The gut-enthesis axis and the pathogenesis of Spondyloarthritis.

Subclinical inflammation is associated with Spondylarthritis (SpA). SpA patients show features of dysbiosis, altered gut barrier function, and local expansion of innate and innate-like cells involved in type 3 immune response. The recirculation of intestinal primed immune cells into the bloodstream and, in some cases, in the joints and the inflamed bone marrow of SpA patients gave the basis of the gut-joint axis theory. In the light of the critical role of enthesis in the pathogenesis of SpA and the identification of mucosal-derived immune cells residing into the normal human enthesis, a gut-enthesis axis is also likely to exist. This work reviews the current knowledge on enthesis-associated innate immune cells' primary involvement in enthesitis development, questions their origin, and critically discusses the clues supporting the existence of a gut-enthesis axis contributing to SpA development.

Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: a post hoc analysis of SELECT-PsA 1 and 2.

OBJECTIVES: To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with psoriatic arthritis from the SELECT-PsA Phase 3 trials. METHODS: Patients with an inadequate response/intolerance to ≥ 1 non-biologic DMARD (SELECT-PsA 1) or ≥ 1 biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0-24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution, and protection from enthesitis development through week 56. RESULTS: Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (-1.7 vs -1.0) and SPARCC index (-3.4 vs -1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in > 80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24. CONCLUSIONS: UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis. CLINICALTRIALS.GOV IDENTIFIERS: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).

Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: a post hoc analysis of the EXCEED study.

OBJECTIVES: To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. METHODS: In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan-Meier analysis for time to resolution, and as-observed data for other outcomes. RESULTS: Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. CONCLUSION: Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02745080.

Ten-year safety and clinical benefit from open-label etanercept treatment in children and young adults with juvenile idiopathic arthritis.

OBJECTIVES: CLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with JIA, categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA) or PsA. METHODS: Participants with eoJIA (2-17 years old), ERA or PsA (each 12-17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA ACR 30/50/70/90/100 criteria and ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis DAS (JADAS) ≤1. RESULTS: Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 [n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 (78%) on active treatment]; 84 (66%) completed 120 months' follow-up [32 (25%) on active treatment]. One malignancy (Hodgkin's disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates (events per 100 patient-years) of TEAEs (excluding infections/ISRs) decreased from 193 (173.81) in Year 1 to 9 (27.15) in Year 10; TE infections and serious infections also decreased. Over 45% of participants (n = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. CONCLUSIONS: Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit-risk assessment of etanercept in these JIA categories remains favourable. TRIAL REGISTRATION: ClinicalTrials.gov IDs: CLIPPER (NCT00962741); CLIPPER2 (NCT01421069).

GRAPPA 2023 Debate: Is Psoriatic Disease Really a Primary Enthesitis That Drives Joint Synovitis? The Enthesitis Hypothesis 25 Years On.

The enthesitis hypothesis posits that enthesitis is a primary lesion and that inflammation at the enthesis initiates the musculoskeletal symptoms of psoriatic arthritis (PsA) and spondyloarthropathies (SpA). The hypothesis suggested that inflamed entheseal tissue near the synovium could trigger cytokine-mediated synovitis, that enthesis bone anchorage could explain osteitis, and that the location of entheses at the soft tissue interface could explain dactylitis. Advances in imaging techniques that allow better visualization of enthesitis lesions and the development of animal models have allowed evolution of the concept of enthesitis as a central mechanistic driver of musculoskeletal symptoms in PsA and SpA. A debate between Drs. Dennis McGonagle and Bruce Kirkham at the Group for Research on Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting discussed the data supporting and refuting this hypothesis in PsA and SpA, respectively. The major points of this debate are summarized in this article.

The Impact of Different MEFV Genotypes on Clinical Phenotype of Patients with Familial Mediterranean Fever: Special Emphasis on Joint Involvement.

