological treatment
in patients with rheumatoid arthritis (RA)
in clinical remission. Methods:
RA patients in clinical remission (DAS28 & 2.6)
receiving biological treatment who agreed to discontinue
the biological treatment were recruited. Patients underwent
a comprehensive ultrasound scan on 134 synovial sites in 40 joints and were
prospectively followed up for 6 months. Physicians who evaluated the patients during
the study period were blinded to the baseline ultrasound findings. Results:
Forty-two patients receiving either a TNF antagonist or tocilizumab
were enrolled. Using the optimal cut-off values determined by receiver
operating characteristic (ROC) analysis, relapse rates were
significantly higher in patients whose total ultrasound scores
at discontinuation were high than in those whose total ultrasound
scores were low (P & 0.001 for both total gray-scale and power Doppler
scores), whereas the difference between high and low DAS28 was not statistically
significant (P = 0.158) (log-rank test). Positive and negative predictive
values were 80.0 % and 73.3 % for the total gray-scale score and 88.9 % and
74.2 % for the total power Doppler score, respectively. Conclusion: In
RA patients in clinical remission receiving biological treatment,
residual synovial inflammation determined by comprehensive
ultrasound assessment predicts relapse within a short
term after discontinuation of
the biological treatment. Our data provide a rationale and groundwork
to conduct a large-scale study for establishment of ultrasound-based strategies
to optimize the period of biological treatment。
摘自：Iwamoto
K, Hosokawa
J, et al. Ultrasonographic assessment predicts relapse after discontinuation of biological agents in patients withrheumatoid arthritis in clinical remission.
Arthritis Care
Res (Hoboken). 2014 Feb 10. doi: 10.1002/acr.22303. [Epub ahead of
肥厚滑膜组织中能量多普勒阳性信号是缓解期RA患者短期内复发的预测指标
摘要：目的：本研究的目的是评价早期类风湿关节炎（RA）患者达到临床缓解后使用超声评价残存疾病活动的价值。
方法：本研究纳入106例早期RA患者，根据DAS28评分调整DMARDs药物的使用方案并随访2年。基线的评价包括临床、实验室、功能及44个关节超声检查。将灰阶（GS）和能量多普勒（PD）超声滑膜炎指数与临床评价、实验室检查及临床结局进行分析。两次间隔3个月的随访DAS28均&1.6定义为临床缓解。
结果：在疾病活动和达到缓解的RA患者中，超声检查比临床检查更敏感。在病情活动的患者中，临床及超声指数均与CRP呈正相关，而在缓解患者中仅PD与CRP正相关。临床缓解的患者中，95%的患者在GS中显示有残存的滑膜炎，41%的患者有阳性的PD信号。单变量及多变量logistic回归分析结果显示，阳性PD信号是6个月内病情复发的预测指标。
结论：在接受传统DMARds治疗的早期RA患者疾病活动及缓解时，二维灰阶超声能检测到残存的疾病活动，并比临床检查更敏感。此外，在缓解期，肥厚滑膜组织中阳性的PD信号表明其存在持续的炎症并预测短期复发的可能。
附原文：Abstract OBJECTIVES:
This study aimed to evaluate the usefulness of a systematic
musculoskeletal ultrasonographic (US) assessment in the detection of
residual disease activity in patients with early RA who
achieved clinical remission. METHODS:
We prospectively studied 106 early RA patients receiving
conventional DMARDs according to a disease activity score (DAS)-steered
therapeutic protocol over a 24-month period.
Standard evaluation included clinical, laboratory, functional
and systematic (44 joints) US assessment. US indexes of grey scale (GS)
and power Doppler (PD) synovitis were correlated
with clinical evaluation, laboratory indexes and clinical outcome.Clinical remission was
defined when DAS was &1.6 at two consecutive visits 3 months apart. RESULTS: US examination was
significantly more sensitive than clinical examination, both in
active disease and in remission. In patients with an active disease,
both clinical and US indexes correlated with CRP, whereas
in remission only PD still remained significantly correlated. In clinical
remission, 95% of the patients showed residual GS synovitis, and 41% of them
showed a positive PD signal. Positive PD signal, even in a single joint,
resulted the main predictor of relapse within 6 months, both in
univariable and multivariable logistic regression analysis. CONCLUSIONS: In a cohort
of early RA patients treated with conventional DMARDs, US-GS can
detect residual disease activity more sensitively
than clinical examination both in active disease and
in remission. Moreover, PD-positive synovial hypertrophy identifies an ongoing
inflammation even
during remission and predicts short-term relapse.
摘自：Scirè
CA, Montecucco C, Codullo V,
et al. Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: power Dopplersignal predicts short-term relapse.
Rheumatology
(Oxford). 2009 S 48(9): 1092-7.
停恩利后再次加用治疗活动性AS患者的长期疗效和安全性
摘要（德国）目的：随机对照试验（RCTs）证实肿瘤坏死因子α（TNF-α）受体融合蛋白依那西普治疗活动期的强直性脊柱炎（AS）患者显示出了良好的疗效。本研究旨在评估依那西普治疗AS 1年后的疗效和安全性，其中包括终止使用后再接受依那西普治疗的患者。
方法：本研究为54周开放性观察研究，26例AS患者接受25mg依那西普每周两次皮下注射治疗。纳入研究的所有患者均为停用依那西普后再出现高疾病活动度，且BASDAI&4分，疼痛评分&4分。研究采用诸如BASFI等标准的评估工具。意向性（ITT）和全量分析用于本次研究。研究结果与本研究的基线数值进行了比较。
结果：最初的30例患者中，有26例（87%）患者符合本次平均长达约27周的开放性扩大研究纳入标准。到第54周时，仍有23例患者（88%）在使用依那西普治疗。ITT分析显示58%（95%的置信区间39-74%）的患者在54周时达到了BASDAI 50%的改善。根据ASA工作组的标准，54周时有8例患者（31%）达到了部分缓解的标准。而且功能和生活质量方面改善明显。仅有一例患者因严重不良事件而停用。
结论：本研究显示超过1年的依那西普单药再治疗活动性AS患者是安全有效的。
附原文：Abstract
OBJECTIVES: Treatment of ankylosing spondylitis (AS) with the tumour
necrosis factor alpha (TNF-alpha) receptor fusion protein etanercept has shown
efficacy in patients with active disease in randomized controlled trials (RCTs)
for limited periods. The objective of the study was to assess the long-term
efficacy and safety of etanercept over 1 yr, including discontinuation and
readministration. METHODS: In
this 54-week open observational study, 26 AS patients received 25 mg etanercept
subcutaneously twice weekly after several months of discontinuation following a
6-month RCT with the same agent. All patients who developed high disease
activity after cessation of etanercept, defined as a Bath Ankylosing
Spondylitis Disease Activity Index (BASDAI) & r = 4 and pain & r = 4 on
a numerical rating scale, entered the study. Standard assessment tools, such as
the Bath Ankylosing Spondylitis functional index (BASFI), were used. An
intention-to-treat (ITT) and a completer analysis were performed. The results
were compared with the baseline values of the open study. RESULTS: Out of the initial 30
patients, 26 (87%) were eligible for the open extension study after a mean of
about 27 weeks. At week 54, 23/26 patients (88%) were still on treatment with
etanercept. The ITT analysis showed that 58% (95% confidence interval 39-74%)
of the patients achieved a 50% improvement of BASDAI at week 54. According to the
Assessments in Ankylosing Spondylitis working group criteria, 8/26 patients
(31%) were in partial remission at week 54. Function, metrology and quality of
life improved significantly. Only one patient had a serious adverse event that
resulted in discontinuation. CONCLUSIONS:
This study shows that treatment with etanercept is efficacious and safe
after readministration over 1 yr in patients with active AS not taking DMARDs
or steroids.
