Chronic Arthropathy Research Articles

Caffeic acid and ellagic acid ameliorate adjuvant-induced arthritis in rats via targeting inflammatory signals, chitinase-3-like protein-1 and angiogenesis

Rheumatoid arthritis (RA) is a chronic inflammatory arthropathy that principally attacks the joints. The present study aimed to explore the potential anti-arthritic effects of caffeic acid and ellagic acid in adjuvant-induced arthritis, compared to celecoxib. The current study also explored the underlying molecular mechanisms e.g., pro-inflammatory signals including chitinase-3-like protein-1 (CHI3L1); a glycoprotein that correlates with RA joint destruction besides angiogenesis, oxidative stres and apoptosis. Interestingly, caffeic and ellagic acids attenuated the severity of arthritis with comparable efficacy to celecoxib. Both agents effectively mitigated paw edema and inflammatory cell infiltration and protected the joint tissues against pannus formation along with cartilage and bone destruction. Notably, they also lowered the paw expression of NF-κB and the downstream effector CHI3L1 and its synthesis inducer IL-1β. They also lowered the levels of the tissue remodeling factor MMP-9 and the angiogenic signal VEGF in rat paws. Both agents also suppressed serum oxidative stress via diminishing lipid peroxides and nitric oxide together with augmentation of reduced glutathione in arthritic animals. Regarding apoptosis, they attenuated paw caspase-3 levels, favoring cell survival. Together, these favorable findings may advocate the use of caffeic and ellagic acids as adjunct modalities for the management of RA to mitigate joint damage.

Thrombin Generation As a Promising Biomarker for the Prediction of Bleeding Phenotype in Patients with Non-Severe Hemophilia

Background: Non-severe hemophilia A and B account for 50% of patients with hemophilia, in which factor level does not consistently correlate with bleeding phenotype. Clinical decision-making in regards to timely prophylaxis initiation and tailored surgical management could be informed by a biomarker that is more predictive of bleeding phenotype. We hypothesized that a global method to assess clotting potential, such as thrombin generation (TG), is more predictive of bleeding phenotype than factor level.Objectives: Determine the ability of TG, as compared to standard baseline factor activity, to differentiate bleeding phenotype severity in patients with non-severe hemophilia.Methods: Subjects were recruited from two hemophilia treatment centers (HTCs): Rady Children's Hospital San Diego (RCHSD) and Center for Inherited Blood Disorders (CIBD). Subjects were eligible for enrollment if they were at least one year of age and had a diagnosis of non-severe congenital hemophilia A or B, or were genetically confirmed or suspected female carriers. All enrolled patients or their parents completed the standardized, self-administered pediatric bleeding questionnaire (Self-PBQ) or bleeding assessment tool (Self-BAT). Clinical and laboratory information were extracted from the medical chart, including age at diagnosis, bleeding event history, past surgical history, treatment history and factor VIII or IX gene analysis.Validation of self-reported bleeding symptoms was performed using chart-derived data. Bleeding phenotype was assessed using standard calculation of the bleeding score, as defined by the respective validated