阿维A与糖皮质激素治疗系统性硬皮病近期疗效初探

系统性硬皮病（SSc）为不明原因的结缔组织病,以细胞外基质成分（主要是Ⅰ、Ⅲ型胶原纤维）过量沉积于皮肤或内脏器官为特征。常规治疗一般选用糖皮质激素、D-青霉胺、秋水仙碱和其他免疫抑制剂等。近年来笔者口使用阿维A治疗SSc取得明显疗效,并与糖皮质激素等药物治疗SSc的近期疗效进行对比,现报告如下。     

阿维A联合脉络宁治疗肢端硬皮病1例

患者男，63岁。因关节酸痛17个月，全身色素沉着12个月，皮肤硬化4个月，于2002年8月14日收入笔者所在医院治疗。17个月前患者无明显诱因出现双侧膝关节和肩关节酸痛，关节无明显红肿，每遇潮湿、寒冷时症状加重；2个月后，全身皮肤出现弥漫性色素沉着，与日晒无关；入院前4个月面部、双侧手足、小腿和前臂皮肤变硬，表皮不能捏起，并呈进行性加     

阿维A对系统性硬皮病成纤维细胞胶原合成及I型前胶原mRNA表达的影响

目的：明确阿维 A 对系统性硬皮病成纤维细胞胶原合成及 I 型前胶原 mRNA 表达的影响。方法：原代培养系统性硬皮病（SSc）患者皮肤成纤维细胞（FB）,使用不同浓度的阿维 A（10-5、10-6、10-7、10-8 mol/ L）作用48 h,用羟脯氨酸法测定胶原的质量浓度,RT-PCR 法 I 型前胶原 mRNA 的表达。结果：阿维 A 实验组 FB 胶原合成及 I 型前胶原 mRNA 的表达较对照组减少,且均与阿维 A 呈浓度依赖性关系。结论：阿维 A 可能通过抑制 FB I 型前胶原基因的表达减少胶原合成。     

阿维A对系统性硬皮病成纤维细胞胶原合成及Ⅰ型前胶原mRNA表达的影响

目的:明确阿维A对系统性硬皮病成纤维细胞胶原合成及Ⅰ型前胶原mRNA表达的影响。方法:原代培养系统性硬皮病(SSc)患者皮肤成纤维细胞(FB),使用不同浓度的阿维A(10~(-5)、10~(-6)、10~(-7)、10~(-8)mol/L)作用48 h,用羟脯氨酸法测定胶原的质量浓度,RT-PCR法Ⅰ型前胶原mRNA的表达。结果:阿维A实验组FB胶原合成及I型前胶原mRNA的表达较对照组减少,且均与阿维A呈浓度依赖性关系。结论:阿维A可能通过抑制FBⅠ型前胶原基因的表达减少胶原合成。     

阿维A及康瑞宝联合复方倍他米松注射液穴位封闭治疗局限性硬皮病18例临床观察

为探索～种新的、合理的治疗局限性硬皮病方案，笔者采用阿维A(重庆华邦制药股份有限公司)口服及康瑞宝(内含洋葱浸液、肝素及尿囊素)外用联合复方倍他米松注射液穴位封闭的三联疗法治疗局限性硬皮病18例，满意效果，现报告如下。     

阿维A对系统性硬皮病患者血清转化生长因子-β1的影响

系统性硬皮病(systemic sclerosis,SSc)是一种以皮肤及各系统胶原纤维进行性硬化为特征的结缔组织疾病.转化生长因子(tansforming growth factor,TGF)β1在SSc发病中起重要作用.     

阿维A酸对系统性硬皮病患者成纤维细胞增殖及分泌TGF—β1的影响

目的：确定阿维A酸对系统性硬皮病患者皮肤成纤维细胞增殖及分泌转化生长因子β1（TGF-β1）的影响。方法：原代培养系统性硬皮病（SSc）患者皮肤成纤维细胞（FB），使用不同浓度的阿维A酸作用48h，四甲基偶氮唑盐（M1T）方法及ELISA法测定阿维A酸对成纤维细胞增殖及分泌TGF-β1的影响。结果：阿维A酸可明显抑制患者皮肤成纤维细胞的增殖，显著减少成纤维细胞TGF-β1的分泌，并具有浓度依赖性。与空白对照组相比，差异有显著性（P〈0．05）。结论：阿维A酸对SSc皮肤成纤维细胞的增殖及TGF—β1的分泌均有显著抑制作用，为其治疗硬皮病提供了理论基础。     

中药联合青霉胺治疗系统性硬皮病疗效观察

目的:研究益气活血温肾中药联合青霉胺小剂量递加疗法治疗系统性硬皮病的疗效及安全性.方法:随机将硬皮病患者分为中药组、西药组、中西药结合组,观察治疗前后的临床表现、实验室检查、肺和食管检查情况,进行临床疗效评价和不良反应观察.结果:中西药结合组对皮肤硬化、关节功能和肺纤维化改善均明显好于中药组和西药组,治疗前后雷诺现象和血内皮素积分差中药组和中西药结合组均大于西药组,血沉在治疗后中西药结合组较其他两组明显降低.中西药结合组治疗有效率较其他两组高,中药组不良反应最小.结论:益气活血温肾中药联合青霉胺小剂量递加疗法治疗系统性硬皮病,对其皮肤硬化、雷诺现象、肺纤维化均有明显的改善,且不良反应较西药组低,疗效亦优于单用中药或西药.     

