Different clinical features in patients with limited and diffuse cutaneous systemic sclerosis

This study aims to analyze differences among established disease damage indicators in patients with limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc). Fifty patients with lcSSc and 55 patients with dcSSc were included in this study. Difference in mean disease duration between the two subgroups of patients was not statistically significant (z=−0.88, p=0.38). Patients with lcSSc and dcSSc were compared, and differences in vascular, esophageal, lung, heart, renal, and musculoskeletal involvement were statistically assessed using χ ², Mann–Whitney, and Kruskal–Wallis tests. Using the technique of nailfold capillaroscopy, we found normal capillaries or nonspecific capillary change in 10.0% of the patients with lcSSc and only in 3.6% of the patients with dcSSc. Dilated capillaries without loss of capillaries were found in 42% of the patients with lcSSc and in 10.9% of the patients with dcSSc (p=0.05). However, severe capillary damage (loss of capillaries) was noticed more frequently in patients with dcSSc (dcSSc/lcSSc: 85.5%/48.0%, p=0.002). Pitting scars or digital ulcers were found in 46.0% of the patients with lcSSc and in 67.3% of the patients with dcSSc (p=0.04). We did not notice a significant difference in frequency of fingertip osteolysis and telangiectasia. Esophageal hypomotility was found in 64% of the patients with lcSSc and in 85.5% of the patients with dcSSc (p<0.01). We found interstitial lung fibrosis more frequently in patients with dcSSc (lcSSc/dcSSc: 16.0%/72.7%, p<0.001). Reduced forced vital capacity (FVC) was found in 6.0% of the of patients with lcSSc and in 41.8% of the patients with dcSSc (p<0.001). A decreased value of the transfer factor for carbon monoxide (DLCO) was also observed more frequently in patients with dcSSc. Heart involvement was found in 29.1% of the patients with dcSSc and less frequently (p<0.001) in patients with lcSSc (8%). Similarly, we found renal involvement more frequently in patients with dcSSc (lcSSc/dcSSc: 2.0%/16.3%). Tendon friction rubs were noticed in 23.6% of the patients with dcSSc and only in 6% of the patients with lcSSc (p<0.01). Joint contractures were observed in 70.9% of the patients with dcSSc and in 26.0% of the patients with lcSSc (p<0.001). Muscle weakness was noticed more frequently in patients with dcSSc (lcSSc/dcSSc: 22.0%/40.0%, p<0.05). Arthralgia was found more frequently in patients with dcSSc, but arthritis became apparent, without significant difference in frequency, in 16% of the patients with lcSSc and in 16.4% of the patients with dcSSc. Loss of capillaries (detected by nailfold capillaroscopy), digital ulcers, interstitial lung fibrosis, decreased FVC and DLCO, esophageal hypomotility, musculoskeletal impairment, and heart and renal involvement are more common in patients with dcSSc. Fingertip osteolysis, telangiectasia, and arthritis are equally frequent in both forms of the disease.     

Multiple sclerosis associated with systemic sclerosis

Multiple sclerosis (MS) has been increasingly reported in association with other autoimmune diseases not primary affected the nervous system. The coexistence of MS and systemic sclerosis (SSc) has been rarely described. We report here the case of a 46-year-old female patient with longstanding MS since the age of 26, who developed SSc 12 years later. Her MS was of the relapsing-remitting type, but the definite diagnosis was not made until the age of 33. MS diagnosis was based on medical history, magnetic resonance imaging (MRI) studies and positive cerebrospinal fluid analysis. One year after the diagnosis of MS, she developed Raynaud’s phenomenon, skin tightness and hypopigmented patches, suggestive of scleroderma. Further investigation with laboratory studies, including serology, hand and chest X-rays, and chest computerized tomography scan confirmed the SSc diagnosis. Our report highlights the interesting association between MS and SSc that may be due to an overlapping pathogenetic mechanism for both processes.     