引自：Brandt J1, Listing J, Haibel H, S&rensen H, Schwebig A, Rudwaleit M, Sieper J, Braun J. Long-term
efficacy and safety of etanercept after readministration in patients with
active ankylosing spondylitis. Rheumatology (Oxford). ):342-8. Epub
2004 Nov 23.
前瞻性研究证实长期中度饮酒可降低女性RA发生风险
摘要：目的：在护士健康研究和护士健康研究Ⅱ两个队列中评估饮酒与类风湿关节炎风险的相关性。
方法：护士健康研究开始于1976年共纳入121701位美国注册护士，护士健康研究Ⅱ开始于1989年，共纳入116430位女性护士。两年一次的问卷调查对生活方式和环境暴露因素进行收集。每四年对饮酒与其他食物频率进行评估。采用结缔组织疾病筛查问卷和医学病历回顾评估RA病例。在上述两个队列中调整潜在混杂因素后采用单独Cox比例风险模型评估风险比。采用DerSimonian和Laird随机效应模型评估两个队列的合并风险比。
结果：在护士健康研究队列中，从1980年到2008年共190万人年，580例RA病例被诊断。在护士健康研究队列Ⅱ中，从1989年到2009年共178万人年，共323例RA病例被诊断。每天摄入5.0-9.9克酒精组与无饮酒组相比，合并的多因素调整后的风险比是0.78（95%置信区间0.61-1.00）。对于血清阳性RA病例，相关性更显著（风险比0.69，95%置信区间0.50-0.95）。同时，每周饮用2-4次啤酒的女性相比从不饮用啤酒的女性RA患病风险下降31%。
结论：我们发现长期中等酒精摄入与降低RA风险有相关性。未来需要在其他人群验证我们的发现。
附原文：Objective.
To evaluate the association of alcohol consumption with risk of rheumatoid arthritis
(RA) in two large prospective cohorts, the Nurses' Health Study (NHS) and
Nurses' Health Study II (NHS II). Methods. The NHS established in 1976 that
enrolled 121,701 US female registered nurses. The NHSII began in 1989,
enrolling 116,430 female nurses. Lifestyle. and environmental exposures have
been collected through biennial questionnaires. Alcohol consumption was assessed
with a food frequency questionnaire completed every 4 years. The incident RA
cases were identified using the connective tissue disease screening
questionnaire and a medical record review. Separate Cox proportional hazards
models were used to estimate hazard ratios (HRs) after adjusting for potential
confounders in NHS and NHSII. Pooled HR from two cohorts was estimated using a
DerSimonian and Laird random-effect model. Results. Among 1.90 million years of
person-time from 1980 to
incident RA cases were diagnosed in NHS, and
among 1.78 million years of person-time from 1989 to
incident RA
cases were diagnosed in NHSII. Compared to no use, the pooled multivariable
adjusted HR for alcohol use of 5.0-9.9 grams/day (g/d) was 0.78 (95% CI,
0.61-1.00). For seropositive RA cases, the association appeared stronger (HR=
0.69, 95% CI: 0.50-0.95). In addition, Women who drank beer 2-4 times a week
had a 31% decreased risk compared with women who never drank beer. Conclusion.
We found a modest association between long-term moderate alcohol drinking and
reduced risk of RA. Future studies are needed to confirm our findings in other
populations.
摘自：Lu B1,
Solomon DH,
Costenbader
KH, Karlson EW.
Alcohol consumption and risk of incident rheumatoid arthritis in women: A
prospective study. Arthritis Rheumatol. 2014
Apr 11. doi: 10.1002/art.38634. [Epub ahead of print]
SLE外周神经病变的特点分析&&李常虹摘要（美国）目的：本研究旨在鉴定系统性红斑狼疮（SLE）患者外周神经病变相关的亚型、辅助研究和免疫谱。&
方法：本研究持续25年，共纳入2097例SLE患者。我们确诊了 SLE导致的外周神经病变，并比较了伴和不伴神经病变患者间临床和SLE相关特征的差异。&
结果：外周神经病变的发生率为5.9%（123/2097），其中66.7%的外周神经病变由SLE所致（82/123）。我们发现SLE导致的外周神经病变患者中约17.1%（14/82）的患者有小纤维神经病变，这是一种痛性的神经病变，不包含于ACR神经精神SLE病例定义范围之内。SLE合并小纤维神经病变的患者往往表现为异常的神经疼痛，同时不具备袜套样分布，皮肤活检提示有背根神经节神经元细胞缺失。与不伴有外周神经病变的SLE患者相比，外周神经病变的患者平均疾病活动度更低（P=0.01），疾病损坏性更高（P&0.01），更倾向于有带状疱疹病毒感染（P&0.01）、骨松性骨质（P&0.01）及机会性感染（P&0.01）的病史。&
结论：小纤维神经病变是一种常见的外周神经病变，不包含在ACR NPSLE病例定义之中。皮肤活检发现小纤维神经病变的有着与众不同的病理基础，其病变部位主要是在背根神经节和远端轴索。SLE合并外周神经病变患者的平均疾病活动度更低，但疾病损害性更高。我们的研究结果提示，ACR NPSLE病例定义有必要进一步修改，因为它目前尚不包括小纤维神经病变。&附原文：Abstract Objective: We sought to characterize peripheral
neuropathy subtypes, ancillary studies, and immunological profiles associated
with peripheral neuropathies in patients with systemic lupus erythematosus
(SLE). Methods: In this 25-year study of 2,097 SLE patients, we characterized
peripheral neuropathies due to SLE, and compared the association of clinical
and SLE-related features in patients with versus without neuropathy. Results:
The prevalence of peripheral neuropathies was 5.9% (123/2,097), with 66.7%
(82/123) having peripheral neuropathies attributable to SLE. We noted that
17.1% (14/82) of patients with peripheral neuropathies due to SLE had
small-fiber neuropathies, which is a painful neuropathy not included in the
American College of Rheumatology neuropsychiatric SLE (ACR NPSLE) case
definitions. SLE patients with small-fiber neuropathies could present with
unorthodox neuropathic pain patterns not consistent with a stocking-and-glove
distribution, and had associated skin biopsies suggestive of dorsal root
ganglia neuronal cell loss. Compared to SLE patients without peripheral
neuropathies, peripheral neuropathy patients had lower mean disease activity
(p=0.01), higher disease damage (p&0.01), and were also more likely to have
a history of herpes zoster virus (p&0.01), osteoporotic fractures
(p&0.01), and opportunistic infections (p&0.01).
