HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis

Objective.To determine the rate of temporomandibular joint (TMJ) involvement and find factors associated with TMJ arthritis in a single-center cohort of patients with juvenile idiopathic arthritis (JIA).Methods.Retrospective analysis of all patients with JIA visiting the rheumatology clinic between January 1, 2005, and December 31, 2006. Followup information was included until August 2008. A diagnosis of TMJ arthritis was based on clinical rheumatological and/or radiological findings.Results.After a mean followup time for JIA of 4.6 years (range 0.08–14.17), 86/223 patients (38.6%) had developed TMJ arthritis. The rate of TMJ involvement differed significantly among JIA subtypes (p = 0.0016), with 61% in extended oligoarticular, 52% in polyarticular rheumatoid factor (RF)-negative, 50% in psoriatic, 36% in systemic, 33% in polyarticular RF-positive, 33% in persistent oligoarticular, 30% in unclassified JIA, and 11% in enthesitis-related arthritis. The rate of TMJ involvement in our cohort was statistically significantly lower for patients who were HLA-B27-positive (p = 0.0002). In a multivariate analysis, the association of the following factors was confirmed: JIA subtype (p = 0.0001), a higher erythrocyte sedimentation rate (ESR) at diagnosis (p = 0.0038), involvement of joints of the upper extremity (p = 0.011), the absence of HLA-B27 (p = 0.023), and younger age at onset of JIA (p = 0.050).Conclusion.In our cohort of children with JIA, the overall rate of TMJ involvement was 38.6%. Patients with certain JIA subtypes, a higher ESR at disease onset, involvement of upper extremity joints, and younger age at diagnosis were more likely to develop TMJ arthritis. The presence of HLA-B27 seemed to be protective.

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HLA-B27 Predicts a More Chronic Disease Course in an 8-year Followup Cohort of Patients with Juvenile Idiopathic Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.121257 ◽

2013 ◽

Vol 40 (5) ◽

pp. 725-731 ◽

Cited By ~ 27

Author(s):

Lillemor Berntson ◽

Ellen Nordal ◽

Kristiina Aalto ◽

Suvi Peltoniemi ◽

Troels Herlin ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Age At Onset ◽

Disease Onset ◽

Clinical Signs ◽

Clinical Manifestations ◽

Population Based ◽

Hla B27 ◽

Disease Characteristics ◽

Serological Data ◽

Longterm Outcome

Objective.We investigated associations of HLA-B27 with clinical manifestations and longterm outcome in a near population-based setting among patients with juvenile idiopathic arthritis (JIA).Methods.We studied clinical and serological data from 410 patients with HLA-B27 results among 440 prospectively collected patients with JIA with 8-year followup data in a Nordic database. The study was structured to be as close to a population-based study as possible.Results.HLA-B27 was analyzed in 93% of patients, and was positive in 21% of the cohort, in 18.4% of the girls and in 25.9% of the boys. Boys who were HLA-B27-positive had significantly higher age at onset compared to HLA-B27-negative boys and compared to both HLA-B27-negative and positive girls. This difference in onset age in relation to HLA-B27 was not found in girls. HLA-B27 was associated with clinical signs of sacroiliitis, enthesitis, and tenosynovitis in boys, but not in girls. After 8 years of disease, 46 children (11.2%) were classified as having enthesitis-related arthritis (ERA). Boys with ERA had clinical signs of sacroiliitis more often than girls with ERA. HLA-B27-positive children, as well as children with clinical signs of sacroiliitis, enthesitis, and hip arthritis, had higher odds of not being in remission off medication after 8 years of disease.Conclusion.In this near population-based Nordic JIA cohort we found significant differences between HLA-B27-positive boys and girls in age at disease onset, clinical signs of sacroiliitis, and ERA classification. HLA-B27 was negatively associated with longterm remission status, possibly because of its association with clinical disease characteristics, such as sacroiliitis, rather than being a general marker of persistent disease.

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Younger age of onset and uveitis associated with HLA-B27 and delayed diagnosis in Thai patients with axial spondyloarthritis

Scientific Reports ◽

10.1038/s41598-021-93001-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Naphruet Limsakul ◽

Praveena Chiowchanwisawakit ◽

Parichart Permpikul ◽

Yubolrat Thanaketpaisarn

Keyword(s):

