False positive results for anti-topoisomerase I (Scl-70) antibodies in clinical practice: a case series from a scleroderma referral center (2023)

Citatuddrag:

Autoantibody reactivity allows stratification of patients early in the disease course, facilitating a personalized approach and treatment [66,85,92]. When considering the prognostic significance of ATA in particular, it is important to take into account the variability in ATA results due to differences in test methods [93,94]. The strong association with SSc and its role as a biomarker may indicate the potential pathogenicity of these autoreactive B-cell responses, similar to those reported for SLE [95], antiphospholipid syndrome [96], and Sjogren's syndrome [97].

Citatuddrag:

The presence of other unknown or unmeasured autoantibodies in these at-risk populations cannot be excluded, but is unlikely to have influenced the results, given the rarity of simultaneous expression of different autoantibodies in patients with systemic sclerosis. We also cannot rule out that some people may have false positive results on the ATA test. 33 However, as all patients in this study were ANA positive and had a clinical diagnosis of systemic sclerosis, we believe that our results were not due to false positive ATA results.

Our objective was to assess the sex-specific risk of anti-topoisomerase I (ATA) antibodies for mortality in patients with systemic sclerosis, diffuse cutaneous systemic sclerosis, interstitial lung disease, and pulmonary hypertension in two groups.

The study was a 10-year analysis of the prospective Combined Care Leiden Systemic Sclerosis (CCISS) cohort in the Netherlands and the European International Scleroderma Trial and Research (EUSTAR) cohort. Patients with systemic sclerosis according to the 2013 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) classification were included; available autoantibody status; available skin subtype; at least one available stromal imaging evaluation of lung disease; and a known start date. Patients with systemic sclerosis were divided into six risk groups by gender and autoantibody status (anti-centromeric antibody [ACA] positive women, ACA positive men, ACA and ATA negative women, ACA and ATA negative men, ATA negative women). positive and ATA positive men). We constructed Kaplan-Meier curves and Cox proportional hazards models considering left-truncated survival to avoid bias, since all patients had a disease onset date (first non-Raynaud's symptom) prior to the date of admission. to the cohort. The primary outcome was all-cause mortality, and the secondary outcomes were diffuse cutaneous systemic sclerosis, interstitial lung disease, and pulmonary hypertension.

445 (63%) of 708 participants in CCISS between April 1, 2009 and January 1, 2022 (101 [23%] men and 344 [77%] women) and June 2004 4,263 (50%) of 8,590 for 1 day and on March 28, 2018 in EUSTAR (783 [18%] men and 3480 [82%] women) were eligible for this study. In both cohorts, ATA expression was significantly more common in men than in women (39 [39%] of 101 men vs. 67 [19%] of 344 women in CCISS; p<0 0001 and 381 [49%] of 783 men vs. .1323 [38%] of 3480 women in EUSTAR; p<0 0001). Based on estimated survival, within 10 years, 30% of ATA-positive men and 12% of ATA-positive women died in the CCISS cohort and 33% and 15%, respectively, in the CCISS cohort. of EUSTAR. After adjustment for age, race, and autoantibody status, male gender remained the most important risk factor for all-cause mortality (HR 2 9 [95% CI 1 5-5 5] in CCISS, p=0 0018; EUSTAR HR 2 6 [2.0 -3.4] inches, p<0.0001).

We show that the association between male gender and increased mortality in systemic sclerosis cannot be explained by a higher incidence of ATA. However, more research is needed on the impact of gender characteristics in people with systemic sclerosis.

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Develop the pediatric glucocorticoid toxicity index (pGTI), an assessment of standardized weighted clinical outcomes to measure changes in glucocorticoid (GC) toxicity over time.

Fourteen medical specialists from seven subspecialties attended the meeting. Specialist physicians represent several subspecialties, of which GC plays an important role in the treatment of inflammatory diseases: nephrology, rheumatology, oncology, endocrinology, genetics, psychiatry, and maternal-fetal medicine. Nine researchers are from Canada, Europe, or New Zealand, and five are from the United States. Group consensus methods and multicriteria decision analysis were used. The pGTI is a comprehensive assessment of common, important, and dynamic GC toxicity. These toxicities were categorized as minor, moderate, or major health domains and weighted by severity. Relative weights are derived from group consensus and multi-criteria decision analysis using 1000Minds^{MT value}software platform Two quantitative scores comprise the overall toxicity profile derived from the pGTI data: (1) cumulative deterioration score, (2) composite improvement score. The pGTI also includes an unweighted qualitative record of GC side effects, called the Impairment Checklist, which documents less common toxicities that, while potentially serious, are unlikely to change with GC dose.

