Limited Systemic Sclerosis Research Articles

E36 Juvenile scleroderma in rheumatology unit Tripoli children hospital

Abstract Introduction Juvenile scleroderma is a rare chronic systemic connective tissue disease. It is classified into two main forms: localized scleroderma and systemic sclerosis. Since it is rare in children, many aspects of the disease remain undiscussed. Aim To study the clinical and demographic characteristics of patients diagnosed with various types of scleroderma who presented at the pediatric rheumatology unit in Tripoli Children hospital from the year 2000–2022 Materials and methods This is a retrospective case series conducted by reviewing the files of patients with scleroderma diagnosed and followed up in pediatric rheumatology unit from year 2000–2022 and collecting the data regarding patients’ demographics, time of diagnosis, clinical features, and laboratory results. Results Seven patients who met preliminary classification criteria for JSS were included. 2 males and 5 females. 1 patient with systemic sclerosis, 1 patient with linear morphea, 2 patients with generalized morphea, 1 patient with Parry Romberg syndrome, 1 patient with CREST syndrome, and 1 patient with deep morphea. The mean age at diagnosis was 8.2 ± 4.5 years. The first symptom attributable to JSS was hyperpigmented skin patches in 5 cases, no one presented with Raynaud's phenomenon. Respiratory involvement occurred in one patient, and it manifested as dyspnea as well as abnormal imaging and/or pulmonary function tests showed mild restrictive lung disease. Dysphagia was the commonest gastrointestinal symptom (4 patients, 57%). The most frequent musculoskeletal symptom was arthritis found in in 4 (57.1%) patients. Uveitis in 1 (14.3%), ANA was positive in 4 (57%) children: RF positive in 2 (28.6%) patients, ENA negative in the 7 (100%) patients. Skin biopsy was done in 2 patients and was consistent with scleroderma. Regarding treatment, six patients received MTX, one patient received prednisolone and one patient received MMF. Conclusion This report is the first describing Libyan patients with scleroderma. As reported in the literature, localized forms are more common than systemic sclerosis. Also a rare form of scleroderma (Parry Romberg syndrome) was present. Data about the disease mainly based on studies on adults and we need more studies on pediatric patients. Ethics Our study was approved by local ethical committee of pediatric department at Tripoli children hospital.

Optical Coherence Tomography Angiography Is a Useful Tool for Distinguishing Primary Raynaud's Phenomenon from Systemic Sclerosis and/or Very Early Disease of Systemic Sclerosis.

This cross-sectional study aimed to compare optical coherence tomography angiography (OCT-A) findings in patients with primary Raynaud's phenomenon (PRP; n = 22), very early disease of systemic sclerosis (VEDOSS; n = 19), and systemic sclerosis (SSc; 25 patients with limited cutaneous SSc (lcSSc) and 13 patients with diffuse cutaneous SSc (dcSSc)). Whole, parafoveal, and perifoveal superficial capillary plexus (SCP) vessel densities (VDs), deep capillary plexus VDs, and whole, inside, and peripapillary VDs were significantly higher in the PRP group (p < 0.001). In the lcSSc group, the FAZ perimeter was significantly higher than that in the VEDOSS group (p = 0.017). Retinal nerve fiber layer VDs were significantly lower in the lcSSc group than in the PRP and VEDOSS groups (p < 0.001). The whole and peripapillary optic disc VDs of the VEDOSS group were significantly higher than in the lcSSc group (p < 0.001). Whole SCP VDs (94.74% sensitivity, 100.00% specificity) and parafoveal SCP VDs (89.47% sensitivity, 100.00% specificity) showed the best performance in distinguishing patients with SSc from those with PRP. OCT-A seems to have potential diagnostic value in differentiating patients with PRP from patients with SSc and VEDOSS, and there is potential value in assessing prognostic roles, since findings from OCT-A images could be early indicators of retinal vascular injury long before overt SSc symptoms develop.

Interstitial lung disease in patients with systemic sclerosis: what can we learn from the SENSCIS trial?

