Electrocardiogram and heart rate variability assessment in patients with common autoimmune diseases: a methodological review.

The aim of this article was to summarize current knowledge about the potential clinical utility of electrocardiogram (ECG) and heart rate variability (HRV) measures in patients with 4 common autoimmune diseases (ADs): rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behcet's disease (BD), and systemic sclerosis (SSc). A search was conducted of the PubMed, Embase, and Scopus databases using terms and a controlled vocabulary associated with these ADs, ECG, and HRV. The available, full-text articles published in English were considered. In all, 20 publications that examined the direct effect of these diseases on the heart were selected according to a systematic review protocol. Time-frequency domain analysis revealed that HRV parameters were lower in patients with the selected ADs in comparison with control groups. An increased QT dispersion and heart rate corrected QT, which are well-known as risk factors for sudden cardiac death, were observed in the patient group. In some studies, a correlation was seen between the duration of the disease and its activity, while others did not report such an association. Heart rate turbulence parameters were also examined. Turbulence onset was increased in SLE and SSc patients, while the turbulence slope was decreased in SLE patients. There was no significant change in these parameters in BD patients. Patients with ADs demonstrate abnormal HRV and ECG parameters, which indicates an autonomic cardiac functional impairment. Measurement of these parameters can be a useful clinical tool in the diagnosis and prediction of some disorders in patients with ADs. Both of these signals can provide helpful information for physicians to trace the efficacy of prescribed medicines.

Assessment of the quality of life of Egyptian and Tunisian autoimmune bullous diseases' patients using an Arabic version of the autoimmune bullous disease quality of life and the treatment of autoimmune bullous disease quality of life questionnaires.

BACKGROUND: The Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires proved to be reliable tools that measure the disease and treatment burden. OBJECTIVES: We aimed to assess the ABQOL and TABQOL in the Arabic population. METHODS: The English questionnaires were translated into the Arabic language by a certified translation agency. Eighty autoimmune bullous disease (AIBD) patients were included in this study. Patients were asked to answer 2 questionnaires. After 1 week the same patients were asked to answer the same questionnaires again. RESULTS: The age of the patients ranged from 19 to 81 years (mean=46), 19 males, 61 females. The ABQOL ranged from 0-37 (mean=16.4±9.2). The TABQOL ranged from 2-43 (mean=21.5±9.4). Test-retest reliability was acceptable, Cronbach's alpha was 0.76 for ABQOL and 0.74 for TABQOL. There was no significant correlation between the age of the patients and ABQOL, r =-0.2, p value was 0.183. There was a significant negative correlation between the age of the patients and the TABQOL, r=-0.2, p value was 0.039. There was a significant negative correlation between the education of the patients and the TABQOL, r=-0.3, p value was 0.007. STUDY LIMITATIONS: Small sample size of some AIBDs and patients with severe disease. CONCLUSION: Objective and valuable measurements such as ABQOL and TABQOL are now available to help physicians understand their patient's distress and should be used in every patient with AIBD. Younger and less educated patients appear to have more effects on their QOL from the treatments.

Assessment of the quality of life of Egyptian and Tunisian autoimmune bullous diseases' patients using an Arabic version of the autoimmune bullous disease quality of life and the treatment of autoimmune bullous disease quality of life questionnaires

Abstract: Background: The Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires proved to be reliable tools that measure the disease and treatment burden. Objectives: We aimed to assess the ABQOL and TABQOL in the Arabic population. Methods: The English questionnaires were translated into the Arabic language by a certified translation agency. Eighty autoimmune bullous disease (AIBD) patients were included in this study. Patients were asked to answer 2 questionnaires. After 1 week the same patients were asked to answer the same questionnaires again. Results: The age of the patients ranged from 19 to 81 years (mean=46), 19 males, 61 females. The ABQOL ranged from 0-37 (mean=16.4±9.2). The TABQOL ranged from 2-43 (mean=21.5±9.4). Test-retest reliability was acceptable, Cronbach's alpha was 0.76 for ABQOL and 0.74 for TABQOL. There was no significant correlation between the age of the patients and ABQOL, r =-0.2, p value was 0.183. There was a significant negative correlation between the age of the patients and the TABQOL, r=-0.2, p value was 0.039. There was a significant negative correlation between the education of the patients and the TABQOL, r=-0.3, p value was 0.007. Study limitations: Small sample size of some AIBDs and patients with severe disease. Conclusion: Objective and valuable measurements such as ABQOL and TABQOL are now available to help physicians understand their patient's distress and should be used in every patient with AIBD. Younger and less educated patients appear to have more effects on their QOL from the treatments.

