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V D Steen

Publications and source records attributed to V D Steen.

At least 19 recordsLinked to original sources
PubMed2006

Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study.

OBJECTIVE: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc). PARTICIPANTS AND METHODS: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose D-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient's health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved. RESULTS: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40-0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15-0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9-14.2 (0.86-1.77 effect size) on the mRSS and 0.21-0.55 (0.32-0.83 effect size) on the HAQ-DI score. CONCLUSION: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.

Adult↗
PubMed2003

Assessment of kidney involvement.

Scleroderma renal crisis (SRC) represents the classic manifestation of kidney involvement in SSc. It particularly occurs in patients with early, rapidly progressive, diffuse skin involvement. Its detection requires the assessment of a few core set variables: arterial blood pressure, serum creatinine, and urinalysis. In clinical investigations SSc patients developing arterial hypertension after the disease onset (new onset hypertension) without SRC should also be reported.

Humans↗
PubMed2001

Improvement in skin thickening in systemic sclerosis associated with improved survival.

OBJECTIVE: The natural history of changes in skin thickening in diffuse scleroderma is quite variable, but the significance of these changes is not clear. Clinical trials are using changes in skin thickening as the primary outcome measure, and thus it would be helpful to determine the significance of improvement in skin thickening. The purpose of the present study was to determine whether improvement in skin thickening over time was associated with improved survival. METHODS: Patients with early (<3 years) diffuse scleroderma who had a baseline evaluation and a repeat skin assessment (modified Rodnan skin score) performed 2 years later (i.e., they had to live for 2 years) were identified from the prospective, observational Pittsburgh Scleroderma Databank. The percentage of improvement and rate of change in the skin score during that time were determined. Patients with an improvement in their skin thickening of >25% of their peak skin score and a rate of change of at least 5 units/year were defined as the improved group; patients with increased skin thickening or no improvement were termed the no improvement group. Demographic and clinical features, organ system involvement, and survival rates were determined and the groups were compared. Regression and Cox regression analyses were used to determine what features were associated with improved skin thickness and survival. RESULTS: Two hundred seventy-eight patients fulfilled the entry criteria, 63% in the improved group and 36% in the no improvement group. The groups were similar in terms of clinical and demographic characteristics at the initial visit. The improved group had an average improvement of 50% of their peak skin score at 2 years after the initial visit. Survival was significantly better in the improved group compared with the unimproved group at 5 and 10 years, with rates of 90% and 80%, respectively, in the improved group and 77% and 60%, respectively, in the no improvement group (P < 0.0001). There were no significant differences in the occurrence of severe organ involvement during the first 2 years to account for the later differences in survival. The duration of the use of D-penicillamine was significantly associated with improved skin thickness and improved survival. CONCLUSION: Among patients surviving the first few years of diffuse scleroderma, striking improvement in skin thickening may occur in up to two-thirds. This improvement in skin thickening is associated with improved survival. Improvement in skin thickening may be useful as a surrogate for improvement in survival in clinical trials.

Disease Progression↗
PubMed2001

Treatment of systemic sclerosis.

Systemic sclerosis is an extremely variable disease in its manifestations and consequently, treatment needs to be individualized depending on the specific problems that each patient has. Limited scleroderma patients have a prolonged duration of Raynaud's phenomenon and puffy fingers before they develop any skin thickening, digital ulcers or gastrointestinal symptoms. They are likely to present with all the classic manifestations of scleroderma. Diffuse scleroderma patients have a much more acute systemic onset with marked whole hand swelling and may initially have only subtle skin thickening. A good understanding of the differences between the natural history of limited and diffuse scleroderma will enable the physician to treat present problems and anticipate future ones more effectively. One should determine which major subset and organ systems are involved before deciding on the appropriate therapy. Advances in organ-specific therapy, particularly calcium channel antagonists in Raynaud's phenomenon, proton pump inhibitors in esophageal reflux, intravenous iloprost and endothelin receptor antagonists in pulmonary hypertension, and ACE inhibitors in renal crisis, have decreased morbidity and mortality in patients with scleroderma. Studies of aggressive therapies to prevent or improve pulmonary fibrosis are in progress. Further clinical experience in wound healing, gastrointestinal malabsorption and physical therapy for loss of motion has helped patients to have a more comfortable life. In recent years, a significant number of controlled clinical trials have been performed and there has been improved understanding of the best way to perform studies and of which patients are most likely to respond to therapy. Penicillamine, methotrexate, photopheresis, relaxin, interferons, and cyclosporine have all been studied in controlled trials with variable outcomes. Although an overall remittive therapy has not yet been determined, new, potentially useful agents are being investigated.