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In this retrospective cohort study, we aimed to assess the effects of various MEFV genotypes on the clinical characteristics of the patients, with a special focus on the joint involvement. In total, 782 patients with FMF were categorized into 3 groups according to the MEFV mutation; Group 1: Patients homozygous for M694V; Group 2: Patients carrying other pathogenic MEFV variants in exon 10 in homozygous or compound heterozygous states; and Group 3: FMF patients with other variants or without mutations. Clinical and demographic findings were compared between groups. Among the 782 FMF patients, total frequency of arthritis was 237 (30.3%): 207 (26.4%) were acute monoarthritis and 67 (8.5%) were chronic arthritis. Both the frequency of arthritis (acute and/or chronic) (40.4% vs. 24.8% vs. 26.7%; p:0.001) and acute monoarthritis (35.4% vs. 20% vs. 23.7%; p:0.001) were significantly higher in Group 1 than in the other groups. FMF patients with chronic arthritis showed a distinct juvenile idiopathic arthritis (JIA) distribution pattern with a more frequent enthesitis-related arthritis (ERA) subtype (43.2%). HLA-B27 was positive in 24% of the ERA patients.Conclusion: Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis comparing to other MEFV genotypes. In addition, the risk of chronic arthritis seems not related to the MEFV mutations. However, FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA and undifferentiated arthritis subtype. What is known: • Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis What is new: • FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA subtype • ERA patients with negative HLA-B27 antigen should also be assessed for polyserositis episodes of FMF, especially in countries with high FMF carrier frequency.

Association of enthesitis with severity of psoriasis in psoriatic arthritis: an observational study.

The relationship between dermatological and articular manifestations of psoriatic disease remains incompletely elucidated. There is no strong correlation between the severity of cutaneous psoriasis and the clinical phenotypes of psoriatic arthritis (PsA). This study aims to examine the correlation between the severity of psoriasis and various clinical features, including measures of severity and activity of PsA, in a real-world clinical setting. Seventy-six consecutive adult patients of both genders with confirmed diagnoses of psoriatic arthritis (PsA) and psoriasis were included in the study. The Psoriasis Area and Severity Index (PASI) was assessed alongside various PsA variables: tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness, presence of dactylitis and number of affected digits, presence of enthesitis and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), patient's global assessment (PGA), and examiner's global assessment (EGA). Associations were analyzed using the Spearman correlation test and the Kruskal-Wallis test. Statistical significance was established at p = 0.05. Forty-two men and thirty-four women, median age of 56 (range 33-85) years, participated in the study. The median duration of psoriasis was 216 (range 0-600) months and median duration of PsA was 120 (range 7-456) months. There was no significant correlation between PASI and any PsA variables, except for the correlation between PASI and the presence of enthesitis (ρ = 0.285; p = 0.013). Moreover, older patients and patients with a long history of psoriasis manifested more often with enthesis as a sign of PsA. Our findings emphasize the correlation between the severity of psoriasis and presence of enthesitis in patients with PsA.

Significant functional impairment and disability in individuals with psoriatic arthritis and Achilles tendon pain: a cross-sectional observational study.

The Achilles tendon (AT) insertion is the most common site of enthesitis in psoriatic arthritis (PsA). The structure and function of the AT in PsA, and the prevalence of mid-portion pathology, is unknown. To compare the structure and function of the AT in people with PsA with self-reported AT pain (PsA + AT), PsA without self-reported AT pain (PsA-AT) and healthy controls. A cross-sectional, observational study was conducted. The ATs were assessed by clinical and US examination (B-mode and Power Doppler), performance-based testing (bilateral heel raise test (HRT) and 10 m walk test), and patient-reported outcome measures (PROMs) (including the Victorian Institute of Sport Assessment-Achilles [VISA-A]). Between-group differences were described using descriptive statistics, Chi-squared testing, parametric (1-way ANOVA) and non-parametric (Mann-Whitney or Kruskal-Wallis) testing. 22 PsA (11 per group) and 11 healthy control participants who were comparable in terms of sex, age, and BMI (PsA-AT = longer PsA disease duration) were recruited. VISA-A scores were significantly worse in the PsA + AT group compared to the PsA-AT group and healthy controls (p < 0.001). Inflammatory US features were significantly more prevalent in the PsA + AT group (p < 0.001). Mid-portion AT pathology was observed in the PsA + AT group, irrespective of entheseal disease. Clinical examination alone missed 5/7 cases of 'active' US-confirmed AT enthesitis. AT functional deficits were significant in the PsA + AT group and both PsA groups had lower HRT repetition rates and walked slower compared to healthy controls. Less than 1/3 of the PsA + AT group had received podiatry or physiotherapy care. Significant differences in the structure and function of the AT in PsA were noted. Despite management in line with current guidance, AT pain appears to persist and can result in severe functional impairment.

