20 Diagnosis and treatment of neuropsychiatric lupus

Neuropsychiatric (NP) involvement is one of the most complex and challenging features of systemic lupus erythematosus (SLE) encompassing the central (CNS), peripheral (PNS) and autonomous nervous system (ANS) as defined by the 1999 American College of Rheumatology standard nomenclature and case definitions. NPSLE has a negative impact on patient's quality of life and is associated with increased morbidity and mortality. The full disease burden of NPSLE is not clearly known, because robust epidemiology studies are lacking or biased by different methodology design. A realistic estimate of the prevalence of NP involvement in SLE is around fifty percent of SLE patients. The challenge of diagnosis: As none of the NP syndromes that occur in SLE have features that are specific for SLE, determination of the correct attribution of NP events in SLE patients is a challenging but critical step in the treatment of individual patients and in performing research studies. In fact, erroneous attribution can lead to suboptimal treatment and to incorrect designation of patient groups in research studies. Approximately 30% of all NP events are attributable to SLE (NPSLE) and present most frequently around the time of SLE onset. Modern and rapidly evolving neuroimaging technologies can help clinicians in both diagnosis and follow up. A multidisciplinary expert team represents the best strategy for NPSLE. The challenge of treatment: The main proposed pathogenetic pathways include both ischemic and neuroinflammatory mechanisms with evidence for complement and microglia activation. Following diagnosis and causal attribution, the treatment of NPSLE should be tailored to the type of NP event, the predominant putative pathogenic mechanism, in addition to the history (acute or chronic), activity and severity of the clinical event. To treat NPSLE, in the absence of high-level evidence, it is necessary to develop pragmatic therapeutic strategies supported by expert opinion, published observational cohort data on NPSLE and extrapolation from experience with other organ system disease in SLE. To date, therapeutic options include symptomatic, anti-thrombotic and immunosuppressive agents. Therapeutic recommendations released by EULAR in 2010 and, more recently, by ACR/EULAR in 2019 are available.1–5 Although neuropsychiatric manifestations of SLE have been recognised for over 100 years, unmet needs for patients with NPSLE still exist, including a lack of diagnostic biomarkers, lack of novel therapies and lack of clinical trials, which should be focused on future research agendas. Learning Objectives Explain the diagnostic challenges in NPSLE with focus on the attribution and neuroimaging Discuss the current knowledge about the main pathogenetic mechanisms of NPSLE Explain the available and novel therapeutic options to treat NPSLE Describe unmet needs in the approach to the diagnosis and management of NPSLE References Govoni M, Bortoluzzi A, Padovan M, et al. The diagnosis and clinical management of the neuropsychiatric manifestations of lupus. J Autoimmun 2016;74:41–72. Bortoluzzi A, Scire CA, Bombardieri S, et al. Development and validation of a new algorithm for attribution of neuropsychiatric events in systemic lupus erythematosus. Rheumatology (Oxford) 2015;54(5):891–8. Hanly JG, Kozora E, Beyea SD, et al. Review: Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions. Arthritis Rheumatol 2019;71(1):33–42. Nikolopoulos D, Fanouriakis A, Boumpas DT. Update on the pathogenesis of central nervous system lupus. Curr Opin Rheumatol 2019;31(6):669–77. Schwartz N, Stock AD, Putterman C. Neuropsychiatric lupus: new mechanistic insights and future treatment directions. Nat Rev Rheumatol 2019;15(3):137–52

The Role of Micro-RNAs in Rheumatic Diseases: An Update

In this article we summarize the new acquisitions about the growing importance of miRNAs in rheumatic diseases as pathogenetic factors, potential biomarkers and possible new therapeutic targets. We also focus on new developments about the possible role of miRNA in the pathogenesis of psoriatic arthritis (PsA) on the basis of our recent experimental results

Focus on Sex and Gender: What We Need to Know in the Management of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease, affecting mostly women with a female/male ratio of 3:1. It is characterized by symmetrical polyarthritis, leading to progressive joint damage. Sex differences have been reported in terms of disease course and characteristics, influencing patients reported outcome measures (PROMs) and pain perception, ultimately leading to male-female disparities in treatment response. Notwithstanding, sex and gender discrepancies are still under-reported in clinical trials. Therefore, there is a consistent need for a precise reference of sex and gender issues in RA studies to improve treat-to-target achievement. This narrative review explores the above-mentioned aspects of RA disease, discussing the latest core principles of RA recommendations, from safety issues to early arthritis concept and management, treat-to-target and difficult-to-treat notions, up to the most recent debate on vaccination. Our final purpose is to evaluate how sex and gender can impact current management guidelines and how this issue can be integrated for effective disease control