self-reported tools. For the purpose of this analysis, we defined a high bleeding score as 13 or more, while a low bleeding score was defined as 12 or less. After a washout period of 5x the standard half-life of the administered factor product, blood samples were collected at time of enrollment. Platelet poor plasma was obtained according to a strict protocol to minimize pre-analytical variables. TG was measured by means of the calibrated automated thrombogram, with three different reagents: low (1 pM of tissue factor [TF]), regular (5 pM of TF) and High (20 pM of TF). The following TG parameters were evaluated: Peak TG (Peak), estimated thrombin potential (ETP) and velocity index (VI).Results: Eighty-one subjects were enrolled. The median age of our cohort was 15.6 years (IQR 21.2, range 4.9 - 59.8), with a slight female predominance (51%) due to inclusion of female carriers. The median follow-up period at the HTC was 5.3 years (IQR 7.5 years), with the majority having follow-up for at least three years. Enrolled patients had the following diagnoses: mild hemophilia A (70%), mild hemophilia B (3%), moderate hemophilia A (13%), moderate hemophilia B (3%), hemophilia A carriers with normal factor VIII levels (10%) and hemophilia B carriers with normal factor IX levels (1%). Median age at diagnosis was 8 years (IQR 26.3, range 0.1 - 56.1), which strongly correlated lower baseline factor activity (r=0.573, p-value < 0.0001). The median baseline factor activity was 21% (IQR 26, range 2 - 249). Factor exposure occurred in 46% of patients (n=37), of which 5 patients were on prophylaxis at time of enrollment. Chronic arthropathy was present in 2 patients (one with mild hemophilia A and one with moderate hemophilia A) and none of the patients had a history of an inhibitor.The majority of patients had a low bleeding score (74% vs. 26%). Baseline factor level and TG values obtained with regular reagent (5 pM of TF) showed significant correlation with bleeding score (r = -0.229 to -0.237, p-value < 0.05), while values obtained with other reagents did not show a significant correlation. Sensitivity/specificity analysis revealed the following optimal cutoff values for differentiating between bleeding severities, as obtained from TG with regular reagent: ETP (<1240 nM min), Peak (<130 nM) and VI (<23 nM/min), with analysis results as shown in Table 1.Conclusion: Even though both TG and baseline factor level had comparable correlation with bleeding severity, all TG values with 5 pM TF showed a much higher sensitivity outcome and greater ability to differentiate between bleeding severities in this population. This approach shows potential for predicting bleeding severity in patients with non-severe hemophilia and should be validated in long-term prospective studies. [Display omitted] DisclosuresNossair:Novo Nordisk: Other: Conference - Haemophilia Acadamy; Novo Nordisk: Research Funding. Hwang:BPI: Consultancy; Bayer: Consultancy; Hema Biologics: Consultancy; Shire: Consultancy; Bioverativ: Other: PI in clinical research study. Thornburg:ATHN: Research Funding; Bayer Pharmaceuticals: Research Funding; Biomarin: Consultancy; CSL Behring: Research Funding; Bioverativ: Consultancy; Genentech: Speakers Bureau; Octapharma: Research Funding; NovoNordisk: Research Funding; Shire: Research Funding; Johns Hopkins All Children's Hospital: Research Funding; Bluebird Bio: Consultancy.

