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Boeskorova S, Afonskaya M, Argunova V, Sleptsova P, Leonteva L, Burtseva T, Kostik MM. Ethnic heterogeneity of juvenile arthritis in the Republic of Sakha (Yakutia) related to a high human leukocyte antigen B27 frequency. World J Clin Pediatr 2025; 14. [DOI: 10.5409/wjcp.v14.i2.101873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 01/26/2025] [Accepted: 02/10/2025] [Indexed: 03/18/2025] Open
Abstract
BACKGROUND
Prevalence of the main rheumatic diseases in the Republic of Sakha (Yakutia) [RS(Y)], one of the regions of the Russian Federation, differs from the other regions of the Russian Federation due to its ethnic and geographic features. Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis (JIA) allows us to shape the work of the pediatric rheumatology service in the region correctly, and optimize the healthcare system and the need for medications.
AIM
To describe the epidemiological, demographic, clinical, and laboratory characteristics of children with JIA in the RS(Y) and evaluate the main outcomes.
METHODS
This retrospective cohort study assessed all the data from the medical histories of the patients (n = 225) diagnosed with JIA (2016-2023) in the Cardiorheumatology Department of the M.E. Nikolaev National Center of Medicine. Pearson's χ ² test, Fisher's exact test, Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.
RESULTS
The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children, respectively. The prevalence of JIA among boys and girls in Sakha was similar, unlike in Russians, where the number of girls predominated. The JIA categories were as follows: (1) Systemic arthritis: 3.5%; (2) Oligoarthritis (persistent and extended): 33.8%; (3) Rheumatoid factor (RF) (+) polyarthritis: 0.9%; (4) RF (-) polyarthritis: 14.7%; (5) Enthesitis-related arthritis (ERA): 44%; and (6) Psoriatic arthritis: 3.1%. Prevalence of the ERA category was 4.4 times higher in Sakha children, but the prevalence of systemic arthritis was 2.9 times lower compared to Russians (P = 0.0005). The frequency of uveitis was 10.2%, and the frequency of human leukocyte antigen (HLA) B27 was 39.6% in JIA children. Biologic treatment was received by 40.4% of JIA children and 45.3% achieved remission.
CONCLUSION
Higher JIA prevalence, male and ERA predominance, related to a higher frequency of HLA B27 are typical in RS(Y). These data might improve the pediatric rheumatology health service.
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Affiliation(s)
- Sargylana Boeskorova
- Department of Pediatry and Pediatric Surgery, North-Eastern Federal University named after M.K. Ammosov, Medical Institute, Yakutsk 677000, Republic of Sakha (Yakutia), Russia
- Department of Pediatric Rheumatology, Republican Hospital No. 1 –National Center of Medicine Named After M.E. Nikolaev, Yakutsk 677019, Republic of Sakha (Yakutia), Russia
| | - Marina Afonskaya
- Department of Pediatric Rheumatology, Republican Hospital No. 1 –National Center of Medicine Named After M.E. Nikolaev, Yakutsk 677019, Republic of Sakha (Yakutia), Russia
| | - Vera Argunova
- Department of Pediatric Rheumatology, Republican Hospital No. 1 –National Center of Medicine Named After M.E. Nikolaev, Yakutsk 677019, Republic of Sakha (Yakutia), Russia
| | - Polina Sleptsova
- Department of Pediatric Rheumatology, Republican Hospital No. 1 –National Center of Medicine Named After M.E. Nikolaev, Yakutsk 677019, Republic of Sakha (Yakutia), Russia
| | - Liudmila Leonteva
- Department of Rheumatology, Yakut Science Center for Complex Medical Problems, Yakutsk 677000, Republic of Sakha (Yakutia), Russia
- Department of Hospital Therapy, Occupational Diseases and Clinical Pharmacology, North-Eastern Federal University Named After M.K. Ammosov, Medical Institute, Yakutsk 677000, Republic of Sakha (Yakutia), Russia
| | - Tatiana Burtseva
- Department of Pediatry and Pediatric Surgery, North-Eastern Federal University named after M.K. Ammosov, Medical Institute, Yakutsk 677000, Republic of Sakha (Yakutia), Russia
- Department of The Children Heath Monitoring and Environmental Research, Yakut Science Center of The Complex Medical Problems, Yakutsk 677000, Republic of Sakha (Yakutia), Russia
| | - Mikhail Mikhailovich Kostik
- Department of Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
