Undifferentiated Connective Tissue Disease Research Articles

The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease

BackgroundDiagnosis of systemic autoimmune rheumatic diseases (SARD) relies on the presence of hallmark anti-nuclear antibodies (ANA), many of which can be detected years before clinical manifestations. However, ANAs are also seen in healthy individuals, most of whom will not develop SARD. Here, we examined a unique cohort of asymptomatic ANA+ individuals to determine whether they share any of the cellular immunologic features seen in SARD.MethodsHealthy ANA− controls and ANA+ (ANA ≥1:160 by immunofluorescence) participants with no SARD criteria, with at least one criterion (undifferentiated connective tissue disease (UCTD)), or meeting SARD classification criteria were recruited. Peripheral blood cellular immunological changes were assessed by flow cytometry and transcript levels of BAFF, interferon (IFN)-induced and plasma cell-expressed genes were quantified by NanoString.ResultsA number of the immunologic abnormalities seen in SARD, including changes in peripheral B (switched memory) and T (iNKT, T regulatory, activated memory T follicular helper) subsets and B cell activation, were also seen in asymptomatic ANA+ subjects and those with UCTD. The extent of these immunologic changes correlated with ANA titer or the number of different specific ANAs produced. Principal component analysis of the cellular data indicated that a significant proportion of asymptomatic ANA+ subjects and subjects with UCTD clustered with patients with early SARD, rather than ANA− healthy controls.ConclusionsANA production is associated with altered T and B cell activation even in asymptomatic individuals. Some of the currently accepted cellular features of SARD may be associated with ANA production rather than the immunologic events that cause symptoms in SARD.

Comparative analysis of the sensitivity and specificity of the classification criteria and correlation with prognosis of disease in patients with Systemic Lupus Erythematosus.

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by significant clinical heterogeneity with early diagnosis being a major challenge, complicated by the absence of formal diagnostic criteria. Instead, classification criteria have been developed to enable the homogenous inclusion of patients in clinical trials, with the most commonly used those of the American College of Rheumatology (ACR 1997) and the Systemic Lupus International Collaborating Clinics Classification Criteria (SLICC 2012). These criteria are widely used in clinical practice as diagnostic tools, although they fail to diagnose up to 20% of patients with SLE or may delay diagnosis. These restrictions have led to the recent (2018) introduction of new classification criteria jointly by the European League Against Rheumatism (EULAR) and ACR.Aims of the Study:We will compare the sensitivity and specificity of the earlier and new classification criteria after a systematic analysis (retrospective study) of a group of SLE patients. In addition, we will examine which set of criteria permits the earliest classification of the disease in a prospective cohort of patients with undifferentiated connective tissue disease (UCTD). The prognostic impact (permanent organ damage) of the classification of SLE patients with the three sets of criteria will also be examined.Methods:Data from the existing Cretan lupus registry will be used to retrospectively include consecutively registered patients aged ≥15 years diagnosed with SLE during 01/2005–12/2016 by an expert physician and followed-up for at least 6 months. All sets of criteria (ACR 1997, SLICC 2012, EULAR/ACR 2018) will be tested at the time of physician-based diagnosis and also at last follow-up. A prospective study arm will include cases with a diagnosis of UCTD and will be followed-up in the outpatient clinic for 3–5 years.Anticipated Benefits:This is the first study to include the application of the new criteria (EULAR/ACR 2018) to a group of SLE patients. Determining their diagnostic value in comparison to existing criteria or diagnosis by a specialist will provide important information both for the value of their application at the level of clinical studies and for their use in clinical practice as diagnostic criteria.

Non-specific interstitial pneumonia and features of connective tissue disease: What are the consequences of a different point of view?

