Prevalence and clinical significance of anti-SSA antibody in the Chinese health screening population.

Anti-Sjögren's syndrome type A (anti-SSA) antibodies are non-organ-specific autoantibodies highly prevalent in various autoimmune diseases. This study primarily investigated the prevalence of anti-SSA antibodies in the health screening population. Additionally, we explored the clinical features of the anti-SSA antibody-positive population and evaluated the development of connective tissue diseases (CTD) over the years in individuals with anti-SSA antibodies for whom follow-up was available. A total of, 64 045 individuals without a history of CTD from 2013 to 2022 who visited Peking Union Medical College Hospital for health screening were screened for autoimmune antibodies: 1.7% (1091/64 045) of the Chinese health screening population were positive for anti-SSA antibodies, with a prevalence of 0.9% (290/33 829) in men and 2.7% (801/30 216) in women. Compared with matched autoantibody-negative controls, anti-SSA antibody-positive individuals had higher levels of serological abnormalities, including erythrocyte sedimentation rate (ESR) [10 (6-15) mm/h vs. 7 (4-12) mm/h, P < 0.0001], rheumatoid factor (RF) [7.15 (4.30-16.90) IU/ml vs. 5.00 (3.20-7.90) IU/ml, P < 0.0001], and immunoglobulin G [13.09 (11.20-15.45) g/L vs. 11.34 (9.85-13.18) g/L, P < 0.0001], and lower levels of white blood cells (WBC; 5.49 ±â€…1.50 × 109/L vs. 5.82 ±â€…1.49 × 109/L, P < 0.0001). Additionally, they had a higher proportion of coexisting thyroid autoantibodies, including anti-thyroid peroxidase antibodies (TPO-Ab) (17.1% vs. 11.3%, P < 0.0001) and anti-thyroglobulin antibodies (Tg-Ab) (17.8% vs. 11.0%, P < 0.0001). Among the 381 subjects who were anti-SSA positive and followed up for a median of 4.6 years, 146 (38.3%) individuals developed CTD, including 68 (17.8%) cases of primary Sjögren's syndrome (pSS), 10 (2.6%) cases of rheumatoid arthritis (RA), 5 (1.3%) cases of systemic lupus erythematosus (SLE), 4 (1.0%) cases of secondary Sjögren's syndrome (sSS), and 59 (15.5%) cases of undifferentiated connective tissue disease (UCTD). In all, 235 (61.7%) individuals did not develop CTD over a median time of 5.9 (2.9-8.1) years after the earliest autoantibody detection. Elevated ESR (>20 mm/h), RF positivity (>20 IU/ml), and female gender were identified as independent risk factors for CTD among the anti-SSA antibody-positive individuals. Anti-SSA antibodies were found in 17 among approximately 1000 individuals without a history of autoimmune diseases. Anti-SSA antibody-positive individuals are advised to periodically monitor thyroid function. Elevated ESR (>20 mm/h), female gender, and RF positivity may delineate a high-risk cohort for CTDs.

Epidemiology of Sjögren syndrome.

Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue diseases (CTDs), including rheumatoid arthritis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The estimation of the prevalence and incidence of Sjögren syndrome varies depending on diagnostic criteria and study design, making it difficult to estimate geographical and temporal trends. Nonetheless, disease phenotype is influenced by geographical origin, which is a risk factor for systemic activity. Whether mortality in primary Sjögren syndrome is increased compared with that of the general population is not yet known, but extra-glandular manifestations, in particular lymphomas, are clear risk factors for mortality. In CTDs associated with Sjögren syndrome, lymphoma risk seems higher than that of patients with CTD alone, and there is potentially lower disease activity in SLE with Sjögren syndrome and in SSc with Sjögren syndrome than in SLE or SSc alone.

Clinical significance of interleukin-6, total bilirubin, CD3 + CD4 + T cells counts in the acute exacerbation of connective tissue disease-associated interstitial lung disease: a cross-sectional study.

