Connective Tissue Disease Patients Research Articles

Clinicoepidemiological Spectrum of Connective Tissue Diseases in the Pediatric Population in a Tertiary Care Center in North India: A Cross-sectional Observational Study

Abstract Background: Connective tissue diseases (CTDs) are chronic in nature and carry a high risk of morbidity, disability, and mortality if not recognized and treated promptly. Data on clinical spectrum of CTDs in the pediatric age group are sparse from developing countries such as India. Objective: To study the clinicoepidemiological spectrum of CTDs in the pediatric age group. Methodology: A hospital-based, cross-sectional, observational study was undertaken over a period of 16 months from January 2021 to June 2022 in the dermatology outpatient department and pediatric rheumatology clinic in a tertiary care hospital in North India. Clinical and laboratory findings were recorded. Results: A total of 100 children diagnosed with a CTD were included in the study. The mean age was 11.11 ± 4.20 years. Out of 100 children, 55% were female and 45% were male with a male-to-female ratio of 1:1.2. Our study included 63% juvenile idiopathic arthritis, 17% systemic lupus erythematosus, 7% juvenile dermatomyositis, 6% Kawasaki disease, 3% systemic sclerosis, and 2% Henoch–Schonlein purpura and mixed CTD patients each. Mucocutaneous features commonly seen were rash (40%), oral ulcers (22%), and photosensitivity (18%). Commonly seen systemic features were joint pain (77%), followed by fever (63%). Conclusion: Mucocutaneous manifestations are frequently seen in CTDs and constitute a frequent and an early manifestation of CTD. Early recognition of CTD in the pediatric age group will help in timely initiation of treatment to prevent disabilities and mortality.

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

ObjectiveInterstitial 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.MethodsThis 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-1β 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.ResultsElevated 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.ConclusionsElevated 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.

Autoantibody status according to multiparametric assay accurately estimates connective tissue disease classification and identifies clinically relevant disease clusters

ObjectiveAssessment of circulating autoantibodies represents one of the earliest diagnostic procedures in patients with suspected connective tissue disease (CTD), providing important information for disease diagnosis, identification and prediction of potential...

The phenotype of mixed connective tissue disease patients having associated interstitial lung disease

ObjectiveWe aimed to compare two matched populations of patients with MTCD with and without associated ILD and to identify predictive factors for ILD progression and severity. MethodsThis international multicenter retrospective study (14 tertiary hospitals), included MCTD patients who fulfilled at least one historical MCTD classification criteria. ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Factors associated with ILD were assessed at baseline. Long-term progressive ILD was assessed in MCTD-ILD patients with multiple forced vital capacity (FVC) measurements. Results300 patients with MCTD were included. Mean age at diagnosis was 39.7 ± 15.4 years and 191 (63.7%) were women. Mean follow-up was 7.8 ± 5.5 years. At baseline, we identified several factors associated with ILD presence: older age (p = 0.01), skin thickening (p = 0.03), upper gastro-intestinal (GI) symptoms (p<0.001), FVC <80% (p<0.0001), diffusing capacity for carbon monoxide <80% (p<0.0001), anti-topoisomerase antibodies (p = 0.01), SSA/Ro antibodies (p = 0.02), cryoglobulinemia (p = 0.04) and elevated C-reactive protein (p<0.001). Patients with MTCD-ILD were more likely to be treated with synthetic immunosuppressant agents (p<0.001) in particular mycophenolate mofetil (p = 0.03). Digital ulcers (DU) were identified as a risk factor for FVC decline >10%. During follow-up mortality was higher in the MTCD-ILD group (p<0.001). ConclusionIn this large international cohort of patients with MTCD, we identified different factors associated with ILD. Our findings also provide evidence that MCTD-ILD patients have increased mortality and that DU are associated with progressive lung disease.

Association of anti-Ro52 antibody with depression and anxiety in patients with connective tissue diseases: an observational, single-centre, cross-sectional study.

To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs). Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616~0.874, p<0.001 and OR=0.684, 95% CI: 0.559~0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978~10.032, p<0.001 and OR=4.075, 95% CI: 2.073~8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

No evidence of increased anti-M3 muscarinic acetylcholine receptor autoantibodies in SSA-positive connective tissue disease patients.

