Scleroderma Health Assessment Questionnaire Research Articles

Hand function in systemic sclerosis: A clinical and ultrasonographic study

Aim of the workTo evaluate hand impairment and functional disability in scleroderma patients using clinical and ultrasonographic (US) measures. Patients and methodsFifteen scleroderma patients and 10 age and sex-matched healthy controls were studied. Patients underwent clinical examination including modified Rodnan skin score. Hand function assessment included pinch and grip strength measurement, finger range of motion (ROM) assessment, Hand Mobility in Scleroderma (HAMIS) test and Hand Functional Index (HFI). Hand disability was assessed by Health Assessment Questionnaire (HAQ), Scleroderma HAQ Visual Analogue Scale (SHAQ VAS) and Cochin scale. US hand examination included measuring hand skin thickness, screening of the finger flexor and extensor tendons, measuring cartilage thickness of the 2nd MCP joint, anteroposterior thickness of the flexor retinaculum, and surface area of the median nerve. ResultsNine patients had healed digital ulcers while only one patient had active ulcers. Seven patients had arthralgia in the hand joints. The patients had a significant decrease in grip strength and finger ROM. By US, patients showed significant increase in hand skin thickness and flexor retinaculum thickness and a significant decrease in median nerve surface area. Hand disability measures showed variable significant correlations with pinch and grip strength and hand mobility measures which were significantly correlated with US skin thickness of the 2nd inter-metacarpal web space. ConclusionsHand disability in scleroderma was mainly related to impaired hand mobility and also diminished strength. The use of US in adjunct to clinical examination refines the evaluation of hand impairment in scleroderma.

Predictors of health-related quality of life and fatigue in systemic sclerosis: evaluation of the EuroQol-5D and FACIT-F assessment tools

This study evaluates predictors of health-related quality of life (HRQoL) and fatigue in systemic sclerosis (SSc) using two novel self-report indices. A cross-sectional study of patients with SSc was undertaken using a postal questionnaire including the EuroQol-5Domain health questionnaire (EQ-5D™), Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) and the Scleroderma Health Assessment Questionnaire (SHAQ). The EQ-5D assesses five domains of health quality and is quantified as a time trade-off (TTO) value and patient global assessment (0-100 visual analogue scale [VAS]). The FACIT-F is a 13-item questionnaire (0-52 scale). Higher scores for both the EQ-5D and FACIT-F indicate better health. Case notes were scrutinised for patient demographics, disease duration, serology and clinical phenotype. Sixty-eight patients (60 females, mean age 62.6 years) completed the questionnaires. Fatigue correlated closely with HRQoL (r (s) = 0.78 and 0.77 for FACIT-F vs. EQ-5D VAS and TTO respectively, p < 0.01) and disability (r (s) = -0.74 for FACIT-F vs. HAQ-DI, p < 0.01). Pain was the most frequently reported health problem (80 %) in the EQ-5D. HRQoL also correlated closely with disability (r (s) = 0.83 for EQ-5D vs. HAQ-DI, p < 0.01). SHAQ-VAS scores correlated well with the FACIT-F, EQ-5D and HAQ-DI scores (p < 0.05 for all comparisons). Of the patient demographics and clinical disease associations, only the absence of upper gastrointestinal complications was associated with better levels of fatigue, HRQoL and function. There is a strong correlation between disability, fatigue and HRQoL measured using self-reports, possibly reflecting similarly perceived health beliefs amongst patients across outcomes. There was little association between self-report indices and patient demographics and/or clinical phenotype.

Validation of the scleroderma health assessment questionnaire and quality of life in English and Chinese‐speaking patients with systemic sclerosis

To perform cross-cultural adaptation and validation of the Scleroderma Health Assessment Questionnaire (S-HAQ) and Systemic Sclerosis Quality of Life scale (SSc-QoL) in English and Chinese-speaking patients with SSc. In this Institutional Review Board approved study, patients seen at the rheumatology outpatient clinics were consecutively recruited over a 10-month period. We evaluated: (i) test-retest reliability using the intraclass correlation coefficient (ICC); (ii) known-groups construct validity by stratifying patients according to organ involvement and symptom severity; and (iii) convergent validity using Spearman's correlation with Short Form 36 version 2 (SF36v2). Forty-nine SSc patients completed the questionnaires: 26 Chinese, 23 English; 30 self-administered, 19 interviewer-administered, of which 35 responded to the retest. The SSc-QoL, HAQ Disability Index, intestinal Visual Analogue Scale (VAS), breathing VAS and overall disease severity VAS demonstrated high reliability (ICCs 0.71-0.93). The intestinal, finger ulcer and breathing S-HAQ VASs were able to differentiate patients according to their respective organ involvement. As hypothesized, the S-HAQ correlated better with the Physical Summary Component (PCS) than the Mental Summary Component (MCS) scores of the SF36v2. The SSc-QoL also demonstrated good convergent validity with the SF36v2 scales. In this pilot study, we provided preliminary evidence to demonstrate the good test-retest reliability and reasonable construct validity of S-HAQ and SSc-QoL for use in English and Chinese-speaking SSc patients. This forms the basis for future studies to assess more extensively their psychometric properties.

