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Objective The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed the most consistent literature to indicate the best strategy for the second-line biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Methods Systematic review of the literature to identify English-language articles on efficacy of second-line biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted from available randomized, controlled trials, national biologic registries, national healthcare databases, post-marketing surveys, and open-label observational studies. Results Some previously stated variables, including the patients׳ preference, the indication for anti-tumor necrosis factor (TNF) monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. In RA, golimumab as second-line biologic has the highest level of evidence in anti-TNF failure. The switching strategy is preferable for responder patients who experience an adverse event, whereas serious or class-specific side effects should be managed by the choice of a differently targeted drug. Secondary inadequate response to etanercept (ETN) should be treated with a biologic agent other than anti-TNF. After two or more anti-TNF failures, the swapping to a different mode of action is recommended. Among non-anti-TNF targeted biologics, to date rituximab (RTX) and tocilizumab (TCZ) have the strongest evidence of efficacy in the treatment of anti-TNF failures. In PsA and AS patients failing the first anti-TNF, the switch strategy to a second is advisable, taking in account the evidence of adalimumab efficacy in patients with uveitis. The severity of psoriasis, of articular involvement, and the predominance of enthesitis and/or dactylitis may drive the choice toward ustekinumab or secukinumab in PsA, and the latter in AS. Conclusion Taking in account the paucity of controlled trials, second-line biologic therapy may be reasonably optimized in patients with RA, SpA, and PsA.

Objective To propose appropriate statements that drive the choice of biologic therapies in patients with rheumatoid arthritis (RA), factoring in their impact on the following issues: anti-drug antibody (ADAb) formation, suspicion and management of infections, lupus-like syndrome (LLS), effects on bone mass and sexual sphere, and relationship between RA and periodontal disease (PD). Methods An overview of existing evidence was undertaken by an expert panel on behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO). Data were extracted from controlled trials, national registries, national health care databases, post-marketing surveys, and, when required by the paucity of controlled studies, from open-label clinical series. Anti-tumor necrosis factor (anti-TNF) and non-anti-TNF-targeted biologics approved for RA were investigated. Results ADAb formation is chiefly associated with anti-TNFs, and it is reduced by combination therapy with methotrexate. To date, ADAb titration is not advisable for clinical practice, and, in case of anti-TNF secondary failure, a non-anti-TNF biologic is indicated. LLS is observed in anti-TNF receivers and, in most cases, resolves without anti-TNF withdrawal. A non-anti-TNF biologic is advisable in patients experiencing LLS. Non-anti-TNFs demonstrated a low or absent infection risk and are preferable in patients with comorbidities. Due to their positive effects on bone mass, anti-TNFs are indicated in women at osteoporosis risk, whereas non-anti-TNF have been poorly investigated. The emerging evidence of the relationship between RA and PD and the effects on anti-TNF efficacy should lead clinicians to consider the periodontal status in RA patients. Anti-TNFs may exert a positive effect on fertility and sexuality, and clinicians should explore these aspects in RA patients. Conclusion The optimization of biologic therapies by taking into proper account the above issues would improve patient outcomes.

Objective.To evaluate the frequency of dactylitis, enthesitis, and anterior uveitis (AU) in spondyloarthritis (SpA) associated with inflammatory bowel disease (IBD-SpA) compared with other SpA, and to assess the role of associated psoriasis in the occurrence of dactylitis and enthesitis.Methods.In a 12-month case-control study, the frequency of dactylitis and enthesitis in 29 patients with ulcerative colitis (UC) and 59 with Crohn disease (CD) who satisfied the Spondyloarthritis international Society criteria for axial or peripheral SpA was compared with 176 controls, including 97 (55.1%) with psoriatic arthritis (PsA), 47 (26.7%) with ankylosing spondylitis (AS), and 32 (18.2%) with nonradiographic axial SpA (nr-axSpA). The occurrence of these features in IBD-SpA with and without psoriasis was also evaluated.Results.Axial, peripheral, or mixed involvement was observed in 46 (52%), 29 (33%), and 13 (15%) patients, respectively; and 14/88 (16%) had psoriasis. Dactylitis was recorded in 4/88 patients (4.5%) with IBD-SpA and in 30 controls (17.4%; p = 0.008), enthesitis in 16 cases (18.1%) and in 78/176 controls (44.3%; p < 0.001), and AU in 3 patients (3.4%) with IBD-SpA and in 26 controls (14.7%; p = 0.01). No significant differences were found between patients with UC-SpA and those with CD-SpA. Dactylitis and enthesitis were significantly more common in patients with IBD-SpA who also had psoriasis compared to those without skin disease (p = 0.009 and 0.003, respectively).Conclusion.Dactylitis, enthesitis, and AU are significantly less frequent in IBD-SpA compared with other types of SpA. Given the frequent association of psoriasis and IBD, overlooking coexistent skin disease may lead to overestimating the frequency of these features.