Anti-muscarinic type 3 receptor autoantibodies (M3R) and anti-SSA antibodies are both related to salivary secretion. The presence of M3R antibodies in Sjögren's syndrome is previously demonstrated; nevertheless, the relationship between the anti-SSA antibodies and M3R fragment antibodies, namely the N terminal, first, second, and third extracellular loops, remains to be elucidated. In this study, we analyzed the antibodies against the M3R epitopes in healthy controls and anti-SSA antibody-positive connective tissue disease patients through ELISA method. Antibodies against the first, second, and third extracellular loop (M3R211-230 ) were not increased in anti-SSA positive patients compared to healthy controls. Indeed, antibodies against the N terminal (M3R1-33 ) were found to be high in healthy controls. High levels of M3R1-33 in healthy controls are a novel original finding; further research is needed for the clinical significance. There is no significant difference between SSA-positive patients and healthy controls in terms of autoantibodies against the remainder of the linear M3R fragments.

Temporal Progression of Aortic Valve Pathogenesis in a Mouse Model of Osteogenesis Imperfecta.

Organization of extracellular matrix (ECM) components, including collagens, proteoglycans, and elastin, is essential for maintaining the structure and function of heart valves throughout life. Mutations in ECM genes cause connective tissue disorders, including Osteogenesis Imperfecta (OI), and progressive debilitating heart valve dysfunction is common in these patients. Despite this, effective treatment options are limited to end-stage interventions. Mice with a homozygous frameshift mutation in col1a2 serve as a murine model of OI (oim/oim), and therefore, they were used in this study to examine the pathobiology of aortic valve (AoV) disease in this patient population at structural, functional, and molecular levels. Temporal echocardiography of oim/oim mice revealed AoV dysfunction by the late stages of disease in 12-month-old mice. However, structural and proteomic changes were apparent much earlier, at 3 months of age, and were associated with disturbances in ECM homeostasis primarily related to collagen and proteoglycan abnormalities and disorganization. Together, findings from this study provide insights into the underpinnings of late onset AoV dysfunction in connective tissue disease patients that can be used for the development of mechanistic-based therapies administered early to halt progression, thereby avoiding late-stage surgical intervention.

The Possible Relation of Demodex and Facial Erythema in Connective Tissue Diseases.

We aimed to investigate the frequency of Demodex infestation and clinical implications in connective tissue disease patients with facial erythema. Patients diagnosed with a connective tissue disease and had facial erythema were consecutively enrolled in the study from 2019-2020. An age and gender matched control group was formed from healthy volunteers. Presence of Demodex was investigated by standardized skin surface biopsy. Number of Demodex mites over 5 per centimeter square was considered meaningful for infestation. Topical or systemic metronidazole treatment was given to the connective tissue disease patients with Demodex infestation. Facial erythema visual analog scale was questioned in patients at treatment onset and one month after. A total of 31 connective tissue disease patients with facial erythema were enrolled. Control group included 31 healthy volunteers. Demographics and comorbidities were similar between groups. Demodex infestation was present in 58.1% of the disease group and in 25.8% of the control group (P=0.01). Pruritus was the most common symptom in patients with infestation. Median (IQR) facial erythema visual analog scale score was 6 (3) at treatment onset and was 2 (2.5) one month later (P<0.001). When evaluating facial cutaneous lesions, Demodex infestation should not be overlooked in a patient group like connective tissue diseases with dysfunctional immune system.

Retrospective cohort study of pulmonary arterial hypertension associated with connective tissue disease effect on patients' prognosis.

