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This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet’s syndrome (BS), their association with other disease manifestations, response to therapy, and long-term prognosis. Data were retrieved from the AIDA Network Behçet’s Syndrome Registry. Out of a total of 141 patients with juvenile BS, 37 had MSM at disease onset (26.2%). The median age at onset was 10.0 years (IQR 7.7). The median follow-up duration was 21.8 years (IQR 23.3). Recurrent oral (100%) and genital ulcers (67.6%) and pseudofolliculitis (56.8%) were the most common symptoms associated with MSM. At disease onset, 31 subjects had arthritis (83.8%), 33 arthralgia (89.2%), and 14 myalgia (37.8%). Arthritis was monoarticular in 9/31 cases (29%), oligoarticular in 10 (32.3%), polyarticular in 5 (16.1%), axial in 7 (22.6%). Over time, arthritis became chronic-recurrent in 67.7% of cases and 7/31 patients had joint erosions (22.6%). The median Behçet's Syndrome Overall Damage Index was 0 (range 0–4). Colchicine was inefficacious for MSM in 4/14 cases (28.6%), independently from the type of MSM (p = 0.46) or the concomitant therapy (p = 0.30 for cDMARDs, p = 1.00 for glucocorticoids); cDMARDs and bDMARDs were inefficacious for MSM in 6/19 (31.4%) and 5/12 (41.7%) cases. The presence of myalgia was associated with bDMARDs inefficacy (p = 0.014). To conclude, MSM in children with BS are frequently associated with recurrent ulcers and pseudofolliculitis. Arthritis is mostly mono- or oligoarticular, but sacroiliitis is not unusual. Prognosis of this subset of BS is overall favorable, though the presence of myalgia negatively affects response to biologic therapies. ClinicalTrials.gov Identifier: NCT05200715 (registered on December 18, 2021).

Polymyalgia rheumatica (PMR) is an inflammatory disease affecting older adults characterized by aching pain and morning stiffness of the shoulder and pelvic girdles. Moreover, PMR can be associated with giant cell arteritis (GCA). Generally, PMR is highly responsive to steroids, reaching complete remission in the majority of cases. However, the possibility of occult diseases, including extra-cranial GCA, should be excluded. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is able to detect the presence of peri-/articular or vascular inflammation, which may be both present in PMR, thus representing a useful diagnostic tool, mainly in presence of extra-cranial GCA. We retrospectively evaluated all consecutive patients who received the diagnosis of PMR in our rheumatology clinic, classified according to the 2012 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, in the period between April 2020 and May 2022. Among this case series, we selected the patients who underwent 18F-FDG-positron emission tomography (PET) because of the persistent increase of acute phase reactants (APR) besides the steroid therapy. Eighty patients were diagnosed with PMR. Nine out of them also presented arthritis of the wrists during the follow-up, whereas none showed signs of cranial GCA at the diagnosis. Seventeen out of eighty subjects (mean age 71.5 ± 7.5 years; M/F 2/15) presented persistent increase of erythrocyte sedimentation rate (mean ESR 44.2 ± 20.8 mm/h) and/or C-reactive protein (mean CRP 25.1 ± 17 mg/l), thus they underwent total body 18F-FDG-PET/CT. Large vessel 18F-FDG uptake indicating an occult GCA was found in 5/17 (29.4%) cases. Twelve out of seventeen (70.6%) patients showed persistence of peri-/articular inflammation, suggesting a scarce control of PMR or the presence of chronic arthritis. Finally, in 2 cases, other inflammatory disorders were found, namely an acute thyroiditis and a hip prosthesis occult infection. 18F-FDG-PET/CT in PMR patients with persistent increase of APR is a useful diagnostic technique in order to detect occult GCA, persistence of active PMR or other misdiagnosed inflammatory diseases.

Purpose: To study the therapeutic effect of 3-O-caffeoylquinic acid (3-O-CQA) from Periploca forrestii extract (PFE) on collagen-mediated arthritis (CIA) in rats, as well as the potential underlying mechanism of action. Methods: PFE and 3-O-CQA were successively and intragastrically administered to CIA rats. Paw swelling, arthritic scores and H & E staining were used to evaluate the therapeutic effect of 3-O-CQA. Moreover, to determine the effects of PFE and 3-O-CQA on fibroblast-resembling synoviocytes obtained from arthritic subjects (RAFLS), the viability of RAFLS cultured in vitro was measured with MMT, while apoptotic lesions were analyzed by flow cytometry. The levels of IL-6 in CIA and RAFLS were determined by enzyme-linked immunosorbent assay (ELISA), while quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) and immunoblotting were used to assess their mRNA and polypeptide levels, respectively. Results: PFE in 3-O-CQA ameliorated swelling and reduced arthritic scores in CIA rat model, and also decreased cytokine levels (p < 0.05). By decreasing mRNA and protein expressions, 3-O-CQA repressed the phosphorylation of STAT3 and JAK2 as well as the protein levels of IL-23 and RORγt (p < 0.05). Conclusion: The results of this study show that CIA and RAFLS are ameliorated in rats by 3-O-CQA in PFE through regulation of IL17/ IL23 and Th17 cells. Thus, 3-O-CQA affords a therapeutic strategy for the management of collagen-induced arthritis. Keywords: Arthriti; Periploca forrestii Schltr extract; 3-O-Caffeoylquinic acid; Interleukin (IL)-17; IL-23; Th17 cells

ObjectiveIn the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination.MethodsVolunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers.ResultsSamples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], pConclusionThe response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients.

