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Transient osteoporosis of the hip (TOH) is usually reported in middle-aged men or during pregnancy as a benign self-limiting condition. Nevertheless, its impact on quality of life in terms of pain and disability is considerable. Also, it can lead to insufficiency fractures or, more rarely, evolve into osteonecrosis. This condition is anecdotally described in the pediatric age and very little is known about how it may affect the growing bone. We herein describe a case of TOH in a 10-year-old child treated at our pediatric rheumatology service and summarize the pediatric cases of TOH previously reported in literature. There are two points of interest in our case report, the first one being the unusual complication of TOH with a femoral physis fracture and the second the complete recovery after the off-label therapy with bisphosphonates. We suggest that interventional medical treatment could be considered in selected cases of juvenile TOH, to prevent any possible irreversible damage on the femoral physis. As far as we know, this is the first report of neridronate employment in children affected by TOH.

BackgroundRheumatoid Arthritis (RA) represents a huge burden for patients’ quality of life and there are still relevant unmet needs in its management due to uncovered patients’ needs even once sustained remission is achieved.ObjectivesThis study aimed to investigate disease burden, treatment priorities and preferences across disease phases comparing patients’ and physicians’ perspectives.MethodsConsultants or residents in rheumatology (across Academic and non-academic hospitals) and patients with RA both aged ≤40 years were reached by an anonymous online survey between November 2021 and November 2022, designed by the SIRyoung commission. For each included RA patient, demographic and clinical parameters (RA diagnosis timing, current and previous treatments) were collected. For each included physician demographic, education and professional profile details were collected.ResultsTwo-hundred seventy-four consultants or residents in rheumatology and 90 RA patients, both aged ≤40 years, completed the online survey. All Italian regions were equally represented for both physicians’ and patients’ subgroups. Considering the patients’ disease referral status, 26(28.9%) received RA diagnosis at the very early stage (≤3 months), 33(36.7%) at early stage (3-12 months) and 31(34.4%) after 12 months from symptoms’ onset. When asked for the priority in RA treatment objectives, the survey revealed a different priority among the subgroups with a higher importance given to fatigue resolution (p<0.0001) and morning stiffness reduction (p<0.0001) by patients and to radiological damage prevention (p=0.01) and disability reduction (p=0.0108) by physicians, while comparable priority was given by the 2 groups to pain relief, physical function restoration and work-ability recover (p>0.05 for all). When asked about the factors that could improve RA management, the survey revealed higher agreement scores for patients compared to physicians in educational need (p<0.0001), increase of outpatient visits and access to treatment (both p<0.0001) and use of digital apps (p<0.0001). Stratifying patients based on self-perceived disease control, 30(33.3%) were well controlled, 52(57.8%) moderately controlled and 8(8.9%) very poorly controlled. When questioned about their will to treatment modification once sustained remission status is achieved, patients showed a higher agreement of maintaining the treatment unchanged (p=0.0002) and a higher fear of modification consequences (p<0.0001) compared to physicians, mostly if not guided by the treating rheumatologist or out of established decisional algorithms.ConclusionYoung patients with RA and young rheumatologists have variable agreements on treatment aims and priority. In particular, when dealing with the sustained remission status, a shared decisional algorithm between physicians and patients is needed to reduce patients fear and improve their empowerment.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundActive sacroiliitis represent the radiological hallmark of Ankylosing Spondylitis (Ax-SPA) and manifest as low back pain accompanied by morning stiffness (MS). The pain at rest as well as MS represent the main symptoms that impair patients’ quality of life. The treatment of Ax-SPA rely on non steroidal anti-inflammatory drugs (NSAIDs), monoclonal antibodies as Anti-TNF-α, anti interluekine-17/23 and, recently, on Janus Kinase Inhibitors; such compounds modify the disease natural history and reduce inflammation, thus restoring patient’s well being and quality of life. However, despite a full treatment regimen, sometimes it is not possible to reach a low disease activity or remission.ObjectivesIn rheumatological practice, corticosteroids (GCs) injections are successfully exploited in the every-day scenario to treat oligo-articular inflammatory disorders. In this context, we decided to evaluate the long-term efficacy of ultrasound-guided sacroiliac joint injections (US-SIJIs) of GCs in the treatment of active sacroiliitis and to understand whether local therapy has a role in the management of active sacroiliitis.MethodsWe enrolled patients affected by Ax-SPA with active sacroiliitis from our outpatient clinic. Some were treated with an US-SIJI when starting a biological disease modifying rheumatic drug (bDMARD) while others were treated with conventional therapy (bDMARD + NSAIDs) and used as controls. Variables such as age, gender, disease duration, type of bDmard, visuo-analogic pain scale (VAS) and MS were collected at baseline. VAS and MS were collected at each follow up visit that were scheduled at 24 and 48 hours, then after 7 days, 14 days, 1, 3, 6, 9 and 12 months. Each patient treated with SIJI received an explanation of the