The objectives of this study are to clarify clinical characteristics and recognize prognostic factors of CTD-PAH patients. A retrospective cohort study of consecutive patients with documented CTD-PAH diagnosis from Jan 2014 to Dec 2019 was conducted, the ones who have other comorbid conditions that cause PH were excluded. Survival functions were plotted using the Kaplan-Meier method. Univariable and multivariable Cox regression analysis was applied to determine the survival-related factors. In 144 patients with CTD-PAH analyzed, the median sPAP value was 52.5 (44.0, 71.0) mmHg, the overall targeted drug usage rate was 55.6%, and only 27.5% patients were given combination. Twenty-four non-PAH-CTD patients with sPAP value were included as the control group. Compared with non-PAH-CTD groups, CTD-PAH patients had worse cardiac function, higher NT-pro BNP and γ-globulin level, and lower PaCO2 level. Compared with the mild PAH group, the moderate-severe PAH group had worse cardiac function; increased Hb, HCT, and NP-pro BNP level; and decreased PaO2. Kaplan-Meier analysis showed significant difference for survival among non-PAH-CTD, mild CTD-PAH, and moderate-severe CTD-PAH groups. The univariate analyses showed that Hb, pH, and Ln (NT-pro BNP) were identified as factors significantly associated with survival, and Hb and pH showed significant association with risk of death in the multivariate model. Kaplan-Meier analysis also showed that Hb > 109.0 g/L and pH > 7.457 affected CTD-PAH patients' survival significantly. PAH is not rare in CTDs patients; PAH affects CTD patients' prognosis significantly. Higher Hb and pH were associated with an increased risk of death. Key Points • Pulmonary arterial hypertension affects connective tissue disease patients' prognosis significantly. • The significantly factors associated with survival is hemoglobin, pH, and Ln (NT-pro BNP).

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

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. 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. 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 β 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. 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.

A meta-analysis of the clinical significance of neutrophil-to-lymphocyte ratios in interstitial lung disease.

Interstitial lung disease (ILD) is a group of diffuse parenchymal infiltrating diseases of different etiologies. The neutrophil-to-lymphocyte ratio (NLR) can reflect ILD's existence, progression, and prognosis and is currently regarded as a promising biological marker. This meta-analysis assessed elevated NLR levels in ILD for their predictive value. From inception to July 27, 2022, the Scopus, Cochrane Library, Web of Science, Embase, and PubMed databases were checked thoroughly. We used the weighted mean difference (WMD) and 95% confidence interval (CI) to compare blood NLR values between groups. We examined the relationship between poor prognoses and elevated NLR concentrations in ILD patients using odds ratios (ORs) and 95% CI. After initially including 443 studies, 24 were ultimately analyzed. Fifteen studies(ILD:n = 2,912, Non-ILD: n = 2,868) revealed that the NLR values in the ILD group were relatively high (WMD = 0.61, 95% CI 0.43-0.79, p = 0.001). Eight articles (with poor prognoses: n = 407, without poor prognoses: n = 340) indicated that ILD patients with poor prognoses had higher NLR values (WMD = 1.33, 95% CI 0.32-2.33, p = 0.01). This distinction was especially noticeable in patients with the connective tissue disease (CTD)associated with ILD subgroup (WMD = 3.53, 95% CI 1.54-5.51, p = 0.0005). The pooled OR for increased NLR levels forecasting poor prognoses of ILD was 1.09 (95% CI 1.03-1.15, p = 0.0008). Increasing blood NLR values have clinical significance and application value for detecting ILD and predicting its poor prognosis, especially in CTD patients.

Clinical features and prognosis of lung cancer in patients with connective tissue diseases: a retrospective cohort study.

Studies have demonstrated a close association between connective tissue diseases (CTDs) and lung cancer (LC). Evidence supports that poor survival may be associated with the presence of CTDs in patients with LC. This retrospective cohort study investigated 29 patients with LC with CTDs, and 116 patients with LC without CTDs were enrolled as case-matched control cohorts. Medical records, therapeutic efficacy of cancer, and outcomes were analyzed. The median duration from the diagnosis of CTDs to LC was 17 years. The Eastern Cooperative Oncology Group (ECOG) performance score for LC-CTD patients was worse than that for matched non-CTD LC patients. The median progression-free survival (mPFS) and overall survival (mOS) of first-line chemotherapy did not differ between patients with lung adenocarcinoma (AC) with and without CTDs. A significant difference was observed in mPFS [4 months vs. 17 months; hazard ratio (HR), 9.987; p = 0.004] and mOS (6 months vs. 35 months; HR, 26.009; p < 0.001) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment between patients with AC with and without CTDs. The presence of CTD, sex, ECOG performance status, and tumor-node-metastasis clinical stage were the independent prognostic factors in all patients with non-small cell LC (NSCLC). ECOG performance status was determined to be an independent prognostic factor in patients with LC-CTD. In patients with NSCLC with CTD (n = 26), sex (male) and worse ECOG score were the independent poor prognostic factors. CTDs were associated with poor survival in patients with LC. The therapeutic efficacy of first-line EGFR-TKI therapy was significantly worse in patients with lung AC with CTDs than in those without CTDs. ECOG performance status was determined as an independent prognostic factor for patients with LC and CTDs.

