Patient-perspective and feasibility of home finger-prick testing to complement and facilitate large-scale research in rheumatology.

BACKGROUND: During the COVID-19 pandemic, we developed a digital research platform to longitudinally investigate COVID-19-related outcomes in patients with rheumatic diseases and healthy controls. We used home finger-prick testing in order to collect serum samples remotely and increase the overall efficiency of the platform. The aim of the present study was to evaluate the success rate of the finger prick and patients' perspective towards the finger prick. METHODS: Serum samples were collected up to five times during follow-up, either via a venepuncture at the research institute or a finger prick from participants' home. Participants were asked to complete a digital evaluation questionnaire of the finger prick after their attempts. RESULTS: A total of 2135 patients and 899 controls performed at least one finger prick and were included in this study. The first finger prick was successfully done by 92% (95% CI: 90% to 93%) of patients, 94% (95% CI: 92% to 95%) of controls, 93% (95% CI: 92% to 94%) of all participants aged ≤70 years and 89% (95% CI: 86% to 92%) of all participants aged >70 years. Sex did not impact these success rates. Repeated failure occurred in 11/439 (0.8%) patients and 4/712 (0.6%) controls. Both patients and controls were less willing to perform a finger prick for individual healthcare compared with scientific research. CONCLUSION: The vast majority of participants, among which elderly and patients with rheumatic diseases, were able to successfully draw the required amount of blood for serological analyses. This shows that finger-prick testing is suitable for a high-throughput implementation to monitor patients remotely.

Antinuclear antibody titration and pattern are helpful in the diagnosis of systemic autoimmune rheumatic diseases.

INTRODUCTION: Anti-nuclear antibody (ANA) testing is among the most common immunological test requested in the diagnostic immunology laboratory. The main purpose of this test is to screen for the underlying systemic autoimmune rheumatic diseases (SARDs). The gold standard laboratory method for ANA detection is by the indirect immunofluorescence (IIF) assay. In most laboratories, positive ANA-IIF is reported in terms of titration and pattern. OBJECTIVE: This study was conducted with the aim of determining the correlation between ANA-IIF titration and pattern for the diagnosis of SARDs. MATERIALS AND METHODS: A retrospective study was conducted whereby the positive ANA-IIF samples from 1st July 2018 until 31st December 2019 and 1st January 2021 until 31st March 2021 were included in this study. The duplicate samples were excluded. ANA-IIF titration and pattern were recorded for all patients. The demographic, clinical, and final diagnosis data were retrieved from each patient's clinical note. RESULTS: A total of 179 patients were included for analysis. The majority of the patients were female (79.9%) and from Malay ethnicity (66.5%). Sixty-five patients (36.3%) had ANA-IIF positive at 1:80 titration followed by 45 patients (25.1%) positive at titration of equal or more than 1:160. Speckled was the predominant pattern visualised in 90 patients (50.3%) followed by homogeneous in 76 patients (42.5%). Forty-five patients (25.1%) were finally diagnosed with SARDs with 41 of them diagnosed as SLE. ANA titration was significantly associated with the final diagnosis of SARDs at all titres (p<0.001) but the best cut-off was noted at a titre of equal or more than 1:320 with the sensitivity and specificity of 86.7% and 77.6% respectively. The homogeneous pattern was also significantly associated with SARDs (p=0.04). The final diagnosis of SARDs were significantly higher in female (p=0.03) and their age was significantly younger (p<0.001). CONCLUSION: ANA-IIF titration of equal or more than 1:320 can be used as the best titration for differentiating between SARDs and non-SARDs in a positive ANA sample. Patients with homogeneous pattern were more likely to be diagnosed with SARDs than other ANA-IIF patterns.

Incidence and disease burden of autoimmune inflammatory rheumatic diseases after non-pharmaceutical interventions in the COVID-19 era: A nationwide observational study in Korea.

