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At least 541 records · Page 30Linked to original sources
PubMed2006

Use of antibodies recognizing cyclic citrullinated peptide in the differential diagnosis of joint involvement in systemic sclerosis.

OBJECTIVE: To determine the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in systemic sclerosis (SSc) and to assess any association between the presence of anti-CCP, radiographic features, and clinical manifestations. MATERIALS AND METHODS: Anti-CCP antibodies and rheumatoid factor (RF) were tested in serum samples from 75 patients with SSc (64 women and 11 men), with a mean age of 59.4 years (range 24-85) with either diffuse (dcSSc) and limited (lcSSc) cutaneous involvement. As a control group, 22 age- and sex-matched healthy controls (HCs) were examined. Standard radiographs of the hands and wrists were examined in each patient. RESULTS: The presence of anti-CCP was found in sera of 10.6% (8/75) patients with SSc (lcSSc 3 of 44, 6.8%; dcSSc 5 of 31, 16.1%). None of the HCs was positive for anti-CCP. The positivity of RF was observed in 19 of 75 (25.3%) SSc patients (lcSSc 10 of 44, 22.7%; dcSSc 9 of 31, 29%). Statistically significant association was found between anti-CCP positivity and the presence of arthritis (p<0.0001) and marginal erosions (p=0.001). CONCLUSION: Our data show that joint involvement is a common presenting feature of SSc. In this report, we show that anti-CCP antibodies can be detected also in patients with SSc, but they are generally less commonly present than in adults with rheumatoid arthritis (RA). Thus, the finding of high titers of anti-CCP antibodies may help to define the diagnosis of overlap syndrome SSc/RA and facilitate diagnosis and appropriate treatment.

Aged↗
PubMed2005

Alpha4beta1 and alpha4beta7 CD4 T cell numbers increase and CLA CD4 T cell numbers decrease in systemic sclerosis.

We studied the expression of adhesion molecules affecting recirculation and homing on peripheral blood CD4(+) T cells of patients with systemic sclerosis (SSc), in order to evaluate whether the distribution of tissue targeted subsets could reflect the participation of internal organs or the extent of cutaneous involvement [i.e. limited cutaneous (lc) and diffuse cutaneous (dc)]. Peripheral blood mononuclear cells (PBMC) from 51 patients with SSc and 19 sex- and age-matched controls were investigated by cytofluorimetric analysis for lymphocyte subpopulations carrying the following surface molecules: CD3, CD4, CLA, alpha4beta7 and alpha4beta1. Standard routine biochemistry and clinical examinations were also performed in all patients. We found that both alpha4beta1(+) and alpha4beta7(+) cells within the CD4(+) T cell population were significantly increased, while CLA(+) CD4(+) T cells were significantly reduced in SSc, compared to healthy donors. Significantly lower absolute numbers of alpha4beta7(+) cells were found in lc- compared to dc-SSc. Patients with oesophageal involvement had high numbers of alpha4beta7(+) cells, while those with nephritis also showed low levels of CLA(+) cells. Lung involvement was related directly to alpha4beta1(+) cell numbers and inversely to alpha4beta7(+) CD4 cell numbers. Taken together, our findings demonstrate that distinct CD4(+) T cell populations with selective homing properties show changes from normal distribution in SSc, and such changes are related to clinical expression and organ involvement in the course of the disease.

Adult↗
PubMed2006

[Gastrointestinal involvement in systemic sclerosis].

Gastrointestinal involvement is frequent in systemic sclerosis (SSc), occurring in 75 to 90% of patients with diffuse or limited cutaneous SSc. Although all regions of the gut may be affected, the esophagus is the most common gastrointestinal localization of this disease. If not diagnosed at an early stage, resulting complications may include esophagitis (leading to stenosis, strictures, and Barrett's esophagus) and increased risk of interstitial lung disease. Esophageal manometry is the most sensitive test for accurate diagnosis of motor dysfunction. Antisecretory agents (mainly proton-pump inhibitors) are effective for treating esophageal manifestations. Gastrointestinal involvement is reported in 50-88% of patients with SSc. It remains associated with a poor prognosis and leads to death in 6 to 12% of cases. Gastrointestinal impairment may lead to life-threatening complications, including severe dyspepsia, hemorrhage related to watermelon stomach (gastric antral vascular ectasia), malabsorption syndrome (related to bacterial overgrowth), and intestinal pseudo-obstruction. Treatment for the latter two remains difficult, although octreotide has proven to be effective in SSc patients. Small bowel manometry is useful for careful selection of SSc patients who will benefit from this treatment. Anorectal involvement is frequent in SSc patients (50-70%) and causes fecal incontinence and rectal prolapse. Other digestive manifestations, including liver impairment, are less common in SSc.

