Lack of Evidence for Bacterial Infections in Skin in Patients With Systemic Sclerosis

BackgroundIn some patients with systemic sclerosis (SSc), persistent bacterial infection involving dermal microvascular endothelial cells may result in endothelial injury, leading to the obliterative microvasculopathy typical of the disease. Alternatively, in some patients with SSc persistent bacterial infection involving activated dermal fibroblasts or other cells found in scleroderma skin might result in the fibrosing features of this disease. In this study, we investigated bacterial infection in skin in patients with SSc.MethodsChlamydiae of many species are known to undergo persistent infection. Highly sensitive and specific PCR assays targeting chromosomal DNA sequences from C. trachomatis and C. pneumoniae were used to screen skin biopsy samples from each of 18 patients and 26 control individuals. Additional screening was performed using a highly sensitive “pan-bacteria” PCR screening system.ResultsAll patient and control samples proved to be PCR-negative for both chlamydial species. Similarly, all patient and control samples were PCR-negative when the broad range pan-bacteria assay system was used.ConclusionAlthough some caveats apply, the data presented here do not support the contention that persistent bacterial infections play an important role in the pathogenesis of SSc.     

系统性硬化患者内皮祖细胞连接黏附分子-A表达

目的研究系统性硬化(SSc)患者外周血内皮祖细胞连接黏附分子-A(JAM-A)表达情况。方法收集13例SSc患者及13例对照组新鲜EDTA抗凝血2ml,采用流式细胞仪方法检测,用PerCP-CY5.5、PE、Alexa Fluor 647和FITC标记CD34、CD133、CD309和JAM-A。内皮祖细胞定义为CD34、CD133、CD309(VEGFR-2,KDR)均阳性的细胞。结果内皮祖细胞表达JAM-A,SSc患者内皮祖细胞中JAM-A表达较正常对照减少(分别为0.0775±0.0385和0.1567±0.1223,P<0.05),SSc患者内皮祖细胞数量亦较对照组少(分别为0.0817±0.0403和0.1746±0.1419,P<0.05)。结论 SSc患者内皮祖细胞中JAM-A的减少是由于患者内皮祖细胞数目减少所致。SSc患者存在血管生成障碍,JAM-A表达异常,并且在SSc发病机制中起一定作用。     

Pulmonary Involvement in Systemic Sclerosis

Scleroderma, also known as progressive systemic sclerosis (SSc), is a multisystem autoimmune disorder characterized by inflammation and fibrosis involving the skin as well as internal organs such as the vasculature, esophagus, and the respiratory tract. Pulmonary involvement consists most often of interstitial fibrosis and pulmonary vascular disease leading to pulmonary arterial hypertension (PAH). Bronchiectasis is an uncommon pulmonary manifestation of systemic sclerosis. Pulmonary hemorrhage with acute renal failure and diffuse alveolar hemorrhage in the absence of a history of renal involvement or penicillamine intake have rarely been reported in patients with systemic sclerosis.On high resolution CT, evidence of interstitial disease is seen in approximately 90% of patients, the main findings being a fine reticular pattern involving the subpleural regions of the lower lobe. Other common findings include ground-glass opacities, honeycombing, and parenchymal micronodules. The most distinctive pulmonary histologic findings in patients with scleroderma are the vascular changes found in PAH in the absence of significant interstitial fibrosis.There is no strong evidence that any drug alters the course of the two main types of lung disease in systemic sclerosis. This apparent failure of therapy may reflect the fact that pulmonary involvement is usually identified at an established or late stage. It has been suggested that, for fibrosing alveolitis, corticosteroids are most effective if given in combination with cyclophosphamide. In some patients with SSc, PAH has been considered as a major cause of morbidity and mortality. Centrally infused prostacyclin (epoprostenol) and its subcutaneously infused analog treprostinil improve hemodynamics, as well as the quality of life and survival in these patients. Iloprost has also shown a positive effect on PAH in SSc patients. More recently, bosentan, an endothelin receptor antagonist, has proved effective in controlling PAH after 6 months' treatment. Sildenafil has been used as a selective pulmonary vasodilator in SSc patients with isolated PAH. This drug decreased mean pulmonary artery pressure and pulmonary vascular resistance, and increased cardiac output, with much improvement of the physical condition of the patients. Lung transplant can be considered as a last option.Clinicians must be aware of the possibility of lung disease in patients with SSc so that it can be treated as early as possible.     

Antihistone Antibodies in Systemic Sclerosis

Objective. To determine the prevalence and clinical significance of antihistone antibodies (AHA) in systemic sclerosis (SSc). Methods. Serum samples from patients with limited cutaneous SSc (n = 44), diffuse cutaneous SSc (dcSSc; n = 48), and other SSc-related disorders (n = 22) were examined by enzyme-linked immunosorbent assay and immunoblotting for AHA. Results. AHA were demonstrated in 29% of the 92 SSc patients and in 44% of those with dcSSc. The presence of AHA correlated with severe pulmonary fibrosis in those with dcSSc. Immunoblotting revealed that the predominant antigen was histone H1. Conclusion. AHA might be a serologic indicator of the severity of pulmonary fibrosis in SSc.     

