Scleroderma Renal Crisis: A Pathology Perspective

Scleroderma renal crisis (SRC) is an infrequent but serious complication of systemic sclerosis (SSc). It is associated with increased vascular permeability, activation of coagulation cascade, and renin secretion, which may lead to the acute renal failure typically associated with accelerated hypertension. The histologic picture of SRC is that of a thrombotic microangiopathy process with prominent small vessel involvement manifesting as myxoid intimal changes, thrombi, onion skin lesions, and/or fibrointimal sclerosis. Renal biopsies play an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in SSc patients, helping to predict the clinical outcome and optimizing patient management. Kidney transplantation may be the only treatment option available for a subset of SRC patients who develop end-stage renal failure despite aggressive angiotensin-converting enzyme inhibitor therapy. However, the posttransplant outcome for SSc patients is currently suboptimal compared to the general renal transplant population

Racial differences in scleroderma among women in Michigan

Objective. To examine racial differences in disease onset, extent, manifestations, and survival among women with scleroderma. Methods. A retrospective cohort study of women with scleroderma, diagnosed in Michigan between 1980 and 1991, was conducted. Clinical, laboratory, and demographic data were abstracted from the patients' medical records. Results. A total of 514 women with scleroderma were identified: 117 (23%) were black and 397 (77%) were white. Among black women, the mean age at diagnosis was lower (44.5 years versus 51.5 years; P 40 mm/hour ( P < 0.001) were more frequent among black women, while white women were more likely to have digital infarctions ( P < 0.001). Survival at 7 years from diagnosis was 72.5% among black women and 77.6% among white women. Age-adjusted survival was significantly reduced among black women ( P = 0.033), most likely because of increased diffuse involvement. Survival among those with renal or pulmonary involvement was also significantly reduced. Conclusion. Black women with scleroderma were significantly more likely than white women to develop diffuse disease, be diagnosed at a younger age, have a higher incidence of inflammatory features, and have a worse age-adjusted survival rate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37812/1/1780400421_ftp.pd

Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort). African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987–2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses. The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud\u27s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort. Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry

What Affects Influenza Vaccination Rates among Older Patients? An Analysis from Inner-city, Suburban, Rural, and Veterans Affairs Practices

BACKGROUND: Despite strong evidence of the effectiveness of influenza vaccination, immunization rates have reached a plateau that is below the 2010 national goals. Our objective was to identify facilitators of, and barriers to, vaccination in diverse groups of older patients. METHODS: A survey was conducted in 2000 by computer-assisted telephone interviewing of patients from inner-city health centers, Veterans Affairs (VA) outpatient clinics, rural practices, and suburban practices. The inclusion criteria were age ≥66 years and an office visit after September 30, 1998. RESULTS: Overall, 1007 (73%) interviews were completed among 1383 patients. Influenza vaccination rates were 91% at VA clinics, 79% at rural practices, 79% at suburban practices, and 67% at inner-city health centers. There was substantial variability in vaccination rates among practices, except at the VA. Nearly all persons who were vaccinated reported that their physicians recommended influenza vaccinations, compared with 63% of unvaccinated patients (P \u3c 0.001). Thirty-eight percent of unvaccinated patients were concerned that they would get influenza from the vaccine, compared with only 6% of vaccinated persons (P \u3c 0.001). Sixty-three percent of those vaccinated, in contrast with 22% of unvaccinated persons, thought that an unvaccinated person would probably contract influenza (P \u3c 0.001). CONCLUSION: Older patients need intentional messages from physicians that recommend vaccination. Furthermore, more patient education is needed to counter myths about adverse reactions

Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database.

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort.Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry

Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis

BACKGROUND: Systemic sclerosis is a disease of unknown origin which often occurs in women after their childbearing years. It has many clinical and histopathological similarities to chronic graft-versus-host disease. Recent studies indicate that fetal stem cells can survive in the maternal circulation for many years post partum. This finding suggests that fetal cells persisting in the maternal circulation or tissues could be involved in the pathogenesis of systemic sclerosis by initiating a graft-versus-host reaction. METHODS: We used the polymerase chain reaction (PCR) to identify Y-chromosome sequences in DNA extracted from peripheral-blood cells and skin lesions from women with systemic sclerosis of recent onset. To confirm the PCR findings, we used fluorescence in situ hybridization of peripheral-blood cells and cells within chronic inflammatory-cell infiltrates in biopsy specimens of affected skin. RESULTS: Y-chromosome sequences were found in DNA from peripheral-blood cells in 32 of 69 women with systemic sclerosis (46 percent), as compared with 1 of 25 normal women (4 percent, P\u3c0.001), and in T lymphocytes from 3 women with systemic sclerosis who had male offspring. Furthermore, Y-chromosome sequences were identified in skin-biopsy specimens from 11 of 19 women with systemic sclerosis (58 percent); 9 of the 11 were known to have carried male fetuses. Nucleated cells containing Y chromosomes were detected by fluorescence in situ hybridization in paraffin-embedded sections of skin lesions from all seven women we tested whose skin-biopsy specimens contained Y-chromosome sequences. CONCLUSIONS: Fetal antimaternal graft-versus-host reactions may be involved in the pathogenesis of systemic sclerosis in some women

Derivation and External Validation of a Prediction Rule for Five-Year Mortality in Patients With Early Diffuse Cutaneous Systemic Sclerosis

OBJECTIVE: Although diffuse cutaneous systemic sclerosis (dcSSc) is associated with a reduction in life expectancy, there are no validated prognostic models for determining 5-year mortality in patients with dcSSc. The objective of this study was to derive and validate a rule for predicting 5-year mortality in patients with early dcSSc. METHODS: We studied an inception cohort of 388 US Caucasian patients with early dcSSc (<2 years from the appearance of the first symptom). Predefined baseline variables were analyzed in a stepwise logistic regression model in order to identify factors independently associated with 5-year all-cause mortality. We rounded the beta weights to the nearest integer and summed the points assigned to each variable in order to stratify patients into low-risk (<0 points), moderate-risk (1-2 points), and high-risk (≥3 points) groups. We then applied this rule to an external validation cohort of 144 Caucasian patients with early dcSSc from the Royal Free Hospital cohort and compared stratum-specific 5-year mortality. RESULTS: Six independent predictors (rounded beta weight) comprised the model: age at first visit (points allotted: -1, 0, or 1), male sex (points allotted: 0 or 1), tendon friction rubs (points allotted: 0 or 1), gastrointestinal involvement (points allotted: 0 or 1), RNA polymerase III antibodies (points allotted: 0 or 1), and anemia (points allotted: 0 or 1). The 3-level risk stratification model performed well, with no significant differences between the US derivation cohort and the UK validation cohort. CONCLUSION: We derived and externally validated, in US and UK cohorts, an easy-to-use 6-variable prediction rule that assigns low-risk, moderate-risk, and high-risk categories for 5-year mortality in patients with early dcSSc. Only history, physical examination, and basic laboratory assessments are required

Sociodemographic and Disease Correlates of Body Image Distress among Patients with Systemic Sclerosis

Body image concerns are infrequently studied in systemic sclerosis (SSc), even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.A total of 489 SSc patients (432 female, 57 male) were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was robustly associated with younger age (-0.017, p<0.001) and upper-body telangiectasias (0.32, p = 0.021). Dissatisfaction with appearance was associated with hand contractures (0.07, p = 0.036).This study found that dissatisfaction with appearance and social discomfort were associated with numerous disfiguring characteristics of SSc, in addition to age. These results underline that there are multiple factors contributing to body image distress in SSc, as well as the need to attend to both disease and social contexts in understanding the impact of disfigurement among patients