A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis

Current therapeutic modalities for the treatment of systemic sclerosis (SSc) have significant limitations. The window of opportunity to prevent tissue fibrosis and irreversible damage occurs during the early inflammatory phase of this condition. A drug that we believe has promise to exert a desired effect in early SSc is cyclophosphamide (CYC). However, there are only a few published reports regarding the use of cytotoxic immunosuppressive medications at the onset of the illness. The goal of this study was to test the efficacy and toxicity of CYC in patients with early diffuse SSc. The study design was a randomized, unblinded, 18 months per patient trial with a comparison group that received azathioprine (AZ). Thirty patients were assigned to receive oral CYC (2 mg/kg daily for 12 months and then maintained on 1 mg/kg daily) and 30 patients were assigned to receive oral AZ (2.5 mg/kg daily for 12 months and then maintained on 2 mg/kg daily). During first 6 months of the trial, the patients also received prednisolone, which was started at a dosage of 15 mg daily and tapered to zero by the end of the sixth month. After treatment there was a statistically significant improvement in the modified Rodnan skin score (MRSS), attack frequency of Raynauds phenomenon (RP), and erythrocyte sedimentation rate (ESR) in the CYC-group, but not in the AZ-group. The forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) did not change after treatment in the CYC-group, but statistically significantly worsened in the AZ-group. No life-threatening or irreversible adverse reactions were observed in either group. This study showed that CYC is a promising disease modifying medication for SSc as it exhibited a positive influence on the evolution of disease.     

Outcomes of patients with systemic sclerosis treated with tocilizumab: Case series and review of the literature

The treatment of systemic sclerosis (SSc) presents a clinical challenge because of the progressive nature of the disease, relatively poor prognosis, and lack of a proven treatment. In the last 10 years, several studies demonstrated the importance of interleukin 6 (IL6) as a pivotal cytokine in the development of fibrosis and angiopathy, especially in SSc. Tocilizumab, an IL6 receptor antibody, has shown promising results for patients with SSc.A total of 16 patients with SSc were treated with tocilizumab; 14 were female and 2 were male, with a median age of 45.5 years and median disease duration of 31.5 months. Ten patients had anti-SCl-70, none had anticentromere, and two had antipolymerase. Tocilizumab treatment was provided as long as the patient's condition improved.Total treatment duration was 30.33 patient-years. Median treatment duration was 18.5 months, and 3 patients were treated for a period of 4 years and longer. Ten patients were treated with tocilizumab to the date of data collection. All were feeling good and maintained the achieved improvement throughout the treatment period. Improvement was recorded in 12 patients (75%). Mean reduction in modified Rodnan skin score was 11 points (p < 0.001), musculoskeletal and joint involvement improved in 75% and 80% of patients, respectively, and improvement in lung function was recorded in 46%. Patients with early SSc responded better to tocilizumab (p = 0.01).This is the largest reported case series of tocilizumab treatment in patients with SSc. The treatment was without significant side-effects and was beneficial for most patients, especially in early disease. The present study reinforces previous findings regarding the efficacy of tocilizumab in treating SSc.     

Free radical activity and antioxidative systems in patients with systemic sclerosis

Background: Free radicals have been said to contribute to vascular damage in patients with systemic sclerosis. The aim of the study was to determine the level of lipid peroxidation products and antioxidative enzyme activity in patients with systemic sclerosis and in healthy controls. Methods: 10 women with definite systemic sclerosis and 10 age-matched healthy women were studied. Results: A significant increase in serum lipid peroxidation product levels (i.e. diene conjugates and thiobarbituric acid-reactive substances) was found in patients with systemic sclerosis. These changes were accompanied by a decrease in superoxide dismutase, catalase, and glutathione peroxidase activity in erythrocyte lysate. Furthermore, there was diminished activity of glutathione reductase and a depressed total serum level of antioxidants compared to the controls. Blood thiol group concentration in patients with systemic sclerosis was also found to be decreased. Conclusions: The results obtained indicate increased oxidative stress in patients with systemic sclerosis.     

A decreased serum leptin level in patients with systemic sclerosis

Serum leptin levels were determined in 31 women with systemic sclerosis and 24 age-matched healthy controls. Both groups were divided into premenopausal and postmenopausal subgroups. A decreased serum leptin was found in the patients with systemic sclerosis. The premenopausal patients and controls had higher serum leptin than those in the postmenopausal subgroups. Serum leptin correlated with body mass index in the patients with systemic sclerosis. Received: 2 June 2000 / Accepted: 15 March 2001     

The impact of depression,microvasculopathy, and fibrosis on development of erectile dysfunction in men with systemic sclerosis

