系统性硬化病合并原发性胆汁性肝硬化的临床分析及文献复习

目的 探讨系统性硬化病(SSc)合并原发性胆汁性肝硬化(PBC)患者的临床特征,提高对此重叠综合征的认识.方法 收集北京协和医院2005年4月至20l0年4月确诊为SSc合并PBC的病例资料,对符合条件的9例患者的临床表现、实验室检查和组织病理检查进行分析.同时进行文献复习,与国外资料进行比较.结果 ①9例患者中男性1例,女性8例,平均年龄(54±8)岁;以SSc起病者7例,以PBC起病者2例,二病发生间隔1～8年、平均(4.3±2.3)年.②弥漫型SSc(dcSSc)仅1例,而局限型SSc(lcSSc)8例(完全型CREST综合征2例,不完全型5例),8例有雷诺现象和食管运动功能障碍,并均以雷诺现象起病.有PBC临床表现者5例,亚临床型4例,胆管酶升高8例,2例行肝穿刺病理检查为PBC的Ⅰ和Ⅱ期.③抗核抗体均阳性,抗着丝点抗体(ACA)阳性8例,抗线粒体抗体(AMA)阳性9例,AMAM2阳性8例.④早期给予糖皮质激素和熊去氧胆酸治疗有效,3例因肺间质纤维化、肺动脉高压和肝硬化疗效欠佳.结论 SSc可以合并PBC,以lcSSc、尤其是CREST综合征多见,筛查ACA、AMA、AMA-M2可早期识别SSc合并PBC,早期干预有助改善预后.     

系统性硬化病合并肾危象16例临床分析

目的 通过分析和总结系统性硬化病(SSc)合并肾危象患者的临床资料,以提高临床医生对其的认识.方法 回顾分析2004年5月至2013年5月北京协和医院住院的16例SSc合并肾危象患者的临床、实验室检查结果、治疗和预后.结果 16例SSc合并肾危象患者中男性5例,女性11例;SSc合并肾危象起病年龄为(49.9±12.3)岁,从SSc起病进展为SSc合并肾危象的时间平均为3.2年;弥漫性皮肤型SSc 10例,局限性皮肤型SSc 6例.16例患者抗着丝点抗体均阴性.16例患者在病初均有高血压和肾功能不全,8例病初需要透析,7例有血栓性微血管病.3例行肾活检,病理均见肾脏小血管管壁增厚和管腔狭窄.16例患者3例失访;13例随访患者中,11例接受了规律的血管紧张素转换酶抑制剂治疗,5例死亡,8例存活者中2例需要长期透析,1例在接受血管紧张素转换酶抑制剂联合内皮素受体拮抗剂治疗后脱离透析,5例无需透析.结论 SSc合并肾危象常在SSc病程早期出现,多见于弥漫性皮肤型SSc患者,抗着丝点抗体阳性患者少见.早期足量使用血管紧张素转换酶抑制剂为治疗SSc合并肾危象的基础.内皮素受体拮抗剂在SSc合并肾危象中的治疗作用还需进一步研究.     

抗膜突蛋白抗体与系统性硬化病相关肺间质病变的临床相关性研究

目的 分析抗膜突蛋白抗体与系统性硬化病(SSc)相关肺间质病变(ILD)的临床相关性.方法 纳入参加欧洲抗风湿病联盟硬皮病试验研究组(EUSTAR)的SSc患者62例,采用酶联免疫吸附试验检测患者血清中的抗膜突蛋白抗体.分别根据高分辨CT特征、肺功能指标、炎症指标和病程的差异进行分组,比较不同分组之间抗膜突蛋白抗体的阳性率和滴度(吸光度值).计量资料采用独立样本t检验和非参数秩和检验,计数资料采用χ2检验.结果 SSc-ILD组的抗膜突蛋白抗体滴度(0.156±0.062)高于无ILD组(0.107±0.026),差异有统计学意义(P=005).在SSc患者中,检测抗膜突蛋白抗体对于诊断其合并ILD的敏感性为44.0%,特异性为91.7%(Kappa=0.2,P=0.022).肺高分辨CT上具有蜂窝样变、小叶间隔增宽及纵隔淋巴结肿大特征的SSc患者抗膜突蛋白抗体的阳性率显著高于不具上述特征者,差异均具有统计学意义(P<0.05).在肺总量(TLC%)减低组的患者中,该抗体的滴度(0.172±0.067)高于正常组(0.133±0.039).差异有统计学意义(P=0.011),一氧化碳弥散量(DLco%)减低组患者的抗体滴度(0.153±0.580)亦高于对照组(0.120±0.340),但差异无统计学意义(P=0.089).抗膜突蛋白抗体的阳性率在红细胞沉降率、C反应蛋白、免疫球蛋白和补体增高组与正常组间的差异无统计学意义(P>0.05).SSc病程≤5年组与>5年组的抗膜突蛋白抗体滴度差异无统计学意义(P=0.272),但ILD病程≤12个月者的抗体滴度(0.182±0.073)显著高于病程>12个月者(0.138±0.049),差异有统计学意义(P=0.040).结论 抗膜突蛋白抗体在SSc相关的ILD患者有较高的特异性,可能为揭示SSc-ILD的发病机制提供了新的线索.在SSc患者血清中检测该抗体对于早期筛查和评估ILD的价值值得进一步验证.     

