Enthesitis-related Arthritis Patients Research Articles

Presentation of enthesitis-related arthritis and juvenile-onset spondyloarthritis: a cross-sectional study in a pediatric and adult clinic

BackgroundJuvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA).MethodsCross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups.ResultsThirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA.ConclusionThe main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.

Does sacroiliitis is a mandatory criterion for enthesitis-related arthritis diagnosis?

Magnetic resonance imaging (MRI) sensitivity and specificity seem to be less studied in enthesitis-related arthritis (ERA). We aimed to determine the ability of sacroiliac MRI to diagnose ERA patients. We conducted a retrospective study including 44 patients with juvenile idiopathic arthritis (JIA). Each patient had a sacroiliac joint MRI. We divided patients into two groups: G1 patients with ERA and G2 patients with non-ERA subtype. ERA was noted in 61% of the cases. Sacroiliac joints were painful in 15 patients (34%). MRI was normal in 25 patients (57%) (G1:11 versus G2:14) and showed bone marrow edema in the sacroiliac joints in 19 patients (34%) (G1=16 versus G2=3, p=0.005). Sacroiliac joints MRI's sensitivity and specificity in the ERA diagnosis were 61.54% and 82.35%, respectively. Positive and negative predictive values were 84.21% and 58.33%, respectively. Furthermore, sacroiliac joint pain in the clinical examination was able to predict sacroiliac bone edema in MRI with an odds ratio of 6.8 (95% CI 1.68-28.09; p=0.006). Our study showed that sacroiliac joint MRI has good specificity and positive predictive value in the diagnosis of ERA patients among JIA patients. This underlines the usefulness of sacroiliac joint MRI in the early diagnosis of ERA patients.

Does sacroiliitis is a mandatory criterion for enthesitis-related arthritis diagnosis?

Introduction and objectivesMagnetic resonance imaging (MRI) sensitivity and specificity seem to be less studied in enthesitis-related arthritis (ERA).We aimed to determine the ability of sacroiliac MRI to diagnose ERA patients. Materials and methodsWe conducted a retrospective study including 44 patients with juvenile idiopathic arthritis (JIA). Each patient had a sacroiliac joint MRI. We divided patients into two groups: G1 patients with ERA and G2 patients with non-ERA subtype. ResultsERA was noted in 61% of the cases. Sacroiliac joints were painful in 15 patients (34%). MRI was normal in 25 patients (57%) (G1:11 versus G2:14) and showed bone marrow edema in the sacroiliac joints in 19 patients (34%) (G1=16 versus G2=3, p=0.005).Sacroiliac joints MRI's sensitivity and specificity in the ERA diagnosis were 61.54% and 82.35%, respectively. Positive and negative predictive values were 84.21% and 58.33%, respectively. Furthermore, sacroiliac joint pain in the clinical examination was able to predict sacroiliac bone edema in MRI with an odds ratio of 6.8 (95% CI 1.68–28.09; p=0.006). ConclusionOur study showed that sacroiliac joint MRI has good specificity and positive predictive value in the diagnosis of ERA patients among JIA patients. This underlines the usefulness of sacroiliac joint MRI in the early diagnosis of ERA patients.

Comparison of Biopsychosocial Characteristics of Children with Juvenile Idiopathic Arthritis According to Common Disease Subtypes.

In this study, we assessed the functional and biopsychosocial characteristics of juvenile idiopathic arthritis (JIA) patients according to disease subtypes. Child Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Disease Activity Score-71 (JADAS-71), and Juvenile Arthritis Biopsychosocial Questionnaire (JAB-Q) scales were administered to 304 JIA patients, and the subscale of JAB-Q was administered to their families. The median age of JIA patients at diagnosis was 7.9 (5.5-13) years (female/male = 1.3). Most patients were under treatment (68.7%) and had inactive disease (69.3%). While there was no significant difference between JADAS-71 scores according to the JIA subtypes, total CHAQ scores in polyarticular JIA patients were higher than in systemic JIA patients (P = .005). Enthesitis-related arthritis (ERA) patients had higher JAB-Q fatigue total scores compared to systemic JJIA patients (P = .001). Juvenile Arthritis Biopsychosocial Questionnaire-child psychosocial status scores were higher in polyarticular JIA patients than oligoarticular and systemic JIA patients (P = .004 and P = .003, respectively), and they had higher JAB-Q child form total scores than systemic JIA patients (P = .006). In addition, systemic JIA patients' parents had higher JAB-Q family total scores compared to oligoarticular JIA patients' parents (P = .03). Our results suggest that polyarticular JIA patients had higher CHAQ, JAB-Q psychosocial status, and child form total scores, and the JAB-Q fatigue score was higher in ERA patients. Also, JAB-Q-parent scores were higher in systemic JIA patients' parents. Biopsychosocial characteristics should be evaluated in both JIA patients and their parents.

