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OBJECTIVES To investigate peripheral enthesitis with power Doppler ultrasound (PDUS) in patients presenting low back pain (LBP) and metabolic syndrome (MetS) in comparison with patients with only LBP, to correlate US scores with clinical-anthropometric characteristics, and to define any relationship between enthesitis and concurrent diffuse idiopathic hyperostosis syndrome (DISH). METHODS Sixty outpatients with LBP and MetS, evaluated with multi-site entheseal PDUS, scoring inflammatory and structural damage changes, were retrospectively analyzed. A group of 60 subjects with LBP, without MetS and evaluated with the same protocol, was analyzed as the control group. RESULTS Patients showed overweight (BMI 29.8) and low-grade inflammatory state (C-reactive protein [CRP] 0.58mg/dL, erythrosedimentation rate [ESR] 20.2mm/h). Enthesitis was demonstrated in 52 (86%) patients (17.6% entheses), and in 8 controls (13.3%) (p

Scleritis refers to a wide spectrum of ocular conditions ranging from mild to sight-threatening scleral inflammation that may compromise visual function and threaten the anatomical integrity of the ocular globe. Most aggressive forms like necrotizing or posterior scleritis are often difficult-to-treat cases, refractory to conventional treatment. The association with systemic diseases, namely rheumatoid arthritis, Sjögren syndrome, granulomatosis with polyangiitis, and relapsing polychondritis, may have prognostic implications as well. A better understanding of the pathogenesis of ocular inflammatory diseases have paved the way to more effective and targeted treatment approaches. In this regard, a growing body of evidence supports the potential role of biologic agents in the management of non-infectious scleral inflammation, either idiopathic or in a background of immune-mediated systemic disorders. Biologic agents such as anti-tumor necrosis factor agents, interleukin-1 and interleukin-6 inhibitors as well as CD20 blockade have displayed promising results. More specifically, several studies have reported their ability to control scleral inflammation, reduce the overall scleritis relapses, and allow a glucocorticoid-sparing effect while being generally well tolerated. Anecdotal reports have also been described with other biologic agents including abatacept, ustekinumab, daclizumab, and alemtuzumab as well as targeted small molecules such as tofacitinib. Further studies are warranted to fully elucidate the role of biologic agents in non-infectious scleritis and investigate specific areas with the aim to administer treatments in the context of personalized medicine. This review summarizes the available data regarding clinical trials, small pilot studies, and real-life experience of the last two decades reporting the use of biologic agents in the management of non-infectious scleritis.

Giant cell arteritis (GCA) is a large-vessel vasculitis, typically affecting the aorta and its branches. The involvement of vertebral and internal carotid arteries occurs in a limited number of cases, and stroke as a presenting symptom of GCA is extremely unusual: this subset of the disease has a poor prognosis and rarely responds to immunosuppression. We report the case of a 70-year-old woman, who presented to the Emergency Department for ische­mic stroke, which appeared to be the first and only symptom of GCA. The prompt administration of steroids and tocilizumab (TCZ) led to clinical and radiological resolution, with no residual disability at 6-month follow-up. Our case-based review, highlighting the rarity of a large vessel vasculitis presenting only with a cerebrovascular accident, provides new evidence for the efficacy of TCZ even in more unusual varieties of GCA: in these cases, TCZ should be immediately prescribed, in order to prevent mortality and severe long-term morbidity.

IntroductionTo evaluate differences of injection related pain, and the accuracy of the techniques in two groups of overweight patients, performing the anterolateral approach for one group (G1) and the superolateral approach for the second group (G2).Material and methodsIn the study, 126 knee joints from 86 osteoarthritis (OA) patients were evaluated. Inclusion criteria were body mass index (BMI) ≥ 25, absence of effusion and coagulopathy. Pain evaluation during injection was evaluated with Visual Analogue Scale (VAS), while accuracy of the procedure was evaluated with ultrasound (US).ResultsThe patients’ mean age was 69.9 ±9.01, VAS for G1 group was 1.71 ±1.89, for G2 group was 1.74 ±1.31. Mean BMI was 29.69 ±2.86, for G1 group was 28.29 ±3.29, for G2 group was 30.32 ±2.41. No adverse events (AE) occurred in both studied groups. The accuracy rate of the procedure was 69.1% for G1 (38/55 knees), 95.7% for G2 (68/71 knees). No significant difference was found in VAS pain score between G1 and G2 group (p = 0.45). We found the significant correlation between BMI and VAS pain score in anterolateral accesses (G1) (r = 0.51; p < 0.005). No correlation was found between age and VAS pain score in anterolateral access (G1). For the superolateral access (G2), no correlation was found for age or BMI and VAS pain score.ConclusionsHyaluronic acid injection is safe therapeutic option for knee OA with no significant differences between anterolateral and superolateral approaches in terms of pain in overweight patients. However, higher BMI seems to be a predictor of pain in anterolateral access, and the superolateral approach should be preferred in this group of patients.

Background Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions. Results The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6–37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17–2.35), congestive heart failure (HR = 2.76, CI 95% 1.80–4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21–4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06–2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008–2017 period. Conclusions The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.

Aim: The aims of the study were to perform an ultrasound assessment of the dorsal portion of the scapholunate interosseous ligament and scapholunate joint space in patients with wrist complaints in a rheumatologic setting, to describe ultrasound abnormalities about scapholunate interosseous ligament region, and to correlate them with clinical data, presence of dorsal ganglion cysts and diagnoses of rheumatic diseases. Material and methods: Seventy-four consecutive patients with wrist pain and/or swelling were evaluated by routine power Doppler ultrasound. Forty normal wrists were studied to confirm the normality values of the scapholunate joint. Results: The mean width of the normal scapholunate joint was 2.49 mm (±0.49 SD), with a coefficient of variation on repeated measurements of 3.662%. The best predictors of scapholunate interosseous ligament degeneration were: older age (p

Purpose: The purpose of this study was to evaluate the prevalence and the underreporting rate of sacroiliitis (SI) in a large cohort of patients with biopsy-proved Crohn&rsquo, s disease (CD) who underwent magnetic resonance enterography (MRE) or computed tomography enterography (CTE). Materials and Methods: Patients with CD were recruited from eight Italian health centers in the period from January 2013 to December 2017. Disease activity was recorded according to the CD activity index (CDAI). The scans were read by two blinded readers who defined the presence of SI according to Assessment of SpondyloArthritis International Society (ASAS) classifications and European League Against Rheumatism (EULAR) recommendations. Moreover, SI was scored using a simplified Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. Results: Interobserver agreement in diagnosing SI on imaging was good (K = 0.72&ndash, 0.83). SI was diagnosed in 129 (14.4%, 54 men, 75 women) out of 894 patients, however, sacroiliac joint (SIJ) abnormalities were not mentioned in the radiological reports of 112 patients (86%). Fifty (38.7%) out of 129 patients also underwent a subsequent SIJ evaluation through a dedicated MRI protocol to confirm SI. SI was found in a higher percentage of patients with &ldquo, active&rdquo, than &ldquo, inactive&rdquo, CD (18% vs. 4%). Conclusion: This study confirms the feasibility of CTE and MRE for the screening of SI in CD patients, however, it also underlines the remarkable problem concerning the underreporting of this entity in radiological practice.

