Course Of Systemic Sclerosis Research Articles

Uveal complications in the course of systemic sclerosis: A clinical case

Uveal complications in the course of systemic sclerosis: A clinical case

Levels of anti-topoisomerase I antibody correlated with short onset of cardiopulmonary involvement in Thai systemic sclerosis patients

Anti-topoisomerase-I antibody (ATA) is associated with disease severity and internal organ involvement in patients with systemic sclerosis (SSc). The correlation between ATA levels and the clinical course of SSc is unclear. We aimed to determine the correlation between ATA level and survival time and the onset of internal organ fibrosis in SSc patients. This historical cohort study was conducted in adult SSc patients with quantitative tests of ATA between January 2019 and December 2022. Patients with overlap syndrome and no quantitative ATA test were excluded. According to the sample size calculation, and 10% compensated for missing data, a total of 153 patients were needed. The respective mean age on the study date and median ATA level was 59.9 ± 11.3 years and 370 U/mL (range 195–652). Most cases (107 cases; 69.9%) were the diffuse cutaneous SSc subset. According to a multivariable analysis, the ATA titer had a negative correlation with the onset of cardiac involvement (Rho − 0.47, p = 0.01), and had a positive correlation with skin thickness progression (Rho 0.39, p = 0.04). Eleven cases exhibited ATA levels < 7 U/mL and outlier ATA levels were excluded, 142 cases were included in the sensitivity analysis, and multivariable analysis showed the correlation between early onset of ILD and cardiac involvement (Rho − 0.43, p = 0.03 and Rho − 0.51, p = 0.01, respectively). The ATA level was correlated with neither the survival time nor the onset of renal crisis in both analyses. High ATA levels were correlated with a short onset of ILD and cardiac involvement and the presence of extensive skin tightness. Quantitative tests of ATA could serve as an effective tool for identifying patients at risk of an unfavorable prognosis.

Immunogenetics of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as primarily a "hyperfibrotic" state towards a recognition of systemic sclerosis as an immune-mediated disease. Consequently, the search for genetic markers has transitioned from focusing on fibrotic mechanisms to exploring immune regulatory pathways. Immunogenetics, an emerging field at the intersection of immunology, molecular biology, and genetics has provided valuable insights into inherited factors that influence immunity. Data from genetic studies conducted thus far indicate that alterations in genetic messages can significantly impact disease risk and progression. While certain genetic variations may confer protective effects, others may exacerbate disease susceptibility. This paper presents a comprehensive review of the most relevant genetic changes that influence both the risk and course of systemic sclerosis. Special emphasis is placed on factors regulating the immune response, recognizing their pivotal role in the pathogenesis of the disease.

Clinical case of systemic sclerosis in a male patient: gender differences and possibilities of capillaroscopy

A patient with a subacute course of systemic sclerosis (SSc) and a three-phase Raynaud's phenomenon at the onset of the disease is described. The diagnosis was made in accordance with the ACR/EULAR 2013 criteria. Within 8 months of disease onset, the patient developed the classic picture of SSc with multiple organ involvement, and nailfold capillaroscopy showed signs of the active stage of scleroderma angiopathy. The factors for an unfavorable course of SSc were analyzed.

Recurrent spontaneous pneumothorax under nintedanib treatment in ınterstitial lung disease associated with systemic sclerosis.

Interstitial lung disease (ILD) is a common complication that can develop during the course of systemic sclerosis (SSc). Nindetanib is an antifibrotic drug approved for the treatment of systemic sclerosis-associated interstitial lung disease. Although there is an insufficient data on the development of pneumothorax, the safety of Nintedanib treatment is also uncertain. We observed recurrent resistant pneumothorax under nintedanib treatment in a patient with systemic sclerosis-associated interstitial lung disease. Nintedanib use may increase the risk of developing refractory pneumothorax. Ssc patients who are started on nintedanib should be followed carefully for pneumothorax.

Preventing Malnutrition through Adequate Management of Gastrointestinal Dysmotility in Systemic Sclerosis Patients: A Literature Review

Gastrointestinal dysmotility in systemic sclerosis occurs as the end result of extensive fibrosis of the gastrointestinal tract. The entire length of the tract from the esophagus to the anorectum could be affected, exerting various gastrointestinal symptoms. Clinical manifestations attributed to gastrointestinal dysmotility are associated with significant distress and an increased risk of nutritional impairment, reducing the the quality of life of systemic sclerosis patients. One of the most commonly overlooked gastrointestinal implications in systemic sclerosis is malnutrition. Once malnutrition ensues in the course of systemic sclerosis, the detrimental effects attributed to nutritional decline are difficult to reverse and pose an increased risk of mortality. Adequate management through timely diagnosis of gastrointestinal dysmotility and utilization of malnutrition screening tools for systemic sclerosis patients could prevent the progression to malnutrition and its negative impacts.

