Search

Sequential digital dermoscopy (SDD) enables the diagnosis of a subgroup of slow-growing melanomas that lack suspicious features at baseline examination but exhibit detectable change on follow-up. The combined use of total-body photography and SDD is recommended in high-risk subjects by current guidelines. To establish the usefulness of SDD for low-risk individuals, we conducted a retrospective study using electronic medical records of low-risk patients with a histopathological diagnosis of cutaneous melanoma between 1 January 2016 and 31 December 2019, who had been referred and monitored for long-term follow-up of clinically suspicious melanocytic nevi. We sought to compare the distribution of “early” cutaneous melanoma, defined as melanoma in situ and pT1a melanoma, between SDD and periodical handheld dermoscopy in low-risk patients. A total of 621 melanomas were diagnosed in a four-year timespan; 471 melanomas were diagnosed by handheld dermoscopy and 150 by digital dermoscopy. Breslow tumor thickness was significantly higher for melanomas diagnosed by handheld compared to digital dermoscopy (0.56 ± 1.53 vs. 0.26 ± 0.84, p = 0.030, with a significantly different distribution of pT stages between the two dermoscopic techniques. However, no significant difference was found with respect to the distribution of pT stages, mean Breslow tumor thickness, ulceration, and prevalence of associated melanocytic nevus in tumors diagnosed on periodical handheld dermoscopy compared to SDD. Our results confirm that periodical dermoscopic examination enables the diagnosis of cutaneous melanoma at an earlier stage compared to first-time examination as this was associated in our patients with better prognostic features. However, in our long-term monitoring of low-risk subjects, Breslow tumor thickness and pT stage distribution did not differ between handheld periodical dermoscopy and SDD.

Background Coronavirus disease 2019 (COVI-19) has resulted in considerable morbidity ans mortality worldwide since December 2019. Cardiac complications are a common condition among patients with COVID-19. The association between elevated hypersensitivity troponin T in COVID-19 disease and risk of mortality remains unclear but data suggest it could be associated with higher risk of in-hospital mortality. Purpose The present study examine the potential association between the level of hypersensitive troponin T (Hs TnT) in emergency department (ED) and mortality among patients hospitalized with COVID-19. Methods Consecutive patients admitted in two hospitals from ED with confirmed PCR COVID-19 were included in this retrospective study. The data were collected from October 1, 2020 to December 31, 2020. The demographic characteristics (age and sex), clinical data (symptoms, comorbidities, laboratory findings, treatments, complications, and outcomes), and results of cardiac examinations (cardiac biomarkers and electrocardiogram) were collected in an electronic database. There data were analyzed and the mortality at 1 month was compared for patients with normal or elevated Hs TnT (>14 ng/L). Results The study population included 413 hospitalized patients with a confirmed PCR COVID-19. The median age was 82. The comorbidities like cardiovascular diseases, cerebrovascular diseases, pulmonary diseases and renal insufficiency are associated with a significant higher mortality (P20/minute) or hypotension (14 ng/L) compared to the patients with normal levels of Hs TnT and the correlation was significant (P14ng/L. Conclusion Elevated Hs TnT levels in the emergency department appear to be a predictive factor of mortality at one month for patients with COVID-19 infection requiring admission. Funding Acknowledgement Type of funding sources: None.

Fibromyalgia or fibromyalgia syndrome (FMS) is defined as a central sensitization syndrome characterized by the dysfunction of neurocircuits detecting, transmitting and processing nociceptive stimuli; the prevalent manifestation is musculoskeletal pain. In addition to pain, there are multiple accompanying symptoms, in common with other algo-dysfunctional syndromes, which are reflected in a broad spectrum of somatic, neurocognitive and neuro-vegetative manifestations. An evidence-based approach is essential in FMS management, in order to improve patient health and to reduce its social burden. Since in the last ten years new international guidelines for clinical practice (Clinical Practice Guidelines or CPGs) concerning FMS diagnosis and pharmacological/ non-pharmacological management have been published, the Italian Society of Rheumatology (SIR) has decided to adapt them to the Italian national setting. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the most recent CPGs on FMS to the needs of the Italian healthcare context. A working group of rheumatologists from SIR epidemiology unit and FMS experts identified relevant clinical questions to guide the systematic review of the literature. The target audience of these CPGs included physicians and healthcare professionals who manage FMS. The adapted recommendations were finally assessed by an external multidisciplinary panel. From the systematic search in databases (Pubmed/Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. The combination of the scientific evidence underlying the original CPGs with expert opinion lead to the development of 17 recommendations. The quality of evidence for each recommendation was reported and their potential impact on clinical practice was assessed. These SIR recommendations are expected to be a valuable aid in the diagnosis and treatment of FMS, as they will contribute to disseminate the best practice on the basis of the current scientific evidence.

Not available

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome due to a phosphaturic tumor, which overproduces Fibroblast Growth Factor 23 (FGF-23), causing hyperphosphaturia, hypophosphatemia, low 1,25(OH)2D and osteomalacia. Tumor localization is critical, diagnostic delay ranges from 2.5 to 28 years and to date surgical removal is considered effective treatment. We retrospectively evaluated patients with definite diagnosis of TIO referred to a tertiary Rheumatology Center between September 2000 and May 2020, investigating clinical management and disease outcome. We included 17 patients: 10 (58.8%) were females, mean age at diagnosis was 55.3 ± 13.9 years (mean ± standard deviation), with a diagnostic delay from symptoms onset to tumor detection of 6.6 ± 6.25 years. Biochemical data were: serum phosphorus 1.3 ± 0.4 mg/dL (Reference Range: 2.5–4.6), serum 1,25(OH)2D 31.8 ± 22.9 ng/mL (RR: 25–86), intact FGF-23, 358.9 ± 677 pg/mL (RR: 25–45); 24 h-Urine Phosphorus was increased in only 2 patients, while tubular reabsorption of phosphate (TRP) was decreased in all patients confirming a renal phosphate wasting. In 2013 68Ga- DOTA-based PET/CT was introduced in routinely practice and diagnostic delay was consistently reduced (from 8.6 ± 7.9 to 4.3 ± 2.4 years). Thirteen patients underwent surgery, one patient underwent radiofrequency ablation; 3 patients, not eligible for surgery, were treated only with supplements of phosphorus and calcitriol. One was started on Burosumab after several unsuccessful surgical attempts. After surgery or ablation, 8 patients had complete remission, 3 TIO persistence, and 3 had overtime relapse. Relapses were observed only in patients who previously underwent closed biopsy. To our knowledge, this is the widest European cohort of TIO patients in the last two decades. We confirm a usual diagnostic delay and recommend a stepwise diagnostic approach. Tumor biopsy is not recommended due to the potential cell spilling. Surgery is generally considered a definitive treatment, even though other approaches have been successful in curing TIO. Active surveillance on possible recurrence is always needed. Burosumab appears a promising therapy.