One hundred seven (107) toxic items are included in the pGTI and thirty-two (32) toxic items are included in the damage list. To assess how well the pGTIs corresponded with expert clinical judgment, the investigators ranked the 15 cases based on clinical judgment from highest to lowest GC toxicity. The expert ratings were then compared with the pGTI case ratings, yielding excellent agreement (weighted kappa 0.86). The pGTI was migrated to the digital environment after its development and initial validation. The digital platform is designed to ensure ease of clinical use, rigor of application, and accuracy of scoring. Clinic staff enter vital signs, laboratory results, and medication changes against the pGTI score. Clinicians document findings of GC myopathy, skin toxicity, mood disturbances, and infection. The pGTI algorithm then applies weights to this raw data and calculates a score. Built-in logic explains the impact of age- and gender-related reference intervals on several domains of health: blood pressure, lipid metabolism, and bone mineral density. Other algorithms account for expected changes in height Z scores used in growth domains, thus addressing issues specific to GC toxicity in children. The impairment checklist provides a comprehensive measure of GC toxicity, but does not affect the pGTI score, as the scoring fields emphasize manifestations of GC toxicity that may change over the course of the assay.

We describe the development and initial evaluation of a weighted composite toxicity index to assess the morbidity associated with GC use in children and adolescents. The development of the pGTI digital platform was essential to perform the detailed calculations required to ensure rigor, precision, and ease of use in clinical and research settings.

Background: It is well known that patients with rheumatic diseases (RD) such as DM are susceptible to various types of infections because the aggressive activity of the disease requires high doses of immunosuppressive therapy. Due to the heterogeneity of the disease, the severity of COVID-19 in ER has been limited in the literature. Therefore, the specific details of mortality are essential to understand the necessary precautions in treatment.

Objective: To determine the outcome of COVID-19 in DM compared to controls and to identify risk associations by sex, race, interstitial lung disease, tumors, and use of immunosuppressants.

Methods: Retrospective data on people with DM and COVID-19 and the general population with COVID-19 between January 2020 and August 2021 were retrieved from the TriNetX database. 1:1 propensity score matching was used to adjust for confounding factors. We assessed COVID-19 outcomes such as mortality, hospitalization, ICU admission, severe COVID-19, mechanical ventilation (MV), acute kidney injury (AKI), venous thromboembolism (VTE), ischemic stroke, acute respiratory distress syndrome (ARDS), renal replacement therapy (RTR) and sepsis. Subgroup analyzes included gender, race, ILD, cancer patients, disease-modifying antirheumatic drug (DMARD) use, and glucocorticoid (GC) use.

RESULTS: We identified 5,574 diabetic patients with COVID-19 and 5,574 general population (control groups) with COVID-19. DM with COVID-19 had lower risk of death compared with controls [RR 0.76], hospitalization [RR 0.8], severe COVID-19 [RR 0.76], AKI [RR 0.83] and sepsis [RR 0.73]. Men and African Americans were more likely to develop AKI [RR 1.35, 1.65], whereas African Americans were more likely to have severe COVID-19 [RR 1.62] and VTE [RR 1.54]. DMs in the EPI group also experienced higher odds of severe COVID-19 infection [RR 1.64] and VTE [RR 2.06].

DM patients treated with DMARDs and corticosteroids had higher odds of hospitalization [RR 1.46, 2.12] and sepsis [RR 3.25, 2.4] Subgroup analysis of DM patients with COVID-19 with a 5-year history of cancer was insufficient for a significant significant comparison .

Conclusions: Patients with dermatomyositis without comorbidity had reasonable COVID-19 outcomes, including mortality and hospitalization. Black race, male gender, ILD, DMARDS, and corticosteroid users were associated with worse outcomes.

A systematic review of the literature and meta-analysis was performed to estimate the proportion of cases of fever of unknown origin (FUO) and inflammation of unknown origin (UIO) due to rheumatic diseases and the relative frequency of specific entities associated with FUO/UIO.

PubMed and EMBASE were searched between January 1, 2002 and December 31, 2021 for studies containing ≥50 patients reporting an FUO/IUO aetiology. The primary outcome was the proportion of FUO/IUO patients with rheumatic disease. Secondary outcomes included associations between study and patient characteristics and the proportion of rheumatic disease and the relative frequency of rheumatic disease in this group. Proportion estimates were calculated using a random effects model.

