Diagnosis Of Rheumatic Diseases Research Articles

Validity and reliability study of the Turkish version of SACRAH (Score for Assessment and quantification of Chronic Rheumatic Affections of the Hands)

Rheumatic diseases cause deformities in the hands and affect daily living activities. Therefore, assessment of hand disabilities is important in rheumatic disease. The aim of this study was to test the validity and reliability of the Turkish version of the A Score For Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SACRAH). A translation and back-translation of the SACRAH were performed, according to the Beaton guidelines. Patients who were between 18-65 years old, who were literate in Turkish, who had rheumatic disease diagnosis and whose hands were affected, were included in the study. Patients who were using a splint during daytime were excluded from the study. They completed the Turkish version of Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH-T) once and the final version of the SACRAH Questionnaire twice with a 7 days' interval. The internal consistency (Cronbach's α) and reliability (test-retest reliability) of the questionnaire were assessed. Besides, correlations between SACRAH and DASH-T scores were analyzed using the Spearman correlation coefficient. One hundred and twenty patients participated in the study. The Turkish version of the SACRAH met set criteria of reliability and validity. Internal consistency was excellent (Cronbach's α=0.88) and test-retest reliability were very good (r=0.73). SACRAH showed a positive and statistically significant correlation with DASH-T scores (r=0.83, p<0.001). Our results show that the Turkish version of the SACRAH has excellent test-retest reliability and validity. As a result of this study we determined that SACRAH is a valid and reliable instrument for assessing functional status and subjective manual function in Turkish-speaking patients.

P3134Variations in anterior mitral valve leaflet restriction that may lead to the erroneous diagnosis of rheumatic heart disease

Abstract Introduction Anterior mitral valve leaflet (AMVL) restriction is a prominent morphological feature of rheumatic heart disease (RHD). The World Heart Federation (WHF) criteria for echocardiographic diagnosis of RHD rely on the use of colloquial terms such as “dog-leg” to define AMVL restriction rather than a strict, reproducible definition. We recognise AMVL restriction when the tip of the leaflet is seen to point away from the interventricular septum and towards the posterior left ventricular (LV) wall at peak diastole in the parasternal long axis (PSLAX) view. This definition however risks inclusion of a finding commonly identified in our high-risk screening program (Echo in Africa- EIA) which demonstrates gradual AMVL bowing (so-called “slow-bow”) from the proximal to mid-leaflet but with free motion ('fluttering') of the tip during diastole. This is in contrast to RHD-related restriction which typically involves the distal AMVL tip only. We propose that the former is a normal variant of the AMVL and is unrelated to the RHD process, provided no concomitant morphological features of RHD are identified. Purpose Determine the prevalence of “slow-bow” AMVL restriction between two cohorts of schoolchildren with a documented high-and low-RHD prevalence. Methods Retrospective analysis of EIA data obtained from children (aged 13–18) attending two separate South African schools. The high-RHD prevalence school (HR) demonstrated a 0.8% rate of WHF “definite RHD”. The low-RHD prevalence school (LR) demonstrated no cases of WHF “definite RHD”. Cases of AMVL restriction were identified and classified according to the definitions provided above. Results A total of 941 screening studies (HR cohort n=577 /LR cohort n=364) were evaluated. 74 cases of AMVL restriction (12.82%, 95%, CI 10.34–15.80) were identified in the HR cohort of which 8 cases demonstrated AMVL-tip restriction (1.39%, 95%, CI 0.70–2.71) and 65 cases demonstrated “slow bow” (11.27%, 95%, CI 8.94–14.11). There were no cases of AMVL-tip restriction observed in the LR-cohort and 35 cases of “slow-bow”(9.62%, 95%, CI 7–13.08). A. “Slow bow”; B. “Distal tip restriction”. Conclusion Our results support the hypothesis that “slow-bow” AMVL restriction is a common variant of the AMVL amongst South African school children and unrelated to the RHD process. Further research is required to investigate the exact mechanism underlying this form of AMVL restriction. Acknowledgement/Funding Edwards Lifescience EHM grant

«Gastroenterological» rheumatology: differential diagnosis of early arthritis

In real clinical practice, rheumatologists constantly face with the problem of differential diagnosis of rheumatic (RDs) and non-rheumatic diseases, as well as various RDs with similar symptoms. Most of the RDs are multisystemic and heterogeneous in clinical symptoms, course, and outcomes. Their clinical, laboratory, and instrumental signs that could be considered as the gold standard to confirm the diagnosis are not defined in all nosological entities. Therefore, the diagnostic process, especially in early arthritis caused by systemic inflammation, is complex cognitive in nature and requires the synthesis of many data that are usually not taken into account in a simple algorithm, the basis of which is a set of classification criteria. The review presents the issues of differential diagnosis of early arthritis in gastrointestinal tract diseases, such as celiac disease, microscopic colitis, PPP syndrome, etc.