ObjectiveAs part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe.MethodsTwo cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0–10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0–100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementationResultsOverall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients.ConclusionsMany problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.

In the past months, mass vaccination represented the turning point of the global battle against the COVID-19 pandemic, an unprecedented challenge for physicians, healthcare professionals, health systems and pharmaceutical companies. More than 6 billion doses of vaccine have been administered to date, covering nearly 50% of the world’s population. Although the vaccination campaign is still thwarted by spread of fake news disseminated by a ubiquitous antivaxxer movement, accumulating real-life data1 confirm the favourable safety profile already demonstrated in phase III clinical trials.2 Despite the lack of a steady literature evidence,3 the potential role of vaccines in promoting autoimmunity continues to intrigue many researchers. The theoretical basis of this association relies on the possible molecular mimicry between macromolecular components of the vaccine and specific human proteins and the exuberant immune response elicited by adjuvants contained in vaccines.4 Adverse events (AEs) associated with COVID-19 vaccines are usually mild and mainly restricted to injection site reactions. Interestingly, among systemic AEs, arthralgia is one of the most common.2 To the best of our knowledge, only isolated cases5 of arthritis developed after COVID-19 …

Background Pyrocardan® (Wright Medical-Tornier) is a pyrocarbon implant proposed in the treatment of trapeziometacarpal joint (TMCJ) osteoarthritis. Our aim was to assess the clinical and radiographic results after Pyrocardan® arthroplasty at midterm follow-up. Methods In this prospective monocentric study, we enrolled 119 patients treated with Pyrocardan® for TMCJ osteoarthritis and followed up at a minimum of four years. The clinical outcome was assessed through the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, the Visual Analog Score (VAS) for pain and the Kapandji score collected pre-operatively, at three, six and 12 months, then yearly. Hand radiographs were taken before surgery, at three months and every year. Complications and re-operations were also recorded. Results The mean follow-up was 5.2 years (range, 4–9). DASH, VAS and Kapandji scores significantly improved at three (p p p = 0.01 and p Conclusion Pyrocardan® arthroplasty provides a satisfactory clinical and radiographic outcome for treating TMCJ osteoarthritis, with a 97% survival rate at four years. We advocate comparative studies with more common techniques (i.e., trapeziectomy) to verify its cost-effectiveness.

The purpose of the present paper was to review the available evidence on intra-articular botulinum toxin (BTX) injection in the treatment of knee osteoarthritis and to compare it to other conservative treatment options. A systematic review of the literature was performed on the PubMed, Scopus, Cochrane Library, Web of Science, Pedro and Research Gate databases with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in the English language, and (3) published on indexed journals in the last 20 years (2001–2021) dealing with the use of BTX intra-articular injection for the treatment of knee OA. The risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. Nine studies involving 811 patients in total were included. Patients in the control groups received different treatments: conventional physiotherapy, hyaluronic acid injection or prolotherapy or a combination thereof in 5 studies, steroid infiltrative therapy (triamcinolone) in 1 study, placebo in 2, and local anesthetic treatment in 1 study. Looking at the quality of the available literature, two of the included studies reached “Good quality” standard, three were ranked as “Fair”, and the rest were considered “Poor”. No major complications or serious adverse events were reported following intra-articular BTX, which provided encouraging pain relief, improved motor function, and quality of life. Based on the available data, no clear indication emerged from the comparison of BTX with other established treatments for knee OA. The analysis of the available RCTs on BTX intra-articular injection for the treatment of knee OA revealed modest methodological quality. However, based on the data retrieved, botulinum toxin has been proven to provide good short-term outcomes, especially in patients with pain sensitization, by modulating neurotransmitter release, peripheral nociceptive transduction, and acting on the control of chronic pain from central sensitization.

ObjectiveTo investigate how the mucosal barrier in the intestine influences the development of arthritis, considering that metabolic changes in the intestinal epithelium influence its barrier function.MethodsIntestinal hypoxia inducible factor (HIF)-2α expression was assessed before, at onset and during experimental arthritis and human rheumatoid arthritis (RA). Intestinal epithelial cell-specific HIF2α conditional knock-out mice were generated (HIF2α∆IEC) and subjected to collagen-induced arthritis. Clinical and histological courses of arthritis were recorded; T-cell and B-cell subsets were analysed in the gut and secondary lymphatic organs; and intestinal epithelial cells were subjected to molecular mRNA sequencing in HIF2α∆IECand littermate control mice. The gut intestinal HIF2α target genes were delineated by chromatin immunoprecipitation and luciferase experiments. Furthermore, pharmacological HIF2α inhibitor PT2977 was used for inhibition of arthritis.ResultsIntestinal HIF2α expression peaked at onset of experimental arthritis and RA. Conditionally, deletion of HIF2α in gut epithelial cells inhibited arthritis and was associated with improved intestinal barrier function and less intestinal and lymphatic Th1 and Th17 activation. Mechanistically, HIF2α induced the transcription of the pore-forming claudin (CLDN)-15, which inhibits intestinal barrier integrity. Furthermore, treatment with HIF2α inhibitor decreased claudin-15 expression in epithelial cells and inhibited arthritis.ConclusionThese findings show that the HIF2α–CLDN15 axis is critical for the breakdown of intestinal barrier function at onset of arthritis, highlighting the functional link between intestinal homeostasis and arthritis.

ObjectivesTo develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs).MethodsEuropean Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously.ResultsA total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel.ConclusionThese are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs.