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Attuparambath S, Venkataraman S, Chanu AR, Handa G, Bagri N. A Cross-Sectional Study Assessing the Functional Status in Children With Juvenile Idiopathic Arthritis and Its Correlation With Their Quality of Life and Burden on Caregivers. Cureus 2024; 16:e66178. [PMID: 39233946 PMCID: PMC11373394 DOI: 10.7759/cureus.66178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/05/2024] [Indexed: 09/06/2024] Open
Abstract
Background Juvenile idiopathic arthritis (JIA) is a common rheumatic disease in children, significantly impacting their functional status and quality of life (QoL), as well as imposing a burden on caregivers. This study aims to assess the functional status of children with JIA, their QoL, and the associated caregiver burden while exploring the correlations between these factors. Methodology A prospective, cross-sectional, observational study was conducted over 18 months. A total of 33 children diagnosed with JIA were evaluated using the Childhood Health Assessment Questionnaire (CHAQ), and Euro Quality of Life-5 Dimension-Youth (EQ-5D-Y). Caregiver burden was assessed using the Family Burden Interview Schedule (FBIS). Data were analyzed using descriptive statistics, regression analysis, and Spearman's rank correlation. Results A total of 33 consecutive children with JIA were prospectively enrolled. The mean age was 10.1 ± 3.7 years, with a male predominance (63.6%, n = 21). Enthesitis-related arthritis was the most common subtype (42%, n = 14). The CHAQ scores indicated moderate disability, with profound impacts on walking and arising. Most children reported "some problems" in all EQ-5D-Y domains, with a mean health status visual analog scale score of 60.97 ± 23.43. The mean FBIS score was 9.64 ± 5.78, indicating a moderate caregiver burden. The majority of caregivers reported moderate financial, family routine, and family leisure disruptions. Significant correlations were found between CHAQ and EQ-5D-Y scores in several domains (p ≤ 0.040), as well as between specific CHAQ domains and FBIS scores (p ≤ 0.037). Conclusions Children with JIA experience significant functional limitations and reduced QoL, which also impacts their caregivers. Early rehabilitation and comprehensive care strategies are crucial for improving functional outcomes and QoL, as well as alleviating caregiver burden.
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Affiliation(s)
- Sangeeth Attuparambath
- Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Srikumar Venkataraman
- Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Asem R Chanu
- Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Gita Handa
- Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
| | - Narendra Bagri
- Pediatrics, All India Institute of Medical Sciences, New Delhi, New Delhi, IND
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Di Gennaro S, Di Matteo G, Stornaiuolo G, Anselmi F, Lastella T, Orlando F, Alessio M, Naddei R. Advances in the Diagnosis and Treatment of Enthesitis-Related Arthritis. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1647. [PMID: 37892310 PMCID: PMC10605472 DOI: 10.3390/children10101647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/24/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023]
Abstract
Enthesitis-related arthritis (ERA) represents 5-30% of all cases of juvenile idiopathic arthritis (JIA) and belongs to the spectrum of the disorders included in the group of juvenile spondyloarthritis. In the last decade, there have been considerable advances in the classification, diagnosis, monitoring, and treatment of ERA. New provisional criteria for ERA have been recently proposed by the Paediatric Rheumatology INternational Trials Organisation, as part of a wider revision of the International League of Associations for Rheumatology criteria for JIA. The increased use of magnetic resonance imaging has shown that a high proportion of patients with ERA present a subclinical axial disease. Diverse instruments can be used to assess the disease activity of ERA. The therapeutic recommendations for ERA are comparable to those applied to other non-systemic JIA categories, unless axial disease and/or enthesitis are present. In such cases, the early use of a TNF-alpha inhibitor is recommended. Novel treatment agents are promising, including IL-17/IL-23 or JAK/STAT pathways blockers.