Conclusions: Small-fiber neuropathy is a frequent
peripheral neuropathy not included in the ACR NPSLE case definitions. The skin
biopsy findings in small-fiber neuropathy patients support distinct mechanisms
targeting the dorsal root ganglia as well as distal axons. SLE peripheral
neuropathy patients had lower mean disease activity and higher disease damage.
Our findings suggest that revision of the ACR NPSLE case definitions is
warranted, which currently does not include small-fiber neuropathies.&&引自：Oomatia A, Fang H, Petri M, Birnbaum J. Peripheral
neuropathies in systemic lupus erythematosus (SLE): Clinical features, disease
associations, and immunological characteristics evaluated over a 25-year study
period. Arthritis Rheum. 2013 Dec 10. doi: 10.1002/art.38302. [Epub ahead of
甲氨蝶呤增加了RA患者肺病发生的机率&&李常虹&
摘要：目的：甲氨蝶呤对于治疗类风湿关节炎（RA）等多种疾病显示出了良好的疗效。也有研究提示甲氨蝶呤是间质性肺病的诱因。RA患者可以累及肺脏，同时具备呼吸道高感染风险。本研究旨在评估接受甲氨蝶呤治疗的RA患者发生肺脏疾病的相对风险（RR）。&方法：我们在Pubmed和Cochrane数据库（发表时间日至日）中搜索有关甲氨蝶呤治疗成人RA的随机双盲对照研究。研究对象少于100例或研究持续时间少于24周的研究不能被纳入分析。2位研究人员独立搜索了2个数据库，随后所有研究人员对入选研究进行审查。我们应用Mantel-Haenszel随机效应的方法比较了不同研究间相对风险的差异。&
结果：总共22个研究，8584例患者符合纳入标准。不同研究间的异质性没有显著差异(I2 = 3%)，使得不同研究可以综合起来进行分析。结果显示甲氨蝶呤与呼吸道不良事件总体发生风险增加相关(RR 1.10，[95% CI] 1.02&#)，与呼吸道感染相关（RR 1.11, 95% CI 1.02&#）。接受甲氨蝶呤治疗的患者不会因肺脏疾病（RR 1.53, 95% CI 0.46&#）或非感染性呼吸道事件(RR 1.02, 95% CI 0.65&#) 出现死亡风险的增加。研究亚组分析显示甲氨蝶呤的应用增加了肺炎发生的风险（RR 7.81, 95% CI 1.76&#）。&
结论：我们的研究表明甲氨蝶呤治疗RA较其他改变病情的抗风湿药和生物制剂增加了患者发生肺病的风险。&附原文：Objective Methotrexate has shown efficacy for the treatment of
several diseases, especially rheumatoid arthritis (RA). Methotrexate has also
been implicated as a causative agent in interstitial lung disease. Patients
with RA may develop pulmonary manifestations of their disease and are at
increased risk of respiratory infection. The aim of this study was to evaluate
the relative risk (RR) of pulmonary disease among patients with RA treated with
methotrexate. Methods We
searched the PubMed and Cochrane databases (publication dates January 1, 1990
to February 1, 2013) for double-blind, randomized, controlled trials of
methotrexate versus placebo or active comparator agents in adults with RA.
Studies with &100 subjects or with a duration of &24 weeks were excluded.
Two investigators independently searched both databases, and all of the
investigators reviewed the selected studies. We compared differences in the RR
using the Mantel-Haenszel random-effects method. Results A total of 22 studies with 8,584
participants met the inclusion criteria. Heterogeneity across studies was not
significant (I2=3%), allowing combination of the trial results.
Methotrexate was associated with an increased risk of all adverse respiratory
events (RR 1.10, 95% confidence interval [95% CI] 1.02&#) and respiratory
infection (RR 1.11, 95% CI 1.02&#). Patients treated with methotrexate were not at
increased risk of death due to lung disease (RR 1.53, 95% CI 0.46&#) or noninfectious
respiratory events (RR 1.02, 95% CI 0.65&#). A subgroup analysis of
studies in which pneumonitis was described revealed an increased risk
associated with methotrexate (RR 7.81, 95% CI 1.76&#). Conclusion Our study demonstrated a
small but significant increase in the risk of lung disease in patients with RA
treated with methotrexate compared with other disease-modifying antirheumatic
drugs and biologic agents.&
引自：Conway R, Low C, Coughlan RJ, O'Donnell MJ, Carey JJ. Methotrexate
and lung disease in rheumatoid arthritis - A meta-analysis of randomized
controlled trials.Arthritis Rheum. 2013 [Epub ahead of print]
尊敬的北医三院领导：
贵院疼痛介入科的柳晨大夫，风湿免疫科的姚中强主任，对待病人就像对待自己亲人一样，他们用温和而慈祥的面孔，朴实的语言，可亲可近的工作态度，结合患者的患病经历和诊断病理，与患者进行面对面的热情接触，一下子就拉近了医生与患者的距离，他们对医术精益求精，使疑难杂症在短期内能够诊断出病因，为对症治疗疾病，减轻病人的痛苦提供了依据，他们的品德高尚，医术精湛，是患者所想象的和最需要的好医生，更是所有在北医三院就诊的患者的救命恩人。这是来自山西省晋城的一名患者，在接触贵院的柳大夫、姚主任之后发自内心的真实感受。
事情的经过还得返回到去年六月。我是在去年六月胸骨开始疼痛，影响了正常生活，当时在当地医院打针吃药，都没有解决根本的胸骨疼痛。后来在地区医院、省肿瘤医院、中国医学科学院肿瘤医院都做过相关检查，然后又住进了解放军301总医院，在那里一住就是4个多月。从那开始，按照医生嘱咐，一边服用德国进口等多种止痛药来维持疼痛，一边开始了必要的检查和诊断。光在我胸骨疼痛的部位就先后穿过两次刺，结果显示：排除了肿瘤的可能性。确定为“不除外朗格罕斯组织细胞增生症”，专家称，这种病在解放军301总医院非常罕见。无奈之下，我只能继续服用止疼药来维持疼痛。