TRF-21-LNK8KEP1B as a potential novel diagnostic biomarker for enthesitis-related arthritis

ObjectivetRNA-derived fragments (tRFs) play crucial roles in the progression of various diseases, and widely distribute in human tissues, including blood and urine. The diagnosis of enthesitis-related arthritis (ERA) is based on the observation of clinical manifestations. Therefore, we aimed to investigate whether serum tRFs can be used as diagnostic markers for ERA. MethodsSerum was collected from children admitted to the Children’s Hospital Affiliated with Nanjing Medical University between February 2022 to October 2022. The expression profiles of tRFs in the serum of ERA patients (n = 5) and healthy controls (HCs; n = 5) were investigated using small RNA high-throughput sequencing. The level and diagnostic value of tRF-21-LNK8KEP1B were evaluated by real-time quantitative PCR in serum samples from 30 ERA patients and 31 HCs. The specificity and sensitivity of tRFs were determined using receiver operating characteristic analyses. Bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs. ResultsNinety-eight upregulated and 63 downregulated tRFs were identified in the serum. We selected tRF-21-LNK8KEP1B as a candidate marker using KEGG pathway enrichment and PCR validation. tRF-21-LNK8KEP1B was substantially increased in the serum of ERA patients compared with that in HCs. The area under the curve (AUC) for tRF-21-LNK8KEP1B in the ERA group was 0.7849. ConclusionsCollectively, we demonstrated the promising role of serum tRF-21-LNK8KEP1B -levels as a diagnostic biomarker for ERA.

C1-C2 subluxation in enthesitis-related arthritis: two case reports and literature review of ten cases

BackgroundC1-C2 subluxation is a rare complication of enthesitis-related arthritis (ERA). If left untreated, it may lead to functional impairment or cervical spinal cord compression. This study aims to highlight key points regarding the management of C1-C2 subluxation in ERA.Case presentationWe present two cases of C1-C2 subluxation: an 8-year-old boy with ERA and 16-year-old boy with ERA with bilateral sacroiliitis. Ten cases of ERA in the literature were reviewed. The diagnosis of C1-C2 subluxation is mostly based on radiographs and cervical spine computed tomography. All patients were treated with non-steroidal anti-inflammatory drugs. Six ERA patients were treated surgically for cervical fusion. Most ERA patients with sacroiliitis had cervical collar protection. Neurologic abnormalities after treatment were not reported. Despite the use of cervical collar, cervical fusion and persisting ankylosis were found in two ERA patients with sacroiliitis without surgical treatment.ConclusionsCervical spine protection and ruling out spinal cord compression should be prioritized, in addition to controlling the underlying inflammation in ERA. Cervical halter traction may be applied after severe cervical inflammation is excluded. To reduce the risk of complications, early recognition and appropriate treatments of C1-C2 subluxation in ERA are essential.

The Juvenile Spondyloarthritis Disease Activity Index Is a Useful Tool in Enthesitis-Related Arthritis: Real-Life Data.

To compare enthesitis-related arthritis (ERA) patients with active and inactive disease at 6 months and define baseline predictors for disease inactivity. In addition, to evaluate the demographic, clinical, and laboratory characteristics of ERA patients and to identify the real-life impact of the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) in predicting active disease in ERA. This medical record review study was conducted with 56 patients who were diagnosed with ERA at our clinic between June 2009 and June 2022. Demographic and clinical characteristics, laboratory parameters, treatment, and JSpADA were recorded. The patients were divided into 2 groups as active (n = 34) and inactive (n = 22) according to their disease activity at the sixth month. Sex, age at diagnosis, number and type of affected joints, and presence of sacroiliitis were similar in both groups. There was no difference in baseline erythrocyte sedimentation rate, but there was a significant difference in erythrocyte sedimentation rate at the third month (p = 0.52 and p = 0.018, respectively). The median JSpADA values at disease onset were 3.5 (interquartile range [IQR], 3-4.5) and 3.3 (IQR, 2.5-4) in the active and inactive groups, respectively (p = 0.27). At the third month, the median JSpADA values were 1.5 (IQR, 0.5-2.1) in the active group and 0.5 (IQR, 0.5-1.5) in the inactive group (p = 0.037). The cutoff value for JSpADA at the third month for active disease persisting at the sixth month was determined as 1 point (area under the curve, 0.662 ± 0.06; p = 0.042; 95% confidence interval, 0.51-0.80) by receiver operating characteristic curve analysis. In ERA patients, a persistently high JSpADA value at follow-up is a predictive factor for active disease at the sixth month.