Association between inactivated influenza vaccine and primary care consultations for autoimmune rheumatic disease flares: a self-controlled case series study using data from the Clinical Practice Research Datalink.

ObjectivesTo examine the association between inactivated influenza vaccine (IIV) administration and primary care consultation for joint pain, rheumatoid arthritis (RA) flare, corticosteroid prescription, vasculitis and unexplained fever in people with autoimmune rheumatic diseases (AIRDs). METHODS: We undertook within-person comparisons using self-controlled case-series methodology. AIRD cases who received the IIV and had an outcome of interest in the same influenza cycle were ascertained in Clinical Practice Research Datalink. The influenza cycle was partitioned into exposure periods (1-14 days prevaccination and 0-14, 15-30, 31-60 and 61-90 days postvaccination), with the remaining time-period classified as non-exposed. Incidence rate ratios (IRR) and 95% CI for different outcomes were calculated. RESULTS: Data for 14 928 AIRD cases (69% women, 80% with RA) were included. There was no evidence for association between vaccination and primary care consultation for RA flare, corticosteroid prescription, fever or vasculitis. On the contrary, vaccination associated with reduced primary care consultation for joint pain in the subsequent 90 days (IRR 0.91 (95% CI 0.87 to 0.94)). CONCLUSION: This study found no evidence for a significant association between vaccination and primary care consultation for most surrogates of increased disease activity or vaccine adverse-effects in people with AIRDs. It adds to the accumulating evidence to support influenza vaccination in AIRDs.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

Rasch analysis suggests that health assessment questionnaire II is a generic measure of physical functioning for rheumatic diseases: a cross-sectional study.

BACKGROUND: Versions of the Health Assessment Questionnaire (HAQ) are commonly used to measure physical functioning across multiple rheumatic diseases but there has been no clear demonstration that any HAQ version is actually generic. This study aimed to show that the HAQ-II instrument is invariant across different rheumatic disease categories using the Rasch measurement model, which would confirm that the instrument is generic. METHODS: HAQ-II responses from 882 consecutive rheumatology clinic attendees were fitted to a Rasch model. Invariance across disease was assessed by analysis of variance of residuals implemented in RUMM2030. Rasch modeled HAQ-II scores across disease categories were compared and the mathematical relationship between raw HAQ-II scores and Rasch modeled scores was also determined. RESULTS: The HAQ-II responses fitted the Rasch model. There was no substantive evidence for lack of invariance by disease category except for a single item ("opening car doors"). Rasch modeled scores could be accurately obtained from raw scores with a cubic formula (R2 0.99). Patients with rheumatoid arthritis had more disability than patients with other kinds of inflammatory arthritis or autoimmune connective tissue disease. CONCLUSIONS: The HAQ-II can be used across different rheumatic diseases and scores can be similarly interpreted from patients with different diseases. Transforming raw scores to Rasch modeled scores enable a strictly linear, interval scale to be used. It remains to be seen how that would affect interpretation of change scores. TRIAL REGISTRATION: ANZCTR ACTRN12617001500347 . Registered 24th October 2017 (retrospectively registered).

What we do and do not know about women and kidney diseases - questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day.

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Indirect costs of absenteeism due to rheumatoid arthritis, psoriasis, multiple sclerosis, insulin-dependent diabetes mellitus, and ulcerative colitis in 2012: a study based on real-life data from the Social Insurance Institution in Poland.

INTRODUCTION: The aim of this study is to assess the indirect costs of six major autoimmune diseases including seropositive rheumatoid arthritis, other types of rheumatoid arthritis, psoriasis, multiple sclerosis, Type 1 diabetes, and ulcerative colitis. METHODS: Relevant data for 2012 on sick leave and short- and long-term work disabilities were obtained from the Social Insurance Institution in Poland. Indirect costs were estimated using the human capital approach based on gross domestic product per capita, gross value added per worker, and gross income per worker in Poland in 2012 and expressed in euro. RESULTS: We recorded data on the total number of 45,500 patients. The total indirect costs were EUR 146,862,569; 353,683,508; and 108,154,271, calculated using gross domestic product, gross value added, and gross income, respectively. CONCLUSIONS: Considering only data on absenteeism collected by the Social Insurance Institution in Poland, we can conclude that the selected autoimmune diseases are associated with great indirect costs.