时间过去两个月，我和家人又来到了解放军301总医院诊断，专家建议：让我把原来做过的胸骨穿刺物的病理切片和病理报告，先后送到了北京大学肿瘤医院、北医三院、北京友谊医院等相关科室，找专家进行会诊。经过会诊以后，仍未确诊出胸骨疼痛的病因。北大肿瘤医院专家称：有可能在解放军301总医院做过的两次穿刺时所取的东西较少的原因。因此解放军301总医院专家建议，在我胸骨处做手术取出一块再作活检。当时，一提说手术，我和家人都非常恐惧，因为胸骨的部位不好，手术创伤也较大，毕竟我是快60岁的人了，也怕留下什么后遗症。当我和家人正在左右为难时，有一天，我们在好大夫在线网站上，发现了“疑难穿刺找柳晨的消息，然后便立即找到了正在出诊的柳大夫。我和女儿一见到柳大夫，说明来意后，就为柳大夫慈祥和微笑的面孔，亲切而朴实的语言而深深感动。柳大夫一边详细的询问我的病情，患病经过，及现在的症状，一边仔细认真地看我所有的病理报告。柳大夫看完后表示：“只要确诊后认为前两次取的东西少，那么，下次我亲自穿，尽可能多取一点。柳大夫的言行举止当时就感动了我和女儿，并留下了眼泪。此时此刻，我和女儿好像吃下了定心丸。接下来柳大夫打电话找风湿免疫科姚中强主任让他接收我。因此，我们挂了号并找到了姚主任。刚到门口，我和女儿在门缝处看见姚主任在帮助刚刚诊断完而且手脚不利索的病人穿袜子。当时在想，我从山西到北京的各个大医院看病近半年多来，从未经见过这么好的医生。接下来在我们说明来意的过程中，姚主任又是很亲切很仔细地问我的病情经过，认真地翻阅了我所有的病理报告等资料，作为病人的感觉，好像姚主任正在给自己的亲人或朋友问诊看病。等姚主任问完看完之后，他建议我们去北京协和医院找有关专家再次进行会诊，于是，我们就按姚主任的建议再次进行会诊。
时间又过去两个月，那就是2014年的2月，在北京协和医院和其他医院送检的胸骨穿刺物病理切片的会诊又是没有结果。因此，我们又一次挂号找到了柳晨大夫，决定重新实施在胸骨穿刺的小手术。
在实施胸骨穿刺的过程中，由于柳大夫高超而精湛的穿刺医术，穿刺的感觉既不是特别疼，而且时间短，当时我内心深处满怀了一种很特别的安全感。穿刺大约用了半小时，柳大夫说非常顺利。穿完刺以后，柳大夫扶住我并帮我穿衣服，我又一次被柳大夫尊老敬老的传统美德深深所感动。
这一次穿刺，找到了病灶，找准了病因，为下一步对症治疗提供了重要依据，也解决了我在北京各大医院已奔波了近10个多月来而诊断不清的“疑难杂症”。
北医三院领导：贵院的柳晨大夫、姚中强主任品德高尚、医术精湛，在工作中做到了处处病人如亲人，虽然是很平凡的言行举动，却代表着北医三院的整体形象。为此，我们全家人非常感谢两位大夫，并永远铭记在心。同时也特别感谢贵院能培养出像柳大夫、姚主任这样的高素质人才。
愿全国的医院都像贵院一样，培养出更多的高素质的好医生，那该有多好啊！
山西省晋城患者：赵立忠&& 日
补充叶酸或亚叶酸能够降低甲氨蝶呤治疗RA的副作用
摘要：目的：对叶酸和亚叶酸降低甲氨蝶呤所致的粘膜、胃肠道、肝脏及血液系统副作用进行系统综述，并且评估是否叶酸或者亚叶酸的补充对甲氨蝶呤的治疗作用有任何影响。
方法：从建库到2012年3月为止，我们检索了Cochrane图书馆、MEDLINE、EMBASE和美国国家健康临床试验注册机构。我们选择甲氨蝶呤（剂量≤25mg/w）治疗成年类风湿关节炎患者同时补充叶酸治疗的所有的随机双盲安慰剂对照临床试验。由于高剂量叶酸不被推荐使用，所以我们纳入低剂量叶酸或亚叶酸（起始剂量≤7mg/w）补充的研究。从试验中提取数据，每项试验都采用预定的标准进行偏倚风险评价。
结果：6项试验共624名患者符合纳入标准。大部分研究对于关键指标存在“低度偏倚”或者“不清楚”。通过GRADE工作组对每项结果进行评估，除血液系统副作用外，其证据质量均被评为“中等”，血液系统副作用证据质量为“低”。研究之间无显著异质性，包括对叶酸和亚叶酸的研究进行合并。对于使用甲氨蝶呤治疗RA患者补充任何形式的外源性叶酸（叶酸或者亚叶酸），其恶心、呕吐或者腹痛等胃肠道反应风险存在26%相对（9%绝对）的下降（RR 0.74, 95% CI 0.59 to
0.92; p = 0.008）。叶酸和亚叶酸也对甲氨蝶呤所致的血清转氨酶升高存在保护作用，75.6相对（16%绝对）风险下降（RR 0.23, 95% CI
0.15 to 0.34; p & 0.00001）。另外，其还能降低任何原因所致的甲氨蝶呤停药，60.8%相对（15.2%绝对）风险降低（RR 0.39, 95% CI
0.28 to 0.53; p & 0.00001）。
结论：结果支持对于使用甲氨蝶呤治疗RA的患者补充叶酸或亚叶酸有保护性作用。临床上，对于减轻胃肠道副作用和肝功能损害（通过血清转氨酶升高评估）有重要作用。同时，能够降低以任何原因所致的中止甲氨蝶呤的治疗。
附原文：OBJECTIVE: To perform. a
systematic review of the benefits and harms of folic acid and folinic acid in
reducing the mucosal, gastrointestinal, hepatic, and hematologic side effects
of methotrexate (MTX); and to assess whether folic or folinic acid
supplementation has any effect on MTX benefit. METHODS:
We searched the Cochrane Library, MEDLINE, EMBASE, and US National
Institutes of Health clinical trials registry from inception to March 2012. We
selected all double-blind, randomized, placebo-controlled clinical trials in
which adult patients with rheumatoid arthritis (RA) were treated with
MTX (dose ≤ 25 mg/week) concurrently with folate supplementation. We included
only trials using low-dose folic or folinic acid (a starting dose of ≤ 7 mg
weekly) because the high dose is no longer recommended or used. Data were extracted
from the trials, and the trials were independently assessed for risk of bias
using a predetermined set of criteria. RESULTS: Six
trials with 624 patients were eligible for inclusion. Most studies had low or
unclear risk of bias for key domains. The quality of the evidence was rated as
"moderate" for each outcome as assessed by the Grading of
Recommendations Assessment, Development, and Evaluation (GRADE) working group,
with the exception of hematologic side effects, which were rated as "low."
There was no significant heterogeneity between trials, including where folic
acid and folinic acid studies were pooled. For patients supplemented with any
form. of exogenous folate (either folic or folinic acid) while receiving MTX
therapy for RA, a 26% relative (9% absolute) risk reduction was seen for the
incidence of gastrointestinal side effects such as nausea, vomiting, or
abdominal pain (RR 0.74, 95% CI 0.59 to 0.92; p = 0.008). Folic and folinic
acid also appear to be protective against abnormal serum transaminase elevation
caused by MTX, with a 76.9% relative (16% absolute) risk reduction (RR 0.23,
95% CI 0.15 to 0.34; p & 0.00001), as well as reducing patient withdrawal
from MTX for any reason [60.8% relative (15.2% absolute) risk reduction, RR
0.39, 95% CI 0.28 to 0.53; p & 0.00001]. CONCLUSION:
The results support a protective effect of supplementation with
either folic or folinic acid for patients with RA during treatment with MTX.