OBJECTIVE: Interstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease. METHODS: This study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1ß were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables. RESULTS: Elevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P < 0.05). Similarly, the levels of IL-6, IL-8 and TNF-α were higher in the acute exacerbation (AE-CTD-ILD) group compared with stable CTD-ILD (S-CTD-ILD) (P < 0.001, P < 0.001, and P = 0.022). Significant correlations between serum IL-6 and PaO2/FiO2 ratio (r = - 0.463, P < 0.001), percent predicted forced vital capacity (FVC%; r = - 0.362, P < 0.05), and total ground-glass opacity (GGO) score (r = 0.439, P < 0.001) were observed in CTD-ILD patients. Multivariate logistic regression analysis revealed that elevated IL-6 levels, total bilirubin (TBil), and decreased CD3 + CD4 + T cells counts were independent risk factors for the occurrence of AE-CTD-ILD (OR = 1.121, P = 0.024; OR = 1.865, P = 0.047; OR = 0.983, P = 0.037, respectively). Furthermore, by employing these three variables in combination for the prediction of AE status, their collective impact surpasses the independent effects of any single biomarker. CONCLUSIONS: Elevated levels of serum IL-6, IL-8, and TNF-α were associated with the complication of ILD in CTD patients and the occurrence of AE in CTD-ILD patients. IL-6 could be a promising serum biomarker of severity and the occurrence of AE in CTD-ILD patients. The combination of the three variables (IL-6 level, TBil and CD3 + CD4 + T cells) predicted the AE-CTD-ILD better.

KL-6 levels in the connective tissue disease population: typical values and potential confounders-a retrospective, real-world study.

Background: Krebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation. Methods: From the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD. Results: Univariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the ß were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P < 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients. Conclusion: KL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account.

[Interstitial pneumonia with autoimmune features: monocentric prospective study].

AIM: To study demographic, clinical, serological and morphological features of interstitial pneumonia with autoimmune features (IPAF), compare survival in IPAF and interstitial lung disease in connective tissue diseases (CTD-ILD), and identify predictors of mortality and transformation to CTD in the IPAF group. MATERIALS AND METHODS: The IPAF group included 48 patients (75.0% women, median age 57.5 years), CTD-ILD - 49 patients (79.6% women, median age 60.0 years). The analysis of demographic, clinical, laboratory and instrumental data was performed, as well as comparison of survival with the Kaplan-Meier method and the log-rank test in the IPAF and CTD-ILD groups. In the IPAF group, predictors of mortality and the development of CTD were studied with multivariate regression analysis. RESULTS: Duration of observation period did not differ significantly in the IPAF and CTD-ILD groups (40.0 and 37.0 months, respectively). Clinical criteria of IPAF were observed in 25 (52.1%) patients, serological - in 44 (91.7%), morphological - in 44 (91.7%). Mortality in the IPAF group was significantly higher than in the CTD-ILD group (29.2 and 6.1%, respectively; p=0.023). The presence of diabetes mellitus, CT-pattern of usual interstitial pneumonia, and an initial low forced vital capacity value were independent predictors of mortality in the IPAF group. During the observation period, the development of CTD was noted in 4 (8.3%) patients with IPAF. The independent predictor of the CTD development was the increased C-reactive protein level. CONCLUSION: IPAF is characterized by a lower survival rate compared to CTD-ILD, and a relatively low risk of CTD transformation.

Comparison of the diagnostic criteria for progressive pulmonary fibrosis in connective tissue disease related interstitial lung disease.

BACKGROUND: Progressive pulmonary fibrosis (PPF) is possible among patients with connective tissue disease (CTD) related interstitial lung disease (ILD). Our aim herein was to compare the prevalence and clinical characteristics of patients with CTD-ILD, with and without PPF, according to the different diagnostic criteria currently used in practice. METHODS: This retrospective study included patients diagnosed with CTD-ILD, with a ≥1-year follow-up of their lung function, at a single tertiary hospital in South Korea. Diagnostic criteria from two clinical trials (RELIEF and TRAIL1) and from a recently updated guideline (ATS/ERS/JRS/ALAT) were applied. RESULTS: Of the 107 patients included, 80% tested positive for Sjogren's disease, rheumatoid arthritis, and systemic sclerosis. The prevalence of CTD-ILD with PPF for the different diagnostic criteria was as follows: RELIEF, 25.2%; TRAIL1, 20.6%; and ATS/ERS/JRS/ALAT, 38.3%. More previous history of pulmonary tuberculosis and less positivity for antinuclear antibodies were identified in the PPF group. The radiologic pattern of ILD did not differ between patients with and without PPF, with a usual interstitial pneumonia pattern identified in 34.6% of the patients. Systemic steroids and immunomodulatory agents were used in about 80% of patients with PPF and 50% without PPF, irrespective of the diagnostic criteria used. Antifibrotic therapy was used in a limited number of patients in both groups. CONCLUSIONS: The proportion of patients with CTD-ILD and PPF was higher for the ATS/ERS/JRS/ALAT guideline criteria, without a between-group difference in clinical characteristics.