Patients with Interstitial Lung Disease (ILD) without a definitive diagnosis of connective tissue diseases (CTD) were historically described as Undifferentiated Connective Tissue Disease (UCTD-ILD). Recently a new classification, Interstitial Pneumonia with Autoimmune Features (IPAF), has been proposed. Aim of this study was to describe the prevalence, clinical characteristics and prognostic factors of UCTD and IPAF subjects in a cohort of Non-Specific Interstitial Pneumonia (NSIP) patients. This retrospective, observational study enrolled 102 adult patients characterized by NSIP pattern on High Resolution Computed Tomography, without a specific diagnosis of CTD. Three groups were identified according to patients' characteristics: IPAF, UCTD or idiopathic NSIP (iNSIP). Forty percent, 27% and 55% of patients showed diagnostic criteria for IPAF, UCTD and iNSIP, respectively. No significant differences in age, gender, smoking habit, pulmonary function tests and three-year survival rate were observed among study groups. IPAF patients with antisynthetase antibodies positivity, in comparison to IPAF without antisynthetase antibodies positivity, showed more frequently an acute onset (44% vs 9%, p<0.012). The presence of autoimmune features seems not to be associated with better outcomes in NSIP patients. IPAF criteria seem to be more representative than UCTD criteria in identifying patients with autoimmune features. Further studies are needed to verify if IPAF should include patients with positive antisynthetase serology.

Uncommon patterns of antinuclear antibodies recognizing mitotic spindle apparatus antigens and clinical associations.

Antinuclear antibodies (ANA) are key biomarkers in the evaluation of rheumatic diseases. The prevalence and clinical significance of uncommon or rare patterns, particularly those directed at the mitotic spindle apparatus (MSA), are not well understood. We aimed to investigate the prevalence and clinical significance of anti-MSA patterns in a Colombian population.During 2013 and 2014, 113,491 consecutive determinations of ANA were studied for the presence of uncommon patterns. Clinical and laboratory data of anti-MSA positive patients were retrospectively collected and analyzed.Of the 113,491 patients tested, 60,501 (53%) were positive for ANA, of which 834 (1.3%) were positive for uncommon/rare patterns of ANA (anti-MSA in 592 cases). Of these 592 cases, complete data were available in 329 patients, of whom 116 had an established diagnosis. Anti-MSA antibodies were the only ANA positive test in 81% patients. At least one fine reactivity was identified in 19/116 (16.3%) of ANA-positive patients, of which anti-Ro was the most prevalent (18/116, 15.5%).The most frequent patterns were nuclear mitotic apparatus (NuMA) (56%) and MSA-2 (25%). The NuMA pattern had the highest ANA titers: mean 320 (range 80-2560) and behaved as monospecific antibodies. The most frequent systemic autoimmune diseases were Sjögren syndrome (SS) (18.1%), rheumatoid arthritis (RA) (13.8%), and systemic lupus erythematosus (SLE) (11%). Undifferentiated connective tissue disease (UCTD) was associated with the centrosome (P < .001), NuMA (P < .02) and MSA-2 (P < .45) patterns. Chronic idiopathic urticaria (CIU) was associated with the NuMA pattern (P < .02) and sensorineural hearing loss (SNHL) was associated with the MSA-2 (P < .001), centrosome (P < .68) and CENP-F (P < .38) patterns, previously unreported findings. Malignancies were found in 8 patients (50% were papillary thyroid cancer).In a large cohort of ANA determinations, uncommon patterns were found in around 1% of cases. The most frequent anti-MSA patterns found were NuMA and MSA-2. More than 50% of patients with anti-MSA had an associated CTD, mainly SS, RA and SLE, and anti-MSA behaved as monospecific antibodies. Other entities of presumed autoimmune origin, like CIU and SNHL, might be associated with these patterns.

