Diffuse Cutaneous Scleroderma Research Articles

Treatment of complications associated with systemic sclerosis

Current and emerging drug therapy options for patients suffering from the complications of systemic sclerosis are presented. Systemic sclerosis is a devastating and rare, chronic, autoimmune disease and is characterized by various disease complications due to skin thickening, vascular damage, and inflammation affecting numerous organs. There are two major subtypes of systemic sclerosis: limited cutaneous scleroderma and diffuse cutaneous scleroderma. Patients suffer from Raynaud's phenomenon, skin changes, musculoskeletal changes, gastrointestinal complications, pulmonary complications, scleroderma renal crisis, and dryness of the eyes and mouth. Currently, there is no cure for systemic sclerosis, but research is focusing on decreasing the progression and symptoms of this disease. Raynaud's phenomenon is the temporary vasoconstriction of the small vessels of the fingers, toes, tip of the nose, and earlobes. Skin thickening is the cardinal symptom of systemic sclerosis, with as many as 50% of patients developing digital ulcers. Care of these ulcers is crucial in the prevention of osteomyelitis and other infections. Malabsorption syndrome may also occur in patients, many of whom will eventually require parenteral nutrition to maintain their caloric needs. Pulmonary interstitial fibrosis and pulmonary arterial hypertension are additional serious complications of systemic sclerosis. The use of prostacyclin analogues, phosphodiesterase inhibitors, calcium-channel blockers, cyclophosphamide, bosentan, and other agents has been investigated in patients suffering from the complications of systemic sclerosis. Systemic sclerosis is characterized by various circulatory, dermatological, gastrointestinal, musculoskeletal, pulmonary, and renal complications. Although there is no cure for systemic sclerosis, management of its associated complications can help improve patients' quality of life.

High-dose cyclophosphamide without stem cell rescue in scleroderma

Objective:To investigate the safety and tolerability of high-dose cyclophosphamide without stem cell rescue in scleroderma.Methods:An open-label, single-site, uncontrolled study design entered patients with active diffuse cutaneous scleroderma. Patients were treated...

Using a self-reported functional score to assess disease progression in systemic sclerosis

This study compares the scleroderma Functional Score (FS) with the validated Disability Index of the Health Assessment Questionnaire (HAQ-DI) and other outcome measures. The aim is to determine if the FS is useful as an objective assessment tool for longitudinal evaluation of the functional impact of systemic sclerosis (SSc). A cohort of 135 patients was studied (M:F, 15:120), with a mean age of 45.7 (S.D. = 13.2) at SSc disease onset. 69 (51%) had diffuse cutaneous scleroderma (dcSSc) and 66 (49%) had limited disease (lcSSc). The mean interval between the two assessments was 1.8 yrs (S.D. = 1.2). Functional impact was determined by evaluating archived self-reported questionnaires (FS, HAQ and scleroderma-VAS). Concurrent evaluation of the disease severity score was derived from clinical data stored in the hospital database and from medical case note reviews. At baseline, the mean FS was 11.0 (S.D. = 9.0) and at reassessment 12.0 (S.D. = 9.2). The mean absolute change in FS between the two assessments was 4.1 (S.D. = 4.9). With time 49% (n = 66) showed a clinically significant change in their functional ability with regard to FS, of these 29% (n = 39) worsened and 20% (n = 27) improved. There was an excellent cross-sectional correlation between the FS and the HAQ-DI (rho = 0.90; P < 0.0001). Also, a strong correlation between longitudinal change in these two outcome measures (rho = 0.59, P < 0.0001) was observed. This is the first longitudinal study of the scleroderma FS. It demonstrates that the FS can capture bidirectional and clinically significant changes in SSc related disability over time. The concurrent validity of the FS is asserted through its strong correlation with the HAQ-DI. The FS is a disease-specific, inexpensive and practical instrument for assessing functional status in SSc. It is a promising self-administered assessment tool for use in evaluating new SSc treatments.

Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension

The aim of the present study was to investigate the presence of anti-fibroblast antibodies in patients with idiopathic or scleroderma-associated pulmonary arterial hypertension (PAH) and healthy controls. PAH was documented by right-heart catheterisation (mean pulmonary artery pressure at rest >25 mmHg). Serum immunoglobulin (Ig)G and IgM reactivities of patients with idiopathic PAH (n = 35), scleroderma-associated PAH (n = 10), diffuse (n = 10) or limited cutaneous (n = 10) scleroderma without PAH and age- and sex-matched healthy individuals (n = 65) were analysed by cell-based ELISA and immunoblotting on normal human fibroblasts. As assessed by ELISA, 14 out of 35 (40%) patients with idiopathic PAH and three out of 10 (30%) patients with scleroderma-associated PAH expressed anti-fibroblast IgG antibodies. IgG from all individuals bound to one major 40-kDa protein band. IgG from patients with idiopathic PAH bound to two 25- and 60-kDa bands with a higher intensity than IgG from other individuals. In conclusion, immunoglobulin G anti-fibroblast antibodies are present in the serum of patients with pulmonary arterial hypertension. Immunoglobulin G from patients with idiopathic pulmonary arterial hypertension or scleroderma-associated pulmonary arterial hypertension express distinct reactivity profiles with fibroblasts antigens, suggesting distinct target antigens.

Ascending aortic aneurysm in a man with scleroderma

Macrovascular involvement in scleroderma has received relatively little attention. We hereby describe a 5.6-cm ascending aortic aneurysm in a 56-year-old man presenting with increased dyspnea, diagnosed with antibody-negative, rapidly progressive diffuse cutaneous scleroderma. The patient had sclerosis and induration of all extremities, face, thorax and abdomen. Other features included Raynaud's phenomenon, arthralgia, dysphagia, dyspnea attributed to pulmonary fibrosis, pericardial effusion, and cardiomyopathy. To the best of our knowledge, there is only one other report to date in the English language of a thoracic aortic aneurysm associated with scleroderma.

Autologous non-myeloablative hematopoietic stem cell transplantation for diffuse scleroderma