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Affiliation(s)
- Simona Di Gennaro
- Section of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy; (S.D.G.); (G.D.M.); (G.S.); (T.L.); (M.A.)
| | - Gennaro Di Matteo
- Section of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy; (S.D.G.); (G.D.M.); (G.S.); (T.L.); (M.A.)
| | - Gianmarco Stornaiuolo
- Section of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy; (S.D.G.); (G.D.M.); (G.S.); (T.L.); (M.A.)
| | - Federica Anselmi
- Unit of Pediatric Infectious Diseases, Mother and Child Department, University Hospital Federico II, 80131 Naples, Italy;
| | - Teresa Lastella
- Section of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy; (S.D.G.); (G.D.M.); (G.S.); (T.L.); (M.A.)
| | - Francesca Orlando
- General Pediatrics and Immuno-Rheumatology Unit, Santobono-Pausilipon Hospital, 80129 Naples, Italy;
| | - Maria Alessio
- Section of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy; (S.D.G.); (G.D.M.); (G.S.); (T.L.); (M.A.)
| | - Roberta Naddei
- Section of Pediatrics, Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy; (S.D.G.); (G.D.M.); (G.S.); (T.L.); (M.A.)
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Ravichandran N, Guleria S, Mohindra N, Aggarwal A. Predictors of long-term functional outcomes of juvenile idiopathic arthritis-enthesitis-related arthritis: a single centre experience. Rheumatology (Oxford) 2023; 62:3110-3116. [PMID: 36702467 DOI: 10.1093/rheumatology/kead032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/29/2022] [Accepted: 01/10/2023] [Indexed: 01/28/2023] Open
Abstract
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.
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Affiliation(s)
- Naveen Ravichandran
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Shivika Guleria
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Namita Mohindra
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Amita Aggarwal
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Naveen R, Guleria S, Aggarwal A. Recent updates in enthesitis-related arthritis. Rheumatol Int 2023; 43:409-420. [PMID: 36629936 DOI: 10.1007/s00296-023-05274-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 01/03/2023] [Indexed: 01/12/2023]
Abstract
Enthesitis-related arthritis (ERA) is a category of juvenile idiopathic arthritis which belongs to the spectrum of diseases that are included in juvenile spondyloarthropathy. In recent years, there have been significant advances in understanding pathogenesis, tools to assess disease activity, early recognition of the axial disease, and targeted therapy using IL-17 inhibitors and small molecule inhibitors. The current narrative review highlights these new advances. Among many hypotheses linking HLA B27 to ERA, one of them is the effect of HLA B27 on gut dysbiosis. However, recent data suggest that gut dysbiosis is probably not determined by HLA B27. Though children present with arthritis and enthesitis, axial disease is present in 50-60% on MRI. Using data-driven approach, discriminative MRI finding for active and chronic diseases has been defined for children. This will help in the early recognition of disease. An abridged version of juvenile spondyloarthropathy disease activity (JSpADA) score without the need for acute phase reactants and Schober test performed as well as the original score may increase its acceptance in routine practice. Secukinumab (anti-IL-17 antibody) has shown a more than 75% response rate in children with ERA and may be a good alternative to anti-TNF therapy. Initial data with tofacitinib also look promising. All these will translate into better outcomes for children with ERA.
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Affiliation(s)
- R Naveen
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Shivika Guleria
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Amita Aggarwal
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
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Li J, Zhu Y, Guo G. Enthesitis-related arthritis: the clinical characteristics and factors related to MRI remission of sacroiliitis. BMC Musculoskelet Disord 2022; 23:1054. [DOI: 10.1186/s12891-022-06028-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 11/25/2022] [Indexed: 12/04/2022] Open
Abstract
Abstract
Background
To describe the clinical characteristics and explore the factors related to the MRI remission of sacroiliitis in patients with enthesitis-related arthritis (ERA).
Methods
Patients 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.
Results
This 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.
Conclusion
We 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.