Assessment of fatigue and its relationships with disease-related parameters in patients with Systemic sclerosis

We aimed to assess the prevalence and severity of fatigue in Moroccan patients with systemic sclerosis (SSc) and its relationship with disease-related parameters of activity and severity and quality of life (QoL). Patients with SSc according to the American College of Rheumatology criteria (diffuse disease) and/or the LeRoy and Medsger criteria (limited disease) for SSc were recruited. The multidimensional assessment of fatigue (MAF), a self-administered questionnaire developed to measure five dimensions of fatigue with a total score ranged from 0 (no fatigue) to 50 (severe fatigue), was used to assess fatigue. The activity of disease was assessed by evaluating the severity of skin involvement, vascular manifestations, pulmonary involvement, joint and/or muscle involvement, and the erythrocyte sedimentation rate. Functional disability was assessed by using the scleroderma health assessment questionnaire. QoL was assessed using the SF-36 generic instrument. Sixty-four patients (91% women) were included. The mean age of patients was 49.5 ± 12.4 years. Fifty-nine patients (92.1%) had diffuse SSc and 5 (7.8%) had limited disease. Among our patients, 89% experienced severe fatigue with a VAS fatigue ≥50 mm. The mean total score of the MAF was 28 ± 8.6 (10-44.8) and all domains of fatigue were affected. In univariate and multivariate analysis, fatigue was correlated with severe joint involvement, pain intensity, low vital capacity, high level of ESR, and with functional disability (for all p ≤ 0.01). There were statistically significant correlations between fatigue and the deterioration of all domains of SF-36. Fatigue is a disabling symptom in our SSc patients and is associated with poor QoL. Pain, joint involvement, functional impairment, and pulmonary involvement seem to be the most important factors that predict severe fatigue. Large studies are necessary in order to confirm those findings.

Measures of systemic sclerosis (scleroderma): Health Assessment Questionnaire (HAQ) and Scleroderma HAQ (SHAQ), Physician‐ and Patient‐Rated Global Assessments, Symptom Burden Index (SBI), University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT) 2.0, Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) (Mahler's Index), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), and Raynaud's Condition Score (RCS)

Measures of systemic sclerosis (scleroderma): Health Assessment Questionnaire (HAQ) and Scleroderma HAQ (SHAQ), Physician‐ and Patient‐Rated Global Assessments, Symptom Burden Index (SBI), University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT) 2.0, Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) (Mahler's Index), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), and Raynaud's Condition Score (RCS)

Work participation and work transition in patients with systemic sclerosis: a cross-sectional study

To describe work participation and work transition due to health in patients with SSc. Associations are assessed between having made a work transition or not and factors possibly influencing that transition. This study included patients visiting the Scleroderma Clinic of the Ghent University Hospital, who regularly undergo an extensive evaluation. For this study, a questionnaire was used to collect work participation and work transition data. Eighty-four patients in the adult working-age population were included. Thirty-eight (45%) out of 84 patients participated in the labour force. Forty-six (55%) out of 84 were not engaged in a paid job; in 34 (74%) out of 46 patients this was attributed to health issues. Seventy-six (90%) out of 84 patients made a work transition. Forty-seven (62%) out of 76 made that transition due to health reasons. The group that made a health-related work transition (47/84, 56%) was compared with the remaining group (37/84, 44%) that made no work transition or a work transition for reasons other than health. There was a significant difference in educational level, skin score, lung disease severity, disease activity, disease duration, scleroderma Health Assessment Questionnaire (sHAQ), visual analogue scale (VAS) for RP, VAS for intestinal disease, VAS for overall disease, VAS for pain, Medical Outcomes Study short form 36 (SF-36), work statute and willingness to participate in training. The multivariate analysis retained sHAQ, SF-36 and disease duration as associating variables. Work participation is limited in patients with SSc and a majority make a work transition because of health problems. Demographic, disease- and work-related variables, as well as willingness to participate in training are associated with (the occurrence of) work transition.

Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status

In this case-control study, our first aim was to evaluate the bone mineral density (BMD) in women with systemic sclerosis (SSc) and its correlates. Secondarily, we aimed to evaluate 25-hydroxyvitamin D3 status and its relationships with disease parameters and BMD. Sixty patients with SSc and 60 age-and gender-matched controls were included in the absence of confounding factors that interfere with bone metabolism. Body mass index, menopausal status, familial history of osteoporosis and/or fractures; personal fracture history; exercise activity and laboratory parameters of bone metabolism were assessed in patients and controls. BMD was measured by using a dual-energy X-ray absorptiometry in lumbar spine (L1-L4) and femoral neck. The 25-hydroxyvitamin D3 was measured in a subgroup of 30 patients and in a subgroup of 30 matched controls. Systemic manifestations of SSc, biological inflammatory parameters, functional disability (scleroderma health assessment questionnaire (S-HAQ)) and immunological status of disease were collected in patients' group. The mean age of patients was 49.44 ± 13.07 years versus 49.55 ± 12.11 in controls. The mean disease duration was 9.63 ± 5.9 years. SSc patients had a significantly earlier age and longer duration of menopause than controls (P = 0.003). Phosphocalcic metabolism parameters were within normal ranges in both groups. BMD was significantly lower in SSc patients than in controls both in lumbar spine (-2.97 ± 0.25 in patients vs. 0.46 ± 0.11 in controls) and femoral neck (-1.93 ± 0.32 in patients vs. -0.81 ± 0.69 in controls) (P < 0.01). Thirty-six (60%) patients versus 15 (25%) controls had osteoporosis and 19 (31.7%) patients versus 13 (21.7%) controls had osteopenia (P < 0.01). In correlation analysis and in multiple regression models, there were significant correlations between BMD and longer duration of SSc, severe joint involvement (severe joint pain and erosive arthropathy), malabsorption syndrome and the positivity of anti-DNA topoisomerase I antibodies. Also, we found very low levels of vitamin D (10.88 ± 2.68 ng/ml) comparing to controls (57.41 ± 4.18 ng/ml) (P = 0.001). Vitamin D levels were correlated with the severity of joint pain, with immunological status and with BMD in lumbar spine and femoral neck (P < 0.01). In our sample, we state the importance of decreased BMD in Moroccan women with SSc with a high frequency of osteoporosis comparing to healthy controls. Bone loss seems to be associated with prolonged disease duration, severe joint involvement, malabsorption syndrome and immunological status. Also, SSc patients had lower levels of 25-hydroxyvitamin D3 than controls. Larger studies are needed to confirm those findings.

Determinants of depression in 111 italian patients with systemic sclerosis

A high prevalence of depressive symptoms has been described in systemic sclerosis (SSc), but no clear association with organ involvement or objective indices of disease severity has been depicted. To date, no effort has been made to determine the prevalence of depressive symptoms in Italian patients with SSc or to clarify their cause. One-hundred-eleven SSc patients were asked to fill in the Beck Depression Inventory (BDI) questionnaire, the scleroderma Health Assessment Questionnaire (sHAQ) and two additional questions assessing the patient's familiar support and the social consequences of the patient's change in physical appearnace. Thirty-seven subjects (33.4%) presented mild to severe depressive symptoms (BDI >/=17). On univariate analysis the diffuse cutaneous form of the disease (p=0.019), higher pulmonary systolic pressures on echocardiogram (p=0.016), lower FVC percentage of predicted values (p=0.022), higher sHAQ values (p<0.001) or higher VAS values for pain (p=0.007), lung involvement (p=0.02), Raynaud's phenomenon severity (p=0.002), ulcers severity (p=0.006) or disease severity (p<0.001), were associated with the presence of pathologic depressive symptoms. On multivariate analysis only the VAS for disease severity relevant to BDI scores (p=0.016). Social behaviour changes due to SSc-related physical involvement were reported in 14 patients (38%) with depressive symptoms (p=0,006) and were more likely to be observed in younger patients (p=0.001) with a more severe Raynauds's phenomenon (p=0.013). Mild to severe depressive symptoms are common in SSc patients especially in those with a worse perception of disease severity, these patients should be carefully monitored and a psychological assistance counselled whenever necessary.