Lung Transplantation: A Viable Option for Connective Tissue Disease?

Interstitial lung disease (ILD) and pulmonary hypertension (PH) caused by connective tissue disease (CTD) are one of the main causes of morbidity and death in patients. Although the International Society for Heart & Lung Transplant suggested that ILD and PH related to CTD are rare indications for lung transplantation in 2006, many lung transplantation centers are concerned that the multisystem involvement of CTD will affect survival outcomes after lung transplantation, and CTD is regarded as a relative contraindication for lung transplantation. However, long-term and short-term survival after lung transplantation in CTD patients is similar compared with survival in common indications for lung transplantation such as idiopathic pulmonary fibrosis (IPF), and no higher incidence of complications after transplantation in many lung transplant centers. This suggests that lung transplantation may be beneficial in CTD patients with disease that progresses to end-stage lung disease, and CTD should not be considered a contraindication for lung transplantation. In the future, more prospective studies are needed to analyze the risk factors of lung transplantation in CTD patients to improve survival rates and reduce the risk of complications. This narrative review summarizes the selection and evaluation of candidates for CTD before lung transplantation and describes the clinical outcomes in CTD after lung transplantation in large-capacity lung transplantation center. The purpose of this review is to help rheumatologists decide when to refer patients with CTD-related lung involvement to a lung transplantation center and the conditions to consider before transplantation and to provide confidence to lung transplant experts.

The concomitant diagnosis of fibromyalgia and connective tissue disorders: A systematic review.

BACKGROUND: Anecdotally, fibromyalgia syndrome (FMS) and connective tissue disorders (hypermobile Ehlers-Danlos Syndrome (hEDS), Hypermobility Spectrum disorders (HSD) and Generalized Joint Hypermobility (GJH)) manifest overlap in their diagnostic approach and symptomatic features. Understanding this overlap is important for accurate diagnosis and the success of subsequent management. This study therefore aimed to identify the prevalence of concomitant diagnosis of FMS and hEDS/HSD/GJH in adults and their shared symptomatic manifestations using a systematic review. METHODS: MEDLINE (via EBSCO host) was systematically searched. Observational research (case-control or single group) studies were considered for inclusion, where adults screened for hEDS/HSD/GJH and FMS were compared in terms of diagnostic prevalence, and musculoskeletal and non-musculoskeletal manifestations. Studies on pediatric populations were excluded. The quality of the included studies was assessed using the National Institute of Health Quality Assessment of Case-Control Studies and Jonna Briggs Critical Appraisal checklist for prevalence studies. The review was registered prospectively in PROSPERO (CRD42020216283). FINDINGS: The review included eleven studies: nine case-control studies and two single group studies. The prevalence of concomitant diagnosis of hEDS/HSD and FMS ranged from 68%-88.9% and from 8.0 to 64.2% for GJH and FMS. The prevalence and severity of a range of objective and patient-reported features were similar between hEDS/HSD and FMS, including joint pain (duration, persistence, SF-36-pain component score); joint swelling; muscle weakness; neurological problems; multidimensional pain inventory-activity; dysautonomia and total autonomic symptoms burden (including orthostatic intolerance, reflex syncope, vasomotor, gastrointestinal, diarrhea, constipation and pupillomotor domains); function; and quality of life. Shared symptomatic features between GJH and FMS were mean pain level, tender points count, total myalgia score and psychological impact. INTERPRETATION: There may be overlapping symptomatology and diagnostic prevalence of FMS and hEDS/HSD/GJH. Clinicians should consider both diagnoses to ensure appropriate diagnosis and management.

Determinants of health-related quality of life across the spectrum of connective tissue diseases using latent profile analysis: results from the LEAP cohort.