Background Low back pain (LBP) is one of the most common spine diseases and represents the most frequent cause of absence from work in developed countries. Approximately 40% of chronic LBP is related to discogenic origin. The goal of the study is producing a review of literature to describe analytically the techniques of intradiscal injections. Methods PubMed database was searched for clinical studies with the different key terms: "intradiscal", "injection", "steroid" "procedures", "techniques", "CT", "MRI", "fluoroscopy", "fluoroscopic", "guidance", "ozone", "ultrasound", "images". Only studies written in English, French, or Italian in which the intradiscal injection represents the main procedure for the low back discopathy treatment on humans were considered. We excluded the articles that do not mention this procedure; those which indicated that the intradiscal injection had happened accidentally during other treatments; those reporting the patient's pain was determined by other causes than the discopathy (facet joint syndrome, tumor, spondylodiscitis). Results Thirty-one articles dated from 1969 to 2018 met the criteria. The examined population was 6843 subjects, 52.3% male and 47.7% female, with a mean age of 45.9±10.1 years. The techniques are highly variable in terms of procedure: different operators, needle guidance, injection sites, drugs, tilt angle of the needle). Conclusion The efficacy and the safety of the intradiscal procedures are not easily comparable due to different types of studies and their limited number. Further studies are needed to standardize the intradiscal injection technique/procedure to improve safety, repeatability and effectiveness, and last but not least to reduce peri- and postoperative care and health-care costs.

Noninfectious uveitis represents one of the leading causes of blindness in developed Countries, compromising patients' quality of life and social functioning. The main treatment goals are the control of ocular inflammation, to avert and treat sight-threatening complications, thus preserving and/or restoring visual function.This manuscript deals with systemic therapy with biologic drugs for noninfectious uveitis. An extensive literature search in the MEDLINE database (via PubMed) has been performed up to June 2020. The major classes of biologic molecules employed in ocular inflammatory diseases have been reviewed, focusing on TNF inhibitors, IL-1, IL-6, IL-17, IL-23 inhibitors, interferons, rituximab, and abatacept efficacy and safety. An overview of most recent developments in the field has been provided as well, with reference to the experience with JAK inhibitors and with biosimilar drugs.The development of the concept of targeted therapy and the subsequent introduction of biologic molecules in clinical practice have revolutionized the prognosis of uveitis. The target of a rapid and sustained steroid-free remission of ocular inflammation should be pursued for all patients early in the disease course, in order to have a better chance to improve the final visual outcome.

Objective. To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p=0.42), between low- and high-penetrance mutations (p=0.62), and according to different dosages (p=0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Conclusions. Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis.

Objectives. To examine demographic and clinical characteristics and long-term visual outcome in a cohort of Italian patients affected by Behçet’s uveitis (BU). Materials and Methods. Retrospective chart review of 47 patients with BU attending our unit between January 2018 and December 2019. Ophthalmologic manifestations, best-corrected visual acuity (BCVA), fluoroangiography and optical coherence tomography findings, and ocular complications were recorded. Predictive factors of a poor visual outcome and long-term complications were also investigated. Results. Forty-seven patients (23 males and 24 females) for a total of 84 eyes were enrolled. Uveitis was bilateral in 37 (78.7%) patients with panuveitis being the most frequent anatomical pattern (40 out of 84 eyes), whereas 27 eyes presented a posterior uveitis. Isolated anterior uveitis was detected in 16 eyes. A significant improvement of median BCVA between baseline and last follow-up values was detected (p=0.042). A higher risk of poor visual prognosis was observed in patients with uveitis duration greater than 15 years (p=0.019). A significant resolution of retinal vasculitis was detected between baseline and last follow-up evaluation (p<0.0001) whereas the mean±SD macular thickness did not decrease significantly between baseline (376.00±97.45 μm) and last follow-up evaluation (338.08±55.81 μm). Forty-two eyes developed 57 complications during the disease course. Cataract was the most frequent (n=12), followed by epiretinal membranes (n=11) and cystoid macular edema (n=6). The following variables were identified as predictors of long-term complications: human leukocyte antigen- (HLA-) B51 (p=0.006), panuveitis (p=0.037), and a uveitis duration of more than 15 years (p=0.049). Conclusions. In Italian patients, BU typically arises in the third decade and predominantly manifests as a bilateral posterior uveitis or panuveitis. Its duration is associated with a poor visual prognosis. Uveitis duration, the presence of HLA-B51, and panuveitis are predictors of long-term structural complications, thus representing main drivers in the treatment decision-making.

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.

Background and Objective Clodronate is a nitrogen-free bisphosphonate that is widely and effectively used in the treatment of many osteo-metabolic disorders. The objective of our study was to evaluate the effectiveness of clodronate in reducing pain and bone marrow edema in knee osteoarthritis. Methods In total, 74 patients were included in the study. Group 1 received intramuscular clodronate 200 mg daily for 15 days and then once weekly for the next 11.5 months; group 2 received intramuscular clodronate 200 mg daily for 15 days and then once weekly for the next 2.5 months. Visual analog scale (VAS) scores were recorded at baseline (T0) and after 30 days (T1), 3 months (T2), 6 months (T3), 9 months (T4), and 12 months (end of study; T5). We also evaluated functional status and use of paracetamol (T0, T1, T2, T3, T4, and T5) and changes in Whole Organ Magnetic Resonance Imaging Score (WORMS; T0, T2, and T5). Results Both groups had a statistically significant reduction in VAS score until 3 months. Group 1 then experienced further VAS reductions, whereas VAS scores for group 2 progressively increased. Pain, stiffness, and physical function also showed the same trend, as did bone marrow edema extension, which was evaluated with WORMS. Conclusion Our study indicates that intramuscular administration of a therapeutic dose of clodronate followed by a maintenance dose is effective in the management of symptomatic knee osteoarthritis, improving functional outcomes and reducing pain and bone marrow edema. Prolonged treatment increases the long-term efficacy of clodronate compared with the shorter schedule.