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Dunga SK, Kavadichanda C, Gupta L, Naveen R, Agarwal V, Negi VS. Disease characteristics and clinical outcomes of adults and children with anti-MDA-5 antibody-associated myositis: a prospective observational bicentric study. Rheumatol Int 2022; 42:1155-1165. [PMID: 34050793 DOI: 10.1007/s00296-021-04897-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 05/15/2021] [Indexed: 12/14/2022]
Abstract
To study the demographic, clinical and serologic characteristics of anti-MDA5-positive DM from two geographically and ethnically disparate inception cohorts in India. To identify the clinical and serological parameters at inception that could predict mortality among these individuals. Individuals with anti-MDA5 antibody-positive DM diagnosed between 2017 and 2020 from two centres in India were prospectively followed up. The clinical and serological characteristics at baseline and the treatment outcome at follow-up were assessed for this study. Anti-MDA5 antibody was positive in 25 (7.5%) out of the 330 individuals with myositis. These 25 (21 adults, 4 juvenile) patients were followed up for a median duration of 14 months. Among adults, a majority had cutaneous manifestations 21 (84%) followed by, arthritis 17 (80%), and interstitial lung disease 12 (ILD, 57.1%). Four (19%) had rapidly progressive ILD (RP-ILD). Eight (38%) presented as clinically amyopathic DM. Among cutaneous manifestations, majority (62%) had classic features (gottron's papules/sign, heliotrope rash) while 8 (38%) had cutaneous ulceration and 2 each had periorbital edema and tendon rupture. Eight (38%) were positive for anti-Ro-52 antibody. Out of 21 adults, 8 (38%) succumbed to the diseases. RP-ILD (n = 4; 19%), ulcerative gottron's (n = 5) and anti-Ro-52 (n = 8) were significantly associated with mortality (p < 0.05). Upon binary logistic regression, positive anti-Ro-52 antibody predicted mortality [HR 17.3 (95%CI 1.4-210, p = 0.025)]. All juvenile anti-MDA5-positive DMs had classic cutaneous features with 2 of them having ulcerative gottron's. None of the juvenile patients had ILD and everyone survived till the last follow-up. Indian adults with anti-MDA5 DM have high mortality. Rarer atypical features like tendon rupture or periorbital edema could assist in diagnosis. Ulcerative gottron's, positive anti-Ro 52 antibodies, and RP-ILD are valuable clinical-serological markers that portend poor prognosis.
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Affiliation(s)
- Sai Kumar Dunga
- Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605006, India
| | - Chengappa Kavadichanda
- Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605006, India.
| | - Latika Gupta
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow, 226014, Uttar Pradesh, India.
| | - R Naveen
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow, 226014, Uttar Pradesh, India
| | - Vikas Agarwal
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow, 226014, Uttar Pradesh, India
| | - Vir Singh Negi
- Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605006, India
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Pediatric Rheumatic Disease in Lower to Middle-Income Countries: Impact of Global Disparities, Ancestral Diversity, and the Path Forward. Rheum Dis Clin North Am 2021; 48:199-215. [PMID: 34798947 DOI: 10.1016/j.rdc.2021.09.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Pediatric rheumatology subspecialists treat chronic autoimmune diseases with onset in childhood. Prompt diagnosis and ongoing management of these conditions are imperative to prevent damage from ongoing inflammation. Here, we aim to describe the current landscape of pediatric rheumatic disease in lower to middle-income countries (LMICs) and explore current barriers to understanding global disease burden. We then examine innovative strategies to promote a more equitable future for children and young people living with rheumatic diseases worldwide.
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Martínez-Nava GA, Zamudio-Cuevas Y, Terrazas-Ontiveros NA, Martínez-Flores K, Espinosa-Morales R, Mijares-Díaz F, Juárez-Barreto SM, Lozada-Pérez C, Valdés-Flores M, Sánchez-Sánchez R, Hidalgo-Bravo A, Fernández-Torres J. A proposed HLA-B*27 screening method for ankylosing spondylitis detection based on tag-single nucleotide polymorphisms: a preliminary study. Mol Biol Rep 2021; 48:7819-7829. [PMID: 34643924 DOI: 10.1007/s11033-021-06801-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/01/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Ankylosing spondylitis (AS) is a type of inflammatory arthritis that affects primarily the spine. There is a strong association of the HLA-B*27 allele with AS pathogenesis, but recent studies have demonstrated the participation of ERAP1 gene in the genetic susceptibility. The aim of this study was to determine whether HLA-B tag-single nucleotide polymorphisms (SNPs) and ERAP1-related genetic variations associated with AS have equal or similarly performance in patients´ screening compared to HLA-B*27 standard genotyping in Mexican population. METHODS AND RESULTS Genomic DNA from patients with AS and population-based controls from Mexico City was analyzed for five single nucleotide polymorphisms (SNPs): rs4349859, rs13202464, rs116488202, tagging HLA-B*27; and rs30187 and rs27044 in ERAP1 gene. TaqMan genotype assay method was used for SNPs genotyping. We found a significant association between AS and the heterozygote genotypes and minor alleles of the HLA-B*27 tag-SNPs, as well as for their haplotypes. With respect to ERAP1 polymorphisms, no significant associations were observed (p > 0.05). The sensitivity and specificity analysis showed values of 0.96 and 1.00 for the rs4349859 SNP, and 0.96 and 0.94 for the rs116488202 SNP, respectively, in detecting HLA-B*27 compared to the B27 test as the gold standard. CONCLUSIONS HLA-B*27 tag-SNPs are associated with AS susceptibility; furthermore, the rs4349859 SNP by its own have an outstanding performance in detecting HLA-B*27 and therefore can be proposed as screening marker in the identification of HLA-B*27 in our population.