Case series: rheumatological manifestations attributed to exposure to Libby Asbestiform Amphiboles

ABSTRACTAn increased risk for Systemic Autoimmune Diseases (SAID) has been reported in Libby, Montana, where extensive exposures to fibrous amphiboles occurred due to mining and use of asbestos-laden vermiculite. In addition, positive antinuclear autoantibody tests are associated with exposure to Libby Asbestiform Amphiboles (LAA) in both humans and mice. Among 6603 subjects who underwent health screening at the Center for Asbestos Related Diseases (CARD, Libby MT), 13.8% were diagnosed with an autoimmune disease, with prevalence values for the most common SAID being significantly higher than expected in the United States. Among the CARD screening population, serological and clinical profiles are diverse, representing symptoms and autoantibodies reflective of systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis, and other rheumatic syndromes, including undifferentiated connective tissue disease (UCTD). Based upon screening of medical records by physicians with rheumatology expertise, the evolving nature of rheumatological disease in these patients is often atypical, with mixed diagnostic criteria and with a 1:1 male-to-female ratio. Through the Libby Epidemiology Research Program, cases were identified that illustrate clinical autoimmune outcomes with LAA exposure. Our goal was to better characterize SAID in Libby, MT in order to improve recognition of autoimmune outcomes associated with this exposure. In view of recent discoveries of widespread exposure to fibrous minerals in several areas of the U.S. and globally, it is critical to evaluate rheumatologic manifestations in other cohorts so that screening, surveillance, and diagnostic procedures are able to detect and recognize potential autoimmune outcomes of asbestos exposure.Abbreviations: ANA, antinuclear autoantibody; ARD, Asbestos-Related Diseases; ATSDR, Agency for Toxic Substances & Disease Registry; CARD, Center for Asbestos Related Diseases; CCP, Cyclic citrullinated peptide antibody; CREST, limited cutaneous form of scleroderma; CT, computed tomography; DIP, Distal Interphalangeal Joint; DLCO, Diffusing Capacity of the Lung for CO2; DMARD, Disease Modifying Anti-Rheumatic Drugs; ENA, Extractable Nuclear Antigen antibodies; FVC, Forced Vital Capacity; LAA, Libby Asbestiform Amphiboles; LERP, Libby Epidemiology Research Program; MCP, Metacarpal Phalangeal Joint; PIP, Proximal Interphalangeal Joint; PIP, rheumatoid arthritis; RV, Residual Volume; SAID, Systemic autoimmune diseases; SLE, systemic lupus erythematosus; SSc, Systemic Sclerosis; TLC, Total Lung Capacity

Treatment of adult idiopathic inflammatory myopathies with conventional immunosuppressive drugs : Results of aretrospective study.

To gain information about the efficacy of immunosuppressive drugs as first-, second-, and third-line treatment of idiopathic inflammatory myopathies (IIM). 112 treatment cycles of 63patients with dermatomyositis (n = 23), polymyositis (n = 33), overlap syndromes (n = 4), and undifferentiated connective tissue diseases (n = 3) were analyzed by retrospective chart analysis. Data regarding muscle strength, muscle enzymes, treatment duration, and treatment discontinuation were collected. Azathioprine (38cycles) and methotrexate (MTX; 24cycles) were applied significantly longer than glucocorticoid monotherapy (9cycles; 25 ± 21, 26 ± 29 and 7 ± 4months, respectively; p < 0.05). MTX and azathioprine achieved asignificant reduction of serum creatine kinase (CK), with MTX showing more marked effects. Treatment cycles with immunosuppressants other than MTX or azathioprine (n = 22) or with combinations of immunosuppressive drugs (n = 19) were mostly applied as third-line therapy, indicating their application in more refractory cases. Significant improvement of muscle strength was confined to MTX and azathioprine and to the first-line treatment. 8% of MTX patients withdrew due to the lack of efficacy, compared with 29% of patients taking azathioprine and 6 of 9patients taking glucocorticoid monotherapy. In the 12patients with Jo-1 syndrome, MTX treatment was effective for alonger time than azathioprine (44 ± 21months vs. 27 ± 24months, p < 0.05). Our data confirm the effectiveness of MTX and azathioprine in the treatment of inflammatory myopathies and stress the importance of apotent first-line therapy.