系统性红斑狼疮并发肺动脉高压1例并文献复习

目的提高对系统性红斑狼疮（SLE）并发肺动脉高压（PHT）的发病机制、临床表现、治疗及预后的认识。方法对1例并发PHT的SLE病例进行分析和讨论,并结合相关文献复习。结果SLE并发PHT的机制尚不明确。其临床表现无特异性,早期症状多为呼吸困难。SLE患者出现雷诺征时,应高度怀疑PHT的存在。大剂量糖皮质激素联合免疫抑制剂可显著降低PHT。结论SLE并发PHT常提示预后不良,应尽早诊断及治疗。针对原发病的强化治疗可有效降低PHT。     

系统性硬化病继发扩张型心肌病一例

SSc是一种免疫介导的CTD,其特征是皮肤和内脏纤维化以及微血管病变,常见的受累脏器包括皮肤、胃肠道、肺、心、肾。本研究报道1例SSc所致心肌纤维化,继发扩张型心肌病、心功能不全[纽约心脏病协会（NYHA） Ⅳ级],表现为胸闷气促、皮肤硬化、雷诺现象和肺间质病变,抗Scl-70抗体阳性,并携带肌球蛋白重链7（MYH7）...     

抗膜突蛋白抗体与系统性硬化病相关肺间质病变的临床相关性研究

Objective To identify a novel auto-antibody in sera of systemic sclerosis (SSc) patients and to analyze its relevance with SSc-associated interstitial lung disease (ILD). Methods The anti-moesin antibody in the sera of 62 SSc patients, who had participated the European League Against Rheumatism's Scl eroderma Trial and Research Group (EUSTAR), were tested by enzyme linked immunosorbent assay (ELJSA). Patients were grouped by high resolution computerized tomography (HRCT) features, pulmonary function test (PFT) abnormalities, inflammatory markers and disease course. The prevalence and titer (Optical density value) of anti-moesin antibody were compared between groups with t and χ2 test. Results The titer of anti-moesin antibody was significantly higher in the SSc-ILD group than non-ILD group (0.156±0.062 vs 0.107± 0.026, P=0.005). Among SSc patients, the diagnostic sensitivity and specificity of the anti-moesin antibody for ILD was 44.0% and 91.7% respectively (Kappa=0.2, P=0.022). Anti-rnoesin antibody was more prevalent in SSc patients with HRCT features of honeycomb-like lesion, lobular septal thickening and mediastinal lymphadenopathy (P<0.05). SSc patients with deteriorated total lung volume (TLC %) had higher titer of anti-moesin antibody significantly (0.172±0.067 vs 0.133±0.039, P=0.011), as the same tendency in patients with decreased diffusing capacity of the lung for carbon monoxide (DLco% ) but without statistical significant difference (0.153±0.580 vs 0.120±0.340, P=0.089). The anti-moesin antibody was equally prevalent between abnormal ESR, C reactive protein, immunoglobulin and complements groups and their normal controls (P> 0.05). Group of patients who had SSc courses more than or less than 5 years demonstrated similar anti-moesin antibody titers (0.146±0.047 vs 0.164±0.077, P=0.272). However, patients with ILD courses less than 12 months had higher liter of the antibody than controls (0.182±0.073 vs 0.138±0.049, P=0.040). Conclusion This study suggests that the novel anti-moesin antibody has comparatively high specificity for SSc-associated ILD patients, which may contribute to further understanding the pathogenesis of ILD in SSc patients. Further investigations are deserved to evaluate the application of anti-moesin antibody in facilitating early screening and evaluation of ILD.     

