Optical coherence tomography angiography as a potential tool in differential diagnosis of multiple sclerosis and rheumatic disorders with central nervous system involvement.

PURPOSE: The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous system (CNS) involvement in rheumatic disorders (RD) from multiple sclerosis (MS). METHODS: A total of 85 patients- 41 with MS, 21 with RD with CNS involvement and 23 healthy controls were included in the study. All individuals underwent OCTA and the following parameters were measured in each eye separately: average foveal and parafoveal vessel density (VD), average foveal and parafoveal vessel length (VL) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as area, perimeter, and circularity of the foveal avascular zone. RESULTS: OCTA showed a VD reduction in the foveal region of the SCP in eyes of RD patients when compared to MS patients (21.96 ± 3.39 vs.23.88 ± 3.05 (p = 0.003)). There have been no significant differences in any of the assessed parameters that is average VD and total average VL in the foveal area of the SCP as well as of the DCP in the general population comprising healthy controls, MS and RD groups (p > 0.05 for all). CONCLUSIONS: Our results suggest that an OCTA finding of decreased VD in the foveal region of the SCP may be considered as a potentially useful biomarker of RD in comparison with MS patients.

MicroRNAs-mediated regulation pathways in rheumatic diseases.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two common rheumatic disorders marked by persistent inflammatory joint disease. Patients with RA have osteodestructive symptoms, but those with AS have osteoproliferative manifestations. Ligaments, joints, tendons, bones, and muscles are all affected by rheumatic disorders. In recent years, many epigenetic factors contributing to the pathogenesis of rheumatoid disorders have been studied. MicroRNAs (miRNAs) are small, non-coding RNA molecules implicated as potential therapeutic targets or biomarkers in rheumatic diseases. MiRNAs play a critical role in the modulation of bone homeostasis and joint remodeling by controlling fibroblast-like synoviocytes (FLSs), chondrocytes, and osteocytes. Several miRNAs have been shown to be dysregulated in rheumatic diseases, including miR-10a, 16, 17, 18a, 19, 20a, 21, 27a, 29a, 34a, 103a, 125b, 132, 137, 143, 145, 146a, 155, 192, 203, 221, 222, 301a, 346, and 548a.The major molecular pathways governed by miRNAs in these cells are Wnt, bone-morphogenic protein (BMP), nuclear factor (NF)-κB, receptor activator of NF-κB (RANK)-RANK ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) receptor pathway. This review aimed to provide an overview of the most important signaling pathways controlled by miRNAs in rheumatic diseases.

A systematic review on mucocutaneous presentations after COVID-19 vaccination and expert recommendations about vaccination of important immune-mediated dermatologic disorders.

With dermatologic side effects being fairly prevalent following vaccination against COVID-19, and the multitude of studies aiming to report and analyze these adverse events, the need for an extensive investigation on previous studies seemed urgent, in order to provide a thorough body of information about these post-COVID-19 immunization mucocutaneous reactions. To achieve this goal, a comprehensive electronic search was performed through the international databases including Medline (PubMed), Scopus, Cochrane, Web of science, and Google scholar on July 12, 2021, and all articles regarding mucocutaneous manifestations and considerations after COVID-19 vaccine administration were retrieved using the following keywords: COVID-19 vaccine, dermatology considerations and mucocutaneous manifestations. A total of 917 records were retrieved and a final number of 180 articles were included in data extraction. Mild, moderate, severe and potentially life-threatening adverse events have been reported following immunization with COVID vaccines, through case reports, case series, observational studies, randomized clinical trials, and further recommendations and consensus position papers regarding vaccination. In this systematic review, we categorized these results in detail into five elaborate tables, making what we believe to be an extensively informative, unprecedented set of data on this topic. Based on our findings, in the viewpoint of the pros and cons of vaccination, mucocutaneous adverse events were mostly non-significant, self-limiting reactions, and for the more uncommon moderate to severe reactions, guidelines and consensus position papers could be of great importance to provide those at higher risks and those with specific worries of flare-ups or inefficient immunization, with sufficient recommendations to safely schedule their vaccine doses, or avoid vaccination if they have the discussed contra-indications.