BackgroundComplex regional pain syndrome type-1 (CRPS-1) is a severely disabling pain syndrome characterized by sensory and vasomotor disturbance, swelling, and functional impairment. Persistence of signs and symptoms has been observed in up to 64% of cases until 5.8 yrs after the onset of manifestations. Long-term disability, such as irreversible functional limitation, has been reported in up to 28% of cases with severe consequences on workability. No scores are validated to evaluate residual disability. Bisphosphonates have the best efficacy profile, compared with other therapeutic approaches, but data on long-term effectiveness are lacking.ObjectivesTo retrospectively evaluate long-term residual disability in patients with CRPS-1 of hand or foot after treatment with IV Neridronate (IVNer). To identify predictors of residual disability. To quantify disease outcomes, such as patient’s subjective perception and residual pain. To assess long-term safety profile.MethodsWe retrospectively collected data of patients affected by CRPS-1, treated with IVNer, referred to a tertiary Rheumatology Centre between Feb 2013 and Dec 2020. Visual analogue scale (VAS) and McGill Questionnaire (McGQ) were used for pain assessment. Disabilities of the Arm, Shoulder and Hand (DASH) and American Orthopaedic Foot and Ankle Society’s (AOFAS) ankle-hindfoot scale for hand and foot involvement, respectively, were administered to explore disability through a phone survey. This kind of investigation was preferred for Covid pandemic.Results106 patients with definite diagnosis of CRPS-1 were included, mean age±standard deviation 55.6±13 yrs, 67% females, mean follow up duration 56.3 months (range 14-94), 46.2% with hand involvement. The mean VAS score before treatment onset was 55.8±23.4mm, while the McGQ was 12.9±6.7 in the sensory domain, 4.9±3.3 in the affective domain and 17.8±9.2 on the total score.Based on the patient’s subjective perception and the proposed semi-quantitative scale, 77.4% described themselves as fully recovered (FR), 15% partially recovered (PR), and 7.6% with persistent disease (PD). Comparison between baseline and follow-up VAS shows a significant reduction (55.8±23.4 vs 15.1±26.4, pPain assessment by McGQ showed a significant improvement in global score (baseline vs follow-up 17.8±9.2 vs 3.9±7.8, pAccording to DASH score, 79.2% of the patients were FR, 3.8% had some difficulties, but with overall preserved use of the upper limb, and 17.0% had permanent functional disability.According to AOFAS ankle-hindfoot scale 76.4% of patients were FR, 16.0% had partial recovery, and 7.6% had severe functional impairment.Percentages of DASH and AOFAS scores showed a complete accordance with patients’ subjective perception (Figure 1a and b).The only predictor of long-term functional impairment for CRPS-1 in the hand was a delayed treatment compared to symptoms onset (p=0.02). No predictors were found for foot localization.No patients reported the occurrence of osteonecrosis of the jaw or atraumatic fractures/atypical fracture features.Figure 1.ConclusionIVNer maintained a good long-term effectiveness and safety profile in the treatment of CRPS-1. The effectiveness of IVNer is maintained on both pain symptoms and function, in terms of reductions in the VAS, McGQ and in hand and foot disability scores.References[1]Varenna M et al. Rheumatology 2013[2]Padua R. et al. J Hand Surg. Br. Eur. 2003[3]Leigheb M et al. Acta Biomed. Atenei Parm. 2016Disclosure of InterestsNone declared

Over the last few years, the landscape of treatments for axial spondyloarthritis (SpA) has been rapidly evolving, urging international scientific societies to draft or update existing clinical practice guidelines (CPGs) on the management of axial SpA. The Italian Society for Rheumatology (SIR) committed to provide revised and adapted evidence- and expert-based recommendations for the management of patients with axial SpA in Italy. A systematic approach to the adaptation of existing CPGs - the ADAPTE methodology - was adopted to obtain updated recommendations suitable for the Italian context. A systematic literature search was performed in Medline and Embase databases to find international CPGs and consensus statements with recommendations for the management of axial SpA published in the previous five years. A working group composed of rheumatologists with proven experience in the management of axial SpA and methodologists identified the key research questions which guided study selection and data extraction. Guideline quality was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The Italian recommendations were developed by endorsing or adapting and rewording some existing recommendations. The draft of the recommendations was sent to a multidisciplinary group of external reviewers for comment and rating. Six original CPGs were selected and used to create this SIR CPG, which includes a final set of 14 recommendations covering the management of patients with axial SpA across the following domains: assessment, pharmacological and non-pharmacological treatment, and follow-up. The dissemination and implementation of these SIR recommendations are expected to support an evidencebased clinical approach to the management of patients with axial SpA in Italy.

Introduction The aim of this work is to investigate the improvement of physical function and its determinants in axial spondyloarthritis (SpA) patients treated with tumor necrosis factor (TNF) inhibitors in a real clinical practice setting. Methods An observational study was conducted in patients with axial SpA treated with anti-TNF from 2010 to 2018 with a minimum 6 months of follow-up. All patients fulfilled ASAS or the modified New York criteria. The Bath Ankylosing Spondylitis Metrology Index (BASMI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) were used as objective and self-reported functional indices. The improvement of function and factors associated were evaluated for the present study, as well as disease activity and patient-reported outcome measures. Results A total of 183 patients with axial SpA were examined. Among them, 27 were non-radiographic axial SpA, while the remaining 156 were ankylosing spondylitis patients. BASFI and BASMI significantly improved during follow-up. Improvement of metrology index BASMI inverse correlated with disease duration (rho − 0.2, p = 0.009) and directly correlated with the improvement of BASDAI (rho 0.26, p = 0.003) and CRP (rho 0.26, p = 0.0003). Improvement of BASFI significantly inversely correlated with disease duration and directly correlated with the improvement of BASDAI, CRP, and baseline ESR. Male sex, lower disease duration, high ESR, and the improvement of BASDAI were found to be associated with the improvement of BASFI. Conclusions Our results showed that in real-life settings, patients improve in BASMI and BASFI. Furthermore, factors associated with this improvement were identified.