High prevalence of sacroiliitis and early structural changes in the sacroiliac joint in children with enthesitis-related arthritis: findings from a tertiary centre in Hong Kong

BackgroundEpidemiological studies have demonstrated a wide, unexplained disparity in the prevalence of juvenile idiopathic arthritis (JIA) subtypes depending on geographical location, ethnicity and other factors. Enthesitis-related arthritis (ERA) is more prevalent in Southeast Asia. Axial involvement in ERA patients is increasingly recognised to occur early in the disease course. Inflammation in the sacroiliac joint (SIJ) observed on MRI seems highly predictive of subsequent structural radiographic progression. The resulting structural damage can have significant impacts on both functional status and spinal mobility. This study aimed to evaluate the clinical characteristics of ERA in a tertiary centre in Hong Kong. The primary objective of the study was to provide a comprehensive description of the clinical course and radiological findings of the SIJ among ERA patients.MethodPaediatric patients diagnosed with JIA attending the paediatric rheumatology clinic from January 1990 to December 2020 were recruited from our registry based at the Prince of Wales Hospital.ResultsIn our cohort, 101 children were included. The median age of diagnosis was 11 years, interquartile range (IQR) 8-15 years. The median follow-up duration was 7 years (IQR 2–11.5 years). ERA was the most prevalent subtype (40%), followed by oligoarticular JIA (17%).Axial involvement was frequently reported in our cohort of ERA patients. 78% demonstrated radiological evidence of sacroiliitis. Among those, 81% had bilateral involvement. The median duration from disease onset to confirmation of radiological sacroiliitis was 17 months (IQR 4-62 months). Among the ERA patients, 73% had structural changes of the SIJ. Alarmingly, 70% of these patients had already developed radiological structural changes when sacroiliitis was first detected on imaging (IQR 0-12 months). Erosion was the most common finding (73%), followed by sclerosis (63%), joint space narrowing (23%), ankylosis (7%) and fatty change (3%). The duration from symptom onset to diagnosis was significantly longer in ERA patients with SIJ structural changes (9 vs 2 months, p = 0.009), comparing with those without.ConclusionWe found that a high proportion of ERA patients had sacroiliitis and a significant number of them had radiological structural changes during early disease. Our findings illustrate the importance of prompt diagnosis and early treatment in these children.

Clues for inflammatory diseases in the differential diagnosis of a child with sacroiliitis.

The purpose of this study was to compare the demographic, clinical and laboratory characteristics of patients with enthesitis-related arthritis (ERA), familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD), which are inflammatory diseases that may develop sacroiliitis. Thus, it was aimed to reveal various findings that may indicate primary disease in patients with sacroiliitis. Pediatric patients aged 6-18 years, who were being followed with a diagnosis of ERA (n= 62), FMF (n= 590), and IBD (n= 56) over the period 2013-2021 were included in the study. Sacroiliitis (n= 55) was diagnosed by magnetic resonance imaging of the sacroiliac joint, obtained from clinically suspected patients. Sacroiliitis was detected in 54.8% of ERA patients, 2.3% of FMF patients, and 12.5% of IBD patients. The mean follow-up period was 4.1± 2.8 years (10 months-8 years) for the entire study group. The most common MRI finding for sacroiliitis was bone marrow edema. Peripheral joint involvement (73.5%) and HLA B27 positivity (64.7%) was significantly higher in ERA patients, and ERA was diagnosed more frequently in patients presenting with sacroiliitis. Non-steroidal anti-inflammatory drugs (NSAIDs) were the first choice of treatment agent when sacroiliitis developed in all three patient groups. The clinical and laboratory findings of ERA, FMF and IBD can sometimes be intertwined or can even coexist. Treatment may differ depending on the disease associated with sacroiliitis, although NSAIDs may be used in the first-line treatment of all three diseases. Sacroiliitis patients with HLA B27 positivity and peripheral arthritis may need to be addressed as ERA.