Barrett Esophagus↗
PubMed2003

Delayed gastric emptying in patients with diffuse versus limited systemic sclerosis, unrelated to gastrointestinal symptoms and myoelectric gastric activity.

OBJECTIVE: To study the gastric function in patients with diffuse and limited systemic sclerosis (SSc) in relation to the degree of upper gastrointestinal symptoms. METHODS: Scintigraphic gastric emptying and recording of the myoelectric signals of the stomach were examined in 15 patients with diffuse SSc (dSSc), 13 patients with limited SSc (lSSc) and 15 healthy controls. The frequency of upper gastrointestinal symptoms was determined using a questionnaire. RESULTS: Patients with dSSc had slower gastric emptying (scintigraphic gastric half-emptying time median (Md) 103 min, range 75-447 min) than control subjects (Md 70 min, range 38-94) and patients with lSSc (Md 76 min, range 43-460). Electrogastrographic recordings did not differ between dSSc, lSSc or controls. Symptoms tended to be more abundant in dSSc patients than in lSSc patients, however, patients with a high frequency of symptoms did not differ from patients with low frequency of symptoms in gastric function, as measured with scintigraphic gastric emptying or electrogastrography (EGG). Neither EGG nor a thorough review of upper gastrointestinal symptoms could predict delayed gastric emptying. CONCLUSION: The higher prevalence of delayed gastric emptying in patients with dSSc in this study indicates a more severe involvement of the gastrointestinal tract in dSSc than in lSSc, and stresses the importance of differentiating between the subtypes of SSc patients. Since EGG dysrythmia did not correlate with gastric emptying we concluded that factors other than defective myoelectric signals might contribute to a disturbed gastric function.

Case-Control Studies↗
PubMed2005

Differential expression of tissue kallikrein in the skin of systemic sclerosis.

Systemic sclerosis (SSc) is characterised by ischemic damage, impaired angiogenesis and skin fibrosis. Tissue kallikrein (t-kallikrein) is involved through kinins in inflammation, vasorelaxation and angiogenesis. T-kallikrein is synthetised by endothelial, smooth muscle, and inflammatory cells and, in skin, also by dark cells of the sweat glands, where it is involved in sweat formation. Our aim was to analyse, by immunohistochemistry and RT-PCR, the expression of t-kallikrein in the skin of patients with different SSc subsets, limited (lSSc) and diffuse (dSSc), and phases, early and advanced. Skin biopsies were taken from 18 SSc patients and 10 controls. Immunohistochemistry was performed on paraffin sections with an antibody against human urinary t-kallikrein. For RT-PCR, cDNA from skin biopsies was amplified using primers specific for human t-kallikrein. In the control skin, dark cells of the secretory units of sweat glands showed immunopositivity for t-kallikrein as well as blood vessels. In the lSSc skin, immunoreactivity was observed only in some glands, with weak staining in the advanced phase. In early lSSc skin, immunoreactivity was observed in microvessel walls and in the inflammatory infiltrate. In dSSc skin, dark cells of the glandular fundus units, and the few remaining vessels showed scarcity (early phase) or lack (advanced phase) of immunoreactivity for t-kallikrein. RT-PCR confirmed a decrease of t-kallikrein mRNA levels from early to advanced phase in SSc subsets, reaching its lowest level in advanced dSSc. In conclusion, immunohistochemical and biomolecular results indicate that t-kallikrein is decreased in the skin of SSc patients and decreases progressively from the early to advanced phase of lSSc and dSSc. The decreased expression of t-kallikrein may be involved in the impairment of the sweating process, vessel functionality and angiogenesis.