Hydroxychloroquine early in pregnancy and risk of birth defects.

BACKGROUND: Hydroxychloroquine is generally considered safe in pregnancy for the treatment of rheumatic conditions, but studies have been too small to evaluate teratogenicity. Quantifying the risk of congenital malformations associated with early pregnancy exposure to hydroxychloroquine is important in both the context of its ongoing use for rheumatological disorders and its potential future use for coronavirus disease 2019 prophylaxis, for which a number of clinical trials are ongoing despite initial trials for coronavirus disease 2019 treatment having been negative. OBJECTIVE: The study objective was to evaluate the risk of major congenital malformations associated with exposure to hydroxychloroquine during the first trimester of pregnancy, the period of organogenesis. STUDY DESIGN: We performed a population-based cohort study nested in the Medicaid Analytic eXtract (MAX, 2000-2014) and IBM MarketScan Research Database (MarketScan, 2003-2015). The source cohort included 2045 hydroxychloroquine-exposed pregnancies and 3,198,589 pregnancies not exposed to hydroxychloroquine continuously enrolled in their respective insurance program for 3 months before the last menstrual period through at least 1 month after delivery; infants were enrolled for at least 3 months after birth. We compared the risk of congenital malformations in women using hydroxychloroquine during the first trimester of pregnancy with that of those not using hydroxychloroquine, restricting the cohort to women with rheumatic disorders and using propensity score matching to control for indication, demographics, medical comorbidities, and concomitant medications (1867 hydroxychloroquine-exposed pregnancies and 19,080 pregnancies not exposed to hydroxychloroquine). The outcomes considered included major congenital malformations diagnosed during the first 90 days after delivery and specific malformation types for which there were at least 5 exposed events: oral cleft, cardiac, respiratory, gastrointestinal, genital, urinary, musculoskeletal, and limb defects. RESULTS: Overall, 54.8 per 1000 infants exposed to hydroxychloroquine were born with a major congenital malformation versus 35.3 per 1000 unexposed infants, corresponding to an unadjusted relative risk of 1.51 (95% confidence interval, 1.27-1.81). Patient characteristics were balanced in the restricted, propensity score-matched cohort. The adjusted relative risk was 1.26 (95% confidence interval, 1.04-1.54); it was 1.33 (95% confidence interval, 1.08-1.65) for a daily dose of ≥400 mg and 0.95 (95% confidence interval, 0.60-1.50) for a daily dose of <400 mg. Among the different malformation groups considered, more substantial increases in the risk of oral clefts, respiratory anomalies, and urinary defects were observed, although estimates were imprecise. No pattern of malformation was identified. CONCLUSION: Our findings suggest a small increase in the risk of malformations associated with first-trimester hydroxychloroquine use. For most patients with autoimmune rheumatic disorders, the benefits of treatment during pregnancy will likely outweigh this risk. If hydroxychloroquine were shown to be effective for coronavirus disease 2019 prophylaxis in ongoing trials, the risk of malformations would need to be balanced against such benefits.

[Flexible programs and advanced training for rheumatological patient education]. / Flexible Programme und Fortbildungen für die rheumatologische Patientenschulung.

In two research projects, rheumatological patient education programmes were updated. The first step was to develop an expert consented framework for all rheumatological patient education programmes. From this, curricula and working materials for rheumatoid arthritis (RA) and axial spondyloarthritis (AS) were derived and two exemplary patient education manuals developed. A randomized controlled trail was designed for the five-hour RA basic education program. Finally, existing train-the-trainer training courses were adapted for these patient education programmes.

Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms.