Not available

Background:Identifying psoriatic arthritis (PsA) among people with psoriasis is often challenging due to low specificity of symptoms at early PsA stage and/or delayed referral to the rheumatologist. Screening instruments -assisting the dermatologist to decide when rheumatological assessment is beneficial- have potential to reduce the diagnostic delay.Objectives:To evaluate the accuracy of a dermatologist-filled-out questionnaire designed for screening PsA among psoriatic patients under dermatology care.Methods:HERACLES is a multicentre, cross-sectional study running at 9 Italian dermatology and rheumatology tertiary centres. All participants were under dermatology care for skin psoriasis. Previous diagnosis of PsA precluded eligibility. Dermatologists at each site assessed consecutive psoriatic subjects, filled in the specifically-designed HERACLES questionnaire (HQ, Figure 1) and finally referred the participants to rheumatologists for clinical evaluation. All participants filled in the ToPAS, PASE, PEST and EARP questionnaires. Rheumatologists assessed the participants regardless of the questionnaires’ scores. The gold standard applied to assess the instruments’ accuracy was the diagnosis of PsA as established by the rheumatologists. ROC curve analysis evaluated the performance of the scores associated with the clinical criteria listed in the HQ, estimating the sensitivity and specificity of different cut-off levels. Further exploratory ROC curve analysis compared HQ performance to that of the other four questionnaires tested.Figure 1.Results:Out of 759 subjects enrolled, 524 (69%) attended rheumatology assessment. Rheumatologists diagnosed PsA in 73/524 patients (13.9%, Figure 2). Mean age was 53 (SD 16) years and 46% were female. Mean psoriasis duration was 20 (SD 19) years. The area under the ROC curve of HQ was 0.775. The HQ score cut-off value of 2 yielded a sensitivity of 92% and a specificity of 47%; a cut-off value of 3 yielded a sensitivity of 66% and a specificity of 75%. The comparison between the ROC curve of the HQ and those of the other four questionnaires evaluated did not show any significant difference (p=0.523 versus TOPAS; p=0.201 versus PASE; p=0.345 versus PEST and p=0.240 versus EARP).Figure 2.Conclusion:The HERACLES questionnaire, a tool designed for dermatologists, showed good sensitivity and specificity in identifying PsA cases among subjects with cutaneous psoriasis.Acknowledgments:The HERACLES project was supported by a research grant from FIRA and Pfizer Italia SRLDisclosure of Interests:Gabriele De Marco: None declared, Maria Manara Consultant of: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Speakers bureau: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Paolo Gisondi: None declared, Luca Idolazzi: None declared, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, Stefano Piaserico: None declared, Alberto Cauli: None declared, Marco Amedeo Cimmino: None declared, Veronica Tomatis: None declared, Carlo Salvarani: None declared, Rosanna Scrivo: None declared, Anna Zanetti: None declared, Greta Carrara: None declared, Carlo Alberto Scirè: None declared, Angelo Cattaneo: None declared, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly

Several studies support the role of Western-style diet (WD) in inflammatory bowel disease (IBD). Toll-like receptors/NOD-like receptors (TLRs/NLRs) are important to maintain a healthy epithelium as well as inducing inflammation. Given that dietary factors influence IBD development, that epithelial dysfunction is thought to be involved in initiating intestinal inflammation and that TLR-NLR are involved in maintenance of the functionality of intestinal epithelium as well as in regulating inflammation, we decided to examine the role of TLR signals in the triggering events that lead to alteration of the small intestinal epithelium associated to consumption of WD. C57BL/6J mice deficient for TLR2, 4, 9, or NOD2 and wild-type (WT) were fed a WD or a standard diet for 3 months. The effects of WD on small intestinal samples were evaluated by histological and immunohistochemical analysis. After 3 months, WD modifies the morphology and the organization of the small intestine in TLR9 KO mice compared with WT mice and the others TLRs. The most interesting change involved the expression of proliferative and differentiation markers of WNT signaling, Ki67 and FzD5. Mice deficient in TLR2, 4, and NOD2 have a significant reduction in the proliferative cell numbers but do not show any signs of histological alterations. Our results suggest that TLR9 is an important protective factor in intestinal epithelial homeostasis and provide new insights into an unrecognized role of TLR9 signaling in the small intestinal mucosa dysfunction associated with WD.

Background: Pain is the hallmark of Complex Regional Pain Syndrome (CRPS). Nerve growth factor (NGF), widely known as pain mediator, is increased in the affected skin1 and in tibia bone of rat models of CRPS, while is lowered by administration of anti-NGF antibodies2. CRPS usually develops after limb trauma, most frequently a fracture3. Some reports considered bone as a main player in CRPS pathogenesis, hypnotizing that sclerostin (SOST)4 and Dickkopf-related protein-1 (DKK-1) may be involved in CRPS pathogenesis. Objectives: To evaluate NGF, SOST, and DKK-1 serum levels from affected arm of CRPS patients and compare them with unaffected one and healthy controls (HCs). Methods: Adults patients affected by CRPS diagnosed according to IASP criteria at upper limb were consecutively enrolled from April 2017 to August 2018. Patients with prior treatment with bisphosphonates, and history of disorders of mineral metabolism were excluded. Sera from the basilica vein of affected and unaffected arm of CRPS patients were collected, as well as sera from HCs paired for age and sex. NGF, SOST, and DKK-1 concentrations were determined by ELISA kit. Comparisons between patients and HCs were performed by Student test, while comparison between affected and unaffected arms were performed with Wilcoxon test for paired data. Pearson correlation was used to correlate NGF, SOST, and DKK-1 levels with demographic and clinical variables. Results: The overall population included 41 patients: males (M) 21.9%, mean age at diagnosis [± standard deviation, SD] 61.9±8.4 yrs, median disease duration 67 days (inter quartile range (IQR) 14.0; 22.5), 39 (95.2%) experienced a fracture as inciting event, mean VAS pain score (0-100) 54.8±18.6 mm. Mean NGF levels (pg/mL) were 12.0±28.8 and 11.4±35.5 in the affected and unaffected side, respectively, and 13.5±55.0 in HCs. NGF was undetectable in most patients; no statistical significant differences of NGF levels were found between patients and HCs. Mean SOST levels (pmol/L) were 32.6±16.1, 29.8±17.7, and 34.0±13.3 in affected, unaffected arm, and in HCs, respectively. No statistical significantly differences of SOST levels were found between patients and HCs, while a significant difference was found between affected and unaffected arms (p=0.03). Mean DKK-1 levels (pmol/L) were higher in affected arm (31.2±29.5) than in unaffected one (29.3±28.6) or in HCs (27.5±18.2) without reaching statistical significance. NGF was significantly correlated with VAS pain score (p=0.04). Conclusion: To our best knowledge, this is the first study to evaluate NGF, SOST, and DKK-1 levels in adults affected by CRPS-1. SOST levels were significantly higher in affected arms compared to unaffected ones, suggesting a possible role of this bone mediator in CRPS pathogenesis. NGF was consistent with the expression of pain, trough VAS pain score. Further studies need to clarify these preliminary findings. References: [1] Li WW, et al. Pain2010; 151:843–52. [2] Sabsovitch I, et al. Pain2008; 138: 47–60. [3] de Mos M, et al. Pain2007; 129:12-20. [4] Robling AG, et al. J Biol Chem2008;283:5866-75. Disclosure of Interests: Chiara Crotti: None declared, Maria Manara: None declared, Francesca Zucchi: None declared, Davide Gatti Speakers bureau: Abiogen, Amgen, Janssen-Cilag, Mundipharma, Pfeizer, Maurizio Rossini: None declared, Massimo Varenna: None declared

