Mean Modified Rodnan Skin Score Research Articles

A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis.

Four intrinsic molecular subsets (inflammatory, fibroproliferative, limited, normal-like) have previously been identified in SSc and are characterized by unique gene expression signatures and pathways. The intrinsic subsets have been linked to improvement with specific therapies. Here, we investigated associations between baseline demographics and intrinsic molecular subsets in a meta-analysis of published datasets. Publicly available gene expression data from skin biopsies of 311 SSc patients measured by DNA microarray were classified into the intrinsic molecular subsets. RNA-sequencing data from 84 participants from the ASSET trial were used as a validation cohort. Baseline clinical demographics and intrinsic molecular subsets were tested for statistically significant associations. Males were more likely to be classified in the fibroproliferative subset (P = 0.0046). SSc patients who identified as African American/Black were 2.5 times more likely to be classified as fibroproliferative compared with White/Caucasian patients (P = 0.0378). ASSET participants sera positive for anti-RNA pol I and RNA pol III autoantibodies were enriched in the inflammatory subset (P = 5.8 × 10-5, P = 9.3 × 10-5, respectively), while anti-Scl-70 was enriched in the fibroproliferative subset. Mean modified Rodnan Skin Score (mRSS) was statistically higher in the inflammatory and fibroproliferative subsets compared with normal-like (P = 0.0027). The average disease duration for inflammatory subset was less than fibroproliferative and normal-like intrinsic subsets (P = 8.8 × 10-4). We identified multiple statistically significant differences in baseline demographics between the intrinsic subsets that may represent underlying features of disease pathogenesis (e.g. chronological stages of fibrosis) and have implications for treatments that are more likely to work in certain SSc populations.

Sonoelastography for Skin Evaluation in Sclerodermic Patients.

Background:The objective of the study is to evaluate elastography ultrasound findings in patients with scleroderma (SS) and to clarify the effectiveness of elastosonography to differentiate scleroderma lesions from any skin lesion considering tissue elasticity.Methods:Thirty-six SS patients definite diagnosis of systemic sclerosis according to American College of Rheumatology criteria and 36 healthy subjects were enrolled. Volar aspect of the middle forearm and arm in addition to the dorsal aspect of the fingers were evaluated by sonoelastography. The RGB (red, green, blue) image is a three-dimensional matrix. A color image RGB is an M × N × 3 array of color pixels. The total pixels, total blue pixels, and blue index compared between SS cases and controls.Results:Mean age of patients was 41.3 ± 10.3 years and mean age of controls was 39.8 ± 9.3 years. Mean-modified Rodnan skin score of the whole body was 11.9 and mean duration of disease was 6.2 years. Mean total blue pixels in the arm were significantly different between cases and controls. Mean total image pixels, total blue pixels, and blue index in the forearm were significantly different between cases and controls. Elastography findings in the finger were not significantly different between cases and controls.Conclusions:Sonoelastography could be used for evaluating skin of forearm in sclerodermic cases which will be helpful for disease evaluation in clinical course.

Are diffuse and limited juvenile systemic sclerosis different in clinical presentation? Clinical characteristics of a juvenile systemic sclerosis cohort.

Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud's and first non-Raynaud's symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

Assessment of modified Rodnan skin score and esophageal manometry in systemic sclerosis: a study correlating severity of skin and esophageal involvement by objective measures

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by immune-mediated activation of tissue fibroblasts and consequent fibrosis, vascular abnormalities, and inflammation. The skin and esophagus are the two most frequently involved organs in this disease. Data regarding the correlation between the severity of skin and esophageal involvement in SSc by objective measures are negligible so far. Thirty-one patients with SSc were subjected to esophageal manometry. A correlation between modified Rodnan skin score (MRSS) and esophageal manometric parameters of lower esophageal sphincter pressure (LESP), percentage relaxation of the lower sphincter, amplitude, and duration of the peristaltic waves was established. The mean MRSS was found to be 16.9 ± 8.7. There was no statistical correlation between MRSS and LESP (p = 0.496), percentage relaxation (p = 0.070), amplitude (p = 0.531), and duration (p = 0.459) of the contractions. No difference between these manometric parameters was found if the patients were divided into limited and diffuse subsets. There exists no correlation between the severity of skin involvement measured by MRSS and manometric abnormalities in SSc. All patients with SSc should undergo esophageal manometry irrespective of the extent of skin involvement.

Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis

BackgroundSystemic sclerosis (SSc) is an autoimmune disease involving the skin and several internal organs. Most therapies available for this disease are symptomatic. Given the difficulty in treating SSc, we conducted this study to investigate the effect of combined plasmapheresis (PE) and allogeneic mesenchymal stem cells transplantation (MSCT) therapy on SSc.MethodsFourteen patients underwent three repeated PE treatments with subsequent pulse cyclophosphamide on days 1, 3 and 5. Patients received a single MSCT (1 × 106 cells/kg of body weight) on day 8. During follow up, evaluations performed included complete physical examination, serologic testing, and organ function.ResultsThe mean modified Rodnan skin score (MRSS) improved from 20.1 ± 3.1 to 13.8 ± 10.2 (P < 0.001) at 12 months of follow up. Three patients had interstitial lung disease, all had improvement of lung function and improved computed tomography (CT) images after 12 months of combined therapy. This combined treatment also significantly decreased the anti-Scl70 autoantibody titer and serum transforming growth factor-β and vascular endothelial growth factor levels during follow up.ConclusionThe results indicate that PE combined with MSCT is a feasible treatment associated with possible clinical benefit for SSc patients.Trial registrationClinicalTrials.gov, NCT00962923. Registered on 19 August 2009.

Intravenous immunoglobulin may be an effective therapy for refractory, active diffuse cutaneous systemic sclerosis.

We sought to retrospectively review a single-center experience using intravenous immunoglobulin (IVIG) for the treatment of refractory, active diffuse cutaneous systemic sclerosis (dcSSc). The mean modified Rodnan Skin score (mRSS) at baseline was compared to the mRSS at 6, 12, 18, and 24 months post-IVIG initiation by the paired Student t test. Changes in mRSS at 6 and 12 months were also compared to data from historical controls of 3 large, negative, multicenter, randomized clinical trials of other medications [D-penicillamine (D-pen), recombinant human relaxin (relaxin), and oral bovine type I collagen (collagen)] and to patients treated with mycophenolate mofetil (MMF) alone using the Student t test. Thirty patients were treated with adjunctive IVIG (2 g/kg/mo) for refractory, active dcSSc. The mean baseline mRSS of our cohort was 29.6 ± 7.2, and this significantly decreased to 24.1 ± 9.6 (n = 29, p = 0.0011) at 6 months, 22.5 ± 10.0 (n = 25, p = 0.0001) at 12 months, 20.6 ± 11.8 (n = 23, p = 0.0001) at 18 months, and 15.3 ± 6.4 (n = 15, p < 0.0001) at 24 months. The mean change in mRSS at 6 months was not significantly different in the IVIG group (-5.3 ± 7.9) compared to the relaxin trial (-4.8 ± 6.99, p = 0.74) or MMF group (-3.4 ± 7.4, p = 0.26); however, at 12 months, the mean change in mRSS was significantly better in the IVIG group (-8 ± 8.3) than in the D-pen (-2.47 ± 8.6, p = 0.005) and collagen (-3.4 ± 7.12, p = 0.005) groups, and was comparable to the group of primary MMF responders (-7.1 ± 9, p = 0.67). Our observational study suggests that IVIG may be an effective adjunctive therapy for active dcSSc in patients failing other therapies.

FRI0537 Update on the Juvenile Systemic Sclerosis Inception Cohort Www.Juvenile-Scleroderma.Com

BackgroundJuvenile systemic sclerosis (jSSc) is a orphan autoimmune disease. Currently only retrospective data is existing without a standardized assessment regarding the organ involvement and evolvement of the disease. Our project...

Increased bone mineral density at the hypoxia prone site of the juxta-articular metacarpal bone in patients with limited systemic sclerosis: a cross-sectional study.