Regression Analysis ◽

Multiple Regression Analysis ◽

Axial Spondyloarthritis ◽

Age At Onset ◽

Delayed Diagnosis ◽

Musculoskeletal Symptom ◽

Hla B27 ◽

Delay In Diagnosis ◽

Factors Associated ◽

Younger Age

AbstractTo identify characteristics associated with HLA-B27, and to identify factors associated with delayed diagnosis in Thai patients with axial spondyloarthritis (axSpA). This cross-sectional study included Thai patients were diagnosed with axSpA by a rheumatologist at Siriraj Hospital. Clinical data were collected. Regression analyses were employed to identify factors associated with study outcomes. Of total 177 patients, 127 (72%) were positive HLA-B27. Uveitis [Odds ratio (OR) 4.0], age at onset of the first musculoskeletal symptom of ≤ 28 years [OR 3.5], female [OR 0.4], and psoriasis [OR 0.4] were significantly associated with HLA-B27 in multiple regression analysis. Those with positive HLA-B27 had less spinal flexibility. Elevated C-reactive protein (p = 0.012) was associated with shorter delay in diagnosis, while uveitis (p < 0.001) and younger age at onset of the first symptom (p = 0.002) were associated with longer delay in diagnosis in multiple regression analysis. Younger age at onset of the first musculoskeletal symptom and uveitis were associated with HLA-B27 and delayed diagnosis in axSpA patients. Young people with musculoskeletal symptom and uveitis should be referred to a rheumatologist to rule out or make a timely diagnosis of axSpA.

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THU0502 EFFICACY AND SAFETY OF SECUKINUMAB TREATMENT IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5847 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 489.3-489

Author(s):

I. Kriulin ◽

E. Alexeeva ◽

T. Dvoryakovskaya ◽

K. Isaeva ◽

A. Chomakhidze ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Psoriatic Arthritis ◽

Response To Therapy ◽

Inactive Disease ◽

Hla B27 ◽

Serious Adverse Events ◽

National Medical ◽

Alternative Drug ◽

Baseline Information

Background:Anti-IL-17A biologic drug secukinumab (SEC) proved to be effective for treatment of psoriatic arthritis. However data about its efficacy in juvenile idiopathic arthritis (JIA) are restricted to off-label experience.Objectives:To evaluate the effectiveness and safety of SEC in JIA patients in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:25 patients started SEC therapy from 12/2017 to 11/2019 in single-center prospective study. 3 patients withdrew treatment: two patients (8%) due to AE (1 - allergy followed by MAS after first injection and 1 – leukopenia) and one patient (4%) – after 10 months of treatment due to secondary inefficacy. Among others, 14 patients which were successfully treated for 6 months or longer were included into analysis. At the baseline, information was collected on the characteristics of the onset of the disease, previous therapy and its success. Patients were monitored at least 1 time per year. At each visit, clinical and laboratory characteristics of JIA severity were assessed. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the C.Wallace criteria for inactive disease (WID) and clinical remission. AEs were assessed at each visit.Results:Among 14 patients received SEC for at least 6 months, 7 (50%) have enthesitis-related arthritis, one (7.1%) – persistent oligoarthritis, 4 (28.6%) – RF-negative polyarthritis, 2 (14.3%) – psoriatic arthritis. 6 patients (42.9%) were HLA-B27 positive. Median age of JIA onset was 8.8 (IQR 5:11), age at SEC initiation – 14 (9.9:16.1), disease duration before SEC start – 3.3 (2.7:5.8). 7 (50%) were biologics-naïve, 2 (14.3%) were previously treated with anti-TNF drug, 5 (35.7%) have 2 or more different biologics in anamnesis.SEC demonstrated high efficacy after the first injection resulting in JADAS-71 decreasing in all patients by median 4.3 (1.6:7.1) points and 7/7/5/2 patients (50%/50%/35.7%/14.3%) achieved ACR Pedi 30/50/70/90 response.After 6 months of treatment, WID was achieved by 7 (50%) patients, JADAS-71 decreased from baseline level 15.2 (12.7:20.5) to 0.8 (0:4.2) points, and 14/13/11/9 patients (100%/92.9%/78.6%/64.3%) achieved ACR Pedi 30/50/70/90 response. One patients who had active uveitis at SEC initiation remained with subactive uveitis; one patient with uveitis remission had not flare episodes during follow-up period. One patient (7.1%) had successfully treated evaluation of transaminases after 4-th injection.Conclusion:Secukinumab showed high effectiveness and safety in children with JIA and can be further used both as a first-line drug in JIA associated with HLA-B27, and as an alternative drug for the ineffectiveness of the standard treatment regimen with biologics. No serious adverse events were registered during follow-up period.Disclosure of Interests:Ivan Kriulin: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Elizaveta Krekhova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared

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Epidemiology of pediatric uveitis and associated systemic diseases

Pediatric Rheumatology ◽

10.1186/s12969-021-00516-2 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yoonkyeom Shin ◽

Ji-Man Kang ◽

Junwon Lee ◽

Christopher Seungkyu Lee ◽

Sung Chul Lee ◽

...