Fructose Malabsorption in Systemic Sclerosis

The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients.The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet.Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated.The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009).Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal clinical manifestations in SSc patients with fructose malabsorption, our findings underscore that fructose malabsorption may play a significant role in the onset of gastrointestinal symptoms in these patients. Finally, we suggest that fructose malabsorption may be due to reduced fructose absorption by enterocytes, impaired enteric microbiome, and decreased intestinal permeability.     

Gynaecologic History in Systemic Sclerosis

The aim of the study was to analyse the gynaecologic history of 150 Brazilian patients with systemic sclerosis (SSc) by comparing the outcome of the pregnancies before and after disease onset and in the two clinical variants of SSc, as well as to assess the effects of the pregnancy on the progress of the disease. A retrospective analysis was carried out of 150 female SSc patients, more than 18 years old, who attended the outpatient clinic of the Unit of Rheumatology of the State University of Campinas. The patients were questioned about the number of pregnancies, deliveries (full-term infants, premature births and twins) and fetal deaths (spontaneous abortions and perinatal deaths). These data were subdivided into pregnancies before and after SSc onset. In those gestations started after disease onset the patients were questioned about the evolution of SSc during the pregnancy. The patients were also asked about dyspareunia and the age at menopause. Thirty-two patients (21%) had never been pregnant, and only five of them were considered infertile. One hundred and eighteen patients (79%) had a total of 406 pregnancies, with an average of 3.4 per patient; there were 364 pregnancies before and 42 after SSc onset. There were 58 fetal deaths (14% of the pregnancies), 50 of these occurring before and eight after disease onset; 55 were spontaneous abortions and the other three were perinatal deaths. The fertility rate was higher in the limited SSc (3.6) than in the diffuse SSc patients (3.1), although the percentage of fetal deaths and the evolution of SSc during the pregnancy were similar in the two clinical variants. In the pregnancies that occurred after the onset of SSc, the clinical course remained stable in 72% of the cases, worsened in 14% and improved in 14%. Dyspareunia was mentioned by 49 patients (37% of those with an active sexual life). Menopause was reported by 72 patients, predominantly with limited SSc (61 patients). The fertility rate in the postmenopausal SSc patients was 3.9, similar to that observed in general postmenopausal population in Brazil. The analysis of the gynaecologic history in this series of SSc patients showed no increased risk in infertility or spontaneous abortions. The fertility rate in the two SSc clinical variants was higher than that observed in the local global population. Most of the patients who became pregnant after the onset of SSc showed no signs of worsening during the course of the disease. Received: 1 February 1999 / Accepted: 22 November 1999     

Intestinal Lymphangiectasia in Systemic Sclerosis

Protein-losing gastroenteropathy is a well-recognized entity in systemic sclerosis, for which several mechanisms have been postulated. Acquired intestinal lymphangiectasia as a cause of increased intestinal protein loss has not previously been described in the literature. We report the first case of acquired intestinal lymphangiectasia in systemic sclerosis.     

Captopril-induced Agranulocytosis in Systemic Sclerosis

Abstract: Captopril-induced agranulocytosis in systemic sclerosis. M. A. Watson, N. J. Radford, B. P. McGrath, G. W. Swinton and J. W. M. Agar, Aust. N.Z. J. Med ., 1981, 11, pp. 79–81.
A 25 year old woman with systemic sclerosis developed severe but reversible agranulocytosis seven weeks after commencing treatment with Captopril for severe hypertension and renal impairment
The evidence suggests that the agranulocytosis was caused by Captopril     

Erectile Dysfunction in Systemic Sclerosis

Erectile dysfunction (ED) is a major issue in systemic sclerosis (SSc) as it is observed in around 80 to 90 % of men with this connective tissue disease. ED greatly impacts the quality of life and should be actively addressed as a common complication. Whereas ED in the general population is usually associated with risk factors for atherosclerosis as well as cardiovascular disease, the main aetiology of ED in SSc is microangiopathic. In SSc, the blood flow is reduced in the small penile arteries due to corporal fibrosis and myointimal proliferation. There are no data on the prevention of ED in SSc. On-demand phosphodiesterase-5 inhibitors have little effect in improving erectile function, but daily or alternate day regimens of long-acting phosphodiesterase-5 inhibitors provide a measurable, although often limited, benefit. When intracavernous prostaglandin E1 injections are also ineffective, the implantation of a penile prosthesis should be considered as an option.     

系统性硬化症动物模型

系统性硬化症是一种自身免疫病,以多系统纤维化、小血管病变、血清自身抗体阳性为主要特点。目前其病因尚未十分清楚,越来越多的证据显示可能有血管病变、炎性反应、纤维化、自身免疫四大机制参与并相互作用。在研究系统性硬化症的发病机制、探索新药治疗效果时需要用到动物模型来模拟病理生理过程,而每一种模型都有其特点却又不完美。本文将根据建模方法分类介绍一些经典的和创新的模型,以及它们各自的特点、应用价值,为研究者选择最合适的动物模型提供帮助。