The association of solid-phase assays to immunofluorescence increases the diagnostic accuracy for ANA screening in patients with autoimmune rheumatic diseases

Abstract Aim This study aimed to investigate whether it is useful both for diagnostic purposes and for cost savings to associate a solid-phase monotest called CTD screen to the immunofluorescence (IIF) test, to detect anti-nuclear and anti-cytoplasmic antibodies (ANA). Methods Fifteen Italian laboratories participated in the study enrolling at least 250-each consecutive unselected samples from patients routinely referred for ANA testing. They all used the conventional IIF method on HEp-2 cells associated to a solid phase CTD screen method. Seven centers used the EliA FEIA CTD screen method on the Phadia 250 instrument (ThermoFisher), five centers used the QUANTAFlash CTD Screen method (Inova Diagnostics) on the BioFlash CLIA instrument, while three centers used both methods, albeit in two different series of patients. Results A total of 5043 samples were tested. We focused attention to the 1674 discrepant results: 106 (2%) were ANA-IIF negative/CTD screen positive and 1568 (31%) were ANA-IIF positive/CTD screen negative. Specific antibodies were detected in 87/106 (82%) of the ANA-IIF negative/CTD screen positive samples, mainly Ro52, Ro60, dsDNA, PM/Scl and Jo1. Thirty four of these patients were diagnosed with an ANA-associated autoimmune rheumatic disease (AARD) (seven SLE, 15 Sjӧgren's syndrome, nine autoimmune inflammatory myositis, three systemic sclerosis). Among 1568 ANA-IIF positive/CTD screen negative discrepant patients, a specific antibody was found in 94 (6%) samples (28 patients with AARD, 13 with undifferentiated connective tissue disease, two with undifferentiated arthritis, and 51 without a rheumatic disease). Conclusions This study is the first that compares the IIF method vs. solid-phase assays in the detection of ANA, on a very large sample size from the routine work-up (real-life approach). Results show that the association of solid-phase CTD screen tests to the ANA-IIF test increases the sensitivity (from 89.2% to 97.4%) and the specificity (from 64.6% to 98.4%) of serological tests for ANA screening. Analysis of costs demonstrated that combination of the two tests is also cost-effective, reducing global costs for the immunoserological diagnosis of AARD by 22%.

Anti-DFS70 autoantibodies in undifferentiated connective tissue diseases subjects: what's on the horizon?

The main objective was to determine the prevalence of anti-dense fine speckled (DFS70) antibodies in a stable population of undifferentiated connective tissue disease (UCTD) to better define their potential role. Immunological and clinical records of 91 long-standing UCTD patients were studied. DFS pattern was determined using the IIF ANA test on HEp-2 cells and anti-DFS70 antibodies were tested by chemiluminescence assay and by DFS70 line immunoassay. Twelve (13.2%) of 91 serum samples were positive for anti-DFS70 antibodies by chemiluminescence assay and line immunoassay. There was no statistical significance between the prevalence of anti-ENA and anti-DNA autoantibodies in patients with and without anti-DFS70 antibodies. No differences were found in the clinical characteristics of both groups. The presence of the anti-DFS70 antibodies was related to the younger age class. The high prevalence of anti-DFS70 antibodies in the UCTD patients suggested the potential role of these autoantibodies as a marker in the evolution of UCTD to CTD.

122 High burden of immunosuppressant use in undifferentiated connective tissue disease: results from the Lupus Extended Autoimmune Phenotype Study (LEAP) cohort

122 High burden of immunosuppressant use in undifferentiated connective tissue disease: results from the Lupus Extended Autoimmune Phenotype Study (LEAP) cohort

Undifferentiated Connective Tissue Disease and Interstitial Lung Disease: Trying to Define Patterns

ObjectivesTo identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. MethodsRetrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: ‘highly specific’ connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1:320), and ‘specific’ ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. ResultsSixty-six patients were included. Twenty-nine (43.94%) showed at least one ‘highly specific’ CTD manifestation, 16 (28.57%) had a ‘specific’ ANA staining pattern and 29 (43.94%) high ANA titer. Patients with ‘highly specific’ CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [−1 to 10] vs −6% [−16 to −4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. ConclusionThe presence of ‘highly specific’ CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD.