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Affiliation(s)
| | - Yessica Zamudio-Cuevas
- Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
| | | | - Karina Martínez-Flores
- Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
| | - Rolando Espinosa-Morales
- Rheumatology Department, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
| | - Fernando Mijares-Díaz
- Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, Mexico
| | | | - Carlos Lozada-Pérez
- Rheumatology Department, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
| | - Margarita Valdés-Flores
- Genetics Service, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
| | - Roberto Sánchez-Sánchez
- Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
| | - Alberto Hidalgo-Bravo
- Genetics Service, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico
| | - Javier Fernández-Torres
- Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico. .,Biology Department, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
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Inflammatory Arthritis following Hepatitis B Vaccination in an Infant. Case Rep Rheumatol 2021; 2021:5598217. [PMID: 33880198 PMCID: PMC8046550 DOI: 10.1155/2021/5598217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/12/2021] [Accepted: 03/27/2021] [Indexed: 11/25/2022] Open
Abstract
Inflammatory arthritis in children may be idiopathic in nature or may be due to or follow infections. Rare reports identify inflammatory arthritis temporally related to vaccination in children. Herein, we describe the first reported case of an infant who developed inflammatory arthritis following hepatitis B vaccination. A 10-day-old female presented for evaluation of decreased movement of the right lower extremity and right knee swelling. Of note, the patient received a hepatitis B vaccine in her right thigh at birth. A workup found the patient to have a negative ANA but the presence of HLA B27. Findings resolved using ibuprofen. A literature review identified reports of what has been termed “reactive arthritis” in adult patients following the hepatitis B vaccine, frequently in association with HLA B27. No prior pediatric cases have been published. Healthcare providers must be aware of the rare development of postvaccination inflammatory arthritis.
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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. J Clin Med 2021; 10:jcm10040568. [PMID: 33546269 PMCID: PMC7913299 DOI: 10.3390/jcm10040568] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 01/29/2021] [Accepted: 01/30/2021] [Indexed: 12/26/2022] Open
Abstract
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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The Multi-Omics Architecture of Juvenile Idiopathic Arthritis. Cells 2020; 9:cells9102301. [PMID: 33076506 PMCID: PMC7602566 DOI: 10.3390/cells9102301] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 09/30/2020] [Accepted: 10/09/2020] [Indexed: 12/12/2022] Open
Abstract
Juvenile idiopathic arthritis (JIA) is highly heterogeneous in terms of etiology and clinical presentation with ambiguity in JIA classification. The advance of high-throughput omics technologies in recent years has gained us significant knowledge about the molecular mechanisms of JIA. Besides a minor proportion of JIA cases as monogenic, most JIA cases are polygenic disease caused by autoimmune mechanisms. A number of HLA alleles (including both HLA class I and class II genes), and 23 non-HLA genetic loci have been identified of association with different JIA subtypes. Omics technologies, i.e., transcriptome profiling and epigenomic analysis, contributed significant knowledge on the molecular mechanisms of JIA in addition to the genetic approach. New molecular knowledge on different JIA subtypes enables us to reconsider the JIA classification, but also highlights novel therapeutic targets to develop a cure for the devastating JIA.
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Majumder S, Aggarwal A. Juvenile idiopathic arthritis and the gut microbiome: Where are we now? Best Pract Res Clin Rheumatol 2020; 33:101496. [PMID: 32171669 DOI: 10.1016/j.berh.2020.101496] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In recent decades, because of advances in technology there has been an explosion of knowledge on how microbiome affects human health. In most chronic immune-inflammatory diseases, alterations in gut microbiome has been shown. The successful use of faecal microbial transplants for the treatment of clostridium difficile associated diarrhoea has also paved the way for novel therapies. Gut microbiome is affected by early life events like the mode of delivery, breast feeding, the use of antibiotics, etc. and that may have an indirect effect on the developing immune system as well as on the predisposition to juvenile idiopathic arthritis (JIA). Multiple studies have found altered gut microbiome in JIA though no single organism or microbial community has been found to be associated with JIA. In JIA, attempts to modify gut microbiome by using probiotics, exclusive enteral nutrition and other modalities have had variable success. The current review discusses the current data available on gut microbiome in different categories of JIA and how this knowledge can translate into new therapies.
