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Results for “Scleroderma, Diffuse”

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At least 1,099 records · Page 61Linked to original sources
PubMed1991

A 15-year prospective study of treatment of rapidly progressive systemic sclerosis with D-penicillamine [see comment].

A 15-year (1973-1988) prospective study was conducted to determine the effectiveness of D-penicillamine (D-pen) in the treatment of rapidly progressive systemic sclerosis (SSc) of recent onset. Sixty-nine consecutive patients fulfilling strict criteria for rapidly progressive diffuse SSc of less than 18 months of duration were enrolled. Sixty received at least 750 mg/day of D-pen for at least 6 months, whereas 9 did not complete 6 months of treatment because of toxicity, noncompliance or death. In 58 of the 60 patients treated for longer than 6 months, there was an arrest in the progression of skin sclerosis followed by regression with softening, increased pliability and reappearance of sweating and hair. In these cases, the extent of sclerotic skin decreased from a maximum of 64.6 +/- 23.1% total body surface to 15.7 +/- 13.2%. In addition, in the group of patients that received D-pen for longer than 6 months, SSc renal disease was uncommon and pulmonary involvement was not progressive. The overall survival in this group was 88.3%. In conclusion, our prospective study showed that the administration of D-pen resulted in significant improvement of skin sclerosis and in prolonged survival of patients with early, rapidly progressive SSc with diffuse cutaneous involvement.

Adolescent↗
PubMed1997

Autoantibodies to myeloperoxidase in systemic sclerosis.

OBJECTIVE: Although antimyeloperoxidase (MPO) antibodies provide a sensitive serological test for vasculitis, their significance in sera from a small proportion (about 10%) of patients with autoimmune rheumatic disease is controversial. Our aim was to determine the incidence of anti-MPO antibodies in sera from patients with systemic sclerosis (SSc) and their relation to renal disease. METHODS: Thirty-eight patients had limited cutaneous SSc (lSSc) and 43 diffuse cutaneous SSc, and within each group, 24 and 27 patients, respectively, had renal impairment (defined as stable creatinine clearance less than 60 ml/min). Six patients previously had had a scleroderma renal crisis. After screening for antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence, the levels of IgM and IgG anti-MPO antibodies in 8 patients with SSc was determined by ELISA, with human MPO as antigen. RESULTS: Sera from 2 patients, both with lSSc and renal impairment, were perinuclear p-ANCA positive and had significant levels of circulating IgM and IgG anti-MPO antibodies. In one patient, anti-MPO antibodies appeared in the serum only after D-penicillamine was introduced, continued to rise after withdrawal of the drug, and fell only after immunosuppressive therapy. Renal biopsy confirmed vasculitis. The 2nd patient died of unrelated disease before further investigations could be performed. CONCLUSION: We suggest that circulating anti-MPO antibodies are not a feature of SSc per se and, if found, may indicate the presence of an unrelated pathology, such as idiopathic or drug induced vasculitis.

Adult↗
PubMed2003

[Clinical value of soluble adhesion molecules in systemic scleroderma].

The aim of the trial was to study clinical significance of estimation of cell adhesion soluble molecules (CASM) in scleroderma systematica (SS). Quantitation of CASM VCAM-1, ICAM-1 and R-selectin was made with enzyme-immunoassay (R&D System kits, USA) in 38 patients with SS (11 with limited SS and 27 with diffuse SS). The levels of VCAM-1, ICAM-1 and R-selectin was elevated in 30 (79%), 17 (45%) and 20 (53%) patients, respectively. Mean values of VCAM-1 and ICAM-1 in patients were significantly higher than in healthy donors. R-selectin was also higher but insignificantly. A mean CASM level and a relative number of patients with elevated count of CASM in patients with diffuse and limited forms of SS did not differ. In 15 patients with active (progressive) course of the disease the level of VCAM-1 was significantly higher than in patients with chronic (non-progressive) course of SS while concentrations of ICAM-1 and R-selectine were almost the same. Thus, SS patients have elevated levels of CASM. CASM VCAM-1 concentration is the most sensitive marker of SS activity compared to other CASM.

Adult↗
PubMed2006

Combination of intravenous pulses of cyclophosphamide and methylprednizolone in patients with systemic sclerosis and interstitial lung disease.