抗膜突蛋白抗体与系统性硬化病相关肺间质病变的临床相关性研究

Objective To identify a novel auto-antibody in sera of systemic sclerosis (SSc) patients and to analyze its relevance with SSc-associated interstitial lung disease (ILD). Methods The anti-moesin antibody in the sera of 62 SSc patients, who had participated the European League Against Rheumatism's Scl eroderma Trial and Research Group (EUSTAR), were tested by enzyme linked immunosorbent assay (ELJSA). Patients were grouped by high resolution computerized tomography (HRCT) features, pulmonary function test (PFT) abnormalities, inflammatory markers and disease course. The prevalence and titer (Optical density value) of anti-moesin antibody were compared between groups with t and χ2 test. Results The titer of anti-moesin antibody was significantly higher in the SSc-ILD group than non-ILD group (0.156±0.062 vs 0.107± 0.026, P=0.005). Among SSc patients, the diagnostic sensitivity and specificity of the anti-moesin antibody for ILD was 44.0% and 91.7% respectively (Kappa=0.2, P=0.022). Anti-rnoesin antibody was more prevalent in SSc patients with HRCT features of honeycomb-like lesion, lobular septal thickening and mediastinal lymphadenopathy (P<0.05). SSc patients with deteriorated total lung volume (TLC %) had higher titer of anti-moesin antibody significantly (0.172±0.067 vs 0.133±0.039, P=0.011), as the same tendency in patients with decreased diffusing capacity of the lung for carbon monoxide (DLco% ) but without statistical significant difference (0.153±0.580 vs 0.120±0.340, P=0.089). The anti-moesin antibody was equally prevalent between abnormal ESR, C reactive protein, immunoglobulin and complements groups and their normal controls (P> 0.05). Group of patients who had SSc courses more than or less than 5 years demonstrated similar anti-moesin antibody titers (0.146±0.047 vs 0.164±0.077, P=0.272). However, patients with ILD courses less than 12 months had higher liter of the antibody than controls (0.182±0.073 vs 0.138±0.049, P=0.040). Conclusion This study suggests that the novel anti-moesin antibody has comparatively high specificity for SSc-associated ILD patients, which may contribute to further understanding the pathogenesis of ILD in SSc patients. Further investigations are deserved to evaluate the application of anti-moesin antibody in facilitating early screening and evaluation of ILD.     

系统性硬化病合并原发性胆汁性胆管炎并发门静脉高压症12例临床特点分析

目的 总结分析系统性硬化病(SSc)合并原发性胆汁性胆管炎(PBC)并发门静脉高压症患者的临床特征。方法 2010年1月～2022年3月于首都医科大学附属北京佑安医院住院的SSc合并PBC并发门静脉高压症患者12例,分析其临床表现、实验室、腹部影像学和胃镜检查等临床资料。结果 5例患者因呕血和/或黑便为首发症状就诊;8例患者SSc诊断早于PBC诊断;10例患者血红蛋白(HGB)下降,9例PLT下降,8例GGT和ALP升高,表现出胆汁淤积现象;10例患者具有电子胃镜检查结果,提示均存在食管静脉曲张;CT/超声检查提示均有脾肿大,8例提示有侧支循环形成,9例有腹水。结论 SSc合并PBC并发门静脉高压症患者临床表现与PBC患者相似,门静脉高压症表现较为明显,胆汁淤积较转氨酶升高更为明显,在诊断SSc后应积极完善PBC诊断的相关检查,早期诊断,早期干预,可能会进一步改善疾病的不良结局。     

系统性红斑狼疮合并脊髓病变10例临床分析及文献回顾

  目的 探讨系统性红斑狼疮（SLE）合并脊髓病变的临床特点、治疗方法及预后。方法回顾性分析北京大学人民医院风湿免疫科1990—2011年住院的10例合并脊髓病变的SLE患者的临床资料,并进行文献复习。结果 10例SLE合并脊髓病变的患者均为女性,年龄23～53岁,病程1～18年。3例患者行脊髓MRI检查,其中1例表现为胸8、胸9椎体内有小类圆形长T2信号影,2例表现为正常信号。10例患者中7例接受甲泼尼龙冲击联合免疫抑制剂治疗,2例单用甲泼尼龙冲击治疗,1例接受甲泼尼龙、环磷酰胺及血浆置换治疗,4例完全缓解,4例部分缓解,2例无明显缓解。结论 脊髓病变是SLE较少见的严重并发症之一,多于SLE早期发病,发病年龄小,预后差。糖皮质激素冲击联合环磷酰胺治疗有效,早期积极干预有助改善预后。     