Objectives: The aim of this study was to describe the cohort of patients who have been treated with Denosumab as neoadjuvant therapy prior to surgery for aggressive giant cell tumor of bone in the extremities, to evaluate the radiological responses to Denosumab comparing Choi criteria and a newly described computerized tomography (CT) classification, and to evaluate the risk of local recurrence after intralesional curettage or radical excision. Methods: We retrospectively evaluated 36 patients (20 females and 16 males; mean age at diagnosis 36 years (range, 18–64)) treated with neoadjuvant Denosumab therapy prior to surgery for aggressive giant cell tumor of bone in the extremities. The radiological responses to Denosumab treatment were analyzed on the preoperative images after the neoadjuvant course with the Choi criteria and with a newly proposed classification based on CT. All these images were independently reviewed by two of the researchers. Surgical intervention methods were noted and local recurrence rates were evaluated. The correlation between radiological response amount and local recurrence were analyzed for both Choi criteria and the new CT classification. Results: Denosumab was administered for a mean of 21 weeks (range 7–133). Five patients also had a short postoperative course. According to Choi criteria there was a radiological response in 32 patients (89%), while the new CT classification identified responses in all the 36 patients (100%). The identification of changes after 7 weeks of treatment was higher using the CT classification compared to Choi criteria (p = 0.043 vs p = 0.462). The surgical interventions after Denosumab comprised curettage in 29 patients (74%) and resection in 7 (26%). Local recurrence was higher in patients managed with intralesional curettage than in those treated with en bloc resection (55.1% vs 0%, p

Devil's Claw is a traditional medicine that has been long used a wide range of health conditions, including indigestion, fever, allergic reactions, and rheumatism. The main compounds are iridoid glycosides, including harpagoside, harpagide, and procumbide. However, harpagoside is the most responsible for therapeutic activity, and its content is used as reference standard. Here, we analyzed and summarized preclinical and clinical studies focusing on therapeutic efficacy of devil's claw preparations in pathological conditions in which inflammation plays a key causative role.Devil's claw (Harpagophytum procumbens) is an herbaceous plant, which can be found in the arid steppes of South Africa, particularly in the Kalahari Desert. As traditional medicine, devil's claw has been long used in the forms of infusions, decoctions, tinctures, powders, and extracts. The main compounds of devil's claw are iridoid glycosides, such as harpagoside, harpagide, and procumbide, which are present in the plant tubers. Additionally, chemical constituents such as sugars (mainly the tetrasaccharide stachyose), triterpenoids (oleanolic and ursolic acid), phytosterols (primarily β-sitosterol), aromatic acids (caffeic, cinnamic, and chlorogenic acids), and flavonoids (luteolin and kaempferol) can be found in the plant. In order to investigate the applicative potential of devil's claw as therapeutic agent, we performed a review by focusing on its potential role in managing inflammation- and oxidative stress-related diseases, including arthritis, osteoporosis, inflammatory bowel disease, low-back pain, diabetes, and neurodegeneration.

Although the diagnosis of arthritis and spondyloarthritis is based on clinical criteria, today the imaging methods are an indispensable aid to the rheumatologist. Imaging has not only the task of helping early diagnosis, but it has also a fundamental role in disease grading and therapeutic monitoring. In this scenario where many publications emphasize the importance of identifying synovitis and erosions at an early stage, it is essential to know the possible pitfalls which can determine both false positives and false negatives. The high variability of the musculoskeletal system anatomy makes it necessary to have a correct knowledge of all anatomical complexes, in order not to confuse them with the pathology. Moreover, the correct and standardized method of the execution and interpretation of the exams, such as ultrasound, is crucial to identifying and correctly monitoring the pathological hallmarks of the arthritis. This paper aims to provide an instrument to radiologists, highlighting the main imaging pitfalls in ultrasound and magnetic resonance which may be encountered in daily practice.

Common variable immunodeficiency (CVID) is the most common clinically significant primary immunodeficiency in adulthood, which presents a broad spectrum of clinical manifestations, often including non-infectious complications in addition to heightened susceptibility to infections. These protean manifestations may significantly complicate the differential diagnosis resulting in diagnostic delay and under-treatment with increased mortality and morbidity. Autoimmunity occurs in up to 30% of CVID patients, and it is an emerging cause of morbidity and mortality in this type of patients. 95 patients (42 males and 53 females) diagnosed with CVID, basing on ESID diagnostic criteria, were enrolled in this retrospective cohort study. Clinical phenotypes were established according to Chapel 2012: i) no other disease-related complications, ii) cytopenias (thrombocytopenia/autoimmune hemolytic anemia/neutropenia), iii) polyclonal lymphoproliferation (granuloma/lymphoid interstitial pneumonitis/persistent unexplained lymphadenopathy), and iv) unexplained persistent enteropathy. Clinical items in the analysis were age, gender, and clinical features. Laboratory data included immunoglobulin (Ig)G, IgM and IgA levels at diagnosis, flow-cytometric analysis of peripheral lymphocytes (CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD4+CD25highCD127low, CD19hiCD21loCD38lo, and follicular T helper cell counts). Comparisons of continuous variables between groups were performed with unpaired t-test, when applicable. 39 patients (41%) showed autoimmune complications. Among them, there were 21 females (53.8%) and 18 males (46.2%). The most prevalent autoimmune manifestations were cytopenias (17.8%), followed by arthritis (11.5%), psoriasis (9.4%), and vitiligo (6.3%). The most common cytopenia was immune thrombocytopenia, reported in 10 out of 95 patients (10.5%), followed by autoimmune hemolytic anemia (n=3, 3.1%) and autoimmune neutropenia (n=3, 3.1%). Other autoimmune complications included thyroiditis, coeliac disease, erythema nodosum, Raynaud’s phenomenon, alopecia, recurring oral ulcers, autoimmune gastritis, and primary biliary cholangitis. There were no statistically significant differences comparing immunoglobulin levels between CVID patients with or without autoimmune manifestations. There was no statistical difference in CD3+, CD8+, CD4+CD25highCD127low T, CD19, CD19hiCD21loCD38lo, and follicular T helper cell counts in CVID patients with or without autoimmune disorders. In conclusion, autoimmune manifestations often affect patients with CVID. Early recognition and tailored treatment of these conditions are pivotal to ensure a better quality of life and the reduction of CVID associated complications.