Autoimmune anterior uveitis (AU) accounts for at least half of the cases of noninfectious uveitis, and similarly to spondyloarthritis (SpA), its occurrence is related to HLA-B27 positivity. AU is significantly more frequently found in HLA-B27-positive subjects with SpA and is characterized by unilateral eye involvement, marked tendency to recur with involvement of both eyes in alternate fashion, and has good prognosis in the majority of cases. The estimated frequency of SpA in patients with AU is around 50%, whereas AU in SpA has been reported in at least 30% of cases. Across the SpA disease spectrum, AU has a frequency peak of 33.4% in patients with ankylosing spondylitis, while the estimated prevalence in psoriatic arthritis (PsA) and inflammatory bowel disease-associated SpA is 2%-25%, and 25%, respectively. In early PsA, the frequency of AU has been found in 9% of patients. The wide range of prevalence reported in PsA may be explained by the variable sets of classification criteria used for patient selection and the different length of followup. AU may precede the clinical features of SpA, may be present at diagnosis, or may complicate the SpA clinical course. However, the occurrence of AU in SpA as well as AU flares has been reduced through treatment of SpA with anti-tumor necrosis factor-α agents.

Modern US equipment allows rheumatologists to directly visualize vascular, musculoskeletal, dermal and internal organ structure. In multisystemic and challenging diseases such as vasculitides and scleroderma, where new outcome measures are required in both clinical practice and trials, US measures promise reproducible and objective scores of disease activity and extension. US reveals early pathognonomic abnormalities and may help start early treatment.

Objective The occurrence of iridocyclitis (IC) in early psoriatic arthritis (PsA) has been rarely assessed. The primary end-point of this study was to evaluate the frequency of IC at onset in patients with early PsA. Methods We evaluated the frequency of IC in a clinical series of consecutive, new outpatients with early PsA observed between January 2000 and December 2009. All patients met the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA and had a disease duration ≤12 months. The following clinical patterns were considered: peripheral PsA (oligoarthritis ≤4 and polyarthritis ≥5 involved joints), axial PsA and mixed. IC diagnosis was made by the ophthalmologist. Follow-up visits were scheduled at baseline and every 4 months with interval shortening in the case of urgent clinical problems. Results Two hundred and forty-two patients, 137 (57%) women and 105 (43%) men (mean age 50.33 ± 11.7 years; mean symptom duration 9.38 ± 3.1 months) were studied. One hundred and thirty-two (51%) patients had peripheral PsA, 41 (17%) axial and 69 (28%) mixed. Twenty-six episodes of IC were recorded at diagnosis in 22 (9%) patients, 17 (77.3%) female and five (22.7%) male; 11 (50%) patients had peripheral PsA, two (9.1%) axial, and nine (40.9%) mixed; 5/22 (22.7%) patients were B27-positive. IC recurred in 2/22 (9%) patients over the follow-up period. Mean follow-up duration was 51 ± 23.2 months. Dactylitis was significantly more frequent in patients with IC compared to those without this feature (P = 0.032). Conclusion IC occurred in 9% of 242 patients with early PsA with no association with the clinical pattern and B27 positivity. This frequency is higher than previously reported.

Fabrizio Cantini1, Laura Niccoli1, Carlotta Nannini1, Olga Kaloudi1, Emanuele Cassarà1, Massimo Susini2, Ivo Lenzetti21Second Division of Internal Medicine, Rheumatology Unit, 2Division of Ophthalmology, Prato Hospital, Prato, ItalyPurpose: To evaluate the long-term efficacy of infliximab in patients with refractory Behçet’s disease (BD)-associated and idiopathic posterior uveitis (PU).Methods: Single center, prospective, 6-year duration, follow-up study on 50 consecutive patients (20 [40%] males and 30 [60%] females with a mean age of 37.5 ± 12.3 years) with refractory BD-associated PU (36 patients) and idiopathic PU (14 patients) who had failed at least one immunosuppressive drug. At baseline, patients received prednisone 1 mg/kg/day with rapid tapering and infliximab infusions (5 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. Nonresponders after the third infusion withdrew from the study. Primary outcome measures were visual acuity (VA) value improvement compared to baseline. Secondary outcome measures were proportion of patients with VA improvement from baseline; proportion of patients achieving disease remission; number of PU flare-ups; and incidence of adverse events.Results: At the final follow-up, mean right and left eye VA respectively increased from 0.57 ± 0.31 at baseline to 0.68 ± 0.33 (P = 0.048) and from 0.67 ± 0.28 to 0.76 ± 0.27 (P = 0.047). None of the patients had VA worsening and new onset ocular complications. A complete response of PU was recorded in 34/50 (68%) patients and partial response in 11/50 (22%). Five patients were nonresponders and withdrew from the study after the third infusion. A significant reduction of ocular attacks and of the proportion of patients with cystoid macular edema was observed. No differences in infliximab efficacy was recorded between patients with BD-associated and idiopathic PU. No serious adverse events occurred. The mean follow-up duration was 36.8 months.Conclusion: Long-term infliximab therapy was equally effective and safe with a significant VA gain in refractory BD-associated and idiopathic PU.Keywords: Behçet’s disease, idiopathic posterior uveitis, infliximab, posterior uveitis, visual acuity

Objective: Primary: to evaluate the frequency of anemia of inflammation (AOI) in a clinical series of patients with ankylosing spondylitis (AS) requiring anti-TNF (tumor necrosis factor) agents. Secondary: to examine anti-TNF therapy-induced changes in AOI. Method: Prospective, follow-up, 6-month study of all consecutive, new patients with AS requiring anti-TNFα drugs observed between January 2004 and December 2008. AOI was defined according to WHO criteria. Primary outcome measure: the proportion of patients showing AOI at baseline. Secondary outcome measures: the proportion of patients achieving resolution of AOI at the 6-month visit; the proportion of patients achieving any improvement in haemoglobin (Hb); the proportion of patients with any improvement in blood results. Results: One hundred and six patients (42 women and 64 men; mean age: 46 years) with AS were evaluated. Sixteen of these (15%) presented with AOI at baseline. After 6 months therapy 13 patients (81%) resolved AOI while two presented an Hb level reduction. After 6 months therapy we did not find a significant statistical improvement in red blood cell numbers (P = 0.85) and transferrin (P = 0.08) levels. Hb, mean corpuscular volume (MCV), iron, ferritin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved reaching statistical significance (P = 0.0002, 0.0001, 0.001, 0.014; 0.007, 0.004, respectively). Conclusion: We found 15% frequency of AOI among a selected series of patients with AS. After 6 months of anti-TNFα therapy AOI resolved in the majority of patients with significant improvement of Hb, MCV, CRP and ESR levels.

Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology occurring in patients with psoriasis. The Classification Criteria for Psoriatic Arthritis study group has recently developed a validated set of classification criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of 98.7%. Three main clinical patterns have been identified: oligoarticular (≤ 4 involved joints) or polyarticular (≥ 5 involved joints) peripheral disease and axial disease with or without associated peripheral arthritis. In this context distal interphalangeal arthritis and arthritis mutilans may occur. According to other reports, also in our centre, asymmetric oligoarthritis is the most frequent pattern at onset. Axial disease has been estimated between 5% and 36% of patients. It is characterized by an irregular involvement of the axial skeleton with a predilection for the cervical spine. Recurrent episodes of enthesitis and dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases distal extremity swelling with pitting edema of the hands or feet is observed. Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the most frequent extra-articular manifestation, and accelerated atherosclerosis is the prominent comorbidity. The clinical course of peripheral and axial psoriatic arthritis is usually less severe than rheumatoid arthritis and ankylosing spondylitis, respectively. Local corticosteroid injections and non-steroidal anti-inflammatory drugs are recommended in milder forms. Sulphasalazine and methotrexate are effective in peripheral psoriatic arthritis. Recent studies have provided evidence on the efficacy of anti-tumor necrosis factor-α drugs to control symptoms and to slow or arrest radiological disease progression.

Juvenile idiopathic arthritis (JIA) may cause damage to the temporomandibular joint (TMJ). In oligoarticular forms of JIA, TMJ involvement is often asymptomatic and consequently overlooked. The aim of this study was to evaluate the presence of TMJ joint effusion (JE) by ultrasonography (US) in patients with early arthritis.We examined 68 children (57 girls, 11 boys, age range 9.1-16.0 years, mean age 11.0 years) recently diagnosed with JIA. None had received any specific treatment for inflammation. Symptomatic TMJ involvement was diagnosed when one or more of the following were present: 1) recurrent pain (spontaneous or on movement of the jaw); 2) crepitation; 3) feeling of stiffness or fatigue of the jaw; 4) intermittent locking. US of the TMJ was performed in static and dynamic phases with a General Electric LOGIQ7 scanner and a linear transducer (8.5 MHz) positioned along the axis of the mandibular ramus. JE was diagnosed when the joint capsule was ≥1.5 mm thick.Forty-six out (68%) of 68 children had US evidence of TMJ effusions (bilateral in 16 [35%] cases), but only 2/46 were symptomatic.These data suggest that children with early stage oligoarticular JIA children are likely to have inflammation of the TMJs even in the absence of symptoms. US is a simple-to-use, noninvasive, radiation-free tool that can provide useful information in the assessment and follow-up of TMJ involvement in children and young adults with JIA.Sommario INTRODUZIONE: L'artrite Idiopatica giovanile (AIG) determina alterazioni a carico della testa condilare dell'articolazione temporomandibolare (ATM). Nell'esordio oligo-articolare (OA) l'interessamento dell'ATM viene spesso trascurato perchè può essere asintomatico. Lo scopo di questo studio è quello di valutare la presenza di versamento intrarticolare (V) dell'ATM, mediante esame ecografico (US), nelle fasi precoci di malattia. MATERIALE E METODI: Sono stati studiati 68 bambini (57 bambine e 11 bambini, di età compresa tra 9,1 e 16, anni, età media: 11,02 ± 4,2 mesi) con AIG ad esordio OA. I pazienti (pz) erano sintomatici quando uno dei quattro sintomi seguenti era presente: 1) dolore ricorrente (a riposo o durante il movimento di apertura della bocca); 2) presenza di scrosci articolari; 3) presenza di limitazione nell'apertura della bocca; 4) locking intermittente. US è stato eseguito su entrambe le ATM sia in fase statica che dinamica, mediante ecografo General Electric (LOGIQ7) con sonda lineare (8,5 MHz) posizionata lungo l'asse maggiore del ramo condilare. Il V era presente quando lo spessore della capsula articolare era ≥1,5 mm. RISULTATI: 46/68 (68%) hanno presentato V a carico delle ATM; in 16 (35%) il V era bilaterale. 2/46 con V erano sintomatici, mentre in 44 non erano presenti sintomi. CONCLUSIONI: Questi dati suggeriscono che un'alta percentuale di bambini e giovani adulti con AIG ad esordio OA, nella fase iniziale della malattia, presenta un interessamento flogistico delle ATM anche in assenza di sintomi. L'US, non invasivo e facilmente ripetibile, ci offre importanti informazioni sul coinvolgimento articolare delle ATM ed è risultato utile nella diagnosi all'esordio.