Low levels of oxygen has been shown to be involved in the induction of osteogenesis, particularly in bone repair. It is unknown whether hypoxia leads to osteogenesis at the hypoxia prone skeletal sites in limited systemic sclerosis. This study determined the total and trabecular volumetric bone mineral density (vBMD) at the hypoxia prone site of the juxta-articular metacarpal bone. In this cross-sectional study, female patients with limited systemic sclerosis were included and compared to healthy controls. Peripheral quantitative computed tomography was used to measure cross-sectional area, total vBMD, and trabecular vBMD at the radius, the tibia and the third metacarpal bone. Disease severity was assessed by the modified Rodnan Skin Score. Twenty consecutive patients were included in the sclerosis group and 20 in the control group. Mean age was 60 years (range 52-68 years), and mean disease duration was 45 months (range 4-156 months). Age, height, and weight were comparable between the groups. The mean modified Rodnan Skin Score was 1.78 (range 0 to 8). The sclerosis group showed both higher total and trabecular vBMD at the distal metacarpal bone (p=0.05 and 0.04, respectively). vBMD of the tibia and radius did not differ in both groups. vBMD at the juxta-articular metacarpal bone in patients with limited systemic sclerosis is increased, possibly due to an alteration in local bone metabolism and hypoxia induced local osteogenesis.

The role of skin trauma in the distribution of morphea lesions: A cross-sectional survey of the Morphea in Adults and Children cohort IV

Skin trauma may play a role in the development of morphea lesions. The association between trauma and the distribution of cutaneous lesions has never been examined to our knowledge. We sought to determine whether patients enrolled in the Morphea in Adults and Children (MAC) cohort exhibit skin lesions distributed in areas of prior (isotopic) or ongoing (isomorphic) trauma. This was a cross-sectional analysis of the MAC cohort. Of 329 patients in the MAC cohort, 52 (16%) had trauma-associated lesions at the onset of disease. Patients with lesions in an isotopic distribution had greater clinical severity as measured by a clinical outcome measure (mean modified Rodnan Skin Score of 13.8 vs 5.3, P= .004, 95% confidence interval 3.08-13.92) and impact on life quality (mean Dermatology Life Quality Index score 8.4 vs 4.1, P= .009, 95% confidence interval 1.18-7.50) than those with an isomorphic distribution. Most frequent associated traumas were chronic friction (isomorphic) and surgery/isotopic. Recall bias for patient-reported events is a limitation. Of patients in the MAC cohort, 16% developed initial morphea lesions at sites of skin trauma. If these findings can be confirmed in additional series, they suggest that elective procedures and excessive skin trauma or friction might be avoided in these patients.

Echocardiographic follow-up of patients with systemic sclerosis by 2D speckle tracking echocardiography of the left ventricle

BackgroundSubclinical myocardial involvement is common in systemic sclerosis (SSc) and associated with poor prognosis. Early detection, particularly during follow-up, is important. Two-dimensional speckle tracking echocardiography (STE) has already been shown to detect early left ventricular systolic impairment in SSc patients with advanced disease. The aim of this study was to assess the ability of STE to diagnose changes in left ventricular function in patients with SSc with preserved LV ejection fraction (LVEF) and normal pulmonary pressure over time.MethodsThis single-center pilot study included nineteen SSc patients without pulmonary hypertension and preserved LVEF (55.2 ± 10.8 years, 13 women, mean modified Rodnan Skin Score of 8.2 ± 6.5, median disease duration 6 ± 4.5 years). We performed STE at baseline and after two years (mean 756.6 ± 8.8 days). Pulmonary hypertension was ruled out in all patients by right heart catheterization (average mean PAP 17.7 ± 3.5 mmHg).ResultsThe LVEF remained unchanged (63.3 ± 4.2% vs. 63.2 ± 5.0%, P = ns), but the global longitudinal peak systolic strain of the left ventricle was significantly lower: baseline -22.0 ± 2.3% vs. follow-up -20.8 ± 2.1% (P = 0.04). The regional analysis showed a heterogeneous distribution of segmental systolic dysfunction that did not match any particular coronary artery distribution. In contrast, the LV diastolic function remained stable during follow-up.ConclusionSTE might be a sensititive and valuable method to detect early LV systolic impairment in patients with SSc and preserved LVEF during two years. Prospective evaluations are needed for prognostic implications of these changes.