The included studies represented 16,884 patients with FUO/IUO. Rheumatic diseases explained 22.2% (95% CI 19.6 – 25.0%) of the cases. Adult Still's disease (22.8% [95% CI 18.4-27.9%]), giant cell arteritis (11.4% [95% CI 8.0-16.3%), and lupus erythematosus systemic (11.1% [95% CI 9.0-13.8]%]) was the most common disease. Rheumatic diseases were significantly more prevalent in high-income countries (25.9% [95% CI 21.5 – 30.8%)] than in middle-income countries (19.5% [95% CI 16.7 – 22.7%) and in prospective studies (27.0) High % [95% CI 21.9–32.8%]) compared to retrospective studies (20.6% [95% CI 18.1–24, 0%]). Multivariable meta-regression analysis showed that rheumatic disease was associated with duration of fever (0.011 [95% CI 0.003-0.021]; P=0.01) and the proportion of patients with OIU (1.05 [95% CI 0.41-1.68], P= 0.002).

Rheumatic diseases are common causes of FUO/IUO. Treatment of patients with FUO/IUO should be supervised by physicians familiar with the diagnosis of rheumatology.

Patient-reported outcomes (PROs) are currently poorly integrated into the clinical assessment of disease activity in patients with ANCA-associated vasculitis (AAV).

To assess the distribution of Patient Global Assessment (PtGA) in AAV patients in stable remission and determine the PtGA correlation; to assess inconsistency between PtGA and Physician Global Assessment (PhGA) scores.

Patients diagnosed with AAV who were in stable remission (BVAS = 0) and Physician's Global Assessment (PhGA) = 0 were included. The following PROs were assessed on a visual analogue scale (VAS) from 0 to 100 based on patient opinion: PtGA , fatigue, pain, general health, sleep quality and chronic deterioration. The Cragg Hurdle model was used to evaluate predictors of PtGA.

65 patients were included, 57% women, mean age 61±12 years. Median duration of the disease 6 years (IQR 3-12). The vasculitic lesion index (VDI) was 4.4±2.3. Despite being classified as in remission, 37% of the patients had elevated PtGA. PtGA was not associated with age, comorbidities, educational level, type of AAV diagnosis, number of organ systems affected, previous relapse, disease duration, or greater VDI. Female gender was significantly associated with PtGA: 51% of female patients reported elevated PtGA compared to 18% of men (p=0.009). PtGA was significantly associated with all other PROs tested. Pain and fatigue are the main determinants of elevated PtGA.

A large proportion of AAV patients who are considered by clinicians to be in remission still report ongoing uncontrolled disease. PtGA is markedly affected by pain and fatigue, and more emphasis should be placed on this in future evaluations of AAV patients.

There is currently a lack of real evidence on the effectiveness of treatments for macrophage activation syndrome (MAS) in adults associated with autoimmune inflammatory rheumatic disease (AIIRD).

To analyze the effectiveness of different treatment methods, especially plasma exchange (PE) in MAS associated with AIIRD.

Among the 5775 AIIRD patients at Tongji Hospital from 2014 to 2020, a total of 62 AIIRD-related MAS cases were collected. Clinical features and potential factors associated with prognosis were characterized using unadjusted logistic regression, operator selection and absolute minimum shrinkage (LASSO), and inverse probability of treatment weights (IPTW) analysis. Paired t-test was used to compare changes in inflammatory indicators before and after PE treatment.

Baseline data were defined as data collected at the start of the MAS, and all 62 patients were diagnosed with AIIRD before the start of the MAS. The prevalence of MAS in the AIIRD was 1.1%, and the most common types of AIIRD were systemic lupus erythematosus (45.2%) and adult Still's disease (33.9%). The 62 patients with MAS were treated with corticosteroids, 87.1% received at least one immunosuppressive agent, and 54.8% received PE. LASSO regression indicated positive effects of PE-based variables. After PE treatment, the serum levels of several inflammatory cytokines decreased rapidly, accompanied by improvements in clinical symptoms and laboratory indicators, including ferritin, lactate dehydrogenase, and C-reactive protein. LASSO regression showed that PE treatment was associated with a significant reduction in mortality (from 53.6% to 11.8%) with a hazard ratio (HR) of 0.148 (p<0.001) after adjustment for confounding factors using IPTW analysis.

With background therapy of glucocorticoids and immunosuppressants, PE is an effective method of rapidly clearing inflammatory cytokines and reducing AIIRD-associated MAS mortality.

This study provides real information on the efficacy of PE in AIIRD-associated MAS.