Enthesitis-related arthritis: the clinical characteristics and factors related to MRI remission of sacroiliitis

BackgroundTo describe the clinical characteristics and explore the factors related to the MRI remission of sacroiliitis in patients with enthesitis-related arthritis (ERA).MethodsPatients with ERA from 2018–2022 in our medical center were retrospectively reviewed, which identified according to Pediatric Rheumatology International Trials Organization (PRINTO) criteria. Demographics, clinical characteristics, examinations, and treatments were described. Univariate and multivariate logistic regression models were used to analyze the factors related to MRI remission of sacroiliitis in ERA.ResultsThis retrospective study included 160 ERA patients (51.9% male) with a mean onset age of 9.2 ± 3.0 years. There were 144 cases (81.9%) with peripheral arthritis, and the hip, knee, and ankle joints were the most commonly involved joints. Enthesitis occurred in 48 cases (30.0%), and sacroiliitis occurred in 142 cases (88.5%) at diagnosis. Human leukocyte antigen (HLA)-B27 was positive in 33 cases (17.1%), and acute uveitis occurred in 3 cases (1.9%). The majority of patients (93.7%) were treated with disease-modifying anti-rheumatic drugs (DMARDs), and 60% with biologics. Among 62 patients with MRI-defined sacroiliitis, 27 (43.5%) cases showed improvement in the sacroiliac joint lesion after treatment. Multivariate logistic regression analysis showed that duration from onset to diagnosis of less than 3 months (OR = 3.609, 95% CI: 1.068–12.192) and active joints of more than 4 (OR = 4.916, 95% CI: 1.006–24.037) were independent factors.ConclusionWe highlighted differences in ERA clinical characteristics. Patients with a shorter diagnosis time and more joint involvement improved more significantly in sacroiliac joint lesions after treatment.

27 Single center inception cohort of enthesitis-related arthritis: spectrum of characteristics, course and treatment approaches

BackgroundEnthesitis-related arthritis (ERA) accounts for ∼10% to 20% of juvenile idiopathic arthritis (JIA) cases. Application of adult data to children with ERA is not ideal as less severe spinal involvement and more pronounced enthesitis and peripheral arthritis are present in children. Therefore, it is very important to conduct research that focuses specifically on the ERA population.ObjectivesThis study aimed to present an ERA inception cohort and determine which entheses and joints are most commonly affected, course of the disease and treatment approaches.MethodsMedical records of 546 patients with JIA who met each of the International League of Associations for Rheumatology (ILAR) criteria were evaluated retrospectively. An inception cohort of children with ERA who were diagnosed at Istanbul Faculty of Medicine between December 2020 and April 2022 was included. Patient characteristics were summarized by median and interquartile range (IQR) for continuous variables and frequency and percentage for categorical variables. P values <0.05 were considered statistically significant. All analyses were performed using SPSS statistical software version 28.ResultsThere were 34 newly diagnosed ERA patients. Sixty percent were male, and the median age at the onset of the disease was 11.5 years (interquartile range [IQR] 9–14.8 years). The majority of the group met the ILAR criteria for a diagnosis of ERA at the first pediatric rheumatology visit (n = 29 [85.2%]), with 5 subjects (14.7%) meeting the criteria at the second visit. Twenty-three (69 %) subjects had enthesitis and arthritis at the time of diagnosis. The median number of tender entheses at presentation was 2 (IQR 0–4), and 20 subjects (58%) had at least 1 tender enthesis. The most frequent enthesitis were located on the patellar ligament insertion at the inferior pole of the patella, the plantar fascial insertion at the calcaneus, the Achilles tendon insertion at the calcaneus, and the plantar fascial insertion at the metatarsal heads. Fifty-five (19)% of patients had symmetric enthesitis. The most commonly affected joints were the sacroiliacs, knees, and ankles. Medication use varied significantly across sites for children with peripheral arthritis (p< 0.001), but not for sacroiliitis or enthesitis only. Nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs were the most commonly prescribed treatments, with anti-TNF agents primarily being initiation for sacroiliitis. HLA-B27 positivity was associated with male sex, higher active joint count, sacroiliitis, and higher disease activity at disease onset. The Juvenile Spondyloarthritis Disease Activity Index (JSpADA) was significantly higher in those who were HLA-B27-positive than in those who were HLA-B27-negative (p = 0.03). Those who were HLA-B27-positive were more likely to develop arthritis after the age of 6 years (p< 0.01).ConclusionEither the observed heterogeneity in clinical presentation may result from differences in patient populations or from differences in the way ILAR criteria are applied. Most children have a pauciarticular onset and lower extremity enthesitis is common when ERA diagnosed.

