4th booster-dose SARS-CoV-2 heterologous and homologous vaccination in rheumatological patients.

Objective: to evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine's immune response. Methods: We designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed. Results: Performing a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p<0.05) in the level of the ID50, both for healthy controls and for patients with IMRDs. The humoral response of patients with IMRDs is significantly lower compared to healthy controls for the Omicron variant of SARS-CoV-2 (p = 0.0015). The humoral response of patients with IMRDs decreases significantly when the time interval between vaccination and sample collection is greater than 35 days. This difference was observed in the response, both for the Wuhan variant and for the Omicron variant. Conclusion: The IMRDs patients, the humoral response variation in the SARS-CoV-2 vaccine depends on doses and type of vaccine administered, the humoral response times and the treatment that these patients are receiving.

Trends in mortality in patients with systemic autoimmune rheumatic diseases (SARD) during the COVID-19 pandemic in Mexico.

The study aimed to analyze the influence of the COVID-19 pandemic on mortality rates in patients with systemic autoimmune rheumatic diseases (SARD) in Mexico. We selected SARD-related deaths using National Open Data and Information from the Ministry of Health, Mexico, and ICD-10 codes. We assessed the observed compared to the predicted mortality values for 2020 and 2021, employing trends from 2010 to 2019 with joinpoint and prediction modelling analyses. Among 12,742 deaths due to SARD between 2010 and 2021, the age-standardized mortality rate (ASMR) increased significantly between 2010 and 2019 (pre-pandemic) (annual percentage change [APC] 1.1%; 95% CI 0.2-2.1), followed by a non-significant decrease during the pandemic period (APC 13.9%; 95% CI 13.9-5.3). In addition, the observed ASMR of 1.19 for 2020 for SARD and of 1.14 for 2021 were lower than the predicted values of 1.25 (95% CI 1.22-1.28) for 2020 and 1.25 (95% CI 1.20-1.30) for 2021. Similar findings were identified for specific SARD, mainly systemic lupus erythematosus (SLE), or by sex or age group. Interestingly, the observed mortality rates for SLE in the Southern region of 1.00 in 2020 and 1.01 in 2021 were both significantly greater than the predicted values of 0.71 (95% CI 0.65-0.77) in 2020 and 0.71 (95% CI 0.63-0.79). In Mexico, the observed SARD mortality rates were not higher than the expected values during the pandemic, except for SLE in the Southern region. No differences by sex or age group were identified.

Construction and validation of a reproductive behavior questionnaire for female patients with rheumatic diseases.

INTRODUCTION/OBJECTIVES: Active autoimmune rheumatic diseases (ARDs) before conception increase the risk of flares and adverse pregnancy outcomes. We aimed to construct and validate a reproductive behavior questionnaire in Spanish for patients with ARDs to assess their knowledge and their reproductive behavior. METHOD: We constructed and validated a reproductive behavior questionnaire in two phases: (1) a literature review followed by interviews of reproductive-age female patients, and (2) a cross-sectional study to complete validation. Convenience sampling was carried out with 165 female patients: 65 participated in the cross-cultural adaptation phase and 100 in the validation phase. The internal consistency was evaluated by estimating Cronbach's alpha and tetrachoric correlation coefficients. Values ≥ 0.40 were considered acceptable (p < 0.05). RESULTS: The initial instrument included 38 questions. Thematic analysis identified 8 important dimensions or topics, which were combined to create the Rheuma Reproductive Behavior interview questionnaire. A final total of 41 items across 10 dimensions were obtained. The test-retest analysis showed perfect correlations in 34 of the 41 items, moderate in 6 items, and negative in one of the items. The mean age of the patients was 35.65 years (SD 9.02), and the mean time to answer the survey was 13.66 min (SD 7.1). CONCLUSIONS: The Rheuma Reproductive Behavior questionnaire showed good reliability and consistency capturing patients' reproductive health knowledge and reproductive behavior. Key Points • We designed and validated a questionnaire to assess reproductive health knowledge and reproductive behavior among female patients with ARDs. • The questionnaire was comprehensible for participants, and showed good reliability and consistency capturing reproductive knowledge and behavior. • This tool may aid in the design of strategies to improve reproductive decision-making for female patients with ARDs.

