Scleroderma Health Assessment Questionnaire Research Articles

Prevalence and Outcomes of Gastrointestinal Manifestations in an Australian Scleroderma Cohort.

The gastrointestinal tract (GIT) is the most commonly affected internal organ in systemic sclerosis (SSc). We sought to determine the prevalence and impact of GIT symptoms on survival and patient-reported outcomes. A total of 907 consecutive patients from the Australian Scleroderma Cohort Study who had prospectively completed the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 Questionnaire (UCLA GIT) between 2015 and 2021 were included. The associations between UCLA GIT scores and physical function (Scleroderma Health Assessment Questionnaire), quality of life (QoL; Short Form 36), mood (Patient-Reported Outcomes Measurement Information System [PROMIS] anxiety and depression domains), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score), and employment were investigated using multivariable population-averaged panel models using generalized estimating equations (GEEs). Kaplan-Meier curves and multivariable Cox proportional hazard regression models were used to evaluate survival according to total UCLA GIT scores. GIT symptoms were reported in 87% of participants, with 46% to 52% reporting moderate to very severe symptoms of reflux, distension, diarrhea, and constipation. Higher total UCLA GIT scores were associated with worse QoL, physical function, fatigue, anxiety, and depression (P < 0.001). In the multivariable GEE analysis, moderate and severe to very severe total scores, reflux scores, and distension scores were associated with worse physical function, QoL, fatigue, anxiety, and depression compared to mild scores (P < 0.05). Patients with severe total scores and diarrhea scores were more likely to be unemployed compared to those with mild scores (P < 0.05). UCLA GIT total scores were not independently associated with death in our cohort. GIT manifestations are common in SSc and negatively impact QoL, physical function, and employment but are not directly associated with increased death.

Do functionality, strength, vascularization, inflammatory and biopsychosocial status improve by biopsychosocial model-based exercise in SSc?

This study aimed to investigation of the effects of the Cognitive Exercise Therapy Approach (Bilişsel Egzersiz Terapi Yaklaşımı-BETY), a supervised biopsychosocial model-based exercise intervention, on functionality, muscle strength, vascularization, anti-inflammatory and biopsychosocial status in Systemic Sclerosis (SSc) patients. Thirty-seven SSc patients were included. Twenty of them were recruited into the study group (SG) undergoing BETY group exercise sessions three times a week for three months and 17 were in the control group (CG) following a home exercise program. Assessments tools were the Modified Rodnan Skin Score (mRSS), Scleroderma Health Assessment Questionnaire (SHAQ), Modified Hand Mobility in Scleroderma (mHAMIS), Duruoz Hand Index (DHI), Six Minute Walk Test (6MWT), skeletal muscle strength measurements using an isokinetic dynamometer (Biodex System 3 Pro), Shear Wave Elastography (SWE), ELISA kits (for tumor necrosis factor-alpha, Interleukin-6, IL-10, serum irisin level), BETY-Biopsychosocial Questionnaire (BETY-BQ), Hospital Anxiety and Depression Scale (HADS), and Short Form-36 (SF-36). The SG demonstrated improvements in SHAQ, mHAMIS, 6MWT, BETY-BQ, HADS, and SF-36 values, excluding the DHI scores (p < 0.05). In contrast, CG showed worsening in SHAQ-general scleroderma symptoms and HADS scores compared to SG (p < 0.05). IL-10 and TNF-alpha increased in both groups, also various vascular parameters were significantly different changed in SG than CG (p < 0.05). Muscle strength values improved in the SG but decreased in the CG however this was statistically not significant (p > 0.05). BETY can be recommended as a nonpharmacologic approach to the disease management of SSc patients.

P132 Longitudinal changes in the Scleroderma Health Assessment Questionnaire visual analogue scales in patients with systemic sclerosis: a retrospective cohort study

Abstract Background/Aims The aim was to examine the course, impact of baseline predictors, and relationship with functional ability, of the six Scleroderma Health Assessment Questionnaire (SHAQ) visual analogue scales (VAS) over time in patients with SSc. Methods A retrospective analysis of patients attending annual review visits at a tertiary SSc center between 2005 and February 2020. Linear Mixed-effect models were used to assess longitudinal trajectories and effect of potential prognostic factors on the six different SHAQ VAS, except finger ulcers where the VAS scale was dichotomised (presence/absence) and analysed using a random intercept logistic regression model. To assess whether longitudinal changes in SHAQ VAS correlated with the HAQ-DI/11-point scleroderma functional index, we obtained the gradients of individual linear regression models, overall and by disease type. Results 537 patients (75% lcSSc) with at ≥ 2 available time-points were included. Mean follow-up time and number of review visits were 6.8 (SD = ±4.2) years 6.4 (SD = ±3.7) visits, respectively. The mean (SD) RP and disease duration (defined as the first non-RP symptom) were 7.6 (11.9) and 8.0 (8.2) years, respectively. Time-in-study (Table 1) was associated with increase in VAS intestinal (p = 0.004), overall disease (p = 0.001) and presence of ulcers (p = 0.013). There was a trend observed concerning RP VAS (p = 0.068) and VAS breathing (p = 0.074), and no difference with VAS pain (p = 0.183). Time since RP onset showed a significant negative association with VAS pain (b=-0.01, [95%CI= -0.01 to 0.00], p = 0.032). Age had a significant negative effect on intestinal VAS (b=-0.01 [95%CI= -0.01 to -0.00], p = 0.040). Presence of ulcers increased with disease duration (OR = 0.97 [95%Cl= 0.94 to 1.00], p = 0.026), and in those with diffuse disease (OR = 0.54 [95%CI= 0.31 to 0.95], p = 0.033). For patients who were anti-RNP positive (compared to negative), the overall disease score VAS was higher (b = 0.23, 95%Cl= 0.00 to 0.45, p = 0.048) higher. All correlations between SHAQ VAS scales and function (HAQ-DI and 11-point scleroderma functional index) were positive (Table 2), and were almost exclusively stronger in patients with diffuse disease. Conclusion Longitudinal assessment of the SHAQ VAS scales provides important insights into disease trajectory. We have identified baseline factors associated with VAS outcomes, and associations with function over time. Disclosure M. Hughes: None. Y. Sylvestre: None. J. Manning: None. M. Mandzuk: None. M. Samaranayaka: None. G. Dinsdale: None. A. Herrick: None.