Prevalence of HLA-B27, clinical characteristics and treatment outcomes in children with enthesitis-related arthritis.

BACKGROUND: Enthesitis-related arthritis (ERA) is a subtype of juvenile idiopathic arthritis with high disease burden. The objectives of this study were to explore the prevalence of HLA-B27, clinical characteristics, and treatment outcomes in children with ERA and compare the differences between HLA-B27 positive and negative patients. METHODS: A retrospective cohort study at a pediatric rheumatology clinic in a tertiary referral hospital in Bangkok, Thailand, including ERA patients with at least 6 months of follow-up (July 2011-April 2022) was performed. Data were collected from medical records from diagnosis to recent follow-up, assessing disease activity and treatment outcomes, with an analysis comparing HLA-B27 positive and negative patients. Descriptive statistics were used for data analysis. RESULTS: There were 59 ERA patients with mean age ± SD at diagnosis 11.2 ± 2.5 years, 53 males (89.8%), and positive HLA-B27 in 38 patients (64.4%). The HLA-B27 positive group had significantly higher levels of inflammatory markers at initial diagnosis (p = 0.001), lower baseline hemoglobin (p = 0.001) and hematocrit (p = 0.002), higher disease activity assessed by the Juvenile Spondyloarthritis Disease Activity score at 6 and 12 months of follow-up (p = 0.028 and 0.040, respectively), increased utilization of bridging systemic corticosteroids (60.5% vs. 14.3%, p = 0.001) and anti-TNF (39.5% vs. 9.5%, p = 0.018), and longer duration of methotrexate (median[IQR] 1.7[1.1-3.1] vs. 1.3[0.6-1.9] years, p = 0.040). The HLA-B27 negative group had more prevalent hip arthritis than the positive group at initial diagnosis (66.7% vs. 28.9%, p = 0.005) and during the course of the disease (71.4% vs. 36.8%, p = 0.011). CONCLUSION: Most of the ERA patients tested positive for HLA-B27. Throughout the follow-up period, these patients demonstrated greater disease activity, greater use of corticosteroids and anti-TNF, and longer duration of methotrexate to control the disease.

Subclinical enthesitis in enthesitis-related arthritis and sacroiliitis associated with familial Mediterranean fever.

OBJECTIVES: In our study, we investigated the presence of subclinical enthesitis by ultrasonography (US) in asymptomatic patients with enthesitis-related arthritis (ERA) and sacroiliitis associated with familial Mediterranean fever (FMF). METHODS: A total of 50 patients, including 35 patients with ERA and 15 with sacroiliitis associated with FMF, were included in the study. All patients were evaluated with US by a paediatric radiologist. Enthesis of seven tendons (common extensor and flexor tendons, quadriceps tendon, proximal and distal patellar tendon, Achilles tendon, and plantar fascia) was examined on both sides. RESULTS: Subclinical enthesitis was detected in 10 ERA (28.5%) and three FMF (20%) patients. Enthesitis was radiologically diagnosed in 16 (2.3%) out of 700 evaluated entheseal sites. The most frequent sites of enthesitis were Achilles (37.5%) and quadriceps (31.3%) tendons. All patients were in clinical remission and had no active complaints, and acute phase reactants were within normal limits. Therefore, the patients were followed up without treatment change. However, disease flare-up was observed in three of these patients (23.1%) during the follow-up, and their treatments were intensified. CONCLUSIONS: Our results showed that the US can be particularly helpful in detecting subclinical enthesitis and predicting disease flare-ups.