Large cohort studies demonstrated that a sizeable proportion of patients with acute COVID-19 present with symptoms or signs of rheumatological interest such as arthralgia/myalgia, inflammatory skin lesions and/or autoantibodies positivity.1 Subsequent clinical observations disclosed the existence of a post-acute COVID-19 syndrome, characterised by a large constellation of manifestations including fatigue, arthralgia and myalgia.2 The potential role of viruses in the development of rheumatic diseases is well recognised, either as causative agents or antigenic triggers for the ensuing development of autoimmunity.3 Consistent with these premises, from the earliest phases of the pandemic, inflammatory musculoskeletal manifestations following COVID-19 have been described in isolated case reports although no systematically collected cohorts are still available to unveil the clinical spectrum of post-COVID-19 arthritis.4 To contribute to shed light on this field, in December 2020, we built a web-based survey platform and invited all members of our study group to submit cases of inflammatory …

Background Type 1 diabetes mellitus could be associated with other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, but the association with Familial Mediterranean Fever is rare, we describe a case of a boy with type 1 Diabetes Mellitus associated with Familial Mediterranean Fever (FMF). Case presentation A 13 year old boy already suffering from Diabetes Mellitus type 1 since the age of 4 years, came to our attention because of periodic fever associated with abdominal pain, chest pain and arthralgia. The fever appeared every 15–30 days with peaks that reached 40 °C and lasted 24–48 h. Laboratory investigation, were normal between febrile episodes, but during the attacks revealed an increase in inflammatory markers. Suspecting Familial Mediterranean Fever molecular analysis of MEFV gene, was performed. The genetic analysis showed homozygous E148Q mutation. So Familial Mediterranean Fever was diagnosed and colchicine treatment was started with good response. Conclusion Familial Mediterranean Fever could be associated with other autoimmune diseases such as Ankylosing Spondylitis, Rheumatoid Arthritis, Polyarteritis Nodosa, Behcet disease, Systemic Lupus, Henoch-Schönlein Purpura, and Hashimoto’s Thyroiditis. Association of type 1 Diabetes Mellitus and Familial Mediterranean Fever has been newly reported in the medical literature, this is the third association of these two diseases described in the medical literature so far.

The treatment of chronic wrist pain, due to posttraumatic, degenerative, or inflammatory arthritis, is challenging to adequately manage. The ideal surgical procedure should preserve wrist mobility and provide long-lasting pain relief. In this regard, denervation aims to decrease wrist pain by interrupting sensory innervation, without impairing motor function, and avoids the need for postoperative immobilization to decrease the risk of stiffness. For these reasons, denervation is particularly attractive as a possible treatment for chronic wrist pain. Our aim was to describe our novel technique for partial percutaneous wrist denervation, performed by radiofrequency ablation of the posterior and anterior interosseous nerves, and to report on the prospective outcomes over a 1-year follow-up for 3 patients (4 wrists) treated as of March 2019. The technique is performed on an outpatient basis and does not require postprocedure wrist immobilization or restriction in activities of daily living or work. Findings at the 1-year follow-up indicate that partial denervation improved grip strength, provided pain relief, maintained wrist motion, and improved subjective report of disabilities of the arm, shoulder, and hand. One patient did not report a benefit of the procedures, with other patients being very satisfied. Our percutaneous procedure is an evolution of the traditional partial denervation technique, providing advantages of being less invasive, not requiring restriction of movement or activities in the postoperative phase, can be performed on an out-patient basis, and does not preclude the subsequent use of invasive surgical procedures, as needed.

Objective Several, but not all studies, have shown a dose-dependent inverse association with alcohol consumption and rheumatoid arthritis (RA), whereas smoking is an established risk factor for RA. We aimed to study the association between alcohol consumption and RA incidence and investigate a potential interaction between alcohol and smoking habits, regarding RA incidence. Methods We used a prospective cohort study, based on 41 068 participants with detailed assessment of alcohol intake, smoking and potential confounders at baseline in 1997. We ascertained a total of 577 incident cases of RA during a mean of 17.7 years of follow-up through linkage to nationwide and essentially complete databases. Multivariate Cox proportional hazards models were used to estimate HR with 95% CI. Interaction on the additive scale between alcohol and smoking was estimated by calculating the attributable proportion due to interaction (AP). Results Overall, alcohol consumption was associated with a 30% reduced incidence of RA (HR 0.69, 95% CI 0.55 to 0.86) with a dose-response relationship (p value for trend

Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing). Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003). Conclusion: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave.

