Impairment In Systemic Sclerosis Research Articles

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.

Clinical trajectories of hand function impairment in systemic sclerosis: an unmet clinical need across disease subsets

BackgroundHand involvement is an early manifestation of systemic sclerosis (SSc), culprit of diagnosis and classification, and recognised major driver of disability. Impairment of hand function burdens both limited and diffuse...

Diffusing capacity of lungs for carbon monoxide associated with subclinical myocardial impairment in systemic sclerosis: A cardiac MR study

BackgroundSystemic sclerosis (SSc) is characterised by microvascular and fibrotic lesions, which are located not only in skin but also in lungs and heart.ObjectiveThis study aimed to investigate the association between...

Subclinical coronary atherosclerosis, detected by computer tomography with coronary calcium score, and the occurrence of major cardiovascular events at 5 years of follow-up in a cohort of patients with systemic sclerosis

BackgroundSpreading data describe cardiovascular disease (CVD) as a growing cause of hospitalization in systemic sclerosis (SSc) patients. Although interstitial lung disease and pulmonary arterial hypertension (PAH) remain the principal causes of mortality, the presence of CVD has been shown to further increase mortality in SSc patients. Few and contrasting data are available on cardiovascular impairment, particularly of subclinical coronary arteries disease, in SSc patients. The aims of this study were: 1) to determine the demographic, clinical, and cardiovascular differences between the groups of SSc patients with and without subclinical coronary atherosclerosis (SCA) assessed by coronary calcium score; 2) to verify the performance of cardiovascular risk scores in SSc for detection of SCA major cardiovascular events (MCVE); 3) to evaluate the risk factors associated to MCVE in 5 years of follow-up in this study group of patients. MethodsSixty-seven SSc patients were enrolled in this study. SCA was assessed using quantification of coronary calcium score by computerized tomography, reported as Agatson. Evaluation of common cardiovascular risk scores, carotid plaques by Doppler ultrasonography, the history of peripheral artery disease (PAD), lipid profiles, and clinical and laboratiristic characteristics of SSc were assessed at baseline visits for each patient. Factors associated with the presence of SCA were assessed by multivariate logistic analysis. A five years prospective study was performed for the evaluation of MCVE occurrence and its possible predictors. ResultsThe prevalence of SCA was 42% (Agatston scores of 266.04 ± 455.9 units) in our group of SSc patients. Patients with SCA were principally older (p = 0.0001) and had higher rates of CENP-B antibodies (57% vs 26%; p = 0.009), pulmonary arterial hypertension (PAH) (25% vs 3%; p = 0.008), dysphagia (86% vs 61%; p = 0.027), and users of statins (36% vs 8%; p = 0.004), carotid plaque (82% vs 13%; p = 0.0001), PAD (79% vs 18%; p = 0.0001), and metabolic syndrome (25% vs 0%; p = 0.002) than patients without SCA. Metabolic syndrome (OR: 8.2, p = 0.0001), presence of a PAD (OR: 5.98, p = 0.031), and carotid plaque (OR: 5.49, p = 0.010) were the main factors associated with SCA in SSc patients, by multivariate regression analysis. MCVE occurred in 7 patients. By multivariate COX regression analysis unique predictor of MCVE in 5 years of follow-up in our SSc patients was the presence of PAH (HR: 10.33, p = 0.009). Of note, the contemporary presence of PAH and SCA (defined as "not pure" pattern of PAH) was observed in 71% of patients with the occurrence of MCVE ConclusionThis study evidenced the high presence of the new “not pure” pattern of PAH, which could worsen the outcome in SSc in a medium-term (5 years) observation period. Furthermore, our data confirmed a higher cardiovascular impairment in SSc due to the presence of both SCA, mainly associated with typical cardiovascular risk factors, and PAH, life-threatening complications of SSc, that is the principal cause of the occurrence of MCVE in our SSc patients. A careful assessment of cardiovascular involvement in SSc and a more aggressive therapeutic strategy for preventing CAD and treating PAH should be highly suggested to reduce MCVE in SSc patients.

Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis.

Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease whose earliest clinical manifestations are microvascular tone dysregulation and peripheral microcirculatory abnormalities. Following previous evidence of an association between circulating neurovascular guidance molecules and SSc disturbed angiogenesis, here, we measured the levels of soluble neuropilin 1 (sNRP1), semaphorin 3E (Sema3E), and Slit2 by enzyme-linked immunosorbent assay in serum samples from a large case series of 166 SSc patients vs. 110 healthy controls. We focused on their possible correlation with vascular disease clinical features and applied logistic regression analysis to determine which of them could better reflect disease activity and severity. Our results demonstrate that, in SSc: (i) sNRP1 is significantly decreased, with lower sNRP1 serum levels correlating with the severity of nailfold videocapillaroscopy (NVC) abnormalities and the presence of ischemic digital ulcers (DUs); (ii) both Sema3E and Slit2 are increased, with Sema3E better reflecting early NVC abnormalities; and (iii) higher Sema3E correlates with the absence of DUs, while augmented Slit2 associates with the presence of DUs. Receiver operator characteristics curve analysis revealed that both circulating sNRP1 and Sema3E show a moderate diagnostic accuracy. Moreover, logistic regression analysis allowed to identify sNRP1 and Sema3E as more suitable independent biomarkers reflecting the activity and severity of SSc-related peripheral microvasculopathy.

Olfactive impairment in systemic sclerosis

Certaines maladies dysimmunitaires font état d’une altération de la fonction olfactive. L’analyse de ce dysfonctionnement a permis des avancées dans la compréhension physiopathologique de ces maladies. Mais qu’en est-il de la sclérodermie systémique ? Nous avons réalisé une étude prospective incluant consécutivement 56 patients atteints de sclérodermie systémique entre le 1er janvier et le 13 mars 2020. L’objectif principal de l’étude était d’étudier la prévalence des troubles olfactifs dans notre population, l’hyposmie étant définie par un résultat au score olfactif ETOC ≤ 27. Les objectifs secondaires reposaient sur l’évaluation d’un potentiel lien entre d’une part les résultats obtenus au score ETOC, et d’autre part les caractéristiques démographiques de notre population, la sévérité de la maladie et sa durée d’évolution, l’atteinte muqueuse en endoscopie nasale, et les résultats obtenus aux questionnaires d’anxiété-dépression. La prévalence des troubles olfactifs dans notre population est de 42,9 %. On met en évidence une corrélation significative entre âge et hyposmie (p = 0,005). Nous ne mettons pas en évidence de lien entre la sévérité de la sclérodermie ou sa durée d’évolution, et la présence de troubles olfactifs. En revanche nous retrouvons une corrélation significative (p = 0,003) entre les résultats du score ETOC, et la présence d’anomalies muqueuses visualisées en endoscopie nasale. La sclérodermie systémique semble être pourvoyeuse de troubles olfactifs hyposmiques. Devant la présence d’œdème et de sécrétions séromuqueuses constatés en nasofibroscopie, notre hypothèse physiopathologique pour expliquer ces troubles olfactifs hyposmiques serait celle d’une dysfonction périphérique : l’altération de la muqueuse nasale et du film muqueux entraverait l’absorption des molécules odorantes et leur diffusion vers le neuroépithélium olfactif. Nous n’excluons cependant pas l’association d’une part centrale à cette part périphérique présumée.

Correlation of retinal and choroidal microvascular impairment in systemic sclerosis

PurposeTo investigate the correlation between retinal and choroidal microperfusion in patients with systemic sclerosis (SSc) using optical coherence tomography angiography (OCTA).MethodsIn this cross-sectional study SSc patients without clinical evidence of ocular involvement and healthy, age- and sex-matched volunteers were recruited. Participants underwent specific rheumatological and ophthalmological examinations, including optical coherence tomography (OCT) and OCTA. Retinal and choroidal thicknesses as well as perfusion of the retina and the choroidal sublayers were evaluated.ResultsA total of 15 SSc patients (30 eyes) with a median disease duration of 60 months and 15 matched, healthy controls (30 eyes) were recruited. OCT data revealed a significantly lower macular volume, as well as Sattler’s layer and Haller’s layer thickness in SSc patients compared to controls. In OCTA analysis, the perfusion of both retinal plexus as well as Sattler’s and Haller’s layer were significantly reduced in the SSc group. Patients with a disease duration of more than 60 months showed a statistically significant positive correlation between retinal and choroidal malperfusion, while those with a shorter disease duration did not.ConclusionOCTA analysis confirmed impairment of retinal and choroidal microperfusion in SSc patients, supporting the hypothesis of wide spreading vascular injury. In early stages, either the retinal or the choroidal perfusion seems to be involved, while later on, vascular impairment affects both tissues alike. Both, retinal and choroidal examinations should be considered as soon as the diagnosis of SSc is made, to avoid missing out on early alterations.