BACKGROUND: Infections are considered risk factors for autoimmune inflammatory rheumatic diseases (AIRDs), the incidence of which is considered to have been impacted by the COVID-19 pandemic. The impact of non-pharmaceutical interventions (NPIs) on the incidence of AIRDs and their associated health care services and medical expenses in Korea was investigated. METHODS: We included all AIRD cases reported between January 2016 and February 2021 based on the National Health Insurance Service data. We evaluated changes in incidence trends for each AIRD before and after NPI implementation (Feb 2020 to Feb 2021) using segmented regression analysis. Changes in health care utilization and medical costs for each AIRD before and after NPI implementation were also investigated. RESULTS: After NPI implementation, monthly incidence rates declined significantly by 0.205 per 1 000 000 (95% confidence interval [CI], -0.308 to -0.101, p < .001) in patients with systemic lupus erythematosus (SLE). No significant changes in the incidence of all AIRDs other than SLE were observed before and after implementation. Further, annual outpatient department visits per patient were lower during implementation for all diseases, except juvenile idiopathic arthritis (JIA). The prescription days per outpatient visit increased significantly during implementation for all diseases, except JIA and ankylosing spondylitis. During implementation, the total annual medical costs per patient tended to decrease for all diseases, except JIA and mixed connective tissue disease. CONCLUSION: Implementation of NPIs to contain the pandemic led to a reduction in the incidence of SLE and changed patterns of medical care utilization and treatment cost for most AIRDs.

Clinical features of patients with rheumatic and musculoskeletal diseases during the coronavirus disease 2019 pandemic and the association of its relapse with infection: Across-sectional study.

AIM: The aim of this study was to investigate the clinical features of patients with rheumatic and musculoskeletal diseases (RMDs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the relationship between RMDs relapse and SARS-CoV-2 infection. METHODS: We carried out a cross-sectional observational study among 585 patients with RMDs and 619 individuals without RMDs. Data on demographics, the clinical features of coronavirus disease 2019 (COVID-19), antirheumatic therapy, and RMD relapse were collected. Differences between RMDs and control groups, infected and uninfected groups, relapse and non-relapse RMDs groups were examined. The influence of COVID-19 infection on medications and relapse of RMDs was also assessed. RESULTS: Among 1204 participants finally recruited for analysis, 1030 (85.5%) were infected with COVID-19. Seven hundred and ninety-five (77.2%) of infected individuals were female, and the median age was 40 years (IQR 33, 50). Patients in the RMD group had a relatively lower risk of COVID-19 symptoms whereas were significantly more likely to require hospitalization (6.7% vs. 2.2%). In the RMDs group, younger patients who were under the age of 65 were more likely to report more symptoms. More patients with RMD relapse (27, 34.6%) adjusted their medications during the period of COVID-19 infection than those without relapse (59, 13.2%). CONCLUSION: Patients with RMDs were at lower risk of symptoms of COVID-19. Rheumatic and musculoskeletal disease patients experience a higher risk of relapse especially when they adjust medications during COVID-19 infection. The long-term prognosis of infected RMDs patients need further investigation.

Look after the COVID-19 pandemic: Mortality rates among patients with rheumatic diseases.

AIM: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may have a more severe course in patients with underlying disease or who have had immunosuppression. In this study, it was aimed to determine the frequency of coronavirus disease 2019 (COVID-19) and the mortality rates related to COVID-19 among patients with rheumatic disease. METHODS: The patients who were followed up with rheumatic disease in the rheumatology outpatient clinic in a tertiary hospital were retrospectively assessed if they had COVID-19 infection or not between March 2020 and January 2022. RESULTS: A total of 10 682 patients were evaluated. There were 2928 (27.4%) COVID-19-positive and 7754 (72.6%) COVID-19-negative patients. The mean age of COVID-19-positive patients was 46.2 ± 14.6 years, and 65.8% were female. Forty-two (1.4%) patients died due to COVID-19. Among COVID-19-negative patients, 192 patients died. The most common rheumatic disease among patients with COVID-19 was spondyloarthritis (SpA) (30.4%). Corticosteroids were the most common treatment agent in COVID-19-positive patients regardless of mortality. Thirty-one (73.8%) patients were receiving corticosteroids, and 35 (83.3%) patients were receiving immunosuppressive agents among patients with mortality. According to the logistic regression analysis, older age, male gender, and receiving corticosteroid, hydroxychloroquine, mycophenolate mofetil, tofacitinib, rituximab, and cyclophosphamide were found to be related to increased mortality. CONCLUSION: COVID-19 is a serious infection and the current study emphasized that patients with rheumatic diseases had increased mortality rates, particularly in patients who were old, male, and on immunosuppressive treatments.