Background: Still’s disease is a rare autoinflammatory disease, presenting in both pediatric [systemic juvenile idiopathic arthritis (SJIA)] and adult patients [adult-onset Still’s disease (AOSD]. Due to the rarity of the disease, clinical trials are limited and treatment guidelines are not available. In patients refractory to the classical therapy with NSAIDs, corticosteroids and DMARDs, the introduction of drugs targeting IL-1 has greatly expanded treatment options. Among these, canakinumab, a human monoclonal anti-IL-1β antibody, and anakinra, a human recombinant IL-1RA, have been recently approved for the treatment of refractory patients. Objectives: To produce recommendations, based on evidence and expert consensus, that can help clinicians in choosing the most appropriate treatment of AOSD, with particular attention to anti-IL-1 therapies, in order to achieve disease remission before the development of complications. Methods: The recommendations development process took place from April to October 2018 and consisted of three steps. The first step was dedicated to a comprehensive literature review and development of statements. Two separate literature searches were performed: a) similarities and differences between SJIA and AOSD; b) efficacy and safety of IL-1 blockade in AOSD. The issue related to the treatment of AOSD with anti-IL1 therapies was specified into 4 questions: 1) efficacy and safety; 2) comparison among IL-1 inhibitors; 3) early versus late treatment; 4) systemic versus chronic articular pattern of the disease. In the second step, the statements were submitted in a Delphi process to a panel of 67 rheumatologists. Consensus threshold was set at 66%: positive, > 66% of voters selected scores 3 to 5; negative, > 66% of voters selected scores 1 or 2. At the third step of the consensus process, the voting results were analyzed, and the statements were finalized. Results: In the two literature searches, 332 and 358 publications were identified; 30 and 25 publications, respectively, were selected according to the inclusion criteria. Based on the review of the literature and personal clinical experience, 11 statements were developed. 48/67 rheumatologists (72%) participated to the Delphi process. Positive consensus was reached after the first round of voting and was full (> 95%) on the majority of statements. A large consensus was achieved in considering AOSD and SJIA as the same disease. The use of anti-IL-1 therapies in refractory patients was considered quite safe and effective both as first and as subsequent line of biologic treatment, especially in systemic patients. Because of the lack of head-to-head comparisons, a different profile of efficacy among IL-1 inhibitors could not be established. There was a large consensus that failure of the first IL-1 inhibitor does not preclude a therapeutic response with another one. The lack of studies comparing early versus late treatment in AOSD patients did not allow to draw conclusions, however data from SJIA suggest a better response in early treated patients. Conclusion: The Delphi method was used to develop recommendations that we hope will help clinicians in the management of patients with AOSD refractory to conventional therapies. Acknowledgement: Editorial support was provided by Springer Healthcare Communications and funded by Novartis Farma, Italy. Disclosure of Interests: Serena Colafrancesco: None declared, Maria Manara: None declared, Alessandra Bortoluzzi: None declared, Teodora Serban: None declared, Gerolamo Bianchi: None declared, Luca Cantarini: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI., Marcello Govoni: None declared, Carlomaurizio Montecucco: None declared, Roberta Priori: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Paolo Sfriso: None declared, Luigi Sinigaglia Speakers bureau: Yes, I,ve been invited speaker by Amgen, Ely Lilly, UCB, Abbvie, Roche and BMS.

Background The treat-to-target concept is currently applied to gout [1] and a composite outcome to measure disease activity may serve as a target in clinical practice. Strategies for achieving the target are still not individualized and the ability to adjust the treatment on an individual basis using prognostic information from predictive models might help practitioners to identify patients with a high or low probability of remission or disease inactivity. Objectives To develop a prediction model for disease inactivity in gouty patients. Methods Data were retrieved from the Kick-off of the Italian Network for Gout (KING) observational cohort multicentre study on behalf of the Italian Society for Rheumatology. The gout activity score (GAS) [2,3] was used as validated outcome to define inactive disease (cut off Results Out of 446 patients enrolled from 30 rheumatology centres, 265 (59%) had active disease at baseline (mean age 63±11 years, male 91%, median disease duration 7 years, tophi 23%, urate lowering therapy 82%, mean serum urate [sUA] levels 6.7±1.6 mg/dl) and a 12-month visit. In 34% (65/206) gout was inactive at 12 months. From 20 candidate predictors (complete cases n=150) disease duration, use of nonsteroidal anti-inflammatory drugs (NSAIDs), number of flares in the previous 12 months, presence of tophi, sUA Conclusion These preliminary prediction models for inactive disease showed good performance in gouty patients from a real-life secondary setting. External validation in ad-hoc studies is required to identify the best model and to search for additional predictors and increase its predictive performance. References [1] Kiltz U, et al. Ann Rheum Dis2017 [2] Scire CA, et al. Arthritis Care Res (Hoboken)2016 [3] La-Crette J, et al. Joint Bone Spine2018 Disclosure of Interests Nicola Ughi Speakers bureau: Pfizer, Grunenthal, Greta Carrara: None declared, Anna Zanetti: None declared, Marco Amedeo Cimmino Grant/research support from: Menarini, Consultant for: Menarini International, Maria Manara: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Fausto Salaffi Grant/research support from: Abbvie, Roche, Novartis, BMS, Pfizer, Sanofi, Speakers bureau: Abbvie, Roche, Novartis, Pfizer, Sanofi, BMS, Leonardo Punzi Consultant for: BMS, Fidia, Grunenthal, Menarini, Speakers bureau: BMS, Fidia, Grunenthal, Menarini, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, giovanni minisola: None declared, Antonella Zambon: None declared, Carlo Alberto Scire: None declared

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterised by chronic joint inflammation, leading to functional disability and increased risk of premature death. Clinical practice guidelines (CPGs) are expected to play a key role in improving management of RA, across the different phases of the disease course. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2011 recommendations on management of RA. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing RA CPGs to the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Research Unit and a committee with experience in RA identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage RA in practice, and the target population includes adult patients diagnosed as having RA. An external multi-disciplinary committee rated the final version of the CPGs. From the systematic search in databases (Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 8 (Management) +6 (Safety) recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the management of RA and to disseminate the best evidence-based clinical practices for this disease.