Objective A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the first-line tailored biologic therapy in patient with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Methods Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictor biomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs. Results Some variables, including the patients’ preference, the indication for anti-TNF monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. Further, evidence of a better cost-effectiveness profile for etanercept (ETN) and biosimilar infliximab (IFX) in RA was found. Any biologic may be employed in absence of choice driving factors in RA. Otherwise, a high infection risk or LTBI positivity drive the choice toward abatacept (ABA), tocilizumab (TCZ), or ETN. TCZ should be the first choice if monotherapy is required. High rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) titers should drive the choice toward TCZ or ABA, while in patients at high CVD risk anti-TNF choice, with preference for ETN, seems appropriate. Presence of anterior uveitis or inflammatory bowel disease drives the choice to monoclonal antibody anti-TNFs (MoAb anti-TNFs). In PsA, ustekinumab (UTK), and to a lesser extent ETN, represents the first choice in patients at high infection and TB risk. Anti-TNFs or UTK choice is guided by skin or articular disease severity, enthesitis, and dactylitis, whereas ETN should be preferred if metabolic syndrome or high CV risk complicate PsA. Conclusion Taking in account of multiple choice driving variables, first-line biologic therapy may be optimized in patients with RA, SpA, and PsA.

Lung involvement frequently complicates systemic sclerosis (SSc), provoking loss of quality of life and a poor expectation of survival. For this reason an early diagnosis of lung involvement is warranted: high-resolution computed tomography (HRCT), pulmonary function tests (PFT), lung scintigraphy with DTPA and bronchoalveolar lavage (BAL) are mandatory to define and follow-up pulmonary interstitium. Coughing and a sensation of breathlessness on exertion are the earliest symptoms of lung involvement. Lung involvement may be investigated with PFTs, which are non-invasive and require breathing into a tube via a mouthpiece. Forced vital capacity, which measures the total amount of air capable of being blown forcefully, and the diffusion capacity for carbon monoxide, a measure of how well oxygen diffuses into blood, are the most important functional measures. A routine chest X-ray may demonstrate fibrosis, but it is not very sensitive for detecting early or mild disease. For this reason, a HRCT scan is required. This non-invasive investigation provides images of multiple slices through the lung, from top (apex) to bottom (base), and can even detect lung involvement in early phases when no symptoms are present. (99m)T-DTPA is recommended in those patients with isolated diffusion deficits on lung function tests and in addition to HRCT in confirming the suspicion of vascular disease rather than early fibrosing alveolitis. Bronchoscopy with BAL is an invasive test that also may provide information about the inflammatory status of the affected areas of the lung detected during HRCT. In order to detect alveolitis, it should be performed as early as possible, to start prompt immunosuppressive treatment.

Background Asbestosis is characterized by lung and pleural fibrosis and by immune system dysregulation, with autoantibody production and systemic immune-mediated disease. No specific therapies are available for asbestosis. Recently, the pivotal pathogenic role exerted by interleukin-1beta has been recently reported. Case presentation We treated with anti-interleukin 1 beta targeted antibody canakinumab a 67 year old man with asbestosis and long lasting systemic autoimmune features. A dramatic improvement in clinical manifestations was observed at 1 week after the first injection, with complete clinical remission at 4 months. Conclusion This case suggests new perspectives for the treatment of asbestosis and its systemic features.

Juvenile Localized Scleroderma (JLS) causes functional disabilities and cosmetic deformities. Evaluation and follow-up of lesions are mandatory to understand the disease evolution. The objective of this study is to evaluate the usefulness of skin ultrasonography (US) in monitoring the response to treatment in JLS.Ten patients (age: 101,7 ± 66,2 months; 7 M, 3 F) affected by juvenile onset LS underwent sequential US exams (at baseline and after 6 months). Skin thickness was measured by using high-frequency US (18 MHz). All patients were evaluated both clinically (modified Rodnan Skin Score, mRSS) and by US (dermal thickness) at baseline and at 6 months. At baseline, 6/10 patients received 3 pulses of corticosteroids (solumedrol 30 mg/kg/day for 3 consecutive days, then oral steroids (1mg/kg), and methotrexate s.c. (15 mg/mq/week). After 6 months, 1/6 was switched to mycophenolate mofetil (25 mg/kg/day) due to inefficacy of MTX; 4/10 did not receive any further therapy.US showed a thicker dermis and a thinned hypodermis in the lesional skin areas in respect to the healthy ones (p0.05). After treatment, in seven patients a clinical improvement (decrease of mRSS) was found. In six of these patients, US showed a decrease of dermal thickness showing a correlation with clinical data. Three patients who did not receive drugs showed unmodified images and clinical findings.US can help the assessment of skin and hypodermis in JLS and can detect an improvement of the lesions.