The profile of adipokines associated with fibrosis and impaired microcirculation in systemic sclerosis

PurposeAdipokines belong to a group of molecules mostly produced by adipose tissue. Abnormalities in the secretion of several adipokines have already implicated to play a pathogenic role in systemic sclerosis (SSc). However, the possible role of numerous molecules still needs to be clarified. The aim of the study was to determine whether the altered level of selected circulating adipokines might correlate with the intensity of fibrosis and vasculopathy in the course of SSc. Materials and methodsSerum concentrations of chemerin, adipsin, retinol-binding protein 4, apelin, visfatin, omentin-1, and vaspin were determined with ELISA in the sera of patients with SSc (n ​= ​55) and healthy controls (n ​= ​25). ResultsThe serum concentration of adipsin (p ​= ​0.03) and visfatin (p ​= ​0.04) was significantly increased and the level of retinol-binding protein 4 (p ​= ​0.03) was decreased in diffuse compared to limited cutaneous SSc. Moreover, serum adipsin level correlated positively with the intensity of skin fibrosis measured with the modified Rodnan skin score (r ​= ​0.31, p ​= ​0.02) and was significantly higher in patients with pulmonary arterial hypertension than in those without the condition (p ​= ​0.03). The concentrations of adipsin (p ​= ​0.01) and visfatin (p ​= ​0.04) were significantly increased and the level of apelin (p ​= ​0.02) was decreased in patients with active digital ulcerations compared to individuals without this complication. ConclusionAdipsin may be considered a pivotal protein in the development of both fibrosis and impaired microcirculation. Its abnormal concentration reflects the intensity of skin thickening and the presence of pulmonary arterial hypertension. Adipsin, visfatin, and apelin are adipose tissue-derived molecules associated with digital vasculopathy.

Association between clinical features and course of systemic sclerosis and serum interleukin-8, vascular endothelial growth factor, basic fibroblast growth factor, and interferon alpha.

Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc). This study aimed to examine the association between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-α), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc. This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-α, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer. The bFGF and IFN-α concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level ≥95.7 pg/mL and IFN-α level ≥3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-α concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9). The SSc group was characterized by higher serum concentrations of bFGF and IFN-α compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-α and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings.

Heart disease in the course of systemic sclerosis - an observational study.

Cardiac involvement is one of the major mortality factors in systemic sclerosis (SSc). This observational study aimed to compare patients with and without heart involvement in the course of SSc. Electronic medical records of patients treated between January 2021 and August 2022 in the Department of Rheumatology were searched for the diagnosis of SSc (ICD-10 code M47). The clinical characteristics of patients with and without heart involvement in the course of SSc were compared. Out of 36 patients with SSc, 7 patients were diagnosed with heart disease in the course of SSc. The major type of cardiac involvement was myocarditis (71%). The majority of patients with heart involvement had elevated troponin (86%) and NT-proBNP (71%) concentrations. The most common finding observed in echocardiography was diastolic failure (71%). The most frequent abnormality found in 24-hour Holter ECG was isolated supraventricular extrasystoles (100%). Risk factors for developing heart disease in the course of SSc were male gender (p = 0.018), diffuse type of SSc (p = 0.03), higher values of modified Rodnan skin score (p < 0.001), gastrointestinal tract involvement (p = 0.027) and myositis (p = 0.018). Optimal screening for heart disease is needed in this group of patients.

Plasma and Urine Levels of Glycosaminoglycans in Patients with Systemic Sclerosis and Their Relationship to Selected Interleukins and Marker of Early Kidney Injury.

Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by immune system dysfunction, vasculopathy, and progressive fibrosis of the skin and internal organs, resulting from excessive accumulation of extracellular matrix (ECM) elements, including collagen and proteoglycans (PGs). An uncontrolled PG proliferation, caused by disturbances in their metabolism in tissues, is most likely reflected in the quantitative changes of their components, i.e., glycosaminoglycans (GAGs), in body fluids. Therefore, the aim of this study was to quantify the different types of GAGs in the blood and urine of systemic sclerosis patients. Chondroitin/dermatan sulfates (CS/DS) and heparan sulfates/heparin (HS/H) were quantified by hexuronic acid assay and electrophoretic fractionation, while hyaluronic acid (HA) and keratan sulfates were evaluated using ELISA tests. In turn, individual urinary GAGs were determined using the Blyscan™ Sulfated Glycosaminoglycan Assay Kit. Our results showed that the plasma concentrations of CS/DS, HS/H, HA, and KS in systemic sclerosis patients were significantly higher compared with those in healthy subjects. In the case of urine measurements, we have found that in SSc patients, CS/DC concentrations were significantly higher, while HA concentrations were significantly lower compared with the values observed in the urine of healthy subjects. Importantly, the found by us correlations between plasma keratan sulfate levels and both the duration of the disease and the severity of skin lesions, as expressed by the Rodnan scale, seems to suggest this GAG as a potential marker in assessing disease progression and activity. In addition, a level of urinary excretion of all types of GAGs due to their high positive correlation with uACR, may be a valuable complementary test in the diagnosis of early renal dysfunction in the course of SSc.

