Change In Skin Score Research Articles

Anti-topoisomerase 1 Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis

The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANAs) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSs) patients on rituximab (RTX) therapy. The prospective study included 88 patients (73 women) with a mean age of 47 (17–71) years. The mean disease duration was 5.9 ± 4.8 years. The mean follow-up period was more than 2 years (27 (12–42) months). We documented a statistically significant change in skin score, the disease activity index, improvement of pulmonary function and reduction of mean dose of prednisolone after RTX treatment. There was a significant decrease in the number of patients with high levels of ANA and overall decrease of the ANA and anti-Topo 1 levels. A moderate positive statistically significant correlation was found between ANA and anti-Topo 1 (r = 0.403). In the group of patients positive for anti-Topo 1 there were a more pronounced depletion of B lymphocytes, significantly higher increase in forced vital capacity and diffusion capacity, decrease in the disease activity index, compared with patients negative for anti-Topo 1. We observed the decline in the level of ANA and anti-Topo 1 in SSc patients after RTX therapy, and it was correlated by an improvement of the main outcome parameters of the disease. Therefore, anti-Topo 1 positivity could be considered as a predictor of a better response to RTX treatment, especially in SSc patients with hyperproduction of anti-Topo 1.

Anti-topoisomerase 1 antibody level changes after B сell depletion therapy in systemic sclerosis

The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANA) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSc) patients on rituximab (RTX) therapy.Materials and methods. The prospective study included 88 patients (73 women) with a mean age of 47 (17– 71) years. The mean disease duration was 5.9±4.8 years. The mean follow-up period was more than 2 years (27 (12–42) months).Results. We documented a statistically significant change in skin score, the disease activity index, improvement of pulmonary function and reduction of mean dose of prednisolone after RTX treatment. There was a significant decrease in the number of patients with high levels of ANA and overall decrease of the ANA and anti-Topo 1 levels. A moderate positive statistically significant correlation was found between ANA and anti-Topo 1 (r=0.403). In the group of patients positive for anti-Topo 1 there were a more pronounced depletion of B lymphocytes, significantly higher increase in forced vital capacity and diffusion capacity, decrease in the disease activity index, compared with a patients negative for anti-Topo 1.Conclusions. We observed the decline in the level of ANA and anti-Topo 1 in SSc patients after RTX therapy and it was correlated by an improvement of the main outcome parameters of the disease. Therefore, anti-Topo 1 positivity could be considered as a predictor of a better response to RTX treatment, especially in SSc patients with hyperproduction of anti-Topo 1.

Changes in skin score in early diffuse cutaneous systemic sclerosis are associated with changes in global disease severity.

To determine whether skin score changes are associated with changes in overall disease severity, function and quality of life in early dcSSc patients. A total of 154 and 128 dcSSc patients from the Canadian Scleroderma Research Group database with 1 and 2 year follow-up and a disease duration ⩽5 years without end-stage organ damage and/or significant comorbidity at the initial visit were included. Skin was assessed using the modified Rodnan skin score (mRSS) and disease severity by the summed Medsger disease severity score (DSS) (without skin domain), physician and patient global assessments, function [HAQ disability index (HAQ-DI)] and quality of life [36-item Short Form Health Survey (SF-36) physical component summary (PCS)]. Analyses were repeated in patients with a disease duration ⩽3 years. At 2 years, 64 (50%) patients had improved skin (mRSS decrease of ⩾5 points and/or ⩾25%). Skin improvers had improved summed DSS (P = 0.002); better physician global assessments of disease activity, severity and damage (all P ⩽ 0.003); better HAQ-DI (P = 0.001) and SF-36 PCS (P = 0.005). Changes in the mRSS were positively correlated with changes in summed DSS (P = 0.006) and other disease outcomes. In the 26 (20.3%) patients with worsened skin (mRSS increase of ⩾5 points and/or ⩾25%), the summed DSS and physician global assessments were worse (P = 0.01 and P ⩽ 0.009, respectively). In the subgroup with a disease duration ⩽3 years, similar associations were found. At 1 and 2 years, overall disease improvement parallels skin improvement in early dcSSc. This is important for prognosis and reflects the value of mRSS as an outcome measure in trials with these patients.