Bilateral, Simultaneous Total Knee Replacement (TKR) Surgery for Hemophilia a with Eloctate (Extended Half Life Product)—A Feasible and Cost Effective Approach

Abstract INTRODUCTION: The majority of bleeds experienced by people with Haemophilia occur into the joints or muscles.The joints most frequently involved are the knees, ankles, and elbows. The consequences of recurrent bleeding into a joint leads to chronic hemophilic arthropathy. Knee arthropathy is crippling situation affecting Quality of Life (QOL) for Patient with Hemophilia (PWH).With the advent of the availability of Clotting Factor Concentrates (CFC), Total Knee Replacement (TKR) can now be performed safely. TKR is performed using Total 2000IU/kg of Plasma Derived (PD) or Recombinant CFC. Literature recommends 1000-1200IU/kg of Total Eloctate for TKR. METHODS: Aim for feasible, safe &amp; cost effective CFC replacement policy for TKR 1) Use lower dose Eloctate during TKR 2) Perform Simultaneous Bilateral TKR Patients and Methods: Total 24 Severe Hemophilia A patients underwent 48 bilateral, simultaneous TKR. Age range was 28-51 years. Pre-operative 50IU/Kg Eloctate was infused. Pre-operative FVIIIc Level was median 108IU/kg (86-126 IU/dl). Post-operative Eloctate replacement was 40-50IU/kg once daily till day 5, then 30IU/kg once daily till Day15. FVIIIc assay was monitored at least once daily till day 10. Dose was tailored according to FVIIIc levels. Trough FVIIIc level was maintained above 60iu/dl for first 5 days. Average duration of surgery was 4 hours. Drains were removed after 48 hours. LMWH Thromboprophylaxis &amp; physiotherapy was started from post-operative Day 2. Clips were removed on Day 14. Eloctate was received through Humanitarian Aid Program of WFH. RESULTS: Total of 48 bilateral, simultaneous TKR were performed on 24 patients. 23 patients had no significant intra or post-operative bleeding &amp; no transfusion support was needed . One patient underwent pseudo tumour excision and TKR in the same sitting &amp; required extra 50IU/kg Eloctate+ 8 packed red cells + 8 FFP + 10 Cryoprecipitate intra operative during excision of Pseudo Tumour for total blood loss of 2200 ml as expected . He also experienced no post-operative bleeding till discharge. No wound or prosthesis infection was noted. Prosthesis survival was 100%. Total Eloctate used was 510- 640 IU/kg over 14 days. DISCUSSION: There was no excess bleeding in our patients. The results from our assessment are quite similar to the overall prosthetic survival rates reported for TKAs performed on patients without hemophilia.In our study there were no periprosthetic infections reported. Other studies have showed rates of periprosthetic infection after primary TKA in patients with hemophilia are much higher (up to 11%). Late infection is a major concern after TKA in patients with hemophilia, an important factor is the high rate of HIV-positive patients (3).Another important complication of TKA surgery is aseptic loosening of the prosthesis. Aseptic loosening was not found in any of our patients. Rates of this complication increase over follow-up (4). In our data the ROM improved and flexion contracture reduced significantly after arthroplasty following the scheduled physiotherapy.As mentioned in an article by Schild FJA et al the Median amount of CFC (Plasma derived &amp; recombinant) used for multi-joint procedure per patient was 57,680 IU; in another retrospective study by A Thes et al where the median CFC (Plasma derived &amp; recombinant) usage per patient was 1,500 IU/kg; whereas we used Total Eloctate of 510- 640 IU/kg and hence reduced CFC usage compared to western protocol. CONCLUSIONS : Low dose Eloctate replacement is safe and cost effective for TKA in PWH. Bilateral TKA in same sitting is feasible and increases cost effectiveness in PWH. Thrombo-prophylaxis with LMWH can be done safely in PWH. Bleeding events did not increase with low dose Eloctate &amp; LMWH. At these doses, total Eloctate replacement was 40-50% lower than previously reported for TKR surgery for PWH. Our protocol offers a cost effective and safe option in resource constraint countries. Disclosures No relevant conflicts of interest to declare.

Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune arthropathy characterized by synovial hyperplasia leading to functional impairment. Although the exact cause of RA is unknown, there is evidence suggesting the role of T cell subtypes in the pathogenesis of RA. Conventional therapy in some RA patients is associated with mild or severe side effects, and resistance of some patients has been reported to these types of therapy. The therapeutic potential of mesenchymal stem cells (MSCs) introduced them as a novel therapeutic choice for the treatment of rheumatic diseases. The aim of our study was to evaluate the effects of intravenous administration of autologous bone marrow-derived MSCs on the immunological, clinical and para-clinical factors such as regulatory T cells, Th17 cells, CD8+ T cells, CD4+ T cells, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), visual analogue scale (VAS), ESR, C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with refractory RA. Nine refractory RA patients with no other rheumatologic disorders were included in this study. All patients received a single intravenous dose of 1 × 106 autologous bone marrow-derived MSCs/kg, and were followed up at 1, 6 and 12 months after injection of MSCs. We found a significant decreasing trend in Th17 percentage and geometric mean fluorescence intensity for IL-17A following injection of MSCs at 12 months compared to the time point zero. Furthermore, a significant increase in regulatory T cells percentage was observed at the end of the first month after the intervention. DAS28-ESR decreased significantly at 1 and 12 months after MSC therapy. VAS score showed a significant decreasing trend during the follow-up periods. No significant difference was found for serum CRP and anti-CCP levels after the intervention. In conclusion, our data indicated that clinical symptoms were significantly ameliorated following the intravenous injection of autologous bone marrow-derived MSCs to the patients with refractory RA.