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, associationof 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 levelssuggest that it may play a role in synovitis seen in ERA. IgA antiCD74 antibodies are rarely seen in ERA.

Comparison of the outcomes between early and late anti-tumor necrosis factor therapy in patients with enthesitis-related subcategory of juvenile idiopathic arthritis: a multi-center study in Southeast Asia

ABSTRACT Background Little is known about the impact of delayed initiation of anti-tumor necrosis factor (TNF) therapy in patients with enthesitis-related arthritis (ERA). Here, we compared the impact of delayed treatment on disease outcomes of ERA patients in Southeast Asia. Research design and methods This retrospective study enrolled 149 ERA patients from Thailand and Singapore. Early (e-aTNF) and late (l-aTNF) treatment groups received anti-TNF therapy starting at ≤6 months and >6 months, respectively, after diagnosis. Outcomes included mean differences in disease activity parameters, Juvenile Spondyloarthritis Disease Activity (JSpADA) score, Juvenile Arthritis Diseases Activity (JADAS)-10 score, and American College of Rheumatology Pediatric (ACR Pedi) criteria, and the frequency of clinically inactive disease and first flare event. Results The mean changes in JSpADA (p = 0.002) and JADAS-10 (p < 0.001) scores over time were significantly higher in the e-aTNF group than in the l-aTNF group. A significantly higher proportion of patients in the e-aTNF group than l-aTNF group satisfied ACR Pedi 100 criteria at 2 years (p = 0.042). All other long-term outcomes were not significantly different between the groups. Conclusions Although early anti-TNF treatment improved disease activity parameters somewhat better than delayed anti-TNF therapy, there was no significant difference in long-term outcomes.

Sacroiliitis at diagnosis as a protective predictor against disease flare after stopping medication: outcomes of a Southeast Asian enthesitis-related arthritis (ERA) longitudinal cohort.

To assess short- and long-term outcomes of ERA in a large monocentric cohort in Singapore. Children diagnosed with ERA according to ILAR criteria from 2002 to 2021 were recruited. Nonparametric statistics were used to describe the data. Outcomes were defined according to modified Wallace criteria, and probabilities and predictors were determined using Kaplan-Meier survival and logistic regression analyses. One hundred fifty-one ERA patients (male 86%; Chinese 81%) were included. The median age at onset was 11.9years (IQR: 9.4-13.9), and disease duration was 5.3years (IQR: 2.9-8.4). At diagnosis, 39% of the patients had sacroiliitis. HLA-B27 was positive in 83%, and biologics were used in 72% of the patients. Clinical inactive disease (CID) was achieved in 92% of the patients, of which 27% achieved within 6months. Sacroiliitis at diagnosis is an unfavorable predictor of early CID at 6months. Medication was discontinued in one-third of the patients. Favorable predictor of medication withdrawal includes male gender, while unfavorable predictors include positive HLA-B27 and ANA. Two-thirds of the patients with CID had at least one disease flare. Sacroiliitis at diagnosis is a protective predictor of flare after stopping medication. Despite a high proportion of ERA patients achieving CID, only one-third could stop medication with high rates of disease flare. Unfavorable predictors include older age at onset, HLA-B27, and ANA positivity. While sacroiliitis at diagnosis is a negative predictor of CID at 6months, it is associated with less disease flare after discontinuing medication.

IL-36γ in enthesitis-related juvenile idiopathic arthritis and its association with disease activity.