Foot involvement in psoriatic arthritis: Prevalence, clinical and radiological features.

BACKGROUND: The purpose of this study was to evaluate the prevalence of foot involvement in psoriatic arthritis and to describe its different clinical and radiological features. PATIENTS AND METHODS: We conducted a cross sectional study including 40 patients with psoriatic arthritis over a period of 12 months. Anamnesis, clinical examination of feet, podoscopic examination, X-rays of feet and heels, and ultrasound in B mode and power Doppler mode were done for each patient. RESULTS: Foot involvement was found in 95% of cases. It was symptomatic in 70% and inaugural of the disease in 20% of cases. The hindfoot and the forefoot were the sites most affected (77.5% and 47.5% respectively). The involvement of the midfoot was rarer (25%). Dactylitis was found in 17.5% and deformities of forefoot were found in 22.5% of cases. Antalgic gait was noted in 17.5% and static disorders of foot at podoscopic examination were identified in 35% of cases. Feet dermatological manifestations were found in 45% of cases. Diagnosis of different rheumatological manifestations was based on clinical findings and caracteristic radiological images on X-rays. We demonstrate he sensitivity of ultrasound in the detection and the diagnosis of different foot lesions including enthesitis, synovitis and tenosynovitis, dactylitis, bone erosions and psoriatic nail dystrophy.

Arthritis in Children with Psychiatric Deteriorations: A Case Series.

Pediatric acute-onset neuropsychiatric syndrome (PANS), pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections, Sydenham chorea, and other postinfectious psychiatric deteriorations are thought to be caused by inflammatory/autoimmune mechanisms, likely involving the basal ganglia based on imaging studies. Patients have a relapsing-remitting course and some develop severe refractory psychiatric disease. We found that 55/193 (28%) of consecutive patients meeting PANS criteria developed chronic arthritis and 25/121 (21%) of those with related psychiatric deteriorations developed chronic arthritis. Here we describe 7 of these patients in detail and one sibling. Many of our patients often have "dry" arthritis (no effusions found on physical exam) but subtle effusions detected by imaging and features of spondyloarthritis, enthesitis, and synovitis. Joint capsule thickening, not previously reported in children, is a common finding in the presented cases and in psoriatic arthritis in adults. Due to the severity of psychiatric symptoms in some cases, which often overshadow joint symptoms, and concomitant sensory dysregulation (making the physical exam unreliable in the absence of effusions), we rely on imaging to improve sensitivity and specificity of the arthritis classification. We also report the immunomodulatory treatments of these 7 patients (initially nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs with escalation to biologic medications) and note any coincidental changes to their arthritis and psychiatric symptoms while on immunomodulation. Patients with overlapping psychiatric syndromes and arthritis may have a unifying cause and pose unique challenges; a multi-disciplinary team can utilize imaging to tailor and coordinate treatment for this patient population.

Prevalence of ultrasound and clinical findings suggestive of inflammatory arthritis in children with skin psoriasis.