There was a clinically important significant reduction shown in the incidence
of GI side effects and hepatic dysfunction (as measured by elevated serum
transaminase levels), as well as a clinically important significant reduction
in discontinuation of MTX treatment for any reason.
摘自：Shea B1,
Swinden MV,
Ghogomu E, Ortiz Z,
Katchamart W,
Bombardier C,
Tugwell P.
Folic Acid and Folinic Acid for Reducing Side Effects in Patients Receiving
Methotrexate for Rheumatoid Arthritis. J Rheumatol. 2014 Apr 15. [Epub ahead of
&良好医患关系沟通典范通信第八十一封&刘主任：&& & 您好！& &在“中国风湿病公众论坛”中，看到您的论坛信息，受到了不少的启发，了解了不少的疾病知识，也看到了病友的想法和心情。我和他们一样，有很多很多的话想对您说，可一想到您整天忙碌，又不忍心去打扰您。真的，有时候想给您留言，但一想起您那忙碌的脚步和身边众多的病人，觉得您已经够累的了，还得花时间回复，不忍心给您填麻烦。现在我能在公众论坛中看到您的信息，感到很温馨！借此机会，我把我最想说的话，也是和病友们一样的话说给您——谢谢您
！谢谢！！！非常感谢您这几年来不厌其烦地给我治疗，可以说是您给了我第二次生命，因为当时我要放弃治疗了。我很希望您在百忙之中，多保重！&
& & 记得日上午，我经309医院李医生的推荐，带着协和医院的化验单找到了您，当时的我三腔积液（胸腔、腹腔和盆腔），双脚浮肿，感觉脚面要崩裂似的，胃涨得不能进食，还饭都不想咽，也咽不下去，原本体重不足60公斤的我，当时是63.5公斤，真是茶饭不思，病体微弱。您见到我，看了化验单当时就说，赶快吃药住院治疗吧，并给我开了口服药，因床位不足，不能立即住院，我带着您的药暂时离开了北医三院，回到了我正在住院的309医院普外一区（因当时怀疑是癌症住哪儿的）。8月1日上午拿到您开的药，中午我就开始吃药，奇迹发生了，8月3日中午我吃了一碗焖面，我能吃饭了（吃药才两天半），真神奇！就在这一天，我从309医院出院。虽然309医院没有确诊我的病（因为不属于这个科），但他们给了我积极的治疗，为我及时补充了液体，维持了我的生命，我非常感谢他们！& & & 8月8日我正式住进了北医三院风湿免疫科，住院时胳膊上的塑料条至今还保留着：姓名：赵杏梅，性别：女，年龄：57，住院号4615572，科别：风湿，床号：25，诊断：结缔组织病(这个条是我生命的延续，我一定保存着)。8月19号，我出院了，这时的体重是49公斤，与当时63.5公斤比，少了14.5公斤。在住院期间，除了检查抽血外，我没打过一针，也没打过点滴，只是口服药就控制了病情，三腔积液没了，真得太神奇了。&
& & &回想我得病的整个过程，象做梦一样，因为发病很急。记得日是端午节，
6月5日到7日是法定休息日。6月4日这天我觉得后背肩胛骨空疼，我以为是连续几天操作电脑累的。当时我市凉城县的同志来报账，他们从40多公里的地方来，第二天又要休假，我得给他们审好材料（我市有9个旗县正在实施国际农发基金贷款项目，在罗马报账），就一直坚持着，下午我实在空疼得难受，就让他们操作电脑，我在旁边看，完成了报表的审核。6月5日休息，觉得后背疼痛好多了，难得有这个休息日（因为做这个项目，我们是没有假节日的，有时加班连续24小时，也有一天不吃东西的时候）我包了棕子。6月6日早晨吃了一个棕子，中午吃的是我们当地莜面、土豆做的炖炖（平时没时间做），下午就胃涨。6
月7日还是胃涨，并伴轻微咳嗽。6月8日一上班，我就去当地医院就诊，挂了消化科主任的号，做了B超，拍了胸片，没什么异常，开了些感冒和消化药就回来了。吃了三天药毫无效果，感觉病情没有丝毫好转。我又在门口小门诊就诊，他们认为是感冒打了三天针，仍没效果，病情还在加重。我决定住院治疗，又返回当地医院，经查还是打了助消化治感冒的点滴，点滴打到第三天，我的脚有些浮肿，胃更涨了，我就要求出院了，同事和家人让我去北京看看。在这三进三出的治疗期间，前前后后用药共20多种，时间耽误了一个月，我才决定去北京。7月5日，我在家人的护理下，来到北京301医院消化科就诊，来到北京时，我的脚浮肿得感觉要破了似的，鞋也穿不进去了。一查说有腹水了，接着做了相关的检查。在不能确诊的情况下，以“癌症”的可能性于7月8日住进了309医院普外科，从7月5日-31日，这25天的时间里，我的家人为我走访了北京肿瘤医院、空军总医院和北京协和医院，他们排队挂号找人（三个人陪我，我的身体状况很差，行动已不方便了），太辛苦了！我看到我妹夫四处奔波求医不易，我妹妹鬓角头发明显变白，女儿站在我床前无奈不语的表情，看着我病情确诊不了他们很无助，他们的心情和压力比我重。我吃不下饭，他们也吃不好，我心疼他们，我要放弃治疗，我要回家。一听说我要回家，我老家的弟弟们更着急了，纷纷打来电话或来北京劝我不让我放弃。在我全家人继续出动到处打听，托人给我联系医院时，我又想，为了我的孩子和我的家人，我得坚持，不然我对不起他们。就这样，经朋友和李医生的介绍找到了您。&
& & &我得病已近三年了，现在我病情平稳，服用的药物有硫酸羟氯喹片1粒/天（0.1g）和白芍总苷胶囊1粒/天（0.3g）。日我停服了甲泼尼龙片。2013年10月复查时，手指夜间有点僵，早晨起来就好了，您给我增加了白芍总苷胶囊2粒/天，吃了一段时间有点腹泻，我又改回了1粒/天。我想顺便问问您，我手指不僵了，要不要停药？本来按与您的约定，我该去复查了，因现在我感觉还可以，想过段时间再去。我从去年4月份开始跳广场舞了，每天早、晚各跳一个半小时，是不是活动量太大了？我准备早晨不去了。现在，我会跳100多个广场舞曲，成为我们120多人广场舞队的领舞之一。我能恢复到今天，是您的功劳，是我身边关心我的亲人和朋友们给我的支持，我再次衷心地谢谢您！也谢谢您团体的成员，我们的朋友李医生！我会随时关注“中国风湿病公众论谈”微信和您的博客，成为您忠实的读者。刘主任祝您事业更有成就，身体永远健康！&
