New horizons in osteoarthritis

Summary Osteoarthritis (OA), also known as degenerative joint disease, is the most frequent chronic musculoskeletal disease and the leading cause of disability in elderly persons. There are currently at least 27 million persons afflicted with OA in the United States, and the annual cost to society in medical care and wage loss is expected to reach nearly $100 billion dollars by 2020, with consequent increased spending on its diagnosis and treatment, side-effect prevention, and loss of productivity. Despite this enormous burden, many aspects of OA are still unknown, with implications not only in terms of diagnosis and assessment but also with regard to therapy. Awareness of this state of affairs has attracted many researchers to this field, making OA one of the most actively studied sectors of rheumatology. Although some clinicians are unaware of recent advances, there is a large body of publications indicating that much has been achieved. Major progress has been made in formulating better definitions of risk factors, in particular in indicating the responsibility of biomechanical and genetic factors, and, with regard to pathogenesis, underlining the role of subchondral bone, cytokines and proteinases. Assessment of OA activity and its progression has been improved with the advent of biomarkers and new imaging procedures, in particular sonography and magnetic resonance imaging (MRI), but also of better clinical instruments, including more reliable patient questionnaires. Information from ongoing studies may improve the to some extent incomplete definition of OA phenotypes. Finally, promising new horizons have been opened up even with regard to the treatment of OA, which is still for the most part unsatisfactory except for surgical replacement therapy. Numerous new substances have been formulated and the findings of trials studying their effects are encouraging, although much has yet to be done

The psoriatic great toe or the psoriatic onycho-pachydermo-periostitis of great toe (OP3gt)

The onycho-pachydermo-periostitis of the great toe is a characteristic feature of psoriatic arthritis first described by Fournie in 1980. In the affected patients, the great toe involvement is characterised by a relevant osteo-periostitis of the distal phalanx, a thickening of the distal soft tissues associated with a psoriatic onychopathy. In most cases, the distal interphalangeal joint is spared. Radiographic and scintigraphic osteo-periostitis of distal phalanx of the great toe are frequent, being found in about 44% of patients with psoriatic arthritis. However, clinical manifestations, with inflammatory inflammation of the great toe, are rare

Influence of intra-articular injections of sodium hyaluronate on clinical features and synovial fluid nitric oxide levels of temporomandibular osteoarthritis

Objective: This study was designed to assess the effect of intra-articular injection of sodium hyaluronate (SH) on clinical findings of temporomandibular osteoarthritis (OA) and on synovial fluid (SF) levels of nitric oxide (NO). Methods: Twenty seven patients (7 men, 20 women, mean (SD) age 53.9 (11.8) years) with OA of the temporomandibular joint were randomly allocated to receive an injection of either SH (2ml, Hyalgan®, Fidia SpA, Abano T., P.M. 500-700.000, 20mg/2ml; once a week for 5 weeks) or a Ringer's lactate solution (once a week for 3 weeks). Clinical evaluation was done before each procedure, and at 1 week, 1, 3 and 6 months post-injection. Intensity of temporomandibular joint pain, jaw function, maximal mouth opening and lateral jaw movements were recorded at each visit. NO was measured on SF collected by rinsing the joint with saline 1 ml before the treatment. Results: Injection of SH caused significant improvement in the main clinical symptoms until the last follow-up which was carried out 6 months after last injection. Among patients who received SH injection, those who reached a good outcome showed the lowest basal levels of NO. Conclusions: The results of this study showed that intra-articular injections of SH lead to a lasting improvement in the clinical symptoms of temporomandibular OA. Furthermore, our findings suggest that low NO levels in SF are related to a better outcome of temporomandibular OA among patients treated with SH intra-articular injection

how the mediterranean diet and some of its components modulate inflammatory pathways in arthritis

Arthritis encompasses a heterogeneous group of diseases characterised by inflammation that leads not only to joint damage, bone erosion, severe pain and disability, but also affects other organs of the body, resulting in increased morbidity and mortality. Although the mechanisms underlying the pathogenesis of joint diseases are for the most part unknown, a number of nutrient and non-nutrient components of food have been shown to affect the inflammatory process and, in particular, to influence clinical disease progression. The Mediterranean diet model has already been linked to a number of beneficial health effects: both fat and non-fat components of the Mediterranean dietary pattern have been shown to exert important anti-inflammatory activities by affecting the arachidonic acid cascade, the expression of some proinflammatory genes, and the activity of immune cells. N-3 polyunsaturated fatty acids, in particular, have been shown to affect lymphocyte and monocyte functions, crucially involved in adaptive and innate immunity. Although some aspects concerning the mechanisms of action through which the Mediterranean diet pattern exerts its beneficial effects remain to be elucidated, arthritis patients may potentially benefit from it in view of their increased cardiovascular risk and the treatment they require which may have side effects