Patients with diffuse cutaneous scleroderma with visceral involvement have an overall 10-year survival of 35–68%. There is no known therapy that is able to alter the natural course of the disease. Here we report outcomes of autologous HSCT phase I study utilizing non-myeloablative lymphoablative conditioning regimen. Nine patients with diffuse scleroderma and poor clinical features were enrolled. Candidates were less than 65 years old and had either Rodnan skin score of more than 14 or lung diffusion capacity of carbon monoxide (DLCO) less than 80%, interstitial lung disease, elevated ESR, renal involvement, or abnormal electrocardiogram. Patients with pulmonary hypertension (pulmonary artery systolic pressure >45 mmHg) were excluded. Peripheral blood stem cells were mobilized with intravenous (IV) cyclophosphamide (CY) 2g/m2 and subcutaneous granulocyte colony-stimulating factor 10 mcg/kg daily. The graft was not manipulated. The conditioning regimen consisted of CY 200 mg/kg and rabbit antithymocyte globulin (rATG) 7.5 mg/kg. The procedure was well tolerated. Anticipated cytopenias, neutropenic fever, and mild fluid overload were easily controlled. White blood cells and platelets both engrafted on average day 8 (range days 7–9 and days 0–10, respectively). The median numbers of infused CD34+ and CD3+ cells were 8.31 × 106/kg (range 2.35–14.7 × 106/kg) and 2.03 × 108/kg (range 0.41–6.83 × 108/kg), respectively. We observed a marked improvement of skin score in all subjects, whereas cardiac function (ejection fraction, pulmonary artery systolic pressure), pulmonary function (DLCO) and renal function (creatinine) remained stable. One patient with advanced disease and poor performance status died 2 years after the transplant from progressive disease. Two patients developed recurrence of skin tightness without compromising organ function, however, with institution of mycophenolate mofetil both showed gradual improvement of skin scores. After median follow-up of 20 (range 5–32) months, the overall survival is 89% (8 out of 9 patients) and progression-free survival with continuing improvement is 67% (6 out of 9 patients). Autologous HSCT with CY/rATG conditioning regimen is safe and effective. A randomized study (ASSIST: American Scleroderma Stem Cell vs Immune Suppression Trial), comparing HSCT to IV pulse CY is now enrolling patients. Patients with diffuse cutaneous scleroderma with visceral involvement have an overall 10-year survival of 35–68%. There is no known therapy that is able to alter the natural course of the disease. Here we report outcomes of autologous HSCT phase I study utilizing non-myeloablative lymphoablative conditioning regimen. Nine patients with diffuse scleroderma and poor clinical features were enrolled. Candidates were less than 65 years old and had either Rodnan skin score of more than 14 or lung diffusion capacity of carbon monoxide (DLCO) less than 80%, interstitial lung disease, elevated ESR, renal involvement, or abnormal electrocardiogram. Patients with pulmonary hypertension (pulmonary artery systolic pressure >45 mmHg) were excluded. Peripheral blood stem cells were mobilized with intravenous (IV) cyclophosphamide (CY) 2g/m2 and subcutaneous granulocyte colony-stimulating factor 10 mcg/kg daily. The graft was not manipulated. The conditioning regimen consisted of CY 200 mg/kg and rabbit antithymocyte globulin (rATG) 7.5 mg/kg. The procedure was well tolerated. Anticipated cytopenias, neutropenic fever, and mild fluid overload were easily controlled. White blood cells and platelets both engrafted on average day 8 (range days 7–9 and days 0–10, respectively). The median numbers of infused CD34+ and CD3+ cells were 8.31 × 106/kg (range 2.35–14.7 × 106/kg) and 2.03 × 108/kg (range 0.41–6.83 × 108/kg), respectively. We observed a marked improvement of skin score in all subjects, whereas cardiac function (ejection fraction, pulmonary artery systolic pressure), pulmonary function (DLCO) and renal function (creatinine) remained stable. One patient with advanced disease and poor performance status died 2 years after the transplant from progressive disease. Two patients developed recurrence of skin tightness without compromising organ function, however, with institution of mycophenolate mofetil both showed gradual improvement of skin scores. After median follow-up of 20 (range 5–32) months, the overall survival is 89% (8 out of 9 patients) and progression-free survival with continuing improvement is 67% (6 out of 9 patients). Autologous HSCT with CY/rATG conditioning regimen is safe and effective. A randomized study (ASSIST: American Scleroderma Stem Cell vs Immune Suppression Trial), comparing HSCT to IV pulse CY is now enrolling patients.

Autoantibodies in Systemic Sclerosis

To describe the clinical, laboratory, and prognostic features associated with the scleroderma-specific autoantibodies. Using the Pittsburgh Scleroderma Databank, all consecutive patients seen between 1980 and 1995 who had autoantibody studies performed were studied. Anticentromere antibodies (ACA), antitopoisomerase (TOPO), anti-U1-RNP (U1-RNP), anti-RNA Polymerase III (Pol 3), anti-U3-RNP (U3-RNP), anti-Th/To (Th/To), and anti-Pm/Scl (Pm/Scl) were determined according to previously described methods. The frequency of clinical features, organ system outcomes, and survival within the patients with a specific antibody were cumulative over the course of the disease. The frequency of a specific feature was compared across groups to identify significant manifestations and outcomes in patients with a specific antibody. Some demographic, clinical, and organ system findings were associated with the specific antibody, and other features with the scleroderma subtype (limited cutaneous or diffuse cutaneous scleroderma). U3-RNP, U1-RNP, and TOPO were seen more commonly in African-American patients, and ACA was seen in older, female Caucasians. Muscle inflammation was seen in patients with U1-RNP and U3-RNP. Digital tip ulcers and digital tuft resorption were seen more frequently in those with ACA and TOPO. A vasculopathy causing pulmonary hypertension typically occurs with ACA and pulmonary fibrosis with TOPO; however, both types of lung disease were seen in patients with nucleolar antibodies, Th/To and U3-RNP. Importantly, severe interstitial fibrosis was rarely seen in cases with Pol 3. Renal crisis was strongly associated with Pol 3. Survival within limited scleroderma was decreased in the Th/To patients compared with ACA patients. Within the diffuse scleroderma group, patients with Pol 3 had the best survival. Scleroderma autoantibodies are associated with very specific demographic, clinical, organ system, and survival features. The determination of scleroderma autoantibodies may be helpful in assessing the prognosis, monitoring, and treatment of scleroderma patients.

