Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVES: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y. METHODS: We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (≥3 months, ≤2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0-not confident at all to 10-very confident). MAIN OUTCOME: axSpA diagnosis with LoC≥7 (d-axSpA) at 2y. RESULTS: In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA. Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y-d-axSpA versus 2y-d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male. CONCLUSION: A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients.

2023 EULAR classification criteria for hand osteoarthritis.

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

Do quality of life and work productivity change in early axial spondyloarthritis and non-axial spondyloarthritis patients after two years?

OBJECTIVE: To compare health-related quality of life (HRQoL) and work productivity in axial spondyloarthritis (axSpA) and non-axSpA patients with chronic back pain of < 2 years (2 y). METHODS: Baseline and 2 y data of patients included in the SPondyloArthritis Caught Early cohort were analyzed. HRQoL was assessed by the physical (PCS) and mental component summary (MCS) scores of the 36-Item Short-Form Health Survey; and presenteeism, absenteeism, work productivity loss (WPL) and activity impairment (AI) by the Work Productivity and Activity Impairment questionnaire. Linear or zero-inflated negative binomial regression was conducted to compare 2 y outcomes between groups (axSpA and non-axSpA), adjusting for the baseline value, sex, age and use of nonsteroidal anti-inflammatory drugs. RESULTS: There were 265 axSpA and 108 non-axSpA patients: males 52% vs 26%, mean age 29 vs 31 years, respectively. At baseline, non-axSpA patients showed worse PCS (mean 28.6 axSpA vs 26.6 non-axSpA), presenteeism (31.1% vs 37.3%), absenteeism (8.2% vs 10.3%), WPL (34.7% vs 44.1%) and AI (39.6% vs 48.5%). MCS was not impaired in either group. After 2 y, PCS, presenteeism, WPL and AI significantly improved in both groups; absenteeism only in axSpA. In multivariable analysis, axSpA (vs non-axSpA) was associated with 22% less WPL (incidence rate ratio [95% CI]: 0.78 [0.62; 0.98]) and 18% less AI (0.82 [0.69; 0.97]). CONCLUSION: HRQoL and work productivity are more impaired in non-axSpA (vs axSpA) at baseline and still after 2 y. Although most outcomes improve in both groups, axSpA is associated with larger improvements in work productivity and activity impairment.

Gout: one year in review 2023.

Gout is a chronic joint disease caused by the deposition of monosodium urate crystals into and around the articular tissues. In the last two years, new insights regarding diagnosis, genetic involvement, pathogenesis, comorbidities, and clinical data, have allowed the identification of new strategies to improve the control of the disease and its flares. In keeping, the discover of new mechanisms concerning crystal-induced inflammation have suggested new ways for the management not only of gout, but also other systemic diseases, mainly including renal and cardiovascular disorders. In this context it is very representative the case of colchicine which, given the surprising results obtained both in laboratory and clinical experiments, has recently received by FDA the approval for the prevention of cardiovascular disorders.

Erosive Hand Osteoarthritis: Recent Advances and Future Treatments.

PURPOSE OF THE REVIEW: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis that leads to significant disability, and recent data suggests that it is increasing in prevalence. This review provides an update of our current understanding of epidemiology, genetic associations, biomarkers, pathogenesis, and treatment of EHOA, with particular focus on studies published within the last 5 years. RECENT FINDINGS: New studies of EHOA have identified new genetic loci associated with disease, including variants in genes involved in inflammation and bone remodeling. Preclinical studies implicate pathways of innate immunity, including some that may be causal in the condition. Recent novel studies showed that inflammatory features identified by ultrasound and MRI are associated with development of erosive lesions over time on conventional radiography. In the future, these imaging modalities may be useful in identifying patients at risk of adverse outcomes. Promising new findings in genetics, biomarkers, and treatment targets will hopefully allow for future therapeutic options for this debilitating condition.

Synovial Fluid from Patients with Osteoarthritis Shows Different Inflammatory Features Depending on the Presence of Calcium Pyrophosphate Crystals.