Cardiovascular and autoimmune diseases in females: The role of microvasculature and dysfunctional endothelium.

Cardiovascular (CV) diseases are becoming increasingly frequent and associated with a high incidence of CV events, disability and death. It is known that there is a relationship between CV burden and systemic autoimmune diseases (SADs) that is mainly due to inflammation and autoimmunity, but the other mechanisms underlying the high CV risk of SAD patients have not yet been fully clarified. The aim of this review article is to discuss some of the specific factors associated with the accelerated atherosclerosis (ATS) characterising SADs (female sex, the microcirculation and the endothelium) in order to highlight the importance of an early diagnosis and the prompt implementation of preventive measures, as well as the possible role of new therapeutic strategies such as vaccine immunomodulation. Finally, as the natural history of ATS begins with endothelial injury (a potentially reversible process that is influenced by various factors) and microvascular damage plays a central role in the etiopathogenesis of SADs, it underlines the crucial need for the development of reliable means of detecting sub-clinical abnormalities in the microcirculation, particularly coronary microcirculation dysfunction.

[Pathophysiology and Assessment of IgG4-Related Disease--Focus on Autoimmune Pancreatitis].

IgG4-related disease is well-known, and while the functions of cytokines which affect IgG4 production are being clarified, it remains unclear what causes it. There are many clinicopathological characteristics of IgG4-related disease and, therefore, comprehensive criteria are used for diagnosis. Notably, histopathological findings are the most important of these, with which we cannot make a definite diagnosis. The model disease of an IgG4-related disease is autoimmune pancreatitis (AIP). Currently, AIP is classified into type 1 (AIP1) and type 2 (AIP2). AIP1 is IgG4-related while AIP2 is not. AIP1 sometimes has localized mass formation, making it difficult to distinguish between AIP1 and pancreatic cancer. Thus, upon biochemical and immunological examination, the IgG4 level is the most useful for the diagnosis, although the levels of IL-2R, ß2MG, C4, and monoclonal rheumatoid factor are also useful for the assessment of disease. In addition, histopathological findings are also important to diagnose AIP1. Typical AIP1 cases show lymphoplasmacytic infiltration including IgG4-positive plasma cells with storiform fibrosis. A careful analysis of cases with the typical features of IgG4-related disease will lead to the elucidation of the mechanism behind IgG4-related disease.

Noninvasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse.

Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.

Cardiac and muscular involvement in idiopathic inflammatory myopathies: noninvasive diagnostic assessment and the role of cardiovascular and skeletal magnetic resonance imaging.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune diseases and include dermatomyositis, polymyositis, necrotizing myopathy and inclusion body myositis; they are characterized by inflammation of skeletal muscle and other internal organs and may potentially lead to irreversible damage and death. Only a small percentage of IIM has clinically overt cardiac disease; however, heart involvement is one of the leading causes of death and therefore, early detection remains a challenge. Biochemical markers and non-invasive methods such as the electrocardiogram and echocardiography have a role in diagnosis, but lack sensitivity in identifying patients with early, sublinical cardiac abnormalities. Endomyocardial and skeletal muscle biopsies are very useful, but invasive techniques and cannot be used for routine follow-up. Cardiac and skeletal magnetic resonance imaging, due to their capability to perform tissue characterization, has emerged as novel techniques for the early detection and follow-up of myocardial and skeletal muscle tissue changes (oedema, inflammation, fibrosis) in IIM. However, the clinical implications of using these approaches and their cost /benefit ratio require further evaluation.

Constitutive antiviral immunity at the expense of autoimmunity.

In this issue of Immunity, Funabiki et al. (2014) have identified in mice a mutation of the IFIH1 gene, encoding the viral receptor MDA5 that causes constitutive IFN production and fatal autoimmune disease. The authors show that the autoimmune disease-associated variant of human MDA5 is permanently switched on.

[Assessment of endothelial function in autoimmune diseases]. / Évaluation de la fonction endothéliale au cours des maladies auto-immunes.

Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases.

Transforming women's oral-systemic health through discovery, development and delivery.

Due to the complexity of women's health issues that involve the interplay between oral and systemic health, a multidisciplinary approach to research and practice is critical to ensure health and quality of life among women across the lifespan. The 2nd Annual Conference entitled 'Transforming Women's Health: Discovery, Development and Delivery of the Oral-Systemic Connection', was held in Tampa (FL, USA) on 26-27 January 2013. The conference addressed complex oral-systemic women's health issues structured by three organizational pillars: discovery, development and delivery, with overarching topic areas of oral human papillomavirus infection, autoimmune conditions and the Affordable Care Act. This conference served as an effective method for bringing together multiple disciplines to discuss emerging women's health issues.