ASSOCIATION OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY IN A SAMPLE OF ADULT PATIENTS WITH PSORIASIS AND PSORIATIC ARTHROPATHY

Objective: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy commonly associated with psoriasis, a large number of patients with PsA that has persistent inflammation may develop progressive joint damage and disability and have reduced life expectancy. This study aims to determine the associations of anti-cyclic citrullinated peptide (CCP) antibodies in adult patients with psoriasis and PsA.Methods: A case–control study was conducted at Baghdad teaching hospital, Units of Rheumatology and Dermatology, during the period from December 2016 to April 2017 including three groups; 40 patients with psoriasis, 40 patients with PsA fulfilling the CASPAR classification criteria, and 40 healthy control persons.Results: Two patients with psoriasis (5%) and 10 patients with PsA (25%) were seropositive for anti-CCP antibodies (ACPA). Healthy controls were negative for anti-CCPA. Regarding ACPA positivity, a significant difference was found between those three studied groups (p&lt;0.001) and there was a significant difference between positive and negative ACPA in PsA patients regarding disease activity score (p=0.044).Conclusion: Positive ACPA were found more significant with PsA than in patients with psoriasis as well as associated with higher disease activity.

Bioinformatics analysis to identify key genes and pathways influencing synovial inflammation in osteoarthritis.

Osteoarthritis (OA) is a chronic arthropathy that occurs in the middle-aged and elderly population. The present study aimed to identify gene signature differences between synovial cells from OA synovial membrane with and without inflammation, and to explain the potential mechanisms involved. The differentially expressed genes (DEGs) between 12 synovial membrane with inflammation and 12 synovial membrane without inflammation from the dataset GSE46750 were identified using the Gene Expression Omnibus 2R. The DEGs were subjected to enrichment analysis, protein-protein interaction (PPI) analysis and module analysis. The analysis results were compared with text-mining results. A total of 174 DEGs were identified. Gene Ontology enrichment results demonstrated that functional molecules encoded by the DEGs primarily had extracellular location, molecular functions predominantly involving ‘chemokine activity’ and ‘cytokine activity’, and were associated with biological processes, including ‘inflammatory response’ and ‘immune response’. The Kyoto Encyclopedia of Genes and Genomes results demonstrated that DEGS may function through pathways associated with ‘rheumatoid arthritis’, ‘chemokine signaling pathway’, ‘complement and coagulation cascades’, ‘TNF signaling pathway’, ‘intestinal immune networks for IgA production’, ‘cytokine-cytokine receptor interaction’, ‘allograft rejection’, ‘Toll-like receptor signaling pathway’ and ‘antigen processing and presentation’. The top 10 hub genes [interleukin (IL)6, IL8, matrix metallopeptidase (MMP)9, colony stimulating factor 1 receptor, FOS proto-oncogene, AP1 transcription factor subunit, insulin-like growth factor 1, TYRO protein tyrosine kinase binding protein, MMP3, cluster of differentiation (CD)14 and CD163] and four gene modules were identified from the PPI network using Cytoscape. In addition, text-mining was used to identify the commonly used drugs and their targets for the treatment of OA. It was initially verified whether the results of the present study were useful for the study of OA treatment targets and pathways. The present study provided insight for the molecular mechanisms of OA synovitis. The hub genes and associated pathways derived from analysis may be targets for OA treatment. IL8 and MMP9, which were validated by text-mining, may be used as molecular targets for the OA treatment, while other hub genes require further validation.