This article is a small case series that aims to discuss the impact of depression, vascular, and fibrotic changes on development of erectile dysfunction (ED) in patients with systemic sclerosis (SSc). In this paper, we present five male patients with SSc, aged 30–48 years. All patients are nonsmokers, and their past medical history does not reveal any other diseases or treatment procedures (drugs) that may have influence on erectile function. We used a five-item questionnaire, the International Index of Erectile Function (IIEF-5), to assess ED in our patients. Microvascular abnormalities (estimated by nailfold capillaroscopy), fibrotic changes (assessed by skin score, chest X-ray and reduction in forced vital capacity), and presence of depression (estimated using the Beck’s Depression Inventory) were evaluated. To assess efficacy of sildenafil citrate (25–50 mg 1 h before each sexual activity), patients with ED filled up the IIEF-5 before and after 1-month therapy. We concluded that ED is a frequent and early clinical feature in men with SSc. Microvascular abnormalities are similar in patients with and without ED. Although patients with ED had higher depression indices, an unsatisfactory response to sildenafil citrate indicates that psychoneurogenic factors are not crucial in development of ED in SSc. Patients with ED had more extended fibrotic changes, which indirectly suggests that fibrosis of the corporal body may play the main role in the pathogenesis of ED in SSc.     

Pulmonary arterial hypertension associated with systemic sclerosis: Current diagnostic approach and therapeutic strategies

Pulmonary arterial hypertension(PAH) represents a devastating vascular complication of systemic sclerosis(SSc) and is found in 10%-15% of cases carrying a severe prognosis. PAH has a dramatic impact on the clinical course and overall survival, being the single most common cause of death in patients with this entity. The clinical course and aggressive progression of PAH has led clinicians to perform annual screening for it, since early detection and diagnosis are the cornerstone of a prompt therapeutic intervention. The diagnosis of PAH can be challenging to clinicians, particularly in its early stages, since in the context of SSc, the multiple causes of dyspnea need to be assessed. Doppler echocardiography represents the best initial screening tool, however, right heart catheterization remains the gold standard and definitive diagnostic means. Remarkable advances have been achieved in elucidating the pathogenesis of PAH in the past two decades, leading to the development of disease-specific targeted therapies: prostacyclin analogues, endothelin receptor antagonists and inhibitors of five phosphodiesterase pathways. However, the clinical response to these therapies in SSc-associated PAH has not been as great as the one seen with idiopathic PAH. This review also focuses on the diagnosis and novel therapies that are currently available for PAH, as well as potential future therapeutic developments based on newly acquired knowledge of diverse pathogenic mechanisms.     

Psychological adjustment to systemic sclerosis

Objective . To examine the role of demographic, disability, appraisal, and coping variables in predicting psychological adjustment in individuals with systemic sclerosis. Methods . Two hundred forty-two individuals with systemic sclerosis (SSc; diffuse and limited) were surveyed by mail. Demographics, functional disability, pain, control appraisals, 8 types of coping, and individual psychosocial adjustment were assessed by selfreport questionnaires with established reliability and validity. Results . In regression analysis, 3 coping strategies emerged as significant predictors of adjustment: Wishful Thinking, Blaming Self, and Problem-Focused Coping. Self-reports of disability and control appraisals were also significant predictors. Collectively, 46% of the variance in adjustment was explained by these 5 predictor variables. The strongest predictor of overall adjustment was wishful thinking, explaining 22% of the variance in adjustment. Conclusions . Potentially modifiable appraisal and coping variables, along with disease-related disability, appear to play an important role in predicting adjustment to SSc, while demographic variables explained little of the variability in patient adjustment.     

Cardiac manifestations in systemic sclerosis

Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis(SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography(especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.     

The development of systemic sclerosis in a female patient with multiple sclerosis following beta interferon treatment

We describe a 38-year-old patient with relapsing remitting multiple sclerosis who subsequently develops systemic sclerosis following a course of interferon B-1a injections. This rare association between MS and systemic sclerosis is interesting due to the added factor of beta interferon therapy prior to the onset of the systemic sclerosis. It is also important, as more patients are treated with interferon B-1a for multiple sclerosis, this is a potential association.     