Anti-Drug Antibodies in the Biological Therapy of Autoimmune Rheumatic Diseases.

Autoimmune rheumatic diseases are a cluster of heterogeneous disorders that share some clinical symptoms such as pain, tissue damage, immune deregulation, and the presence of inflammatory mediators. Biologic disease-modifying antirheumatic drugs are some of the most effective treatments for rheumatic diseases. However, their molecular and pharmacological complexity makes them potentially immunogenic and capable of inducing the development of anti-drug antibodies. TNF inhibitors appear to be the main contributors to immunogenicity because they are widely used, especially in rheumatoid arthritis. Immunogenicity response on these treatments is crucial since the appearance of ADAs has consequences in terms of safety and efficacy. Therefore, this review proposes an overview of the immunogenicity of biological agents used in autoimmune rheumatic diseases highlighting the prevalence of anti-drug antibodies.

COVID-19 quarantine in adolescents with autoimmune rheumatic diseases: mental health issues and life conditions.

OBJECTIVES: To assess mental health and life conditions in adolescents with autoimmune rheumatic diseases (ARDs) and healthy controls quarantined during COVID-19 pandemic. METHOD: A cross-sectional study included 155 ARD adolescents and 105 healthy controls. Online survey included self-reported strengths and difficulties questionnaire (SDQ), and a semi-structured questionnaire with demographic data, daily home and school routine, physical activities, and COVID-19 information during the pandemic. RESULTS: Among patients, 56% had juvenile idiopathic arthritis (JIA), 29% juvenile systemic lupus erythematosus (JSLE), and 15% juvenile dermatomyositis (JDM). No differences were found regarding sex, ethnicity, and current age between ARD patients and controls (p > 0.05). Abnormal emotional SDQ (38% vs. 35%, p = 0.653) were similar in both groups. Logistic regression analyses in ARD patients demonstrated that female (OR = 2.4; 95%CI 1.0-6.0; p = 0.044) was associated with severe emotional SDQ dysfunction, whereas sleep problems were considered as a risk factor for both worse total SDQ (OR = 2.6; 95%CI 1.2-5.5; p = 0.009) and emotional SDQ scores (OR = 4.6; 95%CI 2.2-9.7; p < 0.001). Comparisons between ARD patients with and without current prednisone use showed higher median scores of peer problems in the first group [3 (0-10) vs. 2 (0-7), p = 0.049], whereas similar median and frequencies between JIA, JSLE, and JDM (p > 0.05). CONCLUSIONS: Approximately one third of JIA, JSLE, and JDM patients presented abnormal total and emotional scores of SDQ during COVID-19 quarantine. Sleep problems were the main factor associated with emotional difficulties in these ARD adolescents. The knowledge of mental health issues rates in adolescents with ARD supports the development of prevention strategies, like sleep hygiene counseling, as well as the references of the affected patients to specialized mental health services, as necessary. Key Points • One third of ARD patients presented mental health issues during COVID-19 quarantine • Sleep problems were associated with emotional difficulties. • It is necessary to warn pediatric rheumatologists about the importance of sleep hygiene counseling.

Oral and maxillofacial manifestations of IgG4-related disease: A clinicopathological study.

BACKGROUND: IgG4-related disease is a fibroinflammatory and immune-mediated condition, which has extremely variable clinical manifestations. In this study, we aim to investigate the clinicopathological features of IgG4-related disease involving the oral and maxillofacial region. METHODS: Cases of IgG4-related disease manifesting in the oral and maxillofacial region were retrieved from three Brazilian institutions. Clinical and serological data were obtained from the patients' medical charts, while microscopic and immunohistochemical findings were revised by oral pathologists. Diagnosis followed the American College of Rheumatology/European League against Rheumatism criteria. RESULTS: Seven patients diagnosed with IgG4-related disease were included in this study. Women were affected in all analysed cases, with a mean age of 55.4 years. Two patients presented with the clinical involvement of more than one oral and maxillofacial anatomic site. Therefore, our sample comprised nine oral and maxillofacial anatomic sites affected by IgG4-related disease. The submandibular gland was affected in four cases, the tongue and the parotid gland in two cases each, and the palate in one case. In a few cases, exploratory lower lip biopsy was used as a diagnostic approach. A moderate-to-severe lymphoid infiltrate containing plasma cells and lymphocytes, with an increased IgG4/IgG ratio, was common. Treatment varied and steroids were the most frequently used (57.4%). Six patients remained alive, while one died from unknown causes. CONCLUSION: Although major salivary glands are commonly affected by IgG4-related disease, the oral cavity can also be involved, and lower lip biopsy may be an auxiliary diagnostic tool.