technique and informed written consent was obtained; subsequently, each patient was invited to lay pronated on a medical bed while a musculoskeletal sonographer individuated sacroiliac joints (SIJ) with a convex probe and demarcated the needle entry site with a dermographic pen. A sterile hood was put on the probe, the skin was accurately disinfected, then a 2,5 mL syringe was loaded with 40 mg of triamcinolone acetonide and a spinal needle of 22 gauge was used to reach SIJ. Each SIJI involved crossing the posterior sacroiliac ligament and each injection was carried out following real time the needle trajectory. All of the US-SIJI patients received a bilateral SIJI. The statistical analysis exploited descriptive statistics to define baseline anthropometric variables, ANOVA test and Test U of Mann were used to compare the means between groups. The p<0,05 was considered significant. The present study was conducted in accordance to the Declaration of Helsinki and was approved by the local ethical committee.ResultsWe enrolled 33 subjects: 12 received an US SIJI and 21 were treated with a standard therapy according the most up-to-date recommendations. Both groups were comparable for age and VAS pain at baseline. In US-SIJI group after 24 h was documented a significant reduction of VAS pain that lasted up to 1 year displaying always a persistent significant lower value compared to baseline; in SIJIs group the higher VAS pain reduction from baseline was documented after 7 days (- 71%); in the control group VAS pain reduction reached significance after 3 months from baseline and the higher VAS pain reduction was documented at end of study (-32 %). In the US-SIJI group MS dropped significantly after two weeks from SIJI while in the controls after 3 months from baseline. At the end of study the patients treated with US-SIJI displayed a higher VAS pain (-50 % in SIJIs vs. -32 %, p<0,05) as well as MS reduction compared to controls (- 71 % in SIJIs vs – 42%, p<0,05). Any serious adverse event was recorded.ConclusionThe US-SIJIs represent a safe and useful tool to control the symptoms of an active sacroiliitis and they should be performed concomitantly to the beginning of a bDMARD therapy to guarantee a rapid restoration of patients’ quality of life.Figure 1.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

No clear-cut guidelines exist about the use of diagnostic procedures for idiopathic inflammatory myopathies (IIM) and only scanty and conflicting data report the use of ultrasound (US). We aimed to assess if grey-scale (GS) and Power Doppler (PD) US, graded with a 0-3-points-scale, may be a reliable tool in a cohort of patients affected by IIM. We prospectively collected, since July to October 2020, all patients referred to Vasculitis and Myositis clinic, Rheumatology Unit, University of Siena, for suspected IIM, as well as patients with a previous, definite diagnosis of IIM and evaluated during follow-up or referred from other centers for a second opinion. All patients underwent US examination of both thighs in axial and longitudinal scans. Edema and atrophy, both assessed in GS, and PD, were graded with a 0-3-points-scale. Spearman test was used to identify the correlations between US and clinical and serological variables. A total of 18 patients was included. Four of them were evaluated twice, at baseline and within 3 months of therapy. Muscle edema was found to be directly correlated with physician global assessment (PhGA), serum myoglobin and PD and negatively with disease duration. PD score was positively correlated to PhGA and negatively to disease duration. Muscle atrophy directly correlated with Myositis Damage Index and patients' age. The single-thigh sub-analysis evidenced a direct correlation between PD score and Manual Muscle Test. In our cohort, we found that edema and PD are strictly related to early, active myositis, suggesting that an inflamed muscle should appear swollen, thickened and with Doppler signal. Conversely, muscle atrophy reflects the age of the patient and the overall severity of the disease. Such findings shed a new, promising, light in the role of US in diagnosis and monitoring of IIMs. None declared [Display omitted] Table 1Siena Myositis Ultrasound Grading Scale (SMUGS).Grey-scale edemaGrey-scale atrophyPower Doppler0Normal muscle echotexture with hyperechoic septa and hypoechoic muscle fibers, conserved thickness.Normal muscle echotexture, with hyperechoic septa and hypoechoic muscle fibers, conserved thickness.No PD signal.1Focal hypoechoic areas, where septa are less evident. Conserved thickness.Focal heterogeneously hyperechoic areas, where septa are thicker and more evident, and muscle fibers are thinner. Conserved muscle thickness.One or two PD signals in at least one muscle (PD vascular spots, small vessels of homogenous diameters, vessel diameters approximately not superior to fibrous intramuscular septa)2Diffuse and heterogeneous hypo echogenicity (rectus femoris as hypoechoic or more than vastus intermedius), septa diffusely less evident. Conserved thickness.Diffuse and heterogeneously hyperechoic muscle, with thicker septa and thinner muscle fibers. Conserved muscle thickness.More than 2 PD signals for each muscle (as vascular spots, small vessels of homogenous diameters, vessel diameters approximately not superior to fibrous intramuscular septa).3Diffuse and heterogeneous hypo echogenicity (rectus femoris as hypoechoic or more than vastus intermedius), septa diffusely less evident. Increased thickness (rectus femoris became thicker than vastus intermedius).Diffuse and heterogeneously hyperechoic muscle, with thicker septa and thinner muscle fibers. Reduced muscle thickness.More than 2 PD signals for each muscle with larger diameter of the vessel (at least superior to fibrous intramuscular septa), or vessels with different diameters or branched vessels.