We followed with great interest the numerous reports published by the Annals 1–9 as regards the impact of the COVID-19 pandemic on different rheumatic autoimmune systemic diseases (ASD), including the survey study by Costa et al 9 that underlined the usefulness of telerheumatology in the management of patients with psoriatic arthritis in COVID-19 era. On the same topic, the world literature encompasses a large number of anecdotal observations, cohort studies and telephone surveys.1–15 Overall, the observed prevalence of symptomatic COVID-19, usually as mild-moderate disease, in patients with chronic arthritis was comparable to that found in the general population, while worse outcomes represented almost rare events.1–15 Conversely, increased percentages of symptomatic COVID-19 were observed in patient cohorts with connective tissue diseases, especially systemic lupus or systemic vasculitis.6 7 Of note, in ASD complicated by COVID-19, the baseline use of immune modifiers, namely, conventional synthetic (csDMARD), biological (bDMARD) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD), was not associated with worse COVID-19 disease outcomes.3–5 9 10 Almost invariably these monocentre studies focused on ASD patients’ populations from limited geographical areas.1–15 Given the heterogeneous distribution of pandemic infection within the same country, we investigated the impact of COVID-19 in ASD patients’ populations from three distinct regions of Italy (northern, Emilia Romagna; central, Tuscany; and southern, Calabria), characterised by different spread of the COVID-19 pandemic, prevalent in northern Italy with a marked gradient north-south.16 Our 6-week multicentre telephone survey of 1641 unselected patients with ASD confirmed the quite benign clinical course of COVID-19 in ASD, along with the safety of baseline use of either …

Resilience is defined as “the capacity of individuals to cope successfully with significant change or adversity”. The challenge posed by the COVID-19 pandemic may potentially represent an overwhelmingly stressful event for patients with chronic diseases. Aim of our study was to investigate the levels of resilience in individuals with inflammatory arthritis living in Emilia Romagna, the third hardest-hit Italian region during the ongoing COVID-19 pandemic. To this purpose, we developed a survey consisting of four different sections assessing demographic characteristics, the 14-item resilience scale (RS14) and questionnaires evaluating depression and anxiety. Consecutive patients with inflammatory arthritis were recruited over a short time frame immediately after the end of national lockdown and compared with control individuals from the general population. One hundred twenty-two patients and 173 controls were included. Levels of resilience, as measured by RS14 score, were significantly higher in patients with inflammatory arthritis (82.6 ± 14.0 vs 79.0 ± 12.8, p = 0.018). After stratification for gender, the difference in RS14 score was maintained in women (p = 0.045), but not in men (p = 0.252). High resilience, defined as having a RS14 score > 90, was significantly more prevalent in patients than in controls (30% vs 16%, p = 0.009). In arthritis patients, no significant differences in RS14 were observed after stratification for specific diagnosis, age, or disease duration and activity. Our findings suggest that patients with inflammatory arthritis may be more resilient than the general population towards unexpected stressful events such as the ongoing COVID-19 pandemic.Key Points• Living with inflammatory arthritis may foster resilience.• After COVID-19, patients with inflammatory arthritis were more resilient than the general population. Electronic supplementary material The online version of this article (10.1007/s10067-020-05411-x) contains supplementary material, which is available to authorized users.

Purpose: An unsatisfactory reduction and internal fixation of an ankle fracture can result in an alteration of the anatomical axes and distribution of the load on the ankle, with consequent development of chronic pain and articular degeneration. The aim of this study is to evaluate the results of the articular re-balancing with realignment and lengthening of the fibula in case of malunited distal fibular fractures. Methods: A review of prospectively collected data was performed for all patients with a diagnosis of malunion of the fibula and underwent ankle joint re-balancing with fibular lengthening. Twenty-three patients, with a mean age of 39.4 ± 13.1years, have been evaluated using radiographic parameters, American Orthopaedic Foot and Ankle Surgeons ankle-hindfoot, Ankle Activity scale, and SF-36 score at six, 12, 24, and 36months post-operatively. Results: All cases treated showed at follow-up the osteotomy healed in good correction of the deformities. Clinical scores showed a clear improvement: final 36-month mean AOFAS was 74.0 ± 8.9 point, final 36-month mean HALASI score was 4.9 ± 0.9 points, 36-month follow-up SF-36 score showed an average score of 73.2 ± 10.7 points. Pre- and post-operative radiographic parameters have been registered and described. Conclusions: The ankle joint is a complex structure, and even minor changes of the structure of this joint can significantly compromise its functionality. Ankle joint re-balancing is an effective surgical procedure in case of fibular malunion. This procedure, in patients carefully selected, could procrastinate more disabling surgical procedure, as arthrodesis or prosthesis.

The aim of this systematic review was to understand which procedure – total or partial wrist denervation – provides better results in terms of pain relief and function. This review was registered on PROSPERO (CRD42018088856). We searched the Medline (PubMed), Web of Science and Scopus databases. Twenty-one studies were included in this review. We assessed the quality of the studies using the Coleman Methodological Score. Data on demographics, surgical indications, diagnostic methods, follow-up periods, type and rates of complications, survivorship of the procedure, return to work, and outcome measures were recorded. A total of 1065 patients were included in this review; the mean quality of the studies included was considered poor. The outcomes could not be analyzed because none of the studies had reliable outcome data reported, but both procedures were effective in terms of pain relief and range of motion. Partial wrist denervation has an average subsequent procedure rate of 19%. Total wrist denervation had an average subsequent procedure rate of 4.7%. No complications were reported in any patient who underwent partial wrist denervation versus 20 patients who underwent total wrist denervation. Both partial and total wrist denervation are safe and reliable procedures that can provide good pain relief and preserve wrist range of motion. Total wrist denervation offers better long-term outcomes in term of pain relief, with fewer subsequent procedures being needed compared to partial denervation, and with a low complication rate. Level of Evidence: Level III, Systematic review, Therapeutic.