Two-year Results of an Open Pilot Study of a 2-treatment Course with Rituximab in Patients with Early Systemic Sclerosis with Diffuse Skin Involvement

To study safety and potential efficacy of a 2-treatment course (month 0/6) with rituximab (RTX) in early diffuse systemic sclerosis (dcSSc). Two years' followup (open-label study) was done of 8 patients with early dcSSc. Patients received an infusion of 1000 mg RTX 2 times at months 0 and 6, with 100 mg methylprednisolone. Clinical measurements, Disease Activity Score, functional status, and CD19+ peripheral blood count were performed at months 0, 3, 6, 12, 15, 18, and 24 and histopathological evaluation of the skin at months 0, 3, 12, and 24. There was a clinically significant change in skin score, with a mean Modified Rodnan skin score of 24.8 at baseline (SD 3.4) and 13.6 at Month 24 [SD 5.6; mixed models analyses (MMA) p < 0.0001] and a significant decrease in Disease Activity Score (DAS), with a median of 4.5 at baseline (range 1.5-7.5) and 0.5 at Month 24 (range 0.0-5.5; MMA p < 0.0001). Indices of internal organ involvement remained stable throughout the study. RTX induced effective B cell depletion at baseline and Month 6 (< 5 CD19+ cells/μl blood). The blindly assessed hyalinized collagen score changed significantly over time (MMA p = 0.009), with a mean of 69.3 at baseline (SD 22.8) and 33.1 at 24 months (SD 27.0). Five serious adverse events were considered unrelated to the RTX treatment. A 2-treatment course (months 0/6) with RTX appears to be well tolerated and may have potential efficacy for skin disease and stabilization of internal organ status in early dcSSc. Clinical Trials Registration NCT00379431.

Geographic information system-based decision support for soil conservation planning in Tajikistan

<h3>Aim:</h3> The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). <h3>Methods:</h3> A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg/kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed. <h3>Results:</h3> There was no significant change in skin score at 26 weeks but a trend for lower modified Rodnan skin score at 22 weeks (OR 17, 95% CI 6 to 46) compared with peak value (OR 29, 95% CI 11 to 44; p = 0.10). Serum aminoterminal propeptide of type III collagen level was significantly lower at week 26 compared with baseline (p = 0.03). Secretion of type I collagen by dermal fibroblasts was reduced at 26 weeks compared with baseline (p = 0.02). There were no deaths during the study and no suspected unexpected serious adverse reactions. 21 serious adverse events (AE) occurred in seven subjects, mostly attributable to dcSSc. 127 distinct AE occurred in 16 subjects. Of these, 19 AE (15%) were probably or definitely related to infliximab treatment. Eight (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in five subjects and were significantly associated with suspected infusion reactions (p = 0.025). <h3>Conclusion:</h3> In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis.

B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial

IntroductionAn over-expression of CD19 has been shown in B cells of systemic sclerosis (SSc) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model. The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry.MethodsNine patients with SSc with mean age 40.9 ± 11.1 years were treated with anti-CD20, 1 g at time 0 and after 14 days. Skin biopsy was performed at baseline and during the follow-up. B-cell activating factor (BAFF) and IL-6 levels were also determined at the follow-up times.ResultsAfter 6 months patients presented a median decrease of the skin score of 43.3% (range 21.1-64.0%), and a decrease in disease activity index and disease severity index. IL-6 levels decreased permanently during the follow up. After treatment, a complete depletion of peripheral blood B cells was observed in all but 2 patients. Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline.ConclusionsAnti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms. The clear fall in IL-6 levels could contribute to the skin fibrosis improvement, while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion.Trial registrationISRCTN77554566.

A longitudinal study of anti-RNA polymerase III antibody levels in systemic sclerosis