Treatment of diffuse systemic sclerosis with hyperimmune caprine serum (AIMSPRO): a phase II double-blind placebo-controlled trial

ObjectiveThe primary objective of the study was to explore safety and tolerability of hyperimmune caprine serum (AIMSPRO) in established diffuse cutaneous systemic sclerosis (SSc). Secondary objectives included assessment of potential...

Nailfold capillaroscopy by digital microscope in an Indian population with systemic sclerosis

Nailfold capillaroscopy (NFC) is a simple, non-invasive method with exceptional predictive value for the analysis of microvascular abnormalities, especially in systemic sclerosis (SSc) but remains underutilized due to cost factors of the nailfold videocapillaroscope, lack of expertise and availability issues. The aim of this study was to establish the utility of an inexpensive digital microscope to study NFC changes in SSc in correlation with disease subsets and extent of skin involvement. Twenty-two diffuse cutaneous SSc (DSS), 20 limited cutaneous SSc (LSS) patients and 42 controls were evaluated with NFC using a digital microscope at 30× and 100× magnification. Digital micrographs were used to study qualitative and quantitative changes in microvasculature. The capillary density was significantly less in all cases of SSc as compared to controls (5.3 ± 1.4 vs. 8.7 ± 1.2; P < 0.00001). Disorganized architecture was much more prevalent in DSS versus LSS (86.4%vs. 25%). The vascular deletion score (VDS) was significantly higher in DSS as compared to LSS (P < 0.0001). Scleroderma pattern (SP) was seen in 18 (81.9%) and 15 (75%) of patients with DSS and LSS, respectively. Only 4% of normal subjects showed non-specific pattern and none showed SP. The mean modified Rodnan skin score (MRSS) was positively correlated with vascular deletion score (r = 0.572; P < 0.001) and negatively with capillary density (r = -0.8; P < 0.001). Nailfold capillaroscopy changes in SSc are related to disease subset and MRSS. NFC with digital microscope is a simplified, inexpensive, outpatient procedure with results comparable to previous studies.

Effects of micronutrient antioxidants (alpha-tocopherol and ascorbic acid) on skin thickening and lung function in patients with early diffuse systemic sclerosis

To assess the effects of alpha-tocopherol and ascorbic acid on skin thickening and lung function in patients with early diffuse systemic sclerosis (SSc), thirteen patients with early diffuse SSc, with positive anti-topoisomerase-I antibody, high skin thickening progression rate (STPR ≥ 12/year) and decreased lung diffusing capacity (DLCO ≤ 75%) were included in this study. Patients were randomized into two subgroups: Subgroup A-six patients, treated with intravenous cyclophosphamide (CyP) (500 mg/m(2) of body surface monthly) and antioxidants (alpha-tocopherol 400 IU/day and ascorbic acid 1,000 mg/day), and Subgroup B-seven patients, who received CyP without antioxidants. In both subgroups, effects of treatment on skin thickening and lung function were evaluated by comparison of the modified Rodnan skin score (MRSS), STPR, forced vital capacity (FVC), transfer-factor (DLCO) and diffusing coefficient for carbon monoxide (DLCO/VA) at baseline and 1 month after the sixth pulse of CyP. The mean MRSS did not change from baseline to the end of the follow-up in subgroup A (15.7 vs. 16.4, P = 0.50), but it increased significantly in subgroup B (17.9 vs. 23.6, P = 0.03). Although the mean STPR decreased notably in both subgroups of patients (in subgroup A-from 18.9/year to 2.2/year, P = 0.03, and in subgroup B-from 17.5/year to 8.6/year, P = 0.03), the mean STPR at the end of the treatment period was significantly lower in subgroup A (2.2/year vs. 8.6/year, P = 0.04). The mean value of FVC did not change either in subgroup A (91.0-87%, P = 0.2) or in subgroup B (from 101.2 to 99.7%, P = 0.7). Parameters of lung diffusing capacity improved somewhat in subgroup A (DLCO from 55.7 to 62.0% and DLCO/VA from 68.7 to 74.2%) and decreased in subgroup B (DLCO from 66.2 to 60.6% and DLCO/VA from 76.9 to 71.6%), but differences were not statistically significant. After 6 months of therapy, patients treated with CyP and antioxidants had a significantly lower STPR, compared to patients treated with CyP only. Lung function parameters remained stable in both subgroups. However, lung diffusing capacity improved slightly, without statistical significance, in patients treated with CyP and antioxidants, and it deteriorated in patients without antioxidants.