Exploring paediatric rheumatology care: a ten-year retrospective analysis of the patient population in Ghana.

BACKGROUND: Rheumatic diseases can seriously impact children's general health, development, and growth. However, due to a lack of resources, paediatric rheumatology is a largely underdeveloped speciality in many African nations. Children with rheumatic disorders face obstacles in accessing specialized medical care, including lack of specialists, care centres, medication access, and limited research and education to increase understanding of paediatric rheumatic disease among healthcare practitioners. This study described the disease characteristics, prevalence, and challenges faced by paediatric rheumatic disease patients receiving care at a teaching hospital in Accra, Ghana. METHODS: A retrospective record-based study was conducted among all paediatric cases presenting to the rheumatology clinic of the Korle Bu Teaching Hospital (KBTH) from January 2011 to December 2021. Data collected include clinical features, laboratory findings at disease presentation, andtherapeutic regimens prescribed per standard guidelines and experiences. RESULTS: A total of 121 cases were identified as of 2021, indicating a point prevalence of 0.0011%. The majority (73%) were females with a mean age of 13.4 ± 3.2 years. The mean duration of symptoms in months experienced by patients before being successfully referred to a rheumatologist was 18 months. There were significant differences between referred and confirmed diagnoses, especially in cases involving mixed connective tissue diseases (MCTD), systemic lupus erythematosus (SLE), and juvenile dermatomyositis (JDM), suggesting that these conditions may be under-recognised. Arthralgia and arthritis were the most common presenting symptoms. More than three-quarters (86.8%) of the cases studied were treated with steroids (oral or intravenous). In cases requiring immunosuppressive therapy, methotrexate was the most commonly prescribed in 33.9% of instances. Mortality was recorded at 8.3%, with the majority involving SLE cases. Most (95.7%) of the primary caregivers expressed positive experiences regarding care received at the adult rheumatology clinic. CONCLUSION: There were significant delays in diagnosis and diagnostic accuracy for patients with paediatric rheumatic disease (PRD). This highlights the pressing need for strengthening paediatric rheumatology services in Africa, including increasing awareness about these conditions among the public and healthcare providers to improve early diagnosis and quality of life for children with these conditions.

Association between sinusitis and incident rheumatic diseases: a population-based study.

OBJECTIVES: To determine whether antecedent sinusitis is associated with incident rheumatic disease. METHODS: This population-based case-control study included all individuals meeting classification criteria for rheumatic diseases between 1995 and 2014. We matched three controls to each case on age, sex and length of prior electronic health record history. The primary exposure was presence of sinusitis, ascertained by diagnosis codes (positive predictive value 96%). We fit logistic regression models to estimate ORs for incident rheumatic diseases and disease groups, adjusted for confounders. RESULTS: We identified 1729 incident rheumatic disease cases and 5187 matched controls (mean age 63, 67% women, median 14 years electronic health record history). After adjustment, preceding sinusitis was associated with increased risk of several rheumatic diseases, including antiphospholipid syndrome (OR 7.0, 95% CI 1.8 to 27), Sjögren's disease (OR 2.4, 95% CI 1.1 to 5.3), vasculitis (OR 1.4, 95% CI 1.1 to 1.9) and polymyalgia rheumatica (OR 1.4, 95% CI 1.0 to 2.0). Acute sinusitis was also associated with increased risk of seronegative rheumatoid arthritis (OR 1.8, 95% CI 1.1 to 3.1). Sinusitis was most associated with any rheumatic disease in the 5-10 years before disease onset (OR 1.7, 95% CI 1.3 to 2.3). Individuals with seven or more codes for sinusitis had the highest risk for rheumatic disease (OR 1.7, 95% CI 1.3 to 2.4). In addition, the association between sinusitis and incident rheumatic diseases showed the highest point estimates for never smokers (OR 1.7, 95% CI 1.3 to 2.2). CONCLUSIONS: Preceding sinusitis is associated with increased incidence of rheumatic diseases, suggesting a possible role for sinus inflammation in their pathogenesis.

