Anti-topoisomerase I Research Articles

The Bull’s-Eye Sign in Liver: Are They Liver Metastases?

Question: A 53-year-old man was admitted to our hospital owing to a 2-month history of right upper quadrant abdominal pain with no weight loss. He had no history of drinking or any other documented medication, and denied fever. He never ate raw or undercooked meat and seafood. Two large hepatic masses were detected by screening ultrasound. Abnormalities were not shown in the extrahepatic bile ducts and pancreas by imaging analyses. White blood cell and eosinophil counts were normal. The hemoglobin level was 12.0 g/dL (normal range 13–17.5 g/dL). Aspartate transaminase and alanine transaminase were normal. Alkaline phosphatase (ALP) was 239 IU/L (normal range 50–130 IU/L), and gamma-glutamyl transpeptidase (γ-GTP) was 171 IU/L (normal range 10–60 IU/L). He had a low serum albumin level (35 g/L). Laboratory examination results suggestive of infection with hepatitis A, B, C, and E were negative. Serum alpha-fetoprotein was within the normal range. Initial contrast-enhanced abdominal computed tomography (CT) was performed owing to suspicion of a malignant hepatic tumor. CT confirmed 2 masses 40 mm and 45 mm in diameter with characteristics of a peripheral rim of heterogeneous enhancement in the right hepatic lobe, which resembled the bull’s-eye sign (Figure A). The bull’s-eye sign was more prominent in conventional portal venous-phase contrast-enhanced CT imaging compared with arterial-phase (Figure B). Chest CT, esophagogastroduodenoscopy and colonoscopy were normal. Screening was also negative for the following autoantibodies: antinuclear antibody, anti–double-stranded DNA, antimitochondrial antibodies, anti–liver/kidney microsomal type 1, anti–smooth muscle antibody, anti–SSA/Ro, anti–SSB/La, anti–Scl-70, cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA), and perinuclear antineutrophil cytoplasmic antibody (p-ANCA). CT guided core needle biopsy of the hepatic lesions was done to get adequate tissue for confirmative diagnosis. Photomicrographs of the histologic liver specimen revealed inflammatory cell infiltration consisting of lymphocytes, plasma cells, and neutrophils (Figure C).

874 A NOT-SO-RARE COMPLICATION OF CONNECTIVE TISSUE DISEASE

Abstract Pulmonary hypertension is a not-so-rare complication of connective tissue diseases and is usually related with an inauspicious prognosis. We present the case of a 67-years-old woman hospitalized for progressive dyspnea. Two-dimensional echocardiography showed numerous features related to pulmonary hypertension (PH) with moderate Mitral Regurgitation. The right cardiac catheterization confirmed mixed PH (pre and post capillary) without chest angio-TC evidence of pulmonary thromboembolism. Thanks to optimized medical therapy (B-Blocker, ACE-i and diuretics), there was a significant clinical improvement documented at discharge. After 1 year, due to recurrence of dyspnea, she was admitted to our medical unit. Her clinical examination showed some of the characteristics of a connective tissue disease. Compared to previous echocardiography, a moderate to mild reduction of MR was documented. Chest CT scan revealed interstitial lung disease likely related to patient's underlying pathology. Immunological screening tests detected the presence of antinuclear (ANA) and anti-topoisomerase (ATA) antibodies. Right heart catheterization documented a worsening of PH with only pre-capillary component. On the basis of the above findings, a diagnosis of CREST syndrome complicated with PH was made, and the patient was started on oral combination of macitentan and riociguat. The frequency of this complication in connective tissue disease, the need for screening tests and different treatment approaches of pre and post capillary pulmonary hypertension is discussed.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis

Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (β coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (β coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.