系统性红斑狼疮合并肺动脉高压36例临床分析

目的 分析系统性红斑狼疮(SLE)并发肺动脉高压(PAH)的发生率、临床特点及预后影响因素.方法 对312例SLE患者的临床资料进行回顾性分析.结果 本文合并PAH 36例(11.5%),雷诺现象、抗U1RNP阳性率、SLEDAI评分和肺间质病变与PAH严重程度有关.结论 SLE是自身免疫性疾病中合并PAH的较常见疾病,超声心动图及相关检查有利于早期诊断.     

A case of systemic sclerosis complicated by idiopathic portal hypertension: case report and literature review

We encountered a 62-year-old woman who had systemic sclerosis (SSc) complicated by idiopathic portal hypertension (IPH). She had a 10-year history of scleroderma and Raynaud's phenomenon. She also had pancytopenia, splenomegaly, and esophageal varices. Treatment with prednisolone and endoscopic variceal ligation resulted in improvement of her symptoms. According to our literature review, the prognosis of patients with SSc complicated by IPH is relatively poor. However, the factors that predict outcome of these patients have not been elucidated.     

Suppressive effect of saprogrelate hydrochloride on Raynaud's phenomenon and respiratory failure in patients with systemic sclerosis

OBJECTIVE: In seven patients with systemic sclerosis (SS), we evaluated the clinical effectiveness of oral administration of saprogrelate hydrochloride (SH: 300 mg/day) for 2 months on Raynaud's phenomenon (RP) and respiratory failure estimated by Hugh-Jones classification. METHODOLOGY: We evaluated laboratory data (arterial blood gas (pH, PaO2 and PaCO2), pulmonary function tests (%VC, FEV1/FVC and %DL(CO)), mean pulmonary arterial pressure (mPAP), white blood cell count, C-reactive protein and the plasma levels of fibrinopeptide A (FPA), beta-thrombogloblin (beta-TG), platelet factor 4 (PF4) and thrombomodulin (TM)) before and after SH administration. RESULTS: The frequency and duration of RP, as well as the coldness, numbness and pain of RP were significantly decreased after SH administration (P < 0.05, P < 0.01 and P < 0.001). Respiratory failure estimated by Hugh-Jones classification was also significantly decreased after SH administration (P < 0.05), and the %DL(CO) was significantly increased (P < 0.01). The mPAP decreased significantly after SH administration (P < 0.05). Plasma FPA, beta-TG and PF4 significantly decreased after administration (P < 0.05 and P < 0.01). CONCLUSIONS: SH therapy could prevent RP and respiratory failure in patients with SS.     

The association between homocysteine and systemic sclerosis: A review of the literature and meta-analysis

Objectives: The main objective of this study was to summarize the existing evidence and quantitatively evaluate whether serum/plasma levels of homocysteine (Hcy) were associated with sclerosis (SSc) diseases by performing a meta-analysis of previous studies.

Methods: PubMed, Elsevier ScienceDirect and Cochrane Library databases were used to obtain all relative published literatures. Stata version 11.0 (StataCorp, College Station, TX) was used for statistical analysis. The effect size of each study was calculated by the standardized mean difference (SMD) with 95% confidence interval (CI) or quartiles.

Results: A total of eight studies including 475 cases and 265 controls were finally included in this meta-analysis. We found significant between-study heterogeneity and conducted analyses using random-effects models. No significant association was found between the serum levels of Hcy and SSc (pooled SMD?=1.382?μmol/L, 95%CI?=??0.442 to 3.206, p?=?.137), but there are two outlier studies that deviate significantly from most other studies, which made it difficult to generalize these results. After excluding these two studies, six studies were included in the meta-analysis. The results showed that the serum levels of Hcy in SSc were significantly higher than that in healthy controls (pooled SMD?=?1.182μmol/L, 95%CI?=?0.230–2.134, p?=?.015).

Conclusion: Serum/plasma levels of Hcy in SSc diseases were higher than that in healthy controls.     