Adult↗
PubMed2006

Abnormal nitric oxide metabolism in systemic sclerosis: increased levels of nitrated proteins and asymmetric dimethylarginine.

OBJECTIVES: Endothelial dysfunction is a primary event in systemic sclerosis; however, the aetiology of events and the role of nitric oxide (NO) is still unclear. The aim of the present study is to investigate whether there are abnormalities in NO metabolism in plasma from patients with primary Raynaud's phenomenon (RP) and in the pathogenesis of systemic sclerosis (SSc): limited SSc (lSSc) and diffuse (dSSc). We also wanted to investigate the effect of factors within patients' SSc serum on NO metabolism in human microvascular endothelial cells (HMECs). METHODS: Plasma (n=89) or serum (n=80) was assayed for total nitrate and nitrite (NOx), nitration of proteins and the NO inhibitor asymmetric dimethylarginine (ADMA). HMECs were treated with patients' SSc serum and assayed for indicators of NO metabolism. RESULTS: Plasma NOx was elevated in patients with RP or lSSc (P<0.002), but not in patients with dSSc, compared with controls. Nitrated proteins in plasma, however, were found to be very high in dSSc patients (P<0.03), compared with RP, lSSc or controls. Patients with dSSc also showed increased levels of serum ADMA (P<0.05). The high level of nitrated proteins in dSSc was strongly associated with the severity and duration of dSSc disease. Skin biopsy sections from dSSc patients also showed enhanced nitrotyrosine staining compared with controls. In HMECs, pre-incubation with SSc serum impaired the activity of nitric oxide synthase (NOS) but not the expression of inducible or endothelial NOS. SSc serum also induced a reduction in intracellular cGMP synthesis, and NOx production in the cell culture medium, but was not associated with increased cell cytotoxicity. CONCLUSIONS: NO formation is increased in patients with primary RP or lSSc, but nitration of proteins and elevated ADMA is a particular feature of dSSc and may reflect abnormal NO regulation and/or contribute to endothelial dysfunction in SSc.

Adult↗
PubMedDate not supplied

Prognostic factors of low bone mineral density in systemic sclerosis.

OBJECTIVE: To analyse the results of bone densitometry in patients with systemic sclerosis (SSc), evaluating the prognostic factors of low bone mineral density (BMD) in fertile and postmenopausal patients, and comparing to a control healthy group. METHODS: Cross-sectional study analysing 61 female SSc patients, aged 25 to 51 years, who performed a bone densitometry using dual x-ray absorptiometry. BMD values (lumbar spine, femoral neck, Ward and trochanter) infertile and postmenopausal patients were compared according to SSc clinical variant (limited and diffuse), race, previous use of drugs (corticosteroids and cyclophosphamide) and bone mass index (BMI). These results were compared with 47 fertile and 60 postmenopausal healthy women; multivariate linear regression analysis was used to study the influence of the variables of interest in the BMD results. RESULTS: Twenty-seven SSc patients presented osteopenia and 14 densitometric osteoporosis. No statistical association was found between BMD values and SSc clinical variants, race and previous use of corticosteroids and cyclophosphamide, in the fertile and in the postmenopausal groups. Fertile SSc patients were paired by age and race with the control group, but BMI (p = 0.035) was significantly lower in the SSc group. BMD values of lumbar spine (p = 0.070, statistical trend), femoral neck (p = 0.003), Ward (p < 0.001) and trochanter (p = 0.003) were significantly lower in the SSc group. Postmenopausal SSc patients were paired by age and race with the control group, but BMI (p < 0.001) was also significantly lower in the SSc group. Age at menopause (p = 0.006) was also significantly lower and time from menopause (p < 0.001) was significantly higher in the SSc group. BMD values of femoral neck (p < 0.001), Ward (p < 0.001) and trochanter (p = 0.001) were significantly lower in the SSc group. Multivariate linear regression analysis showed that BMI was the main variable influencing BMD in the fertile and postmenopausal groups. CONCLUSION: In the present study, BMD results in fertile and postmenopausal SSc patients were independent of the SSc clinical variants, race and previous use of corticosteroids and cyclophosphamide. A low BMD in appendicular sites was observed infertile and postmenopausal SSc patients when compared to a control healthy group, associated to a low BMI.