OBJECTIVES: Poor health-related quality of life (HRQoL) is well recognized in patients with CTD. We hypothesized that subgroups of patients across the spectrum of CTD experience different HRQoL patterns and aimed to determine patient-level characteristics associated with these different subgroups. METHODS: Using the eight continuous domains of the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire we performed data-driven clustering to derive latent profiles (LPs) of patients with distinct HRQoL patterns. Multivariable ordinal logistic regression was used to determine patient-level characteristics associated with each HRQoL subgroup identified. RESULTS: A total of 309 CTD patients completed the SF-36 questionnaire. The most impaired SF-36 domains in each disease group were vitality, general health and bodily pain. The physical component of the SF-36 was consistently more impaired compared with the mental component, with similar scores across disease groups. Three LPs were identified with poor [n = 89 (29%)], average [n = 190 (61.4%)] and excellent [n = 30 (9.7%)] HRQoL. LPs were not associated with diagnostic grouping or autoantibody profiles. Black background [odds ratio (OR) 0.22 (95% CI 0.08, 0.63)], Indo-Asian background [OR 0.39 (95% CI 0.19, 0.78)], concomitant fibromyalgia [OR 0.40 (95% CI 0.20, 0.78)], sicca symptoms [OR 0.56 (95% CI 0.32, 0.98)] and multimorbidity [Charlson Comorbidity Index; OR 0.81 (95% CI 0.67, 0.97)] were associated with the 'poor' HRQoL LP. CONCLUSION: Distinct HRQoL subgroups exist that are not primarily driven by a specific diagnosis or autoantibody profiles. We identified a number of key demographic and clinical factors associated with poor HRQoL. These factors need to be addressed across the whole CTD spectrum as part of a holistic management approach aimed at improving overall patient outcomes.

Prevalence and clinical associations of myositis antibodies in a large cohort of interstitial lung diseases.

BACKGROUND: Serologic testing for autoantibodies is recommended in interstitial lung diseases (ILDs), as connective tissue diseases (CTDs) are an important secondary cause. Myositis antibodies are associated with CTD-ILD, but clinical associations with other ILDs are unclear. In this study, associations of myositis antibodies in various ILDs were evaluated. METHODS: 1463 ILD patients and 116 healthy subjects were screened for myositis antibodies with a line-blot assay on serum available at time of diagnosis. Additionally, bronchoalveolar lavage fluid (BALf) was analysed. RESULTS: A total of 394 patients demonstrated reactivity to at least one antibody, including anti-Ro52 (36.0%), anti-Mi-2ß (17.3%) and anti-Jo-1 (10.9%). Anti-Jo-1 (OR 6.4; p<0.100) and anti-Ro52 (OR 6.0; p<0.001) were associated with CTD-ILD. Interestingly, anti-Mi-2ß was associated with idiopathic pulmonary fibrosis (IPF; OR 5.3; p = 0.001) and hypersensitivity pneumonitis (HP; OR 5.9; p<0.001). Furthermore, anti-Mi-2ß was strongly associated with a histological usual interstitial pneumonia (UIP) pattern (OR 6.5; p < 0.001). Moreover, anti-Mi-2ß reactivity was identified in BALf and correlated with serum anti-Mi-2ß (r = 0.64; p = 0.002). No differences were found in survival rates between ILD patients with and without serum Mi-2ß reactivity (hazard ratio 0.835; 95% CI 0.442-1.575; p = 0.577). CONCLUSION: In conclusion, novel associations of antibody Mi-2ß with fibrotic ILD were found. Furthermore, serum anti-Mi-2ß was associated with a histological UIP pattern and presence of anti-Mi-2ß in BALf. Possibly, anti-Mi-2ß could be implemented as a future diagnostic biomarker for fibrotic ILD.

Long-Term Outcomes of Cardiovascular Operations in Children With Connective Tissue Disorders.

Connective tissue disorders can be associated with significant cardiovascular morbidity needing cardiac surgery during childhood. In this retrospective study, we used the Pediatric Cardiac Care Consortium, a multicenter United States-based registry of pediatric cardiac interventions, to describe the long-term outcomes of patients who underwent their first surgery for connective tissue-related cardiovascular conditions aged <21 years. Between 1982 and 2003, a total of 103 patients were enrolled who underwent cardiac surgery for a connective tissue-related cardiovascular disorder, including 3 severe infantile cases operated on within the first year of life. Most patients underwent aortic site surgery (n = 85) as a composite graft (n = 50), valve-sparing (n = 33), or other aortic surgery (n = 2). The remaining patients underwent atrioventricular valve surgery (mitral 17, tricuspid 1). Of the 99 patients surviving to discharge, 80 (including the 3 infantile) had adequate identifiers for tracking long-term outcomes through 2019 through linkage with the National Death Index and the Organ Procurement. Over a median period of 19.5 years (interquartile range 16.0 to 23.1), 29 deaths and 1 transplant occurred in the noninfantile group, whereas all 3 infantile patients died before the age of 4 years. The postdischarge survival for the noninfantile group was 92.2%, 68.2%, and 56.7% at 10, 20, and 25 years, respectively. Cardiovascular-related pathology contributed to all deaths in the infantile and 89% (n = 27) of deaths for the noninfantile cases after hospital discharge. The significant late attrition from cardiovascular causes emphasizes the need for close monitoring and ongoing management in this population.