OBJECTIVE: To evaluate the prevalence of clinical and ultrasound (grey-scale and Doppler) abnormalities in joints, periarticular structures and nails of children affected by skin psoriasis (PsO). METHODS: Cross-sectional study including consecutive children affected by PsO. A systematic clinical and ultrasound evaluation of joints, entheses, tendons and nails were performed by independent examiners blinded to each other assessment. RESULTS: 57 Children: 26 girls (46%), mean age of 9 ± 4 years, divided into two groups, asymptomatic (Asy, 42 children) and symptomatic (Sy, 15 children) according to musculoskeletal pain. Differences were observed between the two groups in relation to age (9 ± 3 in Asy vs 11 ± 4 yrs in Sy, p< 0.05), PsO duration (2.4 ± 2.4 vs 5.4 ± 3.9 yrs, p< 0.001), systemic treatment (23 [54.8%] vs 2 [13.3%], p< 0.01), tender joint count (0 vs 12 children [80%], p< 0.001), swollen joint count (0 vs 3 [20%], p< 0.01) and entheseal pain (0 vs 10 [66.7%], p< 0.001). Ultrasound evaluation showed statistically significant differences between Asy and Sy groups for the presence of ultrasound abnormalities (16/42 [38%] vs 12/15 [80%]), synovitis (1/42 [2%] vs 4/15 [25%]) and enthesitis (4/42 [9.5%] vs 5/15 [33%]). Three children in the Sy group were classified with juvenile psoriatic arthritis (JPsA). CONCLUSIONS: Ultrasound abnormalities were higher in the Sy group with synovitis and enthesitis as the most prevalent findings. Asy patients were more frequently under systemic treatment. Ultrasound and a systematic clinical evaluation are useful tools for detecting subclinical JPsA in children with PsO and musculoskeletal symptoms.

Predictors of long-term functional outcomes of juvenile idiopathic arthritis-enthesitis-related arthritis: a single centre experience.

OBJECTIVES: Long-term functional outcomes in enthesitis-related arthritis (ERA) is limited from developing countries. We assessed the clinical and genetic factors that predicted the long-term functional outcome in ERA. METHODS: Patients with ERA having ≥5 years of disease and >16 years of age were included in this cross-sectional study. Data on clinical features within 6 months of disease onset was collected from hospital records. Bath indices, HAQ Disability Index (HAQ-DI) and World Health Organization's Quality of Life (WHO-QOL) were assessed at last visit. Poor functional outcome (PFO) was defined as BASFI > 1.5 or HAQ-DI > 1. Persistent disease activity (PDA) was defined as BASDAI ≥ 4. Endoplasmic reticulum aminopeptidase 1 (ERAP1) and IL-23 receptor single nucleotide polymorphism genotyping was performed with the TaqMan method and HLA-B27 by PCR. RESULTS: One hundred and eighty-one patients [170 male, median (interquartile range) age of disease onset 12.5 (10-15) years, disease duration 7 (5-11) years] were recruited. There was a delay in diagnosis of 3 (1-5) years. The median Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR, BASDAI, HAQ-DI and BASFI at inclusion were 2.6 (1.8-3.6), 2.6 (1-5.2), 0.5 (0-0.5) and 1.6 (0.3-3.2), respectively. BASFI and HAQ-DI correlated with ASDAS-ESR, ASDAS-CRP and WHO-QOL-BREF. Those with PFO (n = 98) had a longer delay in diagnosis (4 vs 2 years, P < 0.001), lower prevalence of arthritis at onset [odds ratio (OR) = 0.3; 95% CI: 0.1, 0.8], higher prevalence of ERAP1 (rs27044) allele C (OR = 7.2; 95% CI: 1.5, 33.7) and higher disease activity currently. Delay in diagnosis (OR = 1.2; 95% CI: 1.08, 1.4) was the sole predictor of PFO in multivariate analysis. One-third of patients had PDA. Tarsitis at disease onset was the sole predictor of PDA (OR = 2.3; 95% CI: 1.009, 5.4). CONCLUSIONS: PFO was seen in one-half of JIA-ERA in the long-term and was associated with active disease with delay in diagnosis as its sole predictor.

Comparing Canadian paediatric rheumatology practice to the 2019 ACR Juvenile Idiopathic Arthritis guidelines: results from the CAPRI Registry.