Background:Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome due to a phosphaturic tumor, which overproduces fibroblast growth factor-23 (FGF-23), causing hyperphosphaturia, hypophosphoremia, low 1,25(OH)2VitD3and osteomalacia. Locating the tumor is critical, because lesions are typically small, benign mesenchymal tumors, anywhere in the body; the delay between onset of symptoms and diagnosis ranges from 2.5–28 years. Surgical removal is the only effective therapeutic approach.Objectives:To retrospectively evaluate patients affected by TIO, investigating clinical management and disease outcome.Methods:We retrospectively collected data of patients affected by TIO referred to a tertiary Rheumatology Center between Sep 2000 and Jan 2020.Results:We included 16 patients with a definite diagnosis of TIO, mean age±standard deviation 62.4±14.6 yrs, 56.2% females, mean age at symptoms onset 48.0±14.3 yrs (53.8±13.1 at diagnosis). Mean diagnostic delay between symptoms onset and tumor detection was 6.8±6.4 yrs. All patients complained bone pain, muscle weakness, and fractures before diagnosis of TIO. Biochemical findings were: mean serum Phosphorus (PS) 1.4±0.4 mg/dL (reference range (RR) 2.5-4.6), mean serum Calcium 9.4±0.7 mg/dL (RR 8.4-10.2), mean serum 1,25(OH)2VitD330.5±23.4 ng/L (RR 25-86). Intact-FGF-23 was dosed in 9 patients, always resulting elevated: mean 396.6±707.3 pg/mL (RR 25-45). PTH was increased in 30% of cases, while serum alkaline phosphatase was increased in 87.5%. 24h-Urine Phosphorus (PU) was increased in only 13% of patients, but, when renal phosphate wasting by tubular reabsorption of phosphate (TRP) was calculated, PU resulted increased in all.Tumor was localized in all cases (Fig.1) and were localized in bone and soft tissue, by using functional imaging, followed by anatomical techniques. Before the introduction in routinely practice of68Ga-DOTATATE-PET-CT in 2013, Octreoscan-SPECT/CT and18F FDG-PET were used as imaging modalities. Since 2013, diagnostic delay consistently reduced, from 8.6±8.3 yrs (7 patients) to 4.5±2.6 yrs (9 patients), confirming higher diagnostic accuracy of68Ga-DOTATATE-PET-CT.Figure 1.13 patients underwent surgery; in two cases surgery was not possible due to tumor location, so pharmacological support with phosphate supplements and calcitriol was started; a patient underwent to TC-guided radiofrequency ablation. After surgery, 7 patients experienced a complete remission, 3 had a persistence of the disease, and 3 an overtime relapse, even after a longstanding normalization of PS (6 years). After surgical tumor removal, PS significantly increased in few days (from 1.36±0.39 to 2.9±1.1, p=0.0001), while iFGF-23 levels tended to rapidly decreased (from 396.6±707.3 to 62.8±78.4). Before the introduction of68Ga-DOTATATE-PET-CT, 6 patients underwent to imaging-guided closed biopsy to confirm tumor localization; by using68Ga-DOTATATE-PET-CT only 2 subjects had closed biopsy. Furthermore, in our population only patients who had biopsy to detect the lesion (7 patients) had relapses compared to patients who did not.Conclusion:To our knowledge, this is the widest European cohort of patients affected by TIO reported in the last two decades. We confirm an important delay between symptoms onset and diagnosis. To locate tumor, a stepwise approach is recommended, starting with a thorough medical history and physical examination, followed by functional imaging, preferring68Ga-DOTATATE-PET-CT. Tumor biopsy is not recommended due to the potential cell spilling. Surgery is considered the only definitive treatment, aiming to a wider excision. Active surveillance is always needed, due to the possible relapses, even after a long period of complete clinical and biochemical remission.Disclosure of Interests: :Chiara Crotti: None declared, Francesca Bartoli: None declared, Maria Manara Consultant of: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Speakers bureau: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Primo Andrea Daolio: None declared, Francesca Zucchi: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Luigi Sinigaglia: None declared, Massimo Varenna: None declared

Osteoarthritis (OA) is the most common musculoskeletal disease leading to functional decline and loss in quality of life. Knees, hands and hips are frequently affected joints with a relevant clinical and socio-economic burden. An evidence-based approach to OA management is essential in order to improve patients’ health and to decrease social burdens. Since new international clinical practice guidelines (CPGs) focused on diagnosis or pharmacological/non-pharmacological treatment have become available in the last ten years, the Italian Society for Rheumatology (SIR) was prompted to revise and customize them for a multidisciplinary audience of specialists involved in the management of OA. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing CPGs on OA to the needs of the Italian healthcare context. The task force, consisting of rheumatologists from the SIR epidemiology research unit and a committee with experience of OA, identified key health questions to guide a systematic review of published guidelines. The target audience included physicians and health professionals who manage OA. An external panel of stakeholders rated the guidelines. From a systematic search in databases (Pubmed/Medline, Embase) and grey literature, 11 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 16 guidelines were developed and graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. These revised guidelines are intended to provide guidance for diagnosis and treatment of OA and to disseminate best evidence-based strategies management of the disease.

Gout is a chronic disease with an increased risk of premature death related to comorbidities. Treatment of gout has proved suboptimal and clinical practice guidelines (CPGs) are expected to have a key role in achieving improvement. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2013 recommendations on the diagnosis and management of gout. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing gout CPGs to the needs of the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Unit and a committee with experience on gout identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage gout in practice, and the target population includes adult patients suspected or diagnosed as having gout. These recommendations were finally rated by an external multi-disciplinary commission. From a systematic search in databases (Medline, Embase) and grey literature, 8 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 14 recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the diagnosis and the treatment of gout and to disseminate the best evidence-based healthcare for this disease.

Background Disease activity significantly impacts on work ability of patients with Rheumatoid Arthritis (RA). Biologic agents can control disease activity, but their effects on productivity outcomes were not adequately investigated in Italian population. Objectives Aim of the study was to evaluate the impact of biologic therapy on work productivity outcomes in a cohort of biologic-naive patients with active RA from northern Italy. Methods This is a multicentre prospective study on patients with active RA in working age (18–65 years), scheduled to undergo their first biologic treatment. Demographics and clinical data were collected at baseline and at 6 and 12 months, together with productivity outcomes assessed with the RA-specific work productivity survey (WPS-RA)1 and the Health and Labour Questionnaire (HLQ)2. Primary outcome was the productivity loss or gain after 1 year of treatment. Results We included 100 patients from 7 rheumatology centres in northern Italy with active RA [mean DAS28: 5,1 (SD 0,9), median SDAI: 25,2 (IQR 18,7–33,2)]. Most of them were females (85%), with a mean age of 49,1 (SD: 10,3) years and a median disease duration of 7 (IQR: 3–14) years. Patients were treated with TNF-inhibitors (68%), Abatacept (24%) or Tocilizumab (8%). At baseline 39 patients were unemployed. After 1 year of treatment, 85 patients were still on follow-up, with an improvement in all indexes of disease activity [mean DAS28: 2,8 (SD 1,3), median SDAI: 5,1 (IQR 1,9–12,9)]. A significant reduction in number of days of work missed (absenteeism) and of reduced productivity (presenteeism) was observed in employed subjects, as well as a significant decrease in number of days missed of household work and social activities in all the study population (table 1). Conclusions One year of treatment with biological drugs was associated with a significant improvement in outcomes related to productivity both within and outside home in a cohort of patients with RA. References [1] Osterhaus JT. Arthritis Res Ther. 2009;11:R73. [2] Van Roijen L. Int J Technol Assess Health Care1996;12:405–15. Disclosure of Interest M. Manara: None declared, R. Caporali: None declared, R. Gorla: None declared, E. Fusaro: None declared, R. Pellerito: None declared, P. A. Rocchetta: None declared, P. Sarzi Puttini: None declared, S. Capri Consultant for: Pfizer, L. Sinigaglia: None declared

Objective.The aim of this study was to evaluate the influence of sex on response to treatment and disease remission in patients with axial spondyloarthritis (axSpA).Methods.In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria for axSpA, and treated with adalimumab, etanercept, golimumab, or infliximab, were studied. We compared clinical characteristics, patient-reported outcomes, disease activity, function, and response to treatment in male and female patients with this disease.Results.Three hundred forty patients with axSpA (270 with ankylosing spondylitis, 19 with psoriatic arthritis with axial involvement, and 51 with nonradiographic axSpA) were studied. Male subjects had a significantly higher prevalence of grade IV sacroiliitis, higher levels of serum C-reactive protein, lower Maastricht Ankylosing Spondylitis Enthesitis Score, and fatigue when compared with females. Further, Kaplan-Meier survival curves showed that the rate of partial remission, ASAS40 response, and Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement, but not ASDAS inactive disease, were significantly lower in female patients.Conclusion.Our data suggest that female sex was associated with a lower rate of response to treatment and of disease remission in patients with axSpA treated with antitumor necrosis factor-α drugs.