Overlap of interstitial pneumonia with autoimmune features with undifferentiated connective tissue disease and contribution of UIP to mortality.

Criteria for interstitial pneumonia with autoimmune features (IPAF) were recently established for research purposes in a joint statement from the European Respiratory Society (ERS) and American Thoracic Society (ATS). We reviewed the utility of these criteria in patients previously diagnosed as broadly defined undifferentiated connective tissue disease (UCTD) and noted overlapping IPAF findings. Additional review was given to IPAF patients with usual interstitial pneumonia (UIP) on histopathology or radiology in terms of survival and outcome. Patients with prior UCTD-interstitial lung disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along with all-cause mortality were collated and compared with selected idiopathic pulmonary fibrosis (IPF) patients from the same study period. Survival was compared between IPAF subgroups with and without UIP features. One hundred and one UCTD-ILD subjects (91%) evaluated from 2005 to 2012 also met strict criteria for IPAF. Frequent clinical findings included Raynaud's phenomenon, positive anti-nuclear antibody (ANA) and non-specific interstitial pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features of UIP either on histopathology or CT imaging. As compared with IPF, IPAF patients had overall better survival except in those with UIP features. Current IPAF criteria encompassed the majority of broadly defined UCTD-ILD and included those with UIP findings. Survival compared with IPF in those with UIP was similar. Further studies are necessary to refine IPAF definitions for clinical use and guide directed management strategies.

Systemic Diseases in Dakar (Senegal): Spectrum, Epidemiological Aspect and Diagnostic Time-Limit

Introduction: Systemic diseases have been the subject of few studies in the African literature and have probably been under-estimated. The objective of our study was to specify their spectrum, their epidemiological aspects and diagnostic delay in Internal Medicine Departments of Dakar (Senegal). Material and Method: It was a multicentric retrospective and descriptive study regarding all systemic diseases during 119 months from 1st January 2005 to 30 November 2014 in 5 hospital centers down Dakar. Systemic diseases were retained according to their international consensus criteria. Results: During the studying period, 726 patients were included with 632 women and 94 men (sex ratio of 0.14). The average age was 43.76 years. Inflammatory rheumatoid family history was noted in 10.06% of cases. Rheumatoid arthritis (RA) was the predominant affection, recorded on 564 patients, isolated or associated with other systemic diseases. It was followed in a decreasing order, in the systemic auto-immune diseases sub-groupe, by systemic lupus (56 cases), Sjögren’s syndrome (32 cases), Systemic Sclerosis (26 cases), Idiopathic inflammatory myopathies (21 cases), Undifferentiated connective tissue diseases (20 cases), Anti Phospholipid’s syndrome (6 cases) and Mixed connective tissue disease (6 cases). A diagnosis of systemic vasculitis was recorded in 19 patients. The other systemic affections were represented by systemic sarcoidosis (8 cases), Adult-onset Still’s disease (03 cases), amyloidosis (02 cases) and 02 cases of systemic syndrome associated to immunodeficiency. The mean diagnostic delay duration before the diagnostic was 3.46 years. Conclusion: Systemic diseases in internal medicine are characterized by their diversity, the clear predominance of RA, and significant diagnostic delay.

Charakterystyka kliniczna i immunologiczna pacjentów z niezróżnicowaną chorobą tkanki łącznej i dominującą manifestacją skórną