Évaluation de la dépression et de l'anxiété au cours de la sclérodermie systémique

Objective. – To determine the prevalence of depression and anxiety in patients receiving follow-up in France for systemic sclerosis. Patients. – We prospectively evaluated 42 patients admitted for a follow-up evaluation of systemic sclerosis, including 18 with diffuse cutaneous scleroderma and 24 with limited cutaneous scleroderma. Patients admitted for recent organ involvement were excluded. Mean age was 57 ± 13 years, mean disease duration was 10.2 ± 8 years, and the mean functional Health Assessment Questionnaire score was 0.682 ± 0.649. Only four patients had a history of antidepressive drug therapy. We used the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale to evaluate depression and anxiety, respectively. Results. – Eighteen (43%) patients met criteria for depression and 11 (26%) had scores above the cutoff usually taken to define moderate-to-severe depression. Twenty-seven (64%) patients met criteria for minor anxiety and eight (19%) for major anxiety. Depression and anxiety were strongly correlated with each other ( r = 0.89; P < 0.0001). The MADRS score was significantly higher in the patients with pulmonary restrictive disease ( P = 0.009) but was not associated with the extent of skin involvement, organ involvement, or disability. Conclusion. – Systemic scleroderma is associated with a high prevalence of depression and anxiety. These disorders should be looked for routinely and the need for specific treatment evaluated.

Evaluation of depression and anxiety in patients with systemic sclerosis

Objective. – To determine the prevalence of depression and anxiety in patients receiving follow-up in France for systemic sclerosis. Patients. – We prospectively evaluated 42 patients admitted for a follow-up evaluation of systemic sclerosis, including 18 with diffuse cutaneous scleroderma and 24 with limited cutaneous scleroderma. Patients admitted for recent organ involvement were excluded. Mean age was 57 ± 13 years, mean disease duration was 10.2 ± 8 years, and the mean functional Health Assessment Questionnaire score was 0.682 ± 0.649. Only four patients had a history of antidepressive drug therapy. We used the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale to evaluate depression and anxiety, respectively. Results. – Eighteen (43%) patients met criteria for depression and 11 (26%) had scores above the cutoff usually taken to define moderate-to-severe depression. Twenty-seven (64%) patients met criteria for minor anxiety and eight (19%) for major anxiety. Depression and anxiety were strongly correlated with each other ( r = 0.89; P < 0.0001). The MADRS score was significantly higher in the patients with pulmonary restrictive disease ( P = 0.009) but was not associated with the extent of skin involvement, organ involvement, or disability. Conclusion. – Systemic scleroderma is associated with a high prevalence of depression and anxiety. These disorders should be looked for routinely and the need for specific treatment evaluated.

Scleroderma renal crisis: poor outcome despite aggressive antihypertensive treatment.