Antirheumatic Agents↗
PubMed2000

Long-term outcomes of scleroderma renal crisis.

BACKGROUND: Although scleroderma renal crisis, a complication of systemic sclerosis, can be treated with angiotensin-converting enzyme (ACE) inhibitors, its long-term outcomes are not known. OBJECTIVE: To determine outcomes, natural history, and risk factors in patients with systemic sclerosis and scleroderma renal crisis. DESIGN: Prospective observational cohort study. SETTING: University program specializing in scleroderma. PATIENTS: 145 patients with scleroderma renal crisis who received ACE inhibitors and 662 patients with scleroderma who did not have renal crisis. MEASUREMENTS: Among patients with renal crisis, the four outcomes studied were no dialysis, temporary dialysis, permanent dialysis, and early death. Demographic, clinical, and laboratory data were compared to identify risk factors for specific outcomes. Follow-up was 5 to 10 years. RESULTS: 61% of patients with renal crisis had good outcomes (55 received no dialysis, and 34 received temporary dialysis); only 4 of these (4%) progressed to chronic renal failure and permanent dialysis. More than half of the patients who initially required dialysis could discontinue it 3 to 18 months later. Survival of patients in the good outcome group was similar to that of patients with diffuse scleroderma who did not have renal crisis. Some patients (39%) had bad outcomes (permanent dialysis or early death). CONCLUSIONS: Renal crisis can be effectively managed when hypertension is aggressively controlled with ACE inhibitors. Patients should continue taking ACE inhibitors even after beginning dialysis in hopes of discontinuing dialysis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Severe organ involvement in systemic sclerosis with diffuse scleroderma.

OBJECTIVE: To determine the natural history and timing of severe involvement of the kidney, heart, lung, gastrointestinal (GI) tract, and skin in patients with systemic sclerosis (SSc) and diffuse cutaneous involvement. METHODS: This study used the Pittsburgh Scleroderma Databank and included patients with diffuse scleroderma who were seen between January 1, 1972 and December 31, 1995. Patients had frequent follow-ups, and a 95% accountability for these patients was maintained. Severe organ involvement was defined as the presence of any of the following: 1) in the kidney, scleroderma "renal crisis"; 2) in the heart, cardiomyopathy, symptomatic pericarditis, or an arrhythmia requiring treatment; 3) in the lung, pulmonary fibrosis on chest radiograph and a forced vital capacity of <55% of predicted; 4) in the GI tract, malabsorption, repeated episodes of pseudoobstruction, or severe problems requiring hyperalimentation; and 5) in the skin, a modified Rodnan skin score >40. The timing from disease onset to survival for each case of severe organ involvement was determined. RESULTS: Of the 953 patients with diffuse scleroderma, kidney involvement developed in 177 (19%), heart involvement in 143 (15%), lung involvement in 151 (16%), GI tract involvement in 74 (8%), and skin involvement in 233 (24%). Severe skin and kidney involvement occurred during the first 3 years in 70% of those who ever developed these problems throughout a mean of 10 years of followup. Severe heart, lung, and GI tract involvement developed during the first 3 years in 45-55% of those who were ever affected. The survival of patients with severe organ involvement was poor. The 9-year cumulative survival rate of all patients with severe organ involvement was 38%, compared with 72% in patients without such involvement (P < 0.0001). CONCLUSION: This study demonstrates that severe organ involvement in SSc patients with diffuse scleroderma most often occurs early in the course of the disease. Survival for patients with severe organ involvement is markedly reduced. Patients should therefore be monitored very closely during the first 3 years of disease for signs and symptoms that may signal the subsequent development of severe organ damage. Potential disease-modifying therapies must be initiated early to modify the natural history of SSc and to improve survival. Patients who survive the first few years without developing severe organ involvement are less likely to develop such life-threatening involvement later in the disease course.

Female↗
PubMed2000

Skin thickness score as a predictor and correlate of outcome in systemic sclerosis: high-dose versus low-dose penicillamine trial.

