Cumulative Organ Damage Research Articles

Avaliação do índice de danos permanentes através do SLICC/ACR-DI em pacientes brasileiros com lúpus eritematoso sistêmico

to evaluate the frequency and the different types of organ damage in relation to disease duration in Brazilian patients with SLE followed in a tertiary reference center through the application of the SLICC/ACR-DI. sixty SLE patients were enrolled in this study, and relevant data were obtained through medical history, physical and laboratory examinations reviewing the hospital records. The frequency and different types of organ damage were determined using the SLICC/ACR-DI. Statistics were performed through qui-square and t-tests. Multivariate regression was used to correlate damage with disease duration. forty-one patients (68.3%) presented some cumulative organ damage. Non-caucasoid patients and patients with longer disease duration had a slight tendency to have more damage (p = 0.058). Skin (35.0%), neuropsychiatric (18.3%), ocular (15.0%), peripheral vascularization (16.6%) and cardiovascular (10.0%) systems were more frequently affected. Patients with more than 60 months of disease had a slight tendency to present greater ocular, neuropsychiatric, renal, skin and musculoskeletal damage than patients with shorter disease duration. Patients with more than 120 months of disease had greater pulmonary, cardiovascular and peripheral vascular damage. in this study, 68.3% of permanent damage was observed. Skin, neuropsychiatric, ocular, peripheral vascularization and cardiovascular systems were more frequently affected. Renal and gonadal involvement was not as frequent as previously described. Non-caucasoid patients had a tendency to present higher scores, but more studies are necessary to determinate if ethnic or economic factors are involved.

Stammzelltherapie schwerer Autoimmunkrankheiten

Trotz Einsatz aller konventioneller (immunsuppressiver) Therapieformen kommt es in manchen Fällen schwer verlaufender Autoimmunerkrankungen zum Fortschreiten der Erkrankung, irreversiblen Organschäden und Todesfällen. Zusätzlich kann langdauernde immunsuppressive Therapie, v. a. mit Cyclophosphamid und Kortikosteroiden, zu schweren Nebenwirkungen einschließlich einer hohen Rate an Sekundärneoplasien führen. Daher wird seit mehreren Jahren im Rahmen von experimentellen Studienprotokollen der Nutzen einer kurzfristigen dosiseskalierten Immunsuppression in Form der Hochdosischemotherapie (HDCT) mit autologer Stammzelltransplantation bei ansonsten therapierefraktären Patienten erprobt. Im Mittelpunkt dieser Bemühungen stehen bisher Patienten mit progressiver systemischer Sklerose, systemischem Lupus erythematodes, Rheumatoidarthritis, multipler Sklerose, Autoimmunhämolyse und Autoimmunthrombopenie. Auch Patienten mit primär systemischen Vaskulitiden (PSV) könnten geeignete Kandidaten für die HDCT sein. Es müssen die Patienten ausgewählt werden, bei denen die Schwere der Erkrankung, bzw. die krankheitsassoziierte Mortalität die Toxizität der HDCT erheblich überwiegt. Grundsätzlich sollten für die ASCT Patienten ausgewählt werden, deren Erkrankung therapierefraktär, aktiv und progredient ist, und bei denen ein hohes Risiko für bleibende Funktionseinschränkungen und hohe Mortalität trotz konventioneller Therapie besteht. Durch verbesserte Scoring-Systeme, die eine frühere Identifikation dieser Hochrisiko-Patienten schon in frühen Krankheitsstadien erlauben, kann zukünftig der Erfolg der Methode verbessert und die Risiken minimiert werden. Erste Publikationen sowie eigene Erfahrungen bei wenigen, ausgewählten Patienten mit schwer verlaufenden PSV und anderen Autoimmunerkrankungen zeigen, dass langfristige Remissionen auch in vormals therapierefraktären Fällen möglich sind bei akzeptabler Toxizität. Zukünftig können allein durch multizentrische Phase-III-Studien der Nutzen und die Risiken der Stammzelltransplantation im Vergleich zur konventionellen Therapie geklärt werden.

Assessment of damage in juvenile-onset systemic lupus erythematosus: a multicenter cohort study.

