This discussion was moderated by Harrison (Hap) Farber, MD, Professor, Department of Medicine, Boston University School of Medicine, and Director, Pulmonary Hypertension Center, Boston Medical Center, Boston, Massachusetts. Panel members included Richard M. Silver, MD, Professor of Medicine and Pediatrics and Director of the Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina; Virginia D. Steen, MD, Proffessor of Medicine, Georgetown University, Washington, DC; and Charles Strange, MD, Professor of Pulmonary Medicine, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina.

OBJECTIVETo clarify which racial differences in disease manifestations can be attributed to differences in other factors such as gender, education, disease classification, and disease duration.METHODSThe study included white and black patients with systemic sclerosis (SSc) treated at a university hospital rheumatology clinic between November 1997 and April 2003. Demographic, clinical, and immunological measurements were obtained on each subject. Using multivariable statistical techniques we assessed differences in disease manifestations between white and black patients after adjusting for gender and classification and duration of disease.RESULTSTwo hundred sixty-three patients (199 whites, 64 blacks) were enrolled in the study. Blacks experienced an earlier age at disease onset than whites and were significantly more likely to have diffuse disease, digital ulcers, digital pitting, impaired lung function, and anti-RNP, and anti-Ro antibodies. Whites were significantly more likely to have anti-centromere antibodies.CONCLUSIONAfter adjusting for gender, disease classification, and disease duration, whites and blacks with SSc differ in some clinical and immunological manifestations of disease. Whether these differences can be attributed to genetic or environmental factors remains unknown.

OBJECTIVELittle research has examined patterns of hospitalization and use of emergency rooms (ER) among patients with systemic sclerosis (SSc). We compared the incidence of hospitalizations and ER visits across 3 race groups (non-Hispanic white, non-Hispanic black, other) and determined predictors of referral to the Medical University of South Carolina (MUSC), a major referral center for patients with SSc residing in the southeastern United States.METHODSData were obtained on all South Carolina hospitalizations (1996-2000) for patients who were ever hospitalized for a diagnosis of SSc during that time period. Hospitalization and ER incidence rates were determined in conjunction with corresponding population sizes obtained from the 2000 US Census, and rates were compared across race, sex, and age groups using Poisson regression models. Logistic regression was used to determine predictors of being treated at MUSC.RESULTSThe hospitalization incidence rate was significantly (p < 0.05) higher among blacks compared to whites (rate ratio 1.66; 95% confidence interval 1.41, 1.96), as was the ER incidence rate (rate ratio 1.78; 95% CI 1.50, 2.11). Even after adjusting for sex, age, median household income, primary insurance claim payor, county, and comorbidity, blacks were 60% less likely (p < 0.05) than whites to receive inpatient treatment at MUSC. Similar results were observed when comparing other non-whites to whites.CONCLUSIONThe increased hospitalizations and ER visits among non-whites provide additional evidence of greater disease burden among these population groups. Despite this increased burden, non-whites are less likely to receive care at a major SSc referral center.

Acute and chronic interstitial lung diseases are accompanied by evidence of inflammation and vascular injury. Thrombin activity in bronchoalveolar lavage fluid from such conditions is often increased, as well as interleukin (IL)-8. We observed that conditioned medium from lung fibroblasts exposed to thrombin has chemotactic activity for polymorphonuclear cells, and that this activity can be abolished by antibody to IL-8. We report that thrombin stimulates expression of IL-8 in human lung fibroblasts on both the messenger RNA and protein levels in a time- and dose-dependent manner. Stimulation of IL-8 expression by thrombin is inhibited by specific thrombin inhibitors. Synthetic thrombin receptor agonist peptide-14 mimics thrombin's stimulation of IL-8 expression in a dose-dependent manner consistent with the idea that upregulation of IL-8 by thrombin in human lung fibroblasts requires cleavage of proteolytically activated receptor-I. We demonstrate further that thrombin-induced IL-8 synthesis is regulated by protein kinase (PK) C. PKC-gamma may be involved in the upregulation of lung fibroblast IL-8 by thrombin because stimulation of lung fibroblasts with thrombin caused significant upregulation of PKC-gamma and because PKC-gamma antisense oligonucleotides inhibited the accumulation of PKC-gamma protein and IL-8 protein. Our data suggest that the PKC-gamma isoform increase observed after thrombin stimulation is required for thrombin-induced IL-8 formation by human lung fibroblasts.