The SENSCIS trial of nintedanib versus placebo is the largest trial conducted to date in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). This trial enrolled 576 patients with an extent of fibrotic ILD on high-resolution computed tomography of >10%. Median time since first non-Raynaud symptom was 3.4 years. Almost half of the patients were receiving a stable dose of mycophenolate at baseline. Key findings of the trial included that at baseline, despite having significant lung fibrosis on HRCT and impairment in lung function, 20% of the patients did not have cough and 30% did not have dyspnoea. Over 52 weeks, a marked decline in forced vital capacity (FVC) was observed (-112.0 mL/year in patients with diffuse cutaneous SSc [dcSSc] and -74.5 mL/year in patients with limited cutaneous SSc [lcSSc] in the placebo group). Loss of FVC was associated with an increased risk of SSc-related hospitalisation or death. Although certain subgroups of patients were at higher risk of progression, it was not possible to make a robust prediction of FVC decline based on baseline characteristics. The relative effect of nintedanib versus placebo on reducing the rate of FVC decline was consistent across subgroups based on factors including anti-topoisomerase I antibody (ATA) status, dcSSc vs. lcSSc, and use of mycophenolate at baseline. The side-effects of nintedanib were mainly gastrointestinal events, particularly diarrhoea. Nintedanib did not have a significant effect on skin fibrosis or health-related quality of life. Overall, the results of the SENSCIS trial support the importance of prompt identification and treatment of SSc-ILD and the consideration of nintedanib as a treatment option.

Multiple Sclerosis Is Associated With Achalasia and Diffuse Esophageal Spasm.

Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and achalasia are both disorders of esophageal peristalsis which cause clinical symptoms of dysphagia. Mechanisms involving dysfunction of the pre- and post-ganglionic nerve fibers of the myenteric plexus have been proposed. We sought to determine whether MS confers an increased risk of developing achalasia or DES. Cohort analysis was done using the Explorys database. Univariate logistic regression was performed to determine the odds MS confers to each motility disorder studied. Comparison of proportions of dysautonomia comorbidities was performed among the cohorts. Patients with a prior diagnosis of diabetes mellitus, chronic Chagas' disease, opioid use, or CREST syndrome were excluded from the study. Odds of MS patients developing achalasia or DES were (OR, 2.09; 95% CI, 1.73-2.52; P < 0.001) and (OR, 3.15; 95% CI, 2.89-3.42; P < 0.001), respectively. In the MS/achalasia cohort, 27.27%, 18.18%, 9.09%, and 45.45% patients had urinary incontinence, gastroparesis, impotence, and insomnia, respectively. In the MS/DES cohort, 35.19%, 11.11%, 3.70%, and 55.56% had these symptoms. In MS patients without motility disorders, 12.64%, 0.79%, 2.21%, and 21.85% had these symptoms. Patients with MS have higher odds of developing achalasia or DES compared to patients without MS. MS patients with achalasia or DES have higher rates of dysautonomia comorbidities. This suggests that these patients have a more severe disease phenotype in regards to the extent of neuronal degradation and demyelination causing the autonomic dysfunction.

Transcutaneous auricular branch vagal nerve stimulation as a non-invasive add-on therapeutic approach for pain in systemic sclerosis

ObjectiveSystemic sclerosis (SSc) is an autoimmune disease with health-related quality of life (HRQoL) high impairment. Pain is of paramount importance to be targeted by therapeutical approaches. Our study aim was...

Evidence of a Novel Mitochondrial Signature in Systemic Sclerosis Patients with Chronic Fatigue Syndrome.

Symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are common in rheumatic diseases, but no studies report the frequency of these in early systemic sclerosis. There are no known biomarkers that can distinguish between patients with ME/CFS, although mitochondrial abnormalities are often demonstrated. We sought to assess the prevalence of ME/CFS in limited cutaneous SSc (lcSSc) patients early in their disease (<5 years from the onset of non-Raynaud's symptoms) and to determine if alterations in mitochondrial electron transport chain (ETC) transcripts and mitochondrial DNA (mtDNA) integrity could be used to distinguish between fatigued and non-fatigued patients. All SSc patients met ACR/EULAR classification criteria. ME/CFS-related symptoms were assessed through validated questionnaires, and the expression of ETC transcripts and mtDNA integrity were quantified via qPCR. SSc patients with ME/CFS could be distinguished from non-fatigued patients through ETC gene analysis; specifically, reduced expression of ND4 and CyB and increased expression of Cox7C. ND4 and CyB expression correlated with indicators of disease severity. Further prospective and functional studies are needed to determine if this altered signature can be further utilized to better identify ME/CFS in SSc patients, and whether ME/CFS in early SSc disease could predict more severe disease outcomes.

Exploratory study on quantitative assessment of skin hardness in patients with systemic sclerosis using SOFTGRAM.

There is a lack of quantitative and objective methods for measuring skin hardness. This study aimed to verify whether SOFTGRAM, a device that can measure elastic modulus using the Hertz elastic contact theory, could be used to evaluate skin hardness in systemic sclerosis (SSc). Skin score according to the modified Rodnan total skin thickness score and elastic modulus of the skin using SOFTGRAM were measured for 20 patients with SSc and 20 healthy controls on 8 parts of the body, both of the cheeks, forearms, fingers, and hands. Five observers shared to measure skin score 320 times (40 participants × 8 parts). Elastic modulus was measured 1600 times (40 participants × 8 parts × 5 times each). As an additional examination to compare differences between observers, the skin score of another healthy control was measured 40 times (5 observers × 8 parts). Elastic modulus was measured 200 times (5 observers × 8 parts × 5 times each). There was a significant correlation between elastic modulus and skin score (correlation coefficient=0.67, p<0.001) and a significant difference in elastic modulus (8 parts: healthy controls vs. limited cutaneous SSc vs. diffuse cutaneous SSc: 22.6±15.7 vs. 32.0±27.7 vs. 44.8±39.8, p<0.001). Intraobserver reliabilities were sufficient in 6 out of 7 observers; however, interobserver was less satisfactory. This study showed the practicality of SOFTGRAM as an accurate measurement method of skin hardness but also revealed points to be improved. More studies are needed to find an accurate measurement method of skin hardness.

Systemic sclerosis: changes in the incidence rates in the Finnish population during the years 1999–2018

Objective The aim of our study was to examine changes in the incidence of systemic sclerosis (SSc) in Finland using two different classification criteria. Method Medical records of patients who had been registered with ICD-10 code M34 from 1999 to 2018 in two university hospitals were reviewed retrospectively. This period was divided into 5 year periods: 1999–2003, 2004–2008, 2009–2013, and 2014–2018. Using American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 criteria and clinical findings, we reclassified patients into four groups: diffuse SSc, limited SSc, sine SSc, or early SSc. In the same population, we also investigated whether the ACR 1980 criteria were fulfilled. Results In 1999–2018, 246 new patients with SSc and 45 patients with early SSc were identified using ACR/EULAR 2013 criteria. Of these patients, 70 fulfilled the ACR 1980 criteria. Using ACR/EULAR 2013 criteria, the increase in new diagnoses was statistically significant when comparing the fourth period with the first period (p = 0.0012). The increase was due to a rise in limited SSc. Mean annual incidence rates in these groups were 0.9, 1.2, 1.9, and 2.8 per 100 000 inhabitants ≥ 16 years old. An increasing trend was also seen when using ACR 1980 criteria, but this was not statistically significant. Conclusion The incidence of SSc increased during the period between 1999–2003 and 2014–2018 using ACR/EULAR 2013, but not using ACR 1980 criteria. The increase was detected within a limited SSc subclass, owing to more sensitive classification criteria.

Influence of systemic sclerosis on periodontal health: A case-control study.