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Affiliation(s)
- Sanjukta Majumder
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Amita Aggarwal
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
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Shih YJ, Yang YH, Lin CY, Chang CL, Chiang BL. Enthesitis-related arthritis is the most common category of juvenile idiopathic arthritis in Taiwan and presents persistent active disease. Pediatr Rheumatol Online J 2019; 17:58. [PMID: 31443722 PMCID: PMC6708211 DOI: 10.1186/s12969-019-0363-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 08/12/2019] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Juvenile idiopathic arthritis (JIA) has been categorized into seven different categories according to the International League of Associations for Rheumatology (ILAR) criteria. Enthesitis-related arthritis (ERA) was found to represent the largest category in a Taiwanese cohort study. The aim in this study was to compare the clinical characteristics, treatments, and outcomes of ERA in a single tertiary center in Taiwan, as compared to those of other categories of JIA. Furthermore, we determined patients' characteristics and risk factors that can help assess the outcomes in ERA. METHODS A retrospective chart review of all patients with JIA referred to a pediatric rheumatology clinic in the National Taiwan University Hospital between 1993 and 2018 were identified according to ILAR criteria. Outcomes were assessed based on the Wallace criteria to categorize patients into active and non-active, including inactive, remission on medication, and remission off medication, groups. A subset of samples was further tested by DNA sequencing to identify HLA-B27 subtypes. RESULTS One-hundred and eighty-three patients were included in the study, with a mean of 8 years' follow-up. ERA was the single largest category of JIA (39.9%); psoriasis and undifferentiated JIA were both the least common type (0.5%). ERA was male predominant (86%), had a late age of onset (11.0 ± 3.2 years), and the majority of ERA patients was HLA-B27-positive (97%). Of 25 HLA-B27-positive ERA patients checked by HLA-B27 sequencing, 23 were B*27:04 and 2 were B*27:05. ERA patients were significantly less likely to achieve non-active status compared to patients with persistent oligoarthritis (P = 0.036). In terms of treatment response to TNF-α inhibitors in methotrexate-refractory ERA, 26 patients remained active and only 11 patients (30%) achieved a non-active status. Sacroiliitis was a risk factor contributing to poorer treatment response in ERA (P = 0.006). CONCLUSION ERA represented the most common category of JIA in Taiwan. Those ERA patients with sacroiliitis were likely to have persistent active disease and may require a more aggressive treatment strategy to improve their outcomes.
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Affiliation(s)
- Yang-Jen Shih
- Department of Pediatrics, Taipei City Hospital, Zhongxing Branch, Taipei, Taiwan ,0000 0004 0546 0241grid.19188.39Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan South Road, Zhongzheng District, Taipei, 100 Taiwan
| | - Yao-Hsu Yang
- Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan South Road, Zhongzheng District, Taipei, 100, Taiwan. .,Department of Pediatrics, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.