The lungs are often affected in patients with systemic sclerosis (SSc) and lung disease is now the leading cause of mortality, Two types of pulmonary disease predominate: interstitial lung disease and pulmonary hypertension. Both are difficult to detect at the earliest stages, thus management of patients with these manifestations can be difficult. Several recent studies using cyclophosphamide to treat SSc alveolitis, the inflammatory state associated with interstitial lung disease, have yielded promising results in terms of symptomatic improvement, as well as stabilization or improvement of lung volumes, Vasodilator therapy with prostacyclin analogues is being evaluated in SSc patients with pulmonary hypertension, based on results in primary pulmonary hypertension patients. Lung transplantation is often not an option for most SSc patients, thus optimal medical therapy is greatly needed for the SSc patient with severe lung disease.

OBJECTIVETo examine whether those participating in solvent oriented hobbies (SOH) are at greater risk of developing systemic sclerosis (SSc), and if the association is modified by the presence of the anti-Scl70 antibody.METHODSPatients with SSc and controls were recruited from a university hospital rheumatology clinic. Recreational hobby and occupational histories were obtained along with blood samples. Cumulative scores were created for participation in SOH. Logistic regression was used to calculate odds ratios associated with SOH exposure after adjustment for sex, age at diagnosis, and occupational solvent exposure, and to examine the association between SOH exposure and the presence of anti-Scl70.RESULTSSolvent exposure based on hobbies and occupations was determined for 178 cases (141 women, 37 men) and 200 controls (138 women, 62 men). Overall participation in SOH was not associated with SSc. However, odds of high cumulative SOH exposure was 3 times greater in those patients with SSc testing positive for the anti-Scl70 antibody compared to patients testing negative (OR 2.9, 95% CI 1.1, 7.9), and twice as great as controls (OR 2.5, 95% CI 1.1, 5.9).CONCLUSIONWhile patients with SSc did not participate more often in SOH than controls over all, odds of high cumulative SOH exposure was greater among patients with SSc testing positive for anti-Scl70 compared to those testing negative and compared to controls. These results provide further evidence that environmental agents may play a role in the development of Ssc.

Lung disease is a major cause of morbidity and is the leading cause of mortality in patients with systemic sclerosis, most commonly occurring as interstitial lung disease or as pulmonary hypertension. Cyclophosphamide has been used to treat the interstitial lung disease and a placebo-controlled trial is planned. Potent pulmonary vasodilators, many of which have been studied in primary pulmonary hypertension, are now undergoing study in patients with systemic sclerosis.

In addition to its procoagulant properties, the serine protease thrombin increases endothelial permeability, stimulates granulocyte adherence, and serves as a fibroblast mitogen. We demonstrate that thrombin is mitogenic for human lung fibroblasts in vitro. The mitogenic effect of thrombin is associated with an increase in the expression of the ligand PDGF-AA and up-regulation of PDGF alpha-receptor. Since scleroderma (systemic sclerosis; SSc) is characterized by widespread microvascular injury and is frequently complicated by pulmonary fibrosis, we sought to determine the level of thrombin activity in bronchoalveolar lavage (BAL) fluid from SSc patients and normal controls. We report a significantly higher level of thrombin activity in BAL fluid from SSc patients compared with normal controls (P < 0.001). Taken together, the high levels of thrombin in BAL fluid and its demonstrated mitogenicity for lung fibroblasts suggest an important role for thrombin in the pathogenesis of SSc and perhaps other fibrotic lung diseases.

The eosinophilia-myalgia syndrome, which is associated with the ingestion of L-tryptophan that contained products, occurred as an epidemic in the United States in 1989. Eosinophilia-myalgia syndrome is similar in many ways to the toxic-oil syndrome, which occurred in Spain in 1981, and to diffuse fasciitis with eosinophilia, which has been noted since 1974 to occur sporadically. Recent studies have clarified the epidemiology, histopathology, and clinical features of eosinophilia-myalgia syndrome. These studies are reviewed, and comparisons to the related syndromes, toxic-oil syndrome and diffuse fasciitis with eosinophilia, are made.