Patients with systemic sclerosis (SSc) present various clinical and radiological oral manifestations. However, precise evaluation of the oral features associated with diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) is limited. The objective of this study was to evaluate the periodontal ligament (PDL) surface in SSc patients in comparison with controls. Assessment of oral-health-related quality of life (OHRQoL) and the levels of different biomarkers in the gingival crevicular fluid (GCF) was performed. SSc patients and matched controls underwent standardized oral examination and cone-beam computed tomography (CBCT). Levels of interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 4 (CXCL-4) and matrix metalloproteinase-9 (MMP-9) in the GCF were determined by enzyme-linked immunosorbent assay. PDL surface was measured on CBCT axial views. OHRQoL was quantified using the Mouth Handicap in SSc Scale (MHISS). Thirty-nine SSc patients and 39 controls were included. SSc patients exhibited increased PDL surface, higher number of missing teeth as well as elevated IL-6, MMP-9 and CXCL-4 levels. Reduced mouth opening was observed in dcSSc but not in lcSSc patients. MHISS score was higher in dcSSc than in lcSSc patients. Although worse periodontal parameters were found in both subgroups compared with controls, dcSSc patients presented lower gingival inflammation. SSc is associated with PDL space widening, impaired oral health and OHRQoL.

Detection of IgE-autoantibodies to nuclear antigens in patients with systemic sclerosis and analysis of their clinical relevance.

Antinuclear antibodies (ANA) of the IgE-type have been described in several connective tissue disorders (CTD) but not yet in systemic sclerosis (SSc). Aim of the study was, therefore, to establish an ELISA for the demonstration of IgE-autoantibodies to topoisomerase-I (topo-I) and the centromeric proteins A and B (CENP-A/B), to assess their prevalence and reactivity in SSc and to analyse their clinical relevance. One hundred fifty-one patients with SSc and 88 with CREST-syndrome, 291 patients with other CTD, and 23 patients with fibromyalgia syndrome (FM) as a control collective were included into the study. Patients' sera were analysed by an in-house-ELISA for IgE autoantibodies against topo-I and CENP-A/B using recombinant antigens. Patients were assessed for median Rodnan skin score(mRSS), different organ and cutaneous manifestations. Of the patients with CREST syndrome, 67% had IgE-anti-CENP-A- and 77% IgE-anti-CENP-B-antibodies. IgE-anti-topo-I antibodies were found in 56% of patients with SSc. Prevalence and reactivity were significantly higher in CREST and SSc, respectively, than in other CTD or FM. IgE-reactivity strongly correlated with IgG-antibody reactivity. In CRESTsyndrome, IgE-anti-CENP-A (but not CENP-B)-antibodies were significantly higher and more prevalent in patients with skin ulcers, high mRSS, and more than four organ manifestations. They did not correlate with blood eosinophil counts. In contrast, for IgE-anti-topo-I antibodies no correlation with clinical manifestations was observed. IgE-autoantibodies against CENP-A/B and topo-I occur in SSc underlining the concept that SSc may be a T helper cell type 2 mediated disease. IgE-anti-CENP-A-antibodies correlated with disease activity, but this has to be confirmed in larger studies.

Management of Uttana vatarakta (limited cutaneous systemic sclerosis): An experience through Ayurveda management strategies

Abstract Scleroderma (systemic sclerosis) is a group of rare diseases that involve the hardening and tightening of the skin and connective tissues. Diffuse cutaneous scleroderma and Limited Cutaneous Systemic Sclerosis (LcSSC) are the two major classifications of it. LcSSc usually affects the skin and further spreads to muscles and joints, but in about 10% cases, involvement of internal organs like gastrointestinal tract and manifestations like pulmonary hypertension is seen even after 10–15 years. The prevalence of the disease is 17.6/100,000 population. As far as the management of LcSSC in conventional medicine is concerned, other than symptomatic relief; immunosuppressive drugs are given, but long-term use of such medicines suppresses the immunity of the patient and hence the patient may get affected with opportunistic infections and causes severe complications. Hence, some alternatives in this direction are being explored from other systems of medicines for the betterment of patients. The direct description of the disease scleroderma is not available in Ayurvedic literature, but based on its presentation, it can be correlated with different stages of Vatarakta (~rheumatism due to blood tissue). A 20-year-old young male patient with presentation of limited scleroderma managed with Ayurveda therapy by Virechana (~therapeutic purgation) followed by Shamana (~palliative) therapy for one and half months and obtained encouraging results, inferring that Ayurveda therapeutic protocols can be successfully adopted in cases like LcSSC.