We present an update on the effects of methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), and cyclosporine (CSA) in psoriatic arthritis (PsA) by reviewing data published from January 2010 to June 2014. The most relevant study on MTX, the Methotrexate In Psoriatic Arthritis (MIPA) trial, did not show a significant difference between this drug and placebo in improving peripheral synovitis. The trial, however, had several limitations. A cohort study on a small number of patients found that MTX does not inhibit radiographic progression. In a large observational study, 86% of LEF-treated patients met PsA Response Criteria (PsARC) at Week 24. No studies of sufficient relevance on SSZ were published in the examined time frame. In an open-label trial, CSA alone was compared to adalimumab (ADA) alone and to the combination ADA/CSA. The ADA arms showed a significantly higher response rate, but as many as 65% of CSA-treated patients were PsARC responders at Month 12. No relevant data on the effects of these 4 drugs on psoriatic enthesitis, dactylitis, or spondylitis have recently been published, and no new safety signals have been reported. Observational data from 2 registers suggest that concomitant MTX increases the retention rate of tumor necrosis factor-α inhibitors. The studies published in the examined time frame confirm that MTX, SSZ, LEF, and CSA have moderate symptom-modifying effect on psoriatic synovitis, and probably little effect on the other manifestations of PsA.

Background Methotrexate (MTX) is the DMARD of first choice in the treatment of rheumatoid arthritis (RA). Objectives To investigate the clinical characteristics and describe therapeutic approaches in RA patients ongoing MTX not achieving a DAS28 “low disease activity” score. Methods This is a case-control analysis including 186 patients (mean age±SD, 61±12 years, 16% males) who did not achieve a DAS28 “low disease activity” score (defined by a value ≤3.2) and 558 age- and gender-frequency-matched (1:3), randomly selected controls (mean age age±SD, 61±13 years) who achieved a DAS28 “low disease activity” from the original cohort investigated in the MARI study. The MARI study enrolled RA patients on treatment for at least 12-month with MTX. Demographic, clinical, laboratory and pharmacological characteristics of patients recorded at baseline visit were considered for the current analysis. We first compared the characteristics of patients who reached the endpoint with those of subjects who did not by univariate analyses, thereafter, we performed a multivariate model to identify predictors of not achieving the endpoint. We further investigated the therapeutic approaches in patients not achieving the endpoint. Results Compared to patients with a DAS28 ≤3.2, subjects not achieving the endpoint presented with a significant higher (mean±SD) weight and BMI (DAS28 ≤3.2: 25±4 versus DAS28 >3.2: 26±5, P=.022), and longer duration of symptoms (months±SD) before the RA diagnosis (11±15 versus 15±20, P=.009). A higher proportion of subjects within the group not achieving the endpoint presented with polyarticular disease (DAS28 ≤3.2: 57% versus DAS28 >3.2: 96%, P 3.2 (P=.004). In the logistic regression analysis, the variables predictive of a DAS28 >3.2 were polyarticular disease (OR 4.0, 95% CI 2.4–6.7, P 3.2: 13% versus DAS28 ≤3.2: 4%, P Conclusions Our results identified a number of variables potentially associated the risk of not achieving a DAS28 “low disease activity” score in RA patients ongoing MTX treatment. Longitudinal studies are warranted. Disclosure of Interest None declared

Hypertension and related cardiovascular diseases are reported to be associated with osteoporosis. A nutritional pathway related to dairy intake has been postulated for both diseases. The aim of this study was to assess calcium intake from dairy sources as a possible pathogenic link between osteoporosis and hypertension. This was a cross-sectional observational study performed on 3,301 postmenopausal women referred for a densitometry screening. Osteoporosis was diagnosed by lumbar dual-energy X-ray absorptiometry and hypertension was defined by blood pressure data and/or the use of antihypertensive medication. Dairy food consumption was evaluated using a weekly food-frequency questionnaire. The odds of being affected by osteoporosis, hypertension, or both diseases were calculated for quartiles of dairy intake by logistic regression analyses. Women with hypertension were affected more frequently by osteoporosis (33.2 vs. 23.3 %; p = 0.000), and there was a higher prevalence of hypertension among women with osteoporosis (32.2 vs. 22.5 %; p = 0.000). The proportion of women with hypertension, osteoporosis, and both diseases significantly increased across decreasing quartiles of dairy intake. A dairy intake in the lowest quartile was a significant predictor of osteoporosis [OR (95 % CI): 1.43 (1.12, 1.82)] and hypertension [OR (95 % CI): 1.46 (1.15, 1.85)] when compared to the highest quartile. Similarly, a low dairy intake was associated with increased odds to have both the diseases [OR (95 % CI): 1.60 (1.10, 2.34)]. From these results we conclude that osteoporosis and hypertension are associated in postmenopausal women, and a low dairy intake may increase the risk of both diseases, acting as a possible pathogenic link.

Several studies support the role of Western-style diet (WD) in inflammatory bowel disease (IBD). Toll-like receptors/NOD-like receptors (TLRs/NLRs) are important to maintain a healthy epithelium as well as inducing inflammation. Given that dietary factors influence IBD development, that epithelial dysfunction is thought to be involved in initiating intestinal inflammation and that TLR-NLR are involved in maintenance of the functionality of intestinal epithelium as well as in regulating inflammation, we decided to examine the role of TLR signals in the triggering events that lead to alteration of the small intestinal epithelium associated to consumption of WD. C57BL/6J mice deficient for TLR2, 4, 9, or NOD2 and wild-type (WT) were fed a WD or a standard diet for 3 months. The effects of WD on small intestinal samples were evaluated by histological and immunohistochemical analysis. After 3 months, WD modifies the morphology and the organization of the small intestine in TLR9 KO mice compared with WT mice and the others TLRs. The most interesting change involved the expression of proliferative and differentiation markers of WNT signaling, Ki67 and FzD5. Mice deficient in TLR2, 4, and NOD2 have a significant reduction in the proliferative cell numbers but do not show any signs of histological alterations. Our results suggest that TLR9 is an important protective factor in intestinal epithelial homeostasis and provide new insights into an unrecognized role of TLR9 signaling in the small intestinal mucosa dysfunction associated with WD.