Scleroderma renal crisis (SRC) is a rare but feared complication of scleroderma. Angiotensin--converting enzyme (ACE) inhibition has significantly improved survival, but it is unknown whether prophylactic ACE inhibitors will prevent this complication. To determine: (i) the frequency of SRC in our cohort of well-characterized scleroderma patients resident in South Australia, (ii) any predisposing clinical and serological features, (iii) median disease duration at which SRC occurs, (iv) possible precipitants, (v) disease outcome, and (vi) whether patients were taking ACE inhibitors prior to onset of SRC. Systematic review of the clinical course of all patients registered on the South Australian Scleroderma Register. SRC occurred in 16 patients. This constituted 2.8% of a total scleroderma cohort and 15% of the diffuse scleroderma cohort identified in South Australia. All 16 patients had diffuse cutaneous scleroderma. SRC occurred at a median disease duration of 15 months (range 1 week-11 years). Disease outcome was poor (five deaths, three requiring long-term dialysis and only two patients regaining a normal creatinine) despite aggressive antihypertensive treatment (including ACE inhibitors) in an intensive care or specialized renal unit. Two patients were later able to discontinue dialysis. Only two patients were taking small doses of ACE inhibitors prior to the onset of their SRC. The frequency of Scl-70 was decreased in the SRC group (P = 0.003). SRC is a rare event occurring in a small proportion of patients with diffuse scleroderma. The outcome of SRC was poor despite aggressive antihypertensive treatment. It is hypothesized that prophylactic ACE inhibition in susceptible patients might prevent or ameliorate this complication.

Scleroderma fibroblasts promote migration of mononuclear leucocytes across endothelial cell monolayers.

Perivascular infiltrates of inflammatory cells are a hallmark of lesional skin in scleroderma. We have explored the potential for scleroderma fibroblasts to modulate mononuclear leucocyte migration across endothelial cell monolayers in tissue culture, and to regulate expression of endothelial cell adhesion molecules. Fibroblasts were grown from skin biopsies of eight patients with active diffuse cutaneous scleroderma and from four healthy controls. Co-culture and conditioned medium transfer experiments examined the effect of soluble fibroblast products on mononuclear leucocyte (U937) cell migration across endothelial cell (1E-7) monolayers grown on tissue culture inserts. Co-culture of scleroderma, but not control fibroblasts, promoted transendothelial migration of U937 cells. Scleroderma fibroblast-conditioned medium had qualitatively similar effects and equivalent results were obtained using Jurkat-6 (T lymphocyte) cells, and with peripheral blood mononuclear cells from a patient with diffuse cutaneous scleroderma. Promotion of leucocyte migration does not appear to result from increased endothelial adhesion molecule expression, since fibroblast-conditioned medium did not up-regulate endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. Moreover, leucocyte migration across cytokine-activated endothelial cell layers in co-culture with fibroblasts was less than across resting cells, although the selective effect of scleroderma fibroblast co-culture persisted. Recombinant monocyte chemoattractant protein-1 (MCP-1) or IL-8 increased passage of mononuclear leucocytes across endothelial cell monolayers, whilst anti-MCP-1, but not anti-IL-8 antibodies, significantly reduced the effect of fibroblast conditioned medium. These data suggest that systemic sclerosis (SSc) fibroblasts promote leucocyte migration across endothelial cell monolayers in tissue culture via an MCP-1-dependent mechanism. These findings may be relevant to the perivascular mononuclear leucocyte infiltrates characteristic of early SSc lesions.

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

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. 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. 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). 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.

Diffuse and limited cutaneous systemic scleroderma.

Juvenile systemic scleroderma (jSSc) is a rare disease. Based on the first large data collection on this patient group, the disease course was demonstrated to differ from that in adults. The concept of persistence of maternal cells in patients with SSc remains pathogenetically fascinating, as does the resemblance with graft-versus-host-disease. In view of new therapeutic options, controlled trials have not established a gold standard for treatment, but autologous bone marrow transplantation may be considered a rescue therapy for selected patients. Palliative therapies have also improved markedly in recent years. The first controlled trials for patients with jSSc are being proposed.