| | - Chun-Ying Lin
- 0000 0004 0572 7815grid.412094.aDepartment of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Ling Chang
- 0000 0004 0572 7815grid.412094.aDepartment of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Bor-Luen Chiang
- 0000 0004 0546 0241grid.19188.39Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan South Road, Zhongzheng District, Taipei, 100 Taiwan
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Zanwar A, Phatak S, Aggarwal A. Prospective validation of the Juvenile Spondyloarthritis Disease Activity Index in children with enthesitis-related arthritis. Rheumatology (Oxford) 2019; 57:2167-2171. [PMID: 30107576 DOI: 10.1093/rheumatology/key246] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Indexed: 11/12/2022] Open
Abstract
Objective To measure disease activity in children with enthesitis-related arthritis the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) was developed and retrospectively validated. We prospectively validated JSpADA and also assessed performance of adult SpA scores. Methods Children with enthesitis-related arthritis (ILAR criteria) less than 18 years of age were enrolled. Baseline characteristics and different disease activity measures (JSpADA, BASDAI, Ankylosing Spondylitis Disease Activity Score-ESR, juvenile arthritis DAS-10 joints), and Childhood HAQ, physician global assessment and patient global assessment were recorded at baseline. In some children follow-up was also done. Results The mean (s.d.) age of 127 children (116 boys) was 14.3 (2.4) years and disease duration was 36.9 (3) months. Ninety of 104 (86.5%) children were HLA-B27 positive. JSpADA showed high correlation with physician global assessment (r = 0.87; P < 0.0001), patient global assessment (r = 0.80, P < 0.0001), juvenile arthritis DAS-10 joints (r = 0.89; P < 0.0001) and Childhood HAQ (r = 0.83, P < 0.0001). The JSpADA scores showed good internal consistency, discriminative validity and sensitivity to change. In 15% of children back mobility could not be tested due to active arthritis in lower limbs. The 7-variable JSpADA excluding back mobility performed as well as the original JSpADA. Adult scores showed good construct validity, discriminative capacity and sensitivity to change, and had good correlation with JSpADA (BASDAI, r = 0.84; Ankylosing Spondylitis Disease Activity Score-ESR, r = 0.84). Conclusion JSpADA is a valid score for measuring disease activity in enthesitis-related arthritis. Adult scores also performed well. Excluding back mobility needs to be assessed in future to improve JSpADA performance.
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Affiliation(s)
- Abhishek Zanwar
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Sanat Phatak
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Amita Aggarwal
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Kavadichanda CG, Seth G, Kumar G, Gulati R, Negi VS. Clinical correlates of HLA-B*27 and its subtypes in enthesitis-related arthritis variant of juvenile idiopathic arthritis in south Indian Tamil patients. Int J Rheum Dis 2019; 22:1289-1296. [PMID: 30884197 DOI: 10.1111/1756-185x.13551] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 02/02/2019] [Accepted: 02/24/2019] [Indexed: 01/12/2023]
Abstract
AIM The aim of the study was to assess the distribution of human leukocyte antigen (HLA)-B*27 subtypes and its correlation with disease phenotypes in children with enthesitis-related arthritis variant of juvenile idiopathic arthritis (JIA-ERA). METHOD One hundred and sixty patients (132 males, 28 females) satisfying the International League Against Rheumatism (ILAR) classification criteria for JIA-ERA were assessed and relevant demographic, clinical and radiographic data were documented. HLA-B*27 typing was done for all the patients and B*27 positive samples were subjected to high-resolution gene sequencing. The effect of duration of illness, HLA-B*27, its subtypes, and gender on the clinical phenotype were analyzed. RESULTS The mean age of disease onset was 12.69 ± 2.4 years with a male:female ratio of 4.7:1.0. HLA-B*27 was positive in 109/160 patients and HLA-B*27:04 was detected in 63% followed by B*27:05 (30%). Duration of illness was greater in patients with skeletal deformity, hip arthritis, sacroiliitis, cervical spine involvement and acute anterior uveitis (AAU) (P < 0.05). HLA-B*27 positivity was associated with a prolonged course of disease, higher incidence of AAU (14.7% vs 2%, P = 0.015), family history of spondyloarthritis (21.1% vs 5.9%; P = 0.015) and higher erythrocyte sedimentation rate as compared to HLA-B*27 negative patients (P < 0.01). The HLA-B*27:04 and *27:05 positive patients had similar clinical phenotypes. CONCLUSION Presence of HLA-B*27 and long duration of illness results in skeletal deformity, hip arthritis, sacroiliitis, cervical spine involvement and AAU. HLA-B*27:04 followed by B*27:05 are the most common HLA-B*27 subtypes in our study population and both have a similar clinical phenotype.
