Cardiovascular Magnetic Resonance Demonstrates Myocardial Inflammation of Differing Etiologies and Acuities in Patients with Genetic and Inflammatory Myopathies.

INTRODUCTION: Myopathies are heterogeneous neuromuscular diseases of genetic and/or inflammatory etiology that affect both cardiac and skeletal muscle. We investigated the prevalence of cardiac inflammation in patients with myopathies, cardiovascular symptoms, and normal echocardiography using cardiovascular magnetic resonance (CMR). METHODS: We prospectively evaluated 51 patients with various genetic (n = 23) and inflammatory (n = 28) myopathies (median age, IQR: 12 (11-15) years, 22% girls; 61 (55-65) years, 46% women, respectively) and compared their CMR findings to corresponding age- and sex-matched controls (n = 21 and 20, respectively) and to each other. RESULTS: Patients with genetic myopathy had similar biventricular morphology and function to healthy controls but showed higher late gadolinium enhancement (LGE), native T1 mapping, extracellular volume fraction (ECV), and T2 mapping values. Collectively, 22 (95.7%) patients with genetic myopathy had a positive T1-criterion and 3 (13.0%) had a positive T2-criterion according to the updated Lake Louise criteria. Compared with healthy controls, patients with inflammatory myopathy showed preserved left ventricular (LV) function and reduced LV mass, while all CMR-derived tissue characterization indices were significantly higher (p < 0.001 for all). All patients had a positive T1-criterion, and 27 (96.4%) had a positive T2-criterion. A positive T2-criterion or T2-mapping > 50 ms could discriminate between patients with genetic and inflammatory myopathies with a sensitivity of 96.4% and a specificity of 91.3% (AUC = 0.9557). CONCLUSIONS: The vast majority of symptomatic patients with inflammatory myopathies and normal echocardiography show evidence of acute myocardial inflammation. In contrast, acute inflammation is rare in patients with genetic myopathies, who show evidence of chronic low-grade inflammation.

Scleroderma specific autoantibodies in rheumatoid arthritis and Sjögren's syndrome patients with interstitial lung disease: Prevalence and associations.

Systemic sclerosis (SSc) has been classically linked to interstitial lung disease (ILD) development, often in association with specific SSc autoantibodies. In the present report, we aimed to estimate the prevalence of SSc autoantibodies in 60 seropositive RA and 41 primary SS patients complicated or not by ILD. SSc autoantibodies were determined in patients' sera by a commercial immunoblot assay. RA ILD patients displayed higher frequency of SSc-specific antibodies at strong titers compared to RA-with no lung involvement (25% vs 3.1%, p = 0.01)[OR 95% CI:10.9 (1.2-94.5)], with no differences detected between primary SS groups. These data indicate that many seropositive RA ILD patients probably represent an overlap RA/SSc entity, requiring tailored diagnostic and therapeutic approach.

Clinical and laboratory findings of primary Sjögren's syndrome patients without sicca symptoms.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by oral and eye dryness. A minority of patients can present without dryness but studies on their clinico-laboratory manifestations are scarce. Our purpose was to describe the clinical phenotype of pSS patients lacking sicca symptoms. METHODS: From a total of 1738 consecutive pSS patients fulfilling the 2016 ACR-EULAR criteria, those who presented without sicca symptoms were identified (non-dryness group). Their medical data was collected and compared with 2 control groups: a) the remaining unmatched sicca pSS patients with both oral and eye dryness (unmatched dryness group) and b) matched sicca pSS patients according to age, sex, and disease duration, in 1:2 ratio (matched dryness group). RESULTS: Thirty-eight (2.19%) patients lacked sicca manifestations presenting mainly with arthralgias (47%), parotid enlargement (24%), Raynaud's phenomenon (11%) and persistent lymphadenopathy (11%) that led them to be evaluated for pSS. Non-dryness pSS patients were younger than the unmatched sicca controls, displaying a higher frequency of anti-Ro/SSA antibodies (100% vs. 79.7%, p<0.001), ANA positivity (100% vs. 90.4%, p<0.001), neutropenia (20.8% vs. 7.5%, p=0.04) and thrombocytopenia (13.8% vs. 4.2%, p=0.04). They also had lower frequency of positive ocular tests compared to both unmatched and matched dryness patients. No differences were found between non-dryness pSS patients and both control groups regarding focus score or any other extraglandular manifestation. CONCLUSIONS: pSS patients without sicca complaints constitute a distinct phenotype involving younger patients, sharing common immunopathologic mechanisms with typical sicca patients.