Divergent perspectives: exploring the relationships between St. George's Respiratory Questionnaire and outcome measures in systemic sclerosis-associated interstitial lung disease.

Controversy exists regarding the concordance of patient-reported outcome measures (PROMs) with other assessment parameters in systemic sclerosis-associated interstitial lung disease (SSc-ILD). This study aims to explore the association between the St. George's Respiratory Questionnaire (SGRQ) and various outcome measures in patients with SSc-ILD within a real-world cross-sectional setting. Patients with SSc-ILD were consecutively recruited from our SSc cohort. Simultaneous administration of SGRQ, scleroderma Health Assessment Questionnaire (sHAQ), respiratory visual analog scale (R-VAS), pulmonary function tests (PFTs), and the 6-min walking test (6-MWT) was conducted. The total extent of lung fibrosis was quantified using high-resolution computed tomography (HRCT) images. Relationships between SGRQ and functional, radiographic, and other patient-reported outcome measures were analyzed. The total SGRQ score demonstrated correlations with forced vital capacity (FVC) and R-VAS (r = - 0.397, p = 0.016 and r = 0.418, p = 0.027, respectively). Symptom score correlated with ILD-extension (r = 0.430, p = 0.005); activity score correlated with FVC and R-VAS (r = - 0.502, p = 0.002 and r = 0.395, p = 0.038, respectively); impact score correlated with R-VAS (r = 0.386, p = 0.043). In patients with fibrosis extent exceeding 20%, total SGRQ score was associated with sHAQ and R-VAS (r = 0.398, p = 0.049; r = 0.524, p = 0.021, respectively), activity score with R-VAS (r = 0.478, p = 0.038), and impact score with 6-MWT-D and R-VAS (r = - 0.489, p = 0.034; r = 0.545, p = 0.016, respectively). The symptom score and activity score demonstrated optimal performance in identifying patients with interstitial lung disease (ILD) extent exceeding 20% and forced vital capacity (FVC) less than 70% (area under the curve [AUC] 0.799, p = 0.002, and AUC 0.792, p = 0.03, respectively). Our study reveals varying degrees of correlation between SGRQ and distinct outcome measures. Given the incomplete alignment of SGRQ with other outcome measures, an integrative approach utilizing existing criteria as complementary tools is recommended. Key Points • Patient-reported outcome measures (PROMs) derive from patients' subjective evaluations of the impact of the disease on their daily activities, social interactions, and psychological well-being. • PROMs frequently serve as outcome measures in randomized controlled trials, yet conflicting findings have emerged in relation to primary outcomes. • This study aims to assess the appropriateness and interrelation of PROMs with both radiological and functional outcome measures, providing insight into the current state of our patients in a real-life context. The investigation delves into the compatibility of these measures with each other.

Reliability and validity of the Turkish version of Scleroderma Skin Patient-Reported Outcome in patients with systemic sclerosis.

This study aimed to translate the Scleroderma Skin Patient-Reported Outcome (SSPRO) questionnaire to the Turkish (SSPRO-T) language and to assess its validity and reliability. Fifty-four systemic sclerosis (SSc) patients (51 females, 3 males; mean age: 49.8±10.4 years; range, 22 to 65 years) participated in the reliability and validity analysis between October 2022 and December 2022. The translation and cross-cultural adaptation of the SSPRO-T was applied in accordance with the procedure described by the Beaton guidelines. The SSPRO-T, the Scleroderma Health Assessment Questionnaire (SHAQ), the Health Assessment Questionnaire Disability Index (HAQ-DI), Skindex-29, and patient global skin severity were conducted in all participants for construct validity. The SSPRO-T was retested to assess its reliability after seven days. The SSPRO-T had a four-factor structure. The total SSPRO-T score and its subgroups correlated positively with SHAQ, HAQ-DI, Skindex-29, and patient global skin severity. The internal consistency and reliability were excellent in overall SSPRO-T and in the subgroups: physical effect, emotional effect, physical limitation, and social effect (Cronbach's α=0.94, 0.80, 0.95, 0.93, and 0.84, respectively). The SSPRO-T had excellent test-retest reliability (r=0.91, p<0.001). In addition, no floor effect or ceiling effect was observed. The SSPRO-T questionnaire is a reliable and valid tool and can be used in research and clinical practice in Turkish patients with SSc.