Keyword(s):

Rheumatic Disease ◽

Inflammatory Disease ◽

Pediatric Patients ◽

Age At Onset ◽

Laboratory Data ◽

Categorical Variables ◽

Hla B27 ◽

Female Ratio ◽

Systemic Rheumatic Disease ◽

Systemic Inflammatory Disease

Abstract Background The early detection of uveitis associated with systemic inflammatory disease in children is important for proper treatment and prognosis. However, the diagnosis may be delayed because of difficulties in childhood examinations and early minor systemic symptoms. The objective of our study was to identify the pattern of childhood uveitis and investigate the frequency and clinical features of rheumatic diseases in pediatric patients with uveitis. Methods This retrospective observational study reviewed the medical records of children (age ≤ 18 years) with uveitis at a Korean tertiary hospital between January 2005 and December 2018. Data collected included the age at onset of uveitis, sex, anatomic location of ocular inflammation, comorbid disease (including systemic inflammatory disease), ocular complications, relevant laboratory data, and treatment. Fisher’s exact test was used to compare categorical variables and the Mann–Whitney U test was used to compare continuous variables. A p-value of < 0.05 was considered statistically significant. Results A total of 155 pediatric patients with uveitis were included in this study. The median age at diagnosis was 13.0 years (interquartile range, 9.5–16.0 years). The male-to-female ratio was 1.09. The process was unilateral in 51.6% of children. Anterior uveitis, panuveitis, intermediate uveitis, and posterior uveitis represented 51.6, 26.5, 6.5, and 1.9% of the cases, respectively. Idiopathic uveitis (65.2%) was the most frequent type of uveitis. Systemic rheumatic disease associations were responsible for 28.4% of the cases, among which juvenile idiopathic arthritis (JIA) was the most frequent cause (14.8%). Human leukocyte antigen (HLA)-B27 and antinuclear antibody (ANA) positive rates were significantly higher in patients with JIA than in those with idiopathic uveitis (p = 0.006 and p = 0.007, respectively). Conclusions Approximately one-third of children with uveitis in Korea have a systemic rheumatic disease, of which JIA accounts for the majority of cases. HLA-B27 and ANA can serve as risk factors for JIA-associated uveitis.

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STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms as markers of predisposition to juvenile idiopathic arthritis. What can genetics give to understand its heterogeneity?

Modern Rheumatology Journal ◽

10.14412/1996-7012-2019-4-55-60 ◽

2019 ◽

Vol 13 (4) ◽

pp. 55-60

Author(s):

E. S. Fedorov ◽

M. Yu. Krylov ◽

S. O. Salugina ◽

E. Yu. Samarkina ◽

A. N. Latypova

Keyword(s):

Juvenile Idiopathic Arthritis ◽

High Risk ◽

Antinuclear Antibody ◽

Pediatric Population ◽

Human Leukocyte ◽

Control Group ◽

Entire Group ◽

Hla B27 ◽

Systemic Jia ◽

Allele Specific

Juvenile idiopathic arthritis (JIA) is a multifactorial immune-mediated inflammatory disease in childhood, the most common type of rheumatic disease in children. It is characterized by the polygenic type of hereditary predisposition.Objective: to study the association of STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms with the predisposition to certain JIA subtypes in the Russian pediatric population.Patients and methods. The investigation enrolled 177 patients, including 66 patients diagnosed with JIA and 111 healthy unrelated volunteers (a control group). Of the 66 patients with JIA there were 30 (45%) with oligoarthritis: 20 (67%) with human leukocyte antigen B27(HLA-B27)-positive JIA (that was associated with enthesitis, HLA-B27 positive JIA (JIA-B27), 10 (33%) with anterior uveitis concurrent with antinuclear antibody-positive JIA (JIA-uveitis); 20 (30%) with polyarticular JIA (JIA-poly), seronegative for rheumatoid factor; and 16 (24%) with systemic JIA (JIA-sys). As a control for genotyping STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms, the investigators studied 103 and 111 DNA samples from healthy adult volunteers, respectively. STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms were investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results and discussion. In the oligoarticular JIA group, the frequency of the STAT4 T allele was significantly higher than that in the control group (38.3 and 20.4%, respectively; p=0.004). This allele was also significantly more common in the JIA-B27 (35.0 and 20.4%, respectively; p=0.044) and JIA-uveitis (45.0 and 20.4%, respectively; p=0.021) groups compared with the control one. No significant differences were found in the frequency of the mutant STAT4 T allele between the control group and the JIA-sys and JIA-poly groups. Regression analysis showed that the identification of the STAT4 T allele was associated with the high risk of a predisposition to oligoarticular JIA as a whole (odds ratio, OR 2.43; 95% confidence interval (CI) 1.23–4.70; p=0.007), as well as to the antinuclear antibody-positive oligoarticular JIA with uveitis (JIA-uveitis): the risk in T allele carriers was 3.2 times higher than that in the control (OR 3.19; 95% CI 1.09–9.06; p= ). A high risk for predisposition was also found in the JIA-B27 subgroup compared with the control (OR 2.10; 95% CI 0.38–4.60; p=0.070). There were no statistical differences in the frequency of genotypes and alleles of the IRF5 rs2004640 G/T polymorphism between the entire group of JIA as a whole and its individual clinical types, as well as the control group.Conclusion. This pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of oligoarticular JIA, mainly that of JIA-uveitis and JIA-B27.