Absorptiometry, Photon↗
PubMed2006

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 chi (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.

Diagnosis, Differential↗
PubMed2001

Localized and systemic scleroderma.

Scleroderma is a broad term encompassing both localized and systemic sclerosis. Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque morphea, generalized morphea, linear scleroderma, and deep morphea. Systemic scleroderma (sclerosis) can manifest as either limited or diffuse disease. Limited systemic sclerosis is typically preceded by Raynaud's phenomenon, involves cutaneous sclerosis distal to the elbows, with gastrointestinal and pulmonary fibrosis, and anticentromere antibody positivity. Diffuse systemic scleroderma is characterized by simultaneous Raynaud's phenomenon, cutaneous skin involvement proximal to the elbow with gastrointestinal, pulmonary, renal and cardiac fibrosis, and positive serology for antitopoisomerase and anti-RNAP III antibodies. This article discusses the classification, epidemiology, pathogenesis, clinical manifestations, treatment, and prognosis of the scleroderma.

Adult↗
PubMed1990

[Unusual manifestation of scleroderma of the trunk].

We present the case of an 81-year-old women with progressive systemic scleroderma. In addition to the typical manifestations of diffuse (truncal) scleroderma, including involvement of the esophagus, lungs and muscles, there were two unusual findings: large, non-sclerosing areas on the trunk simulating the disabling type of circumscribed scleroderma and high titers of anticentromere antibodies, while there were no anti-Scl-70 antibodies. The disease responded to treatment with griseofulvin.

Aged↗
PubMedDate not supplied

Scleroderma in a young man.

Scleroderma is a chronic disorder, slowly progressing characterized by diffuse fibrosis of the skin and internal organs. There are functional and structural abnormalities small blood vessels, fibrosis of the skin and internal organs, immune system activation and autoimmunity. Female predominance is most pronounced during mid and late childbearing age, women to men ratio is 7-12 : 1. In this case, we found a diffuse cutaneus scleroderma. Skin biopsy result showed hyperkeratosis, increased dermis thickness with deposition of collagen. The antigenic specificities of antibodies were related to distinct connective tissue disease. The diffuse cutaneus subset was associated with antibodies to topoisomerase I, formerly described as Scl-70 or Scl-86. Anti Scl-70 antibodies were shown in many studies as a marker antibodies for SSC. Colchicine was given in this case, which has the effects of microtubule assembly inhibition and interference with transcellular movement of collagen. During colchicine treatment serum hydroxyproline increased and serum proline decreased, suggesting increased collagen degradation.

Adolescent↗
PubMed1999

[Scleroderma in children: a retrospective study of 70 cases].

BACKGROUND: Scleroderma is uncommon in childhood. The aim of our study was to analyze the frequency of different clinical forms, their prognostic significance, biological features, and co-morbidities and to assess the pertinence of therapeutic options. PATIENTS AND METHODS: The files of 70 children with primary scleroderma seen from 1980 to 1997 were retrospectively reviewed. RESULTS: Localized scleroderma was observed in 56 children and diffuse lesions in 14. Localized scleroderma (44 girls, 12 boys) began early at a mean age of 7 years 2 months. The lesions presented as isolated bands (39 p. 100), associated with morphea (36 p. 100), or multiple morphea (5 p. 100). Mean duration of the clinical course was longer in cases with more and deeper lesions. Eosinophilia was observed at onset in 38 p. 100 of the cases and antinuclear antibodies were found in 28 p. 100. Local corticosteroid therapy (level I or II) appeared to be useful in the superficial and active lesions (morphea) but did not halt progression to deep scleroderma. General corticosteroid therapy (1 mg/kg/24 h) did not prevent the development of sequelae in cases with bands (16/16). Diffuse scleroderma corresponded to systemic scleroderma (6 cases), dual morbidity (dermatomyositis, mixed connective tissue disease) (6 cases), or scleroderma after eosinophil fasciitis (2 cases). Age at onset was around 9 years with female predominance. A particular gloves and socks form was observed and cardiac involvement was common, but there was no case of renal involvement. The therapeutic problems were similar to those in adults. DISCUSSION: Our findings emphasize that scleroderma occurs readily in childhood, unlike what has been reported 10 years ago. Prognosis depends on functional impairment resulting from major sequelae particularly important in localized forms and the life-threatening situations occurring in systemic forms.