Objective. The aim of this study was to assess whether the effectiveness of bisphosphonate infusion in patients with complex regional pain syndrome type I (CRPS-I) is influenced by variables related to patient and/or disease characteristics. Methods. This is a retrospective analysis of patients referred in the last five years to our rheumatologic tertiary care center, all fulfilling the Budapest CRPS-I diagnostic criteria and treated with three different bisphosphonate schedules (clodronate, pamidronate, and neridronate). For every subject, demographic and clinical variables were retrieved and retrospectively analyzed. We identified variables that independently influenced the therapeutic outcome of patients by a logistic regression analysis. For exploratory purposes, the effectiveness of the different bisphosphonate treatments employed was compared. Results. Among the 194 patients included in the analysis, the overall therapeutic response rate was 71.6%. Logistic regression analysis showed that the independent predictive variables for therapeutic effectiveness were disease duration (odds ratio [OR] = 0.83, 95% confidence interval [CI] = 0.72–0.96 for a one-month increment), fracture as a predisposing event (OR = 3.23, 95% CI = 1.29–8.03), and “warm” disease subtype (OR = 4.88, 95% CI = 1.57–15.20). These variables were found to influence the odds of responsiveness when analyzed together with age at onset, gender, and disease localization. No significant difference in therapeutic effectiveness was found by comparing the three different bisphosphonate schedules employed. Conclusion. Early disease, fracture as a predisposing event, and “warm” disease subtype are predictors of responsiveness to bisphosphonate treatment in patients with CRPS-I.

Objective.The aim of this study was to evaluate rate and predictive factors of loss of remission and disease flare in patients with axial spondyloarthritis (axSpA) receiving antitumor necrosis factor (anti-TNF) treatment.Methods.In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria, treated with adalimumab, etanercept, or infliximab with a minimum followup of 12 months and satisfying the ASAS partial remission criteria and/or Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were studied. Disease flare was defined as a Bath Ankylosing Spondylitis Disease Activity Index score > 4.5 or ASDAS score > 2.5 on at least 1 occasion.Results.One hundred seventy-four patients with axSpA were studied. After a median [interquartile range (IQR)] followup of 4 years (2–6), 37 patients (21.2%) experienced a loss of remission and 28 (16.1% of the whole study group) a disease flare. Median (IQR) duration of remission in patients who lost this status was 1 year (0.625–2). Higher median erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, continuous nonsteroidal antiinflammatory drug (NSAID) use, and an ASDAS-CRP ≥ 0.8 during the remission period were significantly associated with both loss of remission and disease flare. At the multivariate analysis, continuous NSAID intake (OR 4.05, 95% CI 1.4–11.74, p = 0.010) and ESR > 15 (OR 2.90, 95% CI 1.23–6.82, p = 0.015) were the only factors predictive of disease reactivation.Conclusion.In this study, loss of remission and disease flares occurred, respectively, in about 21% and 16% of the patients with axSpA who achieved a state of remission while receiving anti-TNF therapy. Residual disease activity was associated with disease reactivation.

Objective.To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM).Methods.Our cross-sectional study was carried out in 10 Italian rheumatology centers between January and September 2009, and enrolled all consecutive patients with PsA and FM who agreed to participate. Standard clinical and laboratory data for PsA and FM were collected from all patients. Records were made of somatic symptoms, response to nonsteroidal antiinflammatory drugs (NSAID), self-evaluated pain, general health, disability, and responses to the Fibromyalgia Impact Questionnaire. Data were statistically analyzed by univariate and multivariate analyses, and receiver-operating characteristic curves. The analysis concentrated on the clinical features shared by the 2 conditions.Results.Two hundred sixty-six patients with PsA (mean age 51.7 yrs; disease duration 10.2 yrs) and 120 patients with FM (mean age 50.2 yrs; disease duration 5.6 yrs) were evaluated. Univariate analysis showed that patients with FM had higher mean tender point and enthesitis scores, more somatic symptoms, and responded less to NSAID. Multivariate analysis showed that the presence of ≥ 6 FM-associated symptoms and ≥ 8 tender points was the best predictor of FM.Conclusion.The shared clinical features of PsA and FM that had the greatest discriminating power for FM were the number of FM-associated symptoms and tender point count.

Objective.Paget’s disease of bone (PDB) is a focal disorder of skeletal remodeling that can lead to bone pain, deformity, and fractures, but it can often be asymptomatic for a long time. This study investigated which factors may distinguish patients with clinical manifestations from asymptomatic patients.Methods.The study group consisted of 224 patients with PDB referred to our Bone Disease Unit. For all patients, data were collected about clinical and demographic variables and diagnostic procedures. Logistic regression analyses were used to assess the role of recorded variables on the odds of being diagnosed clinically rather than by chance.Results.Among the 124 patients with clinical manifestations leading to the diagnosis (55.4%), 36 subjects complained of bone pain, 32 articular pain, 42 back pain, 2 headache; 9 had fractures in Paget bone, and 3 had bone deformity. In 100 patients (44.6%) PDB was diagnosed by chance. At the multivariate analysis, only the number of bones involved (OR for 1 site increment = 1.18, 95% CI: 1.007–1.402; p = 0.04) acted as an independent predictor for a clinical diagnosis. Some skeletal localizations were associated with a clinical diagnosis: the involvement of lumbar spine (OR = 2.085, 95% CI: 1.024–4.224; p = 0.043) was more likely in symptomatic patients; pelvis and tibia showed a borderline statistical significance. The skull was predictive for asymptomatic PDB.Conclusion.A systematic laboratory screening including serum alkaline phosphatase of an older subject complaining of bone pain, articular pain, or back pain is the sole strategy to improve the diagnostic sensitivity for PDB.

Despite the recent advances in understanding the pathogenesis of oncogenic osteomalacia, a rare paraneoplastic syndrome related to an excessive production of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) by the tumor, the clinical diagnosis of this entity is still to be considered a clinical challenge, with an usual delay in the identification and treatment of affected patients that may lead to severe consequences for the individual’s quality of life. In this issue, Mathilde M. Bruins Slot-Steenks and colleagues report on a typical case of oncogenic osteomalacia in which a long delay from symptoms onset to correct clinical diagnosis had occurred, as well as a long time before tumor was identified and therefore an effective treatment could be established [1]. From a clinical point of view, it could be hard to suspect an osteomalacia in the initial phases of the disease, since most patients report only nonspecific symptoms such as weakness or diffuse pain, that could be identified as related to muscle or joint involvement, thus mimicking other common clinical conditions. The occurrence of fractures could highly help in the diagnosis, but a low bone mineral density at presentation may be lacking in some patients [2]. Laboratory findings suggestive of oncogenic osteomalacia are hypophosphatemia associated with renal wasting of phosphate, and inappropriate normal or low levels of 1,25OH vitamin D despite normal or mildly elevated parathyroid hormone values. These features are directly related to the effect of FGF-23, which inhibits on one hand tubular phosphate reabsorption, and on the other 1α-hydroxylase activity [3]. However, serum phosphate is frequently not included in routine blood chemistry testing, and hypophosphatemia, when detected, is frequently not regarded as relevant in the clinical judgment. Moreover, renal phosphate wasting is not always evident and it can be often revealed only after a specific evaluation, as in the case reported in this issue. Furthermore, 1,25OH vitamin D level is not routinely assessed and usually it is looked for only when a specific diagnostic hypothesis has been formulated. The dosage of circulating FGF-23 has been performed in some cases as a further help in the diagnosis of oncogenic osteomalacia. This assay however is currently not easily available in everyday clinical practice. Moreover, other phosphatonines have recently been postulated to be implicated in the pathogenesis of phosphaturic osteomalacia related to the tumor, such as fibroblast growth factor 7 [4]. Once the disease has been suspected based on clinical and laboratory findings, and after having ruled out other possible genetically determined renal phosphate-wasting syndromes due to FGF-23 excess, tumor detection is essential to confirm the diagnosis. Tumors responsible for oncogenic osteomalacia are often small, difficult to locate and slowly growing (strange tumors in strange places). Nowadays most osteomalacia-associated tumors are classified under a single histopathologic entity and referred as phosphaturic mesenchymal tumor-mixed connective tissue variant. Due to the high expression of receptors for somatostatin in most of these neoplasms, imaging techniques involving these receptors have been utilized for tumor localization. Whole-body scintigraphy with a radiolabelled somatostatin analogous (Tc-99 octreotide or In-111 pentetreotide) was the first choice in the past, but it provides only * Luigi Sinigaglia luigi.sinigaglia@gpini.it