Behcet’s syndrome (BS) is a multisystemic disorder displaying a marked variability across different geographic areas. The main aim of this study was to analyze demographic and clinical features of a cohort of BS patients diagnosed in three tertiary referral centers in Italy and detect potential associations between the different manifestations. Medical records of 396 patients (218 females, 178 males) were retrospectively analyzed. Mean age at onset was 30.00 ± 18.75 years with a female-to-male ratio of 1.22:1. Mucocutaneous features were the most frequent starting manifestations of BS, followed by eye inflammation. Erythema nodosum (p = 0.007), arthritis/arthralgias (p = 0.0115), and central nervous system (CNS) signs (p = 0.014) were significantly over-represented in female patients, whereas male gender was associated with lower mean age at onset (p = 0.031), higher frequency of pseudofollicular lesions, and uveitis (p = 0.00134 and p

Chronic anterior uveitis is the most frequent among extra-articular manifestations of juvenile idiopathic arthritis (JIA) and a relevant cause of ocular morbidity in children. Asymmetric arthritis, early onset disease, female sex, and anti-nuclear antibody (ANA) positivity are counted among risk factors for developing this complication. It usually has insidious onset and asymptomatic chronic-relapsing course, but the persistence of low-grade chronic inflammation can lead to irreversible structural ocular damage and to vision-threatening complications. For such reasons, achieving a complete absence of inflammation through early targeted and aggressive treatments is a primary therapeutic goal in these patients. This review is aimed at summarizing scientific evidence about biologic rescue therapy of JIA-related uveitis in patients who fail to achieve clinical remission, in spite of being treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) and at least one biologic tumor necrosis factor (TNF)-α inhibitor. Interleukin (IL)-6 inhibition appears a promising and safe option for refractory JIA-related uveitis. Abatacept and rituximab proved to be beneficial as well, but their efficacy together with some safety concerns needs to be more extensively evaluated.

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis.Key points•Smoking habit resulted to be a negative prognostic factor on AOSD.•Smokers were characterised by an increased frequency of serositis and higher values of systemic score.•Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.

After the approval of the first vaccines against SARS-CoV-2, a mass vaccination is currently being performed worldwide. Despite the safety and efficacy of such drugs evidenced by the registration studies, no clinical trial has to date included patients affected by autoimmune diseases nor data coming from real life are currently available. In this regard, we report the case of a patient affected by microscopic polyangiitis who suspended Methotrexate prior to vaccination and relapsed after the administration of the first dosage. The patient required hospitalization and was treated with high dosages of steroids but was rapidly discharged in good clinical condition. Our case evidences that the immune response triggered by the administration of the vaccine against COVID 19 may reactivate autoimmune disorders, but such condition seems manageable and the withdrawal of the immunosuppressants should not be performed. This article is protected by copyright. All rights reserved.

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed.

This paper is aimed at investigating whether peripheral dysfunction at the neuromuscular level may represent a pain generator in fibromyalgia. We studied the prevalence of spasmophilia (SP), carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in a group of 40 subjects suffering from fibromyalgia. Clinical and electrophysiological data were obtained to ascertain whether comorbid conditions were present. For subjective evaluation of symptoms severity, validated questionnaires for CTS and UNE were completed by patients. Twenty subjects were positive for SP (50%); CTS was diagnosed in 12 subjects (30%); no patient suffered from UNE; 6 subjects were affected at the same time by SP and CTS (15%); 14 subjects (35%) were affected by SP alone. The prevalence of CTS and SP was higher in fibromyalgia subjects than in the general population. The scores of the questionnaires related to CTS were significantly higher in fibromyalgia subjects positive for CTS, with respect to the other subjects. In fibromyalgia, CTS and SP may be considered clinical entities in themselves, the importance of which lies in their acting as peripheral pain generators that enhance or initiate central sensitization, thereby contributing to chronic widespread pain. The amplification of pain is indeed a correctable/misguided message that occurs inside the brain of fibromyalgia subjects and identification and local treatment of pain generators would lessen the total pain burden. The magnitude of the overlap in symptoms between fibromyalgia and CTS/SP necessitates careful investigation of these conditions.

Objectives No clear-cut guidelines exist on the use of diagnostic procedures for idiopathic inflammatory myopathies (IIM) and only minimal and conflicting data report the use of ultrasound (US). In this regard, we aimed to assess if grey-scale (GS) and Power Doppler (PD) US, graded with a 0–3-point scale, may be a reliable tool in a cohort of patients affected by IIM. Methods All patients underwent US examination of both thighs in axial and longitudinal scans. Oedema and atrophy, both assessed in GS and PD, were graded with a 0–3-point scale. Spearman’s test was used to identify the correlations between US and clinical and serological variables. Results A total of 20 patients were included. Six and two patients were evaluated twice and three times, respectively. Muscle oedema was found to be directly correlated with physician global assessment (PhGA), serum myoglobin and PD and negatively with disease duration. PD score was positively correlated to PhGA and negatively to disease duration. Muscle atrophy directly correlated with Myositis Damage Index, disease duration and patient’s age. The single-thigh sub-analysis evidenced a direct correlation between PD score and Manual Muscle Test. Conclusions In our cohort, we found that oedema and PD are strictly related to early, active myositis, suggesting that an inflamed muscle should appear swollen, thickened and with Doppler signal. Conversely, muscle atrophy reflects the age of the patient and the overall severity of the disease. Such findings shed a new, promising, light on the role of US in diagnosis and monitoring of IIMs.