Silicone breast implants and connective tissue diseases: How does current evidence add to the no-association consensus? Systematic review and meta-analysis.

To evaluate the current state of the evidence regarding the association of silicone breast implantation with the onset of connective tissue diseases, constitutional symptoms, and rheumatic serological profile in adult women. A comprehensive search was carried out using MEDLINE, Embase, Web of Science and Scopus, from inception to September 2, 2020. Cohort studies assessing the clinical and serological profile of women with cosmetic breast implants were included. Meta-analyses were conducted using risk ratios. A total of 10 cohorts with overall moderate quality of evidence were included in this systematic review. Exposure to silicone breast implants was slightly associated with the development of rheumatoid arthritis [RR: 1.35; (95% CI 1.08 to 1.68); P = .008; I2 = 0%]. However, no significant differences were exhibited between the breast implant-exposed population and controls regarding the rest of the outcomes. In adult women, exposure to silicone breast implantation is not associated with the onset of constitutional symptoms and most connective tissue diseases. A marginal association with rheumatoid arthritis was exhibited, but the certainty of this result is jeopardized by the significant amount of self-reported data for this outcome. Further research is required to adequately explore the clinical significance of these results.

The Impact of Degenerative Connective Tissue Disorders on Outcomes Following Endovascular Aortic Intervention in the Global Registry for Endovascular Aortic Treatment.

OBJECTIVE: Endovascular therapy for the management of aortic pathology in patients with degenerative connective tissue disorder (DCTD) is controversial. Current guidelines are based on a paucity of literature and registry data are lacking. This study reports on medium term outcomes of patients with diagnosed DCTD compared to those without DCTD who were included in the W.L. Gore Global Registry for Endovascular Aortic Treatment (GREAT). METHODS: Patients included in the GREAT registry who underwent treatment for any thoracic or abdominal aortic pathology were included and grouped according to the presence or absence of a DCTD. Baseline demographic and procedural data were collected as well as data relating to key outcomes within 5 years follow-up, including all-cause mortality, aortic-related mortality, reinterventions and serious adverse events (SAE). Multivariable Cox proportional hazards models were built to determine if any association existed between the presence of DCTD and any key outcomes. RESULTS: The analysis included 92 (1.9%) with DCTD and 4741 (98.1%) without DCTD. Patients with DCTD were more likely to be female (34.8% vs. 18.5%, P < .0001) and younger (66.8 [15.1] vs. 71.7 [10.3] years, P = .013) than those without DCTD. They were also more likely to have had prior aortic intervention (22.8% vs. 13.9%, P = .015) and an associated branch vessel procedure with the index operation (30.3% vs. 18.6%, P = .005). The majority of reinterventions in both groups occurred within the first 2 years and multivariable models demonstrated that the presence of DCTD was not predictive of all-cause mortality, aortic-related mortality, reinterventions or SAE within 5 years. CONCLUSIONS: Within the limitations of registry data, this work demonstrates the medium term safety and durability of endovascular stent-grafts across a spectrum of aortic pathology in some patients with DCTD. More work is required to determine the applicability of these findings to specific sub-types of DCTD and aortic pathology.

Prevalence of systemic lupus erythematosus-related symptoms assessed by using the Connective Tissue Disease Screening Questionnaire in a large population-based cohort.