Sinomenine Inhibits the Progression of Rheumatoid Arthritis by Regulating the Secretion of Inflammatory Cytokines and Monocyte/Macrophage Subsets.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy associated with articular damage and attendant comorbidities. Even although RA treatment has advanced remarkably over the last decade, a significant proportion of patients still do not achieve sustained remission. The cause of RA is not yet known despite the many potential mechanisms proposed. It has been confirmed that RA is associated with dysregulated immune system and persistent inflammation. Therefore, management of inflammation is always the target of therapy. Sinomenine (SIN) is the prescription drug approved by the Chinese government for RA treatment. A previous study found that SIN was a robust anti-inflammation drug. In this study, we screened the different secretory cytokines using inflammation antibody arrays and qRT-PCR in both LPS-induced and SIN-treated RAW264.7 cells followed by evaluation of the ability of SIN to modulate cytokine secretion in a cell model, collagen-induced arthritis (CIA) mouse model, and RA patients. Several clinical indexes affecting the 28-joint disease activity score (DAS28) were determined before and after SIN treatment. Clinical indexes, inflammatory cytokine secretion, and DAS28 were compared among RA patients treated with either SIN or methotrexate (MTX). To explore the mechanism of SIN anti-inflammatory function, RA-associated monocyte/macrophage subsets were determined using flow cytometry in CIA mouse model and RA patients, both treated with SIN. The results demonstrated that SIN regulated IL-6, GM-CSF, IL-12 p40, IL-1α, TNF-α, IL-1β, KC (CXCL1), Eotaxin-2, IL-10, M-CSF, RANTES, and MCP-1 secretion in vivo and in vitro and reduced RA activity and DAS28 in a clinical setting. Furthermore, SIN attenuated CD11b+F4/80+CD64+ resident macrophages in the synovial tissue, CD11b+Ly6C+CD43+ macrophages in the spleen and draining lymph nodes of CIA mice. The percentage of CD14+CD16+ peripheral blood mononuclear cells was reduced by SIN in RA patients. These data indicated that SIN regulates the secretion of multiple inflammatory cytokines and monocyte/macrophage subsets, thereby suppressing RA progression. Therefore, along with MTX, SIN could be an alternative cost-effective anti-inflammatory agent for treating RA.

Calcium crystal deposition diseases - beyond gout.

The most common types of calcium-containing crystals that are associated with joint and periarticular disorders are calcium pyrophosphate dihydrate (CPP) and basic calcium phosphate (BCP) crystals. Several diverse but difficult-to-treat acute and chronic arthropathies and other clinical syndromes are associated with the deposition of these crystals. Although the pathogenic mechanism of calcium crystal deposition is partially understood, much remains to be investigated, as no drug is available to prevent crystal deposition, permit crystal dissolution or specifically target the pathogenic effects that result in the clinical manifestations. In this Review, the main clinical manifestations of CPP and BCP crystal deposition are discussed, along with the biological effects of these crystals, current therapeutic approaches and future directions in therapy.

Manual and educational therapy in the treatment of hemophilic arthropathy of the elbow: a randomized pilot study

BackgroundElbow arthropathy is characteristic in patients with hemophilia. Arthropathy is manifested by decreased range of motion, pain, loss of strength and muscular atrophy, and axial changes. The objective is to evaluate the safety of two physiotherapy programs combining manual therapy and home exercises with educational sessions in patients with hemophilic elbow arthropathy.MethodsThis is a randomized study with 27 patients with elbow hemophilic arthropathy with a mean age of 34.48 (SD: 12.99) years, were randomised to Manual Therapy group, educational group and control group. The physiotherapy programmes were: manual therapy through joint traction, passive muscles stretching and proprioceptive neuromuscular facilitation; and educational sessions and daily home exercises. The study lasted for twelve weeks, with two sessions a week in manual therapy group and one session every two weeks with daily home exercises in educational group. The variables measured were range of motion of elbow, biceps strength, circumference of arm, and elbow pain.ResultsThe treatment with manual therapy improved the circumference of arm, flexion elbow and elbow pain. Six months later, MT group still enjoyed improved. In the educational group there were improvements, but not significant, in the measured variables.ConclusionNeither of the two physiotherapy interventions caused elbow hemarthrosis. The treatment with manual therapy improved the range of movement and circumference of arm, and lessened pain in hemophilic patients with chronic elbow arthropathy. No hemarthrosis was recorded during treatment or during the follow-up period. Larger randomized clinical trials are required to confirm the results of this study.Trial registration(NCT02198040). Registered 22 July 2014, retrospectively registered.

Systemic juvenile idiopathic arthritis and macrophage activation syndrome: update on pathogenesis and treatment.