Serum netrin-1 levels in systemic sclerosis patients with capillary abnormalities

BackgroundSystemic sclerosis (SSc) is a rare, potentially destructive systemic autoimmune disease characterized by organ fibrosis and vasculopathy. Netrin-1 is associated with angiogenesis, inflammation, and apoptosis. Aim of the workTo assess the level of serum netrin-1 in SSc patients with capillary abnormalities and to evaluate its relation to disease manifestations. Patients and methodsThis study investigated the relationship between netrin-1 and fibrosis in 56 SSc patientsand 58 matched control. The modified Rodnan skin score (mRss) was used to assess skin thickness. Serum netrin-1 level was quantitatively measured using an enzyme-linked immunosorbent assay. ResultsThe study included 56 patients; 53 females and 3 males (F:M 17.7:1) with a mean age of 48·1 ± 13·6 years and disease duration of 13.01 ± 8·7 years. They were 43 (76.7 %) diffuse and 13 (23.3 %) limited subtypes. The median mRss was 6.58 ± 2.2. Raynaud’s disease was present in 50 % and interstitial lung disease in 57.1 %. The median netrin-1 level was significantly higher in SSc patients (268·8 pg/mL; 82·8-1006·6 pg/mL) than in the controls (108·6 pg/mL;21·02-351·5 pg/mL, p < 0·0001). There was no significant difference in the serum netrin-1 levels in SSc patients with and without Raynaud’s disease (p = 0.55), interstitial lung disease (p = 0.18), anti-Scl70 positive antibodies (p = 0·78), and anti-centromere antibody (p = 0·493). Netrin-1 was significantly related to SSc (OR = 1·02, 95 %CI: 1·01 − 1·03, p < 0·0001). At a cut-off value 126·3 pg/mL, netrin-1 would diagnose SSc (sensitivity 60·3%, specificity 94·6%, 95 %CI: 0·83 − 0·95, p < 0·0001). ConclusionSSc patients had significantly high levels of serum netrin-1 with a potential role in the pathophysiology of the disease.

Contribution of HLA and KIR Alleles to Systemic Sclerosis Susceptibility and Immunological and Clinical Disease Subtypes.

Systemic sclerosis (SSc) is an autoinflammatory, fibrotic condition of unknown aetiology. The presence of detectable autoantibodies against diverse nuclear antigens, as well as strong HLA associations with disease, suggest autoimmune involvement, however the links between endogenous and exogenous risk factors and SSc pathology remain undetermined. We have conducted a genetic analysis of HLA inheritance in two independent and meta-analysed cohorts of 1,465 SSc cases and 13,273 controls, including stratified association analyses in clinical and autoantibody positive subgroups of disease. Additionally, we have used patient genotypes to impute gene dosages across the KIR locus, encoding paired activating and inhibitory lymphocyte receptors for Class I HLA ligands, to conduct the largest analysis of KIR-HLA epistatic interactions in SSc to date. We confirm previous Class II HLA associations with SSc risk and report a new Class I association with haplotype HLA-B*44:03-HLA-C*16:01 at genome-wide significance (GWS). We further report statistically significant HLA associations with clinical and serological subtypes of disease through direct case-case comparison, and report a new association of HLA-DRB1*15:01, previously shown to bind topoisomerase-1 derived peptides, with anti-topoisomerase (ATA) positive disease. Finally, we identify genetic epistasis between KIRs and HLA class I ligands, suggesting genetic modulation of lymphocyte activation may further contribute to an individual’s underlying disease risk. Taken together, these findings support future functional investigation into endogenous immunological and environmental stimuli for disrupted immune tolerance in SSc.

POS0863 ANTI-NOR90 ANTIBODIES IN THE SETTING OF CONNECTIVE TISSUE DISEASE: CLINICAL SIGNIFICANCE AND COMPARISON WITH A COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS

BackgroundAnti-NOR90 antibodies are directed against a 90-kD nucleolar protein located in the nucleolus organizing regions (NORs), mainly described in systemic sclerosis (SSc) [1, 2, 3] but reported also in other rheumatologic and oncologic diseases [4, 5, 6]. The clinical correlates of anti-NOR90 antibodies are still to be defined because the cohorts described thus far include a low number of patients.ObjectivesTo describe the characteristics of a large cohort of anti-NOR90 antibodies positive patients and compare them with a matched cohort of SSc patients negative for anti-NOR90 antibodies.MethodsA retrospective analysis was performed on patients positive for anti-NOR90 antibodies referring to participating centres. The concomitant positivity for anti-RNA polymerase III, Th/To, PM-Scl, Ku, and PDGFR antibodies was an exclusion criterion. In all cases the diagnoses, the different organ involvement and related clinical, instrumental and laboratory characteristics were evaluated. The EUROLINE SystemicSclerosisProfile kit from Euroimmun (Lübeck, Germany) was used to detect anti-NOR90 antibodies.ResultsWe included 101 patients positive for anti-NOR90 (M/F=13/88, mean age 52.5 years). They were mainly classified as SSc (n=38), undifferentiated connective tissue disease (UCTD) (n=21), interstitial pneumonia with autoimmune features (IPAF) (n=11) (graph 1). The most frequent clinical manifestations were arthralgias (n=72), Raynaud’s phenomenon (RP) (n=58), sicca syndrome (n=49), ILD (n=40), puffy fingers (n=32), arthritis (n=30), and limited skin sclerosis (n=24). Anti-NOR90 antibodies were associated with anti-Ro52 antibodies in the 16% of cases, with anticentromere antibodies in the 7% of cases, and with anti-Scl70 in the 5% of cases. After excluding these patients, and considering the isolated anti-NOR90 positivity, 12 patients had SSc, 35 UCTD, and 11 IPAF. The most frequent clinical manifestations were arthralgias (n=40), RP (n=37), and sicca syndrome (n=21). Compared to 242 matched SSc without anti-NOR90 antibodies, patients with anti-NOR90 had more frequently joint manifestations and sicca syndrome and less frequently all vasculopathic manifestations (RP, telangiectasias, pitting scars, acral ulcers), dysphagia and fibromyalgia.ConclusionOur study shows that anti-NOR90 antibodies are more commonly observed in females, and clinically associated with the occurrence of arthritis/arthralgias, sicca syndrome and RP. In more than the 50% of cases they may be found with other autoantibodies, such as the anti-Ro52, the anticentromere, and the anti-Scl70 antibodies. Anti-NOR90 seems to play an accompanying role in the context of CTDs, without strong influence on the clinical phenotype expression of the underlying CTD.

P416 A NOT–SO–RARE COMPLICATION OF CONNECTIVE TISSUE DISEASE

Abstract Pulmonary hypertension is a not–so–rare complication of connective tissue diseases and is usually related with an inauspicious prognosis.We present the case of a 67–years–old woman hospitalized for progressive dyspnea. Two–dimensional echocardiography showed numerous features related to pulmonary hypertension (PH) with moderate Mitral Regurgitation. The right cardiac catheterization confirmed mixed PH (pre and post capillary) without chest angio–TC evidence of pulmonary thromboembolism. Thanks to optimized medical therapy (B–Blocker, ACE–i and diuretics), there was a significant clinical improvement documented at discharge. After 1 year, due to recurrence of dyspnea, she was admitted to our medical unit. Her clinical examination showed some of the characteristics of a connective tissue disease. Compared to previous echocardiography, a moderate to mild reduction of MR was documented. Chest CT scan revealed interstitial lung disease likely related to patient’s underlying pathology. Immunological screening tests detected the presence of antinuclear (ANA) and anti–topoisomerase (ATA) antibodies. Right heart catheterization documented a worsening of PH with only pre–capillary component. On the basis of the above findings, a diagnosis of CREST syndrome complicated with PH was made, and the patient was started on oral combination of macitentan and riociguat. The frequency of this complication in connective tissue disease, the need for screening tests and different treatment approaches of pre and post capillary pulmonary hypertension is discussed.

Clinical assessment of patients with systemic sclerosis: is there a place for thermography?

Recurrent changes of temperature and persistence of cooling along fingers at the room temperature make hands the most frequent region of interest for thermography in systemic sclerosis (SSc). The aim of this study was to evaluate dependance of temperature in hands on a subtype of the disease, immune profile of antinuclear antibodies (ANA), and lung involvement. There were 29 patients with limited cutaneous involvement (lcSSc) and 10 patients with diffuse cutaneous disease (dcSSc) enrolled for the study. To compare measurements to normal values, there were enrolled 29 healthy volunteers (control group). All participants were submitted to thermography with handheld camera FLIR One Pro for iOS, attached to mobile phone iPhone 11, at the fixed temperature of 21°C. Measurements included average temperature (Tavg) over nailfolds in thumbs and fingers II-V, as well as the difference in average temperatures (TΔ) between metacarpus of the hand and its thumb and fingers II-V. Both thumbs and fingers II-V remained cooler in subjects with dcSSc compared to those with lcSSc. This implicated a significantly greater TΔ along thumbs and fingers II-V in dcSSc group. Although Tavg at nailfolds in SSc patients was not lower than in healthy controls, TΔ remained significantly more pronounced in both lcSSc and dcSSc subjects. A positivity to ACA in lcSSc group was found to be associated with significantly lower Tavg and more pronounced TΔ in fingers II-V than the presence of anti-Scl70 antibodies. Temperature measurements remained statistically independent on a presence of ILD in lcSSc group, but both thumbs and fingers II-V in dcSSc group were warmer in case of lung involvement. The study showed the dcSSc subtype, the positivity of ACA in lcSSc, but not lung involvement were associated with poorer thermal control in the hands of SSc patients. A comparison to healthy controls highlighted the weakness of temperature measurements at nailfolds (Tavg) but increased the value of TΔ in thermography of hands.