To investigate the prevalence of cumulative organ damage in patients with juvenile-onset systemic lupus erythematosus (SLE) and its association with demographic and clinical variables, medication use, and quality of life. The occurrence of organ system damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was determined for 387 patients consecutively enrolled in pediatric rheumatology centers from Europe, the US, Mexico, and Japan. Risk factors for damage included demographic variables; clinical manifestations at diagnosis; previous corticosteroid, immunosuppressive, and antimalarial therapies; disease activity; and quality of life. Overall, 195 (50.5%) patients had damage within a mean of 5.7 years after disease onset. Renal (21.8%) and neuropsychiatric (15.8%) system involvement were observed most frequently, followed by musculoskeletal (11.7%), ocular (10.9%) and skin (9.6%) system involvement, with a mean SDI score of 1.1. In multivariate models, the occurrence of neuropsychiatric manifestations at diagnosis, a longer disease duration, and a greater number of intravenous cyclophosphamide pulses showed the strongest association with the presence of damage. We found evidence of cumulative organ damage, as measured by the SDI, in half of the patients with juvenile-onset SLE. Damage was significantly more likely in patients who had experienced neuropsychiatric manifestations at diagnosis, had a longer disease duration, and had received more intravenous pulses of cyclophosphamide.

Stem cell transplantation in primary systemic vasculitis

Many patients with various autoimmune diseases fail to respond to conventional immunosuppressive therapy and develop irreversible organ damage. In some cases the complications might be fatal. Furthermore, prolonged immunosuppression with cyclophosphamide or corticosteroids often leads to long-term side effects, cumulative organ damage, and development of secondary malignancies. Thus, short-term, high-dose immunosuppressive therapy with autologous stem cell transplantation might be an alternative for otherwise refractory patients. This concept has been used mainly in patients with scleroderma, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Patients with primary systemic vasculitis (PSV) seem to be suitable candidates for high-dose chemotherapy (HDCT). Although complete, long-term remissions are possible with standard immunosuppressive therapy, there is a subgroup of patients who cannot be cured by standard therapy. They need long-term immunosuppression and eventually die due to progression of the disease or cumulative therapy-related toxicity. In large series, the 5-year mortality rate was > 20%. The severity of vasculitis rather than the distinction between subgroups should determine whether HDCT might be a life-saving treatment. Careful patient selection with the help of scoring systems and determination of the optimal time in the course of disease are now the major goals in the approach to HDCT. First reports as well as our own single-center experience in HDCT with a limited number of patients with severe PSV have shown that long-term remissions are possible even in patients refractory to conventional immunosuppression.

Application of modified sequential organ failure assessment score in children after cardiac surgery

Objective: To evaluate the usefulness of the modified sequential organ failure assessment (m/SOFA) score for assessing morbidity and mortality in pediatric patients after cardiac surgery. Design: Analysis of a prospectively collected database. Setting: Pediatric intensive care unit of a university-affiliated hospital. Participants: Consecutive pediatric patients (n = 142) undergoing cardiac surgery. Interventions: None. Measurements and Main Results: The m/SOFA score, consisting of 5 organ scores (maximum score of 20 points), was calculated on admission (initial) and at 12 and 36 hours postoperatively. An initial score of >5 points with an unchanged or upward postoperative trend predicted a higher postoperative mortality and a greater need for intensive care intervention. In neonates, sustained higher score >10 points predicted an outcome of death with a sensitivity of 100% and a specificity of 87%. Given the higher mortality related to immature organ function and a greater complexity of heart defects, the application of the m/SOFA score, a less invasive and simple way to assess organ damage, is especially suitable in neonates. The m/SOFA score would be more appropriately assessed according to the congenital heart defect or surgical procedure because the types of cardiac defect after the surgical repair affect each organ score measurement. Conclusion: Application of the m/SOFA score in the early postoperative period, which reflects cumulative perioperative organ damage, would provide some direction to eventual outcomes of morbidity and mortality in patients with congenital heart defects undergoing surgery. Copyright © 2001 by W.B. Saunders Company

Vascular stiffness in women with systemic lupus erythematosus.