Background Musculoskeletal involvement, preferentially affecting hands and feet, represents a frequent feature and may lead to disability in patients with systemic sclerosis (SSc). The most common manifestations are arthralgia, stiffness, synovitis, and tenosynovitis. In a large multicentre study, synovitis, tendon friction rubs, and joint contractures were found in 16%, 11%, and 31% of 7286 SSc patients assessed by clinical examination 1 . However, several ultrasound (US) studies revealed a higher frequency of hand joint involvement 2 . Objectives To investigate the frequency and severity of hand joint involvement in a cohort of SSc patients evaluated by US, and to compare the results of US synovitis detection with those of physical examination. Methods Over a 6-month period, all consecutive (new and old diagnosis) SSc patients (ACR/EULAR 2013 criteria) currently followed in our center underwent clinical and US hand examination. One rheumatologist expert in musculoskeletal US performed all examinations by using Esaote Technos MPX, MyLab 40, employing high frequency (12–18 MHz) transducers. Power Doppler (PD) parameters were adjusted (range of pulse repetition frequency 400–800 Hz; frequency 7–11.1 MHz). Patients were scheduled to be examined at the same hour of the day in the same room with an ambient temperature of 21°C. Hand and wrist joints were evaluated for synovitis, tenosynovitis, calcinosis, acro-osteolysis and distal vascularization. An independent rheumatologist made the clinical examination and US examiner was blind to clinical findings. US assessment of synovitis was scored according to the OMERACT–EULAR PD composite semiquantitative scale (0–3). Results 89 patients, 79F/10M, mean age 61.11±15.1, median disease duration 160 months (min: 2,max: 492), 83 (93%) with limited SSc and 6 (7%) with diffuse SSc were recruited. Synovitis was detected in 15 (16.8%) and in 35 (40.2%) of the cases by clinical examination and US, respectively (p=0.019). PD revealed grade 1 synovitis in 19/35 (54.3%) patients, grade 2 in 14 (40%) and grade 3 in 2 (5.7%). Tenosynovitis, calcinosis and acro-osteolysis were found at US 19 (21.3%), 14 (15.7%), acro-osteolysis in 11 (12.3%) and 8 (9%), respectively. Distal vascularization was detected in 60 patients (67%). Conclusions Confirming previous studies, our results show that hand synovitis in SSc may be underestimated by clinical examination only, while US examination provides an accurate assessment of the frequency and the degree of severity of synovial inflammation. However, synovitis in our cohort of SSc patients resulted mild in the majority of the cases. References Avouac J, et al. J Rheumatol. 2010;37:1488–501.2.Cuomo G, et al. Rheumatology (Oxford) 2009;48:1414–1417. Acknowledgement None Disclosure of Interest None declared

Background Dactylitis, is observed in approximate 30% of patients spodnyloarthritis (SpA),with the highest frequency in psoriatic arthritis (PsA).SpA features complicate inflammatory bowel diseases (IBD) in at least one third of the cases.The frequency of dactylitis in IBD-SpA has been assessed in a few open studies with conflicting results1,2. Objectives Primary end point: To compare the frequency of dactylitis in a clinical series of patients with IBD-associated SpA (IBD-SpA) compared with other types of SpA. Secondary end point: to evaluate the frequency of articular and extra-articular manifestations of IBD-associated SpA compared to controls. Methods 24-month case-control study. Case patients: all consecutive patients meeting the ASAS criteria for both axial and peripheral SpA,and with a diagnosis of Crohn9s disease (CD) or ulcerative colitis (UC) certified by the gastroenterologist. Controls: the 2 consecutive patients with other SpA (ASAS criteria) observed after the case patient during the same time interval. Dactylitis diagnosis was accepted if observed at visit or if certified in the past by a rheumatologist working in our center.Patients were followed by the same rheumatologist,and follow-up visits were scheduled at baseline and every 4 months.All clinical and laboratory data were recorded in a computed patients9chart. The date of the last visit constituted the end of the follow-up. Results Case patients:88 IBD-SpA patients, 29 UC and 59 CD, 42 F/46M, mean age 47.66±15.09 ys, 10 (11.3%) B27+.Mean IBD duration was 60.05±54.66 months. Controls: 176 SpA patients, 98 PsA, 46 AS, and 32 non-radiographic axial SpA (nrx-AxSpA); 89F/87M, mean age 46.35±24.88 ys. 70 (40.7%) B27+, mean disease duration of 43.21±28.34 months. In IBD-SpA axial involvement was observed in 46 (52%) patients, peripheral in 29 (33%) and mixed in 13 (15%). Peripheral SpA was oligoarticular (≤4 joints involvement) in 26/29 (90%) patients and polyarticular in 3 (10%). Psoriasis (Pso) was associated in 14/88 (16%) of the cases. Dactylitis was recorded in 4 (4.5%) of IBD-SpA patients and in 30 (17.4%) of controls with a significant statistical difference (p=0.018). Dactylitis was recorded in only 2/74 (2.7%) IBD-SpA patients without Pso (p vs controls=0.010).Also enthesitis prevalence was significantly lower in IBD-SpA occurring in 16/88 (18.1%) patients and in 78/176 (44.3%) controls (p=0.004). Enthesitis frequency was significantly higher in 14 IBD-SpA patients associating Pso (28.5%) compared with the remaining 74 cases (16.2%) (p=0.012). Dactylitis occurred in 2/29 (6.9%) and in 2/59 (3.38%) patients with UC and CD, respectively. Anterior uveitis was recorded in 3 (3.4%) IBD-SpA patients and in 26 (14.7%) controls (p=0.02). Conclusions Dactylitis and enthesitis were significantly lower in IBD-SpA patients compared to other SpA. As reported3, Pso was frequent in our cohort of IBD-SpA,and its coexistency significantly increased the frequency of enthesitis and to a lesser extent of dactylitis.Anterior uveitis was significantly less frequent in IBD-SpA compared to controls. References Salvarani C, et al. Scand J Rheumatol 2001; Alamino RP, et al. J Rheumatol.2011; Li W-Q, et al. Ann Rheum Dis 2013. Disclosure of Interest None declared

Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital of Prato, Prato,ItalyPurpose: The primary purpose of this study was to evaluate the proportion of psoriatic arthritis (PsA) patients maintaining clinical remission after adalimumab (ADA) dose reduction compared with patients with rheumatoid arthritis. Secondary purposes include evaluating the proportion of PsA patients who achieve remission, the duration of remission after ADA dose reduction, time to relapse, psoriasis course, and the frequency of adverse events at the end of follow-up.Methods: This was a single-center, prospective, follow-up, case-control study of 76 consecutive patients (35 females, 41 males; mean age 46 ± 10.2 years) who met the classification criteria for psoriatic arthritis and required anti-tumor necrosis factor therapy according to Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recommendations. The 76 patients were compared with 55 patients (40 females, 15 males; mean age 50 ± 11.6 years) who satisfied the American College of Rheumatology criteria for rheumatoid arthritis and received the same treatment. Case patients and controls were recruited from January 2008 to December 2010. At baseline, PsA patients and controls received 40 mg of ADA every other week, usually with methotrexate (10 to 20 mg/weekly). In the presence of clinical remission, ADA dose was reduced to 40 mg every 4 weeks in both groups.Results: Fifty-three of the 76 (69.7%) PsA patients and 17 of the 55 (30.9%) rheumatoid arthritis (P < 0.019) controls achieved remission after a mean time of 5.1 ± 1.2 and 6.3 ± 1.6 months, respectively (P = nonsignificant). After halving the dose of ADA, 47 of the 53 (88.6%) PsA patients and three of the 17 (17.6%) controls maintained remission (P = 0.016) over a mean follow-up period of 28.9 ± 8.4 and 24.2 ± 6.4 months, respectively. No significant changes in Psoriatic Arthritis Severity Index scores were observed. The mean time to relapse was 8.3 ± 3.4 months in six case patients and 7.2 ± 4.2 in 14 controls (P = not significant). No serious adverse events occurred in either group.Conclusion: Clinical remission is possible in a high percentage of patients with early PsA receiving ADA. Such remission is maintained in a high proportion of subjects after ADA dose halving, with relevant advantages in terms of patient compliance, drug-exposure risk, and economic burden.Keywords: psoriatic arthritis, anti-TNF, adalimumab, remission, dose reduction

Tumor necrosis factor-α (TNF-α) plays a central role in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Recently, 2 expert committees provided evidence-based recommendations for the treatment of PsA. Anti-TNF-α drugs are indicated in all forms of PsA resistant to traditional therapeutic approaches. Anti-TNF-α infliximab (IFX) is an immunoglobulin G-1 antibody that binds to soluble and cell membrane-bound TNF-α with its inactivation. Confirming previous open-label studies, 2 randomized, placebo-controlled clinical trials, IMPACT and IMPACT2, have provided evidence of the efficacy and safety of IFX in the treatment of PsA as evaluated by American College of Rheumatology (ACR)20, ACR50, and ACR70 response rates. At Week 16, a significant proportion of 51 IFX-treated patients achieved ACR20, ACR50, and ACR70 responses compared to the 51 patients of the placebo arm in the IMPACT trial. In the IMPACT2 study, 58% of the IFX-treated patients and 11% of placebo patients achieved an ACR20 response (p < 0.001), and 41% and 27% of patients in the IFX group were ACR50 and ACR70 responders, compared with 4% and 2% of placebo patients, respectively. Of note, a significant inhibition of radiographic disease progression was observed in the IFX-treated group. In both trials, psoriasis improvement was recorded in more than 80% of patients receiving IFX, with a significant difference compared to placebo group. IFX was well tolerated, with no difference compared to placebo in terms of adverse events. The extension phase of these studies showed the sustained efficacy and safety of the drug.

Primary: to evaluate the frequency of anemia of inflammation (AOI) in a clinical series of patients with ankylosing spondylitis (AS) requiring anti-TNF (tumor necrosis factor) agents. Secondary: to examine anti-TNF therapy-induced changes in AOI.Prospective, follow-up, 6-month study of all consecutive, new patients with AS requiring anti-TNFα drugs observed between January 2004 and December 2008. AOI was defined according to WHO criteria.the proportion of patients showing AOI at baseline.the proportion of patients achieving resolution of AOI at the 6-month visit; the proportion of patients achieving any improvement in haemoglobin (Hb); the proportion of patients with any improvement in blood results.One hundred and six patients (42 women and 64 men; mean age: 46 years) with AS were evaluated. Sixteen of these (15%) presented with AOI at baseline. After 6 months therapy 13 patients (81%) resolved AOI while two presented an Hb level reduction. After 6 months therapy we did not find a significant statistical improvement in red blood cell numbers (P = 0.85) and transferrin (P = 0.08) levels. Hb, mean corpuscular volume (MCV), iron, ferritin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved reaching statistical significance (P = 0.0002, 0.0001, 0.001, 0.014; 0.007, 0.004, respectively).We found 15% frequency of AOI among a selected series of patients with AS. After 6 months of anti-TNFα therapy AOI resolved in the majority of patients with significant improvement of Hb, MCV, CRP and ESR levels.

Objective.Cardiac involvement means a poor prognosis in systemic sclerosis (SSc). Conduction defects and arrhythmias are frequent in patients with SSc, and may result in sudden cardiac death. We tested whether electrophysiologic studies and implantation of cardioverter defibrillators are recommended when ventricular arrhythmias are present.Method.A cardioverter defibrillator was implanted in 10 patients with SSc who had heart involvement.Result.After 36 months, analysis of the device showed several episodes of ventricular tachycardia in 3 patients, which were promptly reverted by electrical shock delivery.Conclusion.In patients with SSc who are affected by ventricular arrhythmias, the implantation of a cardioverter defibrillator may prevent sudden cardiac death.

Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology occurring in patients with psoriasis. The Classification Criteria for Psoriatic Arthritis study group has recently developed a validated set of classification criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of 98.7%. Three main clinical patterns have been identified: oligoarticular (≤ 4 involved joints) or polyarticular (≥ 5 involved joints) peripheral disease and axial disease with or without associated peripheral arthritis. In this context distal interphalangeal arthritis and arthritis mutilans may occur. According to other reports, also in our centre, asymmetric oligoarthritis is the most frequent pattern at onset. Axial disease has been estimated between 5% and 36% of patients. It is characterized by an irregular involvement of the axial skeleton with a predilection for the cervical spine. Recurrent episodes of enthesitis and dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases distal extremity swelling with pitting edema of the hands or feet is observed. Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the most frequent extra-articular manifestation, and accelerated atherosclerosis is the prominent comorbidity. The clinical course of peripheral and axial psoriatic arthritis is usually less severe than rheumatoid arthritis and ankylosing spondylitis, respectively. Local corticosteroid injections and non-steroidal anti-inflammatory drugs are recommended in milder forms. Sulphasalazine and methotrexate are effective in peripheral psoriatic arthritis. Recent studies have provided evidence on the efficacy of anti-tumor necrosis factor-α drugs to control symptoms and to slow or arrest radiological disease progression.

Objective.To assess skin elasticity in systemic sclerosis (SSc) by using a new imaging modality, ultrasound elastography (UE).Methods.Our study included 18 consecutive patients with SSc and 15 healthy controls. Modified Rodnan skin score, physical examination, and assessment of organ involvement were performed. UE was carried out on the middle forearm and on the fingers of the dominant arm. The echo signals recorded in real time during freehand operations of probe compression and relaxation produced images representing tissue elasticity, consisting of translucent colored bands superimposed on the B-mode ultrasonographic images. The color scale varied within a large band spectrum from red, indicative of soft and highly elastic tissue, to blue, which denoted hard and barely elastic tissue.Results.On the forearm of all patients, UE showed a homogeneous blue area corresponding to the dermis visualized in a B-mode ultrasonographic image; in controls, a blue pattern was never detected and a predominance of green with sporadic areas of pale blue was observed. At sequential evaluations, UE of fingers produced inconstant and changeable colored areas.Conclusion.The imaging pattern observed in the forearm of patients with SSc may represent the reduction of strain in the dermis due to loss of elasticity. The variable pattern obtained by finger evaluation demonstrated that UE can assess skin involvement in SSc only in those areas where the dermis is known to be thicker and where the bone hyperreflection is minimal. Further studies are needed to confirm our results and determine the validity of this new imaging modality.

Objective. To evaluate in SSc, the frequency of digital lesions and the morphology, characteristics, natural course and time to healing of 1614 digital ulcers (DUs). Methods. One hundred SSc patients were followed up for 4 years. In the first step, the digital lesions were observed and classified at the time of presentation [digital pitting scar (DPS); DU; calcinosis; gangrene]. In the second step, DUs were divided into subsets according to their origin and main features. In the third step, the time to healing was recorded for each DU and the influence of DU main characteristics on time to healing was also evaluated. Results. In the first step, 1614 digital lesions were observed: DPS, 712 (44.1%) lesions; DU, 785 (48.6%); calcinosis, 110 (6.8%); and gangrene, 7 (0.8%). In the second step, DUs were subsetted as follows: DU developed on DPS (8.8%), pure DU; DU developed on calcinosis (60%); DU derived from gangrene. In the third step, the mean time to healing was 25.6 (15.6) days in DPS, 76.2 (64) days in pure DU, 93.6 (59.2) days in calcinosis ulcers and 281.1 (263.3) in gangrene. Conclusions. In SSc, digital lesions are represented by DPS, DU, calcinosis and gangrene, and provide an evidence-based DU subsetting according to their origin and main characteristics. Subsetting may be helpful for a precise DU evaluation and staging, and in randomized controlled trials for a precise identification of those DUs that are to be included in therapeutic studies. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

BackgroundCurrently, assessment of dermal thickness in systemic sclerosis (SSc) is performed by palpation and assessment using the modified Rodnan skin score (mRSS).ObjectiveTo verify whether high frequency ultrasound (US) may be a reliable and a reproducible method to measure digital dermal thickness.MethodsIn 70 patients with SSc, skin thickness was evaluated with US by 2 observers at 2 different sites on the second digit of the dominant limb to determine the interobserver variability. Patients and controls were examined twice by the first observer for intraobserver variability. Patients were divided into three subgroups according to the phase of the disease (oedematous, fibrotic or atrophic).ResultsAt both examined areas, US showed a significant dermal thickening (pConclusionsUS is a reliable tool giving reproducible results, and is able to detect digital dermal thickening in SSc.