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Celińska-Löwenhoff M, Pastuszczak M, Stec-Polak M, Tyrak K, Wojas-Pelc A, Musiał J. Clinical and immunological characteristics of patients with undifferentiated connective tissue disease and dominating skin manifestation. Dermatology Review/Przegląd Dermatologiczny. 2018;105(6):701-709. doi:10.5114/dr.2018.80838. APA Celińska-Löwenhoff, M., Pastuszczak, M., Stec-Polak, M., Tyrak, K., Wojas-Pelc, A., & Musiał, J. (2018). Clinical and immunological characteristics of patients with undifferentiated connective tissue disease and dominating skin manifestation. Dermatology Review/Przegląd Dermatologiczny, 105(6), 701-709. https://doi.org/10.5114/dr.2018.80838 Chicago Celińska-Löwenhoff, Magdalena, Maciej Pastuszczak, Magdalena Stec-Polak, Katarzyna Tyrak, Anna Wojas-Pelc, and Jacek Musiał. 2018. "Clinical and immunological characteristics of patients with undifferentiated connective tissue disease and dominating skin manifestation". Dermatology Review/Przegląd Dermatologiczny 105 (6): 701-709. doi:10.5114/dr.2018.80838. Harvard Celińska-Löwenhoff, M., Pastuszczak, M., Stec-Polak, M., Tyrak, K., Wojas-Pelc, A., and Musiał, J. (2018). Clinical and immunological characteristics of patients with undifferentiated connective tissue disease and dominating skin manifestation. Dermatology Review/Przegląd Dermatologiczny, 105(6), pp.701-709. https://doi.org/10.5114/dr.2018.80838 MLA Celińska-Löwenhoff, Magdalena et al. "Clinical and immunological characteristics of patients with undifferentiated connective tissue disease and dominating skin manifestation." Dermatology Review/Przegląd Dermatologiczny, vol. 105, no. 6, 2018, pp. 701-709. doi:10.5114/dr.2018.80838. Vancouver Celińska-Löwenhoff M, Pastuszczak M, Stec-Polak M, Tyrak K, Wojas-Pelc A, Musiał J. Clinical and immunological characteristics of patients with undifferentiated connective tissue disease and dominating skin manifestation. Dermatology Review/Przegląd Dermatologiczny. 2018;105(6):701-709. doi:10.5114/dr.2018.80838.

Вміст мінеральних компонентів у ротовій рідині дітей дошкільного віку з патологією опорно-рухового апарату

Musculoskeletal disorders (MSD) occupy a leading place among the diseases affecting the dental health of children. The composition and properties of the oral fl uid are an appropriate refl ection of the various processes in the body and can help to study the pathogenesis of tooth decay associated with MSD.The aim of the study – to determine mineral ingredients composition of saliva in children with MSD and to identify its relationship with dental caries.Materials and Methods. 90 5-year old children were examined and divided into three groups of 30 persons in each: fi rst – children with dental caries and MSD; the second – children with dental caries, MSD and undifferentiated connective tissue disease (UCTD); the third – children with dental caries without somatic pathology (comparison group). The deft values and levels of caries prevalence were evaluated. Mineral components of the saliva were determined by photometric method.Results and Discussion. The deft value was (6.17±0.52) in children with MSD, (8.00±0.50) in children with MSD and UCTD and (4.37±0.47) in children of the comparison group. In children with MSD total calcium level in the saliva was 33.80 % lower compared to that in comparison group and 25.53 % higher than in children with MSD and UCTD. The concentration of inorganic phosphorus in the saliva of children with MSD was 29.73 % lower compared to that in comparison group and 15.71 % higher than in children with MSD and UCTD. The same pattern has shown the magnesium level. Alkaline phosphatase activity in the saliva of both groups of children with MSD was lower than in comparison group.Conclusions. In the saliva of children with dental caries and MSD the defi ciencies of total calcium, inorganic phosphorus and magnesium, as well as reduced activity of alkaline phosphatase were revealed.

Diagnosis of systemic inflammatory diseases among patients admitted for acute pericarditis with pericardial effusion.