Background:Polymyalgia rheumatica (PMR) is the most common inflammatory disorder of elderly; an association with environmental triggers and deregulated immune response has been described.Objectives:The aim of this study was to investigate the presence of environmental triggers before the onset of PMR and its association to a particular subset of disease.Methods:The database of 58 consecutive PMR patients recruited from a single rheumatology secondary care setting was retrospectively analyzed to investigate the frequency of environmental triggers and correlations with clinical characteristics. Patients underwent multidistrict ultrasound examination of both proximal and distal sites. Laboratory tests were repeated after one month from first visit, when steroids were started, and about every three months during follow-up (for at least 24 months)Results:Fifteen PMR patients (26%) described a connection with environmental agents: six PMR patients reported a vaccination, 3 an upper respiratory tract infection and 1 pneumonia before the onset of disease. Five patients reported seasonal influenza as trigger of PMR. The model of multivariate linear regression which better predicted a shorter time to normalize inflammatory reactants (R squared 27,46%, p=0,0042) comprised the presence of an environmental trigger and a higher CRP. A linear regression analysis confirmed an inverse correlation between CRP at onset ant time to normalize inflammatory reactant (r= -0,3031, p=0,0208). A significant correlation was demonstrated between presence of environmental trigger and shorter time to normalize inflammation (r=-0,5215, p<0,0001), lesser frequency of gleno-humeral synovitis on US (r=-0,3774, p=0,0038).Conclusion:Our work describes a correlation between environmental triggers in PMR and higher CRP at diagnosis and faster response to therapy. We may suppose that these patients belong to a more specific subtype of PMR, in whom external stimuli, such as vaccinations or infections, may lead to a deregulated response within the context of an impaired immune and endocrine system. We recommend a systematic research of previous infections or vaccination in recent onset PMRDisclosure of Interests:None declared

Not available.Not available.