Hand osteoarthritis (OA) is a common and potentially disabling disease, with different features from hip and knee OA so that a specific therapeutic approach is required. Evidence based recommendations for the management of hand OA were developed by the European League Against Rheumatism (EULAR) in 2006. The Italian Society for Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the EULAR recommendations for the management of hand OA. The multidisciplinary group of experts included specialists involved in the management of patients with hand OA. In order to maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were reformulated in terms of a search query and for every recommendation a systematic search was conducted updating EULAR recommendations’ review. The propositions were translated in Italian and reformulated basing on collected evidences and expert opinion. The strength of recommendation was measured for each proposition with the EULAR ordinal and visual analogue scales. The original 11 propositions of EULAR recommendations were translated and adapted to Italian context. Further evidences were collected about non-pharmacological therapies, local treatments, intra-articular injection with SYSADOA and corticosteroids, and surgery. The SIR has developed updated recommendations for the management of hand OA adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with hand OA.

Background Golimumab (GLM), a subcutaneous TNF inhibitor, has been licensed for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Data from real-life registries on long term retention rates of GLM in these diseases are scarce. Objectives To assess the 2-year retention rate of GLM in RA, PsA and AS patients from a multicentre observational cohort (the LORHEN registry). Methods We performed a retrospective analysis of data from all patients with RA, PsA and AS included in the LORHEN registry who started GLM from October 2010 to September 2015. Only patients with at least one reported visit of follow-up were included. The 2-year retention rate was calculated by Kaplan-Meier method for each disease. The risk of discontinuation between patients who received GLM as first- or second-line biotherapy was compared by a stratified log-rank test. Results Overall 410 subjects were included in the analysis: 180 patients with RA, 110 with PsA and 120 with AS. RA patients had a mean (Standard Deviation, SD) age of 54,6 (13,6) years and a mean (SD) disease duration of 9,5 (9,3) years; most of them were female (81,6%). Among them, 79 patients stopped the treatment with GLM due to inefficacy or adverse events before 24 months of treatment; the overall 2-year retention rate was 48%. GLM was given as first and second line treatment in 85 and 51 patients, with a 2-year retention rate of 49% and 53%, respectively; the comparison between first and second line treatment groups did not show any significant difference in mean survival time (p=0.724). Among PsA patients, 50% were male, with a mean (SD) age of 47,9 (12,8) years and a mean (SD) disease duration of 7,9 (6,7) years. Among them, 42 patients stopped the treatment with GLM due to inefficacy or adverse events before 24 months of treatment; the overall 2-year retention rate was 48%. GLM was given as first and second line treatment in 47 and 30 patients, with a 2-year retention rate of 66% and 54%, respectively; the comparison between first and second line treatment groups did not show any significant difference (p=0.333). SA patients had a mean (Standard Deviation, SD) age of 45,2 (12,2) years and a mean (SD) disease duration of 9,7 (10) years; 56,7% of patients were male. Among them, 33 patients stopped the treatment with GLM due to inefficacy or adverse events before 24 months of treatment; the overall 2-year retention rate was 65%. GLM was given as first and second line treatment in 51 and 42 patients, and the 2-year retention rate was of 57% and 76%, respectively; the comparison between first and second line treatment groups did not show any significant difference (p=0.127). Conclusions GLM showed a similar 2-year retention rate in first and second line treatment of patients with RA, PsA and SA in real-world data from the LORHEN registry. The 2-year retention rate was higher in SA patients than in RA and PsA patients. Disclosure of Interest None declared

Objective. To compare the power Doppler ultrasonography (PDUS) pictures of peripheral entheses in patients with psoriatic arthritis (PsA) and fibromyalgia (FM). Methods. Thirty patients with PsA and 30 with FM participating in a study aimed at identifying the clinical features that distinguish the 2 conditions underwent the PDUS assessment of 14 major peripheral entheses. All of the detected entheseal changes were recorded and scored, and the data were statistically analyzed by means of univariate analysis and receiver-operating characteristic curves. Results. Four hundred twenty entheseal sites were assessed in each group of patients. At least 1 lesion was detected in each of the patients with PsA and in 80% of the patients with FM (p = 0.01), but inflammatory changes were present in respectively 70% and 23% (p = 0.001). A cutoff point of ≥ 3 involved sites had the greatest discriminating power in the patients with PsA, who were the only patients with bony erosions. PDUS signs of plantar fascia enthesopathy and Achilles tendon inflammation were highly specific of PsA. Conclusion. PDUS assessment of the peripheral entheses distinguishes patients with PsA and patients with FM in terms of the number and distribution of the involved sites, and the presence of inflammatory changes.

Male osteoporosis in young patients is an unusual condition, always worth investigating as a possible manifestation of secondary osteoporosis. Mastocytosis is a clonal disorder of mast cells with heterogeneous presentations; when pathologic cells accumulate only in the bone marrow, vertebral fractures and systemic osteoporosis may represent the sole clinical presentation at the onset of the disease. We report on two young male patients who came to our attention because of multiple dorsal and lumbar vertebral fractures, with no other signs of systemic mastocytosis (SM). Lumbar and femoral dual x-ray absorptiometry showed reduced bone mineral density values; biochemical investigations did not report significant anomalies, suggestive of secondary osteoporosis. One of the patients underwent iliac crest bone biopsy, which was not diagnostic. A vertebral intralesional CT-guided bone biopsy was performed in both patients, which allowed the diagnosis of SM. Our experience pointed out that bone biopsy still remains the gold standard for the diagnosis of SM. However, iliac crest biopsy can be not significant because of circumscribed bone marrow involvement: in these cases only intralesional bone biopsy could be diagnostic.