OBJECTIVE: To identify differences between baseline Canadian JIA practices and the 2019 ACR guidelines for JIA. METHODS: Canadian paediatric rheumatologists were surveyed for their opinions on reasonable a priori target adherence rates for JIA guideline recommendations. Prospectively collected data for 266 newly diagnosed children from 2017 to 2019 were analysed to calculate observed adherence rates. Kaplan-Meier survival curves were used to estimate the cumulative incidence of starting synthetic or biologic DMARDs (sDMARD or bDMARD, respectively) for different patient groups. RESULTS: A total of 25/61 (41%) eligible physicians answered the survey. Most survey respondents (64%) felt that adherence targets should vary depending on the strength of the recommendation and quality of evidence, from a mean of 84% for strong recommendations with high-quality evidence to 29% for conditional recommendations with very low-quality evidence. Data showed 13/19 (68%) recommendations would have met proposed targets and 10/19 (53%) had ≥80% observed adherence. Exceptions were the use of subcutaneous vs oral MTX (53%) and infrequent treatment escalation from NSAIDs to bDMARDs in patients with sacroiliitis (31%) or enthesitis (0%). By 12 weeks, 95% of patients with polyarthritis received sDMARDs, 38% of patients with systemic JIA received bDMARDs and 22% of patients with sacroiliitis received bDMARDs. CONCLUSION: Canadian paediatric rheumatology practices were in line with many 2019 JIA guideline recommendations before their publication, except for frequent use of oral MTX and infrequent direct escalation from NSAIDs to bDMARDs in sacroiliitis and enthesitis.

Non-invasive metabolic profiling of inflammation in joints and entheses by multispectral optoacoustic tomography.

OBJECTIVE: To explore the metabolic characteristics of arthritis and enthesitis using multispectral opto-acoustic tomography (MSOT), a technology using near-infrared multispectral laser to stimulate tissues and detect the emitted acoustic energy, enabling non-invasive quantification of tissue components in vivo based on differential absorbance at multiple wavelengths. METHODS: We performed a cross-sectional study in patients with RA or PsA and healthy controls (HCs). Participants underwent clinical, ultrasonographic and MSOT examination of MCP and wrist joints as well as the entheses of the common extensor tendon at the lateral humeral epicondyles and of the patellar, quadriceps and Achilles tendon. MSOT-measured haemoglobin (Hb), oxygen saturation, collagen and lipid levels were quantified and scaled mean differences between affected and unaffected joints and entheses were calculated as defined by clinical examination or ultrasonography using linear mixed effects models. RESULTS: We obtained 1535 MSOT and 982 ultrasonography scans from 87 participants (34 PsA, 17 RA, 36 HCs). Entheseal tenderness was not associated with significant metabolic changes, whereas enthesitis-related sonographic changes were associated with increased total Hb, oxygen saturation and collagen content. In contrast, the presence of arthritis-related clinical and sonographic findings showed increased Hb levels, reduced oxygen saturation and reduced collagen content. Synovial hypertrophy was associated with increased lipid content in the joints. CONCLUSION: MSOT allows determination of distinct metabolic differences between arthritis and enthesitis in a non-invasive setting in humans in vivo.

Sonographic evaluation of subclinical entheseal involvement in patients with hypoparathyroidism: a case control study.

PURPOSE: Hypoparathyroidism is a disease characterized by low serum calcium, increased serum phosphorus and low PTH levels. Although patients are treated with active vitamin D and calcium, a proper serum calcium phosphorus balance cannot always be achieved. Ectopic calcifications that develop in organs during treatment are the most common complications. To date, there is not any published study on enthesopathy in patients with hypoparathyroidism. The aim of this study was to evaluate subclinical enthesopathy in patients with hypoparathyroidism with ultrasound and to compare the results with those of the control group. METHODS: The study included patients aged 18-65 years with postoperative hypoparathyroidism and hypothyroidism (group hypoP + hypoT), patients with postoperative hypothyroidism (group hypoT), and healthy age and sex-matched volunteers (group C). Ultrasonographic findings of enthesopathy in both extremities were documented according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS). RESULTS: GUESS scores in group hypoP + hypoT, were significantly higher when compared to the other groups. There was a statistically significant correlation between the total GUESS scores and total enthesophyte scores and the duration of hypoparathyroidism (p < 0.05, r = 0.43) (p < 0.05, r = 0.39) respectively. In the correlation analysis of all groups, a significant negative correlation was found between serum Ca and PTH levels and the total GUESS scores (p < 0.01, r = - 0.37; p < 0.01, r = - 0.54, respectively). CONCLUSION: This study showed that GUESS scores were significantly higher in patients with hypoparathyroidism compared to those with hypothyroidism and control subjects. GUESS scores were positively correlated with disease duration. Patients with hypoparathyroidism need to be evaluated for subclinical enthesopathy during follow-up.