BackgroundAlkaptonuria (AKU) is an ultra-rare inborn error of metabolism due to a deficient activity of homogentisate 1,2-dioxygenase. Patients suffer from a severe arthropathy. Evidence was provided on the presence of a secondary serum amyloid A (SAA)-based amyloidosis[.1Here a complete microscopic and ultrastructural analysis of different AKU tissues, taken from six differently aged patients, is presented.ObjectivesSAA amyloidosis is a complication in AKU[,2 making the detection of amyloid deposits at an early phase,important for treatment[.3 We present a study of tissues from patients of different age and relevance of symptoms, providing a detailed overview of AKU amyloidosis.MethodsDifferent tissues were obtained from a cohort of 6 AKU patients: 4 M (63,68,42,44 y) and 2 F (66,71 y) with different severity of symptoms. Histology and amyloid were investigated. A complete microscopic and ultrastructural analysis is presented and patient features as radiological examination, mild-to-severe degenerative changes as joint space narrowing, cartilage irregularities, sub-chondral sclerosis or peripheral osteophytes and linear intervertebral disk calcifications were reported. SAAserum levels and other serological markers were measured too.Specimens were analysed by Congo Red, Immunofluorescence, Transmission Electron Microscopy.ResultsThe analysis of all AKU specimens confirmed the massive presence of amyloid fibrils even in young patients. Alterations in collagen composition, strictly associated to amyloid bundles deposition, were observed especially in labial salivary gland, cartilage, tendons and infrapatellar fat pad. Histological analysis showed depletion of glycosaminoglycans in young patients, whereas, at light microscopy, calcification and fibrillation were observed only in elderly patients. Immunofluorescence assessed undoubtedly the presence of SAA in amyloid deposits in AKU, and we reported for the first timethe finding of amyloid deposition in young AKU patients and in less common regions.ConclusionsWe provide the first detailed overview of amyloidosis in AKU. Overall, our findings depicted a novel biological framework underlining the pathological role of amyloidosis in several AKU tissues. Furthermore, we found that degradation of extra-cellular matrixin AKU is not limited to elderly.The clinical burden of AKU may notably increase, since amyloidosis was foundeven in young AKU patients, whereas degeneration of cartilage and tendons was limited to older subjects.References[1] Millucci L, et al. J Inherit Metab Dis2015Sep;38(5):797–805.[2] Braconi D, et al. Free RadicBiol Med2015Nov;88(Pt A):70–80.[3] Millucci L, et al. DiagnPathol. 2014Sep 26;9:185.Disclosure of InterestNone declared

BackgroundThe pathogenesis of Ochronosis, the musculoskeletal manifestation of alcaptonuria (AKU) is still unclear. The joint damage usually described is similar to osteoarthritis, but in some cases the spinal involvement could resemble spondiloarthritis (SpA). These findings suggest that inflammatory changes could be prevalent in some cases while degenerative aspects could be dominant in others.ObjectivesTo evaluate the prevalence of inflammatory changes in peripheral joints and enthesis of a cohort of patients affected by AKU.MethodsConsecutive patients with definite diagnosis of AKU referred to our clinic from 2014 to 2017 were enrolled. All patients underwent an ultrasound (US) exam of the metacarpo-phalangeal joints (MCP), proximal interphalangeal joints (PIP), radiocarpal/mid carpal joints, elbow, gleno-humeral, hip, knee, ankle and metatarso-phalangeal (MTP) joints bilaterally; flexor and extensor tendons of fingers and wrists and the ankle tendons were also examined. Further, the enthesis of the rotator cuff of the shoulder, triceps, quadriceps, patellar and Achilles tendons were assessed. Joints and tendons with a synovial sheath were assessed for effusion, synovial hypertrophy and power Doppler (PD) signal while enthesis were evaluated for the presence of PD signal, enthesophytes and calcifications. All the US lesions were scored using a dichotomous scale (presence/absence). All US exams were performed by an expert sonographer blind to clinical history, using an Esaote MyLab70 scanner equipped with high resolution linear probes.ResultsWe enrolled 19 patients (11 women) with a mean age of 53 yo (SD ±14,69). Only 2 patients didn’t show inflammation at any joint or tendon. The most involved joint was the knee (11/19), while regarding enthesis, the Achilles tendon (4/19) and the distal patellar tendon insertion were the most frequently involved (6/19). The mean number of joints with effusion or synovial hypertrophy was respectively equal to 2,47 (median 2, range 1–8) and 1,84 (median 2, range 1–7), while 0,21 joints (median 0, range 0–2) presented also PD. The mean of the exudative tenosynovitis was 0,47 (median 0, range 0–3), while for proliferative tenosynovitis was 0,42 (median 0, range 0–2). The PD signal in tendons with sheaths was rare (mean 0,16, median 0, range 0–2). Finally, the mean number of enthesis with PD was 0,95 (median 0, range 0–7) while the mean value was 0,37 (median 0, range 0–3) for enthesophytes and 2,63 (median 1, range 0–9) for calcifications.ConclusionsThe pathological processes that lead to the typical joint damage in ochronosis are not yet completely clarified. The results of this study showed that articular inflammation is common in these patients, sometimes associated with enthesis involvement. The role of inflammation should be further addressed as could be a new therapeutic target for this disease.Disclosure of InterestNone declared