Pentoxyphylline in association with vitamin E reduces cutaneous fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is a disorder characterized by skin thickness and vasculopathy. The objective of the study was to evaluate the therapeutic effect and safety of the association of pentoxyphylline and vitamin E in SSc patients. Twelve SSc patients (American College of Rheumatology criteria) enrolled this 24-week open-label study. Patients received daily 800 mg of pentoxyphylline and 800 UI of vitamin E and were evaluated at 4-week interval. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at week 24. Nine diffuse SSc patients treated 6 months with cyclophosphamide were used as a historical control group. The mean age of the treated group was 43.6 years, and ten of 12 (84%) patients were women. Their mean MRSS reduced from 25.7 to 18.7 (p = 0.03) at 16th week and remained significantly reduced throughout the study. In contrast, only a trend of MRSS reduction was observed in the historical control group (p = 0.06). Two patients started the study with active ischemic ulcers and ended with a complete healing of them. No serious side effects were reported. Pentoxyphylline and vitamin E might be an alternative therapeutic approach in SSc patients.

Establishment and partial validation of a patient skin self-assessment questionnaire in systemic sclerosis

To construct a patient self-assessment questionnaire testing whether patients can provide valid information about their skin thickness, tethering and thinness. The questionnaire contained questions about the 17 body areas identical to those investigated in the Modified Rodnan Skin Score (MRSS). The baseline and 1 yr follow-up values of thickening, tethering and thinning were scored on a scale of 0-3, by 131 consecutive patients. The questionnaire was feasible. The test-retest reliability was good, with an intraclass correlation coefficient of 0.5-0.6. The MRSS correlated with the 17-area thickness score (rho = 0.435, P < 0.001). Both the patient-reported thickness and tethering scores and the expert-measured MRSS and tethering scores correlated highly with each other (rho = 0.523, P < 0.001 and rho = 0.637, P < 0.001, respectively). The patient-reported thinness scores did not show any correlation with the examiner-measured skin thickening/tethering. All thickness-related scores were sorted into the same factor by principal component analysis. Conversely, skin thinness scores were sorted into a distinct factor. Skin thickness scores reported by diffuse SSc patients were different from those of the limited SSc cases (P < 0.05). We validated the skin thickness domain of the questionnaire, except the responsiveness. Because of the low mean MRSS of patients in this investigation, the patient self-assessment validation procedure should be repeated with cases exhibiting more extensive skin involvement. Patient-reported and examiner-measured tethering may not be used as independent instruments of skin involvement. The skin thinness domain may contain valuable independent information, therefore it also merits further investigation.

Healthy children have a significantly increased skin score assessed with the modified Rodnan skin score

The modified Rodnan skin score (MRSS) is used as a primary outcome measure in most therapeutic trials in systemic sclerosis (SSc) in adults. Before we can apply this outcome measure in trials in juvenile patients with SSc, we need to evaluate this assessment method in children without sclerodermatous skin changes, to establish values for the normal paediatric population. To determine the MRSS in healthy paediatric population, patients of the paediatric rheumatology out-patient clinic with mechanical pain or with juvenile idiopathic arthritis at the age of 16 yr or under were assessed between 1 January and 31 March 2004. Patients with any sign of connective tissue disease or skin disorders, such as psoriasis or ectopic dermatitis, were excluded. The MRSS was determined at a standardized location and with a standardized pinching method. Two hundred and seventeen patients, including 100 females, were assessed. The mean age of the patients was 10.5 yr (2.9-16), the mean body mass index (BMI) was 18.3 (9.3-35.7), and the mean MRSS was 13.92 (range 4-25). The MRSS score showed a difference between males and females at every Tanner stage. There was a linear correlation between MRSS and body mass index independently of age and Tanner stage. The mean MRSS in healthy children is 13.92 units and this range would be expected in a patient with a diffuse form of SSc. The MRSS score in children correlates with the body mass index and the Tanner stage, so it should be corrected to these parameters, according to this pilot study.