Shear wave elastography-based skin assessment system for systemic sclerosis: a supplement or alternative to conventional ultrasound?

Although shear wave elastography (SWE) has been found to have the potential to evaluate skin lesions in systemic sclerosis (SSc), current research fails to answer the following questions: (I) can high-frequency ultrasound (HFUS) and SWE at multiple sites throughout the body distinguish SSc subtypes; (II) is HFUS and SWE at every site equally affected by clinical characteristics; and (III) is SWE a supplement or a choice to HFUS. This prospective study aimed to compare the value of SWE-based skin stiffness and HFUS-based skin thickness in distinguishing different SSc subtypes, verify the influence of clinical features on SWE and HFUS, and provide a basis for the screening of the optimal evaluation sites and indicators in the future. Forty-nine limited and 51 diffuse SSc patients were included in this study. Their skin was assessed at 17 sites by palpation using the modified Rodnan skin score (mRSS), skin thickness measured by HFUS, and skin stiffness by SWE. Clinical features, including age, sex, body mass index, and disease duration, were collected. The diffuse SSc patients had higher skin stiffness at most sites (P<0.05), except for the finger, foot, and forehead, and a thicker skin layer at most sites (P<0.05), except for the finger. The area under the curve (AUC) of HFUS, SWE, and the combination of the two in distinguishing diffused and limited SSc were 0.866, 0.921, and 0.973, respectively. The differences were statistically significant (combination vs. SWE, P=0.002, combination vs. HFUS, P=0.021). Longer disease duration was associated with a thinner skin layer at the forearm, arm, chest wall, abdominal wall, and thigh in limited SSc, including the leg in diffused SSc. SWE was less affected by clinical features than HFUS. SWE could achieve greater discrimination between different mRSSs at multiple sites, such as fingers and arms, than HFUS. For the assessment of SSc skin, SWE has several advantages over HFUS, including less influence by clinical features and greater sensitivity to discriminate different mRSSs. SWE has the potential to become a primary imaging assessment tool as well as HFUS.

Methods of Assessing Nailfold Capillaroscopy Compared to Video Capillaroscopy in Patients with Systemic Sclerosis—A Critical Review of the Literature

Introduction: Nailfolds of patients with systemic sclerosis (SSc) provide an opportunity to directly visualize microvascular remodeling in SSc. Nailfold video capillaroscopy (NVC) remains the gold standard for assessing nailfold capillaroscopy (NFC). However, access to NVC is limited by expense and expertise. This review aims to synthesize current research on other NFC devices compared to NVC. Methods: The literature search included the primary research of adult patients with SSc as defined by the 2013 ACR/EULAR criteria. Methods of assessing NFC included stereomicroscopy/wide-field microscopy, ophthalmoscopy, dermatoscopy, smartphone devices, and digital USB microscopy. Primary outcomes included both qualitative (normal vs. abnormal nailfolds, overall pattern recognition, presence/absence of giant capillaries, hemorrhages, and abnormal morphology) and quantitative (capillary density and dimension) measures. Results: The search yielded 471 studies, of which 9 were included. Five studies compared NVC to dermatoscopy, two compared it to widefield/stereomicroscopy, one to smartphone attachments, and one to USB microscopy. In dermatoscopy studies, NVC had a higher percentage of images that were interpretable (63–77% vs. 100%), classifiable (70% vs. 84%), or gradable (70% vs. 79.3%) across three studies. Dermatoscopy had a lower sensitivity (60.2% vs. 81.6%) and higher specificity (92.5% vs. 84.6%) compared to NVC. One stereomicroscopy study found a significant difference between methods in capillary density in limited cutaneous SSc, while another found correlations in all parameters between stereomicroscopy and NVC. One smartphone lens had good agreement with NVC on abnormal capillary morphology and density. USB microscopy was able to differentiate between SSc and healthy controls using mean capillary width but not by capillary density. Discussion: A dermatoscope may serve as a more portable and affordable screening tool to identify a normal “scleroderma pattern”, and images that need further corroboration by NVC. NFC parameters reported are heterogenous and the standardization of these parameters is important, especially in non-gold-standard devices.