Adrenal Cortex Hormones↗
PubMed1995

Circulating interleukin 1 beta and soluble interleukin 2 receptor: evaluation as markers of disease activity in scleroderma.

OBJECTIVES: To investigate whether circulating levels of interleukin 1 beta (IL-1 beta) or soluble interleukin 2 receptor (sIL-2R) reflect clinical disease status and response to therapy in scleroderma. METHODS: Plasma IL-1 beta and serum sIL-2R were measured by ELISA in 19 patients with limited cutaneous scleroderma (9 with extraesophageal internal organ involvement), 5 patients with diffuse cutaneous scleroderma and internal organ involvement, and 11 healthy controls, as well as serially over 12 months in 4 patients with scleroderma treated with cyclosporine. RESULTS: IL-1 beta levels were similar in scleroderma and control subject groups. sIL-2R levels were significantly higher in subjects with scleroderma involving internal organs (elevated in 93%), and correlated with erythrocyte sedimentation rate. sIL-2R levels decreased over 12 months in 2 of 4 patients taking cyclosporine in whom other variables remained unchanged. CONCLUSIONS: Elevated serum sIL-2R is a marker of internal organ involvement in scleroderma and warrants further investigation in assessing disease prognosis and response to therapy.

Adult↗
PubMed1995

High resolution computed tomography for the evaluation of lung involvement in 101 patients with scleroderma.

The aim of the study was to investigate the pulmonary parenchymal abnormalities by high resolution computed tomography (HRCT) in patients with various forms of scleroderma. Three scans were performed sequentially in all cases: one at the level of aortic arch, one at the tracheal carina and one 1-2 cm above the diaphragm. Seventy cases with limited, 21 patients with diffuse cutaneous systemic sclerosis and 10 cases with circumscribed scleroderma were investigated. The 21 patients with diffuse scleroderma included three normal HRCT scan (14%), three with ground glass attenuation (14%), one with ground glass attenuation with fibrosis, three with fibrosis (14%), six with subpleural and five with diffuse honeycombing. The majority of cases with extensive honeycombing of the lungs had anti-Sc! 70 autoantibody which was the characteristic antibody of the diffuse scleroderma subset. The 70 cases with limited cutaneous systemic sclerosis were characterized by normal HRCT (43%), ground glass opacity with or without fibrosis (18.6%), whereas fibrosis was detected in 22.9%, subpleural or diffuse honeycombing in 15.7% of the patients. Six of the ten cases with circumscribed scleroderma also showed a fibrosis. Cases with diffuse scleroderma are characterized by the presence of advanced fibrosis, whereas the extent of fibrosis is far less pronounced in limited scleroderma. Mild fibrosis may also be present in circumscribed scleroderma forms.

Adult↗
PubMed2006

[A case of systemic sclerosis and Sjogren's syndrome with cardiac tamponade due to steroid-responsive pericarditis].

A 75-year-old woman was admitted to our hospital because of abnormal lung shadow and necrosis of the left feet. She had a history of Raynaud's phenomenon from her twenties. On admission, she was diagnosed as having diffuse systemic sclerosis (SSc) and Sjögren's syndrome (SjS) because of scleroderma, interstitial pneumonia (IP), positive result of anti-Scl-70 and SS-A antibody, sicca, decreased tear excretion, and dysfunction of salivary glands. Seventy days after amputation of her left leg, she presented with edema, hypoxemia, chest discomfort, and fever. Blood test revealed inflammation and cardiac echography revealed pericardial effusion with a collapse sign of right atrium, thereby leading to the diagnosis of cardiac tamponade. After starting the daily dose of 20 mg of prednisolone, the pericardial effusion and cardiac tamponade sign disappeared. Pericarditis is seen in half of patients with SSc and rarely with SjS, and is usually asymptomatic. Pericarditis due to SSc has been reported unresponsive to steroid therapy, but several cases of steroid responsive pericarditis due to SSc or SjS have been reported. Clinically, they shared inflammatory responses and the presence of IP in the cases of SSc, which will be important when considering the pathogenesis and treatment of pericarditis due to SSc or SjS.

Aged↗