Characterising Breathlessness in Systemic Sclerosis: Peak Exercise Performance is Linked to Workload-Indexed Blood Pressure Response

Cardiopulmonary involvement from systemic sclerosis (SSc) is common and 50% of patients report feeling breathless. Dyspnoea in SSc is an important determinant of quality of life and function [1]. Exercise capacity is a predictor of mortality in SSc [2], but the underlying mechanisms of the observed functional impairment are not yet elucidated. We hypothesised that vascular dysfunction, measured by the rate of change of systolic blood pressure (SBP) relative to exercise intensity (Watts), would correlate with the degree of exercise impairment in SSc.

Cardiac Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging With T1 Mapping to Assess Myocardial Perfusion and Fibrosis in Systemic Sclerosis: Association With Cardiac Events From a Prospective Cohort Study.

Myocardial involvement may occur during systemic sclerosis (SSc) and can lead to impaired myocardial contraction and/or arrhythmia. Cardiac magnetic resonance imaging (MRI) is used for noninvasive characterization of the myocardium. The aim of this study was to evaluate the utility of cardiac MRI with intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and longitudinal relaxation time (T1) sequence mapping for assessment of myocardial microvascular and interstitium impairment in SSc. In this single-center prospective cohort study, 40 consecutive patients with SSc and 20 healthy controls were assessed by cardiac MRI with IVIM DWI and T1 mapping sequences on a 3T scanning system. Images were analyzed independently by 2 assessors, and Bland-Altman plots were used to assess interreader concordance and reproducibility. Characteristics of the patients were compared according to quartiles of T1 and perfusion fraction (f-coefficient) values, using exact Cochran-Ermitage trend tests for qualitative variables and analysis of variance for quantitative variables. Kaplan-Meier cardiac events-free survival curves were plotted and compared with a log-rank test for trend. T1 values were higher in SSc patients than in healthy controls, and were higher in the diffuse cutaneous SSc (dcSSc) subset (P=0.02). Higher T1 values were associated with the immunologic pattern seen in patients with the dcSSc form (P=0.0001), a higher modified Rodnan skin thickness score (MRSS) (P=0.003), and a higher frequency of interstitial lung disease (P=0.03). Moreover, higher T1 values were correlated with higher MRSS scores (r=+0.32, P=0.04) and reduced forced vital capacity (r=-0.34, P=0.048), and tended to be correlated with reduced total lung capacity (r=-0.30, P=0.07). Lower f-coefficient values, as a measure of decreased tissue perfusion, were associated with less frequent use of vasodilators (P=0.02 for angiotensin-converting enzyme inhibitors and P=0.06 for calcium-channel blockers) and more frequent use of glucocorticoids (P=0.02). The f-coefficients were inversely correlated with the T1 values (r=-0.31, P=0.02). Furthermore, higher T1 values were associated with higher incidence of cardiac events (log-rank test for trend P=0.03). Increased T1 values, potentially suggesting microscopic fibrosis, were observed more frequently in patients with dcSSc, and higher T1 values were associated with interstitial lung disease and more frequent cardiac events during follow-up. The results of this study show that cardiac MRI with T1 mappingsequences and IVIM DWI may be useful in assessing myocardial involvement in patients with SSc.

The impact of altered hands function on working ability of patients with systemic sclerosis