BackgroundNeutrophil extracellular traps (NETs) are web-like structures, composed of nucleic acids, histones and granular enzymes, including myeloperoxidase and elastase, that have a physiological crucial role in innate immunity response by trapping microbes. In addition, NETs have been identified as regulators of many inflammatory and autoimmune disorders, including crystal-induced arthritis.[1,2] In particular, a key role in the pathogenesis of gout flares has been postulated for NETs. During gout attacks, NET aggregates should package MSU crystals with a concomitant degradation of proinflammatory cytokines, leading to the rapid resolution of the inflammatory phase.[3]ObjectivesTo evaluate NET expression in synovial fluid from acute CPPD arthritis and to compare NET release between acute MSU and CPPD arthritis.MethodsSynovial fluid was collected from patients with active gout or pseudogout attack (n=5 for each group) and immediately centrifuged (805 rad) to separate cells from supernatant.Polymorphonuclear leukocytes were counted and immediately processed for morphological evaluation under transmission electron microscopy (Zeiss EM 109; 4000x). NET expression was evaluated by fluorescence microscopy using SYTOX Green (Life Technologies) and neutrophil elastase specific antibody (ABCAM). Fluorometric quantification of NET components, DNA and neutrophil elastase, was performed in supernatant (Cary Eclipse Varian; exc/em 503/526). Results were normalized to cells/mm3. Peripheral blood neutrophils from healthy donors stimulated with PMA were used as positive controls whereas PMA-untreated neutrophils were used as negative ones.All the experiments were performed according with Helsinki guidelines.ResultsExtracellular material morphologically compatible with NETs was observed by electron microscopy in samples from both acute MSU and CPPD arthritis. NET structures were confirmed by the presence of extracellular DNA and neutrophil elastase at immunofluorescence.Fluorometric quantification of extracellular DNA and neutrophil elastase showed an increased NET release in both gout and pseudogout samples compared with negative controls (p<0.01). No significant differences in NET release were measured between acute MSU and CPPD arthritis samples.ConclusionsBeyond confirming NETs in acute MSU arthritis, we have evidence of NET release in synovial fluid from acute CPPD arthritis. Our preliminary data suggest that the release of NETs could be a common physiophatological pathway to both crystral induced arthropaties.Disclosure of InterestNone declared

BackgroundAlkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces an ochronotic pigment of unknown composition. The role of proteins has been hypothesized as additional causal factors of ochronosis. Evidence has been provided on the presence of serum amyloid A (SAA) in AKU tissues (1-5), which allows classifying AKU as a secondary amyloidosis (6).ObjectivesTo collect direct and indirect indications of secondary amyloidosis in AKU patients and find a correlation between serum levels of inflammation and oxidative stress markers and clinical parameters.MethodsIn a cohort of 15 Italian AKU ochronotic patients an analysis for amyloid in different tissues has been carried out, adopting Congo Red, Thioflavin T and SAA-immunofluorescence staining. Tissues were also probed for the presence of inflammation and lipid peroxidation. Clinical parameters as osteopenia of the hip, kyphosis, scoliosis, fractures, disc disease of the thoracic and lumbar spine and joint disease as assessed by MRI or X-ray, range of joint and spine motion were assessed. Patient sera were analysed for inflammation (SAA, CRP) and oxidative stress (AOPP, TAC) markers.ResultsAmyloid, ochronosis, lipid peroxidation, inflammation, tissue calcification, cell death and tissue degeneration were found to co-localize in AKU. These findings are in very good agreement with high plasma SAA levels and other clinical and biochemical diagnostic parameters in AKU patients and related to HGA-induced oxidative stress.ConclusionsAKU is a complicating inflammatory multisystemic disease, where any body district expressing HGD may be affected by ochronosis and related AA amyloidosis. A chronic inflammatory status experienced by patients, paralleled by inadequate antioxidant defences, may thus promote the synthesis of amyloidogenic proteins ultimately leading to secondary amyloid deposition, which is in turn cytotoxic, pro-inflammatory and pro-oxidant, further complicating AKU pathogenic lesions and clinical deterioration of AKU patients.ReferencesL. Millucci, et al. Secondary amyloidosis in an alkaptonuric aortic valve. Int J Cardiol. 2014 1; 172: e121–e123.A. Spreafico et al. Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria. Rheumatology (Oxford) 2013 52: 1667–1673.L. Millucci et al. Diagnosis of secondary amyloidosis in alkaptonuria. Diagn Pathol. 2014; 9: 185L. Millucci, et al. Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient. Mediators Inflamm. 2014; 258471.L. Millucci et al. Chondroptosis in alkaptonuric cartilage. J Cell Physiol. 2015 23:1148-57.L. Millucci et al. Alkaptonuria is a novel human secondary amyloidogenic disease. Biochim Biophys Acta 2012 1822: 1682–1691.Disclosure of InterestNone declared