PURPOSE Several concerns have arisen with biosimilars in terms of immunogenicity, safety issues, loss of efficacy, and extrapolation to other indications. The study aim was to evaluate the efficacy of SB5, an adalimumab biosimilar, in noninfectious uveitis (NIU). DESIGN Retrospective nonrandomized study. METHODS Data from patients with refractory NIU treated with SB5 (Imraldi, Biogen) were analyzed at baseline, 3 months after SB5 initiation and at the last follow-up in terms of uveitis relapses, occurrence of retinal vasculitis, resolution of uveitic macular edema (UME), best-corrected visual acuity, glucocorticoids (GCs)-sparing effect and drug survival. RESULTS Uveitis relapses decreased from 121 relapses/100 patients/year in the 12 months before SB5 initiation to 4 relapses/100 patients/year during the first 12 months of treatment (P = 0.0004). Uveitis was inactive in 46/47 eyes at the end of the study period. The number of eyes with active retinal vasculitis decreased during the study period (P

BACKGROUND Krebs von den Lungen-6 (KL-6) is a high-molecular-weight (200kDa) glycoprotein proposed as a diagnostic biomarker for differentiating interstitial lung disease (ILD). Systemic sclerosis (SSc) is a rare immune-mediated disorder, and ILD is the leading cause of morbidity and mortality. Pleuroparenchymal fibroelastosis (PPFE) has been described to have a poor prognosis in SSc-ILD patients. This study undertook to compare serial changes in KL-6 in SSc-ILD patients with and without PPFE, to verify its prognostic value as a disease biomarker. MATERIALS AND METHODS Twenty-five SSc-ILD patients (median IQR, 62 (56-58); 20% males) were retrospectively enrolled. 12 SSc-ILD patients (48%) had also a radiological diagnosis of PPFE. Serum KL-6 concentrations were measured by KL-6 reagent assay (Fujirebio Europe, Ghent, Belgium). RESULTS Serum KL-6 measurements were increased in SSc-ILD patients with and without PPFE compared with healthy controls (P

Background Convalescent plasma (CP) and hyperimmune plasma (HP) are passive immunotherapies consisting in the infusion of plasma from recovered people into infected patients. Following pre-existing evidence in many other viral diseases, such as SARS, MERS and Ebola, CP and HP have also been proposed for the treatment of COVID-19. Nevertheless, due to the lack of large, well-designed, clinical trials, no clear-cut guidelines exist about what subtype of patient CP and HP should be administered to. Case presentation We have reported the cases of 3 patients, all immunosuppressed and affected by non-severe, prolonged COVID-19. They were treated with HP, whose neutralizing titer was higher than 1/80. The first patient was a 55-year-old male, who had undergone lung transplant. He was under therapy with Tacrolimus and developed non-neutralizing antibodies against SARS-CoV2. The second patient was a 77-year-old female, affected by follicular lymphoma. She had tested positive for SARS-CoV2 after 6 months. The third was a 60-year-old patient, affected by chronic leukemia. He did not develop antibodies after 2-month disease. All 3 patients received HP and had tested negative for SARS-CoV2 within 2 weeks. Conclusion Despite encouraging initial data, no strong evidence exist in support of CP and HP to treat COVID-19. In our experience, although limited due to the reduced number of patients, we found a good safety and efficacy of HP in 3 immuno-deficient subjects. Further data are needed in order to assess whether this subtype of patients may particularly benefit from passive immunization.

IntroductionOsteoporosis is the most common bone tissue disease and it is characterized by a re�duced bone mineral density (BMD). The main physiopathological mechanisms converge on the un�coupling between bone formation and resorption, thus leading to an enhanced risk of fractures. Several papers have documented the inverse relationships linking high inflammatory cytokines, anti�citrullinated protein antibodies, rheumatoid factor, and BMD in rheumatoid arthritis (RA). Rituximab (RTX) is a chimeric monoclonal antibody directed against the CD20 receptor of B cells. Since the Food and Drug Administration approved it for RA in 2006, there have been many clinical experiences regarding its use. Nevertheless, few studies evaluate the effect of rituximab on BMD. RA is a disease characterized by immune dysfunction with high levels of inflammatory cytokines, autoantibodies, and it is reasonable that a B cell depleting therapy could restore a physiological cytokine balance, thus exerting an osteoprotective effect on the bone tissue. The purpose of this paper is to highlight any difference in BMD and to assess differences in body composition over a retrospective 18-month follow-up period after RTX treatment with a B cell depleting therapy.Material and methodsWe analyzed by dual energy X-ray absorptiometry BMD expressed as g/cm2 and body composition modifications over 18 months with RTX treatment of 20 postmenopausal RA patients.ResultsAfter eighteen months of therapy with RTX, a statistically significant increase in vertebral (L1–L4) BMD and the stability of femoral BMD were documented.ConclusionsRituximab is associated with an improvement of vertebral and preservation of femo�ral BMD, suggesting a bone-sparing effect due to B cell depletion. Furthermore, patients displayed a redistribution of fat masses toward the hip region.

IntroductionSarcopenia is the pathological reduction of skeletal muscle mass and strength. This condition is often underestimated in clinical practice, particularly in connective tissue diseases. The purpose of this study is to evaluate the prevalence of low muscle mass in primary Sjögren’s syndrome (pSS) and to explore the relationships linking muscles and bone tissue.Material and methodsTwenty-eight postmenopausal pSS patients were matched with 30 healthy controls and their body composition analysis was performed by dual-energy X-ray absorptiometry to investigate for sarcopenia considering appendicular lean mass (ALM) and the skeletal muscle mass index (SMI) as references. Bone mineral density analysis of lumbar spine (L1–L4), whole femur, femoral neck and whole body was also performed. Linear regression was used to assess the relationship between body composition and bone mineralization.ResultsLow muscle mass was significantly higher in the pSS group compared to controls whether expressed as ALM, SMI [odds ratio (OR) = 18.40, confidence interval (CI): 4.84–72.08, p < 0.0001] or considering total body lean masses. Lean masses appeared to be the best estimators of bone mineralization: total lean body mass (TLBM) lumbar spine R2 = 0.72, p < 0.0001; TLBM femoral neck R2 = 0.36, p < 0.004; lean mass of upper limbs lumbar spine R2 = 0.70, p < 0.0001; femoral neck R2 = 0.66; lean mass of lower limbs lumbar spine R2 = 0.66, p < 0.0001; femoral neck R2 = 0.44, p = 0.008). Primary Sjögren’s syndrome patients had a significantly higher android/gynoid fat ratio compared to controls.ConclusionsFemale pSS patients have lower muscle mass compared to healthy controls and are exposed to a higher risk of developing sarcopenia than healthy subjects. Our research demonstrates that the amount of lean tissue is the main predictor of bone mineralization in pSS.