Acute pericarditis may be the heralding manifestation of various systemic inflammatory diseases (SIDs). The aim of this study was to identify clinical indicators for SIDs in patients admitted for acute pericarditis with pericardial effusion. All consecutive adult patients hospitalized in a Department of Internal Medicine over a 10-year period for acute pericarditis with pericardial effusion were retrospectively reviewed. Patients with cancer and tuberculosis were excluded. A structured clinical panel for extra-cardiac symptoms of SIDs was applied. SIDs were classified using current international criteria. Ninety-nine patients were admitted for acute pericarditis with pericardial effusion. After exclusion, 74 (49.7 ± 19.7 years, 56.7% women) patients were analyzed. Among them, 23 (23.2%) patients had a SID that was revealed by pericarditis in 12 cases. Systemic lupus erythematosus, undifferentiated connective-tissue disease, and Sjogren's syndrome accounted for 75% of the SID. Patients with SIDs were younger (P < 0.001), more frequently of female sex (P = 0.025), and had a higher frequency of extra-cardiac symptoms (P < 0.001) including arthralgia, myalgia, Raynaud phenomenon, and skin rash, as compared with patients with idiopathic pericarditis (n = 51). Overall, after exclusion of neoplasm and tuberculosis, the probability of SIDs in patients admitted with an acute pericarditis with pericardial effusion was 89.7% in patients younger than 50 who had extra-cardiac symptoms. Conversely, the probability fell to 8.4% in patients older than 50 with no extra-cardiac symptoms. Both age and extra-cardiac symptoms suggest an underlying SID as a possible cause of acute pericarditis.

Cardiac involvement in undifferentiated connective tissue disease at risk for systemic sclerosis (otherwise referred to as very early-early systemic sclerosis): a TDI study.

Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47±13years, range 21-70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E m 15±4 vs. 19±5, p=0.0004; E/E m 6.1±1.7 vs. 4.8±1.2, p=0.001; E t 14±3 vs. 16±2, p=0.02; E t/A t 0.9±0.4 vs. 1.3±0.3, p=0.002; E/E t 3.5±1.2 vs. 4.2±0.9, p=0.02) and systolic function (S m 13±3 vs. 15±2cm/s, p<0.0003; S t 14±2 vs. 16±3cm/s, p<0.0001) and increased estimated pulmonary artery wedge pressure (9±2 vs. 8±1, p=0.001) in UCTD-risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E'/A't, (71% of UCTD-risk-SSc patients vs. 19% of controls; p<0.0001). Our study shows that UCTD-risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated.

029. Kikuchi disease as a heralding feature of Undifferentiated Connective Tissue Disease (MCTD predominant)

029. Kikuchi disease as a heralding feature of Undifferentiated Connective Tissue Disease (MCTD predominant)

CLINICAL SIGNIFICANCE OF ANTI-RO52/TRIM21 ANTIBODIES IN SYSTEMIC AUTOIMMUNE RHEUMATIC DISORDERS: PRELIMINARY RESULTS

Although antibodies targeting Ro52 protein/TRIM21 are commonly detected in systemic autoimmune rheumatic disorders (SARDs), their clinical significance and pathobiologic role remains incompletely understood. Objectives. We aimed to define clinical relevance and immunological associations of anti-Ro52/TRIM21 positivity in a cohort of patients with SARDs. Methods. We retrospectively reviewed medical records of 97 consecutive SARDs who attended at least once our Rheumatology Department between March 2016 and June 2017. Clinical manifestations, rheumatoid factor (RF) (Latex and Waalter-Rose tests), antinuclear antibodies (ANA&gt;1:100, immunofluorescence assays) as well as detailed ANA profile (nRNP/Sm, Sm, SS-A/Ro, Ro52/TRIM21, SS-B/La, Scl-70, PM/Scl, Jo-1, CENP-B, PCNA, dsDNA, nucleosome, histone, P-ribosomal protein, AMA-M2, DFS70) (line immunoblot assay) were systematically evaluated. Statistical analysis was performed in SPSS19.0, assuming significance for p&lt;0.05; the chi-squared test was applied to determine the association between anti-Ro52/TRIM21 status and clinical manifestations of SARDs. Results. Only 27 patients (23.7%) had anti-Ro52/TRIM21 positive disease and were further analyzed. Isolated anti-Ro52/TRIM21 were detected in 7/27 (25.9 %) cases, while the majority had dual anti-Ro52/TRIM21 positivity and anti-Ro (n=7/20; 35%), anti-dsDNA (n=3/20, 15%), anti-Jo1 (n=3/20, 15%), anti-centromere B (n=2/20; 10%), anti-Scl70 (n=2/20; 10%), anti-RNP/Sm (n=2/20, 10%), anti-Pm/Scl (n=1/20, 5%), and RF (n=13; 65%). Patients were classified as Sjögren’s syndrome (n=7/27, 25.9%), myositis (n=3/27, 11.1%), systemic lupus erythematosus (n=3/27, 11.1%), systemic sclerosis (n=4/27,15.2%), mixed (n=3/27, 11.1%) or undifferentiated connective tissue disease (n=7/27, 25.9%). More than half of anti-Ro52/TRIM21 positive patients presented with interstitial lung fibrosis (18/27, 66.6%), insolated (33.3%) or in association with anti-Jo1 (33.3%). Conclusions. Anti-Ro52/TRIM21 antibodies should be systematically evaluated in patients with SARDs, as anti-Ro52 positivity (either isolated or in combination with different other ANA specificities) may be associated with definite clinical features. Anti-Ro52/TRIM21 may be useful in identifying a subgroup of patients at risk for developing certain symptoms (particularly interstitial lung disease) of SARDs, with specific therapeutic outcomes.