Cost-of-illness of patients with systemic sclerosis in a tertiary care centre

The aim of our study was to assess the costs of SSc and to analyse cost drivers. A cross-sectional survey of consecutive patients with SSc was performed in a rheumatology centre in Hungary. Clinical characteristics, the European Scleroderma Study Group activity index, disease severity scale (DSS), scleroderma HAQ (S-HAQ) and health care utilization were recorded. Cost calculation was performed and correlation with clinical variables was analysed. Results were compared with RA and PsA. Eighty patients were involved: 72 (90%) women, mean age (s.d.) 57.4 (9.6) years and disease duration of 6.2 (6.6) years and 25% of the cases had dcSSc. Mean total cost was 9619 (s.d. 6444) euros/patient/year with rate of indirect cost being 56%. Disability-related productivity loss (55.2%) and hospitalization (28.3%) were the highest among the cost items. Patients with dcSSc had significantly higher direct costs (P = 0.005) compared with the lcSSc subset. Disease activity showed significant correlation with total costs, DSS and S-HAQ with direct costs. SSc-related costs were higher than in matched RA and PsA cases. The cost-of-illness of SSc is high with a dominance of productivity loss related costs. Moreover, the disease activity is an important cost driver.

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.

Systemic Sclerosis

We designed the current study to describe the spectrum of disease expression in systemic sclerosis (SSc) in a large cohort and to develop diagnostic criteria for SSc. We assessed patients in the Canadian Scleroderma Research Group Registry by standardized history, physical examination, and laboratory testing. We performed regression tree analysis to determine the sensitivity of various clinical and serologic features for diagnosing SSc. Over 1000 (n = 1048) patients were included: mean age 55 (+/- 12) years, 87% female, 90% white, mean disease duration 11 (+/- 10) years, and 38% with diffuse skin involvement. Common clinical features were Raynaud phenomenon (98%), sclerodactyly (92%), clinically visible mat-like telangiectasias (78%), skin involvement above the fingers (58%), lung fibrosis (35%), pulmonary hypertension (15%), and gastrointestinal tract involvement (mean number of self-reported symptoms, 4 (+/- 3) out of a possible 14). Almost 90% of patients had at least 1 SSc-related autoantibody, including 34% with anti-centromere and 16% with anti-topoisomerase I. The sensitivity of Raynaud and proximal finger skin thickening for the diagnosis of SSc was only 57%. Addition of clinically visible mat-like telangiectasias and SSc-related antibodies improved the sensitivity to 97%. We conclude that important diagnostic clues in patients with SSc include Raynaud phenomenon, skin involvement, clinically visible mat-like telangiectasias, and SSc-related autoantibodies.

Effect of bosentan on skin fibrosis in patients with systemic sclerosis: a prospective, open-label, non-comparative trial

To assess the effect of the ET-receptor antagonist bosentan on skin fibrosis and functionality in patients with SSc. In this prospective, open-label, non-comparative trial, a total of 10 patients with SSc received 62.5 mg of bosentan twice daily for 4 weeks and then 125 mg twice daily for 20 weeks. The primary endpoint was skin thickening as measured by the modified Rodnan skin score (mRSS). Further assessments included 20 MHz ultrasound, examination of digital ulcers (DUs) and evaluation of hand function by examining patients' fist closure. Furthermore, patients with SSc used the UK SSc Functional Score (UKFS), the modified scleroderma HAQ (SHAQ) and its visual analogue scale (VAS) to rate their disability related to specific organ systems. The mean change from baseline mRSS (the primary endpoint) was 6.4 at Week 24 of bosentan treatment, which was statistically significant (P < 0.001). Patients with both diffuse and limited SSc exhibited a statistically significant mean difference in the mRSS. Moreover, there was a significant healing of DUs noted between baseline and at Week 24 of bosentan treatment (P < 0.001); however, the 20 MHz ultrasound and the fist closure evaluation revealed no significant differences. There were also no statistically significant changes between baseline and Week 24 in the UKFS, the modified SHAQ and its VAS. In addition to the well-known effect of bosentan in prevention of DUs, the results of this study demonstrate that bosentan may also be effective at reducing skin fibrosis in patients with SSc.