Cutaneous Manifestations, Clinical Characteristics, and Prognosis of Patients With Systemic Sclerosis Sine Scleroderma

Systemic sclerosis (SSc) sine scleroderma (ssSSc) is a subset of SSc defined by the absence of skin fibrosis. Little is known about the natural history and skin manifestations among patients with ssSSc. To characterize the clinical phenotype of patients with ssSSc compared with patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) within the EUSTAR database. This longitudinal observational cohort study based on the international EUSTAR database included all patients fulfilling the classification criteria for SSc assessed by the modified Rodnan Skin score (mRSS) at inclusion and with at least 1 follow-up visit; ssSSc was defined by the absence of skin fibrosis (mRSS = 0 and no sclerodactyly) at all available visits. Data extraction was performed in November 2020, and data analysis was performed from April 2021 to April 2023. Main outcomes were survival and skin manifestations (onset of skin fibrosis, digital ulcers, telangiectasias, puffy fingers). Among the 4263 patients fulfilling the inclusion criteria, 376 (8.8%) were classified as having ssSSc (mean [SD] age, 55.3 [13.9] years; 345 [91.8%] were female). At last available visit, in comparison with 708 patients with lcSSc and 708 patients with dcSSc with the same disease duration, patients with ssSSc had a lower prevalence of previous or current digital ulcers (28.2% vs 53.1% in lcSSc; P < .001; and 68.3% in dcSSc; P < .001) and puffy fingers (63.8% vs 82.4% in lcSSc; P < .001; and 87.6% in dcSSc; P < .001). By contrast, the prevalence of interstitial lung disease was similar in ssSSc and lcSSc (49.8% and 57.1%; P = .03) but significantly higher in dcSSc (75.0%; P < .001). Skin telangiectasias were associated with diastolic dysfunction in patients with ssSSc (odds ratio, 4.778; 95% CI, 2.060-11.081; P < .001). The only independent factor for the onset of skin fibrosis in ssSSc was the positivity for anti-Scl-70 antibodies (odds ratio, 3.078; 95% CI, 1.227-7.725; P = .02). Survival rate was higher in patients with ssSSc (92.4%) compared with lcSSc (69.4%; P = .06) and dcSSc (55.5%; P < .001) after up to 15 years of follow-up. Systemic sclerosis sine scleroderma should not be neglected considering the high prevalence of interstitial lung disease (>40%) and SSc renal crisis (almost 3%). Patients with ssSSc had a higher survival than other subsets. Dermatologists should be aware that cutaneous findings in this subgroup may be associated with internal organ dysfunction. In particular, skin telangiectasias in ssSSc were associated with diastolic heart dysfunction.

Association of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathic changes in limited systemic sclerosis.

Pathways contributing to endothelial dysfunction in patients with limited cutaneous systemic sclerosis (lcSSc) are largely unknown. The aim of this study was to investigate potential associations of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathy-related changes in patients with lcSSc and early-stage vasculopathy. Amino acids, calciotropic parameters, including 25-hydroxyvitamin D and parathyroid hormone (PTH), and bone turnover parameters, including osteocalcin and N-terminal peptide of procollagen-3 (P3NP), were measured in 38 lcSSc patients and 38 controls. Endothelial dysfunction was assessed by biochemical parameters, pulse-wave analysis, flow-mediated and nitroglycerine-mediated dilation. Additionally, vasculopathy-related and SSc-specific clinical changes including capillaroscopic, skin, renal, pulmonary, gastrointestinal and periodontal parameters were recorded. No significant differences in amino acids, calciotropic and bone turnover parameters were observed between lcSSc patients and controls. In patients with lcSSc, several significant correlations were found between selected amino acids, parameters of endothelial dysfunction, vasculopathy-related and SSc-specific clinical changes (all with p < 0.05). In addition, significant correlations were observed between PTH and 25-hydroxyvitamin D with homoarginine, and between osteocalcin, PTH and P3NP with modified Rodnan skin score and selected periodontal parameters (all with p < 0.05). Vitamin D deficiency defined as 25-hydroxyvitamin D < 20 ng/ml was associated with the presence of puffy finger (p = 0.046) and early pattern (p = 0.040). Selected amino acids may affect endothelial function and may be associated to vasculopathy-related and clinical changes in lcSSc patients, while the association with parameters of bone metabolism seems to be minor.