OBJECTIVE: To study the clinical implications of a skin thickness score > or =20 at first visit and of softening of sclerodermatous skin in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma. METHODS: Skin and visceral involvement were assessed in 134 SSc patients with diffuse scleroderma (mean +/- SD duration of SSc 10 +/- 4 months) as they entered a multicenter drug trial and again at 2 years of followup. Advent of mortality and scleroderma renal crisis (SRC) were assessed during a followup of 4.0 +/- 1.1 years (mean +/- SD). Logistic and linear regression were used to examine the relationship of baseline skin score to morbidity, mortality, and visceral involvement and the relationship of changes in skin score to changes in physical examination, laboratory, and functional variables over 2 years. RESULTS: A baseline skin score > or =20 was associated with heart involvement at baseline (odds ratio [OR] 3.10, 95% confidence interval [95% CI] 1.25-7.70) and was predictive of mortality (OR 3.59, 95% CI 1.23-10.55) and SRC (OR 10.00, 95% CI 2.21-45.91) over 4 years. Multivariate linear regression demonstrated that a model with skin score at baseline (P = 0.0078) and changes in large joint contractures (P = 0.0072), tender joint counts (P = 0.0119), handspread (P = 0.0242), and Health Assessment Questionnaire disability index (HAQ-DI) (P = 0.0244) explained the change in skin score over 2 years (R2 = 0.567). Multivariate logistic regression demonstrated that the investigator's global assessment of improvement was best explained by a model with skin score and HAQ-DI (R2 = 0.455). CONCLUSION: A baseline skin score > or =20 was associated with heart involvement at baseline and predicted mortality and SRC over the subsequent 4 years. Improvement in skin score in these patients with diffuse cutaneous scleroderma was associated with improvement in hand function, inflammatory indices, joint contractures, arthritis signs, overall functional ability, and the examining investigator's global assessment of improvement.

Adult↗
PubMed1999

Fertility and pregnancy outcome in women with systemic sclerosis.

OBJECTIVE: To determine fertility and pregnancy outcome in women with systemic sclerosis (SSc; scleroderma) who had disease onset before age 45 years. METHODS: All living women with scleroderma who had first been evaluated at the University of Pittsburgh Scleroderma Clinic after January 1, 1972 were sent a detailed self-administered questionnaire in 1986 specifically concerning pregnancy outcomes and infertility. This group was compared with 2 race- and age-matched control groups, one comprising women with rheumatoid arthritis (RA) and one comprising healthy neighborhood women identified by random-digit dialing. We determined the number, history, treatment, and outcome of women who either had never been pregnant or had attempted to become pregnant unsuccessfully for more than 1 year. We also obtained data regarding pregnancy outcomes, including the frequency of miscarriage, premature births, small full-term infants, perinatal deaths, and births of live healthy infants. RESULTS: The study group comprised 214 women with SSc, 167 with RA, and 105 neighborhood controls. There were no significant differences in the overall rates of miscarriage, premature births, small full-term births, or neonatal deaths between the 3 groups. Women with SSc were more likely than those without SSc to have adverse outcomes of pregnancy after the onset of their rheumatic disease, particularly premature births (also seen in RA women after disease onset) and small full-term infants. Although a significantly greater number of women with SSc had never been pregnant, there were no significant differences in the frequency of never having been pregnant or of infertility in the 3 groups after adjustment for contributing factors. CONCLUSION: This study indicates that women with SSc have acceptable pregnancy outcomes compared with those of women with other rheumatic disease and healthy neighborhood controls. Infertility was not a frequent problem. We believe that there are no excessive pregnancy risks to women with SSc or their infants. However, a well-timed pregnancy with careful obstetric monitoring will maximize the likelihood of a successful outcome.

Adult↗
PubMed1999

Pregnancy in women with systemic sclerosis.

OBJECTIVE: To determine pregnancy outcomes in women with systemic sclerosis. METHODS: Women of childbearing age with systemic sclerosis seen at the University of Pittsburgh between 1987 and 1996 were observed prospectively. Pregnancy outcomes included abortion, miscarriage, preterm and term birth, and perinatal death. Complications of pregnancy and scleroderma were determined during and after pregnancy. RESULTS: Fifty-nine women with systemic sclerosis had 91 pregnancies during the 10-year period. No increase in the frequency of miscarriage was found, except in those with long-standing diffuse scleroderma. Preterm births occurred in 29% of pregnancies, and all but one of the infants survived. Symptoms related to scleroderma, particularly Raynaud phenomenon, improved during pregnancy, but esophageal reflux became worse. After pregnancy, some women with diffuse scleroderma had increased skin thickening. There were three cases of renal crisis during pregnancy, all in women with early diffuse scleroderma. Four women had five healthy infants while taking angiotensin-converting-enzyme inhibitors. CONCLUSION: Women with systemic sclerosis can safely have healthy pregnancies. Those with early diffuse scleroderma should wait until their disease stabilizes before becoming pregnant to decrease the risk of renal crisis. High-risk pregnancy management should be standard for all scleroderma pregnancies because of the high frequency of premature births.

Adult↗
PubMed1999

Early undifferentiated connective tissue disease (CTD). VI. An inception cohort after 10 years: disease remissions and changes in diagnoses in well established and undifferentiated CTD.