IntroductionCovid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic.MethodThis observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1)definitediagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2)highly suspectedCovid-19 disease: presence of highly suggestive symptoms, in absence of a swab test.ResultsA significantly higher prevalence of patients withdefinitediagnosis of Covid-19 disease,or withhighly suspectedCovid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to “Italian general population” (p = .030,p = .001,p = .000, respectively); and fordefinite + highly suspecteddiagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population).Moreover, significantly higher prevalence ofdefinite + highly suspecteddiagnosis of Covid-19 disease was found either in patients with various “connective tissue diseases” compared to “inflammatory arthritis group” (p p = .011).ConclusionsThe finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases.Key Points• Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients’ increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement.• The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing.• Patients with “connective tissue diseases” show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to “inflammatory arthritis group”.• Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.

Background: A new design of 3-part ankle replacement was developed to achieve compatibility with the natural ligaments by allowing certain fibers to remain isometric during passive motion. Methods: We evaluate 75 ankle prostheses implanted from July 2003 to December 2008, at a mean follow-up 6.5. ±. 1.1. years (range 5-9 years). The mean age at surgery was 62. ±. 13. years (range 29-82). Results: The mean AOFAS scores achieved at pre-op and at last follow-up were respectively 37. ±. 5 (23-45) and 78. ±. 8 (64-98). (p.

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition. ispartof: JOURNAL OF CLINICAL MEDICINE vol:8 issue:11 ispartof: location:Switzerland status: published

In recent scientific literature, oral infections and systemic manifestations, or correlations between oral health and systemic diseases are a topic of discussion. Porphyromonas gingivalis is one of the bacteria implicated in the biofilm formation of bacterial plaque, and plays an important role in the progression of periodontal disease. In this systematic review authors have evaluated the literature of the last 10 years on P. gingivalis and all the systemic implications proven. This study therefore evaluates all the districts of the organism in which this bacterium may have implications. From the results it emerges that P. gingivalis has implications in the onset of different systemic pathologies, including rheumatoid arthritis, cardiovascular pathologies, and neurodegenerative pathologies. Surely, understanding the mechanisms of diffusion of this bacterium, it would be possible to prevent a series of pathologies. Thus, putting the dentist clinician at the center of prevention for these diseases.

Rheumatoid arthritis (RA) is an autoimmune disease affecting joints due to the persistent inflammation of the synovial tissue. It affects 1% of the worldwide population with high socioeconomic costs. Patients usually require lifetime treatments in order to prevent late stage of the disease, which leads to a condition of disability and pain. Despite the introduction of biological drugs, Methotrexate (MTX) is still the gold standard. However, it shows some weakness such as inefficacy or adverse events after long term usage. For this reason, there is the need to develop drugs with an improved safety profile and higher therapeutic efficacy. Moreover, it is of primary importance to develop diagnostics with enhanced sensitivity and tissue specificity. In order to meet these needs, the purpose of this work is to develop a nanotechnological agent capable to delivery its content, such as drugs or diagnostic tracers, specifically into pathological joints, avoiding healthy tissues. These aims have been achieved exploiting peculiar features of biodegradable nanoparticles (BNPs), such as improved pharmacokinetic and bioavailability, associated to a peptide specific for the inflamed synovia. Recently, the heterogeneity of the molecules present in the endothelium has allowed to develop peptides capable to target vessels of specific tissues. In this project, a cyclic peptide able to target the microvasculature of the inflamed synovia has been exploited to drive BNPs only into inflamed joints. BNPs have been characterized for their physicochemical features, polymers’ toxicity and drug release. Targeted polymeric nanoparticles (tBNPs) demonstrated, both in vitro and in vivo, to preferentially bind inflamed synovial tissue, and their accumulation depends from the degree of inflammation. Targeted BNPs loaded with MTX showed higher efficacy compared to free MTX in two different animal models of RA. In addition, reduced dose of tBNPs-MTX demonstrated to maintain its efficacy, showing fewer side effects compared with systemic administration of free MTX. This new therapeutic approach provided a new mechanism of action from approved therapy and suggest potential application in non-responding patients. All these evidences highlight the potential use of tBNPs as biocompatible and adaptable tool for the diagnosis and the treatment of RA showing important efficacy, reduced side effects and with the potential to enhance the sensitivity of several imaging technologies.

Objective To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). Methods The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). Results 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). Conclusion In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility

Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false. We examined models of three different diseases caused by organ-specific autoimmune responses: primary biliary cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators of relative abundance of Treg compared to pro-inflammatory T cells, during peak inflammation. In all cases, the results were compatible with a relative enrichment of Treg at the site of inflammation or its most proximal draining lymph node. Conversely, in healthy mice or mice successfully protected from disease via a Treg-mediated mechanism, the data did not suggest that any Treg accumulation was occurring. This counter-intuitive finding may appear to be at odds with the immunosuppressive nature of Treg. Yet extensive previous studies in RA show that an accumulation of Treg occurs at peak inflammation, albeit without resulting in suppression, as the Treg suppressive function is overcome by the cytokine-rich environment. We suggest that this is a ubiquitous feature of autoimmune inflammation. Treg abundance in patient samples is increasingly used as an indicator of a state of immunosuppression. We conclude that this strategy should be revisited as it may potentially be a source of misinterpretation.