Role of cognitive impairment and malnutrition as determinants of quality of life in patients with systemic sclerosis.

Increasing evidence supports the presence of cognitive impairment in patients with systemic sclerosis. Malnutrition is a well-known severe complication of systemic sclerosis and is a consequence of multiple factors, mainly oropharyngeal and gastrointestinal involvement. Recent studies have shown a link between nutrition and cognitive decline in several chronic diseases. Thus, we decided to evaluate a possible association between malnutrition and cognitive impairment in patients with systemic sclerosis. In total, 100 consecutive systemic sclerosis patients were enrolled in a cross-sectional study to assess clinical and demographic features, nutritional status (body mass index, Global Leadership Initiative on Malnutrition criteria), gastrointestinal involvement (University of California Los Angeles Gastrointestinal Scale 2.0, Eat Assessment Tool 10), cognitive function (Montreal Cognitive Assessment), anxiety and depression (Patient Health Questionnaire 9, Beck Depression Inventory II), and quality of life (Short Form 36, Health Assessment Questionnaire-Disability Index, Scleroderma Health Assessment Questionnaire). Patients were stratified for the presence/absence of malnutrition and cognitive decline and compared for clinical characteristics and quality-of-life measures. Half of the patients had cognitive impairment (Montreal Cognitive Assessment < 26). These patients were older, had more comorbidities, and a significantly worse quality of life. There were no statistically significant associations with body mass index, malnutrition, and gastrointestinal involvement. About one-third of patients had clinically relevant malnutrition. They were older, had higher skin score, lung and esophageal involvement. They also showed significantly worse scores for dysphagia, gastrointestinal symptoms, functional disability, and quality of life. Gastrointestinal symptoms and dysphagia, but not body mass index and Montreal Cognitive Assessment, were significantly associated with depression scores, which in turn were negatively associated to quality-of-life measures. With regression analysis, cognitive impairment was predicted only by age, whereas malnutrition was significantly associated with age, dysphagia, and modified Rodnan skin scores. In this study, we showed that cognitive impairment and malnutrition are not directly linked but are both independently associated with greater functional disability and worse quality of life of patients with systemic sclerosis. Early recognition of these comorbidities is therefore pivotal to better address the chronic needs of patients affected by this disease.

Assessment of foot impairment in systemic sclerosis: a cross-sectional study.

To assess foot function in Systemic Sclerosis (SSc) and its association with sociodemographic and clinical factors. To evaluate mobility, foot alterations, foot pain, and foot care in these patients. Consecutive SSc patients underwent structured interviews and physical examinations. Disability was assessed using Health Assessment Questionnaire (HAQ) and Scleroderma Health Assessment Questionnaire. (SHAQ). Foot function was measured using Foot Function Index (FFI), foot pain using a numeric pain scale (NPS), and mobility using Timed-UP-Go test (TUG). 101 patients were included. Forefoot pain was observed in 50.5%, hindfoot pain in 31.7%, foot ulcers in 6.9%, foot plantar callosities in 38.6%, foot arthritis in 2.97%, hallux valgus in 9.9%, claw toes in 5%, and valgus ankle in 3% of patients. The mean FFI was 3.54 (±2.6), NPS was 6.08 (±3.58), and TUG test was 10.52 (±6.5) seconds. Higher FFI scores, increased NPS, and prolonged TUG were associated with Raynaud's phenomenon severity, SHAQ, and HAQ. 36.6% of patients reported never having their feet examined, and only 32.7% had their feet examined within the past year. Foot dysfunction and pain are common in SSc. Higher FFI scores, increased pain, and prolonged TUG duration were linked to disability (HAQ and SHAQ). These analyses should be considered exploratory and require confirmation in external cohorts. Routine foot examinations were lacking in clinical practice. Improved attention for evaluating and caring for the feet in SSc patients is needed.

Quality of sleep in individuals with systemic sclerosis and its correlation with functional disability and quality of life: a cross-sectional study.

This study aimed to evaluate the quality of sleep in individuals with systemic sclerosis and its correlation with the quality of life and disability. This is a cross-sectional study, carried out in a tertiary service of a university hospital. Inclusion criteria were diagnosis of systemic sclerosis according to the criteria of the American College of Rheumatology/European League Against Rheumatism 2013 or the preliminary criteria of the American College of Rheumatology 1980, age ≥ 18 years; regularly monitored at the outpatient clinic of rheumatology. Clinical and demographic data of the patients were obtained through a structured interview and evaluation of the medical records. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire, daytime sleepiness using the Epworth Sleepiness Scale, quality of life using 12-item short-form health survey, and disability using the scleroderma health assessment questionnaire. A total of 50 patients with systemic sclerosis were included, with 92% female, mean age 48.9 years, mean disease duration 8.9 years, and 60% limited cutaneous form. Most systemic sclerosis patients (84%) have poor sleep quality and 20% have excessive daytime sleepiness. There was a significant negative correlation between Pittsburgh Sleep Quality Index and the physical and mental components of the 12-item short-form health survey (r=-0.42, p=0.003 and r=-0.43, p=0.002, respectively) and a positive correlation with the scleroderma health assessment questionnaire (r=0.52, p=<0.001). This study showed that poor sleep quality is a very common finding among systemic sclerosis patients, and it negatively affects both the quality of life and the degree of disability. Sleep quality is an unmet need in patients with systemic sclerosis Poor sleep quality is very common in patients with systemic sclerosis Poor sleep quality correlated with worse quality of life and greater disability.