Contraception Use Among Reproductive-Age Women With Rheumatic Diseases.

To determine contraception use among a cohort of reproductive-age women (ages 18-50 years) with rheumatic diseases. We conducted a study of administrative data from a single, large medical center between the years 2013 and 2014. Women who had 1 of 21 possible rheumatic disease diagnoses and had at least 2 outpatient rheumatology visits were included in this analysis. We used logistic regression analyses to evaluate adjusted associations between the use of prescription contraception, use of potentially fetotoxic medications, and visits with rheumatologists, primary care providers, and gynecologists. Of 2,455 women in this sample, 32.1% received any prescription contraception, and 7.9% of women used highly effective prescription methods (intrauterine devices, implants, and surgical sterilization). More than 70% of women took ≥1 type of fetotoxic medication during the 2-year study timeframe. Fetotoxic medication use was not associated with overall use of prescription contraception, but was associated with the use of highly effective contraceptive methods (adjusted odds ratio [OR] 2.26 [95% confidence interval (95% CI) 1.44-3.54]). Women who saw gynecologists or primary care providers were more likely to use prescription contraception overall (adjusted OR 3.35 [95% CI 2.77-4.05] and 1.43 [95% CI 1.18-1.73], respectively). Women who saw gynecologists were more likely to use highly versus moderately effective contraceptive methods (adjusted OR 2.35 [95% CI 1.41-3.94]). Rheumatology visits were not associated with use of prescription contraception in any models. This is the largest study to date to describe contraceptive use among reproductive-age women with rheumatic diseases, and the findings reveal low use of prescription contraception. Urgent efforts are needed to improve contraceptive care and access for some women with rheumatic diseases.

Effect of anaemia on the diagnosis of rheumatic heart disease using World Heart Federation criteria

There is overlap between pathological mitral regurgitation seen in borderline rheumatic heart disease using World Heart Federation echocardiography criteria and physiologic regurgitation found in normal children. One possible contributing factor is higher rates of anaemia in endemic countries. To investigate the contribution of anaemia as a potential confounder in the diagnosis of rheumatic heart disease detected in echocardiographic screening. A novel Server 2012 data warehouse tool was used to incorporate haematology and echocardiography databases. The study included a convenience sample of patients from 5 to 18 years old without structural or functional heart disease that had a haemoglobin value within 1 month prior to an echocardiogram. Echocardiogram images were reviewed to determine presence or absence of World Heart Federation criteria for rheumatic heart disease. The rate of rheumatic heart disease among anaemic and non-anaemic children according to gender- and age-based norms groups was compared. Of the 935 patients who met the study inclusion criteria, 406 were classified as anaemic. There was no difference in the rate of echocardiograms meeting criteria for borderline rheumatic heart disease in anaemic (2.0%, 95% CI 0.6-3.3%) and non-anaemic children (1.3%, 95% CI 0.3-2.3%). However, there was a statistically significant increase in rates of mitral regurgitation of unclear significance among anaemic versus non-anaemic patients (8.6 versus 3.6%; p = 0.0012). Anaemia does not increase the likelihood of meeting echocardiographic criteria for borderline rheumatic heart disease. Future studies should evaluate for the correlation between anaemia and mitral regurgitation in endemic settings.

Pregnancy outcomes in Icelandic female patients with inflammatory arthritides. Nationwide results from the ICEBIO and the Icelandic Medical Birth Register

We used multivariate analysis to evaluate the risk of preterm birth, Caesarean section, low Apgar score at 5-minutes and low birth weight among females with inflammatory arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) in comparison with healthy controls matched on age and parity. We also investigated pregnancies before and after the diagnosis of respective rheumatic disease and especially in respect to treatment with TNFα inhibitors (TNFi). In the end of 2016, 723 female patients were registered in ICEBIO as they had received treatment with TNFi due to inflammatory arthritis. Of those, 412 women had given birth to 801 children, whereof 597 were delivered before confirmed diagnosis of the mother and 53 were delivered after the start of the TNFi treatment. Relative risk of Caesarean section among these female with various arthritis conditions were 1.47 (95% CI: 1.19-1.82; p < 0,001) compared to controls and was highest in the group with PsA or 2.06 (1.41-3.02; p<0,001). We did not find increased risk of preterm delivery or low Apgar score. Patients with inflammatory arthritis had lower risk of children with low birth weight or 0.37 compared to healthy controls (95% CI: 0.36-0.37; p < 0.05). Due to low numbers of deliveries after the initiation of TNFi therapy (n=53) we were not able to perform any analysis for that group. Icelandic female patients with inflammatory arthritis are at an increased risk of Caesarean section in comparison to healthy controls. However, their newborns are in good condition and healthy at birth. Analysis of the impact of treatment with TNFi on pregnancy is not yet possible due to limited data.