Scleroderma-specific autoantibodies: Should they be included in the diagnostic work-up for Sjögren's syndrome?

OBJECTIVES: Sicca complaints are a frequent reason for rheumatologic consultation. Testing for specific antibodies against Ro/SSA and La/SSB antigens and minor salivary gland (MSG) biopsy are among the main tools implemented in the diagnostic work-up. Anticentromere antibodies and sicca manifestations are frequently detected in Sjögren's syndrome (SS) and systemic sclerosis (SSc), respectively. Herein, we aimed to determine the frequency and clinical associations of a wide spectrum of scleroderma (SSc)-specific autoantibodies in consecutive patients referred for evaluation of possible SS. METHODS: Demographic, clinico-pathological, and laboratory data were recorded in 216 consecutive patients with sicca complaints. All study participants were tested for SSc-specific autoantibodies (against CENP, PM/Scl, Scl-70, Ku, NOR90, RP11, RP155, fibrillarin, PDGFR, and Th/To) using a commercially available immunoblot kit. According to band intensity, the identified autoantibodies were further classified in those with strong and medium titers. RESULTS: SSc-specific autoantibodies were detected in 41.7% (90/216) patients evaluated (19% at strong, 22.7% at medium titers) without significant differences between anti-Ro/SSA positive and negative groups. At strong titers was significantly higher in patients with MSG biopsies fulfilling SS histopathological criteria (30% vs 12.5%, p = 0.009). This association remained significant after adjustment for antibodies against Ro/SSA and La/SSB autoantigens [OR 95% (CI): 4.1 (1.5-10.6)]. CONCLUSION: SSc-specific autoantibodies are frequently detected among patients presenting with sicca complaints and at strong but not medium titers are independently associated with MSG biopsy positivity. Taken together, these data imply a useful role of SSc antibody testing in the diagnostic work-up and possibly in the classification criteria for SS.

Polyarthritis and Psoriasiform Skin Lesions following Pembrolizumab Therapy.

A notable feature of immune checkpoint inhibitor (ICI) therapy in oncology patients is its association with increased frequency of immune related adverse reactions, directly associated with their unique mechanism of action. These adverse events are of great interest to rheumatologists, as not only do they commonly require immunosuppressive therapeutic intervention, but can also aid in unveiling important immunopathogenetic pathways that underlie autoimmune phenomena. Herein we describe a case of psoriasiform skin lesions and polyarthritis in a patient receiving ICI for lung cancer.

Tuberculosis and targeted synthetic or biologic DMARDs, beyond tumor necrosis factor inhibitors.

Patients with autoimmune rheumatic diseases (ARD) have an increased risk for tuberculosis (TB). The use of tumor necrosis factor inhibitors (TNFi) and glucocorticoids in these patients has been associated with an increased prevalence of latent TB reactivation. Over the last few years, several biologic disease-modifying anti-rheumatic drugs (bDMARDs), other than TNFi (e.g. rituximab, abatacept, tocilizumab, secukinumab) and targeted synthetic DMARDs (tsDMARDs) [e.g. apremilast, Janus kinase (JAK) inhibitors] have been used for the treatment of patients with ARD. For many of these drugs, especially the newer ones like JAK inhibitors or antibodies against interleukin (IL)-23, most data stem from randomized clinical trials and few are available from real life clinical experience. We sought to review the current evidence for TB risk in patients with ARD treated with tsDMARDs or bDMARDs, other than TNFi. It seems that some of these drugs are associated with a lower TB risk, indirectly compared with TNFi treatment. In fact, it appears that rituximab, apremilast and inhibitors of IL-17 and IL-23 might be safer, while more data are needed for JAK inhibitors. As seen in TNFi, risk for TB is more pronounced in TB-endemic areas. Screening for latent TB must precede initiation of any tsDMARDs or bDMARDs. The growing use of non-TNFi agents has raised the need for more real-life studies that would compare the risk for TB between TNFi and other treatment modalities for ARD. Knowledge about the TB-safety profile of these drugs could help in the decision of drug choice in patients with confirmed latent TB infection or in TB endemic areas.