The past decade has seen substantial progress in defining the cause and pathogenesis of the chronic childhood arthropathy systemic juvenile idiopathic arthritis (SJIA) and its related complication macrophage activation syndrome (MAS). The purpose of this review is to describe and synthesize advances in this field, particularly since 2016, with the potential to transform clinical practice. Newly developed MAS classification criteria have been further studied and validated in other diseases and populations, as well as a recently proposed score to distinguish MAS from familial hemophagocytic lymphohistiocytosis. There has also been substantial progress toward understanding the genetic underpinnings of SJIA and MAS, both through targeted study of specific genes and the results of a large genome-wide association study. The immunopathogenesis of SJIA has been further elucidated through several studies regarding the proinflammatory cytokines interleukin-18, interferon (IFN)γ, and how their interplay impacts emergence of MAS. Finally, big data studies integrating genomic information with immunophenotypes have potential to provide novel insights into disease mechanisms in SJIA. Collectively, these research advances have significant implications regarding the classification and diagnosis of SJIA and MAS, and support a next generation of biologic treatments including kinase inhibitors and targeted interleukin-18 or IFNγ blockade.

Severe Pyogenic Arthritis in a 10-Year Old Girl Due to Streptococcus dysgalactiae

Introduction: We describe the case of a 10-year-old girl with an unusually severe and complicated episode of acute septic arthritis due to Streptococcus dysgalactiae, and systematically review the literature describing osteoarticular infections with this organism. Case Presentation: A 10-year-old girl with hereditary sensory and autonomic neuropathy type 5 and chronic (Charcot) arthropathy of the right knee presented with severe swelling and warmth of the right knee associated with 2 days of fever. She was ultimately diagnosed with septic arthritis of the right knee due to S. dysgalactiae. Her subsequent clinical course was abnormally prolonged and complicated, requiring an 8-week hospitalization, 7 arthrotomies and 8 months of total antimicrobial therapy. Conclusions: Group G Streptococci, including S. dysgalactiae, are unusual causes of septic arthritis. Our patients’ clinical course was more severe than typically seen with more common osteoarticular pathogens. We conducted a systematic review of the literature on this condition, which demonstrated 7 previously reported cases of septic arthritis due to this pathogen in children, and also review the most current nomenclature and classification scheme for the organism.

Hemofilia

Hemophilia A and B are X-linked recessive diseases that are caused by gene mutations in factors VIII adan IX of the blood clotting cycle. Hemophilia C is an autosomal recessive disease caused by a mutation in factor XI, and acquired hemophilia is largely is an autoimmune process. Hemophilia A and B cannot be distinguished clinically, and severe cases can cause bleeding in the joints and lead to chronic hemophilic arthropathy. The main treatment of hemophilia is infusions of factor VIII and IX, and DDAVP in less severe cases. The main complication that can rise from the use of clotting factors is the appearance of specific inhibitor antibodies that can neutralize the work of the factors. Severe cases of hemophilia A and B by itself carries a poor prognosis, but proper treatment throught the use of clotting factors can give a very good prognosis

Haemochromatosis and Arthropathies

Arthropathy is the most common and often the earliest clinical manifestation of hereditary hemochromatosis (HH). It is difficult to treat and there is a high risk for early endoprosthetic joint replacement. Research done during the last decade shows that it is a joint disease in its own right. Clinically, there are degenerative articular changes with an atypical pattern of distribution, a crystal arthropathy (CPPD) with congenital joint swelling and synovitis like in RA. The X-ray image shows typical but not exclusive findings. In MRI, groundbreaking subchondral findings are found, especially in the large joints, and ultrasound shows inflammatory lesions in non-arthropathy patients as well. In animal experiments and pathomorphological studies of the synovial membrane, the arthropathy can be differentiated from osteoarthrits and RA. The pathophysiological significance of iron overload can be distinguished from immunohistochemical and cytogenetic investigations in chronic degenerative HH arthropathy and inflammatory-destructive arthropathy in hemophilia. By elucidating the pathophysiology, new therapeutic approaches can be formulated. In addition to colchicine, the IL-1 receptor antagonist anakinra is available for activation of the NLRP3 inflammasome by CPPD crystals and subsequent induction of IL-1β overproduction. Other manifestations include symptomatic pain therapy and intensive physiotherapy and occupational therapy. To promote further research into hemochromatosis arthropathy, the Hemochromatosis Arthropathy Research Initiative (HARI) was established in 2016.