The purpose of the study was to examine prospectively the efficacy and safety of the combination of intravenous pulses of cyclophosphamide and methylprednizolone, in the treatment of scleroderma lung disease. Thirteen patients were treated with the above combination for up to 24 months. Prior to this treatment, they underwent a pulmonary function evaluation and high resolution computed tomography (HRCT). Carbon monoxide diffusion lung capacity and forced vital capacity were repeated at 6, 12, 24 and 48 months. HRCT was repeated at the end of the treatment period, but in between and afterwards in some patients, as well. A significant percentage of patients (66.6%) showed stabilization or improvement of their pulmonary function. Patients with already seriously compromised function, before treatment, were the least likely to exhibit this evolution pattern. There was a tendency in some individuals to deteriorate on later evaluations, off treatment, although they had stabilized at the end of the treatment. There was rather a poor correlation between functional evolution and HRCT appearance. Finally, the regimen was well tolerated. Our results suggest that the employed combination is safe and effective, mainly in stabilizing the respiratory function of the patients. This goal is more realistic when treatment is given before significant functional compromise has ensued. The need for long-term immunosuppression to maintain the initial favorable response is suggested.

Adolescent↗
PubMed1985

Diffuse fasciitis with eosinophilia associated with morphea and lichen sclerosus et atrophicus.

Diffuse fasciitis with eosinophilia (DFE) is a well described syndrome, among the connective tissue disorders. However, DFE is not commonly accepted as an own entity, because of its rare evolvement in scleroderma and the often indistinguishable histological pattern of both diseases. Here we report on the association of DFE and morphea in two patients and an additional lichen sclerosus in one of them. This points to a close relationship of DFE and other connective tissue diseases.

Adult↗
PubMed1999

Identification of cation-independent mannose 6-phosphate receptor/insulin-like growth factor type-2 receptor as a novel target of autoantibodies.

Two human monoclonal autoantibodies, B-33 and B-24, were generated from the B cells of a patient with scleroderma. Both monoclonal antibodies (mAbs) were composed of mu and lambda chains, and recognized cytoplasmic vesicular structures by indirect immunofluorescence on Hep-2 cell line slides, although mAb B-24 showed an additional diffuse cytoplasmic staining pattern. By Western blot, mAb B-24 exhibited a polyreactive-like binding pattern, whereas mAb B-33 failed to recognize any electroblotted Hep-2 antigen. The polyreactive versus monospecific behaviour of mAbs B-24 and B-33 was further confirmed by enzyme-linked immunosorbent assay (ELISA) with a variety of foreign and autoantigens. The N-terminal sequence of a protein band isolated by affinity chromatography with mAb B-33 was identical to that of cation-independent mannose 6-phosphate receptor (CI-MPR), also known as the insulin-like growth factor type-2 receptor (IGF-2R). Immunofluorescence experiments on Hep-2 cell line slides demonstrated a striking co-localization between the staining pattern exhibited by these mAbs and the pattern obtained using a goat anti-CI-MPR serum, indicating the recognition by B-24 and B-33 of a structure located predominantly in late endosomes. Sequence analysis of the V-region gene segments of B-33 and B-24 showed both to be identical, except for the existence of a point mutation in B-33 located in the H-complementarity-determining region 3 (H-CDR3) (position 100D), which produces a non-conservative replacement of Gly by Ser. This single replacement appears to be responsible for the dramatic change in reactivity of human mAb B-33. The data shown here provide new evidence of the critical role played by the H-CDR3 region in distinguishing a polyspecific from a monospecific antibody. A population study demonstrated the existence of immunoglobulin G (IgG) reactivity against CI-MPR/IGF-2R in serum specimens from five individuals with different pathological conditions, thus indicating that this molecule is a potential target for the human autoimmune response.

Amino Acid Sequence↗
PubMed1981

Progressive systemic sclerosis subgroups: variable pulmonary features.

Evidence has accumulated which enables subdivision of progressive systemic sclerosis (scleroderma) into three categories: (1) classic progressive systemic sclerosis (PSS); (2) the CRST/CREST syndrome; or (3) overlap syndromes. Previous reports of the chest film manifestations of PSS have used only the broad category of scleroderma without subdivision. This study analyzed the chest film manifestations of 73 PSS patients which have been subgrouped. Radiographic abnormalities, either interstitial lung disease or pleural effusion, were present as follows: PSS, 18% (8/44); CRST/CREST, 0% (0/9); and PSS-overlap, 75% (15/20). Interstitial lung diseases in the PSS-overlap group was usually basilar and of mild severity on the initial chest film obtained. While the classic PSS group had a very much lower incidence of lung disease, it was usually more diffuse and severe.

Adult↗
PubMed2003

A cross-sectional comparison of three self-reported functional indices in scleroderma.