中西医结合治疗系统性硬皮病疗效观察

系统性硬皮病是一种以结缔组织广泛性、弥漫性硬化和胶原纤维的增生过度为特点的结缔组织疾病。主要表现为皮肤萎缩变硬,并可累及食管、胃肠、肺、心等。其病因和发病机理尚不明确,治疗也较困难。近年来,我们采用中西医结合治疗,收到较好的效果。现选择其中６０例分析...     

伴有血管扩张的局限性硬皮病一例

血管扩张是系统性硬皮病特征性的临床表现,但是少见于局限性硬皮病。本文报道1例57岁女性以毛细血管扩张为突出表现的乳房局限性硬皮病患者。     

Retinoic acid for treatment of systemic sclerosis and morphea: A literature review

Systemic sclerosis and morphea are connective tissue diseases characterized by tightening, thickening, and hardening of the skin, leading to significant morbidity. Unfortunately, current treatment options have limited efficacy for many patients. Cutaneous manifestations of these diseases arise from excess collagen deposition and fibrosis in the skin, through pathogenic mechanisms which have yet to be extensively detailed at the causal immune and cellular levels. Research elucidating the mechanism of action of retinoic acid on collagen production in the skin and case series highlighting the success of retinoic acid on the skin manifestations of systemic sclerosis and on morphea demonstrate its promise as a treatment. Herein they will briefly review the treatment options for both systemic sclerosis and morphea, and will discuss the potential of retinoic acid as a therapy and the supporting evidence from the literature, highlighting the previously published basic science and clinical studies investigating the role of retinoic acid in the treatment of sclerotic skin diseases.     

系统性硬化症163例临床分析

回顾性分析163例系统性硬化症(SSc)患者的临床资料,分析其类型、临床表现、实验室检查及治疗的特点,增加对该罕见病的认识。结果示本组病例中dcSSc 95例,lcSSc 49例,重叠综合征14例,UCTD 4例和sine scleroderma 1例。皮肤表现包括肿胀(18例),硬化(106例),萎缩(11例)。SSc患者163例平均mRSS评分12.0。全身各器官系统均有不同程度受累,雷诺现象最多见(51.0%)。多因素logistic回归分析示球蛋白升高是SSc累及血液系统的独立危险因素。150例患者使用糖皮质激素联合抗风湿药(DMARDs)治疗,13例使用糖皮质激素联合DMARDs及托珠单抗治疗,有一定疗效。     

The polymorphism of telomerase RNA component gene in patients with systemic sclerosis

BACKGROUND: The molecular basis of senescence and immortalization is not still understood, but one hypothesis for which there has recently been much evidence involves the shortening of telomeres. It can be hypothesized that abnormalities of telomerase contribute to the emergence of abnormal fibroblast clones in systemic sclerosis (SSc). OBJECTIVES: To study possible telomere abnormalities with respect to polymorphism of the telomerase RNA component gene. METHODS: Fifty-three patients with SSc and 98 normal controls were studied. Polymerase chain reaction was used to amplify 598 bp of the telomerase RNA component gene. Amplified fragments were digested with restriction enzyme BsrDI. RESULTS: The frequency of the A allele in SSc (41.5%) showed no significant difference from that in the normal controls (32.1%). The frequency of the A/A alleles in SSc (18.9%) was significantly higher than in normal controls (5.1%), compared with G/G (35.8% and 40.8%, respectively; P < 0.02), G/A (45.3% and 54.1%, respectively; P < 0.01) and G/G plus G/A (81.1% and 94.9%, respectively; P < 0.01). CONCLUSIONS: These results showed the possible involvement of a telomerase abnormality in the emergence of abnormal fibroblast clones in SSc skin-derived fibroblasts.     