Characteristics of musculoskeletal ultrasound and its relationship with systemic inflammation in systemic sclerosis patients

Aim of the workTo describe musculoskeletal ultrasound (MSUS) findings in patients with systemic sclerosis (SSc) and to study their relation with cardiopulmonary and skin affection.Patient and methodsIn 50 SSc patients, hands, wrists and six entheses sites were evaluated by MSUS. Entheses were scored using the Madrid Sonography Enthesitis Index (MASEI). The modified Rodnan skin score (mRSS) was assessed.ResultsThey were 42 females/8males with a mean age 36.2 ± 11.6 years, disease duration 3.5 ± 4.2 years, 27 had limited skin affection and 23 diffuse and the mRSS was 4.1 ± 15.3. 54% had arthritis, 10% tendon friction rub, 16% joint contractures and 10% calcinosis. 18% had left ventricular hypertrophy, 34% had pulmonary hypertension, 20% had restrictive pulmonary function test (PFT) and 24% had interstial lung disease (ILD). Synovitis was detected in 58% and was significantly related to mRSS, left ventricular hypertrophy, PFT, pulmonary hypertension and ILD (p = 0.023, p = 0.03, p = 0.006, p = 0.026 and p = 0.039 respectively). Common extensor tenosynovitis was detected in 82% and was significantly related to mRSS, PFT and ILD (p = 0.019, p = 0.043 and p = 0.032 respectively). Joint erosions were detected in 36% and were significantly related to age and C-reactive protein (CRP) (p = 0.01 and p = 0.034). Enthesopathy showed a significant relation with erythrocyte sedimentation rate (ESR), CRP and mRSS (p = 0.014, p = 0.013, p = 0.025, respectively).ConclusionArticular involvement is common in SSc and underestimated by clinical examination. Synovitis is associated with cardiovascular complication in SSc. Tenosynovitis is clinically related to restrictive pulmonary function. Enthesopathy should be kept in mind in symptomatic patients with systemic sclerosis.     

Left ventricular aneurysms developed in a patient with systemic sclerosis

A 60-year-old woman with systemic sclerosis, lung fibrosis, and primary biliary cirrhosis was admitted to our hospital because of heart failure. Ventricular aneurysms were found in the apex and the posterior wall of the left ventricle by angiocardiography; however, there was no sign of coronary artery stenosis. A myocardial biopsy specimen revealed diffuse focal myocardial fibrosis. In this case, the patient with systemic sclerosis developed a rare complication of ventricular aneurysms without coronary disease.     

Left ventricular aneurysms developed in a patient with systemic sclerosis

Abstract

A 60-year-old woman with systemic sclerosis, lung fibrosis, and primary biliary cirrhosis was admitted to our hospital because of heart failure. Ventricular aneurysms were found in the apex and the posterior wall of the left ventricle by angiocardiography; however, there was no sign of coronary artery stenosis. A myocardial biopsy specimen revealed diffuse focal myocardial fibrosis. In this case, the patient with systemic sclerosis developed a rare complication of ventricular aneurysms without coronary disease.     

Familial risk estimation in systemic sclerosis

Background: Familial systemic sclerosis has been rarely reported. Assumptions have therefore been made implying no familial disease aggregation. This study critically challenges the assumption using a methodical population-based epidemiological approach to quantify the prevalence and characteristics of familial systemic sclerosis. Methods: In this retrospective cohort study the systemic sclerosis prevalence in first degree family members was compared between 715 systemic sclerosis patients (710 families) and 371 randomly ascertained age and gender group-matched general practice controls (371 families). These data, obtained by telephone questionnaire (living patients) or medical records review (deceased patients and untraceable patients of unknown living status), were validated, where necessary, and expressed in terms of relative risk, absolute risk and population point prevalence. Results: Systemic sclerosis affecting first degree members was validated in ten of 710 families. Reporting of systemic disease in another four more distant family members, and the co-occurrence of systemic and localised disease in three families was also documented. Observed and expected disease subtype concordance was 80% (44–97%) and 68% respectively and the female predominance among familial cases was similar to that for non-familial disease. The risk of disease in a subsequent first degree relative was compared to the risk in an initial first degree family member. Its estimated magnitude was wide (11–158). However, use of population prevalence data to determine the expected number of systemic sclerosis patients in the negative cohorts' families suggests the higher estimate is more realistic. Despite the high magnitude, the absolute disease risk in first degree family members remained low – approximating 1%. The population prevalence of familial systemic sclerosis approximated 1.4/million. Conclusions: This study substantially increases the otherwise small list of documented instances of familial systemic sclerosis. More importantly, it quantifies the risk for the first time, ranking it as the disease's most powerful determinant identified to date.     