Optic neuropathy as a presenting feature of systemic lupus erythematosus: two case reports and literature review

Systemic lupus erythematosus (SLE) may affect the eyes and/or visual system in up to a third of patients; however, optic nerve involvement has been rarely reported. SLE presenting as optic neuropathy is exceptional. We report two new cases of optic neuropathy as a presenting feature of SLE. The first patient presented with an ischemic optic neuropathy and antiphospholipid antibodies, and the second presented with optic neuritis. A literature review for previous cases of SLE presenting as optic neuropathy was performed. Early diagnosis of SLE-associated optic neuropathy is warranted and leads to a better prognosis.     

Incidence and prevalence of systemic sclerosis: a systematic literature review

OBJECTIVES: To determine the incidence and prevalence of systemic sclerosis (SSc) in adults, its epidemiological tendencies over time, and its possible key determinants. METHODS: We performed a systematic literature review using the keywords "systemic sclerosis," "incidence," "prevalence," and "epidemiology." RESULTS: We found 32 articles published from 1969 to 2006 in which the prevalence of SSc ranged from 7/million to 489/million and its incidence from 0.6/million/y to 122/million/y. There were many geographical variations: SSc prevalence was higher in the USA (276/million in 1990) and Australia (233/million in 1999) than in Japan and Europe, where a north-south gradient was also observed (France: 158/million in 2001 and England: 88/million in 2000). In some regions (Ontario, Rome, near London's airports) there was an unusually high number of SSc cases (3, 5, or 1000 times greater than expected), suggesting spatiotemporal clustering, although no key determinants could be identified. Furthermore, there seemed to be a trend toward an increase in the incidence of SSc over time, but this tendency is uncertain due to lack of uniformity in study methods and designs. We also found that susceptibility to the disease differed according to sex, age, and race. CONCLUSION: Uniform clinico-epidemiological studies with standard diagnostic and classification criteria are needed to refine the epidemiological features of SSc. Homogeneous study methods with exhaustive case ascertainment as seen in a "capture-recapture" analysis will also be necessary to obtain reliable data.     

Peripheral neuropathy: a complication of systemic sclerosis

We performed bedside testing for peripheral neuropathy in our systemic sclerosis (SSc) population to determine whether foot care guidelines should be developed for SSc. Twenty consecutive SSc patients and 20 healthy control (HC) patients were evaluated for peripheral neuropathy in both feet using the 10-g Semmes–Weinstein monofilament examination (SWME) and 128 Hz vibration sensation using the on–off method. Independent, blinded, vibratory sensation, and SWME evaluations were performed on each subject by two investigators who had completed a training session to standardize each exam. An additional consecutive 20 patients with type 2 diabetes mellitus (DM) were examined by a diabetologist to compare with peripheral neuropathy prevalence in SSc patients. We examined the inter-rater variability using Cohen’s kappa. We compared SWME and vibratory sensation in SSc to HC using Fisher’s exact. The t test was used to compare duration of disease and modified Rodnan skin score (mRSS) for those with abnormal SWME or vibratory sensation. Two of 20 SSc patients reported sensory foot symptoms consistent with peripheral neuropathy prior to the examination. Inter-rater agreement for both SWME and vibratory sensation was strong (kappa: 0.72 and 0.83, respectively). Two HC and 12 SSc patients demonstrated abnormal vibratory sense (one-sided Fishers’ exact, p?<?0.002). No HC and four SSc patients had abnormal monofilament exams (one-sided Fisher’s exact, p?=?0.053). Neither mRSS (p?=?0.28) nor duration of non-Raynauds (p?=?0.07) symptoms differed between those with peripheral neuropathy and those without. Duration of Raynaud’s symptoms were clinically significantly associated with presence of peripheral neuropathy (p?=?0.04). The prevalence of sensory loss to monofilament in SSc was identical to DM patients (4/20). SSc patients have a considerable prevalence of pedal peripheral neuropathy as detected by loss of vibratory sensation or inability to sense the 10-g SWME. Further studies are indicated to determine if routine screening for neuropathy and subsequent podiatric care for SSc patients with abnormalities can reduce pedal complications.     

以水肿为主要表现的系统性硬化症1例

笔者成功诊断1例76岁男性系统性硬化症患者。本患者主要表现为水肿,发病初期一直未明确诊断,对症支持治疗仅暂时缓解病情。水肿加重后查血清相关自身抗体示抗核抗体阳性,结合皮肤活检病理明确诊断为系统性硬化症。根据文献报道和笔者的临床经验,系统性硬化症临床表现复杂多样,缺乏特异性,早期诊断困难。对于临床上难以解释的水肿,应考虑本病的可能,重视患者皮肤的改变及血清相关自身抗体的检查,及早做出正确诊断。