Assessing the Prevalence of Disease-Specific Antinuclear Antibodies and their Detection in Diagnosis of Rheumatic Disorders in Syria

Background: Antinuclear antibodies (ANA) detection is a crucial laboratory test for diagnosing systemic autoimmune disorders and is commonly the initial step in autoantibodies screening. ANA are immunoglobulins that differentiate a wide range of nuclear and cytoplasmic components. ANAs are consistently present in the sera of patients with a variety of rheumatic disorders. The purpose of the study was to investigate the kinds and the expansion of disease-specific antinuclear antibodies (ANAs) and their link to rheumatic disorders in the general Syrian people. &#x0D; Method: Immunofluorescence (IIF) was used for testing ANA in serum samples gained from 529 patients. Individualities positive for IF­ ANA were further tested for disease­ specific ANAs using line Immunoblot assay. &#x0D; Results: Based on the result of the IF­ ANA assay, the rates of positive samples were 7.9%. Anti-SSA/Ro and anti-dsDNA antibodies were detected in 7and 6 individuals, respectively, anti Scl70, anti-Nucleosome, anti-U1-RNP, anti-CENP B were detected in 4 different individuals, but anti-Sm, anti-PCNA, and anti-Jo-1 antibodies were undetectable. Among 42 IF­ ANA­ positive individualities, 24 were found to have disease ­specific ANAs: nine SLE, three Sclerosis, and two rheumatoid arthritis.&#x0D; Conclusions ANA should generally not be examined without a clinical indication. Positive ANA finding in the absence of clinical symptoms and signs has limited diagnostic usefulness and should be interpreted by a rheumatologist constantly, in the context of clinical symptoms and the results of laboratory tests for specific autoantibodies.

Nintedanib in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: Subgroup Analyses by Autoantibody Status and Modified Rodnan Skin Thickness Score.

ObjectiveUsing data from the SENSCIS trial, these analyses were undertaken to assess the effects of nintedanib versus placebo in subgroups of patients with systemic sclerosis–associated interstitial lung disease (SSc‐ILD), based on characteristics previously identified as being associated with the progression of SSc‐ILD.MethodsPatients with SSc‐ILD were randomized to receive either nintedanib or placebo, stratified by anti–topoisomerase I antibody (ATA) status. We assessed the rate of decline in forced vital capacity (FVC) (expressed in ml/year) over 52 weeks in subgroups based on baseline ATA status, modified Rodnan skin thickness score (MRSS) (<18 versus ≥18), and SSc subtype (limited cutaneous SSc [lcSSc] versus diffuse cutaneous SSc [dcSSc]).ResultsAt baseline, 60.8% of 576 patients who received treatment with either nintedanib or placebo were positive for ATA, 51.9% had dcSSc, and 77.5% of 574 patients with MRSS data available had an MRSS of <18. The effect of nintedanib versus placebo on reducing the rate of decline in FVC (ml/year) was numerically more pronounced in ATA‐negative patients compared to ATA‐positive patients (adjusted difference in the rate of FVC decline, 57.2 ml/year [95% confidence interval (95% CI) –3.5, 118.0] versus 29.9 ml/year [95% CI –19.1, 78.8]), in patients with a baseline MRSS ≥18 compared to those with a baseline MRSS of <18 (adjusted difference in the rate of FVC decline, 88.7 ml/year [95% CI 7.7, 169.8] versus 26.4 ml/year [95% CI –16.8, 69.6]), and in patients with dcSSc compared to those with lcSSc (adjusted difference in the rate of FVC decline, 56.6 ml/year [95% CI 3.2, 110.0] versus 25.3 ml/year [95% CI –28.9, 79.6]). However, all exploratory interaction P values were nonsignificant (all P > 0.05), indicating that there was no heterogeneity in the effect of nintedanib versus placebo between these subgroups of patients.ConclusionIn patients with SSc‐ILD, reduction in the annual rate of decline in FVC among patients receiving nintedanib compared to those receiving placebo was not found to be heterogenous across subgroups based on ATA status, MRSS, or SSc subtype.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Interstitial pneumonia with autoimmune features (IPAF): A distinct group of idiopathic interstitial pneumonia - A case report on organizing pneumonia with positive anti Scl-70