Validation of the Portuguese Version of the Scleroderma Health Assessment Questionnaire.

The Health Assessment Questionnaire Disability Index (HAQ-DI) was completed with five visual analog scales to assess systemic sclerosis (SSc) called Scleroderma HAQ (SHAQ). We performed a validation of the European Portuguese version of SHAQ for patients with SSc. Patients with different forms of SSc from five Hospital Centers were invited. The reliability of the Portuguese SHAQ was evaluated by internal consistency and by test-retest reliability. Content validity was checked by two rheumatologists and by a panel of patients. Construct validity was assessed by structural validity and by known-groups hypothesis tests. Criterion validity was addressed with selected dimensions from the UCLA GIT 2.0, the SF-36v2, and the EuroQoL EQ-5D-5L. A total of 102 SSc patients agreed to participate, 31 of which answered to the retest. HAQ-DI demonstrated high internal consistency reliability (α = 0.866) and SHAQ also showed high test-retest reliability (ICC 0.61-0.95). We evidenced the unidimensionality of all VASs. HAQ-DI scores were worse in males, patients older than 65 years, and individuals with a diffuse form of SSc. Criterion validity was mainly evidenced through the correlation between the HAQ-DI and SF-36v2 physical summary measure (r = -0.688) and EQ-5D-5L index score (r = -0.723). Likewise, the SHAQ overall disease severity VAS was also correlated with SF-36v2 physical summary measure (r = -0.628). Mental score correlations were smaller. With the exception of the Raynaud's VAS, all the other VASs correlated well with similar clinical variables. This paper provides evidence to demonstrate how reliable and valid the European Portuguese version of SHAQ is, to be used in SSc patients to assess the clinical severity under the perspective of patients.

The validity and reliability of the Turkish version of the Brief Fear of Negative Evaluation Scale - straight forwardly in patients with systemic sclerosis.

This study aimed to examine the validity and reliability of Turkish version of Brief Fear of Negative Evaluation Scale-Straightforwardly (BFNE-S (TR)) in patients with Systemic Sclerosis (SSc). 35 individuals (mean age: 53.3±13.0 years) diagnosed as SSc were included. Data on demographics, were collected via structured interview. All participants were evaluated by same investigator. The disability was evaluated with Scleroderma Health Assessment Questionnaire (SHAQ), disease severity with Medsger's Disease Severity Scale, and skin involvement with Modified Rodnan Skin Score. BFNE-S (TR) was applied to the patients with SSc who did not receive any treatment for test retest at one-week intervals. The one-factor structure was provided for all indices except Chi-Square. Factor loadings were significant. The patient responses to the BFNE-S (TR) demonstrated excellent internal consistency (Cronbach's α: 0.95). The floor effect (20%) percentage of patients who scored at floor level, was observed. Test-retest reliability of the scale was excellent with 0.91 (95%CI: 0.78-0.96). BFNE-S (TR) total score had positive correlation with SHAQ_Digestive (r=0.503) and SHAQ_Raynaud phenomenon (r=0.343)(p<0.05). The BFNE-S (TR) is a reliable and valid scale and can be used for measurement of fear of negative evaluation in SSc.

FUNCTIONS, SLEEP, FATIGUE AND QUALITY OF LIFE IN PATIENTS WITH SCLERODERMA DURING COVID-19: CROSS - SECTIONAL STUDY

Purpose: COVID-19, which has affected people in various ways, has also shown to cause various limitations on the lives of Scleroderma patients. The current study aims at evaluating the upper extremity functions, sleep quality, fatigue, and health-related quality of life in Scleroderma patients and to determine the factors affecting upper extremity functions.&#x0D; Methods: A total of 83 participants were recruited in this study. Of the participants, 39 were Scleroderma patients (mean age 43.28±9.96 years) and 44 were healthy controls (mean age 40.05±8.89 years). The Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH) and Michigan Hand Outcomes Questionnaire (MHQ) were applied to evaluate upper extremity functions of the participants. Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), and the Scleroderma Health Assessment Questionnaire (SHAQ) were used to evaluate the sleep quality, fatigue, and health-related quality of life, respectively.&#x0D; Results: Scleroderma patients had significantly lower scores in hand functions, sleep quality, fatigue, and health-related quality than the healthy group (p=0.001). The correlations between DASH and PSQI (r=0.559, p=0.001), FSS (r=0.496, p=0.001), SHAQ scores (r=0.754, p=0.001) were highly positive. Similarly, a high correlation was found between MHQ and SHAQ scores (r=-0.679, p=0.001).&#x0D; Conclusion: Upper extremity functions and health-related quality of life were found to be affected in patients with Scleroderma. It was revealed that upper extremity functions were affected by sleep quality, fatigue, and health-related quality of life. Therefore, knowing all these effects and their relationships with each other allows to draw a systematic treatment plan on Scleroderma patients.