Real-life drug retention rate and safety of rituximab when treating rheumatic diseases: a single-centre Swiss retrospective cohort study

BackgroundIn Switzerland, rituximab (RTX) is licenced for the treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) but is frequently used off-label to treat other auto-immune diseases (AID), especially connective tissue diseases (CTD). We aimed to characterise the use of RTX in AID in a real-life Swiss setting and compare RTX retention rates and safety outcomes between patients treated for RA, CTD and AAV.MethodsA retrospective cohort study of patients who started RTX in the Rheumatology Department for RA or AID. The RTX retention rate was analysed using Kaplan–Meier survival curves. Occurrences of serious adverse events (SAE), low IgG levels and anti-drug antibodies (ADA) were reported.ResultsTwo hundred three patients were treated with RTX: 51.7% had RA, 29.6% CTD, 9.9% vasculitis and 8.9% other AIDs. The total observation time was 665 patient-years. RTX retention probability at 2 years (95%CI) was similar for RA and CTD 0.65 (0.55 to 0.73), 0.60 (0.47 to 0.72) and lower for vasculitis 0.25 (0.09 to 0.45). Survival curves for RTX retention matched closely (p = 0.97) between RA and CTD patients but were lower for patients with vasculitis due to a higher percentage of induced remission. Patients with vasculitis (95%) and CTD (75%) had a higher rate of concomitant glucocorticoid use than RA (60%). Moderate to severe hypogammaglobulinaemia was observed more frequently in patients with vasculitis (35%) than with RA (13%) or CTD (9%) and was associated with an increased risk of presenting a first infectious SAE (HR 2.01, 95% CI 1.04 to 3.91). The incidence rate of SAE was 23.3 SAE/100 patient-years (36% were infectious). When searched, ADAs were observed in 18% of the patients and were detected in 63% of infusions-related SAE. 10 patients died during RTX treatment and up to 12 months after the last RTX infusion, 50% from infection.ConclusionRTX retention rates are similar for patients with RA and CTD but lower for those with vasculitis due to more frequent remission. Patients treated with RTX for vasculitis present more SAE and infectious SAE than patients with RA and CTD, potentially due to a higher use of concomitant glucocorticoids and the occurrence of hypogammaglobulinaemia.

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 mortality in patients. Although International Heart and Lung Transplant Society (ISHLT) suggested that ILD and PH related to CTD are rare indications for lung transplantation(LTx) in 2006, many LTx centers are concerned that the multi-system involvement of CTD will affect the survival outcome after lung transplantation, and CTD is regarded as a relative contraindication for LTx. However，long-term and short-term survival after LTx in CTD patients is similar to that in common indications for LTx such as idiopathic pulmonary fibrosis(IPF)，and no higher complications after transplantation in many lung transplant centers. This suggests that LTx may be beneficial for CTD patients who progress to end-stage lung disease, and CTD patients should not be considered a contraindication to LTx. In the future, more prospective studies are needed to analyze the risk factors of LTx in CTD patients to improve survival and reduce the risk of complications. This narrative review summarizes the selection and evaluation of candidates for CTD before LTx, and describes the clinical outcome of CTD after LTx in large-capacity lung transplantation center, the purpose is to help rheumatologists decide when to refer patients with CTD lung involvement to an LTx center and the conditions to consider before transplantation, and to provide confidence to lung transplant experts. This article is protected by copyright. All rights reserved.