Objectives. To investigate joint involvement in SSc and its relationship with autoantibody to the hnRNP and to anti-cyclic citrullinated peptide (anti-CCP). Methods. Sera from 55 SSc patients were investigated. Joint involvement was determined by clinical, radiological and ultrasonographical evaluation. Anti-hnRNP proteins A1 and A2 (anti-hnRNP-A1/A2) antibodies were determined by immunoblotting. Anti-CCP, ACA, anti-topo I (ATA), Sm, U1-RNP, ribosomal RNP, Ro/SSA, La/SSB autoantibody and RF were determined. Results. Six patients were positive for anti-hnRNP-A2 autoantibody and two were anti-A1 positive. Eight patients had joint erosions: seven of the eight patients positive for anti-hnRNP-A2 or A1 presented articular involvement (P < 0.04) and five of the eight erosive patients were positive for either of the two autoantibodies (P < 0.02). Of the four patients positive for anti-CCP, none had anti-hnRNP but three had erosive aspects. ATAs were found in 10 patients, six of which were also positive for anti-hnRNP (P < 0.05). RF was positive in 16 patients and in seven among those with articular involvement (P < 0.04). RF was significantly associated with anti-hnRNP in patients with erosive arthritis (P < 0.02), but not with the presence of anti-hnRNP alone. Epitope mapping of the three strongest anti-hnRNP-A2-positive sera recognized the same major epitope as patients with RA. SSc patients have higher incidence of erosions and anti-hnRNP-A2/A1 positivity. RF test and anti-hnRNP had a statistically significant diagnostic value for articular involvement. Conclusions. These parameters might suggest that autoantibody to both hnRNP antigens might become a non-specific but useful marker for joint involvement in SSc patients and identify SSc patients prone to develop joint damage.

Background: Induced sputum (IS) is a noninvasive tool, which can be used to collect cellular and soluble materials from lung airways. Objective: To evaluate if IS may be a useful and safe tool for the detection of airway inflammation in patients with interstitial lung disease (ILD) in systemic sclerosis (SSc). Methods: Sixty-eight patients with SSc and ILD as well as 18 healthy individuals (controls) were selected and submitted to IS examination. In 34 of 68 patients with SSc, bronchoalveolar lavage (BAL) was also performed. Safety of IS was assessed by comparison of forced expiratory volume in the first second (FEV1), FEV1/forced vital capacity ratio and peak expiratory flow before and after the IS procedure. Cell composition in samples collected by BAL and IS was correlated, and IS total and differential cell count in SSc patients and controls were compared. Results: The total number of cells was significantly higher in IS samples of SSc patients compared to those of healthy controls. Mean percentage of neutrophils was also higher in SSc patients (41.79 ± 23.89 vs. 27.37 ± 17.90), as well as lymphocytes (17.42 ± 19.70 vs. 3.13 ± 2.28) and eosinophils (2.35 ± 4.43 vs. 0.41 ± 0.46). On the other hand, mean percentage of macrophages was higher in healthy individuals (69.10 ± 19.15 vs. 36.96 ± 20.68). In fluid recovered by BAL, the most frequent cells were macrophages (67.89% ± 17.26), while neutrophils (14.77 ± 17.18%) and lymphocytes (15.62 ± 13.46%) were less frequent and eosinophils (1.66 ± 2.08%) were rare. A similar pattern of cell composition was found in IS samples (41.15 ± 21.67% of macrophages, 39.72 ± 23.15% of neutrophils, 15.28 ± 19.46% of lymphocytes and 2.56 ± 5.03% of eosinophils). Strength of correlation between BAL and IS was significant for macrophages and neutrophils. After IS procedure was performed, improvement of FEV1 (mean value before IS was 85.09 ± 14.44 and 88.93 ± 16.40 after IS) and FEV1/forced vital capacity (mean value before IS was 98.53 ± 12.11 and 105.22 ± 10.78 after IS) was observed. Conclusion: The IS method may allow a noninvasive assessment of cell composition in airway fluid and may contribute to the better understanding of upper/medium airway inflammation in SSc. Future studies are needed to verify whether IS can replace invasive procedures for the detection and monitoring of lung inflammation in SSc.

OBJECTIVE Advanced glycation endproducts (AGEs), including Nepsilon-(carboxymethyl)lysine-protein adducts (CML) are involved in micro/macrovascular changes and are co-localized with adhesion molecules in inflamed tissues. Serum levels of CML were investigated in systemic sclerosis (SSc) characterized by microvascular modifications and correlated with indices of micro/macrovascular damage. METHODS In 66 SSc patients (limited SSc, n = 55; diffuse SSc, n = 11) and 20 controls, CML serum levels were measured by enzyme-linked immunosorbent assay. Nailfold capillaroscopy, intima-media thickness (IMT) and the ankle-brachial index (ABI) were also recorded, to characterize micro/macrovascular involvement. RESULTS CML levels were significantly higher in SSc (79.2 +/- 39 mg/ml vs 49.6 +/- 26.1 mg/ml, mean +/- s.d.; P

Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital, Prato, ItalyBackground: The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly.Methods: In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up.Results: During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years) were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1%) patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1) and 21 received etanercept 50 mg weekly (group 2). At the end of follow-up, 19 of 22 (86.3%) subjects in group 1 and 19 of 21 (90.4%) in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group 1 and group 2 was 22 ± 1 months and 21 ± 1.6 months, respectively.Conclusion: Remission of ankylosing spondylitis is possible in at least 50% of patients treated with etanercept 50 mg weekly. After halving of the etanercept dose, remission is maintained in a high percentage of patients during long-term follow-up, with important economic implications.Keywords: ankylosing spondylitis, anti-tumor necrosis factor, etanercept, remission, dose reduction