Background/Aim. Hand impairment in systemic sclerosis (SSc) patients is the most frequent manifestation of this progressive disease and often cause problems in daily activities and working ability. The correlation of altered hand functions in patients with SSc and their impact on working ability is not fully explained. The objective of this study is to assess the impact of altered hand functions of patients with SSc on their working ability. Methods. We assessed 20 patients with SSc (17 females, 3 males), with mean age of 45.5 ? 11.9 years (min 29, max 69, Med 44.0 years). The movements of fingers, wrist and forearm were examined by measuring active range of motion of the hand and fingers, muscle strength of the fingers, the skin lesions by modified Rodnan score, the function of the fingers, hands and forearms by the Hand Mobility in Scleroderma (HAMIS) test, as well as the condition of the capillaries in the fingers by capillaroscopy and working capacity by Work Ability Index (WAI). Results. Reduced strength on at least one tested muscle, was established in all patients, thickening of the skin on the hands in 14/20 (70%) and the fingers in 19/20 (95%), ?scleroderma type? capillary changes in 15/17 (85%), decreased range of motion in finger joints in 16/20 (80%) of the patients. Also, 14/20 (70%) of subjects reported problems at work [decrease performance achieved in 8/20 (40%), reduction of working hours in also 8/20 (40%), leaving out some of the work in 14/20 (70%), and investing of extra effort in 15/20 (75%)]. By means of WAI, work ability assessment questionnaire, it was found that the working capacity was reduced in 11/20 (55%) of our patients. None of the patients was in the group of the most serious cases, the ?poor? category; in the ?moderate? category there were 6/20 (30%), while 5/20 (25%) of the patients were in the group with minimally reduced working capacity (?good? category). There was a statistically significant correlation between the thickened skin on the fingers (p < 0.05), reduced muscle strength in the fingers (p < 0.002) and limited mobility of the individual finger joints (p < 0.05), with information on reduced working capacity obtained by means of WAI questionnaire and with answers to questions about problems at work. Conclusion. The thickened skin on the fingers, reduced fingers muscle strength and limited mobility of certain finger joints in patients with SSc cause decreasing working capacity for all jobs that include manual activities.

The Skin ultrasound in systemic sclerosis patients: an update

Although there has been an increase in the use of skin high frequency ultrasound for the evaluation of dermal thickness and skin impairment in systemic sclerosis, its role is still under debate and its use has not yet been fully validated. Herein we discuss the recent data from research and clinical practice on methods for sonographic evaluation of dermal thickness in systemic sclerosis.

Renal Impairment in Systemic Sclerosis

Systemic sclerosis (SSc) represents a connective tissue disease, characterized by progressive fibrosis of the skin and internal organs, microvascular abnormalities, and alterations in cellular and humoral immunity. Renal impairment is a relatively common feature in patients with systemic sclerosis. It can take various clinicopathological forms, of which the most specific and severe manifestation is represented by scleroderma renal crisis. This presentation is characterized by acute onset of moderate to malignant hypertension and acute kidney injury. Although some progress has been made in management of scleroderma renal crisis with the introduction of angiotensin-converting enzyme inhibitors therapy, a large population of patients still presents a poor outcome, with up to 50 percent needing renal replacement therapy. Further understanding of disease pathogenesis may lead to improvement in patient’s outcome and survival.

Alteration of Right Ventricular to Pulmonary Artery Coupling in Systemic Sclerosis

Purpose Pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) has a worse prognosis than idiopathic PAH. This may be explained, at least in part, by an uncoupling of the right ventricle (RV) to the pulmonary artery (PA). It has been shown by Guazzi that the RV/PA coupling may be assessed non-invasively by echocardiograpy, using the TAPSE/PAPs ratio². We therefore sought to determine whether this ratio was impaired in SSc and whether this may be associated with other variables assessing the RV function. Methods In our retrospective, single center analysis, 3 groups of subjects were compared: 1) healthy subjects; 2) SSc patients without cardiac or pulmonary impairment; 3) SSc-related PAH patients. We collected anthropometrics, clinical, functional, biological and echocardiographic (focusing the right ventricle function) data. We also analyzed some hemodynamic data of patients who had a right-heart catheterization (RHC), according to international guidelines. Results The TAPSE/PAPs ratio, obtained among 10 patients with SSc-related PAH (Mean ± S.D: 0.26 ±0.13), 66 SSc-patients without PAH (0.91±0.30) and 34 healthy subjects (1.13±0.24) was significantly different between the 3 groups, even after correction for age and sex (figure). The decrease of the RV coupling was related, in the SSc group PAH-free, with a decreased s’ wave and an increased blood level of NT-proBNP. In the PAH group, there is a relation between the decrease of the RV-arterial coupling and a decreased s'wave, an increased PVR and a decreased right ventricular ejection volume. Conclusion The right ventriculo-arterial coupling, assessed by the TAPSE/PAPs ratio, is impaired in systemic sclerosis, regardless of the presence of PAH. A decrease in TAPSE/PAPs is correlated with the level of NT-proBNP and the s’ wave. This suggest a myocardial impairment in SSc which is non-related to the vascular complications.