Clinical Presentation of Connective Tissue Disease Patients with and without Interstitial Lung Disease: A Retrospective Study

Background: Connective tissue diseases (CTDs) are responsible for about 20% of interstitial lung disease (ILD) cases, but their diagnosis in a pulmonary unit (PU) is not always straightforward due to a heterogeneous clinical picture. Objectives: The aim of this study was to evaluate the clinical presentation of rheumatoid arthritis (RA) and CTD-ILD cases diagnosed in PU, compared to RA and CTD patients diagnosed in a rheumatologic unit (RU). Methods: Patients with RA, systemic sclerosis (SSc), primary Sjӧgren’s syndrome (pSS), and idiopathic inflammatory myopathy were retrospectively enrolled from an RU and a PU designated to manage ILD during a period from January 2017 to October 2022. The classification of CTD-PU was carried out in a multidisciplinary setting, including the same rheumatologists that diagnosed CTD in the RU. Results: ILD-CTD-PU patients were prevalently male and older. Progression from undifferentiated CTD to a specific condition was more common in ILD-CTD-PU, and those patients generally obtained a lower score on specific classification criteria. RA-PU patients resembled polymyalgia rheumatica in 47.6% of cases, also showing a greater proportion of typical joint deformities (p = 0.02). SSc-PU patients showed a usual interstitial pneumonia pattern in 76% of cases and, compared with SSc-RU, were more commonly seronegative (p = 0.03) and generally lacked fingertip lesions (p = 0.02). The majority of the diagnoses of pSS-PU were in patients with previously diagnosed ILD, in which seropositivity and sicca syndrome developed during follow-up. Conclusions: CTD-ILD patients diagnosed in the PU show severe lung involvement and a nuanced autoimmune clinical picture.

Acute Outcomes of Cardiac Operations in Patients With Autoimmune Disorders: A National Analysis.

Accelerated atherosclerosis, inflammation, and valve pathology are known complications of autoimmune connective tissue diseases (AID). However, outcomes of coronary artery bypass graft surgery (CABG) or valve operations among these patients remain underexamined. All adult hospitalizations for elective CABG or valve procedures were identified from the 2010-2019 Nationwide Readmissions Database. Autoimmune connective tissue disease was defined to include systemic lupus erythematosus (SLE), antiphospholipid syndrome (APLS), polymyalgia rheumatica (PMR), and other autoimmune AIDs. Entropy balancing was applied to generate balanced patient cohorts. Multivariable regression models were constructed to assess the independent associations between AID and outcomes of interest. Of ∼1 652 573 patients, 21 019 (1.3%) had AID (23.7% SLE, 17.2% APLS, 29.5% PMR, and 29.6% other). Autoimmune connective tissue disease patients were more frequently female (60.8 vs 33.1%, P < .001) and insured by Medicare (71.4 vs 62.2%, P < .001) and presented with a higher comorbidity index (5.2 ± 1.8 vs 4.1 ± 1.8, P < .001). Further, AID less frequently underwent isolated CABG (39.0 vs 52.3%) but more commonly isolated valve operations (41.9% vs 31.0%, P < .001), relative to non-AID. Following risk-adjustment, AID was not linked with increased odds of mortality or cardiac complications. However, AID was linked with a greater risk of thrombotic complications, blood transfusion, and non-elective readmission within 30days, as well as a +$900 decrement in hospitalization costs. Autoimmune connective tissue disease patients demonstrated acceptable outcomes following CABG and valve procedures. However, novel prophylactic care pathways should be developed and instituted to address greater thrombotic and blood transfusion risk. Further investigation is needed to identify factors contributing to greater non-elective readmissions among these patients.

Mean pulmonary artery pressure estimated by echocardiogram rapidly exceeds 20mmHg from the normal range in patients with connective tissue disease.

Earlier intervention for pulmonary hypertension (PH) has been reported to improve the prognosis of patients with connective tissue disease (CTD). However, it is not fully elucidated how rapidly PH develops in patients showing normal mean pulmonary arterial pressure (mPAP) at the index investigation. We evaluated 191 CTD patients with normal mPAP retrospectively. The mPAP was estimated by the formerly defined method employing echocardiography (mPAPecho). We investigated predictive factors that predict increasing mPAPecho at follow-up transthoracic echocardiography (TTE) using uni- and multi variable analysis. The mean age was 61.5years old, and 160 patients were female. The percentage of patients in whom mPAPecho exceeded 20mmHg at follow-up TTE was 38%. Multivariable analysis revealed that acceleration time/ejection time (AcT/ET) measured at the right ventricular outflow tract at initial TTE was independently associated with the consequent increase of mPAPecho at the follow-up TTE. When using 0.43 of best cutoff value in AcT/ET calculated by receiver operating characteristic analysis, the change in mPAPecho in patients with low AcT/ET was significantly higher than in those with high AcT/ET (3.05mmHg in patients with AcT/ET < 0.43 and 1.00mmHg in patients with AcT/ET ≥ 0.43, p < 0.001). Thirty-eight percent of CTD patients who show the normal estimated mPAP by TTE develop gradual elevation of mPAP to the level to consider early intervention within 2years. AcT/ET at initial TTE can predict increasing mPAP at follow-up TTE.