Adverse events of six COVID-19 vaccines in patients with autoimmune rheumatic diseases: a cross-sectional study.

Data regarding COVID-19 vaccine efficacy and adverse events (AE) in patients with autoimmune and inflammatory rheumatic diseases (AIIRD) have been published recently although these mostly include the mRNA vaccines (Pfizer-BioNTech and Moderna) and the ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca). This research aimed to study the prevalence of AE presented with six different SARS-CoV-2 vaccines {ChadOX1 nCoV-19 (AZD1222), Ad5-nCoV2, Ad26.COV2.S, mRNA-1273, BNT162b2, and CoronaVac} in Mexican patients with AIIRD. We performed a cross-sectional study about vaccine history. Two hundred and twenty five consecutive patients were recruited, mean age was 50.7 years and the majority (n = 213; 94.6%) were females. One hundred and seven (47.5%) received BNT162b2 mRNA, 34 (15.1%) Ad5-nCoV, 29 (12.8%) mRNA-1273, 28 (12.4%) ChAdOX1 nCoV-19 (AZD1222), 22 (9.7%) CoronaVac and 5 (2.2%) Ad26.COV2.S. The vaccines that had the most AE proportionally to the number of patients vaccinated were Janssen (5; 100%) followed by Pfizer-BioNTEch (86; 80%) and CanSinoBIO (27; 79.4%). Localized pain was the most frequent (158; 70.2%) AE. Fatigue (78; 34.7%), headache (69; 30.6%) and muscle ache (66; 29.3%) were the most common systemic symptoms. No serious AE that required medical attention or hospitalization were reported. The current results support the safety of different COVID-19 vaccines in patients with AIIRD. This information can help fight vaccine hesitancy in this population.

Adverse drug reactions associated with treatment in patients with chronic rheumatic diseases in childhood: a retrospective real life review of a single center cohort.

BACKGROUND: Adverse drug reactions (ADRs) are the sixth leading causes of death worldwide; monitoring them is fundamental, especially in patients with disorders like chronic rheumatic diseases (CRDs). The study aimed to describe the ADRs investigating their severity and associated factors and resulting interventions in pediatric patients with CRDs. METHODS: A retrospective, descriptive and analytical study was conducted on a cohort of children and adolescents with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). The study evaluated medical records of the patients to determine the causality and the management of ADRs. In order to investigate the risk factors that would increase the risk of ADRs, a logistic regression model was carried out on a group of patients treated with the main used drug. RESULTS: We observed 949 ADRs in 547 patients studied. Methotrexate (MTX) was the most frequently used medication and also the cause of the most ADRs, which occurred in 63.3% of patients, followed by glucocorticoids (GCs). Comparing synthetic disease-modifying anti-rheumatic drugs (sDMARDs) vs biologic disease-modifying anti-rheumatic drugs (bDMARDs), the ADRs attributed to the former were by far higher than the latter. In general, the severity of ADRs was moderate and manageable. Drug withdrawal occurred in almost a quarter of the cases. In terms of risk factors, most patients who experienced ADRs due to MTX, were 16 years old or younger and received MTX in doses equal or higher than 0.6 mg/kg/week. Patients with JIA and JDM had a lower risk of ADRs than patients with JSLE. In the multiple regression model, the use of GCs for over 6 months led to an increase of 0.5% in the number of ADRs. CONCLUSIONS: Although the ADRs highly likely affect a wide range of children and adolescents with CRDs they were considered moderate and manageable cases mostly. However, triggers of ADRs need further investigations.