Hypoxia-Inducible Factor-1α (HIF-1α) as a Biomarker for Changes in Microcirculation in Individuals with Systemic Sclerosis.

Systemic sclerosis is an autoimmune disease characterized by tissue fibrosis and microangiopathy. Vascular changes such as a decrease in capillary density diminish blood flow and impair tissue oxygenation. Reliable ways to monitor disease activity and predict disease progression are desired in the process of patient selection for clinical trials and to optimize individual patient outcomes. Hypoxia-inducible factor-1 (HIF-1) is a dimeric protein complex that plays an integral role in the body's response to hypoxia. Our study aimed to investigate the potential abnormalities of HIF-1α plasma concentration and its possible association with disease activity and vascular abnormalities in patients with systemic sclerosis. Blood plasma levels of HIF-1α were measured in patients with systemic sclerosis (n = 50) and in healthy individuals (n = 30) using commercially available ELISA test kits. The results showed a marked increase in HIF-1α levels in patients with systemic sclerosis (3.042ng/ml [2.295-7.749]) compared to the control group (1.969ng/ml [1.531-2.903] p < 0.01). Patients with diffuse cutaneous SSc (2.803ng/ml, IQR 2.221-8.799) and limited cutaneous SSc (3.231ng/ml, IQR 2.566-5.502) exhibited elevated serum HIF-1α levels compared to the control group (p < 0.01). We found a notable increase in HIF-1α plasma concentration in patients with an "active" pattern (6.625ng/ml, IQR 2.488-11.480) compared to those with either an "early" pattern (2.739, IQR 2.165-3.282, p < 0.05) or a "late" pattern (2.983ng/ml, IQR 2.229-3.386, p < 0.05). Patients with no history of digital ulcers had significantly higher levels of HIF-1α (4.367ng/ml, IQR 2.488-9.462) compared to patients with either active digital ulcers (2.832ng/ml, IQR 2.630-3.094, p < 0.05) or healed digital ulcers (2.668ng/ml, IQR 2.074-2.983, p < 0.05). Our results indicate that HIF-1α may serve as a biomarker in assessing microcirculatory changes in individuals with systemic sclerosis.

Clinical and Serological Profile of Systemic Sclerosis Patients in a Tertiary Care Center in Kashmir, North India

Abstract Background: Systemic sclerosis (SSc) is an autoimmune disease that varies by ethnicity and geography. India, being a multiethnic country with many different geographical regions, could have such differences. However, due to a lack of data, such differences remain unknown. Aim: The aim of the study was to study clinical manifestations, organ involvement, autoantibodies, and associated autoimmune diseases in subtypes of SSc patients from Jammu and Kashmir. Materials and Methods: This single-center observational study was conducted in two parts, retrospective and prospective. A total of 112 patients were included. Data were compiled from inpatient and outpatient department records of 66 patients for retrospective part from 2012 to 2016. Prospective data were taken from 46 patients from 2016 to 2018. Patient history, clinical examination, pulmonary function test, high-resolution computed tomography (HRCT), and echocardiography findings were recorded. Results: The female: male ratio was 15:1, with a mean age of 38.3 ± 12.51 years. Sixty-five (58%) patients had limited cutaneous SSc (LcSSc), 22 (19.6%) had diffuse cutaneous SSc, 5 (4.4%) had early scleroderma, and 20 (17.8%) patients had overlap with other autoimmune diseases. Antinuclear antibody was present in 87.5% of patients. Interstitial lung disease was seen in 80.41% of the patients by HRCT, with majority having nonspecific interstitial pneumonitis pattern. Pulmonary artery hypertension was present in 14.28% of the study patients. Conclusions: In the current study and the rest of India, disease onset is a decade earlier than in the Caucasian population. There is a significant variation in presentation among patients in India, with patients from Jammu and Kashmir reporting a higher prevalence of Raynaud’s phenomenon and LcSSc.

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.

The association between CONUT score, mRSS, and development of digital ulcers in SSc patients

Objective: Digital ulcers (DUs) are a common manifestation of digital vascular damage in patients with Systemic Sclerosis (SSc), with more than half of SSc patients experiencing DUs at some point in their lives. Currently, there is a need for biomarkers related to inflammation or vascular damage that can predict the development of DUs. Methods: In this cross-sectional study, we included 42 patients with diffuse (n=26) and limited cutaneous (n=16) SSc. All patients were followed for one year to monitor the occurrence of DUs. DUs occurred at least once in 20 patients, while 22 patients never developed DUs. Patient characteristics and baseline CONUT scores were compared between SSc patients with and without DUs. Data were analyzed using the SPSS 25.0 software (IBM SPSS Statistics 25, Armonk, NY: IBM Corp.). Continuous variables were presented as mean ± standard deviation, and the Independent samples t-test was used for parametric test assumptions, while the Mann-Whitney U test was used for non-parametric test assumptions to compare independent groups. The difference between categorical variables was analyzed using Chi-Square analysis. Statistical significance was set at P&lt;0.05. Results: The average age of the study group was 50.29 ± 13.9 years, and the disease duration was 9.31 ± 7.11 years. There were no significant differences in terms of age, disease duration, body mass index, serum levels of albumin and vitamin D, lipid panels, and inflammatory indexes (NLR, PLR) between SSc patients with and without digital ulcers (p&gt;0.05 for all). The CONUT score was 0.86 ± 1.49 in patients without DUs and 1.2 ± 1.01 in patients with DUs (p: 0.092). The baseline modified Rodnan skin score (mRSS) was significantly higher in SSc patients with DUs. Conclusion: The baseline CONUT score was not significantly different in SSc patients with and without DUs. However, a higher mRSS was positively correlated with an increased risk of developing DUs in SSc patients.

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis.

Systemic sclerosis is a connective tissue disease characterized by vasculopathy and progressive fibrosis, leading to multiorgan dysfunction. Given the complex and not fully elucidated pathogenesis, biomarkers of rapid disease progression and therapeutic response are lacking. Copeptin, which reflects vasopressin activity in serum, is used in diagnosing or prognosing different cardiometabolic conditions. The aim of study was to investigate the concentration of copeptin in patients with systemic sclerosis and correlate it with specific clinical symptoms. Serum copeptin was measured in patients with systemic sclerosis (34 women and 3 men; mean age 57.6 years) and in healthy individuals (n=30) using commercially available ELISA kits. According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). The median duration of the disease was 10 [4-14] years. We found significantly higher copeptin concentration in patients with systemic sclerosis (4.21 pmol/L [3.04-5.42]) in comparison to control group (3.40 pmol/L [2.38-3.76], p<0.01). Copeptin significantly correlated with Raynaud's condition score (r=0.801, p<0.05). Patients with "late" capillaroscopic patterns had higher copeptin concentrations (5.37 pmol/L [4.29-8.06]) than patients with "early" (2.43 pmol/L [2.25-3.20], p<0.05) and "active" patterns (3.93 pmol/L [2.92-5.16], p<0.05]). Copeptin was found to be significantly higher in SSc patients with DUs (5.71 pmol/L [IQR 4.85-8.06]) when compared to SSc patients without DUs (3.31 pmol/L, [2.28-4.30], p<0.05). Additionally, copeptin concentration had good diagnostic accuracy in discriminating between patients with and without digital ulcers (AUC=0.863). Alprostadil decreased copeptin concentration from 4.96 [4.02-6.01] to 3.86 pmol/L [3.17-4.63] (p<0.01) after 4-6 cycles of administration. Our findings suggest that copeptin may be a promising biomarker of microcirculation alterations in systemic sclerosis.