The Role of Novel Autoantibodies in the Diagnostic Approach and Prognosis of Patients with Raynaud's Phenomenon.

Raynaud's phenomenon (RP) is a condition characterised by distinct colour changes of the digits upon exposure to sympathomimetic conditions, such as cold temperature. It can be either primary or secondary, depending on whether it presents alone or as part of an underlying disorder. One of the most common causes of secondary RP are systemic autoimmune rheumatic diseases (SARDs), in which RP may precede the onset of other autoimmune features by many years. Thus, timely and accurate recognition of secondary RP is of great importance as it alters patient management and prognosis. An important step in the diagnostic approach of RP is the detection of antinuclear antibodies (ANAs) by indirect immunofluorescence. However, identification of specific autoantibodies is not yet common practice, though many of them have shown important clinical associations. Moreover, the role of some autoantibodies has not yet been elucidated, given their relatively recent discovery and low reported prevalence rates in autoimmune population. The goal of this study is to reveal clinical associations of these novel autoantibodies in SARDs through the application of an extended serology workup in patients presenting with RP.

B cells and atherosclerosis in systemic lupus erythematosus.

INTRODUCTION: Cardiovascular (CV) events, as a result of accelerated atherosclerosis, are an important cause of mortality in patients with Systemic lupus erythematosus (SLE). The etiology of SLE is multifactorial and still unclear; among other potential culprits, excessive B cell activation seems to play a crucial role. Accumulating evidence supports a contributory role of B cells in the pathogenesis of atherosclerosis as well. Areas covered: This article focuses on the contribution of both B cells and autoantibodies in the pathogenesis of atherosclerosis in both general and lupus populations. Review of the published literature on experimental models has also been performed. Expert opinion: Distinct B cell subsets seem to exhibit separate effects on the progression of atherosclerosis, with B2 B cells displaying a mainly atherogenic phenotype, while B1 B cells are mostly viewed as atheroprotective. Selective B2 inhibition by anti-B cell therapies seems a promising therapeutic strategy against atherosclerosis development in the setting of lupus.

Nitric oxide modulates apomorphine-induced recognition memory deficits in rats.

Nitric oxide (NO) is an important intracellular messenger in the brain. The implication of NO in schizophrenia is well documented although it is not yet clear whether net over or underproduction of NO is typical of this disease. In line with this, either NO donors or NO synthase (NOS) inhibitors were found to abolish psychotomimetic effects, including cognition deficits, produced by N-methyl-D-aspartate (NMDA) receptor hypofunction. In addition, there is poor experimental evidence concerning the efficacy of NO to modulate memory deficits produced by dopamine (DA) dysfunction. The present study was designed to investigate the ability of NO modulators (NO donors and NOS inhibitors to reverse recognition memory impairments produced by the DA D(1)/D(2) mixed receptor agonist apomorphine in rats. For these studies, the novel object recognition test (NORT) was used as the memory test. Apomorphine (0.05, 0.1, 0.5 and 1.0 mg/kg), dose-dependently, disrupted performance in this recognition memory procedure in rats. The NO donors molsidomine (2.0 and 4.0 mg/kg) and SNP (0.3 and 1.0 mg/kg), reversed the impairing effects of apomorphine (1.0 mg/kg) in the NORT. Administration of the NOS inhibitors L-NAME (1.0 and 3.0 mg/kg) or 7-NI (1.0 and 3.0 mg/kg) produced similar results. The present findings indicate a) that apomorphine dose-dependently impaired recognition memory and b) that a cognitive deficit produced by DA dysfunction is sensitive to NO.