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P035 Hip involvement in Tunisian Juvenile Idiopathic Arthritis patients

Rheumatology ◽

10.1093/rheumatology/keab722.027 ◽

2021 ◽

Vol 60 (Supplement_5) ◽

Author(s):

Makhlouf Yasmine ◽

Wafa Triki ◽

Kaouther Maatallah ◽

Hanene Ferjani ◽

Dorra Ben Nessib ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Rheumatoid Factor ◽

Age At Onset ◽

Joint Damage ◽

Joint Effusion ◽

Male Predominance ◽

Disease Characteristics ◽

Tunisian Patients ◽

The Mean ◽

Magnetic Resonance Imaging Mri

Abstract Background Juvenile idiopathic arthritis (JIA) is characterized by a widely variable clinical course and outcome. If uncontrolled, joint damage may occur. In this context, coxitis is a feared complication. The aim of our study was to determine the prevalence and patterns of hip involvement in Tunisian JIA patients. Methods A retrospective study including children with JIA according to the International League of Associations for Rheumatology (ILAR)) was conducted between 2012and 2021. Sociodemographic data as well as disease characteristics were collected. Laboratory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were recorded. Hip involvement was assessed clinical exam and imaging (standard radiograph, ultrasound or magnetic resonance imaging (MRI)). We compared these parameters between the two groups: G1: presence of coxitis and G2: absence of coxitis. Results The study included 40 patients with a male predominance: sex ratio was 1.6. The mean age was 11.1 years-old [3–16]. The mean age at onset of the disease was 18.1 years old [8–30]. The distribution of the different subsets was as follows: polyarticular with rheumatoid factor (n = 1), polyarticular without rheumatoid factor (n = 2), enthesitis-related arthritis (n = 29), oligoarthritis (n = 7), psoriatic arthritis (n = 1). Extra-articular manifestations were found in 21.2% of cases: ocular (n = 4), pulmonary (n = 2) and cardiovascular (n = 1). The mean ESR and CRP was 30.9 mm/h [2–90] and 15.8 mg/l [1–70] respectively. A high ESR or CRP were found in 67% of cases. Hip involvement concerned 70% of the patients and was bilateral in 67.9% of them. Hip radiographs were normal in 50% of cases. Ultrasound was performed in 9 patients and revealed a positive Doppler synovitis (n = 2), a negative Doppler synovitis (n = 7) and joint effusion (n = 2). MRI was performed in 20% of cases and revealed synovitis (67%) and joint effusion (33%). Overall, 79.3% of patients had medical treatment combining NSAIDs and rehabilitation, 39% of the patients had had local infiltration with Hexatrione and only two patients had hip replacement. Hip involvement was not correlated with age at onset (P = 0.2), subtype (P = 0.8), sex (P = 0.7), extraarticular manifestations (P = 0.4). Similarly, there was no correlation between the presence of coxitis and ESR (P = 0.07) as well as CRP (P = 0.5). Conclusion Our study showed that hip involvement is frequent among Tunisian patients with JIA. Although not correlated with disease characteristics, hip involvement should be assessed frequently and carefully.