Cultural adaptation and validation of the scleroderma health assessment questionnaire into Arabic language

BackgroundSystemic sclerosis is an autoimmune multisystem disorder which affects the patients’ physical and psychological functioning. Scleroderma health assessment questionnaire used to measure physical disability in systemic sclerosis patients. It consists of Health Assessment Questionnaire Disability Index plus five visual analogue scores related to systemic sclerosis symptoms. There is no Arabic questionnaire specifically measuring physical disability in Arabic systemic sclerosis patients; therefore, this study aimed to translate the scleroderma health assessment questionnaire, culturally adapt it, and test its reliability and validity.MethodThe scleroderma health assessment questionnaire was translated into Arabic according to translation and cross-cultural adaptation guidelines. Convergent validity is measured by correlation of scleroderma health assessment questionnaire scores for 56 patients with short-form health survey scores, while discriminate validity is tested by stratifying clinical manifestations of patients and disease subtypes. Reliability measured by the intraclass correlation coefficient by interviewing patients twice 14 days apart.ResultsThere was a strong correlation between the short-form health survey scores: physical component score and Health Assessment Questionnaire Disability Index and scleroderma health assessment questionnaire global scores (r = − 0.659**, − 0.727**), while a moderate correlation between the short-form health survey scores physical component score, and scleroderma health assessment questionnaire, visual analogue scores, and all scleroderma health assessment questionnaire visual analogue score subtypes except for Raynaud’s and digital ulcer, was found (r = − 0.495**, − 0.458*, − 0.495**, − 0.403*). The mental component score of the short-form health survey scores was moderately correlated with Health Assessment Questionnaire Disability Index and scleroderma health assessment questionnaire global scores (r = − 0.507**, − 0.51**), while it was mildly correlated with scleroderma health assessment questionnaire visual analogue score and only its subtype overall severity score (r = − 0.398*, − 0.375*). Also, statistically significant association is between diffuse disease type and digestive visual analogue score (p = 0.001). The Arabic edition of scleroderma health assessment questionnaire has a Cronbach’s alpha of 0.845.ConclusionThe translated Arabic version is a valid and reliable questionnaire to assess Egyptian systemic sclerosis patients’ functional disability.

Construct validity and reliability of the Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) questionnaire.

Assessment of construct validity and reliability of a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of RP in SSc. An international multicentre study validation study of the 27-item Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon (ASRAP) and 10-item short-form (ASRAP-SF) questionnaires. The relationship between ASRAP questionnaires and demographics, clinical phenotype and legacy instruments for assessing SSc-RP severity, disability and pain was assessed. Repeatability was evaluated at 1 week. Anchor-based statements of health status facilitated assessment of ASRAP thresholds of meaning. A total of 420 SSc subjects were enrolled. There was good correlation between ASRAP (and ASRAP-SF) with RP visual analogue scale (VAS) and Scleroderma Health Assessment Questionnaire RP VAS (rho range 0.648-0.727, P < 0.001). Correlation with diary-based assessment of SSc-RP attack frequency and duration was lower (rho range 0.258-0.504, P < 0.001). ASRAP questionnaires had good correlation with instruments for assessing disability, hand function, pain and global health assessment (rho range 0.427-0.575, P < 0.001). Significantly higher ASRAP scores were identified in smokers, patients with active digital ulceration (DU), previous history of DU and calcinosis (P < 0.05 for all comparisons). There was excellent repeatability at 1 week among patients with stable SSc-RP symptoms (intra-class coefficients of 0.891 and 0.848, P < 0.001). Patient-acceptable symptom state thresholds for ASRAP and ASRAP-SF were 45.34 and 45.77, respectively. A preliminary Minimally Important Clinical Difference threshold of 4.17 (95% CI 0.53, 7.81, P = 0.029) was estimated. ASRAP and ASRAP-SF questionnaires are valid and reliable novel PRO instruments for assessing the severity and impact of SSc-RP.

The evaluation of tibial nerve using shear-wave elastography and ultrasound in patients with systemic sclerosis: A cross-sectional study.