BACKGROUND: To assess the prevalence of self-reported SLE-related symptoms associated with demographic and biochemical data and connective tissue disease (CTD)-related autoantibodies in a large population-based cohort. METHODS: Participants of the Dutch Lifelines population cohort filled out the Connective Tissue Disease Screening Questionnaire (CSQ), including 11 questions focusing on SLE-related symptoms (SLE-CSQ) based on the American College of Rheumatology classification criteria. CTD autoantibody screen was performed in 25% of participants. RESULTS: Of 85 295 participants with complete SLE-CSQ data, after excluding patients with SLE and other CTDs (n=126), 41 781 (49.1%) had no positively answered questions and 2210 (2.6% of total) had ≥4 positive answers. Participants with ≥4 answers on the SLE-CSQ were significantly younger, more frequently female, had lower body mass index (BMI) and were more often smokers than those with negative scores. Furthermore, counts of leucocytes, neutrophils and monocytes were significantly higher in these participants, while the levels of haemoglobin and creatinine were lower. CTD autoantibodies were present in 2.2% of participants with SLE-CSQ score of 0, compared with 3.5% with SLE-CSQ score ≥4 (p=0.001). Multivariate analysis showed, after adjusting for age, gender, BMI and smoking, that haemoglobin levels remained significantly lower in participants with SLE-CSQ score ≥4. CONCLUSIONS: In this large population-based cohort, 2.6% of participants without diagnosed CTD reported ≥4 positive answers on the SLE-CSQ, indicating high suspicion for SLE. These individuals had demographic and haematological characteristics that differed from the remaining population. Potentially, this questionnaire, in combination with autoantibody determination, can be used as a starting point of a screening cascade in order to detect SLE at an early stage.

Clinical significance of anti-Ro52 (TRIM21) antibodies in adult patients with connective tissue diseases.

OBJECTIVES: Clinical significance of anti-Ro52 antibodies in connective tissue diseases (CTD) is controversial. Anti-Ro52 antibodies might be associated with a more severe CTD phenotype, especially interstitial lung disease (ILD). The aims of this study were to evaluate ILD prevalence and severity, the prevalence of micro- or macroangiopathy and CTD-associated cancers in CTD with anti-Ro52 antibodies. METHODS: CTD patients with anti-Ro52 antibody screening by immunoblot at diagnosis were enrolled. Two groups were retrospectively formed according to the presence of anti-Ro52 antibodies with an unbiased 1:1 matching on CTD types. Unsupervised multiple correspondence analysis and hierarchical clustering analysis were used to aggregate anti-Ro52 positive patients in subgroups. RESULTS: 408 CTD patients were included. Anti-Ro52 antibodies were detected in 33 % of CTD patients. Anti-Ro52 antibodies were associated with ILD at CTD diagnosis (47.8% vs. 23.0%, OR 3.3 95% IC 1.4 to 8.0, p = 0.008), even after adjusting for the presence of anti-Ro60 antibodies, especially in patients with antisynthetase syndrome, primary Sjögren syndrome and systemic sclerosis. Micro- or macroangiopathy was more frequent in anti-Ro52 positive CTD patients (18.6% vs. 9.7%, p = 0.02) and CTD patients with anti-Ro52 antibodies experienced more frequent relapses and required more immunosuppressive drugs. Clusters 4 and 5 identified anti-Ro52 positive CTD patients with severe ILD and with clinical features of systemic sclerosis or antisynthetase syndrome respectively. CONCLUSIONS: We found that anti-Ro52 antibodies were independently associated with ILD in CTD patients irrespective of CTD type. Anti-Ro52 antibodies could be associated with severity and a more relapsing disease course in CTD patients.

Nutritional status and quality of life in interstitial lung disease: a prospective cohort study.

BACKGROUND: Malnutrition and altered body composition are well-documented in chronic pulmonary diseases; however, investigation of nutritional status in interstitial lung disease (ILD) is limited. This study aimed to describe the nutritional status of ILD patients within three diagnostic groups and explore the relationship between nutritional status and quality of life (QoL). METHODS: Consecutive patients attending an ILD clinic within a tertiary referral hospital in Sydney, Australia were studied. Weight, body-mass-index, anthropometrics, handgrip strength (HGS), subjective global assessment and QoL questionnaires (EQ-5D-5L and King's-Brief Interstitial-Lung-Disease 'K-BILD') were collected. Associations between nutritional status and QoL were analysed. RESULTS: Ninety participants were recruited and categorised: (1) Idiopathic Pulmonary Fibrosis (IPF) (2) Connective-Tissue Disease associated-ILD (CTD-ILD) or (3) Other (non-IPF/non-CTD ILD). Median age was 66.5 (18) years. Four-percent of patients were underweight and 50% were overweight or obese. Median HGS was 71%-(25.3) of predicted and was correlated to all measures of QoL including EQ-5D health-state index (r = 0.376, p < 0.0001), patient-reported EQ-5D-5L Visual Analogue Score (r = 0.367, p < 0.0001) and K-BILD total score (r = 0.346, p = 0.001). Twenty-three percent of the variance in K-BILD total score (F = 12.888, p < 0.0001) was explained by HGS (ß = 0.273, p = 0.006) and forced vital capacity % predicted (ß = 0.331, p = 0.001). CONCLUSIONS: Although a small number of ILD patients were malnourished, a large proportion of the cohort were overweight or obese. Handgrip strength was compromised and correlated to QoL. Future research with a larger cohort is required to explore the role of HGS as a predictor of QoL.