IL-36 has been implicated in the pathogenesis of spondyloarthropathies (SpA) like psoriasis and inflammatory bowel disease. Enthesitis-related arthritis (ERA) category of juvenile idiopathic arthritis is a form of juvenile SpA, however, no data is available on the role of IL-36 in this disease. IL-36α, β, γ and IL-36R mRNA expression in blood and synovial fluid mononuclear cells and IL-36α, γ, IL-36Ra, IL-6, and IL-17 levels were measured in serum and synovial fluid (SF). IL-36γ production by fibroblast-like synoviocytes (FLS) upon stimulation with pro-inflammatory cytokines and its effect on FLS were also studied. mRNA levels of IL-36α, IL-36γ, and IL-36R were increased in PBMCs of ERA patients as compared to healthy controls however only IL-36γ was measurable in the serum of one-third of patients. In SFMCs, all four mRNA were detectable but were lower than RA patients. SF IL-36γ levels correlated with disease activity score (r = 0.51, P < 0.0001), SF IL-6 (r = 0.4, P = 0.0063) and IL-17 levels (r = 0.57, P = 0.0018). Pro-inflammatory cytokines increased the expression of IL-36γ and IL-6 in FLS cultures. SFs from five ERA patients also increased expressions of IL-36γ and IL-6 in FLS which could be blocked by using IL-36Ra. This suggests that pro-inflammatory cytokines aid in the upregulation of IL-36γ which in turn may upregulate the expression of IL-6. This might lead to a positive feedback loop of inflammation in ERA. Association of SF levels of IL-36γ with disease activity further supports this possibility. IL-36Ra based therapy may have a role in ERA.

The performances of the ILAR, ASAS, and PRINTO classification criteria in ERA patients: a comparison study.

Enthesitis-related arthritis (ERA) could be considered the pediatric equivalent of ankylosing spondylitis in adults albeit with certain significant differences. We aim to evaluate the sensitivity and specificity of the International League of Associations for Rheumatology (ILAR), the Assessment of Spondyloarthritis International Society (ASAS), and the preliminary Pediatric Rheumatology International Trials Organization (PRINTO) classification criteria in ERA patients. The medical records of ERA patients who were followed up between January 2005 and September 2020 have been analyzed. The control group consisted of patients with oligoarticular JIA (n = 146), polyarticular JIA (n = 55), and psoriatic arthritis (n = 20). This retrospective study included 108 ERA (73.1% male) and 221 control patients (25.8% male). The median age at diagnosis for ERA and control patients were 12.5 and 4.0years, respectively (p < 0.001). Arthritis was observed more frequently in the control group at diagnosis and in the follow-up (p < 0.001 for both), while enthesitis, sacroiliac joint tenderness, and inflammatory back pain were more common in the ERA group both at diagnosis and in the follow-up (p < 0.001 for all). In sacroiliac imaging, 70.1% of ERA patients had positive findings suggestive of sacroiliitis at diagnosis and 78% in the follow-up. The sensitivities of ILAR, PRINTO, ASAS criteria for axial SpA, and peripheral SpA at diagnosis were 74.0%, 57.4%, 21.3%, and 85.1%, respectively which increased to 82.4%, 78.7%, 35.1%, and 92.5%, respectively at follow-up. The specificities were 100%, 100%, 99.1%, and 90.9%, respectively at both diagnosis and follow-up. The ASAS criteria for peripheral SpA were the most sensitive while ILAR and the preliminary PRINTO criteria were the most specific criteria for classifying ERA patients. The ASAS criteria for peripheral SpA were the most sensitive criteria for classifying ERA patients. The use of ASAS axial SpA criteria may provide early detection of axial involvement.

P009 Osteoporosis is a frequent complication in enthesitis related arthritis patients