Genetically transitional disease: conceptual understanding and applicability to rheumatic disease.

In genomic medicine, the concept of genetically transitional disease (GTD) refers to cases in which gene mutation is necessary but not sufficient to cause disease. In this Perspective, we apply this novel concept to rheumatic diseases, which have been linked to hundreds of genetic variants via association studies. These variants are in the 'grey zone' between monogenic variants with large effect sizes and common susceptibility alleles with small effect sizes. Among genes associated with rare autoinflammatory diseases, many low-frequency and/or low-penetrance variants are known to increase susceptibility to systemic inflammation. In autoimmune diseases, hundreds of HLA and non-HLA genetic variants have been revealed to be modest- to moderate-risk alleles. These diseases can be reclassified as GTDs. The same concept could apply to many other human diseases. GTD could improve the reporting of genetic testing results, diagnostic yields, genetic counselling and selection of therapy, as well as facilitating research using a novel approach to human genetic diseases.

Novel multiclass classification machine learning approach for the early-stage classification of systemic autoimmune rheumatic diseases.

OBJECTIVE: Systemic autoimmune rheumatic diseases (SARDs) encompass a diverse group of complex conditions with overlapping clinical features, making accurate diagnosis challenging. This study aims to develop a multiclass machine learning (ML) model for early-stage SARDs classification using accessible laboratory indicators. METHODS: A total of 925 SARDs patients were included, categorised into SLE, Sjögren's syndrome (SS) and inflammatory myositis (IM). Clinical characteristics and laboratory markers were collected and nine key indicators, including anti-dsDNA, anti-SS-A60, anti-Sm/nRNP, antichromatin, anti-dsDNA (indirect immunofluorescence assay), haemoglobin (Hb), platelet, neutrophil percentage and cytoplasmic patterns (AC-19, AC-20), were selected for model building. Various ML algorithms were used to construct a tripartite classification ML model. RESULTS: Patients were divided into two cohorts, cohort 1 was used to construct a tripartite classification model. Among models assessed, the random forest (RF) model demonstrated superior performance in distinguishing SLE, IM and SS (with area under curve=0.953, 0.903 and 0.836; accuracy= 0.892, 0.869 and 0.857; sensitivity= 0.890, 0.868 and 0.795; specificity= 0.910, 0.836 and 0.748; positive predictive value=0.922, 0.727 and 0.663; and negative predictive value= 0.854, 0.915 and 0.879). The RF model excelled in classifying SLE (precision=0.930, recall=0.985, F1 score=0.957). For IM and SS, RF model outcomes were (precision=0.793, 0.950; recall=0.920, 0.679; F1 score=0.852, 0.792). Cohort 2 served as an external validation set, achieving an overall accuracy of 87.3%. Individual classification performances for SLE, SS and IM were excellent, with precision, recall and F1 scores specified. SHAP analysis highlighted significant contributions from antibody profiles. CONCLUSION: This pioneering multiclass ML model, using basic laboratory indicators, enhances clinical feasibility and demonstrates promising potential for SARDs classification. The collaboration of clinical expertise and ML offers a nuanced approach to SARDs classification, with potential for enhanced patient care.

A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Portable Mid-Infrared Spectroscopy Combined with Chemometrics to Diagnose Fibromyalgia and Other Rheumatologic Syndromes Using Rapid Volumetric Absorptive Microsampling.