The enthesopathy of vitamin D-resistant osteomalacia in adults

A case of an adult patient with vitamin D-resistant osteomalacia or X-linked hypophosphatemic osteomalacia (XLH) with diffuse calcification of entheses was reported. XLH is the most frequent cause of rickets in developed countries. It is characterized by an impaired renal transport of the phosphate and mutation of PFEX (phosphate regulating gene, with homologies to endopeptidase on the X-chromosome). In childhood, the classic clinical presentation includes short stature and bow leg. While at this age the main radiographic features are characterised by rickets, in adult life they are dominated by a generalised calcific enthesopathy. Concerning the pathogenesis of the enthesopathic lesions of XLH, no convincing hypothesis has yet been made. As in our patient, the extension and the severity of enthesopathy seems not related to the severity of the biochemical changes nor to the treatment with calcitriol. The calcified enthesopathy is an integral part of XLH and it is possible that it is found in adult because many years are necessary to produce it

The natural history of ankylosing spondylitis in the 21st century

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects the axial skeleton and evolves in stiffnes followed by ankylosis and disability. However, it may be difficult to exactly establish the natural history of the disease and the influence of risk factors of progression, since most patients are treated with various pharmacologic or non-pharmacologic agents, which may potentially influence the natural progression of the disease. In this context, we report here a very interesting case of a 40 year old man, presented to our outpatient clinic, 28 years after the onset of AS. Previously for personal reasons, did not choose not to undergo any treatment. This case allows us to evaluate the natural radiological progression of the disease and the influence of predictive risk factors