Behçet’s syndrome (BS) represents an understudied topic in pediatrics: the main aims of our study were to characterize demographic and clinical features of a cohort of BS patients with juvenile-onset managed in three tertiary referral centers in Italy, evaluate their evolution in the long-term, and detect any potential differences with BS patients having an adult-onset. Medical records of 64 juvenile-onset and 332 adult-onset BS followed-up over a 2-year period were retrospectively analyzed and compared. Mean age ± SD of first symptom-appearance was 10.92 ± 4.34 years with a female-to-male ratio of 1.06:1. Mucocutaneous signs were the most frequent initial manifestations, followed by uveitis. Throughout the disease course, genital aphthae (76.56%) and pseudofolliculitis (40.63%) prevailed among the mucocutaneous signs, while major organ involvement was represented by gastrointestinal and ocular involvement (43.75 and 34.38%, respectively). No significant differences emerged for both mucocutaneous signs and specific major organ involvement between juvenile-onset and adult BS patients. After excluding nonspecific abdominal pain, juvenile-onset BS patients were less frequently characterized by the development of major organ involvement (p = 0.027). Logistic regression detected the juvenile-onset as a variable associated with reduced risk of long-term major organ involvement (OR 0.495 [0.263–0.932],p = 0.029). In our cohort, juvenile-onset BS resembled the clinical spectrum of adult-onset patients. Pediatric patients with a full-blown disease at onset showed a more frequent mucocutaneous involvement. In addition, patients with juvenile-onset seemed to develop less frequently major organ involvement and had an overall less severe disease course.

EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA.Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149.During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy.According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread all over the globe from China. Pleural involvement is not common; around 5–10% of patients can develop pleural effusion and little is known about the involvement of pleural structures in this new infection. A 61-year-old male kidney transplant patient with a history of multiple biopsy-confirmed acute rejections and chronic allograft rejection was admitted to our COVID-19 Unit with dry cough, exertional dyspnea, oliguria, and abdominal distension. Lung ultrasound imaging, chest X-ray, and CT scan showed left pleural effusion and atelectasis of the neighboring lung parenchyma. RT-PCR was positive for SARS-CoV-2 in the pleural fluid and cytology showed mesothelial cells with large and multiple nuclei, consistent with a cytopathic effect of the virus. This is one of few reports describing detection of SARS-CoV-2 in the pleural fluid and to the best of our knowledge, is the first to document the simultaneous presence of a direct cytopathic effect of the virus on mesothelial cells in a kidney transplant patient with COVID-19 pneumonia. The pleura proved to be a site of viral replication where signs of a direct pathological effect of the virus on cells can be observed, as we report here. RT-PCR for SARS-CoV-2 should be part of routine examination of pleural effusion even in patients with mild respiratory symptoms or with comorbidities that seem to explain the cause of effusion.

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Aims: Switching from originator to biosimilar is part of current practice in inflammatory rheumatic musculoskeletal diseases (iRMDs) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA), with evidences derived from both etanercept (ETN) to SB4-switching randomized controlled trials and real-life registries. We investigated the safety and treatment persistence of ETN/SB4 in a multi-iRMD cohort derived from two rheumatology departments in our region. Methods: Adult patients with iRMDs, treated with ETN for at least 6 months and switched to SB4 in stable clinical condition, were eligible for this retrospective evaluation. Retrospective data on adverse events, loss of efficacy and persistence on treatment were collected until latest available follow-up. Results: A total of 220 patients (85 RA, 81 PsA, 33 axSpA, 14 juvenile idiopathic arthritis and seven other conditions; 142 females, mean age 58 ± 7 years, disease duration 12 ± 4 years, ETN duration 7 ± 4 years) were enrolled, with median follow-up of 12.1 (9.7–15.8) months. A total of 50 patients (22.7%) presented with at least one adverse event, with 36 (16.4%) disease flares and 30 (13.6%: 11 for safety and 19 loss of efficacy) SB4 withdrawals. Cumulative SB4 treatment persistence was 99.1%, 88.6% and 64.6% at 6, 12 and 18 months respectively. Back-switch to ETN was performed in 17/30 cases, the remaining cases were managed with change of biologic disease modifying or conventional synthetic anti-rheumatic drug. Age was the only significant predictor of SB4 interruption at 6 months. Conclusion: Our real-life data confirm the safety profile of switching from ETN to SB4, with slightly higher treatment persistence rates compared with other real-life registries.

Ultrasound imaging of the lung (LUS) and associated tissues has demonstrated clinical utility in coronavirus disease 2019 (COVID-19) patients. The aim of the present study was to evaluate the possibilities of a portable pocket-sized ultrasound scanner in the evaluation of lung involvement in patients with COVID-19 pneumonia. We conducted 437 paired readings in 34 LUS evaluations of hospitalized individuals with COVID-19. The LUS scans were performed on the same day with a standard high-end ultrasound scanner (Venue GO, GE Healthcare, Chicago, IL, USA) and a pocket-sized ultrasound scanner (Butterfly iQ, Butterfly Network Inc., Guilford, CT, USA). Fourteen scans were performed on individuals with severe cases, 11 on individuals with moderate cases and nine on individuals with mild cases. No difference was observed between groups in days since onset of symptoms (23.29 ± 10.07, 22.91 ± 8.91 and 28.56 ± 11.13 d, respectively; p = 0.38). No significant differences were found between LUS scores obtained with the high-end and the portable pocket-sized ultrasound scanner. LUS scores in individuals with mild respiratory impairment were significantly lower than in those with moderate and severe cases. Our study confirms the possibilities of portable pocket-sized ultrasound imaging of the lung in COVID-19 patients. Portable pocket-sized ultrasound scanners are cheap, easy to handle and equivalent to standard scanners for non-invasive assessment of severity and dynamic observation of lung lesions in COVID-19 patients.

We read with interest the article by Ramiro et al 1 about a cohort of patients affected by severe COVID-19 pneumonia. The authors evidenced the efficacy of 5 days of methylprednisolone (MP) (a single bolus of 250 mg, followed by 80 mg on days 2–5) plus, in case of insufficient response, tocilizumab (TCZ) 8 mg/kg, in reducing mortality and preventing invasive ventilation (IV). As the massive lung damage during COVID-19 pneumonia is thought to be caused by an aberrant inflammatory response mediated by a massive release of inflammatory cytokines and chemokines, the use of biological immunosuppressants has been widely proposed. The rationale supporting their use is not only an antiviral effect,2 but the selective anti-inflammatory role and the capability of interrupting the cytokine cascade eventually responsible for lung failure. TCZ, a monoclonal antibody directed against interleukin 6 (IL-6) receptor, was the first biological drug administered in a Chinese cohort of patients. Despite preliminary promising data, recent reviews and meta-analysis did not find statistically significant differences, in terms of mortality, intensive care unit (ICU) admission and requiring of IV, between patients treated with TCZ and …

Objectives Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis. Methods SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot. Results We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway. Conclusions Our findings suggest that a role of NETs in crystal-induced arthritis is to ‘trap extracellular particles’, including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack.