The diagnostic criteria for fibromyalgia (FM) have relied heavily on subjective reports of experienced symptoms coupled with examination-based evidence of diffuse tenderness due to the lack of reliable biomarkers. Rheumatic disorders that are common causes of chronic pain such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and chronic low back pain are frequently found to be comorbid with FM. As a result, this can make the diagnosis of FM more challenging. We aim to develop a reliable classification algorithm using unique spectral profiles of portable FT-MIR that can be used as a real-time point-of-care device for the screening of FM. A novel volumetric absorptive microsampling (VAMS) technique ensured sample volume accuracies and minimized the variation introduced due to hematocrit-based bias. Blood samples from 337 subjects with different disorders (179 FM, 158 non-FM) collected with VAMS were analyzed. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. The OPLS-DA algorithm enabled the classification of the spectra into their corresponding classes with 84% accuracy, 83% sensitivity, and 85% specificity. The OPLS-DA regression plot indicated that spectral regions associated with amide bands and amino acids were responsible for discrimination patterns and can be potentially used as spectral biomarkers to differentiate FM and other rheumatic diseases.

Performance of the 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease in a Latin American Cohort.

BACKGROUND/OBJECTIVE: The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria (2019 AECC) for IgG4-related disease (IgG4-RD) is considered a significant advancement in the study of this condition. Most studies evaluating their performance have focused on White and Asian patients, leaving a knowledge gap regarding Latin American populations. Therefore, this study aimed to assess the performance of the 2019 AECC for IgG4-RD in a cohort of Latin American patients. METHODS: A multicenter medical records review study was conducted, involving centers from Argentina, Chile, Mexico, Peru, and Uruguay. Data on IgG4-RD patients and mimicker conditions were collected through a standardized online form. The criterion standard for diagnosing IgG4-RD was based on the fulfillment of the Comprehensive Diagnostic Criteria for IgG4-RD and/or the Consensus Statement on Pathology. The 2019 AECC was retrospectively applied. RESULTS: We included 300 patients, with 180 (60%) having IgG4-RD and 120 (40%) having mimicker conditions. The 2019 AECC had a sensitivity of 66.7% and a specificity of 100%. Sensitivity increased to 73.3% when disease-specific autoantibody items were removed, without affecting specificity. The true-positive cases had more involved organs, a higher availability of biopsy results, and were more likely to belong to the Mikulicz/systemic and proliferative phenotypes. CONCLUSIONS: The use of the 2019 AECC for IgG4-RD in a Latin American population confirms its high specificity in excluding those without the disease. The presence of concomitant autoimmune diseases and clinically nonsignificant disease-specific autoantibodies excludes a significant number of patients from fulfilling the criteria.

Systematic review to estimate the prevalence of inflammatory rheumatic diseases in Germany.

OBJECTIVE: This study aimed to update the prevalence estimates of inflammatory rheumatic diseases (IRD) in Germany. METHODS: A systematic literature search in PubMed and Web of Science (last search 08 November 2022) identified original articles (regional and nationwide surveys and claims data analyses for arthritides, connective tissue diseases, and vasculitides) on prevalences for the period 2014-2022. Data sources, collection period, case definition, and risk of bias are reported. Prevalences were estimated from available national data, with consideration of international data. RESULTS: Screening by two authors yielded 263 hits, of which 18 claims data analyses and 2 surveys met the inclusion criteria. Prevalences ranged from 0.42 to 1.85% (rheumatoid arthritis), 0.32-0.5% (ankylosing spondylitis), 0.11-0.32% (psoriatic arthritis), 0.037-0.14% (systemic lupus erythematosus), 0.07-0.77% (Sjögren's disease/sicca syndrome), 0.14-0.15% (polymyalgia rheumatica, ≥ 40 years), 0.04-0.05% (giant cell arteritis, ≥ 50 years), and 0.015-0.026% (ANCA-associated vasculitis). The risk of bias was moderate in 13 and high in 7 studies. Based on the results, we estimate the prevalence of IRD in Germany to be 2.2-3.0%, which corresponds to approximately 1.5-2.1 million affected individuals. The prevalence of juvenile idiopathic arthritis was reported to be around 0.10% (0.07-0.10%) of 0-18-year-olds, corresponding to about 14,000 children and adolescents in Germany. CONCLUSION: This systematic review shows an increase in the prevalence of IRD in Germany, which is almost exclusively based on claims data analyses. In the absence of multistage population studies, the available data are, overall, uncertain sources for prevalence estimates, with a moderate to high risk of bias.