Official journal of the Postgraduate Institute of Medicine, University of Colombo, Sri Lanka.Interested in submitting to this journal? We recommend that you review the About the Journal page for the journal's section policies, as well as the Author Guidelines. Authors need to register with the journal prior to submitting or, if already registered, can simply log in and begin the five-step process.

Therapeutic Approaches to Systemic Sclerosis: Recent Approvals and Future Candidate Therapies.

Systemic sclerosis is the rheumatic disease with the highest individual mortality. The severity of the disease is determined by the extent of fibrotic changes to cutaneous and internal organ tissues, the most life-threatening visceral manifestations being interstitial lung disease, SSc-associated-pulmonary arterial hypertension and myocardial involvement. The heterogeneity of the disease has initially hindered the design of successful clinical trials, but considerations on classification criteria have improved patient selection in trials, allowing the identification of more homogeneous groups of patients based on progressive visceral manifestations or the extent of skin involvement with a focus of patients with early disease. Two major subsets of systemic sclerosis are classically described: limited cutaneous systemic sclerosis characterized by distal skin fibrosis and the diffuse subset with distal and proximal skin thickening. Beyond this dichotomic subgrouping of systemic sclerosis, new phenotypic considerations based on antibody subtypes have provided a better understanding of the heterogeneity of the disease, anti-Scl70 antibodies being associated with progressive interstitial lung disease regardless of cutaneous involvement. Two targeted therapies, tocilizumab (a monoclonal antibody targeting interleukin-6 receptors (IL-6R)) and nintedanib (a tyrosine kinase inhibitor), have recently been approved by the American Food & Drug Administration to limit the decline of lung function in patients with SSc-associated interstitial lung disease, demonstrating that such better understanding of the disease pathogenesis with the identification of key targets can lead to therapeutic advances in the management of some visceral manifestations of the disease. This review will provide a brief overview of the pathogenesis of SSc and will present a selection of therapies recently approved or evaluated in this context. Therapies evaluated and approved in SSc-ILD will be emphasized and a review of recent phase II trials in diffuse cutaneous systemic sclerosis will be proposed. We will also discuss selected therapeutic pathways currently under investigation in systemic sclerosis that still lack clinical data in this context but that may show promising results in the future based on preclinical data.

Laboratory strategy for autoantibodies testing as a diagnostic marker of pulmonary fibrosis in systemic sclerosis: A preliminary study prior to cohort registry of systemic sclerosis in West Java Indonesia