Undifferentiated connective tissue diseases and adverse pregnancy outcomes. An undervalued association?

Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100000 people. UCTDs are associated with the persistence of several circulating autoantibodies including antinuclear, antiphospholipid or antithyroid antibodies. Immunological evaluation of subjects with UCTDs suggests a proinflammatory state and dysregulation of the Th1/Th2 balance. Autoantibodies have well-known deleterious effects on placentation and have been associated with an increased risk of prematurity, fetal growth restriction (FGR), preeclampsia, and congenital atrioventricular heart block. Although epidemiological and biological data suggest a potential negative impact on reproductive outcomes, the relationship between UCTD and pregnancy outcomes has not been adequately studied. While awaiting definitive data from large studies, obstetricians should be aware that rheumatic disorders in their early, incomplete, or undifferentiated phases can adversely affect pregnancy outcomes, increasing the likelihood of pregnancy loss, FGR, preeclampsia, and prematurity.

Sicca syndrome ‐ disease continnum. Anatomical, functional and systemic assessment

PurposeTo evaluate objective findings in the ophthalmologic examination and search for patterns of association with the clinical and laboratory characteristics in patients with Sicca Syndrome (SiS).MethodsCross‐sectional study of 80 eyes of 80 patients with SiS divided into four groups. 20 patients with pSS for more than 10 years (group1), 20 patients with pSS for less than 2 years (group 2), 20 patients with SiS associated to undifferentiated connective tissue disease (UCTD) (group 3) and 20 patients with SiS without UCTD (group 4). Demographic, clinical and immunologic data were recorded. Ophthalmologic examinations included Schirmer test, break up time (BUT), Corneal Staining Score (CSS), tear meniscus evaluation in Anterior Segment – Optical Coherence Tomography (AS‐OCT) and corneal sub‐basal nerve plexus (CSNP) measurements with in vivo Confocal Microscopy (IVCM).ResultsGroup 1 had an early diagnosis when compared with group 2. Group 1 presented a higher frequency of positivity for anti‐SSA, anti‐SSB, Rheumatoid Factor and ANA titers compared to groups 2‐4 (p&lt;0.05). Patients in group 1 presented more frequently systemic manifestations compared to groups 2‐4 (p&lt;0.05). Sjogren Syndrome Activity Index (SSDAI) correlated positively with positive anti‐SSA (r=0.470, p&lt;0.0005). Group 1 showed a higher CSS and a lower BUT, tear meniscus height and area compared to group 2 and 3 (p&lt;0.005). CSNP's length and density were significantly smaller in group 1 compared to group 2 and 3 (p&lt;0.05).ConclusionsCSNP's density and length, as well as tear meniscus area and height are smaller in advanced pSS compared to pSS with recent diagnostic and SiS‐UCTD. AS‐OCT and IVCM may be useful for risk stratification in SiS.