OBJECTIVES: In scleroderma, outcome measures such as skin score provide only limited information about the functional impact of the disease. The requirement for validated and convenient instruments that reliably reflect disease morbidity is now recognized. This study compares the Disability Index of the Health Assessment Questionnaire (HAQ-DI) with two more recently developed scleroderma-specific tools: scleroderma-visual analogue scales (scleroderma-VAS) and the UK scleroderma Functional Score (UKFS). In addition, the use of clinical and laboratory measures as predictors of disease severity have been examined. METHODS: One hundred and fifteen consecutive patients were studied. Subjects completed the 20-item HAQ-DI, the scleroderma-VAS and a questionnaire related to hand and muscle function (UKFS). Clinical details, measurement of maximal hand-spread, fist-closure and investigations for internal organ involvement were recorded. RESULTS: Over 68% of patients with diffuse disease had moderate to severe disease on the UKFS, compared with 44% with limited disease. The mean UKFS in diffuse disease was 14.7 (s.d. 9.1) and 10.6 (s.d. 8.5) in the limited subset (P=0.02). The mean HAQ-DI in diffuse disease was 1.23 (s.d. 0.77) and 0.79 (s.d. 0.75) in the limited subset (P=0.005). The HAQ-DI showed significant correlation with UKFS (r=0.9; P < 0.001). Several clinical and laboratory measures were associated with higher HAQ-DI and UKFS. CONCLUSIONS: This is the first comparative study of the UKFS and the HAQ-DI. These data show a strong correlation between assessment methods. Higher scores correlated with clinical and laboratory indicators of severe disease. Used together, these inexpensive tools assess general and organ-specific symptoms, as well as functional limitation.

Adult↗
PubMed1991

[Tryptophan-induced fasciitis-scleroderma-eosinophilia syndrome].

A fasciitis-sclerodermia-eosinophilia syndrome developed in four female patients, aged between 55 and 75 years, after the ingestion of tryptophan, 1.5-6.0 g daily, for 13 months to 7 years. It began characteristically with hard oedema of the limbs, sometimes also of the trunk. Later there occurred diffuse indurations of the body surface with fixation of the skin to fascial planes. This was associated with mainly sensory peripheral neuropathy. Three of the patients had an eosinophilia (12-30%). Histological examination revealed a cell-poor fasciitis, fibrosis of the cutis and subcutis, perimyositis and epidermal atrophy of varying degree. Erythrocyte sedimentation rate was at most slightly increased. Antinuclear antibodies were demonstrated in one patient (1:80). Serum aldolase concentration was raised (3.4-5.4 U/l), while creatine kinase was normal. The disease progressed even after tryptophan was discontinued, in only one patient there was improvement during glucocorticoid treatment. In two cases the skin induration regressed slowly after administration of methotrexate (15 mg weekly) and hydroxychloroquine (400 mg daily).

Aged↗
PubMed1993

The course of skin involvement in systemic sclerosis over three years in a trial of chlorambucil versus placebo.

OBJECTIVE: To describe the course of cutaneous involvement in systemic sclerosis (SSc; scleroderma) over 3 years, in the context of a placebo-controlled drug trial. METHODS: The course of skin tethering (assessed by a semiquantitative skin scoring technique) was documented annually for 3 years in 64 SSc patients with early (< 3 years duration at entry), intermediate (3-8 years duration), or late (> 8 years duration) diffuse or limited SSc. RESULTS: Mean +/- SD entry skin scores were significantly greater in the 33 diffuse SSc patients (13.1 +/- 5.0) than in the 31 limited SSc patients (4.3 +/- 2.1) (P < 0.001). In patients with diffuse SSc, the skin score remained stable for the first 12 months, but had decreased significantly by 24 months (P < 0.022) and 36 months (P < 0.004). In those with limited SSc, the skin score did not change significantly over 3 years. CONCLUSION: Trials of treatments designed to affect skin thickening/tethering should be conducted in patients who have diffuse SSc (of short, intermediate, or long duration) at entry. The best time to study therapies designed to affect skin thickening may be in the first year after entry.

Adult↗
PubMed1998

[Iloprost administration over 21 days as an effective therapy in systemic scleroderma--case report and review of the literature].

A 57-years old female patient with systemic sclerosis underwent a prolonged intravenous therapy during 21 consecutive days with iloprost, a stable analogue of prostacyclin. Beginning with 0.5 ng/ kg/minute the dose was increased every 2 days up to 2 ng/kg/minute. At the end of follow up, Iloprost was shown to enhance the perfusion of the finger and to improve pulmonary-function tests including the diffusion-capacity. Furthermore, the Erythrocyte Sedimentation Rate and the C-reactive protein decreased. The case report shows the necessity of a controlled study of prolonged iloprost therapy.