The study aimed to evaluate stiffness and the cross-sectional area (CSA) of the tibial nerve (TN) using shear wave elastography (SWE) and ultrasound (US) and investigate the relationship of these with disease activity, quality of life, and severity of neuropathic pain in patients with systemic sclerosis (SSc). This cross-sectional study included 28 SSc patients (1 male, 27 females; mean age: 50±11 years; range, 28 to 67 years) and 22 age- and sex-matched healthy controls (4 males, 18 females; mean age: 48±6 years; range, 37 to 66 years) between March and April 2022. US and SWE were performed on the TN, and CSA and nerve stiffness were measured. The TN was examined by a radiologist, 4 cm proximal to the medial malleolus. A few days later, an evaluation was performed in the second session by a second observer to investigate inter-and intraobserver agreement. Interobserver agreement was evaluated using the intraclass correlation coefficient (ICC). The Scleroderma Health Assessment Questionnaire, European League Against Rheumatism European Scleroderma Trial and Research (EUSTAR) group activity index, and Douleur-Neuropathique 4 scores of the patients were evaluated. Correlations between the questionnaires and measurements of nerve stiffness and CSA were assessed. Patients with SSc had significantly higher stiffness and CSA values of the right TN compared to healthy controls (p<0.001 and p=0.015, respectively). The nerve stiffness values of the right TN were positively correlated with the EUSTAR activity index (p=0.004, r=0.552). The CSA of the left TN was larger in patients with SSc (21.3±4.9 mm2 ) than in controls (12.8±3.4 mm2 ), and the nerve elasticity was positively correlated with the EUSTAR activity index (p=0.001, r=0.618). The interobserver agreement was moderate to good for measuring stiffness and CSA of the TN (ICC were 0.660 and 0.818, respectively). There was a good to excellent intraobserver agreement for measuring stiffness and CSA of TN (ICC were 0.843 and 0.940, respectively). The increased disease activity in patients with SSc is associated with TN involvement, which can be demonstrated by US and SWE.

Systemic Sclerosis Quality of Life Questionnaire (SScQoL): translation into Turkish and assessing its psychometric properties.

Systemic sclerosis (SSc) is a chronic autoimmune disease that affects the connective tissues and leads to physical, emotional, and social challenges for patients. Evaluating health-related quality of life (HRQoL) with a disease-specific tool may be preferable for improving patient care and treatment outcomes. The aim of this study was to translate the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into Turkish and to investigate its psychometric properties. Eighty-six patients with SSc (mean age 51.8 ± 11.7years, 80 females) participated in the study. Convergent validity was explored by correlation analyses between Turkish SScQoL and Short-Form 36 (SF-36), European Quality of Life Survey-5 Dimensions (EQ-5D), EQ-5D Visual Analog Scale (EQ-VAS), and Scleroderma Health Assessment Questionnaire (SHAQ). Cronbach's alpha was calculated to test internal consistency. Turkish SScQoL was readministered after 7-14days to fifty-eight patients for determining test re-test reliability. Intraclass correlation coefficients in 95% confidence interval (ICCs [95%CI]) were calculated to examine the agreement between two assessments. Values greater than 15% and an absolute skewness value < 1 were recognized as the presence of a floor or ceiling effect. SScQoL correlated significantly with SF-36 subdomains (r = -0.347 to -0.618, p < 0.01), EQ-5D (r = -0.535, p < 0.01), EQ-VAS (r = -0.636, p < 0.01), and SHAQ global score (r = 0.521, p < 0.01). SScQoL demonstrated excellent internal consistency (Cronbach's alpha = 0.917), and good to excellent test-retest reliability (ICC [95%CI] = 0.85 [0.76-0.91]). No floor/ceiling effects were observed. The Turkish version of SScQoL seems to have adequate psychometric properties and can be used to evaluate HRQoL in clinical and research settings. Key points • Turkish version of SScQoL is a valid and reliable tool for measuring health-related quality of life of patients with systemic sclerosis. • SScQoL is the only diseases-specific quality of life measurement for systemic sclerosis available in Turkish. • Patients with limited and diffuse SSc seem to be similar in terms of self-reported health-related quality of life.

Factor XIII and Endothelial Dysfunction in Patients with Systemic Sclerosis.

Systemic sclerosis (SSc, scleroderma) is a severe autoimmune connective tissue disease which affects the skin and internal organs. There has been evidence that coagulation factor XIII (FXIII) has a positive impact on clinical results in patients with SSc. In a single-center cohort study, we investigated the relationship between coagulation FXIII, endothelial dysfunction, and skin infection in SSc. Fifty-six patients could be included and were divided into two groups (with and without scleroderma). Markers of inflammation, coagulation, and endothelial dysfunction like C-reactive protein, leucocytes, fibrinogen, FVIII, VWF-Ag (von Willebrand factor antigen), D-dimers, and vascular endothelial growth factor were analyzed as well as MRSS (modified Rodnan skin scores) data were evaluated. Reduced daily activities were evaluated by the Scleroderma Health Assessment Questionnaire (SHAQ). There were no significant correlations between FXIII activity, MRSS, and SHAQ score. There were correlations between FXIII activity and Raynaud's phenomenon-related symptoms and a weak but not significant positive correlation with the level of pain. A significant correlation between VWF-Ag and lung-associated complaints (n = 56; p = 0.41, p < 0.0001) was found. Moreover, the study showed a correlation between VWF-Ag and MRSS (r [N = 48] = 0.4, p = 0.01), which means that higher VWF-Ag levels come along with more severe skin involvement. A trend toward a negative correlation between FXIII activity and VWF-Ag as marker of endothelial dysfunction was found (r [N = 56] = - 0.20, p = 0.15). In our cohort, there is no FXIII deficiency in patients with SSc. FXIII might have a role in improving cutaneous manifestations indirectly by means of a moderating influence on endothelial dysfunction. Further clinical evaluation is needed.