& & &您的内蒙古患者：微波名自由（） && & &回复& & &赵女士：& & &您好！感谢你来信分享你患病的诊治过程及好转后的喜悦！你的成功救治对很多类似风湿病患者很有启发性和教育意义，必将给他们带来信心和勇气。你通过积极有效的治疗，病情得到控制，已停用激素1年多，仅留羟氯喹和白芍总苷，还能跳广场舞了，由衷为你感到高兴！&&&&& 你的主要症状是多浆膜腔积液及全身水肿，曾住309医院，并在北京多家权威医院会诊，怀疑“恶性肿瘤”。的确，多浆膜腔积液的主要原因就包括恶性肿瘤，随着我国环境污染的加重，肿瘤发病率直线上升，加上你的年龄较大，一般情况不好，因吃不好饭而体重又明显降低，自然让医生首先考虑到肿瘤的可能性。不过，引起多浆膜腔积液的原因除肿瘤以外，还需要考虑我们的风湿免疫病，尤其是系统性红斑狼疮和未分化结缔组织病等，我们结合你的实验室检查等综合判断，最终诊断为未分化结缔组织病，进行了积极治疗，终于转危为安！值得庆贺！& & & 所谓未分化结缔组织病，就是尚不能满足某具体结缔组织病（如类风湿关节炎、系统性红斑狼疮、系统性硬化症、多肌炎/皮肌炎、血管炎和干燥综合征等）的诊断或分类标准，但又有这些结缔组织病部分特点（如关节肿痛、肌痛、肌无力、雷诺现象、口眼干燥和光过敏等）的疾病，其化验也常无特征性自身抗体。本病也许是某一种结缔组织病的早期，如果不有效控制，可继续发展，转化为某一具体的结缔组织病。&
& & &你所使用的药物包括激素、羟氯喹和白芍总苷，应该还有预防骨质疏松的钙剂和维生素D。目前激素已停用1年多，病情仍保持稳定，不过，羟氯喹还是不建议停，其长期使用对预防本病的继续发展很有好处。你服用白芍总苷每日2片即出现腹泻，1片就好转消失，该药的个体差异挺大，主要副作用就是腹泻，可通过减少药物剂量或加复方甘草片消除，不过，某些平时便秘的风湿病患者尤为适合。&
& & &长期使用激素确实会带来很多的不良反应，因此，去年有研究者针对狼疮患者的治疗提出“无激素时代”概念，这些狼疮患者应用生物制剂美罗华和吗替麦考酚酯联合治疗，而不加激素，结果发现，病情控制良好，复发率比较低。不过，其随访多年后的情况尚不得而知，需要进一步的研究。你还不属于狼疮患者，故停用激素未尝不可，但需要定期复诊复查，随时观察病情变化，调整方案。& & & 跳广场舞是一种非常好的锻炼方式，身体随着优美的音乐运动，既使人心情愉悦，又能增强人体体质，值得推广。不过，要把握几点，第一，最好不要在空气污染重的地方如马路边（汽车尾气多）锻炼，第二，锻炼应循序渐进和持之以恒。第三，不要影响邻居的休息。
最后，祝你保持充足的信心，长期坚持规范治疗，最终战胜病魔！
&& & &朱桂华（yeah-） 刘湘源（liu-） &
病例介绍：患者，28岁，女性。以“间断腰痛2年，加重7月”之主诉入院。
现病史：患者2年前无明显诱因出现腰痛，呈锐痛，无双下肢放射痛。疼痛于翻身时加重。伴有晨僵，持续1-2分钟，活动后可缓解。逐渐双下肢站立不稳。此后症状反复发作，未做特殊治疗。1年前患者跌倒后上述症状加重，同时出现双侧肋骨疼痛，呼吸轻度受限，未予特殊诊治。9月前患者于按摩过程中给予轻度外力时出现腰痛，伴有全身僵硬，紧缩。全程意识清楚，伴有头痛和恶心，无呕吐。伴有畏光、畏声，持续8分钟左右自行缓解。就诊于当地医院，行腰椎MRI提示腰椎间盘突出。予以牵引理疗等治疗后，症状较前好转，但仍有腰痛发作，疼痛症状减轻，伴有双下肢乏力。7月前上述症状再发，程度、性质、持续时间、诱因同前。并出现双膝关节、髋关节疼痛，以左髋关节疼痛较重。掌指关节、指间关节活动时疼痛。就诊于当地医院，完善骨穿检查，结果未见异常。予以对症治疗，具体未明。患者症状仍反复发作，现为求进一步诊治收住我院。患者病程中无发热、皮疹，无口腔溃疡、雷诺现象，有眼干，哭泣有泪，脱发，每天5根左右。患者精神可，睡眠差，大、小便正常，体重无明显减轻。
入院查体：T 36.8℃，P 68次/分，R16次/分，Bp 120/80mmHg。神清，精神可。双肺呼吸音清，未闻及明显的干湿罗音。心律齐，心音强而有力。各瓣膜听诊区未闻及杂音。腹软，无压痛。双下肢无水肿。胸椎、腰痛压痛、叩击痛。双侧颈部、肩部、腰部、臀部、肘关节、膝关节压痛，余关节未见红肿变形。4字试验阳性，直腿抬高试验阳性。患者无法配合，未行胸廓活动度试验。
辅助检查：以下均为外院检查。
腰椎椎体平扫CT 腰5-骶1间盘突出。
胰腺CT 未见明显异常。 骶髂关节CT 骶骨及双侧髂骨面内多发小灶低密度伴双侧骶髂关节面毛糙。
肺部CT 未见明显异常。 抗核抗体谱 阴性。 HLA-B27 阴性。 风湿系列 ASO RF CRP 阴性。 尿轻链检查 尿免疫球蛋白轻链K 43.8 尿免疫球蛋白轻链λ 6.59 尿K/尿λ=6.65 。电解质 K=3.80mmol/L Na=135.7mmol/l，Cl=107.1mmol/L ，P=0.55mmol/L，Ca=2.26mmol/L 。
骨髓部分中性粒细胞为感染性改变，其余未见异常。
传染肝炎系列监测
第4腰椎、双侧骶髂关节股骨头区骨代谢异常活跃。
腹部超声：肝胆胰脾肾未见明显异常，双侧肾上腺未见明显异常。
布氏杆菌凝集实验
初步诊断：腰痛原因待查：腰椎间盘突出；低磷血症
入院后完善的化验及检查：血镁、血常规、尿常规、电解质（血钾、血钠、血氯、总二氧化碳）、肝功、肾功、粪便常规未见明显异常。全身+局部骨显像：多发骨软骨炎、终板炎，考虑代谢性疾病可能性大，请结合临床注意钙、磷、维生素D及粘多糖代谢情况，感染性及免疫性亦不除外。双侧股骨头坏死？建议活检。
入院后给予的治疗：改善骨代谢：骨化三醇 0.25ug bid；肌肉松弛剂：巴氯芬 5mg tid ；治疗疼痛：普瑞巴林 75mg
查房目的：确定低磷血症病因；指导下一步治疗方案
&& 如下PDF文件文章发表在《中国医学论坛报》日周四的A6版上，为我科金银姬、姚中强和刘湘源大夫答复辽宁抚顺第三人民医院大夫的来信。
RA患者停用恩利治疗后长期维持临床缓解不是梦
摘要（日本）：肿瘤坏死因子抑制剂的出现使得类风湿关节炎的治疗目标不仅仅是阻止骨破坏的发生，而是诱导疾病缓解。在此，我们报道了两例停用依那西普治疗后长期维持缓解的RA病例。两例患者的年龄分布是27和38岁，疾病持续时间分别是6和14个月。治疗前的疾病活动度评分（DAS28）分别是4.43和5.07。第二例患者在先前接受英夫利昔单抗治疗时出现了抵抗现象。两例患者均对依那西普临床反应良好，并且分别在用药15和14个月时停用了依那西普。停用依那西普后一直没有发现关节炎病情的加重，DAS28评分始终在2.6以下。此外，停用依那西普后，影像学进展不明显，两例患者均在至少1年内观察到了改良的Sharp评分的下降。这些资料表明对于某些RA患者来说停用依那西普治疗后临床和影像学长期维持缓解是可以实现的。
附原文：Abstract
The appearance of tumor necrosis factor
blockers changes the treatment goal of rheumatoid arthritis (RA) to include not
only the inhibition of bone destruction, but also the induction of remission.