Cardiovascular Risk Markers and Major Adverse Cardiovascular Events in Psoriatic Arthritis Patients.

Background: Psoriatic arthritis is a chronic inflammatory arthropathy that affects 14%-30% of patients with skin and/or nail psoriasis, leading to severe physical limitations and disability. It has been included in the group of spondyloarthropathy with which it shares clinical, radiologic, and sero-logic features in addition to familial and genetic relationship. Beyond skin and joint involvement, psoriat-ic arthritis is characterized by a high prevalence of extra-articular manifestation and comorbidities, such as autoimmune, infectious and neoplastic diseases. In particular, an increased risk of cardiovascular comorbidity has been observed in psoriatic arthritis patients.Methods: A systematic search was performed in the electronic databases (PubMed, Web of Science, Scopus, EMBASE) up until January 2017. Studies were included if they contained data on CV disease and/or risk factors in PsA and each article was then reviewed for quality and clinical relevance. After completing the literature search all screened literature was summarized and discussed in our study group (CaRDDs study group). All literature and comments were included in the systematic review.Results: The initial search produced 278 abstracts, which were narrowed to 83 potentially relevant arti-cles by preliminary review of the titles and by excluding review articles and case report (n = 195). Thirty articles were deemed ineligible after examining the abstracts. Full texts of the remaining 53 articles were retrieved. The majority of articles excluded were due to only providing data on patients with psoriasis or due to being not relevant to the CV risk in PsA. In the end, 32 articles were deemed eligible for this re-view.Conclusion: Psoriatic arthritis appeared significantly associated with subclinical atherosclerosis and en-dothelial dysfunction and, in turn, with an increased cardiovascular risk. Thus, patients with psoriatic ar-thritis may benefit from a periodic assessment of surrogate markers of cardiovascular risk. This could help to establish more specific cardiovascular prevention strategies for these patients

Prophylactic bypassing agent use before and during immune tolerance induction in patients with haemophilia A and inhibitors to FVIII.

The development of high-titre inhibitory antibodies (inhibitors) against factor VIII (FVIII) remains a challenge in the management of patients with haemophilia A (HA). Patients with high-titre inhibitors are more likely to experience uncontrolled bleeding, physical disability from chronic arthropathy and premature death compared with those without this complication. Immune tolerance induction (ITI), utilizing repeated infusions of FVIII, is an effective therapeutic approach to eliminating inhibitory antibodies. This strategy can eradicate FVIII inhibitors, so that FVIII-specific tolerance is induced. However, patients undergoing ITI are still vulnerable to the development of serious and/or repeated bleeding events. The efficacy of bypassing agents in preventing bleeding episodes has been widely proven in patients with HA and inhibitors to FVIII. Evidence suggests that reducing bleeding during ITI can also shorten the time to tolerance. There are concerns with the use of bypassing agents, including the cost of treatment, short half-life, management of non-responders and the risk of thrombosis. Despite these concerns, and the still limited evidence from prospective studies and consensus reports, the use of prophylaxis with bypassing agents during ITI has been gaining support. This review presents a rationale and current data supporting the use of prophylactic bypassing agents as effective and safe therapies to reduce the incidence of joint bleeding due to inhibitors and improve quality of life in patients with HA undergoing ITI.