Assessment of Toxic Effects Associated With Dose-Fractionated Radiotherapy Among Patients With Cancer and Comorbid Collagen Vascular Disease.

Importance: The adoption of alternative fractionated radiotherapy regimens for the treatment of patients with cancer and comorbid collagen vascular disease (CVD) is controversial among oncologists because of concerns about potentially severe toxic effects; however, the association between fractionated radiotherapy and toxic effects in the modern era has not been well studied. Objective: To compare acute and late toxic effects among patients with cancer and comorbid CVD who received dose-fractionated radiotherapy. Design, Setting, and Participants: This retrospective cohort study examined 197 adult patients with cancer and CVD who received radiotherapy at a single-institution tertiary academic center over a 12-year period (February 1, 2007, to April 30, 2019), with a median follow-up of 23 months (range, 0-108 months). Data were analyzed from February 1 to August 31, 2020. Exposures: Three dose-fractionated radiotherapy regimens: conventional fractionation (CF; ≤2 Gy per fraction), moderate hypofractionation (MH; >2 Gy to <5 Gy per fraction), and ultrahypofractionation (UH; ≥5 Gy per fraction). Main Outcomes and Measures: The main outcomes were the incidence and severity of acute and late radiotherapy-associated toxic effects, which were assessed separately by dose-fractionation regimen. Toxic effects occurring within 90 days after radiotherapy completion were considered acute, and toxic effects occurring after that 90-day period were considered late. Secondary goals were to identify covariates associated with toxic effects and to characterize the incidence of CVD symptom flares (defined as worsening clinical symptoms and/or worsening results [transient or permanent] on associated blood tests compared with baseline, as documented by managing physicians) after radiotherapy. Results: Of 197 patients with cancer and comorbid CVD (mean [SD] age, 69 [12] years; 134 women [68.0%]; and 149 White participants [75.6%]), 80 patients (40.6%) received CF radiotherapy, 55 patients (27.9%) received MH radiotherapy, and 62 patients (31.5%) received UH radiotherapy. The most common CVD diagnoses were rheumatoid arthritis (74 patients [37.6%]), psoriasis (54 patients [27.4%]), systemic lupus erythematosus (34 patients [17.3%]), and scleroderma (8 patients [4.1%]). The most common radiotherapy sites were the breast (48 patients [24.4%]), thorax (25 patients [12.7%]), central nervous system (24 patients [12.2%]), and prostate (23 patients [11.7%]). Data on acute toxic effects were available for 188 patients (95.4%) and missing for 9 patients (4.6%). Data on late toxic effects were available for 142 patients (72.1%) and missing for 55 patients (27.9%). Over 12 years, the unadjusted incidences of severe acute toxic effects associated with CF, MH, and UH radiotherapy were 5.4% (95% CI, 0.3%-10.5%), 7.4% (95% CI, 0.4%-14.4%), and 1.7% (95% CI, 0%-5.0%), respectively. The incidences of severe late toxic effects associated with CF, MH, and UH radiotherapy were 8.3% (95% CI, 1.3%-15.3%), 0%, and 2.2% (95% CI, 0%-6.4%), respectively. No significant associations were found between severe acute or late toxic effects by dose fractionation regimen. In the multivariable analysis, MH radiotherapy was associated with a lower likelihood of developing late toxic effects (odds ratio [OR], 0.21; 95% CI, 0.05-0.83; P = .03) compared with CF radiotherapy. Those who received UH radiotherapy had a lower likelihood of experiencing late toxic effects (OR, 0.22; 95% CI, 0.04-1.21; P = .08). A total of 19 of 80 patients (23.8%), 15 of 55 patients (27.3%), and 10 of 62 patients (16.1%) experienced CVD symptom flares after receiving CF, MH, and UH radiotherapy, respectively (P = .33). Conclusions and Relevance: In this study, the incidences of unadjusted severe toxic effects over 12 years were less than 10% and were not significantly associated with dose fractionation. When clinically indicated, patients with cancer and comorbid CVD may not require immediate exclusion from the receipt of currently used hypofractionated radiotherapy regimens.