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Affiliation(s)
- Chengappa G Kavadichanda
- Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
| | - Gaurav Seth
- Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
| | - Gunjan Kumar
- Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
| | - Reena Gulati
- Genetic Services Unit, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
| | - Vir Singh Negi
- Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
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Phatak S, Mohindra N, Zanwar A, Aggarwal A. Prominent midfoot involvement in children with enthesitis-related arthritis category of juvenile idiopathic arthritis. Clin Rheumatol 2017. [PMID: 28634696 DOI: 10.1007/s10067-017-3733-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Foot involvement is common in juvenile idiopathic arthritis (JIA) but is often unrecognized and difficult to treat. This study was done to assess clinical and radiological involvement of the feet and its impact on function in Indian children with enthesitis-related arthritis (ERA). We enrolled consecutive children with ERA with disease duration of less than 5 years. All patients underwent clinical examination of the feet and filled the juvenile arthritis foot index (JAFI) questionnaire. Ultrasound (US) of foot joints and entheses and extremity magnetic resonance imaging (MRI) scan of one foot were done. Fifty-five patients (53 boys), with median 14 years and disease duration 1.9 years, were included. Thirty-seven of 46 were HLA-B27-positive. Mean juvenile spondyloarthritis disease activity (JSpADA) index and juvenile idiopathic arthritis disease activity scrore-10 (JADAS10) scores were 4 and 14.25. Forty-six had history of foot pain, 36 had foot involvement on examination (15 ankle, 8 subtalar, 24 midfoot, 10 forefoot, and 21 tendoachilles), and 7 had plantar fascia involvement. On US (N = 55), 16 had ankle involvement and 8 had subtalar involvement, and 19 patients had midfoot arthritis, 24 had tendoachilles enthesitis, and 11 had plantar fasciitis. On MRI (N = 50), 27 had midfoot involvement. Thirty-three had bone edema. Fourteen had midfoot enthesitis and 17 had tenosynovitis. Clinical and US had 82% concordance at the midfoot and 90% at the ankle. MRI had 74% concordance with examination and 72% with US at the midfoot. The median JAFI scores were as follows: total JAFI = 4 (0-11), impairment = 1, activity limitation = 2, and participation restriction = 1. JAFI total and individual domains correlated with JADAS10, JSpADAS, and childhood health assessment questionnaire (CHAQ) but not duration of foot disease. JAFI was higher in children with midfoot arthritis on US. Foot joints and entheses are involved in a substantial proportion of patients with ERA patients and the midfoot is commonly involved. Foot disease produces significant functional limitation.
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Affiliation(s)
- Sanat Phatak
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Namita Mohindra
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Abhishek Zanwar
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Amita Aggarwal
- Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
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Gmuca S, Xiao R, Brandon TG, Pagnini I, Wright TB, Beukelman T, Morgan EM, Weiss PF. Multicenter inception cohort of enthesitis-related arthritis: variation in disease characteristics and treatment approaches. Arthritis Res Ther 2017; 19:84. [PMID: 28464909 PMCID: PMC5414167 DOI: 10.1186/s13075-017-1297-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 04/07/2017] [Indexed: 12/20/2022] Open
Abstract
Background Enthesitis-related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA) defined according to the International League of Associations for Rheumatology (ILAR) criteria. We aimed to characterize the clinical features and treatment regimens in an inception cohort of children with ERA. Methods We performed a retrospective, cross-sectional, multicenter cohort study including subjects diagnosed with ERA between 1989 and 2012. Patients all fulfilled the ILAR criteria for ERA within 3 months of initial presentation to the rheumatology clinic. Differences in the prevalence of clinical criteria across study sites and by human leukocyte antigen (HLA)-B27 status were assessed using the Wilcoxon rank-sum or chi-square test, as appropriate. Results Two hundred thirty-four children met the inclusion criteria. Their median age at diagnosis was 11.6 years, and 59% were HLA-B27-positive. Sixty-nine percent had enthesitis and arthritis at the time of diagnosis. Seventy-eight percent had a pauciarticular onset. The prevalence of all ILAR criteria at diagnosis, except arthritis and acute anterior uveitis, differed significantly across sites (all p < 0.01). 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. Conclusions The majority of children had a pauciarticular onset, and several statistically significant clinical differences based on HLA-B27 status were identified. The observed heterogeneity in clinical presentation across sites reflects either true differences in patient populations or differences in how the ILAR criteria are being applied.
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Affiliation(s)
- Sabrina Gmuca
- Division of Rheumatology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Rui Xiao
- Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Timothy G Brandon
- Division of Rheumatology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Ilaria Pagnini
- University of Florence and Anna Meyer Children's Hospital, Florence, Italy
| | - Tracey B Wright
- University of Texas Southwestern Medical Center and Texas Scottish Rite Hospital of Children, Dallas, TX, USA
| | | | - Esi M Morgan
- Cincinnati Children's Hospital, Cincinnati, OH, USA
| | - Pamela F Weiss
- University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA, USA. .,Department of Pediatric Rheumatology, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Wood Building, Fourth Floor, Philadelphia, PA, 19104, USA.
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