Late skin fibrosis in systemic sclerosis: a study from the EUSTAR cohort.

The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Prostaglandin E1 — salvage therapy in the treatment of difficult-to-heal ulcers in systemic sclerosis

Involvement of blood vessels in the form of Raynaud’s phenomenon and microcirculatory dysfunction as well as accompanying skin lesions of the fingers in patients with systemic sclerosis lead to easy skin damage and difficult-to-heal ulcers. Patient education regarding, among other things, the avoidance of injuries, exposure to cold or smoking and pharmacological treatment are becoming important. The choice of drugs listed in current recommendations depends on the clinical manifestation, i.e. the presence and severity of Raynaud’s phenomenon, the treatment or prevention of ulceration and the response to previous treatment. The paper presents a case of a 79-year-old woman with advanced necrotic lesions of the fingers in the course of systemic sclerosis diagnosed late in life. Due to the advancement of the lesions and the lack of improvement after first-line oral medications, the patient required intravenous prostaglandin. Six months of effective therapy and additional surgical treatment led to complete healing and inhibition of new ulcer formation. Intravenous prostaglandin is an effective alternative for the treatment of difficult-toheal ulcers in the course of systemic sclerosis while preventing the formation of new lesions.

Pleural Effusion in Limited Cutaneous Systemic Sclerosis : A Report

Systemic sclerosis (SSc) is a chronic autoimmune multisystem disorder characterized by endothelial dysfunction and fibroblast dysfunction, which results in progressive fibrosis of the skin and internal organs more frequently the lungs and gastro intestinal tract. Pulmonary involvement is common in the course of SSc, with Interstitial Lung Disease (ILD) and Pulmonary Arterial Hypertension (PAH) along with pleural effusion being the leading causes of death. Here we report, case of an elderly male patient presenting with cutaneous SSc with multiple uncommon pulmonary manifestations like ILD with right sided pleural effusion with hepatic cyst.

Clinical Relevance of Liver Involvement in the Clinical Course of Systemic Sclerosis.

Liver involvement in systemic sclerosis (SSc) is rare. We evaluated the prevalence of liver fibrosis and hepatic autoimmunity in SSc patients in a retrospective observational cohort (97 SSc or mixed connective tissue disease with sclerodermic manifestations patients undergoing transient elastography, evaluating liver stiffness (LS) and controlled attenuation parameter (CAP), due to clinical indications along with biochemistry assessments and major antibodies associated to liver autoimmunity). Among them, 11 had LS ≥ 7.5 kPa and 5 showed an LS compatible with cirrhosis (LS ≥ 12.5 kPa). Predictors of LS ≥ 7.5 fibrosis were alcohol consumption (>14 or >7 alcoholic units/week for men and women, respectively), waist circumference (>102 or >88 cm for men and women, respectively), elevated alkaline phosphatase, and anti-La and anti-mitochondrial antibody (AMA) positivity. Six patients had CAP values compatible with severe steatosis (≥280 dB/m). Waist circumference, body mass index and diabetes mellitus were significant predictors of steatosis. Out of 97 patients, 19 were positive for AMA, 4 for anti-Sp100, 1 for anti-Gp210 and 7 were diagnosed with primary biliary cholangitis. Among SSc patients, hepatic fibrosis biomarkers and AMA prevalence are relatively high, suggesting the opportunity of performing a transient elastography and a screening for hepatic autoimmunity at diagnosis and/or during disease progression.

A comprehensive framework for navigating patient care in systemic sclerosis: A global response to the need for improving the practice of diagnostic and preventive strategies in SSc.

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis

POS0289 CANCER RISK IN IMMUNOSUPPRESSED SCLERODERMA PATIENTS: A PROPENSITY SCORE MATCHING ANALYSIS

Background:An increased incidence of cancer in patients with systemic sclerosis (SSc) is well-established1. Current knowledge about the onco-transforming power of immunosuppressive treatments in both non-rheumatological and rheumatological pathologies, suggests an increased incidence of hematological and solid neoplasms2. Evidences on the possible role of the immunosuppressants in the onset of cancer during SSc are lacking.Objectives:To evaluate the incidence of malignancies in SSc patients exposed to immunosuppressive therapy.Methods:The incidence of neoplasia in a cohort of 600 patients with SSc was evaluated retrospectively. Patients diagnosed with malignancy within 36 months from SSc onset were excluded from the analysis since suspected for paraneoplastic form. Patients exposed to methotrexate, cyclophosphamide, azathioprine and mycophenolate were confronted with a group comparable for age at onset, sex, disease variant, autoantibodies and exposure to other disease-specific therapies, using propensity score matching analysis. The considered follow-up was between the clinical onset and the diagnosis of cancer or the last available visit or the twenty-fifth year of illness.Results:The analysis was carried out on 526 patients observed for an average period of 12.1 ± 6.0 years (males 9.5%, age at onset 49.0 ± 15.3 years); 24.9% had diffuse cutaneous variant of the disease and 39.0% and 34.8% were respectively positive for anti-centromere and anti-Scl70 antibodies. During the follow-up, 19.0% of patients were exposed to cyclophosphamide, 15.3% to azathioprine, 14.4% to methotrexate and 11.6% to mycophenolate mofetil. Sixty-five cancer diagnoses were made after the 36th month from onset (incidence 1.02: 100 patients/year), comprising 16 mammary cancers, 12 cancers of the gastro-intestinal tract, 11 cancers of the head-neck area, 10 cancers of the lungs, 9 cases of skin-cancer, 5 haematological malignancies and 1 brain tumour. The incidence of cancers did not differ in relation to treatment with cyclophosphamide (X2 = 0.001, p = 0.961), azathioprine (X2 = 2.141, p = 0.143), mycophenolate mofetil (X2 = 0.001, p = 0.993) or methotrexate (X2 = 0.920, p = 0.337) (Figure 1).Conclusion:Our data are consistent with an increased incidence of neoplasms in the course of SSc, with a rate that appears almost doubled compared to the general Italian population with similar sex and age distribution (0.55: 100 patients/year; Italian Association of Tumor Registries data3). In our SSc cohort this risk is independent of exposure to immunosuppressive drugs commonly used for the treatment of scleroderma disease.

The relationship between Sjogren's syndrome, systemic sclerosis and lymphoproliferative diseases

To study demographic, clinical, laboratory and immunological characteristics of patients with a combination of primary Sjogrens syndrome (pSS) and SSc and diagnosed lymphoproliferative diseases (LPDs); to characterize morphological/immunomorphological variants and course of non-Hodgkins lymphomas (NHL), developing in patients with these rheumatic diseases (RDs). In 19982018 at the Nasonova Research Institute of Rheumatology, 13 patients with clinical and laboratory manifestations of pSS (12) and SSc (13) were diagnosed with various lymphoproliferative diseases (LPDs). In 3 cases, an induced RD was observed: 1 case of a diffuse, rapidly progressive form of SSc, 2 cases of pSS in combination with a limited form of SSc after chemotherapy and radiation therapy of Hodgkins lymphoma (1), B-cell NHL (1) and CR of the breast (1) respectively. The first 2 cases were excluded from the analysis, since the development of lymphomas is not pathogenetically associated with RD. Of 11 patients with LPDs, 10 after a long course of RDs were diagnosed with NHL [MALT lymphoma of the parotid salivary glands 7, disseminated MALT lymphoma 2, disseminated MALT lymphoma with transformation into diffuse large B-cell lymphoma (DLBCL) 1]. RDs debuted with Raynauds phenomenon (RP) in 64.5% and pSS manifestations in 45.5% of patients. Stomatological manifestations of pSS were characterized by recurrent parotitis in 36%, significant parotid gland enlargement with massive infiltration of labial salivary glands (focus score 4) in 100%, severe xerostomia in 70%, extraglandular manifestations and lymphadenopathy in 50% of patients. The course of the SSc was characterized by mild RP with various types of capillaroscopic changes and mild lung changes and non-significant progression during long-term follow-up (median 22 years). The entire spectrum of SSс specific antibodies (anticentromere antibodies 60%, antibodies to ribonucleoprotease III 30%, Pm/Scl 10%), excepting antibodies to topoisomerase I, as well as pSS specific autoantibodies (antiRo/La 70%, RF (rheumatoid factor) 90%), were detected in patients with a combination of these RDs. pSS is often combined with a limited form of SSc regardless of the type of autoantibodies detected. The presence of pSS, rather than SSc, is a high-risk factor for the development of NHL in this group of patients. The patients with pSS and SSc are characterized by a steady progression of pSS with a slow and mild course of SSc throughout the observation period. The development of severe stomatological manifestations and high immunological activity of pSS contribute to the development of localized MALT lymphomas (70%) and disseminated MALT lymphomas (30%) with primary lesions of the salivary glands and transformation into DLBCL in case of their late diagnosis. The optimal method for preventing the development of NHL in this group of patients is the early diagnosis of pSS, the appointment of alkylating cytotoxic agents and/or anti-B-cell therapy in the early stages of pSS. Given the possibility of transformation of localized NHL into DLBCL, for early diagnosis, minimally invasive surgical biopsies of significantly enlarged parotid salivary glands should be performed before glucocorticoids are prescribed. Detection of positive B-cell clonality and lymphoepithelial lesions in the parotid salivary gland is considered a predictor of MALT lymphoma development during follow-up. Localized and disseminated MALT lymphomas in patients with pSS and SSc respond well to therapy, in contrast to MALT lymphomas transformed into DLBCL.

High NEMO score values in nailfold videocapillaroscopy are associated with the subsequent development of ischaemic digital ulcers in patients with systemic sclerosis

BackgroundNailfold videocapillaroscopy (NVC) is a feasible method that allows the observation of the microvascular changes that mark the course of systemic sclerosis (SSc). In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages and microthromboses, is a good indicator of the steady-state level and overtime changes of disease activity (DA) in SSc.ObjectivesTo verify whether high NEMO scores, which mirror a very active microvascular derangement in the fingers, may be associated with the subsequent development of ischaemic digital ulcers (IDUs).MethodsThe NEMO score was assessed at baseline (T0) in 98 patients with SSc, all classified according to the ACR-EULAR criteria. Of them, 90 were females, 48 had the limited and 50 had the diffuse cutaneous variant of SSc. Afterwards, the patients were closely followed up for 2 years, and the appearance of new IDUs recorded at any time of the follow-up. The T0-NEMO score values of patients who developed IDUs were compared to those of patients who did not. A receiver operating curve (ROC) was constructed, and the area under the curve (AUC) calculated by plotting the sensitivity and 1-specificity of the different NEMO score values in predicting the subsequent development of IDUs.ResultsDuring the follow-up, 38 out of 98 patients developed one or more IDUs. The NEMO score at T0 was significantly higher in those who developed IDUs with respect to those who did not [median 14.5 (95% CI 11.0–21.5) and 4.5 (95% CI 4.0–6.0), respectively, p < 0.0001]. The ROC curve derived from different T0-NEMO score values had an AUC of 0.79 (95% CI 0.69–0.86, p < 0.0001). A NEMO score of ≥ 12 had a sensitivity of 83.3% (95% CI 71.5–91.7) and a specificity of 63.2% (95% CI 46.0–78.2), with positive (P) and negative (N) predictive (PV) values of 58.9% (95% CI 44.7–72.2) and 85.6% (71.8–94.4), respectively. A NEMO score of ≥ 16 had a sensitivity of 95.0% (95% CI 86.1–99.0) and a NPV of 93.4% (77.5–99.2).ConclusionsBeing a valid tool to measure DA levels in SSc, the NEMO score also appears to be closely related to the subsequent development of IDUs in this disease.

Circulating biomarkers of systemic sclerosis - interstitial lung disease.

Interstitial lung disease is a frequent organ manifestation in systemic sclerosis and is associated with high mortality. It is crucial to diagnose interstitial lung disease in systemic sclerosis and to assess severity and identify patients prone to progression at an early stage to ultimately decrease organ damage and improve outcome. Circulating anti-topoisomerase-I autoantibodies have long been associated with the presence and development of systemic sclerosis - interstitial lung disease, evidence on their potential to further predict the clinical course of systemic sclerosis is however conflicting. C-reactive protein is a marker of infection and systemic inflammation with widespread clinical application and is elevated in systemic sclerosis with a tendency towards higher abundancy in patients with early disease. The role of other circulating biomarkers is promising but hampered by the lack of standardized criteria and guidelines for sample/data collection, analyses, reporting and validation and has not reached prime time for clinical application. However, epithelial markers including Krebs von den Lungen-6 and surfactant protein D and several cytokines and chemokines including CCL2 and CCL18 for severity assessment of systemic sclerosis - interstitial lung disease patients at the time of interstitial lung disease diagnosis and to predict interstitial lung disease progression have been reported and seem to be promising candidate biomarkers in the future.