Can transbronchial lung cryobiopsy benefit adaptive treatment strategies in connective tissue disease-associated interstitial lung disease?

BackgroundSome patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) progress to pulmonary fibrosis over their disease course despite initial improvement, potentially indicating a poor prognosis. Transbronchial lung cryobiopsy (TBLC) is a new bioptic approach used in diffuse parenchymal lung diseases. This study of CTD-ILD assessed the utility of TBLC in determining therapeutic decision-making strategies.MethodsWe analyzed medical records of 31 consecutive CTD-ILD patients who underwent TBLC focusing on radio-pathological correlation and disease course. A TBLC-based usual interstitial pneumonia (UIP) score was used that assessed three morphologic descriptors: i) patchy fibrosis, ii) fibroblastic foci, and iii) honeycombing.ResultsAmong the patients with CTD-ILD, 3 had rheumatoid arthritis, 2 systemic sclerosis, 5 polymyositis/dermatomyositis, 8 anti-synthetase syndrome, 6 Sjögren’s syndrome, and 5 had microscopic polyangiitis. Pulmonary function test results showed a mean %FVC of 82.4% and %DLCO of 67.7%. Among the 10 CTD patients and TBLC-proven pathological UIP, 3 patients had prominent inflammatory cells in addition to a framework of UIP, and pulmonary function of most patients improved with anti-inflammatory agents. Six (40%) of 15 patients with TBLC-based UIP score ≥ 1 had a progressive disease course during follow-up, of whom 4 patients received anti-fibrotic agents.ConclusionsTBLC in patients with CTD-ILD can help determine an appropriate medication strategy, particularly when UIP-like lesions are present. TBLC may be useful when judging which agents to prioritize, anti-inflammatory or anti-fibrotic, is difficult. Moreover, additional information from TBLC may be beneficial when considering early intervention with anti-fibrotic agents in clinical practice.

Pneumoconiosis combined with connective tissue disease in China: a cross-sectional study

ObjectiveTo describe the prevalence, clinical features and potential risk factors of pneumoconiosis in combination with connective tissue disease (CTD) or positive autoantibodies.DesignCross-sectional study.SettingA retrospective study of adults recruited in China...

Supporting the differential diagnosis of connective tissue diseases with neurological involvement by blood and cerebrospinal fluid flow cytometry

ObjectiveNeurological manifestations of autoimmune connective tissue diseases (CTD) are poorly understood and difficult to diagnose. We here aimed to address this shortcoming by studying immune cell compositions in CTD patients with and without neurological manifestation.MethodsUsing flow cytometry, we retrospectively investigated paired cerebrospinal fluid (CSF) and blood samples of 28 CTD patients without neurological manifestation, 38 CTD patients with neurological manifestation (N-CTD), 38 non-inflammatory controls, and 38 multiple sclerosis (MS) patients, a paradigmatic primary neuroinflammatory disease.ResultsWe detected an expansion of plasma cells in the blood of both N-CTD and CTD compared to non-inflammatory controls and MS. Blood plasma cells alone distinguished the clinically similar entities N-CTD and MS with high discriminatory performance (AUC: 0.81). Classical blood monocytes indicated higher disease activity in systemic lupus erythematosus (SLE) patients. Surprisingly, immune cells in the CSF did not differ significantly between N-CTD and CTD, while CD4+ T cells and the CD4+/CD8+ ratio were elevated in the blood of N-CTD compared to CTD. Several B cell-associated parameters partially overlapped in the CSF in MS and N-CTD. We built a machine learning model that distinguished N-CTD from MS with high discriminatory power using either blood or CSF.ConclusionWe here find that blood flow cytometry alone surprisingly suffices to distinguish CTD with neurological manifestations from clinically similar entities, suggesting that a rapid blood test could support clinicians in the differential diagnosis of N-CTD.