Correlates of the disability index of the health assessment questionnaire: a measure of functional impairment in systemic sclerosis.

To evaluate functional impairment in systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma at the time of entry into a trial of a therapeutic intervention (D-penicillamine). The 20-item Disability Index of the Health Assessment Questionnaire (HAQ-DI) was administered to 134 patients as they entered a multicenter trial of high-dose versus low-dose D-penicillamine. All patients had diffuse SSc of < 18 months' duration. SSc patients who had severe organ system involvement and recent renal crisis and who were receiving prednisone > 10 mg/day were excluded from entry. Logistic regression modeling was used to examine the relationship of HAQ-DI scores to SSc skin and organ system involvement. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to estimate effects. The mean (+/-SD) HAQ-DI score at entry was 1.04 +/- 0.67. Fifty-three percent of patients had HAQ-DI scores > or = 1.0 (signifying moderate-to-severe functional impairment). Multivariate logistic regression demonstrated that impaired fist closure > or = 23 mm (OR 4.24, 95% CI 1.68-10.70), reduced handspread < or = 175 mm (OR 4.5, 95% CI 1.80-11.24), joint tenderness count > or = 1.0 (OR 2.93, 95% CI 1.16-7.40), age > or = 43 years (OR 2.44, 95% CI 1.01-5.95), platelet count > or = 330,000/mm3 (OR 2.30, 95% CI 0.96-5.57), and female sex (OR 2.43, 95% CI 0.77-7.73) were the most important correlates of HAQ-DI scores > or = 1.0. Increased HAQ-DI scores at baseline were correlated with reduced fist closure, reduced hand-spread, elevated platelet count, presence of tender joints, older age, and female sex. The most important contributor to functional impairment was hand dysfunction. Even within the first 18 months after SSc onset, moderate-severe functional impairment (HAQ-DI scores > or = 1.0) was frequent (53%) in this group of diffuse SSc patients. In early diffuse SSc, the self-administered HAQ-DI is therefore a valuable assessment of function that correlates with objective physical and laboratory measures of SSc disease involvement. Abnormal HAQ-DI scores may support patient claims of functional impairment, help to focus physician attention on implementing measures to reduce functional impairment, and be useful in reflecting the disease course over time.

Is Anti-Topoisomerase I a Serum Marker of Pulmonary Involvement in Systemic Sclerosis?

To determine the value of the level of anti-topoisomerase I (anti-topo I) to evaluate lung involvement defined by abnormal high-resolution computed tomography (HRCT) score and pulmonary function tests (PFTs) in systemic sclerosis (SS). Forty-eight patients with SS, 20 with lung involvement and 28 with no lung involvement. PFT measurement, HRCT scoring of lung involvement, and anti-topo I assay by enzyme-linked immunosorbent assay. Normal anti-topo I level was defined as < 30. There was a significant association between cutaneous extent and anti-topo I level (6.5% of patients with limited cutaneous scleroderma had abnormal anti-topo I levels vs 70.6% of patients with diffuse cutaneous scleroderma, p = 0.0001). In patients with diffuse cutaneous scleroderma, pulmonary involvement was associated with a higher percentage of abnormal anti-topo I level: 91.7% vs 20% (p = 0.010). In patients with diffuse cutaneous scleroderma, a significant association was found between the class of anti-topoII level and total lung capacity (median, 69 in patients with abnormal anti-topo I level vs 87 in patients with normal anti-topo I level, p = 0.010), between the class of anti-topo I level and HRCT score (median, 12 in patients with abnormal anti-topo I level vs 5 in patients with normal anti-topo I level, p = 0.05). Anti-topo I can be considered as a marker of lung involvement in patients with diffuse cutaneous scleroderma.