Background: Interstitial lung disease (ILD) is a complication often found in patients with Systemic Sclerosis (SSc). This usually manifests as pulmonary fibrosis and is the leading cause of death in SSc patients. Antinuclear antibodies indirect immunofluorescence (ANA-IIF) test and specific autoantibodies testing could be employed as a diagnostic marker to detect pulmonary fibrosis, but the high cost of these tests often burdens patients in developing countries. This study aims to compare ANA-IIF and an alternative, possibly inexpensive method to detect pulmonary fibrosis in SSc. Methods: This is a preliminary study prior to the cohort systemic sclerosis registry conducted in Rheumatology Outpatient Clinic and Clinical Pathology Department at Dr. Hasan Sadikin General Hospital, Bandung, from January 1, 2018 to December 31, 2020. Two contrastive laboratory testing strategies were followed to confirm pulmonary fibrosis in 61 SSc patients. The first strategy was to perform antinuclear antibodies indirect immunofluorescence (ANA-IIF) test followed by specific autoantibodies detection [anti-topoisomerase-I (ATA), Anti-Th/To, SSc Profile, Immunoblot]. The alternative strategy included conducting the tests for SSc autoantibodies in the reverse order. Results: A total of 42 out of 61 (68.8%) subjects were diagnosed with pulmonary fibrosis by high-resolution computed tomography (HRCT) scan. The first strategy detected dominant specific pulmonary fibrosis autoantibodies in subjects with pulmonary fibrosis: homogeneous nucleolar pattern was dominant (n = 25, 59.52%), followed by nucleolar pattern (n = 17, 40.48%). Of all the subjects with a homogeneous nucleolar pattern, ATA was detected in 15 subjects (60%), the combination of ATA and Th/To in 9 subjects (36%), and Ro52 in one subject (4%). The second strategy yielded positive autoantibodies results in 29 out of 42 (69.05%) subjects, ATA in 20 subjects (47.61%), and Th/To in 9 patients (21.44%), but failed to detect any autoantibodies specific to SSc-ILD in 13 subjects (30.95%). Conclusion: The first strategy [ANA-IIF followed specific autoantibodies testing (ATA, Th/To, SSc profile and immunoblot)] is more likely to detect specific autoantibodies toward ILD in SSc patients.

Anti-RNA polymerase III antibodies in systemic sclerosis: Multicentric study from Argentina

ObjectiveTo describe the frequency of anti-RNA polymerase III antibody in patients with Systemic Sclerosis (SSc) of a group of healthcare centres from Argentina and to explore differences among patients with positive and negative anti-RNA polymerase III antibody. Patients and methodsData from clinical records, anamnesis and physical examination were collected from 135 patients with SSc (ACR/EULAR 2013). A serum sample from each patient was obtained for the detection of anti-RNA polymerase III IgG antibodies by ELISA. ResultsIn all, 97.8% were women and the median age at diagnosis was 53 years (range 12–87), 77.7% had limited cutaneous SSc (lcSSC), 19,3% patients had diffuse cutaneous SSc (dcSSC) and 2.9% had scleroderma sine scleroderma. The 67.5% of the patients were from a Mestizos or Amerindian ethnic group. Anti-RNA polymerase III was positive in 5.9% of the patients. In 36 patients, the anticentromere (ACA) and anti-Scl70 antibodies were negative; anti-RNA polymerase III was positive in 16.7% of these 36 patients. Pitting scars and pulmonary artery hypertension were more frequent in anti-RNA polymerase III positive patients who were also older at diagnosis. No association with gastric antral vascular ectasia was found. The only patient with scleroderma renal crisis was anti-RNA polymerase III positive. ConclusionsAnti-RNA polymerase III frequency found in this study was one of the lowest reported, which could be related to the predominance of the Amerindian and Mestizo ethnic group. It is possible that the detection of anti RNA polymerase III allows better classification of SSc patients, to know their prognosis and to improve their follow-up, therefore more studies are needed.

Predictive value of immunological markers in systemic sclerosis.

Systemic sclerosis (SSc) is a collagenosis characterized by excessive deposition of collagen in the skin and viscera, in a background of immune disorder. The immunological profile of SSc often shows elevated levels of antinuclear antibodies (ANAs). However, many authors have identified cases of SSc having normal ANA levels, framed as paraneoplastic SSc. Among patients with negative ANAs in our group, we did not identify any neoplastic process that could support this hypothesis. The extended detection of autoantibodies is extremely useful in establishing the subset of SSc. Thus, anti-Scl70 antibodies are specific for the diffuse subset of SSc, while anticentromere antibodies (ACAs) have specificity for a limited subset. However, studies have shown the existence of cases of diffuse SSc having high titers of ACAs and cases of limited SSc with high titers of anti-Scl70 antibodies. This indicates an inconsistent association between the disease subset and the autoantibodies specific to each subset. Our study found a more balanced consistency between disease subsets and autoantibodies specific for each subset. Therefore, the percentages of patients having an immunological profile inconsistent with the subset of SSc, are lower than those found by other authors. This observation opens the perspective of larger studies on the immunological profile in SSc.

Comprehensive analysis of the major histocompatibility complex in systemic sclerosis identifies differential HLA associations by clinical and serological subtypes

ObjectiveThe greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region...