Abstract Background Enthesitis related arthritis (ERA) represents a clinical entity of juvenile idiopathic arthritis. This chronic rheumatic disease may lead to early bone mass loss and increase risk fracture. The aims of this study were to evaluate the prevalence of clinical osteoporosis in patients with ERA and to identify what factors are associated with increased occurrence of osteoporosis. Methods We reviewed the medical records of patients with confirmed ERA. We analyzed their demographic data and the clinical characteristics. Dual-energy X-ray absorptiometry (DEXA) was used to determine bone status. Osteoporosis was defined as Z score &amp;lt;-2.5DS. Disease activity was evaluated by: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were analyzed using the SPSS statistical package. A P-value &amp;lt; 0.05 was considered significant. Results Thirty-three patients (27 male and 7 female) with a mean age at of 23.8 ± 7.5 years were enrolled. The mean age at disease onset was 12 ± 2.6 years. Median disease duration was 108 months [12–408]. The median ESR and CRP levels were 35 mm/h [8–90] and 20 mg/l [1–70] respectively. Median BASDAI score was 4.7 [1–9.7]. At bone densitometry, osteoporosis and osteopenia were found in 44.1% and 23.5% cases respectively. None of the patients had a history of osteoporotic fractures. Long term corticosteroid therapy and sedentarily were noted in 18.2% and 47.1% of patients respectively. On statistical analysis, osteoporosis was associated with these parameters: age at ERA onset (P = 0.035), disease duration (P = 0.04), CRP (P = 0.009), BASDAI score (P = 0.05) and sedentarily (P = 0.031). Neither corticosteroid therapy (P = 0.68) nor high ESR level (P = 0.73) were associated with osteoporosis. Conclusion In this study, osteoporosis was a common extra articular feature during ERA. As adult spondyloarthritis, disease activity, duration and sedentarily seem to be associated with the bone loss.

Enthesitis Related Arthritis: A Single Center Experience

Objective: Enthesitis-related arthritis is a subtype of juvenile idiopathic arthritis category, characterized by enthesitis, arthritis, and the risk of axial involvement. We aimed to summarize the demographics, clinical, and laboratory findings of enthesitis-related arthritis patients and to identify the distinguishing features of enthesitis-related arthritis patients with HLA B27 positive compared to the patients who were HLA B27 negative.&#x0D; Materials and Methods: This retrospective study included patients with Enthesitis-related arthritis who followed up between 2015 and 2018. Demographical, clinical, and laboratory data were retrospectively reviewed from the patient files and computerized medical charts.&#x0D; Results: A total of 72 patients diagnosed with enthesitis-related arthritis were included in the study. The male/female ratio was 2.1/1. Fifty-three (73%) of them presented with peripheral arthritis. The most commonly affected joint was knee (81.1%), followed by the ankle (43%), hips (32%), and wrist (5%). HLA B27 was positive in 36 (50%) patients. During follow-up, the number of patients who developed enthesitis-related arthritis -associated uveitis was 8 (11.1%). During follow-up, 56 patients with inflammatory back pain and/or sacroiliac tenderness underwent spinal MRI. Ten (17.8%) patients had only thoracal and/or lumbar involvement, 18 (32%) had only sacroiliitis, and 9 (16%) patients had both of them on spinal MRI. In comparison with HLA-B27-negative children, HLA-B27-positive patients were more likely to have enthesitis (16 (44.4%) vs 8 (22.2%), p=0.046), MRI proven sacroiliitis (19 (52.7%) vs 8 (22.2%), p=0.031), MRI proven spinal involvement (13 (36.1%) vs 6 (16.6%), p=0.031), and uveitis (8 (100%) vs 0(0%), p=0.014). During follow up, 65/72 (90.2 %) of them needed disease-modifying antirheumatic drugs (DMARD), and 51/72 (70.8%) needed anti-tumor necrosis factor-α (TNF-α) therapy.&#x0D; Conclusion: We found that patients who were HLA-B27- positive had significantly more enthesitis, MRI-proven sacroiliitis, MRI-proven spinal involvement, and acute anterior uveitis, in comparison to patients who were HLA B27 negative. It is crucial to carefully assess those patients with concern for enthesitis-related arthritis to determine the expected prognosis and make therapeutic decisions appropriately.

Associations between HLA-B27 subtypes and outcomes in Thai children with enthesitis-related arthritis.