OBJECTIVE: (1) To review the diagnoses after 10 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD). (2) To examine the death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients had less than one year of signs and/or symptoms of CTD. Diagnoses of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and poly/dermatomyositis (PM/DM) were made in 197 patients using accepted diagnostic and classification criteria. Diagnoses of undifferentiated CTD were made in 213 patients. These latter patients were placed in 3 categories: isolated Raynaud's phenomenon (RP), unexplained polyarthritis (UPA), and undifferentiated CTD (UCTD), defined as meeting at least 3 of 11 specific manifestations of CTD. The diagnoses and remissions in all patients after 10 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The 10 year survival was at least 87% in all diagnostic categories, with the exception of SSc, in which it was 56%. The progression of UPA to RA occurred infrequently. The presence of antinuclear antibodies suggested that UPA may develop additional symptoms and/or a specific diagnosis, and RP in these patients increased the likelihood of progressing to UCTD or a specific well established CTD. Ten percent of patients with RP progressed to SSc. In patients with UCTD, joint pain/tenderness and swelling counts were associated with progression to other diagnoses including RA, while either serositis, malar rash, or discoid lupus suggested the eventual diagnosis of SLE. CONCLUSION: The survival of patients with SSc was poor, with most dying early in the course of their disease. Remissions were seen in all groups of patients except SSc. The remissions were sometimes transient in SLE. Undifferentiated disease at initial examination within 12 months of onset usually remains undifferentiated.

Connective Tissue Diseases↗
PubMed1999

A disease severity scale for systemic sclerosis: development and testing.

OBJECTIVE: To develop and test a severity scale for individual organ involvements in systemic sclerosis (SSc, scleroderma). METHODS: An international study group completed the following tasks: (1) developed a glossary of terms including all pertinent variables for 9 potentially affected organ systems; (2) collected prospective data to determine the feasibility and practicality of each proposed variable; (3) revised the initial list of variables; (4) determined the association of each variable with mortality (a proxy for morbidity) using 579 patients in an existing comprehensive longitudinal scleroderma databank; (5) developed a severity grading scale for each organ system by discussion and consensus; and (6) externally validated the scale using an independent group of 680 patients from the same databank. RESULTS: Nine organ-specific severity scales were developed from 0 (no documented involvement) to 4 (endstage disease). The data required for scale completion are relatively easy and practical for all physicians to obtain. CONCLUSION: This preliminary severity scale will be useful for assessing disease severity status in individual patients both at one point in time and longitudinally. The severity scale will assist in the design and conduct of clinical trials and the comparison of study populations with one another. The scale will serve as a framework for developing a scleroderma disease activity index.

Humans↗
PubMed1999

Occupational scleroderma.

Various occupations and environmental exposures have been suggested to possibly cause or precipitate systemic sclerosis. This article reviews studies of vinyl chloride, silica dust, and chemicals, including trichloroethene and epoxy resins, that may play a role in triggering the disease. Although we would like to believe that this disease is caused by an external source, the lack of similarity of exposures, the low frequency of the disease in comparison to the exposure rate, and the lack of a convincing association with any substance make it impossible to identify a specific trigger.

Female↗
PubMed1998

Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States.

OBJECTIVE: To provide a single source for the best available estimates of the national prevalence of arthritis in general and of selected musculoskeletal disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain). METHODS: The National Arthritis Data Workgroup reviewed data from available surveys, such as the National Health and Nutrition Examination Survey series. For overall national estimates, we used surveys based on representative samples. Because data based on national population samples are unavailable for most specific musculoskeletal conditions, we derived data from various smaller survey samples from defined populations. Prevalence estimates from these surveys were linked to 1990 US Bureau of the Census population data to calculate national estimates. We also estimated the expected frequency of arthritis in the year 2020. RESULTS: Current national estimates are provided, with important caveats regarding their interpretation, for self-reported arthritis and selected conditions. An estimated 15% (40 million) of Americans had some form of arthritis in 1995. By the year 2020, an estimated 18.2% (59.4 million) will be affected. CONCLUSION: Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.

Adolescent↗
PubMed1998

Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis.