Correlation Between Skin and Affected Organs in 52 Sclerodermic Patients Followed in a Diseases Management Team: Development of a Risk Prediction Model of Organ-Specific Complications.

ObjectiveTo identify the existence of a correlation among the various organs affected, focusing primarily on immuno-dermatological aspects, and to create a risk prediction model of organ-specific complications.Material and MethodsFifty-two patients with stable scleroderma, followed between 2015 and 2019, were investigated through an extensive multidisciplinary evaluation in the last year.ResultsPatients with lung involvement presented a worse degree of skin fibrosis than patients without it (p <0.001). No relationship was observed for the heart, kidney, and esophagus. Patients with pulmonary involvement had a lower pressure of the low esophagus sphincter and a higher Warrick score than patients without it (p <0.05). Age was significantly higher in patients with kidney involvement. Diffuse scleroderma patients had a worse pulmonary impairment than limited scleroderma patients (p <0.05). The manometric “sclerodermic” pattern was observed to be the most frequent (55.6%, p <0.05) in dcSSc patients while the sclerodermic and normal pattern were equally represented (41.2 and 32.4% respectively, p <0.05) in lcSSc patients. When compared to the negative serological groups, anti-Scl-70 positive patients presented a worse lung involvement while anti-centromere patients presented a better lung outcome (p <0.05). PM-Scl 100/75 positive patients presented mostly a pulmonary fibrotic pattern (p <0.05) and, also, heart complications were more likely associated with anti PM-Scl 100/75 positivity (p <0.05). The risk prediction model for organ-specific complications had an accuracy of 84.4% (95%CI 78, 89) in complication-site prediction, AUC of 0.871, 86% of sensitivity, and 83% of specificity, Cohen’s Kappa (k) of 0.68.ConclusionsOut of all the organs studied, the skin is the one that correlates with the lung. Patients with a diffuse form of disease presented more frequently the anti Scl-70 antibody and had a worse lung and esophageal involvement (scleroderma pattern) than the negative group. Conversely, patients with limited disease presented all positive for the anti-centromere antibody with a better lung involvement than the negative group, without any difference among the esophageal manometric pattern. Anti PM-Scl 100/75 antibody patients were associated with pulmonary fibrosis and presented cardiac involvement. The model created has demonstrated excellent values of sensitivity, specificity, and accuracy, but further studies are needed for validation.

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.

A Rare Case Report of Acquired Bartters With Positive Anti Scl70 Antibody

Introduction: Bartter syndrome autosomal recessive renal tubular disorders usualy presents in infant age group or antenatallyCase Description64 years housewife, a known case of hypothyroidism with in emergency with generalized weakness and hypotension. She had an small adrenal nodule work up which showed that it was non functional. On evaluation at time of stress (blood pressure 70/50) her serum cortisol was 300nmol/l and she was therefore started on hydrocortisone. Her records revealed hypokalemia for last 2 years. Workup of hypokalemia showed kaliuresis, metabolic alkalosis, hypercalciuria and excess chloride excretion in the urine, suggestive of bartter’s syndrome. But this needed further confirmation as bartter’s is rare in this age group and also the test was done at the time of stress. She was started on spironolactone and oral potassium supplementation. CECT head done for evaluation of postural dizziness showed chronic cortical venous thrombosis. On follow up ACTH stimulated cortisol was done which showed normal cortisol level so steroid was stopped. She was readmitted one month later with hypokalemia(K-1.8 meq/l) while being on same dosage of spironolactone and potassium. Workup of hypokalemia showed same feature of bartter’s syndrome. Considering the chain of events, a suggestion of bartter’s and response to steroid, a diagnosis of acquired autoimmune bartter’s syndrome along with hypothyroidism was made. An autoimmune work up showed anti SCL 70 positive2+(++). Patient responded to steroid, spironolactone, indomethacin and oral potassium supplementation. Discussion: Bartter’s syndrome can rarely happen in old age too. Seek for autoimmune cause once we suspect acquired bartter’s. To best of our knowledge previously only one case has been reported of acquired Bartter with systemic sclerosis. Patient may develop systemic sclerosis in future as anti SCL70 antibody is very specific for it. It is positive in less than 1 % of general population. Anti SCL70 antibody is rarely positive in Sjogrens syndrome. Our patient did not feature of sjogren or systemic sclerosis even after 4 years follow up