Today, inflammatory rheumatic disorders are effectively treated, but many patients still suffer from residual fatigue. This work presents pathophysiological mechanisms of fatigue. First, cytokines can interfere with neurotransmitter release at the preterminal ending. Second, a long-term increase in serum concentrations of proinflammatory cytokines increase the uptake and breakdown of monoamines (serotonin, noradrenaline and dopamine). Third, chronic inflammation can also decrease monoaminergic neurotransmission via oxidative stress (oxidation of tetrahydrobiopterin [BH4]). Fourth, proinflammatory cytokines increase the level of enzyme indoleamine-2, 3-dioxygenase activity and shunt tryptophan away from the serotonin pathway. Fifth, oxidative stress stimulates astrocytes to inhibit excitatory amino acid transporters. Sixth, astrocytes produce kynurenic acid that acts as an antagonist on the α7-nicotinic acetylcholine receptor to inhibit dopamine release. Jointly, these actions result in increased glutamatergic and decreased monoaminergic neurotransmission. The above-described pathophysiological mechanisms negatively affect brain functioning in areas that are involved in fatigue.

Risk factors for incident shoulder soft tissue rheumatic disorders: a population-based case-control study in Lebanon.

BACKGROUND: Soft tissue rheumatic disorders (STRDs) are very common and impact enormously general population, working groups and physiotherapist practices. However, they do not have neither a clear case definition nor objective tests to be accurately diagnosed rendering them neglected with poorly-estimated burden. Shoulder is one of the most frequent sites for STRDs. AIM: The aim of this study was to identify risk factors for shoulder STRDs among Lebanese adults aged ≥ 15 years. METHODS: A case-control study was designed based on data from the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) study conducted in Lebanon in 2009. Cases were defined as those who recently suffered from shoulder pain, tenderness or stiffness with duration not exceeding 12 months (52 cases). These were frequency-matched by age and gender with 208 controls who never experienced any musculoskeletal pain. RESULTS: Area of residence, physical activity, family history and stress-induced sleep difficulty were significantly associated with shoulder STRDs after adjusting for cigarette smoking, job nature and family monthly income. CONCLUSION: Factors associated with shoulder STRD among the Lebanese population include geographical location, psychosocial factors, physical activity and familial predisposition. Further longitudinal studies are needed to establish a temporal sequence and explore other potential determinants, especially among the working population.

Paraneoplastic systemic sclerosis associated with colorectal carcinoma.

A number of rheumatic disorders may appear as paraneoplastic syndromes, the most common being dermatomyositis or polymyositis. Systemic sclerosis is associated with a slightly increased risk of cancer, although its direct association with malignancies is controversial. We describe a case of a 57-year-old male with rectal adenocarcinoma and systemic sclerosis. Close temporal relationship between the initial presentation and parallel course of both conditions, as well as atypically rapid progression of systemic sclerosis symptoms, were observed in the reported case. The strict relation between these two conditions suggested that systemic sclerosis was a paraneoplastic syndrome rather than a concomitant morbidity in the presented patient. Current literature on systemic sclerosis coexisting with colorectal tumours is very limited, especially in the paraneoplastic setting.

The effects of bolus supplementation of branched-chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment.

OBJECTIVES: To test the effects of bolus supplementation of branched-chain amino acids (BCAA) on skeletal muscle mass, strength, and function in patients with rheumatic disorders taking glucocorticoid (GC). METHODS: Patients with rheumatic disorders treated with prednisolone (≥10 mg/day) were randomized to ingest additional daily 12 g of BCAA (n = 9) or not (n = 9) for 12 weeks. At baseline, and 4, 8, and 12 weeks, they underwent bioelectrical impedance analysis, muscle strength and functional tests, and computed tomography analysis for cross-sectional area of mid-thigh muscle. RESULTS: Disease activities of the patients were well controlled and daily GC dose was similarly reduced in both groups. Limb muscle mass was recovered in both groups. Whole-body muscle mass and muscle strength and functional mobility were increased only in BCAA (+) group. The effects of BCAA supplementation on recovering skeletal muscle mass were prominent in particular muscles including biceps femoris muscle. CONCLUSIONS: This trial is the first-in-man clinical trial to demonstrate that BCAA supplementation might be safe and, at least in part, improve skeletal muscle mass, strength, and function in patients with rheumatic disorders treated with GC.