OBJECTIVE: To determine whether the initiation of corticosteroids or other types of therapy affects the development of scleroderma renal crisis (SRC). METHODS: Using a case-control study, 110 patients with systemic sclerosis who developed SRC between 1981 and 1993 were closely matched with controls on sex, race, age, disease duration, skin score, levels of creatine phosphokinase, and presence of tendon friction rubs. Corticosteroid use was determined prior to the onset of SRC in cases or prior to the first visit in controls. Cases were compared with matched controls using McNemar's matched-pair analysis and conditional logistic regression analysis. The effects of other drugs, including D-penicillamine, nonsteroidal antiinflammatory drugs (NSAIDs), calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors, were also evaluated. RESULTS: In the 6 months prior to SRC onset or to the first visit, high-dose corticosteroids (> or =15 mg/day prednisone or equivalent) were administered significantly more frequently in SRC patients (36%) than in the controls (12%) (McNemar's odds ratio 4.37, 95% confidence interval 2.03-9.43, P < 0.0001). New use of low-dose steroids, continuous use of any steroid dose, NSAIDs, calcium channel blockers, and ACE inhibitors were not associated with an increased risk of SRC. Antecedent D-penicillamine therapy may have been protective against the development of SRC in controls. CONCLUSION: This retrospective case-control study has shown a significant association between antecedent high-dose corticosteroid therapy and the development of SRC. These results should discourage the use of high-dose corticosteroids in patients with early diffuse scleroderma who are at increased risk of developing SRC.

Acute Kidney Injury↗
PubMed1998

Clinical manifestations of systemic sclerosis.

Systemic sclerosis is a multisystem disease characterized by inflammation and fibrosis of many organs. There are two major subsets, limited cutaneous (the old CREST syndrome) and diffuse cutaneous scleroderma. The major difference is the pace of disease. Limited scleroderma patients often have a long history of Raynaud's phenomenon before other symptoms. They have skin thickening limited to hands and frequently have problems with digital ulcers and esophageal dysmotility. Although generally a milder form than diffuse scleroderma, they can have life-threatening complications from small intestine hypomotility and pulmonary hypertension. Diffuse scleroderma patients have a much more acute onset, with many constitutional symptoms, arthritis, carpal tunnel syndrome, and marked swelling of hands and legs. They get widespread skin thickening, progressing from their fingers to their trunk. Internal organ problems, including gastrointestinal and pulmonary fibrosis, are common, but severe life-threatening involvement of the heart and kidneys occurs. Understanding the type of disease that occurs in these two subsets will enable the physician to anticipate problems, aggressively treat those that can be treated, and give the patient a better understanding of their disease.

Adult↗
PubMed1998

The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis.

OBJECTIVE: To test the ability of the modified Rodnan skin score to reflect skin thickness in skin biopsies from 141 patients with systemic sclerosis (SSc) obtained at entry during a prospective, double blind study of ketanserin versus placebo in SSc. METHODS: Punch skin biopsies (4 mm) were obtained from the dorsal surface of the distal forearm of 141 patients. Biopsy specimens were trimmed and weighed (wet weight) and then desiccated and reweighed (dry weight). Skin score was recorded for 17 areas, graded 0-4+, while edema was graded 0-4+ in 10 of the same sites using finger pressure. RESULTS: Total skin score correlated with wet weight (r = 0.553) and dry weight (r = 0.517) of the skin biopsies. Local skin score from the biopsied forearm also correlated with wet and dry weight (r = 0.536 and 0.530, respectively). Dry weight as a percentage of wet weight was the same for diffuse cutaneous SSc (dSSc) and limited cutaneous SSc (lSSc) (30.7% for both, NS), despite increased wet weight in patients with dSSc versus lSSc (17.75 vs 13.03 g; p < 0.001). Edema scores correlated poorly both with wet weight (r = 0.069) and dry weight (r = 0.169). CONCLUSION: Total and forearm skin score correlates well with both wet and dry forearm skin biopsy weight from forearm biopsies, indicating that skin score reflects the underlying pathology of SSc. Further, the percentage of dry to wet weight is similar for lSSc and dSSc, supporting the usefulness of skin score in differentiating SSc disease subtypes.

Adolescent↗
PubMed1998

Early undifferentiated connective tissue disease. V. An inception cohort 5 years later: disease remissions and changes in diagnoses in well established and undifferentiated connective tissue diseases.

OBJECTIVE: To review the diagnoses after 5 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD); to examine death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients was identified in 10 academic rheumatology practices. They had less than one year of signs and/or symptoms of CTD. Diagnoses of specific well established CTD were made using accepted diagnostic and classification criteria. The diagnoses after 5 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The progression of unexplained polyarthritis to rheumatoid arthritis occurred infrequently. Ten percent of patients with isolated Raynaud's phenomenon progressed to systemic sclerosis (SSc). The 5 year survival was over 90% in all diagnostic categories, with the exception of SSc, in which it was 64%. CONCLUSION: Patients with a well established CTD usually continued with the same diagnosis. Patients with undifferentiated CTD tended to remain undifferentiated or to remit.

Arthritis↗