Background: The Coronavirus disease (COVID-19) pandemic is causing millions of infections and hundreds of thousands of deaths worldwide. Cumulative clinical and laboratory evidence suggest that a subset of patients with severe COVID-19 may develop a cytokine storm syndrome during the course of the disease, with severe respiratory impairment requiring ventilatory support. One field of research nowadays is to identify and treat viral-induced hyperinflammation with drugs used in other clinical conditions characterized by an hyperinflammation status. These drugs might help to reduce COVID19 mortality.Methods: Ruxolitinib, a JAK1 and JAK2 inhibitor, has been successfully used to treat severe immune-mediated diseases, such as graft vs. host disease and Hemophagocytic lymphohistiocytosis. We used ruxolitinib in 18 patients with clinically progressive COVID-19 related acute respiratory distress syndrome, with a primary endpoint to rapidly reduce the degree of respiratory impairment and as a secondary endpoint to rapidly restore the PaO2/FiO2 ratio, as an evaluation of clinical status, and monitoring of drug related Adverse Events. Parameters of inflammation responses and organ functions were assessed and monitored. The treatment plan was ruxolitinib 20 mg bid for the first 48 h and subsequent two-step de-escalation at 10 mg bid and 5 mg bid for a maximum of 14 days of treatment.Results: Our data collection shows a rapid clinical response with no evolution from non-invasive ventilation to mechanical ventilation in 16/18 patients and no response in two patients (overall response rate—ORR 89%). Already after 48 h of ruxolitinib treatment 16/18 patients showed evident clinical improvement, and after 7 days of treatment 11/18 patients showed fully recovered respiratory function (pO2 > 98% in spontaneous breathing), 4/18 patients had minimal oxygen requirement (2–4 L/m), 1/18 patient showed stable disease, and 2/18 patient showed progressive disease. After 14 days, 16/18 patients showed complete recovery of respiratory function (ORR 89%). Compliance to ruxolitinib planned treatment was 100% and no serious adverse event was recorded. In our case series of 18 critically ill patients with COVID-19 and ARDS, administration of ruxolitinib resulted in a clinical improvement that concurred to modify the standard course of disease. Ruxolitinib can be a therapeutic option for patients with respiratory insufficiency in COVID-19 related ARDS. RESPIRE Study (Ruxolitinib for the treatment of acute rESPIratory distREss syndrome, ClinicalTrials.gov Identifier: NCT04361903).

This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients’ data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p<0.01 and p<0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p<0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p<0.01), while oral aphthosis was more frequently found in the LP variant group (p<0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p<0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p<0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p<0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p<0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p<0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p<0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.

Objectives The objectives of this study were to study with Power Doppler US (PDUS) the SI joints (SIJs) of patients with suspected active sacroiliitis, to describe SIJ flows with spectral wave analysis (SWA) on Doppler US, and to correlate US data with both clinical characteristics and presence of SIJ bone marrow oedema (BME) in subsequent MRI. Methods A total of 42 patients (32 females and 10 males, mean age 46.8 years) with recent onset of inflammatory back pain (IBP) were included. Every patient underwent US examination with a convex 1–8 MHz probe [scoring PDUS signals with a three-point scale and describing flows in SWA calculating the mean Resistive Index (RI)] and subsequent MRI of the SIJs. Results PDUS signals were detected in 34 patients and 62 SIJs. In 29 patients and 56 SIJs, MRI revealed BME. A definite diagnosis of SpA was made in 32 patients. PDUS signals were more frequent (P Conclusions PDUS and SWA of SIJs demonstrate good diagnostic accuracy for active sacroiliitis compared with MRI.

We read with interest the article by Monti et al ,1 who evidenced, in a cohort of subjects affected by COVID-19, a low prevalence of patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). Despite a notable heterogeneity in different countries and even in different regions of the same country, a high lethality is reported among elderly patients with several comorbidities.2 National and international registers have been created to collect patients affected by rheumatic diseases, as well as patients with interstitial lung disorders.3 Since 20 February to 7 April 2020, we collected clinical data of 859 patients affected by different rheumatic diseases and sarcoidosis, treated with stable and full dosage of bDMARDs or tsDMARDs at Siena Rheumatology Unit and Siena Regional Referral Centre for Sarcoidosis. All patients underwent a telephone survey in order to establish their clinical status, the appearance of signs and symptoms of COVID-19 and the presence of …

The letter of Monti et al 1 on covid-19 in patients with chronic arthritis treated with immunosuppressive therapies stimulates some considerations. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects cells through the ACE-2 receptor, which is highly expressed in both the lung and the heart. Besides direct tissue injury, SARS-CoV-2 infection can also induce an exaggerated host immune response, frequently inducing a cytokine release syndrome contributing to multiorgan dysfunction. Indeed, high levels of circulating cytokines, particularly interleukin (IL)-6, IL-1β and tumour necrosis factor-alpha (TNFα), are commonly found in patients with covid-19, correlating with mortality (IL-6).2 Current therapeutic strategy involves agents counteracting viral invasion and replication, and inhibitors of cytokine-sustained inflammatory reactions. Indeed, different cytokines involved in the acute inflammatory response are currently targeted by specific medications otherwise employed in the treatment of rheumatic diseases. Agents inhibiting the activity of IL-1β, TNFα, IL-6 and the Janus Kinase 1 and 2 (JAK 1/2)-Signal Transducer and Activator of Transcription (STAT) pathway are currently under consideration in the treatment of covid-19-associated respiratory syndrome.3 We are here providing some arguments to help achieve a more rational therapeutic decision. In any case, as a general consideration, the short-term period of administration of these agents is …

This paper investigates the correlation between the high level of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) lethality and the atmospheric pollution in Northern Italy. Indeed, Lombardy and Emilia Romagna are Italian regions with both the highest level of virus lethality in the world and one of Europe's most polluted area. Based on this correlation, this paper analyzes the possible link between pollution and the development of acute respiratory distress syndrome and eventually death. We provide evidence that people living in an area with high levels of pollutant are more prone to develop chronic respiratory conditions and suitable to any infective agent. Moreover, a prolonged exposure to air pollution leads to a chronic inflammatory stimulus, even in young and healthy subjects. We conclude that the high level of pollution in Northern Italy should be considered an additional co-factor of the high level of lethality recorded in that area.