Effect of ambrisentan on peripheral circulation in patients with systemic sclerosis

Systemic sclerosis (SSc) is characterized by disturbed blood circulation. The effect of ambrisentan, an endothelin-A receptor-selective antagonist, on impaired peripheral circulation in SSc remains largely elusive. Here we show SSc patients, whose clinical symptoms such as cyanosis and Raynaud's phenomenon, were ameliorated by the treatment with ambrisentan. Additionally, objective evaluations with thermography showed improvement of hand coldness in steady-state and cold challenge tests. Ambrisentan might have a potential to improve peripheral circulation in SSc.     

The natural course of progressive systemic sclerosis patients with interstitial lung involvement

Objective The aim of the study is to assess the natural course of systemic sclerosis (SSc) in patients with interstitial lung involvement and to evaluate the effects of treatment. Materials and methods Sixty SSc patients with interstitial lung involvement were included in the study and history and retrospective data records of the patients were reviewed. Results It was observed that 47 patients (78.3%) had Raynaud’s phenomenon, 7 patients (11.7%) had skin involvement, 5 patients (8.3%) had joint involvement, and 1 patient (1.7%) had gastrointestinal system involvement as the first manifestation of the disease. Lung involvement had developed on an average of 113±106 months after the first manifestation of the disease and was apparent within the first year in 10 patients (16.7%), between 1 and 2 years in 3 patients (5%), between 2 and 3 years in 2 patients (3.3%), between 3 and 4 years in 5 patients (8.3%), between 4 and 10 years in 21 patients (35%), and after 10 years in 19 patients (31.7%). When the symptoms of lung involvement appeared, 37 patients (61.7%) were not receiving treatment while 23 (38.3%) were using an immunosuppressive agent. The time interval of lung involvement for the treated patients was 131±95 months while it was 101±112 months in untreated patients (p>0.05). Conclusion In SSc patients with intersititial pulmonary involvement, the disease frequently starts with Raynaud’s phenomenon and pulmonary symptoms tend to appear at a mean of 7 years after the onset of disease. The first sign of the disease, the probability of interstitial pulmonary involvement, is highest during the first 15 years after. Although this probability decreases after 15 years, in up to 10% of the patients, interstitial pulmonary involvement can still occur even up to 40 years. Immunosuppressive treatment is not effective in preventing the development of pulmonary involvement. However, it delays the manifestation of pulmonary symptoms for nearly 4 years.     

Serum adipokines levels in patients with systemic sclerosis: A meta-analysis

Background: Systemic sclerosis is an chronic inflammatory autoimmune diseases. Adipokine has been reported to play an important role in modulating immune responses. Recent studies suggest that adipokine also plays some roles in the pathogenesis of systemic sclerosis (SSc). However, published data regarding the relationship between plasma/serum adipokine levels and SSc are contradictory. The aim of this study was at performing a meta-analysis to derive a more accurate estimation and further investigate the association of plasma/serum leptin and adiponectin levels with SSc patients.

Methods: PubMed, and Web of Science databases (up to Feb 20, 2016) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle–Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis.

Results: A total of fourteen studies were finally included in this meta-analysis. Among them, six of which were studied for the serum adiponectin levels in SSc patients, six of which were studied for the serum leptin levels in SSc patients, and two of them were studied both for serum adiponectin levels and serum leptin levels in SSc patients. The meta-analysis results showed that the serum adiponectin levels in SSc patients were significantly lower than that in normal controls (SMD = ?0.608?ng/ml, 95% CI = ?1.029 to ?0.186, p?=?0.005). However, there were no significant differences in serum leptin levels between SSc patients and healthy controls (SMD = ?0.990?ng/ml, 95% CI = ?2.340 to 0.359, p?=?0.150). The subgroup analysis showed that Asia SSc patients with age less than 50 years old had lower plasma/serum adiponectin levels when compared with controls.

Conclusion: The serum adiponectin levels, but not serum leptin levels, in SSc patients were significantly lower than that in normal controls.     

Brachial plexopathy associated with systemic sclerosis

Neurological involvement is uncommon in systemic sclerosis. Most of the reported cases concern trigeminal neuropathy or peripheral nerve entrapment. We report a third case of brachial plexopathy, presumably related to vasculitis, in a patient with systemic sclerosis, which improved after cyclophosphamide therapy. Received: 7 September 2001 / Accepted: 3 April 2002