Phenotypic Alterations Involved in CD8+ Treg Impairment in Systemic Sclerosis

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis, vasculopathy, and autoimmunity. Although the exact pathogenetic mechanisms behind SSc remain to be fully elucidated, a great deal of evidence suggests the existence of an unbalanced ratio between the effector and regulatory arms of the immune system. With regard to the T regulatory (Treg) compartment, we observed that CD8+ Treg subsets display functional defects in SSc-affected patients. Since CD127 down-modulation and CD39 upregulation have been observed on Treg subsets, the phenotypic expression of these molecules was analyzed on the CD8+CD28− Treg precursors and on CD8+ Treg cells generated in vitro through interleukin-10 commitment. Immunophenotypic data from SSc patients were compared to those obtained from healthy subjects. The analyses performed on ex vivo-isolated CD8+CD28− Treg precursors did not show any significant differences in CD39 or CD127 expression as compared to values obtained from healthy donors. On the contrary, in vitro-generated CD8+ Tregs obtained from SSc patients displayed reduced expression of the CD39 molecule as compared to controls. Moreover, the percentage of CD127+ cells was significantly higher in in vitro-generated CD8+ Tregs from SSc patients compared to CD8+ Tregs obtained from healthy donors. Taken together, these findings may indicate an impairment of maturation processes affecting CD8+ Treg cells in SSc patients. This impairment of maturation involves phenotypic alterations that are mainly characterized by a deficient CD39 upregulation and a lack of down-modulation of the CD127 molecule.

Imaging of connective tissue diseases: Beyond visceral organ imaging?

Connective tissues diseases (CTDs) can also be diagnosed early by "external" and safe imaging methods beyond the visceral organ analysis. This study aims to explore various imaging techniques used in diagnosing CTDs. Skin impairment in systemic sclerosis (SSc) may be recognized and studied by the modified Rodnan skin score (mRSS), which has some drawbacks, whereas high-frequency ultrasound (US) seems advantageous for the early identification of skin involvement. Salivary gland involvement in Sjögren syndrome (SS) can be assessed using standard tests such as unstimulated salivary flow test, salivary gland scintigraphy or contrast sialography. However, US of the major salivary glands, as an alternative, seems a reliable method with good sensitivity and specificity for the diagnosis of SS. Both the qualitative and quantitative nailfold capillaroscopic (NVC) assessments in SSc patients affected by the Raynaud's phenomenon (RP) may assist in making a differential diagnosis between primary and secondary RP. Microcirculatory imaging by NVC, along with the laser Doppler analysis, seems useful in the prediction of complications and prognosis in CTDs (i.e. SSc) and in monitoring therapeutic trials.

Hand Impairment in Systemic Sclerosis: Various Manifestations and Currently Available Treatment.

Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud's phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often co-exist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life. However, despite this knowledge, most diagnostic and treatment principles in SSc are focused on visceral manifestations due to known associations with morbidity and mortality. Treatment of inflammatory arthritis is symptom based and involves corticosteroids ≤10mg daily, methotrexate, tumor necrosis factor inhibitors, tocilizumab, and abatacept. Small joint contractures are managed by principles of occupational hand therapy and rarely surgical procedures. TFRs may be treated similar to inflammatory arthritis with corticosteroids. All patients with RP and DU should keep digits covered and warm and avoid vasoconstrictive agents. Pharmacologic management of RP begins with use of calcium channel blockers, but additional agents that may be considered are fluoxetine and phosphodiesterase 5 (PDE5) inhibitors. DU management also involves vasodilators including calcium channel blockers and PDE5 inhibitors; bosentan has also been shown to prevent DU. In patients with severe RP and active DU, intravenous epoprostenol or iloprost can be used and surgical procedures, such as botulinum injections and digital sympathectomies, may be considered. For those with early diffuse cutaneous SSc needing immunosuppression for skin sclerosis, methotrexate or mycophenolate mofetil can be used, but the agent of choice depends on co-existing manifestations, such as inflammatory arthritis and/or lung involvement. Various pharmacologic agents for calcinosis have been considered but are generally ineffective; however, surgical options, including excision of areas of calcinosis, can be considered. Overall management of hand impairment for all patients with SSc should include occupational hand therapy techniques such as range of motion exercises, paraffin wax, and devices to assist in ADL. Thus, treatment options for the various manifestations contributing to hand impairment in SSc are limited and often modestly efficacious at best. Robust studies are needed to address the manifestations of SSc that contribute to hand impairment.