T28. Neuropathies in haemophylics: Preliminary evaluation of four cases and literature review

Peripheral neuropathy is an uncommon complication in patients with hemophilia, usually characterized by mononeuropathies, caused by hematoma and compartmental syndrome. The femoral nerve is the most affected, but several other locations have been described. The purpose of this article is to describe four cases of peripheral nerve injury in hemophiliacs comparing with data from the literature. This is a descriptive study, carried out by reviewing the medical record of four hemophiliac patients diagnosed with peripheral nerve injury, performed at a hematology and hemotherapy center in the state of Ceara, Brazil. The literature review was performed on the PubMed platform. All four patients underwent imaging and electromyography studies. The data collected were compared with those of the literature. The first case involves a male patient, twenty-nine years old, with a massive hematoma encapsulated in the right thigh (pseudotumor), and associated with paresthesia and a sensory and motor NCS evidencing sciatic nerve involvement. The second case refers to a male patient, forty-seven years old, with chronic hemophilic arthropathy at the right elbow, presenting with tactile-painful hypoesthesia at the medial border of the hand and the fifth finger. The study of nerve conduction revealed ulnar neuropathy at the elbow. In this case, the probable pathophysiology involves the stretching of the ulnar nerve by the pronounced valgus of the elbow. The last two patients were a man of forty-two and a boy of sixteen, both with left iliopsoas hematoma, accompanied by paresthesia in the anterior and lateral aspect of the thigh. The evaluation of the sensory e motor NCS revealed the involvement of the sensory branch of the femoral nerve (saphenous) and acute denervation in quadriceps muscle on needle EMG. Even in a limited sample, the four reported cases are in accordance with the literature data. The main publications on the subject indicate the nerves of the lower limbs as the most affected ones, predominating the femoral nerve, followed by the sciatic nerve.

Public social security burden of musculoskeletal diseases in Brasil-Descriptive study.

To present data on the social security burden of diseases of the musculoskeletal system and connective tissue (DSOTC) in Brasil in 2014, and evolution of these social security expenditures between 2009 and 2014. Compilation and analysis of data on the granting of disability pensions and sickness benefits in the year 2014, available on the official website of Social Security, classified according to ICD 10. It was evaluated the evolution between 2009 and 2014, using the F test to compare the curves with the growth of the active age population (PIA). Among the 22 disease groups classified according to ICD-10, the DSOTC group led benefits grants in 2014, with 19% of the sickness benefits and 13.5% of the disability pensions. The main causes of sickness benefit and disability retirement were, respectively: dorsopathies (43.3% and 41.2%), soft tissue diseases (27.3% and 19.7%), osteoarthritis (7.6% % And 27.8%) and chronic inflammatory arthropathies (2.8% and 7.9%). In the evolution of the number of sickness benefits granted between 2009 and 2014, both INSS and DSOTC totals showed an increasing tendency (35.9 and 35.3%, respectively, with p = 0.000 for both). As for disability retirement, there was a 5.9% increase in the INSS total (p = 0.039), while for the DSOTC there was a decrease of 7.6% (p = 0.005). These data point to a progressive increase in the granting of sickness pensions and disability benefits in the country, superior to the growth of the PIA, as well as a high participation of DSOTC in these benefits.

A Beacon in the Dark: Canakinumab. A New Therapeutic Perspective in Chronic Tophaceous Gout.

Novartis Farma, Italy.

Infrared Thermography as a Non-Invasive Tool to Explore Differences in the Musculoskeletal System of Children with Hemophilia Compared to an Age-Matched Healthy Group.

Recurrent joint bleeds and silent bleeds are the most common clinical feature in patients with hemophilia. Every bleed causes an immediate inflammatory response and is the leading cause of chronic crippling arthropathy. With the help of infrared thermography we wanted to detect early differences between a group of clinical non-symptomatic children with hemophilia (CWH) with no history of clinically detected joint bleeds and a healthy age-matched group of children. This could help to discover early inflammation and help implement early treatment and preventative strategies. It could be demonstrated that infrared thermography is sensitive enough to detect more signs of early inflammatory response in the CWH than in healthy children. It seems to detect more side differences in temperature than clinical examination of silent symptoms detects tender points. Silent symptoms/tender points seem to be combined with early local inflammation. Using such a non-invasive and sensor-based early detection, prevention of overloading and bleeding might be achieved.

Content analysis of Twitter in relation to biological treatments for chronic inflammatory arthropathies: an exploratory study

ObjectiveTo analyse the volume and content of tweets in relation to biological treatments for chronic inflammatory arthropathies.MethodsA Twitter analysis was carried out during one month using the following keywords: ’rheumatoid...