Anti-RNA-polymerase antibodies (ARAs) are associated with the diffuse cutaneous subset of SSc (dcSSc) and particularly with scleroderma renal crisis (SRC). We analysed serial ARA levels and explored the relationship with clinical features and disease outcome. A commercially available ELISA method with a recombinant peptide of RNA polymerase III was used and ARA levels were measured in a well-characterized cohort of SSc cases. ARA levels were measured in 64 SSc patients. Of them, 78% (n = 50) were females and 92% (n = 59) had dcSSc, 39% (n = 25) had SRC, 20% (n = 13) had pulmonary fibrosis (PF), 9% (n = 6) had pulmonary arterial hypertension and 3% (n = 2) had cardiac involvement. There was considerable inter- and intra-patient variability in ARA levels (11-210 U/ml). There was no correlation between absolute ARA levels (at baseline or throughout the disease course) and outcome. There was a moderate correlation between time to peak ARA level and development of significant PF (Pearson correlation = 0.669, P = 0.034), but no correlation between peak ARA levels and onset of SRC. ARA levels change correlated with change in skin score (correlation coefficient within subjects = 0.236, P = 0.011). The pathogenic significance of ARA is unclear. Despite the very strong association of ARA with SRC, we could not show the clinically significant association between absolute levels of antibody and development of internal organ complications, which makes repeated measurements of ARA levels unnecessary. However, changes in ARA level over time occur and may reflect changes in skin score.

Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study

Objectives:The safety and potential efficacy of rituximab was examined in diffuse cutaneous systemic sclerosis (dc-SSc).Methods:A 24 week open-label study in which eight patients with dc-SSc received an infusion of 1000...

An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis

Aim:The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc).Methods:A 26-week open-label pilot study in which 16...

Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: Application of a latent linear trajectory model

To explore the relationship between changes in the severity of skin disease and morbidity and mortality in patients with diffuse cutaneous systemic sclerosis (dcSSc). From a large single-center cohort, we identified 225 patients with dcSSc for whom serial clinical information was available from within 24 months of the onset of the first non-Raynaud's phenomenon manifestation of SSc. The end points analyzed included death and heart, lung, kidney, and gastrointestinal tract involvement. Latent linear trajectory modeling (LTM) was applied to identify patients with a similar trajectory of modified Rodnan skin thickness score (MRSS) changes over the first 3 years of followup. Clinical outcomes were compared between 3 different LTM subgroups. LTM permitted classification of 131 patients (58%) into 1 of 3 subgroups with different skin score trajectories. Survival was lowest in the subgroup of patients who had a high baseline skin score and experienced little improvement during followup (P = 0.003). However, the frequency of clinical end points was similar in the subgroup with the most favorable trajectory (i.e., a low initial MRSS and subsequent improvement) and the subgroup with a high baseline MRSS and no improvement. Interestingly, the end point frequency was greatest in the subgroup with a high initial MRSS and subsequent improvement, suggesting that sustained severe skin disease does not necessarily predict the number of visceral complications, and that the relationship between the skin score and internal organ involvement in dcSSc is more complex than previously thought. Although mortality was highest among patients with the worst skin-related outcomes, no simple relationship between burden of disease and change in skin score was observed.

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.

The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time.

To determine the validity and usefulness of a modified Health Assessment Questionnaire (HAQ) for measurement of disease status and changes in disease status over time in patients with systemic sclerosis (SSc). Since 1985, 1,250 patients attending the University of Pittsburgh Scleroderma Clinic have completed a modified HAQ annually. In addition to the standard HAQ questions about disability, the questionnaire includes visual analog scales (VAS) to evaluate SSc organ system symptoms, Raynaud's phenomenon, gastrointestinal (GI) tract and lung involvement, pain, and overall disease severity. In this study, the disability index (DI) (from the HAQ) and the VAS scores (on a 0-3 scale) were compared with various clinical and laboratory features recorded within 3 months of administration of the HAQ and VAS, using t-tests and Spearman's correlation tests. The HAQ DI correlated directly with skin involvement, scleroderma heart or kidney disease, tendon friction rubs, hand contractures, and proximal muscle strength. Over time, the DI correlated with changes in skin score and was a good predictor of survival. There was a significant improvement in the DI during a 2-year time period in patients treated with D-penicillamine. The VAS for digital ulcers, GI symptoms, and lung symptoms correlated very closely with subjective and objective findings for these organ systems. The presence of new digital ulcers or improvement in digital ulcers showed significant associations with the Vascular scale, new GI symptoms or improvement in GI symptoms and institution of H2-blockers showed appropriate strong correlations with the GI scale, and changes in the forced vital capacity had an excellent correlation with the Lung scale (r = 0.58, P < 0.001). By Cox regression analysis, the HAQ DI was one of the best predictors of survival. These data provide convincing evidence that a self-administered questionnaire is an accurate and inexpensive tool to measure disease status changes in SSc. Prospective studies with the HAQ administered at regular intervals, as in controlled trials, should be performed to further assess the benefits and limitations of this instrument.