Translation and validation of the Persian version of the scleroderma health assessment questionnaire (SHAQ).

The present study aimed to translate and validate the Scleroderma Health Assessment Questionnaire (SHAQ) for Persian-speaking patients (SHAQ-P), using a cross-sectional study. This cross-sectional study included SSc patients with 2013 ACR/EULAR criteria. The SHAQ was translated using a "forward-backward" method. HAQ-DI and SSc-HAQ scores were calculated from the patient-answered questionnaires. Rheumatology experts assessed the face and content validities of the SHAQ-P. Psychometric properties of the SHAQ-P were then assessed: Structural validity was analyzed using principal component factor analysis. Discriminant and convergent validities were measured on subgroups of the initial patient population. Test-retest reliability was measured on patients who filled the SHAQ-P again after 1month. The Scale-CVI-average (S-CVI/Ave) score for content validity was 88.7%. Face validity was measured to be 68.17% using the QQ10 questionnaire. Factor analysis revealed a two-factor structure with 20 out of 26 questions loading on the first factor (N = 285). One-way ANOVA showed that patients with a higher number of involved organs had higher average HAQ-DI and SSc-HAQ-scores (N = 60, P = 0.019 and 0.023, respectively). HAQ-DI and SSc-HAQ-scores were significantly correlated with the physical component score of SF36 (N = 31, correlation coefficient = - 0.65 and - 0.72, respectively). Reliability testing after one month demonstrated that HAQ-DI and SSc-HAQ-scores were significantly correlated with their initial (N = 40, correlation coefficient = 0.86 and 0.84, respectively), proving that the Persian SHAQ was a valid and reliable questionnaire to evaluate scleroderma patients' quality of life.

Ruxolitinib for Treatment of Steroid Refractory Sclerotic Chronic Graft-Versus-Host Disease (cGVHD): Results of a Multicenter Phase II Trial

Background: Sclerotic cGVHD is a highly morbid form of cGVHD, often refractory to standard and secondary therapies and associated with significant decline in patients' quality of life and functioning. We conducted a single-arm phase II multicenter trial to test the hypothesis that ruxolitinib is effective treatment for steroid refractory sclerotic cGVHD (ClinicalTrials.gov ID: NCT03616184). Methods: Eligibility criteria included adults with cGVHD and skin, joint and/or fascia sclerosis, who had received systemic corticosteroids for >12 months and at least one additional line of therapy, or systemic corticosteroids and at least two additional lines of therapy. Subjects received oral ruxolitinib 10 mg twice daily for 6 months, which was subsequently tapered over another month. Treatment could be extended up to 12 months in patients deriving clinical benefit. The primary objective was to determine the proportion of patients with an NIH-defined response in skin or joints at 6 months. A sample size of 47 patients (estimated 10% drop out) had α of 0.044 and a power of 84% to test the null hypothesis response rate of 25% (Clin Cancer Res. 2016; 22: 319-327) compared to an alternative of 45%. Other endpoints included overall response, non-relapse mortality (NRM), treatment failure (administration of additional systemic therapy, malignancy relapse or mortality), glucocorticoid dose reduction, and patient-reported outcomes (PROs) (Lee symptom scale and Scleroderma Health Assessment Questionnaire). Results: 49 patients were consented between November 2018- June 2021; 2 patients were screen failures. Baseline characteristics of 47 patients included a mean age of 58 (range 23-76) years, 40% female, and 91% white. 87% had peripheral blood as a graft source. 66% had matched unrelated donor transplant. 66% had prior acute GVHD. Median time from cGVHD diagnosis to enrollment was about 48 months. All patients had classic cGVHD at enrollment. Severity included mild (2%), moderate (13%) or severe (85%). Patients had received a mean of 3 prior lines of treatment. Patients received a mean of 8.6 cycles of ruxolitinib. 13% had missing data that precluded response assessment; these patients were considered non-responders. Partial responses (PR) in skin or joint (primary endpoint) were seen in 49% (95% CI 34-64%) at 6 months; other responses included stable disease (19%), progression (19%) and missing (13%) (Fig 1). No complete responses were observed in skin or joint. Overall cGVHD partial responses were seen in 47% (95% CI 32-61%); other responses included stable disease (13%), mixed responses/progression (27%) and missing (13%). PR/CR in individual organs (among those with organ involvement after excluding missing data) were as following: eye (12/32, 37%), mouth (9/17, 53%), esophagus (5/9, 55%), upper GI (2/3, 67%), lower GI (2/3, 67%), lung (1/9, 11%), and liver (5/14, 36%). 24% (95% CI 11.8-41.2%) had >50% reduction in glucocorticoid dose from baseline to 6 months. The cumulative incidences of treatment failure and NRM at 6 months were 15.2% (95% CI 6.6- 27.1%) and 2.2% (95% CI 0.2-10.3%). No patients have had relapse of malignancy. 6-month failure free survival was 84.8% (95% CI 70.7-92.4%) (Fig 2). Any grade and grade 3 or higher adverse events occurred in 55% (n=26) and 36% (n=17) of patients. 6 out of 17 grade 3 or higher adverse events were considered possibly or probably related to ruxolitinib. AE occurring in >10% of patients included dry eye, diarrhea, nausea, vomiting, infection, upper respiratory tract infection, weight gain, laboratory and other abnormalities. PRO analyses are ongoing and will be presented. Discussion: The trial met its primary endpoint with half of adults with moderate-severe sclerotic cGVHD achieving partial responses in skin or joint as well as overall cGVHD responses. The use of ruxolitinib was associated with high rates of failure-free survival. In conclusion, the use of ruxolitinib results in high rate of responses in highly morbid sclerotic form of cGVHD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association of pain and clinical factors on disability and quality of life in systemic sclerosis: A cross-sectional study from Turkish League Against Rheumatism Network.