Objectives. The primary aim of our study was to evaluate long-term efficacy of secukinumab (SCK) in patients with axial spondyloarthritis (axSpA); secondary aims were to evaluate drug retention rate and to identify differences in the clinical and laboratory assessment according to axSpA clinical features, dosage administered, and biologic treatment lines.Patients and Methods. We collected clinical, demographical, and treatment data from 39 patients affected by axSpA consecutively treated with SCK. Laboratory assessment was based on inflammation parameters; clinical assessment was performed with the Ankylosing Spondylitis Disease Activity Score- (ASDAS-) CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were recorded at baseline and every 3 months for the first year and then every 6 months in the second year.Results. Twelve males and 27 females were enrolled; both BASDAI and ASDAS-CRP showed a statistically significant reduction during the observation period (p<0.0001andp<0.0001, respectively). C-reactive protein significantly decreased (p=0.006), with significant reduction at the post hoc analysis between baseline and both 6-month evaluation (p=0.02) and 24-month visit (p=0.036). No statistical significance was observed in BASDAI and ASDAS-CRP improvement (p=0.482andp=0.164, respectively) between different dosages administered. No significant differences emerged in the BASDAI and ASDAS-CRP variations between biologic-naïve patients and subjects previously failing to tumour necrosis factor (TNF) inhibitors (p=0.53andp=0.148, respectively). At the end of our observation, 7 out of 39 patients discontinued SCK. The global retention rate at the end of the study period was 78.2%, without any significant differences between biologic-naïve and anti-TNF-failure patients (p=0.619) or between subjects administered with different SCK dosages (p=0.614). No adverse events were reported.Conclusions. In our cohort, SCK has proved a remarkable effectiveness regardless biologic treatment line and dosages employed. As suggested by the notable drug retention rate, SCK has been able to maintain its effectiveness over a considerable long period of treatment.

ObjectivesPolymyalgia rheumatica (PMR) is the commonest inflammatory disorder of the elderly; an association with environmental triggers and a deregulated immune response have been described. The aim of this study was to investigate the association of environmental triggers before the onset of PMR.Material and methodsThe database of 58 consecutive PMR patients recruited from a single rheumatology secondary care setting was retrospectively analyzed to investigate the frequency of environmental triggers and correlations with clinical characteristics, ultrasound and laboratory data.ResultsFifteen PMR patients (26%) described a connection with environmental agents: six PMR patients reported a vaccination, 4 reported a respiratory tract infection, 5 reported seasonal influenza before the onset of the disease. The model of multivariate linear regression which better predicted a shorter time to normalize inflammatory reactants (R2 = 27.46%, p = 0.0042) comprised the presence of an environmental trigger and a higher PCR. A linear regression analysis confirmed an inverse correlation between PCR at onset and time to normalize inflammatory reactant (r = –0.3031, p = 0.0208). A significant correlation was demonstrated between presence of environmental trigger and shorter time to normalize inflammation (r = –0.5215, p < 0.0001), and lesser frequency of gleno-humeral synovitis on US (r = –0.3774, p = 0.0038).ConclusionsOur work describes a correlation between environmental triggers in PMR and higher CRP at diagnosis, faster response to therapy, and milder shoulder synovitis. We may suppose that these patients belong to a more specific subtype of PMR, in whom external stimuli, such as vaccination or infection, may lead to a deregulated response within the context of an impaired senescent immuno-endocrine system.

Alberto Migliore,1,2 Bruno Frediani,3 Gianfranco Gigliucci,1 Calogero Foti,4 Sergio Crimaldi,5 Orazio De Lucia,6 Giovanni Iolascon7 1Rheumatology Unit, S. Pietro FBF Hospital, Rome, Italy; 2Department of Internal Medicine, S. Pietro FBF Hospital, Rome, Italy; 3Medical and Surgical Science and Neuroscience Department, Rheumatology Section, University of Siena, O.U. of Osteo-Articular Diagnostic Procedures, Siena, Italy; 4Physical and Rehabilitation Medicine Department, University of Rome Tor Vergata, Rome, Italy; 5Orthopaedics and Traumatology Department, Lucca Hospital, USL Tuscany Northwest, Lucca, Italy; 6Division of Rheumatology, Gaetano Pini Institute, Milan, Italy; 7Physical and Rehabilitation Medicine Department, Napoli University, Naples, ItalyCorrespondence: Alberto MiglioreDepartment of Internal Medicine, S. Pietro FBF Hospital, Rome 00189, ItalyTel +39 049 7443620Fax +39 049 7443622Email alberto.migliore.12@outlook.itPurpose: The use of ultrasound (US) guidance has allowed hip osteoarthritis to be treated with intra-articular (IA) injections. HYMOVIS ONE (HYADD4-G) is a new hyaluronic acid (HA) derivative product with unusual characteristics, and it has been used with good results in knee osteoarthritis (OA). This study assessed the efficacy and safety of a single HYMOVIS ONE injection in patients affected by symptomatic hip OA.Patients and Methods: This post-marketing cohort study assessed data from the ANTIAGE Register. Inclusion criteria were age ≥ 40 years, symptomatic hip OA (Kellgren-Lawrence grade I–III) of ≥ 1-year duration, and ≥ 12 months follow-up. All patients received a single HYMOVIS ONE (32 mg/4 mL) injection at baseline. Values for 10-cm visual analogue scale (VAS) pain scores, the Lequesne index, and nonsteroidal anti–inflammatory drug (NSAID) consumption were evaluated at 6 and 12 months. Adverse events were also recorded.Results: The included patients (n = 198) consisted of 42.5% women, with a mean (± SD) age at baseline of 62 (± 14.2) years and a mean (± SD) body mass index of 26.3 (± 2.5). The mean (SD) Lequesne index and VAS pain scores at baseline were 11.5 (± 4.6) and 6.4 cm (± 2.2), respectively. All groups exhibited statistically significant reductions at all time points compared to baseline. At 12 months, the VAS pain score was reduced by 17.2%, the Lequesne index by 33.7%, and NSAID consumption by 41.7%.Conclusion: Our study supports the clinical efficacy and safety of a single HYMOVIS ONE injection for managing symptoms in patients with hip OA, confirming previous data on the use of HYMOVIS as a background therapy in the management of knee osteoarthritis.Keywords: hip osteoarthritis, viscosupplementation, HYMOVIS ONE, HYADD4-G