Auditory and vestibular dysfunctions in systemic sclerosis: literature review.

To describe the prevalence of auditory and vestibular dysfunction in individuals with systemic sclerosis (SS) and the hypotheses to explain these changes. We performed a systematic review without meta-analysis from PubMed, LILACS, Web of Science, SciELO and SCOPUS databases, using a combination of keywords "systemic sclerosis AND balance OR vestibular" and "systemic sclerosis AND hearing OR auditory." We included articles published in Portuguese, Spanish, or English until December 2011 and reviews, letters, and editorials were excluded. We found 254 articles, out of which 10 were selected. The study design was described, and the characteristics and frequency of the auditory and vestibular dysfunctions in these individuals were listed. Afterwards, we investigated the hypothesis built by the authors to explain the auditory and vestibular dysfunctions in SS. Hearing loss was the most common finding, with prevalence ranging from 20 to 77%, being bilateral sensorineural the most frequent type. It is hypothesized that the hearing impairment in SS is due to vascular changes in the cochlea. The prevalence of vestibular disorders ranged from 11 to 63%, and the most frequent findings were changes in caloric testing, positional nystagmus, impaired oculocephalic response, changes in clinical tests of sensory interaction, and benign paroxysmal positional vertigo. High prevalence of auditory and vestibular dysfunctions in patients with SS was observed. Conducting further research can assist in early identification of these abnormalities, provide resources for professionals who work with these patients, and contribute to improving the quality of life of these individuals.

THU0548 Hand Function in Systemic Sclerosis: A Clinical and Ultrasonographic Study

BackgroundHand involvement is one of the earliest clinical manifestations of systemic sclerosis (SSc) that results in major functional compromise. Several factors may be responsible including skin and periarticular thickening, arthralgias...

Indoleamine 2,3 dioxygenase gene polymorphisms correlate with CD8+ Treg impairment in systemic sclerosis

Systemic sclerosis (SSc) is characterized by tissue fibrosis, vasculopathy and autoimmunity. Indoleamine 2,3 dioxygenase (IDO) plays a pivotal role in immunological tolerance modulating regulatory T cell (Treg) generation and function. Single nucleotide polymorphisms (SNPs) of IDO gene could impact on Treg function and predispose to autoimmunity. Here, the existence of an association between specific IDO SNPs and SSc was analyzed. Five specific SNPs in IDO gene were searched in 31 SSc patients and 37 healthy controls by gene sequencing or restriction fragment length polymorphism. The function of both CD4+CD25+ and CD8+ Treg from SSc patients was analyzed by proliferation suppression assay. SNP rs7820268 was statistically more frequent in SSc patients than in controls. Notably, SSc patients bearing the T allelic variant of the rs7820268 SNP showed impaired CD8+ Treg function. Our unprecedented data show that a specific IDO gene SNP is associated with an autoimmune disease such as SSc.

Comparative Analysis of Different Specific Indices of Hand Impairment in Systemic Sclerosis

To the Editor: Hand involvement is often the first clinical manifestation of systemic sclerosis (SSc) during the disease course. Some indices such as finger-to-palm distance in flexion (FTP)1, the Hand Anatomic Index (HAI)2, and the Hand Mobility in Scleroderma test (HAMIS)3 have been developed to assess functional impairment by testing the reduction in range of motion or evaluating inability, but there is still no consensus whether they yield different information or are mutually interchangeable. We compared these 3 assessment tools used to quantify hand impairment in SSc, considering their associations with organ involvement. Our analyses were based on 80 consecutive patients with SSc (68 women, 12 men) referred to the Division of Rheumatology, Istituto Gaetano Pini, Milan; 60 were classified as having limited cutaneous disease (lcSSc; mean age 61.3 yrs) and 20 as having diffuse cutaneous disease (dcSSc; mean age 58.9 yrs). Judged from the first symptom attributable to SSc, 20 (33.3%) lcSSc and 6 (30%) dcSSc patients had disease of recent onset (< 5 and 3 years, respectively), whereas 40 (66.7%) lcSSc and 14 (70%) dcSSc patients had intermediate/late onset disease (≥ 5 and 3 years)4. To determine patients’ disease profiles on the basis of the pattern of … Address correspondence to Dr. Ingegnoli; E-mail: francesca.ingegnoli{at}unimi.it