Delivering on George Eisenbarth's visionary pursuit of understanding pathogenesis and prevention of type 1 diabetes.

George Eisenbarth's pioneering and visionary research has provided a critical foundation that will be built on in the years ahead as we progress toward prevention of type 1 diabetes. His almost 30-year old model that type 1 diabetes was a chronic and predictable autoimmune disease with multiple identifiable progressive stages with a potential for interventions to prevent progression to symptomatic diabetes has stood the test of time. To deliver on the Eisenbarth vision and his "unfinished journey," the field needs: (1) to improve detection of risk of type 1 diabetes, (2) to improve staging and prediction of progression, (3) to perform smaller, shorter, practical, and an increased number of prevention clinical trials, and (4) to increase awareness of the potential for risk detection, staging, and prevention of type 1 diabetes and benefit/risk of prevention.

Multiparametric assessment of vascular function and atherosclerosis in patients with autoimmune gastritis: a comparative study.

BACKGROUND/AIMS: Patients with autoimmune gastritis might have accelerated atherosclerosis due to autoimmunity and chronic inflammation. Endothelial dysfunction often precedes manifest atherosclerosis. The aim of the present study was to evaluate the risk factors of early atherosclerosis by using several different techniques. METHODS: A total of 99 patients with autoimmune gastritis were compared to 42 healthy age sex-matched subjects. Patients with a known risk factor for atherosclerosis were excluded. Intima-media thickness of the common carotid artery, pulse wave velocity and flow-mediated dilation of brachial artery were measured. Clinical data and laboratory parameters (serum gastrin, antiparietal cell antibody, anti-Hp IgG, serum vitamin B(12) and lipid profile) were also determined. RESULTS: Intima-media thickness (mm) of the carotid artery was significantly higher in autoimmune gastritis (0.062 ± 0.031 vs. 0.042 ± 0.007, P < 0.001) than in healthy individuals. Flow-mediated dilation was significantly lower in patients with autoimmune gastritis compared to control group (13.91 ± 6.68% vs. 20.37 ± 7.80%, P = 0.021) and there was a significant increase in pulse wave velocity (m/s) in autoimmune gastritis patients compared to controls (9.25 ± 3.42 vs. 6.40 ± 0.91, P = 0.001). Antiparietal cell antibody positivity (P = 0.05), low vitamin B(12) level (P = 0.05), and age (P = 0.002) were the predictors of high pulse wave velocity (>14 m/s). CONCLUSION: Patients with autoimmune gastritis may have an increased risk for the development of early atherosclerosis. As early preventive treatment for accelerated atherosclerosis is available, it is important to detect those patients with autoimmune gastritis who would benefit from such treatment.

Clinical characteristics of 327 Asian patients with autoimmune pancreatitis based on Asian diagnostic criteria.

OBJECTIVES: To clarify the clinical and pathophysiological characteristics of autoimmune pancreatitis (AIP) in Asia. METHODS: A retrospective, actual situation survey of AIP diagnosed by Asian criteria was conducted in 10 centers of Japan, Korea, Taiwan, China, and India. RESULTS: A total of 327 AIP cases (258 male and 69 female subjects; average age, 60.0 years) were enrolled. Obstructive jaundice was the most frequent initial symptom (46%-74%), followed by weight loss (4%-51%) and abdominal pain (19%-44%). Diffuse swelling of the pancreas was frequent in Japan (64%) and Korea (81%), but segmental swelling of the pancreas was more frequent in Taiwan (70%) and China (72%) (P < 0.01). Serum immunoglobulin G4 levels were elevated in 58%-100% of cases in Japan, Korea, and Taiwan. Pathologically, almost all AIPs in Asia were lymphoplasmacytic sclerosing pancreatitis. Sclerosing cholangitis was the most frequent extrapancreatic lesion (60%-81%). Steroid therapy was a major and effective therapeutic strategy in Japan, Korea, and Taiwan. However, the rate of resection or bypass operation was higher in Taiwan (40%) and China (72%) (P < 0.01). CONCLUSIONS: Features of AIP are fundamentally similar in Japan, Korea, Taiwan, and China. Knowledge of emerging AIP should be more widespread in Asia to avoid unnecessary operation.