Clinical Trials as Topic↗
PubMed1993

The surgical management of motility disorders.

Surgical treatment is either the therapy of choice or a facultative procedure in various types of esophageal motility disorders. In achalasia, cardiomyotomy, frequently combined with fundoplasty, achieves good or excellent results in > 80% of cases, and is, therefore, advised in cases when pneumostatic dilatation fails. Diverticulectomy and myotomy of the upper or lower esophageal sphincter are proven procedures to treat cervical and epiphrenic diverticula, leading to good/excellent results or at least an improvement in more than 95%. If, exceptionally, parabronchial diverticula require therapy, they should be excised transthoracically. Cervical myotomy is indicated in cases of cervical achalasia, when sufficient pharyngeal propulsion is preserved. In systemic diseases like scleroderma reflux induced complications may require surgical intervention in medically intractable cases. In these rather few cases, subtotal gastrectomy with a Roux-en-Y anastomosis is advised. In patients suffering from diffuse esophageal spasm or symptomatic "nutcracker" esophagus, extended esophageal myotomy can relieve symptoms. If a clear diagnosis is provided, about 75% of patients will have an improvement of symptoms.

Esophageal Diseases↗
PubMed1997

Ineffective esophageal motility (IEM): the primary finding in patients with nonspecific esophageal motility disorder.

Nonspecific esophageal motility disorder (NEMD) is a vague category used to include patients with poorly defined esophageal contraction abnormalities. The criteria include "ineffective" contraction waves, ie, peristaltic waves that are either of low amplitude or are not transmitted. The aim of this study was to identify the prevalence of ineffective esophageal motility (IEM) found during manometry testing and to evaluate esophageal acid exposure and esophageal acid clearance (EAC) in patients with IEM compared to those with other motility findings. We analyzed esophageal manometric tracings from 600 consecutive patients undergoing manometry in our laboratory following a specific protocol from April 1992 through October 1994 to identify the frequency of ineffective contractions and the percentages of other motility abnormalities present in patients meeting criteria for NEMD. Comparison of acid exposure and EAC was made with 150 patients who also had both esophageal manometry and pH-metry over the same time period. Sixty-one of 600 patients (10%) met the diagnostic criteria for NEMD. Sixty of 61 (98%) of these patients had IEM, defined by at least 30% ineffective contractions out of 10 wet swallows. Thirty-five of these patients also underwent ambulatory esophageal pH monitoring. Patients with IEM demonstrated significant increases in both recumbent median percentage of time of pH <4 (4.5%) and median distal EAC (4.2 min/episode) compared to those with normal motility (0.2%, 1 min/episode), diffuse esophageal spasm (0%, 0.6 min/episode), hypertensive LES (0%, 1.8 min/episode), and nutcracker esophagus (0.4% 1.6 min/episode). Recumbent acid exposure in IEM did not differ significantly from that in patients with systemic scleroderma (SSc) for either variable (5.4%, 4.2 min/episode). We propose that IEM is a more appropriate term and should replace NEMD, giving it a more specific manometric identity. IEM patients demonstrate a distinctive recumbent reflux pattern, similar to that seen in patients with SSc. This finding indicates that there is an association between IEM and recumbent GER. Whether IEM is the cause or the effect of increased esophageal acid exposure remains to be determined.

Adult↗
PubMed1984

Pathology of the kidney in "toxic oil epidemic syndrome".

In May 1981, a massive intoxication of people who had ingested adulterated cooking oil took place in Madrid and nearby provinces. Although the patients presented, in the first phase of the disease, with acute respiratory illness, later on thromboembolic complications, severe neuromuscular involvement, and scleroderma-like cutaneous lesions appeared. Kidneys were apparently spared; however, 4 out of 842 admitted patients developed glomerulonephritis; kidney biopsies revealed glomerular, vascular, tubular, and interstitial changes. Cases 1 and 3 had diffuse proliferative endocapillary glomerulonephritis; case 2 had diffuse membranoproliferative glomerulonephritis; and case 4 had diffuse extracapillary glomerulonephritis. Three cases had vascular lesions characterized by degenerative and proliferative endothelial changes, intimal foamy macrophages, and partial or complete obliteration of the vascular lumen by concentric myxoid fibrosis. There were signs of necrosis of tubular epithelium along with edema and lymphocytic and eosinophilic interstitial infiltration. Two out of 22 autopsies had segmentary glomerulonephritis, and 17 out of 22 autopsies showed renal vascular lesions.

Adult↗