Effect of the dual endothelin receptor antagonist bosentan on Raynaud's phenomenon secondary to systemic sclerosis: a double-blind prospective, randomized, placebo-controlled pilot study

To investigate the efficacy of the endothelin receptor antagonist, bosentan, in patients with RP secondary to SSc without pre-existing digital ulcers. Single-centre, randomized, prospective, double-blinded comparison of bosentan and placebo. Patients received either 62.5 mg bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 12 weeks or matching doses of placebo. Of the 17 patients enrolled, 16 completed the study and 1 withdrew from the study due to the reversible development of peripheral oedema. Compared with placebo, bosentan did not improve the frequency, duration, pain or severity of RP attacks. However, in contrast to placebo, bosentan significantly improved the functional scores. With respect to baseline, the scleroderma HAQ disability index changes were in favour of bosentan at Weeks 12 (P = 0.03) and 20 (P = 0.01), and the United Kingdom functional score changes at Weeks 8 (P = 0.038) and 16 (P = 0.039). Bosentan is not effective in SSc-related RP without pre-existing digital ulcers, but it might benefit functional impairment in those patients. European Union Drug Regulating Authorities Clinical Trials, https://eudract.emea.europa.eu, EudraCT-Nr 2004-002686-21.

Perceived Functioning Has Ethnic-specific Associations in Systemic Sclerosis: Another Dimension of Personalized Medicine

To measure self-reported physical and mental functioning and associated clinical features at study entry in 3 ethnic groups with systemic sclerosis (SSc). Sixty Hispanic, 39 African American, and 104 Caucasian patients with recent-onset SSc (< 5 yrs) were assessed for perceived physical and mental functioning, using the Medical Outcomes Study Short Form-36 (SF-36) and Scleroderma-Health Assessment Questionnaire (Scleroderma-HAQ). Socioeconomic, demographic, clinical, immunologic, immunogenetic, behavioral, and psychological variables (Interpersonal Support Evaluation List, ISEL; Illness Behavior Questionnaire, IBQ; and Arthritis Helplessness Index, AHI) were analyzed by linear regression models for associations with SF-36 and mHAQ scores as dependent variables. Perceived physical functioning scores had ethnic-specific associations with AHI > fatigue scores > IBQ > clinical variables (hypertension, skin score, and percentage predicted DLCO). Scleroderma-HAQ scores had ethnic-specific associations with IBQ > AHI scores > most clinical and laboratory variables. Decreased mental component summary (MCS) scores associated with AHI > ISEL. Ethnic-specific immunogenetic variables HLA-DQB1*0202 (Caucasian) and HLA-DRB 1*11 (African American), and HLA-DQA1*0501 (Hispanic) also associated with MCS. Antinuclear autoantibodies, anti-topoisomerase I, and RNA polymerases I and III also demonstrated associations with functioning in African American and Hispanic groups. Clinical, psychosocial, and immunogenetic variables had ethnic-specific associations with perceived physical and mental functioning. Consideration of ethnic-specific psychological and behavioral support in designing more personalized, relevant therapeutic interventions for the patient may improve therapeutic efficacy in SSc.

Digital ulcers and outcomes assessment in scleroderma

Ischaemic ulcerations of the fingertips are common in SSc and a source of pain and disability. Healing has been demonstrated with intravenous iloprost and two studies with bosentan have demonstrated reduction in the occurrence of new digital ulcers (DUs) over 4-6 months of treatment. Both bosentan studies showed no benefit in healing DU and because of this, net DU burden is no different between drug and placebo and accordingly secondary measures of outcome including pain and hand functionality are inconsistently affected. While it is likely an artefact, it remains unclear that current outcome measures including the Scleroderma Health Assessment Questionnaire (SHAQ), the UK Functional Score and the Michigan Hand Questionnaire are sensitive to change in the domain of digital ischaemia. Major events including amputation and hospitalization occur too infrequently to serve as practical measures of outcome in trials. Future studies of DU therapies will benefit from development of an ulcer-specific measure of outcome.

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...