Recurrent pericarditis (RP) is a troublesome and debilitating complication of acute pericarditis. Although the etiopathogenesis of this condition remains unknown, an intricate overlap of autoimmune and autoinflammatory pathways has been hypothesized to explain its beginning and recurrence over time. The majority of cases are defined as "idiopathic", reflecting our awkwardness to unravel the intimate mechanisms of RP. Given the possible occurrence of anti-nuclear, anti-heart and anti-intercalated disk antibodies as well as the association with peculiar human leukocyte antigen haplotypes, an autoimmune contribution has been claimed to specify the nature of RP. However, the most innovative pathogenic scenario of RP has been conferred to the innate immune system, mainly involving neutrophils and macrophages that produce a large amount of interleukin (IL)-1 via inflammasome activation. The clinical resemblance of RP with autoinflammatory diseases that may be marked by symptomatic serositis, high fevers and strikingly increased inflammatory parameters further suggests a similar inflammasome-mediated pathogenesis. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of therapy in RP, whereas colchicine is recommended on top of standard anti-inflammatory therapy, due to its role in inhibiting the IL-1 converting enzyme (caspase 1) within the inflammasome as well as the release of additional pro-inflammatory mediators and reactive oxygen species. With regard to treatment of RP refractory to NSAIDs and colchicine, blockade of IL-1 is the most relevant advance achieved in the last decade: the outstanding effect of the short-acting IL-1 receptor antagonist anakinra has been first recognized in the pediatric population, giving a proof of its practical feasibility. Over a more recent time, a growing experience with anakinra deriving from both large and small studies has further confirmed that RP might be regarded as an IL-1-mediated disease. This review aims to provide a contemporary insight into the mechanisms leading to RP as well as into the most recent literature data showing the beneficial approach originating from IL-1 blockade in this intriguing disorder.

Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017). Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.

Introduction. Giant cell arteritis (GCA) is a large vessel (LV) vasculitis, mainly affecting elder patients. Monitoring GCA activity during tocilizumab (TCZ) treatment is an unmet need, since low serum levels of C-reactive protein (CRP) during treatment may underestimate disease activity. To date, few data are available on the role of different imaging techniques in monitoring GCA activity and response to treatment. We report herein a cohort of GCA patients treated with TCZ and followed up with multimodal imaging. Patients and Methods. We collected clinical, laboratory, and imaging data of 11 GCA patients treated with TCZ 162 mg subcutaneously every week. Disease activity was assessed at baseline and within 12 months from the start of treatment using different imaging techniques such as color Doppler ultrasonography (CDUS), magnetic resonance imaging/angiography (MRI/MRA), computed tomography angiography (CTA), and/or positron emission tomography (PET). Results. Four patients were affected by cranial and 7 by LV-GCA. All patients were treated with oral glucocorticoids (GCs) (mean dose 55.68 mg±8.19 of prednisone or equivalent) in combination with TCZ. Treatment was preceded in 5 cases by 3 intravenous boluses of 1000 mg methylprednisolone. A significant decrease of the mean dose of oral GCs was observed between baseline and the last follow-up visit (4.65±3.69 mg) (p=0.003). TCZ treatment significantly decreased erythrocyte sedimentation rate (p<0.01) and CRP levels (p<0.01). At follow-up (mean 8.18±3.63 months), all patients were in clinical and serological remission. Moreover, PET, CDUS, MRI/MRA, and CTA did not show any LVV finding. Conclusions. Our study highlights TCZ efficacy in inducing GCA remission and its steroid-sparing effect. We highlighted a reliability of imaging procedures in the evaluation of disease activity and treatment response. A close disease monitoring with imaging techniques should be taken into account in GCA patients during TCZ treatment.

To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA).We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biologic IR, ≥2-biologics IR patients. Hazard ratios (HRs) of discontinuing golimumab at 2 years were assessed by multivariate Cox regression. Patients achieving CDAI based low disease activity (LDA) or BASDAI4 were calculated at 6 and 12 months.In RA (n.370), the 2-years survival on golimumab was 61.4% in 1-biologic IR, 51.9% in≥2-biologics IR, and 73.1% in biologic-naive patients (P=0.002 vs≥2-biologics IR). In SpA (n.502), the survival was similar among 1-biologic IR (80%), ≥2-biologics IR (76.5%), and biologic-naive (74.6%) patients (P0.05). In PsA (n.552) the survival was 72% in 1-biologic IR, 72.5% in≥2-biologics IR, and 71.8% in naïve-biologic (P0.05). Predictors of golimumab discontinuation were monotherapy (HR 1.65) for RA, female gender for SpA (HR 2.48) and PsA (HR 1.57). In RA, patients on CDAI-LDA were lower in 1-biologic IR (40%) or≥2 biologics IR (40%) than in biologic-naïve (60%) group at 6 months (P=0.02), but no difference was observed at 12 months. In PsA and SpA, the percentage of patients on CDAI-LDA or BASDAI4 at 6 months was almost identical across the subgroups.Golimumab had similar effectiveness in biologic-failure and biologic-naïve SpA and PsA, but seems to be less effective in multi-failure RA patients, especially as monotherapy. The best outcomes were seen in male patients.

Background Baricitinib is a JAK inhibitor that blocks intracellular signalling pathways of inflammatory cytokines recommended for Rheumatoid arthritis (RA) patients not responding to initial treatment. Among RA extrareticular features, interstitial lung involvement is primarly characterized by fibrotic evolution. The aim of the present study was to analyse the effects of baricitinib in a population of RA and RA-ILD patients in a real-life setting, describing any changes in lung function parameters, serum inflammatory biomarkers and fibrotic biomarkers after 6 months of treatment. Materials and methods 15 patients (median (IQR) 65 (55–66); 13% males and 74% smokers) treated with baricitinib were enrolled. 4 patients (27%) were classified as RA-ILD before baricitinib therapy. Our study is the first to evaluate adipokine levels in RA patients (including a small population with RA-ILD) after six months of baricitinib treatment with a novel multiplex method. Results The modulatory effects of baricitinib on lipid mediators were associated with clinical and functional improvement, demonstrated by the significant increase in DLco and KCO percentages after six months of treatment. Baricitinib decreased the systemic inflammation by lowering expression of IL-6 and CRP and reducing ESR and serum concentrations of adiponectin. A significant reduction of KL-6 levels in RA-ILD patients after six months of baricitinib therapy reflects the stability of interstitial lung involvement in these patients. Conclusion Baricitinib was demonstrated to be a safe immune modulator that reduces the concentrations biomarkers of lung fibrosis and inflammation in RA patients, including a subgroup with interstitial lung involvement.