Background Severe ankle arthritis is a life-limiting condition which often requires surgery. Ankle arthroplasty via artificial or “biological” reconstruction is a viable option in those patients who are not comfortable with arthrodesis. More functional studies are needed to compare the performance and outcomes of the two function-preserving arthroplasties. Methods In this study two groups of 10 patients affected by severe ankle arthritis were treated either with a 3-component ankle prosthesis or with bipolar fresh osteochondral allograft transplantation. Patients were evaluated pre-operatively and at 5-year follow-up. The American Orthopaedic Foot and Ankle Society score was used for clinical evaluation, and gait analysis for functional assessment. Activation pattern of lower limb muscles was obtained by surface electromyography (EMG). In each group, kinematic, kinetic, and EMG data were compared between pre-op and follow-up assessments, and also versus corresponding data from a 20 healthy subject control group. The median clinical score significantly increased between pre-op and follow-up from 53 to 74.5 in the transplantation and from 28.5 to 80 in the prosthesis group. Spatio-temporal parameters showed a statistically significant improvement in cadence and cycle time. Improvement of gait speed was also observed only in the prosthesis group. EMG patterns at follow-up were strongly correlated with the corresponding control data for both groups. Although no significant amelioration in the joints' range of motion was detected in either surgical procedure, preservation of the functional conditions at medium-term, along with significant improvement of the clinical score, may be considered a positive outcome for both techniques.

Blau syndrome (BS) and early onset sarcoidosis (EOS) are, respectively, the familial and sporadic forms of the pediatric granulomatous autoinflammatory disease, which belong to the group of monogenic autoinflammatory syndromes. Both of these conditions are caused by mutations in the NOD2 gene, which encodes the cytosolic NOD2 protein, one of the pivotal molecules in the regulation of innate immunity, primarily expressed in the antigen-presenting cells. Clinical onset of BS and EOS is usually in the first years of life with noncaseating epithelioid granulomas mainly affecting joints, skin, and uveal tract, variably associated with heterogeneous systemic features. The dividing line between autoinflammatory and autoimmune mechanisms is probably not so clear-cut, and the relationship existing between BS or EOS and autoimmune phenomena remains unclear. There is no established therapy for the management of BS and EOS, and the main treatment aim is to prevent ocular manifestations entailing the risk of potential blindness and to avoid joint deformities. Nonsteroidal anti-inflammatory drugs, corticosteroids and immunosuppressive drugs, such as methotrexate or azathioprine, may be helpful; when patients are unresponsive to the combination of corticosteroids and immunosuppressant agents, the tumor necrosis factor-α inhibitor infliximab should be considered. Data on anti-interleukin-1 inhibition with anakinra and canakinumab is still limited and further corroboration is required. The aim of this paper is to describe BS and EOS, focusing on their genetic, clinical, and therapeutic issues, with the ultimate goal of increasing clinicians' awareness of both of these rare but serious disorders.

BACKGROUND: Nucleotide-binding oligomerization domain 2 (NOD2) is a key intracellular protein of the innate immune system. NOD2 variants are associated with inflammatory bowel disease (IBD) and other inflammatory phenotypes. We described the case of a baby with a very early-onset IBD who is characterized by a rare homozygous variant in NOD2, found through whole-exome sequencing, Its pathogenic effect was investigated through bioinformatics and functional studies. METHODS: The microbicide activity of the patient's phagocytes was analyzed using Escherichia coli. HEK293 and Caco2 cell lines were transfected with wild-type and mutated NOD2 cDNA to evaluate the NF-kB activity and the protein distribution. The functionality of the NOD2 pathway was assessed through analysis of the expression of tumor nectrosis factor alpha (TNFα) on monocytes. The levels of various cytokines were quantified in the patient plasma by a multiplex suspension array. RESULTS: A missense NOD2 mutation, c.G1277A; p.R426H in homozygosis, was found. The patient's microbicide activity was comparable to that observed in controls. HEK293 cells transfected with the mutated cDNA showed a 20-fold increase of NF-kB activation in basal condition. Moreover, Caco2 immunostaining revealed a different cytoplasmic distribution of the mutated protein compared with wild-type. A higher production of TNFα by monocytes and elevated levels of plasmatic cytokines and chemokines were evidenced in the patient. CONCLUSIONS: This homozygous mutation is functionally relevant and shows a different NOD2 involvement in the IBD phenotype. In our patient, this mutation caused a gain of function typical of the Blau syndrome phenotype, manifesting, however, an IBD-like phenotype.

Although the better management of rheumatoid arthritis (RA) has significantly improved the long-term outcome of affected patients, a significant proportion of these may develop associated comorbidities including cardiometabolic complications. However, it must be pointed out that a comprehensive cardiometabolic evaluation is still poorly integrated into the management of RA patients, due to a limited awareness of the problem, a lack of appropriate clinical studies, and optimal strategies for cardiovascular (CV) risk reduction in RA. In addition, although several studies investigated the possible association between traditional CV risk factors and RA, conflicting results are still available. On this basis, we planned this cross-sectional study, aimed at investigating the prevalence of type 2 diabetes (T2D) and impaired fasting glucose (IFG) in RA patients compared with age- and gender- matched control individuals. Furthermore, we analyzed the role of both traditional and RA-related CV risk factors in predicting T2D and IFG. We observed an increased prevalence of T2D in RA patients when compared with age- and gender-matched controls. Regression analyses demonstrated that the presence of high blood pressure (HBP), a longer disease duration, and exposure to corticosteroids (CCS) were significantly associated with an increased likelihood of being classified as T2D. In addition, we observed an increased prevalence of IFG in RA patients when compared with age- and gender-matched controls. Regression analyses demonstrated that a higher body mass index (BMI), the presence of metabolic syndrome (MetS), higher levels of total cholesterol, the presence of radiographic damage, and higher serum levels of C-reactive protein (CRP) were significantly associated with an increased likelihood of presenting IFG. In this cross-sectional study, we observed an increased prevalence of T2D and IFG in an Italian cohort of RA patients when compared with age- and gender-matched control individuals. Interestingly, both RA-specific features, such as disease duration, CCS exposure, and radiographic damage, and traditional CV risk factors, such as HBP and MetS, were significantly associated with glucose metabolism abnormalities.