Validity, reliability, and feasibility of durometer measurements of scleroderma skin disease in a multicenter treatment trial

To determine the validity, reliability, and feasibility of durometer measurements of skin hardness as an outcome measure in clinical trials of scleroderma. Skin hardness was measured during a multicenter treatment trial for scleroderma using handheld digital durometers with a continuous scale. Skin thickness was measured by modified Rodnan skin score (MRSS). Other outcome data collected included the Scleroderma Health Assessment Questionnaire. In a reliability exercise in advance of the trial, 9 investigators examined the same 5 scleroderma patients by MRSS and durometry. Forty-three patients with early diffuse cutaneous systemic sclerosis were studied at 11 international centers (mean age 49 years [range 24-76], median disease duration 6.4 months [range 0.3-23], and median baseline MRSS 22 [range 11-38]). The reliability of durometer measurements was excellent, with high interobserver intraclass correlation coefficients (ICCs) (0.82-0.92), and each result was greater than the corresponding skin site ICCs for MRSS (0.54-0.85). Baseline durometer scores correlated well with MRSS (r = 0.69, P < 0.0001), patient self-assessments of skin disease (r = 0.69, P < 0.0001), and Health Assessment Questionnaire (HAQ) disability scores (r = 0.34, P = 0.03). Change in durometer scores correlated with change in MRSS (r = 0.70, P < 0.0001), change in patient self-assessments of skin disease (r = 0.52, P = 0.003), and change in HAQ disability scores (r = 0.42, P = 0.017). The effect size was greater for durometry than for MRSS or patient self-assessment. Durometer measurements of skin hardness in patients with scleroderma are reliable, simple, accurate, demonstrate good sensitivity to change compared with traditional skin scoring, and reflect patients' self-assessments of their disease. Durometer measurements are valid, objective, and scalable, and should be considered for use as a complementary outcome measure to skin scoring in clinical trials of scleroderma.

Assessing disability and quality of life in systemic sclerosis: Construct validities of the Cochin Hand Function Scale, Health Assessment Questionnaire (HAQ), Systemic Sclerosis HAQ, and Medical Outcomes Study 36‐Item Short Form Health Survey

To assess the construct validity of the Cochin Hand Function Scale (CHFS) and the relevance of using aggregate scores for the scleroderma Health Assessment Questionnaire (sHAQ) and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) in systemic sclerosis (SSc). We evaluated 50 patients with SSc (mean +/- SD age and disease duration 54 +/- 12 years and 9 +/- 8 years, respectively), of which 26 had limited cutaneous SSc (lcSSc) and 23 diffuse SSc (dSSc). Quality of life was assessed by the SF-36, global disability by the Health Assessment Questionnaire (HAQ) and sHAQ, and hand disability by the CHFS. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis. The CHFS had good construct validity and its total score explained 75% of the variance of the HAQ. The HAQ had better construct validity than the aggregate sHAQ and their scores correlated well (r = 0.88). The aggregate sHAQ was no better than the HAQ in discriminating between lcSSc and dSSc. SF-36 physical and mental components had acceptable convergent and divergent validity. Factor analysis of the 8 subscales extracted 3 factors explaining 72% of the variance, which differed from the a priori stratification with physical and mental subscales extracted in the same factor. In patients with SSc, the CHFS has good construct validity, the HAQ should be preferred over the aggregate sHAQ for assessing physical functioning, and use of SF-36 physical and mental components aggregate scores is questionable.

Recombinant human anti–transforming growth factor β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo‐controlled phase I/II trial of CAT‐192

To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta1 (TGFbeta1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFbeta1 and TGFbeta2. Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFbeta1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.

Successful treatment of patients with severe secondary Raynaud's phenomenon with the endothelin receptor antagonist bosentan

Secondary Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc) and other collagen vascular diseases is a serious manifestation of microvascular damage that may precede the onset of visceral and/or cutaneous sclerosis for years. Recent studies have demonstrated that the endothelin receptor antagonist bosentan prevents the development of new digital ulcers in SSc. We investigated the potential benefits of bosentan in patients with secondary RP associated with pre-scleroderma and with SSc, independent of digital ulcers. Three patients with secondary RP received bosentan 62.5 mg twice daily for 4 weeks followed by 125 mg twice daily for 12 weeks during the winter season. Pain (visual analogue scale), Raynaud's disease activity (Scleroderma Health Assessment Questionnaire), number and severity of daily Raynaud's attacks (diary) and peripheral thermoregulation (thermography) were assessed during treatment periods. Pain, Raynaud's disease activity, number and severity of Raynaud's attacks significantly decreased during treatment periods. Thermography after 16-week treatment demonstrated improved peripheral thermoregulation. Although this is a small observational study, treatment with bosentan appears to measurably reduce the daily impact of Raynaud's disease and improve peripheral thermoregulation in patients with secondary RP, independent of digital ulcers.