Stickler Syndrome: Airway Complications in a Case Series of 502 Patients.

BACKGROUND: Patients with Stickler syndrome often require emergency surgery and are often anesthetized in nonspecialist units, typically for retinal detachment repair. Despite the occurrence of cleft palate and Pierre-Robin sequence, there is little published literature on airway complications. Our aim was to describe anesthetic practice and complications in a nonselected series of Stickler syndrome cases. To our knowledge, this is the largest such series in the published literature. METHODS: We retrospectively identified patients with genetically confirmed Stickler syndrome who had undergone general anesthesia in a major teaching hospital, seeking to identify factors that predicted patients who would require more than 1 attempt to correctly site an endotracheal tube (ETT) or supraglottic airway device (SAD). Patient demographics, associated factors, and anesthetic complications were collected. Descriptive statistical analysis and logistic regression modeling were performed. RESULTS: Five hundred and twoanesthetic events were analyzed. Three hundred ninety-five (92.7%) type 1 Stickler and 63 (96.9%) type 2 Stickler patients could be managed with a single attempt of passing an ETT or SAD. Advanced airway techniques were required on 4 occasions, and we report no major complications. On logistic regression, modeling receding mandible (P = .0004) and history of cleft palate (P = .0004) were significantly associated with the need for more than 1 attempt at airway manipulation. CONCLUSIONS: The majority of Stickler patients can be anesthetized safely with standard management. If patients have a receding mandible or history of cleft, an experienced anesthetist familiar with Stickler syndrome should manage the patient. We recommend that patients identified to have a difficult airway wear an alert bracelet.

Association of Breast Implants with Nonspecific Symptoms, Connective Tissue Diseases, and Allergic Reactions: A Retrospective Cohort Analysis.

BACKGROUND: Given the rising media attention regarding various adverse conditions attributed to breast implants, the authors examined the association between breast implantation and the risk of being diagnosed with connective tissue diseases, allergic reactions, and nonspecific constitutional complaints in a cohort study with longitudinal follow-up. METHODS: Women enrolled in a regional military health care system between 2003 and 2012 were evaluated in this retrospective cohort study. A propensity score was generated to match women who underwent breast implantation with women who did not undergo breast implantation. The propensity score included age, social history, health care use, comorbidities, and medication use. Outcomes assessed included International Classification of Diseases, Ninth Revision, diagnoses codes for (1) nonspecific constitutional symptoms, (2) nonspecific cardiac conditions, (3) rheumatoid arthritis and systemic lupus erythematosus, (4) other connective tissue diseases, and (5) allergic reactions. RESULTS: Of 22,063 women included in the study (513 breast implants and 21,550 controls), we propensity score-matched 452 breast implant recipients with 452 nonrecipients. Odds ratios and 95 percent confidence intervals in breast implant recipients compared to nonrecipients were similar, including nonspecific constitutional symptoms (OR, 0.77; 95 percent CI, 0.53 to 1.13), nonspecific cardiac conditions (OR, 0.97; 95 percent CI, 0.69 to 1.37), rheumatoid arthritis and systemic lupus erythematosus (OR, 0.66; 95 percent CI, 0.33 to 1.31), other connective tissue diseases (OR, 1.02; 95 percent CI, 0.78 to 1.32), and allergic reactions (OR, 1.18; 95 percent CI, 0.84 to 1.66). CONCLUSIONS: Women with breast implants did not have an increased likelihood of being diagnosed with nonspecific constitutional symptoms, connective tissue disorders, and/or allergic reaction conditions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Ocular Manifestations in Rheumatoid Arthritis, Connective Tissue Disease, and Vasculitis: A Systematic Review and Metaanalysis.

OBJECTIVE: Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review. METHODS: A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis. RESULTS: There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome ("dry eye"; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3-28) and 6% (95% CI 3-9) of patients, respectively. CONCLUSION: Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.