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OP0173 HLA-B27 and classification of enthesitis-related arthritis in an eight year follow up study of nordic patients with juvenile idiopathic arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-eular.1856 ◽

2013 ◽

Vol 71 (Suppl 3) ◽

pp. 113.2-113

Author(s):

L. Berntson ◽

K. Aalto ◽

A. Fasth ◽

T. Herlin ◽

S. Nielsen ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Hla B27 ◽

Enthesitis Related Arthritis ◽

Follow Up Study

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Patterns of pain over time among children with juvenile idiopathic arthritis

Archives of Disease in Childhood ◽

10.1136/archdischild-2017-313337 ◽

2017 ◽

Vol 103 (5) ◽

pp. 437-443 ◽

Cited By ~ 21

Author(s):

Amir Rashid ◽

Lis Cordingley ◽

Roberto Carrasco ◽

Helen E Foster ◽

Eileen M Baildam ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Multinomial Logistic Regression ◽

Age At Onset ◽

Management Strategies ◽

Disease Onset ◽

Common Symptom ◽

Pain Outcomes ◽

First Pain ◽

Over Time

ObjectivesPain is a very common symptom of juvenile idiopathic arthritis (JIA). Disease activity alone cannot explain symptoms of pain in all children, suggesting other factors may be relevant. The objectives of this study were to describe the different patterns of pain experienced over time in children with JIA and to identify predictors of which children are likely to experience ongoing pain.MethodsThis study used longitudinal-data from patients (aged 1–16 years) with new-onset JIA. Baseline and up to 5-year follow-up pain data from the Childhood Arthritis Prospective Study (CAPS) were used. A two-step approach was adopted. First, pain trajectories were modelled using a discrete mixture model. Second, multinomial logistic regression was used to determine the association between variables and trajectories.ResultsData from 851 individuals were included (4 years, median follow-up). A three-group trajectory model was identified: consistently low pain (n=453), improved pain (n=254) and consistently high pain (n=144). Children with improved pain or consistently high pain differed on average at baseline from consistently low pain. Older age at onset, poor function/disability and longer disease duration at baseline were associated with consistently high pain compared with consistently low pain. Early increases in pain and poor function/disability were also associated with consistently high pain compared with consistently low pain.ConclusionsThis study has identified routinely collected clinical factors, which may indicate those individuals with JIA at risk of poor pain outcomes earlier in disease. Identifying those at highest risk of poor pain outcomes at disease onset may enable targeted pain management strategies to be implemented early in disease thus reducing the risk of poor pain outcomes.

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Enthesitis Related Arthritis in a Longitudinal Southeast Asian Registry: High Prevalence of HLA-B27, Different Sacroiliitis Risk Factors and Less Common Drug-Free Remission

Journal of Clinical Medicine ◽

10.3390/jcm10040568 ◽

2021 ◽

Vol 10 (4) ◽

pp. 568

Author(s):

Thaschawee Arkachaisri ◽

Kai Liang Teh ◽

Yun Xin Book ◽

Sook Fun Hoh ◽

Xiaocong Gao ◽

...

Keyword(s):

Clinical Characteristics ◽

Cox Regression ◽

Age At Onset ◽

Human Leukocyte ◽

Common Disease ◽

Hla B27 ◽

Significance Level ◽

Enthesitis Related Arthritis ◽

Joint Deformity ◽

Kaplan Meier

Objective. To describe the clinical characteristics, predictors and treatment of children with Enthesitis Related Arthritis (ERA) in a Singapore longitudinal cohort over 11 years. Methods. ERA patients were recruited from our registry (2009–2019). Nonparametric descriptive statistics including median (interquartile range, IQR) were used to describe data. Kaplan–Meier survival and logistic/Cox regression analyses were used to estimate the probabilities and determine predictors of clinical variables, respectively. The significance level was set at <0.05. Results. One hundred and forty-six ERA patients (87% male, 82% Chinese) were included. Median onset age was 11.9 years (IQR 9.4–14.0) and median disease duration was 4.9 years (IQR 2.6–8.3). Family history of Human Leukocyte Antigen (HLA)-B27 associated diseases was positive in 7.5%. Acute uveitis occurred in 3.4%. Oligoarthritis was present in 89.7%. Hip, knee and ankle joints were among the most common joints involved. One-fourth had enthesitis at diagnosis (Achilles tendon entheses, 82.9%). Sacroiliitis occurred in 61%. Probabilities of sacroiliitis development were 0.364, 0.448 and 0.578 at 1, 2 and 5 years after onset, respectively. Negative HLA-B27, female, older age at onset and hip arthritis at diagnosis were associated with shorter time for sacroiliitis development (p = 0.001–0.049). Methotrexate (MTX) remained the most common disease modifying anti-rheumatic drug (DMARD) used (77.4%). However, 77.9% required anti-TNF (aTNF) therapy secondary to MTX failure. Among MTX-treated sacroiliitis patients, 85.3% failed, requiring aTNF, as compared to 63.2%patients without axial disease. Longer duration to diagnosis (p = 0.038) and MTX use (p = 0.007) predicted aTNF therapy. None had joint deformity. Conclusions. This study underscores differences in ERA clinical characteristics, predictors and treatment responses. Our ERA population had many unique findings but good functional outcomes.

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