Adverse drug reactions associated with treatment in patients with chronic rheumatic diseases in childhood: a retrospective real life review of a single center cohort

Abstract Background: Adverse drug reactions (ADRs) are the sixth leading causes of death worldwide; monitoring them is fundamental, especially in patients with disorders like chronic rheumatic diseases (CRDs). The study aimed to describe the ADRs investigating their severity and associated factors and resulting interventions in pediatric patients with CRDs. Methods: A retrospective, descriptive and analytical study was conducted on a cohort of children and adolescents with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). The study evaluated medical records of the patients to determine the causality and the management of ADRs. In order to investigate the risk factors that would increase the risk of ADRs, a logistic regression model was carried out on a group of patients treated with the main used drug. Results: We observed 949 ADRs in 547 patients studied. Methotrexate (MTX) was the most frequently used medication and also the cause of the most ADRs, which occurred in 63.3% of patients, followed by glucocorticoids (GCs). Comparing synthetic disease-modifying anti-rheumatic drugs (sDMARDs) vs biologic disease-modifying antirheumatic drugs (bDMARDs), the ADRs attributed to the former were by far higher than the latter. In general, the severity of ADRs was moderate and manageable. Drug withdrawal occurred in almost a quarter of the cases. In terms of risk factors, most patients who experienced ADRs due to MTX, were 16 years old or younger and received MTX in doses equal or higher than 0.6 mg/kg/week. Patients with JIA and JDM had a lower risk of ADRs than patients with JSLE. In the multiple regression model, the use of GCs for over 6 months led to an increase of 0.5% in the number of ADRs. Conclusions: Although the ADRs highly likely affect a wide range of children and adolescents with CRDs they were considered moderate and manageable cases mostly. However, triggers of ADRs need further investigations.(AU)

What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases.

Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases.

What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases / O que o reumatologista deve saber sobre as manifestações orofaciais das doenças reumáticas autoimunes

ABSTRACT Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases.

RESUMO Manifestações orofaciais ocorrem com frequência nas doenças reumáticas e, comumente, representam sinais iniciais ou de atividade da doença que ainda são negligenciados na prática clínica. Entre as doenças reumáticas autoimunes com possíveis manifestações orais, incluem-se a artrite reumatoide (AR), miopatias inflamatórias (MI), esclerose sistêmica (ES), lúpus eritematoso sistêmico (LES), policondrite recidivante (PR) e síndrome de Sjögren (SS). Sinais e sintomas orofaciais como hipossalivação, xerostomia, disfunções temporomandibulares, lesões na mucosa bucal, doença periodontal, disfagia e disfonia podem ser a primeira expressão dessas doenças reumáticas. Esse artigo revisa as principais manifestações orofaciais das doenças reumáticas que podem ser de interesse do reumatologista, para diagnóstico e acompanhamento das doenças reumáticas autoimunes.

What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases. / O que o reumatologista deve saber sobre as manifestações orofaciais das doenças reumáticas autoimunes.

Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases.

The challenge of identification of autoantibodies specific to systemic autoimmune rheumatic diseases in high throughput operation: proposal of reliable and feasible strategies.

BACKGROUND: Autoantibodies to extractable nuclear antigens (ENA) are good biomarkers for systemic autoimmune rheumatic diseases (SARD), but no one assay for the detection of these antibodies provides satisfactory sensitivity and positive predictive value (PPV). Here we evaluate current assays and propose novel strategies to detect anti-ENA antibodies. METHODS: Diagnostic performance of double immunodiffusion (DID) and several enzyme immunoassays (EIA) for the detection of anti-ENA autoantibodies was determined using samples from 144 patients with a previous clinical diagnosis of SARD and 121 non-autoimmune individuals. A 2-step assay combining EIA and DID was developed and tested on 16,458 serum samples. RESULTS: EIA was more sensitive than DID for all anti-ENA antibodies, but yielded lower PPV (mean=66%) than DID (mean=96%) and a higher percentage of unexpected positive results. ROC-curve guided cut-off adjustments improved PPV for most EIA kits. Using the 2-step assay, over 80% of the samples were screened out by the first step (EIA), with results available within 24h, leaving only about 20% to be confirmed by DID. 2.9% of the 16,485 samples were found to be positive. CONCLUSIONS: A 2-step assay combining the speed and potential for automation of EIA with the high specificity and PPV of DID allows efficient and reliable detection of anti-ENA antibodies. Alternatively, improved PPV can be achieved by adjusting cut-off values for EIA assay results.