POS1221 SARS-COV2 SEROLOGY SCREENING IN SPONDYLOARTHRITIS PATIENTS IN NORTH-EASTERN ITALY: A PILOT STUDY

Background:Serology could help defining the real extent of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) diffusion in the population, especially in individuals considered at higher risk of SARS-CoV2 infection (COVID-19), such as Spondiloarthritis (SpA) patients undergoing immunosuppressive therapy or health care workers (HCW). In fact, COVID-19 detection is complicated by the fact that many patients can be asymptomatic. In these cases, it has also been suggested that a weaker immune response might be elicited.In this context, the role of anti-cytokine targeted therapy –commonly used as treatment in SpA- is uncertain, as it is not clear whether it is detrimental or protective towards severe disease forms.Objectives:The aim of the study was to explore the potential role of serology in detecting previous contact with SARS-CoV2 in SpA patients and HCW, and compare the frequency of positive findings with a control population.Methods:Consecutive patients affected by axial or peripheral SpA, classified according to Assessment of SpondyloArthritis international Society (ASAS) criteria and undergoing cytokine-targeted therapy, as well as HCW and controls from the pre-COVID-19 era (control group, 2015) were recruited. In SpA patients, disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Disease Activity Score on 28-joint-count (DAS28).Sera from all patients were analysed through chemiluminescent analytical system (CLIA) for the presence of IgG and IgM anti-SARS-CoV2. Patients with a positive serological test (either IgM or IgG) additionally underwent real time Polymerase Chain Reaction (RT-PCR) in nasopharyngeal swabs in order to test for active infection. In SpA patients, serology was repeated after 3 months. Data across the 3 groups were compared by ANOVA or Chi-square, while comparison between 2 groups were conducted by Wilcoxon signed rank test or Chi-Square, for continuous and categorical data respectively. P ≤ 0.05 were considered as significant.Results:A total of 396 patients were recruited: 200 SpA, 95 HCW and 101 healthy controls. SpA patients were mostly (54%) males, with mean age 49.6 ±14.7 years, and all were treated with anti-TNFα (78%), anti-IL-17 (9%) and anti-IL-23 drugs (7%), or small molecules (6%). Their disease activity level was moderate-low as assessed by ASDAS (1.95 ±0.98) and DAS28 (2.33 ±2.02). Among HCW and controls, 35% and 62% were male, with mean age 46.7 ±12.9 and 50.6±10.6 respectively.Positive serology (IgM or IgG, or both) was found in 12.5% SpA patients, 8.4% HCW, 0% controls (p=0.001). Among these, IgM titres were higher in the SpA group than in HCW (2.76±2.94 versus 0.80±0.67 KU/L, p= 0.016), while IgG mean titres were lower in the SpA group than in HCW (0.88±3.18 KU/L versus 1.05±0.88, p= 0.035). SpA patients with positive serology more frequently reported COVID-19 like symptoms than those with negative serology (20% vs 4%, p=0.009) and 2 had COVID-19 as confirmed by RT-PCR, none with a severe disease course. None of the HCW reported symptoms or tested positive by RT-PCR. In the SpA patients, at 3 months, the mean IgM titre decreased from 2.76±2.93 to 2.38±2.95 (p=0.001), while the IgG titres decreased from 0.89±3.25 to 0.31±0.87 (p=ns). Interestingly, the IgM or IgG titer at a single-patient level did not seem to change much in terms of absolute value (Figure 1), except in one patient, with documented COVID-19 (positive RT-PCR), in whom IgG level even decreased at 3 months.Conclusion:Serology revealed that exposure to COVID-19 in SpA patients, as well as HCW, was higher than expected based on reported symptoms. Targeted anti-cytokine therapy could act as a protective factor for a severe disease course in SpA patients. However, in this population, IgG and IgM titres did not change in a clinically significant manner at 3 months, and patient did not seem to develop an immune profile consistent with durable response. This result could be due to a weaker immune response in mild infections, but further studies are warranted to clarify the pathophysiology beyond these observations.Figure 1.Disclosure of Interests:Augusta Ortolan: None declared, Chiara Cosma: None declared, Mariagrazia Lorenzin: None declared, Giacomo Cozzi: None declared, Andrea Doria Speakers bureau: Novartis, Abbvie, Pfizer, MSD, Janssen, Glaxosmithkline, Mario Plebani: None declared, Roberta Ramonda Speakers bureau: Novartis, Abbvie, Pfizer, MSD, Jansse

II Course on synovial fluid analysis organized by the Italian Society of Rheumatology

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Laboratory findings in psoriatic arthritis.

Psoriatic arthritis (PsA) has been classically defined as an inflammatory arthritis associated with psoriasis. However, in comparison with other relevant inflammatory arthropathies, in which a definite diagnosis is frequently possible only by means of laboratory investigations, in PsA true laboratory diagnostic markers are lacking. Some markers are utilised more to differentiate other diseases than to characterise PsA. For example in polyarticular PsA, which may be in some cases indistinguishable from RA, the rheumatoid factor (RF) or the more specific and recently introduced antibodies to cyclic citrullinated peptides (anti-CCP), may be useful to better identify RA. However, RF was found in 5% to 13% of patients with PsA, and anti-CCP may be observed in almost similar percentage. The determination of ESR and/or CRP is frequently disappointing in PsA, since they are both elevated in only half of the patients with PsA. However, ESR and/or CRP are included in the most utilised response criteria for RA, such as ACR and DAS, and, in addition are also considered reliable in the assessment of PsA. Furthermore, elevated levels of ESR have been proposed as one of the best predictors of damage progression and, in addition, a low ESR seems protective, while an ESR >15 mm/h is one of the factors associated with an increased mortality in PsA. The synovial fluid (SF) effusion is much higher in PsA, in comparison with other arthropathies. When available, SF analysis may offer additive information useful for the diagnosis, such as the increased number of leukocytes, which underlines the inflammatory nature of the effusion even in a patient with normal serum levels of acute phase response. We found that elevated IL-1 levels in SF of patients with early disease (<6 months), may be predictive of an evolution in polyarticular form at follow-up. This observation is in keeping with the crucial role that inflammatory cytokines play in PsA, probably related to a genetic predisposition. The recent introduction in PsA of anti-TNF-α agents and the demonstration of their efficacy in the management of many clinical disease expressions including peripheral arthropathy, axial involvement, enthesopathy and skin manifestations, have stimulated the research also in the field of the possible laboratory markers. Key words: Psoriatic arthritis, laboratory investigations arthriti