Inter-rater and intra-rater reliability and agreement of echocardiographic diagnosis of rheumatic heart disease using the World Heart Federation evidence-based criteria

ObjectiveDifferent definitions have been used for screening for rheumatic heart disease (RHD). This led to the development of the 2012 evidence-based World Heart Federation (WHF) echocardiographic criteria. The objective of...

Task Sharing in the Diagnosis, Prevention, and Management of Rheumatic Heart Disease: A Systematic Review

BackgroundGlobally, rheumatic heart disease (RHD) is a major contributor to the burden of cardiovascular disease. Major gaps in RHD prevention and treatment have been documented at all levels of health systems in low- and middle-income countries. Task sharing is an approach that could prove effective in remediating bottlenecks in RHD-related care. ObjectivesThis study conducted a systematic review to assess the state of the evidence for the use of task sharing in the diagnosis, prevention, and management of RHD. MethodsGuided by a previously published protocol, we searched various databases using a systematic search strategy including MeSH and free-text terms for (1) group A streptococcus, acute rheumatic fever, and RHD and (2) strategies of task sharing in limited-resource settings. Two investigators independently screened the search outputs, selected the studies, extracted the data, and assessed the risk of bias, resolving discrepancies by discussion and consensus. ResultsThe publications search yielded 212 records, of which 18 articles were deemed as potentially eligible for inclusion. None of the studies, however, met with the inclusion criteria. ConclusionsThere is a lack of evidence for the use of task-sharing approaches in scaling up RHD prevention and treatment services in limited-resource settings. Considering the persistent burden of group A streptococcus, acute rheumatic fever, and RHD in low- and middle-income countries, this work highlights the urgent need to develop and test models of RHD-related care utilizing an evidence-based approach to task sharing. [Task Sharing in the Diagnosis, Prevention, and Management of Rheumatic Heart Disease: A Systematic Review; CRD42017072989].

Detection of Specific Autoantibodies in Sera with Negative Antinuclear Antibody by Indirect Immunofluorescence Assay but Positive by Enzyme Immunoassay

Objective: The aim of this study was to investigate the predictive value of positive enzyme immunoassay (EIA) for detection of specific autoantibodies in sera negative for antinuclear antibody (ANA) by indirect immunofluorescence (IIF) assay, but positive for ANA by EIA. Methods: Eighty sera that tested negative for ANA by IIF, but positive for ANA by EIA were included. All sera were tested for specific autoantibodies by line immunoassay (LIA). The positive predictive value (PPV) of EIA was calculated using LIA result as a reference standard. Medical records of patients were reviewed. Clinical findings at the time of blood sampling for ANA testing and at 5 years after sampling were obtained. Results: Twenty-eight sera (35%) were found to be positive by LIA. The PPV of EIA for detection of specific autoantibodies at the manufacturer’s recommended cut-off was 35.0% (95% CI: 24.5-45.5%). The most prevalent antibodies were anti-SSA/Ro60 (64.3%, 95% CI: 46.5-82.0%), anti-Ro52 (25.0%, 95% CI: 9.0-41.0%), and anti-SSB/La (10.7%, 95% CI: 0-22.2%). A diagnosis of systemic autoimmune rheumatic disease was established in 7 patients (25%) at the time of blood sampling, and 4 patients (14.3%) were diagnosed with non-rheumatic autoimmune disease. Conclusion: EIA testing in IIF-ANA negative sera yielded a chance to detect antinuclear antibodies. However, the poor PPV of EIA may have low benefit in real-life clinical practice. Anti-SSA/Ro60 was the most prevalent antibody detected. A high proportion of LIA-ANA positive patients were not diagnosed as autoimmune disease at the time of antibody detection.