Systemic Sarcoidosis With Neurosarcoidosis Features as a Risk Factor for Multifocal Osteonecrosis.

Sarcoidosis is a systemic inflammatory disease that affects diverse organs such as the lungs, skin, eyes, and brain. Osseous involvement in sarcoidosis usually affects bones of the appendages with direct infiltration of non-caseating granulomas without bony infarcts. Symptoms of sarcoid bone lesions respond well to corticosteroid therapy. In contrast, corticosteroids act as a risk factor for the development of osteonecrosis resulting in pain and disability. Osteonecrosis that involves three or more different anatomic sites, defined as multifocal osteonecrosis (MFON), is rare. MFON has not been documented in the setting of sarcoidosis. We report a systemic sarcoidosis patient with predominant neuropsychiatric manifestations, who progressively developed MFON. Despite the limited use of corticosteroid treatment, the high burden of systemic sarcoidosis and its related neuropsychiatric involvementmay have collectively contributed to the development of MFON. This case highlights the rare association of MFON with systemic sarcoidosis and the need for further investigation into the underlying pathogenesis of MFON to prevent disability and morbidity.

Double-negative T cells in pediatric rheumatic diseases.

Double-negative (CD4-CD8-) T (DNT) cells have been implicated in Autoimmune Lymphoproliferative Syndrome (ALPS), where their expansion inside the circulating pool of T cells represents a diagnostic criterion. Recent experimental evidence has supported the immunomodulatory roles of DNT cells, and studies in adult patients have suggested that they may be altered in some immune-mediated conditions. This study aimed to retrieve available data on circulating DNT cells in pediatric rheumatic disorders that do not arise in the context of ALPS through a systematic literature review of three scientific databases (PubMed, Scopus, and Web of Science). The final output of the systematic literature search consisted of eight manuscripts, including cross-sectional (n=6) and longitudinal (n=2) studies. Overall, the pooled population of patients includes children affected with pediatric Systemic Lupus Erythematosus (n=104), Juvenile Idiopathic Arthritis (n=92), Behçet's disease (n=15), mixed connective tissue disease (n=8), Juvenile Dermatomyositis (n=6), and Kawasaki disease/multisystem inflammatory disease in children (n=1 and n=14, respectively); moreover, one study also included 11 children with a high titer of antinuclear antibody but no diagnosis of rheumatic disease. All studies except one included a control group. The number of DNT cells were increased in most studies of children with rheumatic diseases. Even if such a limited number of studies and their great heterogeneity in several methodological aspects do not allow for reliable conclusions about the relevance of DNT cells in specific rheumatic conditions in children, this cell population deserves further investigation in this pathological setting through well-designed clinical studies.

Compensation mechanisms for lost productivity: a comparison between four European countries.

OBJECTIVE: Productivity costs are usually estimated by multiplying the wage with the period absent. This can lead to an overestimation if compensation mechanisms occur. Until now only Dutch data are available on the influence of compensation mechanisms on lost productivity, but between-country differences in frequency and type of compensation mechanisms can be expected. The objective of this study was to understand whether compensation mechanisms for days absent from paid work differ in type and frequency across countries and to explore whether this would result in between-country differences in relevant lost productivity. METHODS: Data from a cross-sectional survey among respondents with rheumatic disorders from four countries were the basis for this study. Analyses focused on respondents with paid employment who reported absence in the last 3 months. The different compensation mechanisms are described and the resulting lost productivity in terms of days absent was calculated with and without taking compensation mechanisms into account. Logistic regression analyses were performed to examine which variables influence compensation mechanisms leading to relevant lost productivity. RESULTS: The results indicate that compensation mechanisms occur and are relevant in all four countries. Between-country differences in the type and frequency of compensation mechanisms and relevant lost productivity were observed. The logistic regression analyses indicate that, correcting for other variables, this is also the case for the use of compensation mechanisms leading to relevant lost productivity. CONCLUSIONS: Between-country differences in compensation mechanisms in case of absenteeism exist and could vary to such an extent that foreign relevant lost productivity data should be used with caution.