The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. We also explored the effect of OA SF on monocytes response. SFs were collected from adult patients with OA and subdivided according to the presence of crystals. Local cellular and humoral inflammatory mediators were analysed in the SF samples. The expression levels of IL-1ß, IL-18, CASP-1, NLRP3, and GAPDH were measured by RT-PCR in the cells obtained by pelleting the SF samples. For the in vitro study, a monocytic cell line was treated with selected SF samples. SF with CPP crystals showed a significant increase in inflammatory cellular indices and higher levels of IL-1ß, IL-8, and caspase-1 transcript with respect to SF without crystals. Higher concentrations of VEGF were also observed in the early stages of the whole OA patients. THP-1 cells stimulated with OA SF released a significant amount of IL-1 ß in culture supernatants. This study demonstrated that SF collected from patients with OA shows different inflammatory features depending on the presence of CPP crystals.

Is sarcopenia a real concern in ankylosing spondylitis? A systematic literature review.

PURPOSE: Sarcopenia is a condition defined as loss of muscle mass and strength, associated with poor functional performance and disability. Sarcopenia can be exacerbated or worsened in presence of inflammation, sedentary lifestyle and cytokine imbalance, thus it frequently occurs in people affected by rheumatic diseases. This systematic literature review aims to explore the association between sarcopenia and spondyloarthritis (SpA) and its most frequent manifestation, i.e. ankylosing spondylitis (AS). METHODS: The Scopus, PubMed, and Web of Science databases were searched for articles on muscle mass, muscle strength and axial SpA, from any date to November 2023. Only studies written in English were considered. The methodological quality of the studies included in the review was evaluated using the Newcastle-Ottawa Scales for observational studies and for case-control studies. RESULTS: 190 papers were retrieved from the searches, 14 of which met the inclusion criteria. Rather than diagnosis of sarcopenia, pre-sarcopenia or probable sarcopenia were frequent in people with AS, with a great reduction especially of muscle strength. The pre-sarcopenia status appears to be related to high AS disease activity, suggesting that chronic inflammation resulting in pain, less movement and decreased physical activity could play a role in the muscle heath of AS patients. CONCLUSIONS: Our review confirms the existence of an association between AS and loss of muscle strength-likely sarcopenia-already at a young age. Preventive and early strategies should be adopted to ensure successful aging for individuals with AS.

Relapses of juvenile idiopathic arthritis in adulthood: A monocentric experience.

INTRODUCTION: Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. METHODS: We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. RESULTS: Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. CONCLUSION: In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.

Fertility issues in women of childbearing age with spondyloarthritis.

The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.

Assessment of Neuropathic Pain in Erosive Hand Osteoarthritis.

Background/Objectives: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis (OA) and a severely disabling condition. Patients affected by OA frequently lament symptoms suggestive of neuropathic pain (NP). The aim of our study was to ascertain the presence and severity of NP in patients with EHOA and correlate its presence with EHOA clinical characteristics. Methods: In this retrospective study, we included all consecutive EHOA patients with NP symptoms who underwent upper limb electroneurography (ENoG) and nerve ultrasound. The presence of NP was screened using the ID pain neuropathic pain-screening questionnaire (ID-Pain). In addition, the following NP questionnaires were also used: Douleur Neuropathique en 4 Questions (DN4), PainDETECT, and Neuropathic Pain Symptom Inventory (NPSI). Moreover, patients completed the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Dreiser's algofunctional finger index questionnaires assessing EHOA disease activity. The following clinical and laboratory data were collected: age, sex, BMI, disease duration, intensity of pain (VAS 0-10), painful and swollen joints, and inflammatory indices, as well as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results: Of the 34 patients studied, 24 (70.6%) presented NP to the ID-Pain questionnaire. According to DN4, 14 (41.2%) patients had NP, while using the PainDETECT questionnaire, 67.6% had NP. Patients with NP were statistically younger and had a higher VAS pain score compared to subjects without NP. The ENoG and median nerve ultrasound were normal in 81% of patients, while four patients had carpal tunnel syndrome. The ID-Pain questionnaire correlated with the number of painful joints (r = 0.48, p = 0.03) and with the AUSCAN questionnaire (r = 0.37, p = 0.05). The DN4 questionnaire correlated with PainDETECT (r = 0.58, p < 0.01). The PainDETECT questionnaire correlated with VAS pain (r = 0.49, p = 0.02), the DN4 questionnaire (r = 0.58, p < 0.01), and AUSCAN (r = 0.51, p = 0.02). The NPSI questionnaire correlated negatively with BMI (r = -0.53, p = 0.01) and positively with the PainDETECT questionnaire (r = 0.49, p = 0.02). Conclusions: Our study revealed that 32% to 70% of EHOA patients exhibited symptoms consistent with NP, with observed variability depending on the questionnaire utilized. Despite patients frequently exhibiting symptoms compatible with NP, only 19% of patients presented alterations on ENoG and ultrasound examinations confirming CTS. This suggests a probable nociplastic component for pain in patients with EHOA, which warrants tailored treatment. In the present study, NP correlated with clinical and functional indices of EHOA.