Pattern and Frequency of Anti-nuclear Antibody Positivity in Paediatric Rheumatic Diseases

Background: Anti-nuclear antibodies (ANAs) are specific antibodies directed against a variety of nuclear antigens detected in the serum of patients with many rheumatic and non-rheumatic diseases.These antibodies are not only involved in the pathogenesis, but also constitute the basis for diagnosis and treatment of paediatric rheumatic diseases. The objective of the study was to identify the patterns and frequency of ANA positivity in Paediatric Rheumatic Diseases.&#x0D; Methodology: It was a retrospective study. Fourteen hundred and sixty eight records of paediaric rheumatology patients were analyzed. Statistical analysis were done to observe the frequency and association of different patterns of ANA in Juvenile idiopathic arthritis and systemic lupus erythematosus patients.&#x0D; Results: Among the 1468 patients of PRDs, frequency of JIA cases was the highest (65 %) followed by SLE, Scleroderma, juvenile dermatomyositis, and others. Among the 261 PRD patients ANA positivity was 65%. ANA positivity was 100%, 92%, 40% and 31.5% in Mixed connective tissue disease, SLE, JDM and Scleroderma patients respectively. Homogenous staining pattern was found in 59% and speckled pattern in 22.9%. There was significant association between ANA positivity and uveitis in oligoarticular JIA patients. Significant association was also found between homogeneous patterns of ANA and renal involvement in SLE patients.&#x0D; Conclusion: ANA positivity was highest in MCTD cases followed by SLE cases. Majority of SLE cases had homogeneous pattern of ANA.Staining patterns of ANA had significant association with the clinical manifestations in SLE and JIA cases.&#x0D; Bangladesh J Child Health 2019; VOL 43 (1) :21-26

Insights into rheumatic diseases from next-generation sequencing.

Rheumatic diseases have complex aetiologies that are not fully understood, which makes the study of pathogenic mechanisms in these diseases a challenge for researchers. Next-generation sequencing (NGS) and related omics technologies, such as transcriptomics, epigenomics and genomics, provide an unprecedented genome-wide view of gene expression, environmentally responsive epigenetic changes and genetic variation. The integrated application of NGS technologies to samples from carefully phenotyped clinical cohorts of patients has the potential to solve remaining mysteries in the pathogenesis of several rheumatic diseases, to identify new therapeutic targets and to underpin a precision medicine approach to the diagnosis and treatment of rheumatic diseases. This Review provides an overview of the NGS technologies available, showcases important advances in rheumatic disease research already powered by these technologies and highlights NGS approaches that hold particular promise for generating new insights and advancing the field.

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

The role of autoantibodies in the early diagnosis of systemic immunoinflammatory rheumatic diseases

The majority of systemic immunoinflammatory rheumatic diseases (SARDs — systemic autoimmune rheumatic diseases) have several stages. The most important characteristic of SARDs is pathological activation of B cells and overproduction of organ-specific autoantibodies (auto-Abs), which react with different peptides and cell components and are regarded as biological markers of rheumatic diseases. The main serological markers of SARDs include antinuclear antibodies, rheumatoid factors, anticyclic citrullinatedpeptide antibodies, antiphospholipid antibodies, and antineutrophil cytoplasmic antibodies. Positive tests for these auto-Abs are among the classification criteria for SARDs and are used to evaluate the activity and severity of the diseases, to identify some clinical laboratory subtypes, to predict the development and progression of organ pathology, therapy effectiveness, etc. Moreover, they may serve as predictors of SARD development at a preclinical stage. It has been proved that immunopathological disturbances associated with the loss of immune tolerance to self-antigens and with the initiation of systemic autoimmunity and inflammation develop 5 years on average before the appearance of the first clinical symptoms. Thus, detection of serological markers for SARDs at a preclinical stage, i.e. in the absence of extensive clinical manifestations, makes it possible to use preventive strategies in people at high risk for these diseases. Using rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis as an example, the paper analyzes the clinical significance of detection of auto-Abs at preclinical or early clinical stages of SARDs when immunopathological disorders have not yet become severe and/or irreversible.

Janus kinase inhibitors in immuno-inflammatory rheumatic diseases: new opportunities and prospects

Despite the great success in the diagnosis and treatment of immuno-inflammatory rheumatic diseases (IIRD), which led to a significant improvement in the prognosis in many patients, the fundamental medical problems of this pathology – the restoration of quality of life and reduction of mortality to the population level – are far from solution. This served as a powerful impetus to the study of new approaches to pharmacotherapy of IIRD, one of which is associated with the use of low-molecular synthetic drugs that inhibit intracellular "signal" molecules-Janus kinase (JAK), the socalled Jakinibs. The current achievements and trends concerning the use of JAK inhibitors in the treatment of IIRD are considered.

Alarmins of the S100-Family in Juvenile Autoimmune and Auto-Inflammatory Diseases.

Autoimmune and auto-inflammatory diseases in children are causing chronic inflammation, organ damage, and pain. Although several options for treatment are nowadays available a significant number of patients does not respond sufficiently to current therapies. In these diseases inflammatory processes are triggered by numerous exogenous and endogenous factors. There is now increasing evidence that especially a novel family of pro-inflammatory molecules, named alarmins, play a significant role in inflammatory processes underlying these diseases. Alarmins are endogenous proteins released during stress reactions that confer inflammatory signaling via Pattern Recognition Receptors (PRRs), like the Toll-like receptor 4 (TLR4). The most abundant alarmins in juvenile rheumatic diseases belong to the family of pro-inflammatory calcium-binding S100-proteins. In this review we will give a general introduction in S100-biology. We will demonstrate the functional relevance of these proteins in animal models of autoimmune and auto-inflammatory diseases. We will show the expression patterns of S100-alarmins and correlation to disease activity in different forms of juvenile idiopathic arthritis, auto-inflammatory diseases, and systemic autoimmune disorders. Finally, we will discuss the clinical use of S100-alarmins as biomarkers for diagnosis and monitoring of rheumatic diseases in children and will point out potential future therapeutic approaches targeting inflammatory effects mediated by S100-alarmins.

Simplified Echocardiography Screening Criteria for Diagnosing and Predicting Progression of Latent Rheumatic Heart Disease.

The 2012 World Heart Federation Criteria are the current gold standard for the diagnosis of latent rheumatic heart disease (RHD). Because data and experience using these criteria have grown, there is opportunity to simplify and develop outcome prediction tools. We aimed to develop a simple echocardiographic score applicable for RHD screening with potential to predict disease progression. This study included 3 cohorts used for score derivation (n=9501), score validation (n=7312), and assessment of outcomes prediction (n=227). In the derivation cohort, variables independently associated with definite RHD were assigned point values proportional to their regression coefficients. The sum of these values was stratified into low (0-6), intermediate (7-9), and high (≥10) risk. Five components were selected for score development, including mitral valve anterior leaflet thickening, excessive leaflet tip motion, and regurgitation jet length ≥2 cm, and aortic valve focal thickening and any regurgitation. The score showed optimal discrimination and calibration for RHD diagnosis in the derivation and validation cohorts (C statistic, 0.998 and 0.994, respectively), with good discrimination for predicting disease progression (C statistic, 0.811). Progression-free survival rate in the low-risk children at 1-, 2-, and 3-year follow-up was 100%, 100%, and 93%, respectively, compared with 90%, 60%, and 47% in high-risk group. The point-based score was strongly associated with disease progression (hazard ratio, 1.270; 95% CI, 1.188-1.358; P<0.001). This simplified score, based on components of the World Heart Federation criteria, is highly accurate to recognize definite RHD and provides the first tool for risk stratification, assigning children with latent RHD to low, intermediate, or high risk based on echocardiographic features at diagnosis.

"Disease knowledge index" and perspectives on reproductive issues: A nationwide study on 398 women with autoimmune rheumatic diseases.

The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Agranulocytosis in Felty’s syndrome: a case from clinical practice

Differential diagnosis of articular syndrome is one of the leading issues of primary medical sanitary care. Timely and correct diagnosis of rheumatic diseases made by an internist in an out-patient setting is a cornerstone of successful treatment and prevention of possible complications. The masks of clinical course, subtle symptoms, as well as pathomorphosis of the disease make the accurate diagnosis difficult to establish. Among rheumatic diseases more and more often isolated hematological manifestations are observed on the onset of the disease. Among them the leading place is taken by Felty’s syndrome. Being a form of seropositive rheumatoid arthritis, it is often associated with cytopenia. The aim of the article is to draw attention to the problem of timely diagnosis of Felty’s syndrome. The presented clinical case of Felty’s syndrome with agranulocytosis was based on clinical, laboratory, instrumental data obtained on examination of a patient. The features of the course, diagnostic methods and treatment methods of the pathology are discussed. The treatment efficacy of corticosteroids and cytostatics, similarities in clinical presentation and course of the syndrome with lymphoproliferative diseases and liver cirrhosis are presented. According to the obtained data a conclusion was made about the need for early diagnosis and complex examination in case of Felty’s syndrome for successful treatment of the nosology.

Can solid-phase assays replace immunofluorescence for ANA screening?

The paper by Pisetsky et al 1 has stimulated a timely and interesting debate on a focal point in the diagnosis of autoimmune rheumatic diseases, that is, the accuracy of...

Harmonisation of laboratory tests for rheumatic diseases: still a long way to go

Antinuclear antibodies (ANAs), antineutrophil cytoplasmic antibodies (ANCAs), rheumatoid factor (RF) and antibodies to citrullinated peptides (ACPA) are widely used laboratory markers to support the diagnosis of ANA-associated systemic rheumatic diseases,...