All risk factor data were collected on the day of the ultrasound examinations. PWV waveforms were collected from the right carotid and femoral arteries by Doppler probes. The mean age of the women was 45.5+/-10.8 years, the median SLE disease duration approximated 9 years, and the mean PWV was 6.1+/-1.7 m/s. Multiple regression models were stratified by menopausal status. Among postmenopausal women, PWV risk factors were primarily traditional factors and included age, systolic blood pressure, family history of vascular disease, carotid plaque, creatinine, obesity, glucose, white cell count, and cumulative SLE organ damage. Among premenopausal women, PWV risk factors consisted of a mix of SLE-related and traditional variables and included higher C3 levels, presence of ds-DNA antibodies, nonuse of hydroxychloroquine, lower leukocyte count, higher mean arterial pressure, and carotid plaque. SLE-specific variables appeared to be associated with increases in aortic PWV, indicating central artery stiffening. This was seen most clearly among premenopausal women. This finding may partially explain the higher rates of cardiovascular disease and hypertension observed in young women with SLE.

The Effect of Race on Cumulative Organ Damage in Systemic Lupus Erythematosus

The Effect of Race on Cumulative Organ Damage in Systemic Lupus Erythematosus

Serum levels of soluble Fas correlate with indices of organ damage in systemic lupus erythematosus.

To evaluate whether the levels of soluble form of the Fas apoptosis antigen (sCD95/sFas) varied from those of healthy control subjects in a group of patients with systemic lupus erythematosus (SLE). This was done to determine whether sFas has a role in either the disease activity or the organ damage in SLE. Serum levels of sFas were measured over a period of 4 y (277 determinations) in 39 Arab patients with SLE and 22 age-, gender-, and race-matched healthy controls using double antibody ELISA. SLEDAI scores for disease activity and SLICC/ACR scores for cumulative organ damage were determined. Serum levels of acute phase reactants, complement, inflammatory cell counts, levels of autoantibodies, and kidney and liver function test results were obtained retrospectively from clinical records. sFas levels were significantly higher in patients with SLE (n = 39, 277 determinations) (0.60 ng/ml +/- 0.38) than in healthy controls (n = 22) (0.26 ng/ml +/- 0.11) (P < 0.00001). The levels of sFas correlated with SLICC/ACR (r = 0.36; P < 0.02), but not with SLEDAI. sFas correlated with renal and liver function tests measured by s-creatinine (r = 0.38; P < 0.0001), creatinine clearance (r = -0.30, P < 0.001), s-albumin (r = -0.28, P < 0.0001), and ALT (r = 0.35; P < 0.00001), but did not correlate with the levels of acute phase reactants. sFas is elevated in sera of SLE patient. Since sFas correlates with indices of organ damage but not with disease activity, it may be a marker of organ damage in SLE and may act to protect certain organs from further damage by inhibiting Fas-mediated apoptosis.

The American College of Rheumatology criteria for the classification of systemic lupus erythematosus: strengths, weaknesses, and opportunities for improvement.

The American College of Rheumatology classification criteria were developed to operationalize the definition of systemic lupus erythematosus (SLE) to allow comparison of clinical research from different centers, but also serve to facilitate education and to guide clinical practice. The classification criteria have been critical to research, but should be viewed as a temporary step until improved understanding of the pathogenesis of SLE emerges. Criteria have inherent limitations, including bias towards more severe and longer duration disease, equal weighting of features that vary in clinical significance, and exclusion of patients with SLE from research because they do not meet criteria. For some SLE research questions, it may be appropriate to include patients diagnosed with SLE who do not meet criteria, if these patients' manifestations and criteria are documented explicitly. SLE disease activity, cumulative organ damage, disease duration, criteria ever met, and criteria met at time of enrollment are important data that should be presented in clinical studies of SLE regardless of the number of criteria met. The criteria should be reevaluated periodically, utilizing patients and controls with a range of diseases and disease severity. A simplified weighting system may more accurately reflect clinical practice.

Systemic lupus erythematosus VII: frequency and impact of secondary Sjøgren's syndrome.