JAK ACADEMY in Rheumatoid Arthritis (RA)

The latest update of the EULAR recommendations for the treatment of RA maintain csDMARD (conventional systemic DMARDs) as the first line treatment, with methotrexate (MTX) still identified as the anchor drug, to which it is possible to add, in failure patients with negative prognostic factors, a biological drug or a tsDMARD (target synthetic DMARD), i.e JAK inhibitors

Uterine artery Doppler in predicting pregnancy outcome in women with connective tissue disorders

n/

Editorial: Lupus and the Brain: Advances in Neuropsychiatric Systemic Lupus Erythematosus

Editorial on the Research Topic Lupus and the Brain: Advances in Neuropsychiatric Systemic Lupus Erythematosu

[Semeiology of "early arthritis"].

The main problems related to "early arthritis" are making an accurate diagnosis and predicting the outcome. Clinical evidence strongly suggest that structural damage occur early and that early DMARD treatment improves the long term outcome of disease. Clinical criteria would facilitate early referral of the patients to establish the risk of persistent disease. From the "early arthritis clinics" (E.A.C.) experience has been developed a set of diagnostic criteria characterized by an excellent ability to discriminate, at the first visit, between self-limiting, persistent non-erosive and persistent erosive arthritis. The proposed set consists of 7 criteria: symptom duration (6 weeks – 6 months), morning stiffness of at least 1 hour, arthritis in ≥ 3 joints, bilateral compression pain in the metatarsophalangeal joints, IgM-rheumatoid factor positivity, anti-cyclic-citrullinated-peptide antibody positivity and erosions on radiographs of the hands or feet. This approach requests an easy organization to simplify the access to sanitary services and represents an hard challenge both for rheumatologist and health administration

A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release

Introduction The reduction of the inflammatory status represents one of the most important targets in rheumatoid arthritis (RA). A central role of A2A and A3 adenosine receptors (ARs) in mechanisms of inflammation has been reported in different pathologies. The primary aim of this study was to investigate the A2A and A3ARs and their involvement in RA progression measured by Disease Activity Score in 28 or 44 joints (DAS28 or DAS). Methods ARs were analyzed by saturation binding assays, mRNA and Western blotting analysis in lymphocytes from early and established RA patients. The effect of A2A and A3AR agonists in nuclear factor kB (NF-kB) pathway was evaluated. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) release was carried out by A2A and A3AR activation. AR pharmacological regulation in matrix metalloproteinase-1 (MMP-1) and metalloproteinase-3 (MMP-3) release was also studied. Results In lymphocytes obtained from RA patients, A2A and A3ARs were up-regulated if compared with healthy controls. A2A and A3AR activation inhibited the NF-kB pathway and diminished inflammatory cytokines such as TNF-α, IL-1β and IL-6. A2A and A3AR agonists mediated a reduction of MMP-1 and MMP-3 release. A2A and A3AR density inversely correlated with DAS28 and DAS suggesting a direct role of the endogenous activation of these receptors in the control of RA joint inflammation. Conclusions Taken together these data demonstrate that the inflammatory and clinical responses in RA are regulated by A2A and A3ARs and support the use of A2A and/or A3AR agonists as novel and effective pharmacological treatment in RA patients

Recurrent and refractory lower limbs lymphedema in psoriatic arthritis: a case description and literature review

Lymphedema is an uncommon extra-articular complication of rheumatoid arthritis (RA), but it can also be associated with psoriatic arthritis (PsA), although rarely. While lymphedema associated with RA is well characterized in literature, only few cases have been described among patients with PsA. Upper limbs are the most common sites involved, with asymmetric pattern, even if some patients may present lower limb oedema, or progressive bilateral oedema. Chronic established lymphoedema deriving from lymphatic vessel dysfunction should be clearly distinct from inflammatory distal pitting edema (IDPE), resulting from tenosynovitis and frequently encountered in PsA. In contrast to lymphedema, the latter condition generally presents an excellent response to steroid therapy, therefore it is essential to recognize the exact etiology of lymphoedema to approach the correct treatment. Here we report a case of lower limbs lymphedema in PsA and review the available literature upon the topic