Arteriographic evaluation of vascular changes of the extremities in patients with systemic sclerosis

BACKGROUND: Although digital ulcerations frequently occur in patients with systemic sclerosis (SSc), there have been few reports on the macrovascular involvement. OBJECTIVES: To evaluate the macrovascular involvement in patients with SSc exhibiting digital ulceration or gangrene. METHODS: Transfemoral catheter arteriography of the upper and/or lower extremities was performed in eight patients (one man and seven women, age range 42-71 years) with SSc exhibiting digital ulceration or gangrene. The background of the patients, such as autoantibody profiles and vascular risk factors including smoking habits, was also investigated. RESULTS: Macrovascular involvement was detected in seven of eight patients. In three of seven patients who underwent arteriography of the upper extremity, occlusion was limited to the digital arteries. Obliteration of the ulnar artery and superficial palmar arch was detected in three of seven patients, and the radial artery in one patient. Only one of five patients who underwent arteriography of the lower extremity showed the occlusion limited to digital arteries of the foot. Occlusion of the posterior tibial artery, dorsalis pedis artery and arcuate artery was detected, each in one patient. Two patients showed occlusion of the plantar arch. Overall, the occlusion of arteries proximal to the digits was demonstrated in four of eight patients. Three of the four patients were positive for antitopoisomerase-1 antibody and had diffuse cutaneous SSc (dcSSc) with multiple skin ulcers or gangrene. CONCLUSIONS: Macrovascular involvement as detected with arteriography is not rare in SSc patients with digital ulceration or gangrene. Moreover, the vascular occlusion proximal to the digits seemed to be frequent in antitopoisomerase-1 antibody-positive dcSSc patients with multiple skin ulcers or gangrene.     

Mental health in patients with systemic sclerosis: a controlled investigation

Background Despite the undeniable impact of systemic sclerosis (SS) on quality of life, only a few studies so far have focused on its psychiatric or psychological aspects. We aimed at assessing psychiatric symptoms and self‐image in inpatients with SS and comparing them with patients with either a very mild skin condition or a serious skin condition. Methods Three groups were recruited: (i) 38 consecutive female inpatients with SS; (ii) 38 age‐matched female outpatients with melanocytic naevi; (iii) 35 age‐matched female inpatients with melanoma. All participants completed the Zung Anxiety Scale, the Zung Depression Scale and a self‐report questionnaire measuring self‐perceived personal qualities. Patients with SS were also clinically interviewed by a psychologist. Results The clinical interview revealed the presence of a psychiatric disorder in most (81%) patients with SS. The Zung scales corroborated the presence of mild to moderate anxiety and depression among patients with SS, who scored significantly higher than patients with either naevi or melanoma on both scales. Scores on the questionnaire assessing self‐perceived personal qualities were very similar in the three groups and indicated a fairly high level of self‐esteem. Conclusions This study suggested that psychosocial issues are quite relevant in patients with SS and underscored the need for a biopsychosocial approach to the clinical management of these patients. Timely detection of psychosocial difficulties and appropriate psychological or psychiatric intervention may represent important steps toward better adherence to medical treatment and improved psychological well‐being and quality of life.     

Dermoscopic detection of nail fold capillary abnormality in patients with systemic sclerosis

The diagnosis of systemic sclerosis (SSc) is often difficult. The purpose of the present study was to find the distribution of nail fold capillary abnormality in SSc. Sixty-two patients with SSc (male : female = 7:55, age 21-86 years, mean 60.1) admitted to the outpatient clinics were studied. Eighteen age- and sex-matched normal subjects, 28 patients with systemic lupus erythematosus (SLE) and 10 with dermatomyositis (DM) were also studied. Nail fold capillary loops were observed under immersion oil at a magnification of ×40 with a light microscope. Dilated capillaries, nail fold bleeding and avascular areas were found by dermoscopic observation. The distribution of dilated capillaries, nail fold bleeding and avascular areas in normal controls showed in one (5.6%), one (5.6%) and four cases (22.2%), respectively. The distribution of dilated capillaries, nail fold bleeding and avascular area in SSc patients showed in 27 cases (43.5%), eight cases (12.9%) and 16 cases (25.8%), respectively. The distribution of dilated capillaries and/or nail fold bleeding in SSc patients (29/62, 46.8%) was significantly elevated than that of normal controls (2/18, 11.1%) (P < 0.01). The distribution of overall abnormality in SSc (30/62, 48.4%) showed no significant difference compared with that of normal controls (4/18, 22.2%). Sensitivity and specificity for dilated capillaries and/or nail fold bleeding and overall nail fold abnormality in SSc patients compared with normal controls was calculated as 40.8% and 93.5%, 34.8% and 88.2%, respectively. Dermoscopic observation of dilated capillaries and/or nail fold bleeding is a sensitive and specific method for the detection of SSc.     

Endothelin receptor antagonist bosentan improves the dermal sclerosis in a patient with systemic sclerosis

We report a case of systemic sclerosis with interstitial pneumonia and severe pulmonary hypertension treated with bosentan, an endothelin receptor antagonist. Within a short period of administration of the bosentan the skin sclerosis improved.