The prognosis of patients with systemic lupus erythematosus (SLE) largely depends on the severity of cumulative organ damage during the course of the disease. While Sjøgren's syndrome (SS) predominantly affects exocrine glands, a considerable number of patients develop visceral organ damage. Thus, the occurrence of a secondary SS (2(o)SS) in SLE patients, may result in more extensive organ damage and thereby adversely affect prognosis. 138 patients meeting the 1982 American College of Rheumatology (ACR) classification criteria for SLE were prospectively studied over a mean period of ninety months. 2(o)SS was diagnosed according to the 1993 European Study Group criteria and complication rates and prognosis were compared between patients with and without SS. 27 patients (19%) developed SS after a mean period of 48 months. There was a gradual increase in SS prevalence over time after SLE-onset. 2(o)SS patients were older (mean age 41 vs 35 years, P = 0.03), had less renal disease (19% vs 38%, P = 0.04), more thrombocytopenia (26% vs 9%, P = 0.05) and similar serological profiles (including anti-SSa) as patients without SS. Overall mortality was lower in patients with SS (4% vs 13.5%, P = 0.01), while lifetable analysis showed improved survival estimates for 2 SS patients with borderline statistical significance (P = 0.06). 2(o)SS develops in about one-fifth of SLE patients in a time-dependent fashion: these patients are older, have less renal involvement and their prognosis is at least as good as for those remaining free of SS.

Risk factors for early work disability in systemic lupus erythematosus. Results from a Multicenter Study

To study the risk factors for early work disability in systemic lupus erythematosus (SLE). A sample of 159 SLE patients who had been employed at some time since diagnosis was drawn from a multicenter study of outcome in SLE. Disease activity, organ damage, education, income, source of health insurance, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not working because of SLE. The outcome measure was current work status. Seven patients were excluded from the analysis because their choice not to work was unrelated to SLE. An average of 3.4 years after diagnosis, 40% had quit work completely, and job modification was substantial. Univariate analysis (chi-square and t-test) showed that significant predictors of early work disability included having a high school education or less, receiving Medicaid or having no health insurance, having a job which required more physical strength, having an income below poverty level, and having greater disease activity at diagnosis. In multivariate models, significant predictors were education level (P = 0.0004), higher physical demands of the job (P = 0.0028), and higher disease activity at diagnosis (P = 0.0078). Race, sex, cumulative organ damage at diagnosis, and disease duration were not significant. Early work disability in SLE is strongly associated with some sociodemographic factors that might be amenable to intervention.

The relationship of socioeconomic status, race, and modifiable risk factors to outcomes in patients with systemic lupus erythematosus.

To study the relationship of race, socioeconomic status (SES), clinical factors, and psychosocial factors to outcomes in patients with systemic lupus erythematosus (SLE). A retrospective cohort was assembled, comprising 200 patients with SLE from 5 centers. This cohort was balanced in terms of race and SES. Patients provided information on socioeconomic factors, access to health care, nutrition, self-efficacy for disease management, health locus of control, social support, compliance, knowledge about SLE, and satisfaction with medical care. Outcome measures included disease activity (measured by the Systemic Lupus Activity Measure), damage (measured by the SLICC/ACR damage index), and health status (measured by the SF-36). In multivariate models that were controlled for race, SES, center, psychosocial factors, and clinical factors, lower self-efficacy for disease management (P < or = 0.0001), less social support (P < 0.005), and younger age at diagnosis (P < 0.007) were associated with greater disease activity. Older age at diagnosis (P < or = 0.0001), longer duration of SLE (P < or = 0.0001), poor nutrition (P < 0.002), and higher disease activity at diagnosis (P < 0.007) were associated with more damage. Lower self-efficacy for disease management was associated with worse physical function (P < or = 0.0001) and worse mental health status (P < or = 0.0001). Disease activity and health status were most strongly associated with potentially modifiable psychosocial factors such as self-efficacy for disease management. Cumulative organ damage was most highly associated with clinical factors such as age and duration of disease. None of the outcomes measured were associated with race. These results suggest that education and counseling, coordinated with medical care, might improve outcomes in patients with SLE.