We, herein, report two cases with RA that showed a prolonged remission after
the discontinuation of etanercept. The two cases were 27 and 38 years of age, and
their disease durations were 6 and 14 months, respectively. Their disease
activity score 28 (DAS28) before treatment were 4.43 and 5.07, respectively. Case
two was resistant to infliximab as determined by previous treatment with this
therapy. Both cases showed a dramatic clinical response and discontinued
etanercept in the 15th month and the 14th month after the start of treatment,
respectively. No exacerbation of arthritis was evident after the
discontinuation of etanercept as supported by the maintenance of DAS28 at less
than 2.6. Moreover, after the discontinuation of etanercept, radiographic
progression was not evident and decreased modified Sharp scores were observed
for at least 1 year in both cases. These findings indicate that clinical and
radiographic remission is possible in some patients with RA after the
discontinuation of etanercept.
引自：Tomoya Miyamura & Koshiro Sonomoto &Masataka
Nakamura & Yoshiro Horai & Soichiro Takahama & Hitoshi Ando &
Rumi Minami & Masahiro Yamamoto & Eiichi Suematsu. Discontinuation of etanercept in patients with rheumatoid
arthritis who were in clinical remission. Clin Rheumatol,–90.
抗核糖体P蛋白抗体是自身免疫肝炎的新抗体
摘要：背景:抗核糖体P蛋白(anti-rib P)抗体是系统性红斑狼疮(SLE)特异的血清学标志物并与SLE出现肝损伤相关联。因自身免疫性肝炎(AIH)和SLE-相关的肝炎之间有的相似的自身免疫性背景，故增加了anti-rib P抗体成为AIH相关抗体的可能性。
目的:评估anti-rib P抗体在大型AIH队列出现的频率和临床意义。
方法:采集96例诊断AIH的患者和82名健康对照的血清，用ELISA方法检测IgG型anti-ribP抗体。所有的血清均检测狼疮其他特异性自身抗体,三个患者因存在anti-dsDNA(n = 1)和anti-Sm(n = 2)被排除在外。
结果:9.7%(9/93)的AIH患者检测到中度到高滴度的anti-rib P(& 40 U)抗体而对照组没有检出(P = 0.003)。在临床表现中,AIH患者有和没有anti-rib P抗体组有类似的人口学及临床特征,包括肝硬化的频率(44.4和28.5%,P = 0.44),肝实验的结果(P & 0.05)。重要的是,在最后的观察(随访时间10.2±4.9年),存在anti-rib P抗体的 AIH患者较阴性组肝硬化的频率显著升高(100 vs 60%,P = 0.04)。
结论:研究显示anti-rib P抗体阳性的 AIH患者即使没有临床或实验室证据表明存在系统性红斑狼疮，但有一个共同的肝病发病机制。此外,这种抗体的存在似乎提示AIH患者的预后更差。
附原文：BACKGROUND: Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE-associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH.AIMS: To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort.METHODS: Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n = 1) and anti-Sm (n = 2) were excluded.RESULTS: Moderate to high titres (&40 U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P = 0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4 vs. 28.5%, P = 0.44), hepatic laboratorial findings (P & 0.05). Importantly, at the final observation (follow-up period 10.2 ± 4.9 years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared with the negative group (100 vs. 60%, P = 0.04).CONCLUSION: The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses.
引自：Calich AL, Viana VS, Cancado E,et al. Anti-ribosomal P protein: a novel antibody in autoimmune hepatitis.Liver Int. ):909-13.
甲氨蝶呤联合来氟米特治疗类风湿关节炎的安全性研究
摘要：目的：在临床实践中对甲氨蝶呤(MTX)和来氟米特(LEF)联合治疗类风湿关节炎和MTX单药治疗的安全性进行评估
方法:MTX联合LEF治疗类风湿关节炎的安全性研究（SMILE）是一个多中心、观察性、横断面的回顾安全性研究。这项研究是由澳大利亚风湿病倡议用药质量及预期结果部门(OPALQUMI)主导的。数据来自13个参与单位的25名风湿病医生对患者临床和临床前的数据进行收集。对不同治疗方法的安全进行比较分析,主要对中性粒细胞减少和肝异常进行安全性观察。
结果:总共2975名患者纳入研究:74%为女性,26%为男性,平均年龄62岁(SD13.6)。用药情况:MTX单药治疗占52.2%,LEF治疗占7.3%,MTX加LEF 占13.9%,非MTX非LEF占26.6%。有肝脏疾病的患者为8.1%。其中MTX单药治疗组12%患者报告肝功能异常，LEF单药治疗组为16%,MTX-LEF联合治疗组为19%,非MTX及LEF组为14%。2.3%的MTX单药治疗组患者报道中性粒细胞减少,LEF单药治疗组为5.5%,MTX-LEF联合治疗组为3.9%,非MTX及LEF组为4.2%。
结论:通过和单药治疗组及非生物制剂的其他抗风湿药物治疗组的不良事件相比较，MTX和LEF联合治疗的耐受性良好。
附原文：OBJECTIVE: To assess the safety of treating patients with rheumatoid arthritis with a combination of methotrexate (MTX) and leflunomide (LEF) in comparison to MTX monotherapy, in clinical practice.METHODS: The Safety of Methotrexate in Combination with Leflunomide in Rheumatoid Arthritis (SMILE) study was a multicenter, observational, cross-sectional, retrospective safety study. The study was conducted by the Optimising Patient Outcomes in Australian Rheumatology-Quality Use of Medicines Initiative (OPAL QUMI). Data were deidentified for patient, clinic, and clinician prior to collection from 13 participating rheumatology practices (25 rheumatologists). Comparative analysis of safety for the different treatments, primarily with regard to neutropenia and liver abnormalities, was performed.RESULTS: In total, 2975 patients were included in the study: 74% female, 26% male, mean age 62 years (SD 13.6). Distribution of therapy: MTX monotherapy 52.2%, LEF monotherapy 7.3%, MTX plus LEF 13.9%, and neither MTX nor LEF 26.6%. Comorbid liver disease was reported in 8.1% of patients. Liver function abnormalities were reported in 12% of the MTX monotherapy group, 16% of the LEF monotherapy group, 19% of the MTX-LEF combination group, and 14% of the group not taking either drug. Neutropenia was reported in 2.3% of the MTX monotherapy group, 5.5% of the LEF monotherapy group, 3.9% of the MTX-LEF combination group, and 4.2% of the group not taking either drug.CONCLUSION: The combination of MTX and LEF was well tolerated, with adverse events comparable to those of monotherapy and the other nonbiologic disease-modifying antirheumatic drug treatment group.