African-American Race and Antibodies to Topoisomerase I Are Associated With Increased Severity of Scleroderma Lung Disease

To determine whether African-American race is independently associated with lung disease in scleroderma. Retrospective review. University medical center in Baltimore. One hundred one patients with diffuse cutaneous scleroderma with available serum samples. Patients underwent lung function testing as part of their routine clinical care. Percent predicted values adjusted for race were calculated for FVC, single-breath carbon monoxide diffusing capacity (Dco), and FEV1. Serum samples were assayed for the presence of antibodies to topoisomerase I and RNA polymerase II. Scleroderma patients of African-American race had lower percent predicted values than white patients for FVC (p<0.002), Dco (p<0.0001), and FEV1 (p<0.0001). Antibodies to topoisomerase I but not antibodies to RNA polymerase II were also associated with lung function. African-American scleroderma patients were distinct from white patients in having younger age of onset and higher prevalence of antibodies to topoisomerase I. In multivariate analyses accounting for sex, age, smoking history, years of scleroderma symptoms, and RNA polymerase II antibody status, African-American race and topoisomerase I antibody status independently predicted lower lung function. African-American race and antibodies to topoisomerase I are independent risk factors for scleroderma lung disease.

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.

The palpable tendon friction rub

AbstractObjective. To evaluate the clinical and prognostic significance of palpable tendon friction rubs in patients with systemic sclerosis (SSc).Methods. SSc patients evaluated prospectively at the University of Pittsburgh were examined serially for the presence of tendon friction rubs on physical examination. Demographic, clinical, and laboratory features of disease were obtained by patient examination, annual patient questionnaire, and medical record review. Patients were classified as having limited or diffuse scleroderma according to standard definitions. The prognostic significance of the presence of tendon friction rubs was determined using this comprehensive database.Results. The SSc patients (n = 1,305) were first evaluated during 1972 through 1991 and were followed up for a mean of 6.3 years. Tendon friction rubs were detected most frequently in patients who had or who developed diffuse cutaneous involvement. There were strong correlations between the presence of tendon friction rubs and symptoms and signs typical of diffuse scleroderma, including more severe skin thickening, more frequent heart and kidney involvement, and decreased survival. In multiple regression analyses, the presence of 1 or more tendon friction rubs was one of the best predictors of both evolution to diffuse scleroderma and reduced survival.Conclusion. The palpable tendon friction rub is an easily detected, inexpensively obtained physical examination finding which is highly associated with diffuse cutaneous scleroderma and decreased survival. This observation should lead to the early diagnosis of diffuse scleroderma and should identify patients at high risk for serious visceral involvement who are thus candidates for potential disease‐modifying therapy.

The palpable tendon friction rub: an important physical examination finding in patients with systemic sclerosis.

To evaluate the clinical and prognostic significance of palpable tendon friction rubs in patients with systemic sclerosis (SSc). SSc patients evaluated prospectively at the University of Pittsburgh were examined serially for the presence of tendon friction rubs on physical examination. Demographic, clinical, and laboratory features of disease were obtained by patient examination, annual patient questionnaire, and medical record review. Patients were classified as having limited or diffuse scleroderma according to standard definitions. The prognostic significance of the presence of tendon friction rubs was determined using this comprehensive database. The SSc patients (n = 1,305) were first evaluated during 1972 through 1991 and were followed up for a mean of 6.3 years. Tendon friction rubs were detected most frequently in patients who had or who developed diffuse cutaneous involvement. There were strong correlations between the presence of tendon friction rubs and symptoms and signs typical of diffuse scleroderma, including more severe skin thickening, more frequent heart and kidney involvement, and decreased survival. In multiple regression analyses, the presence of 1 or more tendon friction rubs was one of the best predictors of both evolution to diffuse scleroderma and reduced survival. The palpable tendon friction rub is an easily detected, inexpensively obtained physical examination finding which is highly associated with diffuse cutaneous scleroderma and decreased survival. This observation should lead to the early diagnosis of diffuse scleroderma and should identify patients at high risk for serious visceral involvement who are thus candidates for potential disease-modifying therapy.