In this study, we aimed to evaluate the factors associated with disability and quality of life (QoL) in Turkish patients with systemic sclerosis (SSc). Between January 2018 and January 2019, a total of 256 SSc patients (20 males, 236 females; mean age: 50.9±12.4 years; range, 19 to 87 years) who were diagnosed with SSc were included in the study. Disability and health-related QoL (HRQoL) were evaluated by the Health Assessment Questionnaire (HAQ), scleroderma HAQ (SHAQ), Duruöz Hand Index (DHI), and Short Form-36 (SF-36). Linear regression analysis methods were used to describe factors associated with disability and QoL of the patients. All disability scores were higher and HRQoL scores were lower in diffuse cutaneous SSc patients compared limited cutaneous SSc, and differentiations were significant (p=0.001 and p=0.007). In multiple regression, pain (VAS) was the strongest predictor for high disability and low QoL scores (p<0.001) as HAQ (β=0.397, 0.386, 0.452), SHAQ (β=0.397, 0.448, 0.372), DHI (β=0.446, 0.536, 0.389), PCS (β=-0.417,-0.499, -0.408) and MCS (β=-0.478, -0.441, -0.370) in combined, lcSSc and dcSSc patients respectively. The factors associated with high disability and low QoL scores were forced vital capacity for HAQ (β=-0.172, p=0.002) and SF-36 PCS (β=0.187, p=0.001); disease duration for HAQ (β=0.208, p<0.001), DHI (β=0.147, p=0.006), and SF-36 PCS (β=-0.134, p=0.014); 6-minute walk test for HAQ (β=-0.161, p=0.005) and SF-36 PCS (β=0.153, p=0.009); and modified Rodnan skin score for SHAQ (β=0.250, p<0.001) and DHI (β=0.233, p<0.001) in SSc patients. Diffusing capacity of the lungs for carbon monoxide for HAQ (β=-0.189, p=0.010) and SHAQ (β=-0.247, p=0.002); erythrocyte sedimentation rate for DHI (β=0.322, p<0.001); age for SF-36 PCS (β=-0.221, p=0.003) and body mass index for SF-36 PCS (β=-0.200, p=0.008) and MCS (β=-0.175, p=0.034) were the other variables associated with high disability or low QoL scores in SSc subsets. Clinicians should consider the management of the pain and its sources as a key to improve better functional state and quality of daily life in SSc.

Validation of the Swedish version of PROMIS-29v2 and FACIT-Dyspnea Index in patients with systemic sclerosis

Purpose To evaluate the reliability, internal consistency, and construct validity of the Swedish versions of PROMIS-29 and Functional Assessment of Chronic Illness Therapy-Dyspnea (FACIT-Dyspnea) instruments in patients with systemic sclerosis (SSc). Methods In a cross-sectional study, consecutive SSc patients completed a paper-based survey. Internal consistency was assessed using Cronbach’s alpha. Test–retest reliability was tested employing weighted Kappa (K w) and intra-class correlation coefficient (ICC). Construct validity was evaluated by hypotheses testing using RAND-36, MRC Dyspnea score, Scleroderma Health Assessment Questionnaire (SHAQ) and clinical measurements. Results Forty-nine patients (86% female; 73% limited cutaneous SSc) completed the survey. The mean disease duration was 11 years and mean SHAQ was 0.5. Internal consistency and test–retest reliability were good with the exception of PROMIS-29 anxiety. PROMIS-29, FACIT-Dyspnea, and Functional limitation showed strong correlations to corresponding RAND-36 domains (|r s|=0.67 to −0.85). Relevant PROMIS-29 domains, FACIT-Dyspnea and Functional limitation correlated strongly to SHAQ and VAS overall disease severity (|r s|=0.60 to −0.75). Ceiling effects (>15%) were found in six PROMIS-29 domains and in both FACIT-Dyspnea and Functional limitations. Four (4/5) hypotheses were confirmed. Conclusions PROMIS-29 and FACIT-Dyspnea meet the requirements for reliability and have adequate construct validity in Swedish patients with SSc. Implications for rehabilitation PROMIS-29v2 and Functional Assessment of Chronic Illness Therapy-Dyspnea (FACIT-Dyspnea) Index are patient outcome measures that gain increasing interest for the evaluation of patient with rheumatologic diseases. PROMIS-29v2 and FACIT-Dyspnea Index meet the requirements for reliability and have adequate construct validity compared to legacy measures in Swedish patients with systemic sclerosis. Translation and validation of PROMs is important for studies of rare diseases in multi-center collaborations.