引自：Bird P, Griffiths H, Tymms K,et al. The SMILE study -- safety of methotrexate in combination with leflunomide in rheumatoid arthritis.J Rheumatol. ):228-35.
病例介绍：患者,女性,48岁。发现双手雷诺现象20余年，口眼干5年余住院。患者20余年出现双手遇冷时发白，保暖后变红变紫，伴有指端至掌指关节皮肤僵硬，不易捏起，伴有双手触觉消失，温度觉及疼痛觉减退。无呼吸困难，无夜尿增多。5年前出现口干、眼干，吞咽干食时困难，需饮水辅助吞咽，伴有多发龋齿及牙齿发黑片状脱落。近2年出现出现间断反酸、烧心及呕吐，食欲及体重下降，外院行胃镜检查诊断为反流性食管炎，给予抑酸及促胃肠动力药物治疗后症状好转。偶有左膝关节及双侧大腿内侧肌肉疼痛，无关节肿胀及变形。伴有光过敏，无皮疹，无发热，无咳嗽、咳痰，无活动后气短，无心慌，无腹痛、腹泻，无乏力，无尿频、尿急、尿痛，无口腔溃疡，无脱发。就诊于我院急诊，ANA散点型1：320，斑点型1:80，抗ACA及抗SSA阳性，为求进一步治疗收入院。自发病以来，精神不佳，饮食差，睡眠尚可，大小便正常，2月体重减轻10kg。
既往史及家族史：既往体健。否认吸烟、饮酒史，否认高血压、糖尿病、心脏病及脑血管病史
。否认家族性遗传病史。
入院时查体：T 36. 0℃，P 76次/分，R15次/分，Bp 100/60mmHg，营养不良，全身皮肤黏膜无黄染，猖獗龋齿，唾液池无唾液，甲状腺未触及肿大，双肺呼吸音清，未闻及干湿性啰音，心律齐，各瓣膜听诊区未闻及杂音。腹部凹陷，无腹壁静脉曲张，剑突下压痛，无反跳痛，腹部无包块。肝脾未触及，Murphy氏征阴性，肾区无叩痛，移动浊音界阴性。脊柱正常生理弯曲，四肢活动自如，双手皮温降低，手背可见网状青斑，手指硬肿，远端指间关节有压痛，近端指间关节肿胀，双下肢无浮肿。四肢肌力及肌张力未见异常，双手指及肘关节触觉消失，位置觉、痛觉及温度觉减退，右侧为著，双下肢踝关节及膝关节平面触觉消失，位置觉、痛觉及温度觉减退，右侧明显。后背右侧肩胛部位可见痛觉减退，双侧肱二头肌及肱三头肌反射未引出，双侧膝、跟腱反射未引出。右侧巴氏征阳性。
入院前辅助检查：自身抗体：ANA散点型1：320，斑点型1:80，anti-dsDNA阴性，抗SSA阳性，抗SSB阴性，抗Sm阴性，抗rRNP阴性，抗JO-1阴性，抗SCL-70阴性，抗ACA阳性，抗CCP阴性，抗ACL-IGM阴性。ANCA阴性，MPO-ANCA阴性，PR3-ANCA阴性。
免疫球蛋白七项:CH50 47U/L, IgG10.6g/L, IgA 2.97 g/L，IgM0.88 g/L, IgE0.37
g/L,C30.5 g/L, C4 0.29 g/L。风湿三项：ASO阴性，RHF 37.6IU/ml,CRP 0.33mg/dl, ESR 31mm/HR。甲状腺功能：FT3
1.6pg/ML, FT4 1.04 ng/dl, TSH 1.54 uIU/ml。肿瘤标志物：AFP 2.61ng/ml， CA153 6.95 IU/ml,
CEA 0.86 ng/ml， CA125 19.82U/ml, CA199 6.84 U/ml。胸部正位：右肺纤维硬结灶？支扩？建议进一步检查。双上肢动脉彩超：未见异常。腹部彩超：餐后胆囊，余未见异常。超声心动图：心内结构大致正常，LVEF74%。腹部CT:肝小血管瘤？膀胱结石？
入院诊断：系统性硬化症；继发干燥综合征；周围神经病变；反流性食管炎。
入院后辅助检查：血常规：WBC 4.70*109/L, RBC .27*1012/L，HGB 113G/L,PLT 211*109/L，凝血功能：PT
10.0s, PTA 112%, FIB 4.32, APTT 35.6S。肝肾功能：ALT 27U/l, AST
21U/L, TBIL 7.4mmol/L, DBIL 2.6mmol/L,BUN 4.7umol/L, CR 48umol/L。叶酸 ：4.9ng/ml，维生素B12 204 ng/ml。心磷脂抗体-IgG 阴性，RPR阴性，β-GP1
IgM/IgG阴性，狼疮抗凝物阴性。脑脊液检查：生化及常规未见明显异常，涂片找结核菌、细菌及真菌阴性，抗脑组织抗体阴性。
血结核抗体阴性，TBSPOT 阳性。心电图：胸部导联可见T波低平倒置。胸部CT: 右肺上叶见片状、斑片状高密度影，边缘模糊，内可见支气管充气征；左肺下叶背段间小片状高密度影，边缘清晰。纵膈内可见多发肿大淋巴结，大者约13*10mm。心包少量积液。颅脑CT:头颅CT未见异常。静息门控心肌灌注显像：左心室各壁未见心肌严重缺血或心肌梗塞表现，左心室收缩功能大致正常，室壁运动未见明显异常。肌电图检查：双正中神经、双尺神经及双腓肠神经SNAP未测出。左胫神经H反射潜伏期延长，左第一骨间肌示神经源性损害，双上下肢深感觉径路传导阻滞。骨密度：骨质疏松。气管镜检查：右肺上叶开口可见色素沉着，开口呈瘢痕样挛缩。管腔相对狭窄，气管镜无法通过，可见少量脓性分泌物。
入院后治疗：给予羟氯喹及帕夫林治疗。给予耐信抑酸、吗丁啉促进胃肠动力。给予维生素B1及弥可保营养神经，凯时及丹参滴丸改善微循环。给予碳酸钙及骨化三醇补钙治疗。
查房目的：1.明确周围神经病变病因，指导治疗。2.明确肺部病变性质，指导治疗。
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