Expression of human leukocyte antigen B27 (HLA-B27) has been identified as a predictor of severe disease in enthesitis-related arthritis (ERA) patients. However, the associations between HLA-B27 subtypes and outcomes of this disease are still unclear. Here, we examined the distributions of HLA-B27 subtypes among ERA patients and the associations with disease outcomes. This was a historical cohort study of ERA patients. Patients were followed from diagnosis to the most recent visit. Relationships between outcomes and the HLA-B27 subtype were assessed by mixed-effect regression, Kaplan-Meier survival, and Cox proportional hazards regression analyses. Of the 66 ERA patients, 50 HLA-B27-positive (86% male) and 16 HLA-B27-negative (69% male) patients were included in this study. Patients with HLA-B27-positive were classified into HLA-B*27:04-positive (84%), including combined HLA-B*27:04 and HLA-B*27:07 (2%), and HLA-B*27:04-negative (16%), including HLA-B*27:05 (10%), HLA-B*27:06 (2%), HLA-B*27:07 (2%), and HLA-B*27:15 (2%). HLA-B*27:04-positive (83.3%) and HLA-B*27:04-negative patients (100%) had refractory disease more than HLA-B27-negative patients (37.5%, p = 0.001). HLA-B*27:04-negative patients (57%, 1.73years) had relapsing disease more and earlier than HLA-B*27:04-positive (35%, 5.54years) and HLA-B27-negative patients (40%, 6.92years; p < 0.001). Furthermore, HLA-B*27:04-negative was predictors of refractory disease (HR 4.56, 95%CI 1.40-14.87; p = 0.012) and relapsing disease (HR 3.80, 95% CI 1.18-12.30; p = 0.026). The duration before anti-tumor necrosis factor treatment initiation > 1year was also a predictor of refractory disease (HR 116.08, 95% CI 14.67-918.26; p < 0.001). HLA-B*27:04 was the most common HLA-B27 subtype in Thai ERA patients. HLA-B*27:04-negative was associated with more unfavorable outcomes than HLA-B*27:04-positive and HLA-B27-negative patients. Key Points • Most ERA patients in Thailand had HLA-B27-positive, and HLA-B*27:04 was the most common HLA-B27 allele in these patients. • The outcomes of ERA were associated with the presence of HLA-B27 and its subtypes. • HLA-B*27:04-negative patients had unfavorable outcomes, including refractory and relapsing disease, compared to HLA-B*27:04-positive and HLA-B27-negative patients.

Hip involvement in children with enthesitis related arthritis (ERA) is associated with poor outcomes in adulthood.

BackgroundThe data on long-term outcome in enthesitis-related arthritis (ERA), the commonest category of JIA in India, is scant. Thus, we studied outcomes of ERA in a resource-constrained setting.MethodsPatients with ERA (ILAR classification) (≥ 5 years of disease and ≥ 18 years) were included. Data on clinical features, Bath indices (BASMI, BASDAI, BASFI), ASDAS, and health assessment questionnaire-disability index (HAQ-DI) was collected. X-ray pelvis including hips was obtained and compared with baseline X-ray for progression of sacroiliitis and hip arthritis. Fulfillment of adult criteria of spondyloarthropathy (SpA) were also assessed.ResultsSeventy-three 73 patients (72 males) of median age 20 (18–23) years and disease duration 8 (5.5–11) years were recruited. There was delay in diagnosis of 4 (1.75–6) years. Thirty-nine (53%) had BASDAI ≥ 4 and 63 (91%) had ASDAS-CRP > 1.3. Two-third (60%) had functional disability (HAQ-DI ≥ 0.5). Poor outcome (BASDAI ≥ 4, ASDAS > 2.1, BASFI > 0.9, or HAQ-DI ≥ 0.5) was seen in three-fourths (n = 56.76%) of patients and was associated with hip involvement, HLA-B27 positivity, and fulfillment of axial ASAS criteria. Sixty-seven (91%) patients fulfilled axial ASAS criteria, while 71 (97%) fulfilled peripheral ASAS criteria.Overall, 81% had X-ray sacroiliitis and 37% had hip involvement. Nearly half (46.6%) and one-fourths (25%) of the patients had X-ray sacroiliitis and hip arthritis progression, respectively. Those with X-ray hip arthritis had longer delay in diagnosis (6 vs 3 years), higher Bath indices, ASDAS, and HAQ-DI. Hip arthritis correlated with radiological sacroiliitis (r = 0.301). Fulfillment of modified NY criteria was seen more often in patients with hip arthritis (95 vs 63%; p < 0.002).ConclusionMost ERA patients had active disease in adulthood. Hip involvement, axial involvement, and HLA-B27 positivity were predictors of poor outcome. Key Points • Almost 90% of adults with ERA had active disease even after 8 years of disease. • Poor outcomes were seen in three-fourths of patients and hip involvement, presence of HLA B27, and axial involvement were the predictors of poor outcome. Supplementary InformationThe online version contains supplementary material available at 10.1007/s10067-021-05807-3.