Bibliometric analysis of publications on enthesitis in spondyloarthritis in 2012-2021 based on web of science core collection databases.

Enthesitis, a characteristic of spondyloarthritis, has been paid considerable attention by researchers, and numerous enthesitis-related studies have been published in recent years. However, no study has been conducted to analyze enthesitis-related researches with bibliometric methods. This study aimed to provide a broad understanding of enthesitis-related researches and explore the direction of hot topics and future research trends from a bibliometric perspective. The global literatures on enthesitis published from 2012 to 2021 were scanned in the Web of Science Core Collection databases. Visualization and bibliometric analyses were generated by an online bibliometric platform and VOSviewer software to explore the hot topics and research trends. A total of 1,181 documents were included in this study. Publications were mainly from these countries in North America and Western Europe. Among these countries, the United States was the leading country with the maximum publication counts (210), highest h-index (47), and largest collaboration network as of June 29, 2022. The most influential journal and powerful author were Journal of Rheumatology and Professor Mease PJ, respectively. Co-occurrence analysis of keywords identified that "axial spondyloarthritis", "interleukin 23", and "secukinumab" might be the future hotspots. More and more attention had been paid to enthesitis in the past 10 years. Present studies focused on the effect of inflammatory cytokines involved in the pathogenesis and the development of antibodies against these factors. These studies played a key role in understanding the research direction and subsequent management of enthesitis, and helped researchers extract hidden valuable information for further study.

Macrophage migration inhibitory factor (MIF) and IgA anti CD74 antibodies in Indian patients with enthesitis-related arthritis category of Juvenile idiopathic arthritis.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in pathogenesis of ankylosing spondylitis (AS). CD 74 is the receptor for MIF and IgA antiCD74 autoantibodies have been described from different parts of the world in patients with AS. As enthesitis-related arthritis (ERA) is a form of juvenile spondyloarthropathy, we studied the serum and synovial fluid levels of MIF in ERA and looked for the IgA antiCD74 antibodies in patients with ERA in our population. Patients with JIA (ILAR classification) were studied. Serum MIF levels were measured by ELISA in 101 patients of ERA (synovial fluid also where available) and compared to 28 patients of other categories of JIA, 25 patients each of ankylosing spondylitis and rheumatoid arthritis, and 38 healthy controls. In addition, association of MIF with disease activity was assessed. Ig A antiCD74 antibodies were measured in sera of ERA, AS and healthy controls. Median serum MIF levels were higher in ERA [2.50 (1.20-4.85) ng/ml] than in healthy controls [0.28 (0.16-0.48); p < 0.0001] and patients with RA [1.13 (0.44-2.45); p < 0.01] MIF levels in ERA were comparable to other categories of JIA [2.63 (1.70-4.05)] and patients with AS [3.62 (0.52-6.51)]. Synovial fluid MIF levels were higher than serum levels (p < 0.01). Serum MIF level had an association with the JSpADA score (r = 0.29, p < 0.01). Serum MIF levels had no association with presence of inflammatory markers, enthesitis, inflammatory back pain or sacroiliitis. IgA AntiCD74 antibody was positive only in 3/88 (3.41%) of ERA patients and was not detected in any patients of AS or healthy controls. Patients with ERA have high MIF levels that show modest correlation with disease activity. Higher synovial fluid MIF levels suggest that it may play a role in synovitis seen in ERA. IgA antiCD74 antibodies are rarely seen in ERA.

Apremilast for biologic-naïve, peripheral psoriatic arthritis, including patients with early disease: results from the APROACH observational prospective study.

To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast's safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0-29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient's health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.