Immunological Pathways in Sarcoidosis and Autoimmune Rheumatic Disorders-Similarities and Differences in an Italian Prospective Real-Life Preliminary Study.

BACKGROUND: The pathogenesis of sarcoidosis involves T cells and B lymphocytes that produce autoantibodies. We compared the expression of different T and B cell subsets in sarcoidosis and three B-mediated rheumatic diseases that can affect the lungs in an attempt to identify similarities and differences that distinguish these diseases. METHODS: The study included patients referred to Siena University Hospital's respiratory disease and rheumatology units. Patients were enrolled prospectively and consecutively. Healthy volunteers were also included. Multicolor flow cytometry was performed on phenotype T and B cell subsets. Multivariate analysis was carried out to reduce the dimensionality of the data. RESULTS: Fifteen patients had a diagnosis of sarcoidosis, fourteen idiopathic inflammatory myopathies (IIM), five granulomatosis with polyangiitis (GPA), ten microscopic polyangiitis (MPA), and seven were controls. Thirty-five T and B cell subsets were phenotyped, 15 of which were significantly different in sarcoidosis, B-mediated rheumatic disorders, and controls. Principal components analysis distinguished the four groups of patients with a total explained variance of 54.7%. A decision tree was constructed to determine which clustering variables would be most useful for distinguishing sarcoidosis, IIM, MPA, and GPA. The model showed regulatory T helper cells (Th-reg) > 5.70% in 91% of sarcoidosis patients as well as Th-reg ≤ 5.70 and Th17 > 43.27 in 100% of MPA. It also showed Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≥ 7.81 in 100% of GPA patients, and Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≤ 7.81 in 100% of IIM patients. CONCLUSION: The immune cell profile sheds light on similarities and differences between sarcoidosis and B-mediated rheumatic diseases. Sarcoidosis and autoimmune diseases show similar patterns of cellular immune dysregulation, suggesting a common pathogenic pathway that may provide an opportunity for further understanding autoimmunity and exploring biological therapies to treat sarcoidosis.

Potential Phytoconstituents of Genus Vitex for the Management of Rheumatoid Arthritis: A Review.

Rheumatoid arthritis is one of the most predominant conditions which have utmost influence on the society. The disease is an inflammatory disorder which affects joints, connective tissues, muscles, tendons and fibrous tissues. Approximately 270 known species of vitex genus are known, extending from shrubs to trees in the tropical, sub-tropical regions and temperate zones. Several species of vitex have been used traditionally over world-wide. The main focus of the present study is to review various phytoconstituents isolated from the genus vitex which can be used for the treatment of rheumatic disorders. The study also covers the underlying targets of the phytoconstituents which can be possible potential hits for the management of Rheumatic disorders.

Monocyte subpopulations display disease-specific miRNA signatures depending on the subform of Spondyloarthropathy.

Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations.

Very low calorie ketogenic diet and common rheumatic disorders: A case report.

BACKGROUND: The scientific literature provides evidence that nutritional ketosis can be an important support in the treatment of pathologies in which inflammation is present, as recent studies have shown that ketone bodies have anti-inflammatory activity in numerous diseases, including rheumatic diseases. We report the case of a 22-year-old woman with class I obesity and juvenile idiopathic arthritis who started treatment with a very low calorie ketogenic diet (VLCKD). CASE SUMMARY: The patient was a 22-year-old woman diagnosed with juvenile idiopathic arthritis at age 4 years and with a body mass index (BMI) of 30.8 kg/m2, waist circumference (WC) 80 cm, fat mass (FM) 28.1 kg, free FM 45.7 kg, and visceral adipose tissue (VAT) 3.5 kg, assessed on bioimpedance analysis. She was treated using a commercial VLCKD weight-loss program (PNK® method); this program provides high-biological-value protein preparations and natural foods. Each protein preparation contains 15 g protein, 4 g carbohydrate, 3 g fat, and 50 mg omega-3 docosahexaenoic acid, with an energy content of 90-120 kcal. After four months on the program, the BMI was 28.6 kg/m2, WC 73 cm, FM 23.2 kg, free FM 41.9 kg, and VAT 2.9 kg. CONCLUSION: VLCKD enabled the patient to reach her target weight and to reduce her joint pain and headaches. Laboratory inflammatory indices also normalized.

Knowledge About and the Use of Oral Nonsteroidal Anti-inflammatory Drugs Among Patients With Rheumatic Disorders in Saudi Arabia: A Cross-Sectional Study.

AIMS: The aims were to evaluate rheumatic disorder patients' knowledge of the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), dosage (from where the knowledge is acquired), contraindications (in pregnancy), and drug interactions (such as drug-related disorders), to improve their knowledge about taking NSAIDs in Saudi Arabia. STUDY DESIGN: It is a descriptive cross-sectional study. PLACE AND DURATION OF STUDY: The study was conducted among patients with rheumatic disorder (RD) in Saudi Arabia who were invited to join by completing an online questionnaire, from August to November 2022. METHODOLOGY: Patients with RD who were 16 years and older, received oral NSAIDs, and agreed to participate were included in the study. The data was collected using an Internet-based questionnaire. The Internet-based questionnaire was designed using the Google Forms (Google LLC, Mountain View, California, United States) online survey platform. A consent form accompanied the questionnaire in a cover letter briefly describing the investigation. RESULTS: A total of 756 participants answered the questionnaire and participated in the final analysis. Most of the participants (75.93%) were female. The type of NSAID used by the participants was Ibuprofen. The majority (83.41%) reported that they responded to the medication. When asked about the primary source of information about the correct dose of these medications, more than two-thirds (69.32%) reported that physicians are the main source of information. The majority of the participants (83.39%) denied using NSAIDs during pregnancy. Half of the participants (49.22%) said they had discussed these medications' harmful effects with their doctors or pharmacists. The female participants were more knowledgeable about NSAIDs and their side effects than the males. CONCLUSION: The patient's knowledge related to the use of oral NSAIDs was not that satisfactory. There is an urgent need to educate the public regarding the appropriate use of NSAIDs by healthcare providers, particularly in relation to their proper use, potential side effects, and risks associated with long-term use.

Immunogenicity of Rituximab biosimilar GP2013 in chronic inflammatory rheumatic disorders in daily clinical practice.

OBJECTIVE: To study in daily practice the risk of immunogenicity of patients treated with the biosimilar rituximab (RTX) GP2013 used for chronic inflammatory rheumatic disorders. METHODS: A prospective monocentric routine care study was carried out between September 2018 and May 2021, including consecutive patients treated with the biosimilar RTX GP2013. Biosamples were taken before each infusion to quantify anti-RTX antibodies (ADAbs) and serum RTX trough levels by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag). RESULTS: 168 GP2013-treated patients were included (129 who switched from originator RTX and 39 originator RTX naïve). The analysis of 602 samples identified 15 patients (8%) with positive ADAbs including 6 and 9 with transient and persistent ADAbs, respectively. The switch from originator RTX to GP2013 did not increase the risk of immunogenicity, with an incidence rate of 0.8 for 100 patient years. The frequency of persistent ADAs was higher in non-RA patients (5/56, 9% vs. 4/112, 3.5%). Patients with positive persistent ADAbs were more frequently non-caucasian (7/9, 78%, vs. 56/159, 35%, p<0.01) and all had detectable circulating B cells (vs. 40% in ADAb-negative patients, P<0.001). ADAb positivity was not associated with disease activity or RTX discontinuation but patients with ADAb titers >100 ng/mL experienced reduced treatment efficacy or severe infusion-related reaction. CONCLUSION: Within the study duration, the immunogenicity of GP2013 is a rare event affecting the pharmacodynamics of RTX. Although development of ADAbs had no impact on treatment discontinuation, possible harmful consequences may be observed in patients with high antibody levels.

Rheumatological Adverse Events of Cancer Therapy with Immune Checkpoint Inhibitors.

Latin America is experiencing a demographic and epidemiological transition, with an increase in non-communicable diseases such as cancer. One of the greatest advances in the therapeutic approach to cancer has been the discovery of immunotherapy, and specifically of checkpoint inhibitors (CPIs). Since inhibition of CTLA-4 and PD-1/PD-L1 enhances the immune response, cancer immunotherapies are associated with a new class of toxicities of autoimmune and/or autoinflammatory origin. These immune-related adverse events (irAEs) result in a broad spectrum of clinical events including rheumatic clinical syndromes, which may resemble classic rheumatic diseases. The most common rheumatic manifestations include inflammatory arthritis, myositis, vasculitis, and sicca syndrome. Recognizing rheumatologic irAEs is challenging due to the wide spectrum of clinical presentations that often do not fulfill traditional classification criteria of rheumatic diseases. A delayed diagnosis and treatment can lead to long-term disability, and disorders may become chronic and require ongoing immunosuppressive therapy. The management of irAEs includes the prompt detection and appropriate grading since their management is dictated by their severity. The growing use of CPIs, and the ensuing increase in irAEs, warrants an increasing collaboration between rheumatologists and oncologists. Understanding the pathophysiology, diagnosis, grading, and therapeutic implications of irAEs in patients with cancer is thus a requirement for Latin American oncologists and rheumatologists alike.

Treatment of Sexual Dysfunction in Women with Systemic Autoimmune Rheumatic Disorders: A Systematic Review.

INTRODUCTION: Female sexual dysfunction (SD) is an under-recognized and undertreated problem in patients with systemic autoimmune rheumatic disorders (SARDs). OBJECTIVES: To summarize and evaluate the existing treatment modalities for SD in females with SARDs. METHODS: A systematic review was conducted following the PRISMA guidelines. Electronic databases were searched up to April 2022 for studies that assessed the use of pharmacological and non-pharmacological treatment modalities for the management of SD in females with SARDs. Randomized and observational studies were included. (PROSPERO: CRD42022296381). RESULTS: Seven studies with 426 females with SD were included. Seven different treatment modalities belonging to 5 different classes (androgen therapy, phosphodiesterase-5 inhibitors, exercise, education and local creams) were evaluated in patients with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. The majority of the studies were of low methodological quality. Standardized patient education and 8-week aerobic walking programs were successful in improving female SD. Local creams improved dyspareunia in females with systemic sclerosis. Testosterone did not significantly improve SD in patients with systemic lupus erythematosus. Accordingly, tadalafil did not result in a significant improvement of SD in females with systemic sclerosis, based on the Female Sexual Function Index. CONCLUSION: There is a lack of sufficient evidence to recommend a certain management strategy for SD in females with SARDs. Nonpharmacological therapy and lubricant creams may be beneficial in females with SARDs. No benefit was demonstrated after androgen therapy or tadalafil. Still, no definite conclusions can be drawn due to the important limitations of the available literature. Overall, our results may be considered preliminary and further research in the field is mandatory. Baniotopoulos P, Pyrgidis N, Minopoulou I, et al. Treatment of Sexual Dysfunction in Women with Systemic Autoimmune Rheumatic Disorders: A Systematic Review. Sex Med Rev 2022;10:520-528.