Since the introduction of biologics, many concerns about the increased risk of infections have been reported and, to date, the real impact of infections on the daily practice in the rheumatologic centers is still largely unknown. In this work, we evaluated the infection rates associated with the use of biologics in a large cohort of patients. A prospective study, between January 2010 and December 2013, enrolling 731 rheumatic patients, was performed. Demographic and disease characteristics, therapies, comorbidities, and infectious events were recorded and statistically analyzed by multivariate analysis. Two-hundred thirty-five infectious episodes were observed in 28.4 % of patients. About total infections, bacteria were identified in 70.6 % of total cases and viruses in 18.3 %. The most common site of not-serious infection was the urinary tract. Duration of disease, longer follow-up, concomitant steroid therapy, and comorbidities were significantly associated with not-serious infection. In our cohort, 17 episodes fulfilled the criteria of serious infection and occurred in 17 different patients (2.3 %), the majority involving the lower respiratory tract. Serious infections were associated with the beginning of biologics in older age. Our prospective, observational study showed that, in daily practice, a lesser rate of serious as well as not-serious infections may be observed in rheumatic patients treated with biologics than those reported in previous papers. The most common sites of not-serious infections are both the urinary and the respiratory tracts, and for serious infections, the respiratory tract. When pathogens were isolated, we did not find any multidrug-resistant organism.

Background Ring chromosome 14 syndrome is a rare chromosomal disorder characterized by early onset refractory epilepsy, intellectual disability, autism spectrum disorder and a number of diverse health issues. Results The aim of this work is to provide recommendations for the diagnosis and management of persons affected by ring chromosome 14 syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years subjects affected by ring chromosome 14 syndrome. The literature search was performed in 2016. Original papers, meta-analyses, reviews, books and guidelines were reviewed and final recommendations were reached by consensus. Conclusion Conventional cytogenetics is the primary tool to identify a ring chromosome. Children with a terminal deletion of chromosome 14q ascertained by molecular karyotyping (CGH/SNP array) should be tested secondarily by conventional cytogenetics for the presence of a ring chromosome. Early diagnosis should be pursued in order to provide medical and social assistance by a multidisciplinary team. Clinical investigations, including neurophysiology for epilepsy, should be performed at the diagnosis and within the follow-up. Following the diagnosis, patients and relatives/caregivers should receive regular care for health and social issues. Epilepsy should be treated from the onset with anticonvulsive therapy. Likewise, feeding difficulties should be treated according to need. Nutritional assessment is recommended for all patients and nutritional support for malnourishment can include gastrostomy feeding in selected cases. Presence of autistic traits should be carefully evaluated. Many patients with ring chromosome 14 syndrome are nonverbal and thus maintaining their ability to communicate is always essential; every effort should be made to preserve their autonomy.

BACKGROUND - Fino al 36% dei bambini colpiti da malattia infiammatoria cronica intestinale (MICI) presentano sintomi non intestinali, che nel 7-25% dei casi consistono in un coinvolgimento articolare. OBIETTIVO - Lo scopo del presente studio è descrivere i sintomi del coinvolgimento articolare in bambini con MICI. MATERIALI E METODOLOGIA - Sono stati analizzati i dati clinici di pazienti con MICI seguiti dall'IRCCS “Burlo Garofolo” (Trieste, Italy) tra il 1987 e il 2015. Sono stati esaminati il tipo di MICI, la localizzazione e l'evoluzione del disturbo, in accordo con la classificazione di Parigi, la presenza di coinvolgimento articolare ed i suoi sintomi, in accordo con la classificazione del Gruppo di Studio Europeo per le Spondiloartropatie, ed i trattamenti. Sono stati messi a confronto i casi clinici di bambini con e senza coinvolgimento articolare. RISULTATI - 13 dei 240 pazienti colpiti da MICI (5%) presentavano un coinvolgimento articolare: 11 dei 13 pazienti con sintomi articolari presentavano il morbo di Crohn (MC); 2 avevano una colite ulcerosa e 9 pazienti avevano un'artrite periferica con andamento polifasico legato all'infiammazione intestinale. Il coinvolgimento articolare era contemporaneo all'esordio dell'infiammazione intestinale in 5 casi (38%), precedente in 4 casi (31%) e successivo in 4 casi (31%). Dai controlli fatti risulta che i pazienti con MC e artrite presentavano più spesso complicazioni - nel MC un fenotipo stenosante, fistolizzante e infiammatorio - 2 casi su 11 (18%) a fronte di 3 casi su 111 (3%) - e usavano più spesso farmaci immunosoppressivi e metotressato - 4 casi su 13 (30%) a fronte di 26 controlli su 227 (11%) - e infliximab - 12 casi su 13 (92%) a fronte di 82 controlli su 227 (36%). CONCLUSIONI - Nel presente studio il 5% dei bambini avevano un'artrite relativa alle articolazioni periferiche associata alla MICI, contemporanea alla malattia intestinale e degenerata in una malattia polifasica. L'artrite era molto più frequente in bambini con MC ed in questi casi la malattia intestinale aveva un fenotipo più complesso che richiedeva un uso più frequente di farmaci immunosoppressivi e biologici.