Four-year real-world experience of secukinumab in a large Italian cohort of axial spondyloarthritis.

Objectives: This study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA). Methods: Consecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded. Results: We enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex. Conclusions: Secukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.

Features Associated With Different Inflammatory Phenotypes of Calcium Pyrophosphate Deposition Disease: Study Using Data From the International American College of Rheumatology/EULAR Calcium Pyrophosphate Deposition Classification Criteria Cohort.

OBJECTIVE: The study objective was to examine the disease, demographic, and imaging features associated with different inflammatory phenotypes of calcium pyrophosphate deposition (CPPD) disease, ie, recurrent acute calcium pyrophosphate (CPP) crystal arthritis, chronic CPP crystal inflammatory arthritis, and crowned dens syndrome (CDS). METHODS: Data from an international cohort (assembled from 25 sites in 7 countries for the development and validation of the 2023 CPPD classification criteria from the American College of Rheumatology/EULAR) that met the criteria were included. Three cross-sectional studies were conducted to determine the phenotypic characteristics of recurrent acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and CDS. Multivariable logistic regression analysis was used to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI) to examine the association between potential risk factors and the inflammatory phenotype. RESULTS: Among the 618 people included (56% female; mean age [standard deviation] 74.0 [11.9] years), 602 (97.4%) had experienced acute CPP crystal arthritis, 332 (53.7%) had recurrent acute arthritis, 158 (25.6%) had persistent inflammatory arthritis, and 45 (7.3%) had had CDS. Recurrent acute CPP crystal arthritis associated with longer disease duration (aOR 2.88 [95% CI 2.00-4.14]). Chronic CPP crystal inflammatory arthritis was associated with acute wrist arthritis (aOR 2.92 [95% CI 1.81-4.73]), metacarpophalangeal joint osteoarthritis (aOR 1.87 [95% CI 1.17-2.97]), and scapho-trapezo-trapezoid (STT) joint osteoarthritis (aOR 1.83 [95% CI 1.15-2.91]), and it was negatively associated with either metabolic or familial risk for CPPD (aOR 0.60 [95% CI 0.37-0.96]). CDS was associated with male sex (aOR 2.35 [95% CI 1.21-4.59]), STT joint osteoarthritis (aOR 2.71 [95% CI 1.22-6.05]), and more joints affected with chondrocalcinosis (aOR 1.46 [95% CI 1.15-1.85]). CONCLUSION: CPPD disease encompasses acute and chronic inflammatory phenotypes, each with specific clinical and imaging features that need to be considered in the diagnostic workup.

Management of psoriatic arthritis: a consensus opinion by expert rheumatologists.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA. Methods: A group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: "early PsA," "axial-PsA," "extra-articular manifestations and comorbidities," "therapeutic goals." Relevant articles from the literature (2016-2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated. Results: Ninety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for "early PsA"; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for "axial PsA"; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for "comorbidities and extra-articular manifestations"; target and tools, treat-to-target strategy, role of imaging for "therapeutic goals." The final document consisted of 49 statements. Discussion: The final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease.