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Gicchino MF, Marzuillo P, Zarrilli S, Melone R, Guarino S, Miraglia Del Giudice E, Olivieri AN, Di Sessa A. Uric acid could be a marker of cardiometabolic risk and disease severity in children with juvenile idiopathic arthritis. Eur J Pediatr 2023; 182:149-154. [PMID: 36229695 DOI: 10.1007/s00431-022-04657-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 09/26/2022] [Accepted: 10/09/2022] [Indexed: 01/12/2023]
Abstract
UNLABELLED In addition to disease-specific complications, juvenile idiopathic arthritis (JIA) has been linked to metabolic impairments in adults. Recent data supported the usefulness of uric acid (UA) as risk factor for cardiometabolic derangements. Given the lack of pediatric evidence in this field, we aimed to explore this association in a cohort of children diagnosed with JIA. We retrospectively evaluated 113 children diagnosed with JIA classified according to the International League of Association for Rheumatology (ILAR) criteria attending our Rheumatology Clinic. Both clinical and biochemical assessments were performed. Participants were stratified in four groups according to quartiles of serum UA. Disease activity was calculated by the Juvenile Arthritis Disease Activity Score 10 (JADAS-10) joint reduced count, and cut-offs for disease states were applied. Patients belonging to the highest UA quartile showed higher serum triglycerides, total cholesterol, creatinine, and glucose levels (p = 0.01, p = 0.025, p = 0.04, and p = 0.005, respectively) and lower HDL cholesterol values (p < 0.0001) than subjects belonging to the lowest quartiles. Ferritin, erythrocyte sedimentation rate levels, and age at disease onset did not significantly differ across UA quartiles (all p > 0.05). As activity disease index, JADAS-10 score significantly increased across UA quartiles (p = 0.009). CONCLUSION Children with JIA presented with a worse cardiometabolic profile and a greater disease severity across UA quartiles. Our findings suggest that in clinical practice, UA might represent a useful marker of cardiometabolic risk and disease severity in children with JIA. WHAT IS KNOWN • JIA has been linked to metabolic derangements in adulthood. • UA has been recognized as a marker of cardiometabolic risk both in adults and children. WHAT IS NEW • Children with JIA belonging to the highest UA quartile showed a worse cardiometabolic profile and a greater disease severity. • UA might represent a helpful marker not only of cardiometabolic risk but also of disease severity in children with JIA.
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Affiliation(s)
- Maria Francesca Gicchino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy
| | - Sarah Zarrilli
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy
| | - Rosa Melone
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy
| | - Alma Nunzia Olivieri
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio n° 2, 80138, Naples, Italy.
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Allogeneic Hematopoietic Cell Transplant for Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome. Case Rep Rheumatol 2021; 2021:9323141. [PMID: 34123455 PMCID: PMC8166505 DOI: 10.1155/2021/9323141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 05/19/2021] [Indexed: 12/29/2022] Open
Abstract
Systemic juvenile idiopathic arthritis (sJIA) is characterized by arthritis, fever, rash, lymphadenopathy, hepatosplenomegaly, and serositis. Macrophage activation syndrome is the most feared complication of sJIA with a high risk of mortality. We report a 16-year-old female diagnosed with refractory systemic juvenile idiopathic arthritis (sJIA) complicated by recurrent macrophage activation syndrome (MAS), severe joint disease, and lung involvement requiring prolonged immunosuppressive therapy. She received a matched unrelated allogeneic hematopoietic cell transplant (Allo-HCT) using a reduced-intensity conditioning regimen and is now, 3 years after the transplant, with complete resolution of sJIA symptoms, off immunosuppressants, and with significant improvement in the quality of life.
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Bovid KM, Moore MD. Juvenile Idiopathic Arthritis for the Pediatric Orthopedic Surgeon. Orthop Clin North Am 2019; 50:471-488. [PMID: 31466663 DOI: 10.1016/j.ocl.2019.06.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Juvenile idiopathic arthritis includes conditions characterized by joint inflammation of unknown etiology lasting longer than 6 weeks in patients younger than 16 years. Diagnosis and medical management are complex and best coordinated by a pediatric rheumatologist. The mainstay of therapy is anti-inflammatory and biologic medications to control pain and joint inflammation. Orthopedic surgical treatment may be indicated for deformity, limb length inequality, or end-stage arthritis. Evaluation of the cervical spine and appropriate medication management in consultation with a patient's rheumatologist are essential in perioperative care. Preoperative planning should take into account patient deformity, contracture, small size, osteopenia, and medical comorbidities.
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Affiliation(s)
- Karen M Bovid
- Department of Orthopaedic Surgery, Western Michigan University Homer Stryker M.D. School of Medicine, 1000 Oakland Drive, Kalamazoo, MI 49008, USA.
| | - Mary D Moore
- Department of Pediatrics, Central Michigan University College of Medicine, 1000 Houghton Avenue, Saginaw, MI 48602, USA
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Khan S, Mancini J, Hopper C, Rennick JE. Perceptions of Methotrexate Intolerance and Its Impact on Daily Life in School-Age Children with Juvenile Idiopathic Arthritis. J Pediatr Nurs 2019; 48:49-54. [PMID: 31254860 DOI: 10.1016/j.pedn.2019.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 06/05/2019] [Accepted: 06/06/2019] [Indexed: 11/16/2022]
Abstract
PURPOSE Methotrexate (MTX) is a disease modifying anti-rheumatic drug commonly used to treat children with Juvenile Idiopathic Arthritis (JIA). Unfortunately, half of children taking MTX will experience MTX intolerance, which includes distressing gastrointestinal and behavioural symptoms associated with weekly MTX treatment. This qualitative study aimed to explore the perceptions of school-age children with JIA experiencing MTX intolerance, how they managed MTX intolerance, and how it impacted their daily life. DESIGN AND METHODS An interpretive descriptive design was used. Twelve children participated in one individual 30-minute semi-structured interview using a storyboard technique to elicit their perceptions through storytelling. Interview transcripts and observational data collected during the interviews were analyzed using inductive content analysis. RESULTS Children described MTX intolerance as extremely challenging. Three themes emerged from the data: (1) "No kid likes taking MTX". This theme was comprised of two subthemes related to: (a) associative MTX intolerance; namely, "Talking about it sometimes makes me feel sick"; and (b) anticipatory MTX intolerance, "Before [I take it], I have a little stomach ache". Other themes included: (2) The importance of strategies and routines; and (3) Working hard to live with MTX intolerance. CONCLUSIONS This study sheds new light on MTX intolerance as perceived by school-aged children with JIA. Results highlight the importance of providing families and healthcare professionals with the necessary information for early recognition of MTX intolerance and optimizing care through the development of early intervention strategies. PRACTICE IMPLICATIONS Study findings highlight the importance of prioritizing early identification and prevention of MTX intolerance.
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Affiliation(s)
- Sarah Khan
- Ingram School of Nursing, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; The Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
| | - Jacqueline Mancini
- Ingram School of Nursing, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
| | - Charlene Hopper
- The Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
| | - Janet E Rennick
- Ingram School of Nursing, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; The Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Centre for Outcomes Research & Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
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Bilateral Destructive Hip Disease from Untreated Juvenile Idiopathic Arthritis. Case Rep Orthop 2019; 2019:4593129. [PMID: 30963013 PMCID: PMC6431357 DOI: 10.1155/2019/4593129] [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: 12/03/2018] [Revised: 01/22/2019] [Accepted: 01/30/2019] [Indexed: 11/18/2022] Open
Abstract
We report a novel case of a pediatric patient with bilateral hip destruction from untreated Juvenile idiopathic arthritis (JIA). She was presented at the age of 9 with hip pain associated with bilateral acetabular dysplasia and a dislocated left femoral head. Only 1.5 years later, the patient developed complete destruction of the left femoral head and dislocated right femoral head. The authors have not identified literature describing a similar case report of bilateral femoral head destruction resulting from Persistent Oligoarticular JIA. Pediatric patients presenting with rapidly evolving destructive process should be evaluated for rheumatologic, infectious, and spinal etiologies.
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Elitsur R, Hollenbeck A, Tasan L, Torok KS, Cassidy E, Blasiole B, Parsons E, Acock C, Angelelli J, Angelelli IC. Efficacy and cost savings with the use of a minimal sedation / anxiolysis protocol for intra-articular corticosteroid injections in children with juvenile idiopathic arthritis: a retrospective review of prospectively collected data. Pediatr Rheumatol Online J 2019; 17:11. [PMID: 30894194 PMCID: PMC6425704 DOI: 10.1186/s12969-019-0312-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 02/28/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Intra-articular corticosteroid injections (IACI) are frequently used in the treatment of juvenile idiopathic arthritis. There is a paucity of evidence-based research describing methods of pain and anxiety control for this procedure. IACI were mostly performed under general anesthesia for children younger than 13 years old in our institution as of 2014. We started to integrate sedation services more commonly in our institution with the minimal sedation/anxiolysis (MSA) protocol outlined as an alternative to general anesthesia for IACI in 2015. The purpose of this study was to evaluate the effectiveness and cost savings of a minimal sedation protocol for intra-articular corticosteroid injections in juvenile idiopathic arthritis patients after instituting this protocol at our institution. METHODS The MSA protocol included nitrous oxide, intranasal fentanyl, a topical numbing agent, acetaminophen, ibuprofen, ondansetron and child life intervention. A retrospective review of prospectively collected data was performed on a total of 80 consecutive patients with juvenile idiopathic arthritis who underwent joint injections using the protocol. RESULTS The procedure was successfully completed in greater than 95% of the patients. The median pain score (measured on a verbal numeric scale of 0-10) reported by the patient was 1 (IQR 0-2.5), by the parent 1 (IQR 0-2), by the rheumatologist 1 (IQR 0-1), and by the sedationist 1 (IQR 0-1). Degree of motion during the procedure was reported by the rheumatologist and the sedationist as none in 68% of the patients, mild in 36% and moderate in 6%. Patient, parent, rheumatologist and sedationist rated satisfaction as very high in the vast majority (94%). Emesis was reported in only 2 (2.5%) patients, no significant adverse events were reported, and no patients progressed to a deeper level of sedation than intended. Financial analysis revealed a 33% cost reduction compared with the use of general anesthesia in the operating room. CONCLUSIONS A minimal sedation/anxiolysis protocol (including nitrous oxide, intranasal fentanyl, a topical numbing agent, acetaminophen, ibuprofen, ondansetron and child life intervention), provides safe and effective analgesia for intra-articular corticosteroid injection in a subset of patients with juvenile idiopathic arthritis and offers a lower cost alternative to general anesthesia.
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Affiliation(s)
- Rotem Elitsur
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatrics - Division of Pediatric Emergency Medicine, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - April Hollenbeck
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatric Anesthesiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - Laura Tasan
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatrics - Division of Pediatric Rheumatology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - Kathryn S. Torok
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatrics - Division of Pediatric Rheumatology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - Elaine Cassidy
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatrics - Division of Pediatric Rheumatology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - Brian Blasiole
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatrics - Division of Pediatric Emergency Medicine, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - Erika Parsons
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatric Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - Chelsea Acock
- 0000 0000 9753 0008grid.239553.bDepartment of Pediatric Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA 15224 USA
| | - Joseph Angelelli
- 0000 0001 0650 7433grid.412689.0UPMC Center for High Value Health Care, UPMC Health Plan, 600 Grant St, Pittsburgh, PA 15219 USA
| | - Isabela-Cajiao Angelelli
- Department of Pediatric Anesthesiology, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue Pittsburgh, Pittsburgh, PA, 15224, USA.
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Zylberberg HM, Lebwohl B, Green PHR. Celiac Disease-Musculoskeletal Manifestations and Mechanisms in Children to Adults. Curr Osteoporos Rep 2018; 16:754-762. [PMID: 30350261 DOI: 10.1007/s11914-018-0488-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW We aim to review the current literature on the association of musculoskeletal disorders and celiac disease that is a common disorder, affecting about 1% of the population. Extra-intestinal symptoms and presentations predominate. RECENT FINDINGS While the literature supports an association with reduced bone mineral density and increased fracture risk and celiac disease, there is little evidence supporting associations with other rheumatological conditions. Patients frequently report musculoskeletal symptoms; however, studies of specific disease entities suffer from a lack of standardization of testing for celiac disease and a lack of control groups. Well-controlled, preferably population-based studies are required to further explore a relationship between celiac disease and musculoskeletal disorders.
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Affiliation(s)
- Haley M Zylberberg
- Celiac Disease Center, Columbia University Medical Center, 180 Fort Washington Ave, New York, NY, 10032, USA
| | - Benjamin Lebwohl
- Celiac Disease Center, Columbia University Medical Center, 180 Fort Washington Ave, New York, NY, 10032, USA
| | - Peter H R Green
- Celiac Disease Center, Columbia University Medical Center, 180 Fort Washington Ave, New York, NY, 10032, USA.
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Juvenile Idiopathic Arthritis: A Focus on Pharmacologic Management. J Pediatr Health Care 2018; 32:515-528. [PMID: 30177013 DOI: 10.1016/j.pedhc.2018.02.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Accepted: 02/27/2018] [Indexed: 12/29/2022]
Abstract
Juvenile idiopathic arthritis is a chronic condition that affects many pediatric patients. It is a prevalent disease and has become the most common rheumatologic disease of childhood. The condition encompasses multiple different forms of chronic arthritides classified based on the location and number of joints affected as well as the presence or lack of a number of different inflammatory markers. The exact etiology is unknown but is thought to be multifactorial with genetic, humoral, and environmental factors playing a key role. Many pharmacologic agents are available for use in the treatment of juvenile idiopathic arthritis, with management involving the use of symptom-reducing agents and disease-modifying antirheumatic drugs. Treatment is not without adverse events, with many of the agents require monitoring regimens and patient education. Without treatment, the progression and chronicity of the disease can result in significant morbidity, with the potential for devastating consequences on the child's quality of life.
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Vermaak PV, Southwood TR, Lindau TR, Jester A, Oestreich K. Wrist Arthroscopy in Juvenile Idiopathic Arthritis: A Review of Current Literature and Future Implications. J Wrist Surg 2018; 7:186-190. [PMID: 29922493 PMCID: PMC6005783 DOI: 10.1055/s-0038-1639508] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 02/21/2018] [Indexed: 10/17/2022]
Abstract
Introduction Juvenile Idiopathic Arthritis (JIA) is the most common rheumatological condition in children and frequently affects the wrist. The roles for wrist arthroscopy and arthroscopic synovectomy (AS) in JIA are unclear. Our aim was to find the current evidence supporting its use. Methods Systematic literature review of relevant publications from 1990 to present in the Cochrane Library, Clinical Knowledge Summaries, DynaMed, PEMSoft, NICE Guidance, MEDLINE, EMBASE, and PubMed. Results We found no publications detailing the use of arthroscopy or AS specifically in patients with JIA involving the wrist. There is evidence that AS reduces pain, improves function, and induces remission in patients with rheumatoid arthritis resistant to medical management. Discussion and Conclusion Although there is paucity in evidence for the use of AS in the wrists of patients with JIA, studies suggest it to be safe and effective, and could be applied to patients with refractive JIA. It is possible that early identification of patients suffering from JIA with extensive joint destruction and little symptoms could benefit from AS, delaying joint destruction and preserving function.
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Affiliation(s)
- P. V. Vermaak
- Department of Plastic and Reconstructive Surgery, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - T. R. Southwood
- Department of Plastic and Reconstructive Surgery, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | | | - A. Jester
- Department of Plastic and Reconstructive Surgery, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - K. Oestreich
- Department of Plastic and Reconstructive Surgery, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
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Rezaieyazdi Z, Kochakzadeh M, Hatef MR, Esmaily H, Malek A, Valizadeh N, Tabaei S, Rafatpanah H. Protective role of HLA-DRB1*11 against juvenile idiopathic arthritis living in North Eastern Iran. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2018; 21:564-568. [PMID: 29942445 PMCID: PMC6015248 DOI: 10.22038/ijbms.2018.25022.6215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Objective(s): Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases in children. The complex nature of this immune-mediated disease owes itself to several predisposing genes and environmental factors affecting its pathogenesis. Conducted in Iran, this study was originally intended to investigate every possible association between HLA DRB1 alleles and a susceptibility to JIA. Materials and Methods: In this case-control study, 45 patients with a definite diagnosis of JIA based on International League against Rheumatism (ILAR) criteria were compared against 46 healthy controls. DNA samples taken from both groups were analyzed using PCR-sequence specific primers (PCR-SSP) method. Data analysis including parametric and nonparametric test and multivariate analysis was undertaken using the SPSS 11.5 software. A P-value< 0.05 was regarded as statistically significant. Results: Mean ages in case group and healthy controls were 14.64±6.21 and 13.73±6.39, respectively with no significant difference between the two groups (P=0.515). Sex difference between JIA group and healthy controls was also not significant (P=0.068). The frequency of HLA-DRB1*01 was found the most frequent HLA-RB1 in our patients (33.3%). No significant statistical correlation between various HLA-DRB1 alleles and clinical subtypes of the disease could be established from the data. HLA-DRB1*11 was shown to raise protection to JIA (P=0.035, OR=2.755, 95% CI=0.963-8.055) in northeastern Iran. In addition, we found that HLA-RB1*09 is nominally associated with an increased risk of JIA (P=0.56, OR=2, 05, 95% CI=0.18-23.63). Conclusion: HLA-DRB1*11 was shown to raise protection to JIA in northeastern Iran. The disparity of findings in other ethnicities prompts further investigations with larger sample sizes.
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Affiliation(s)
- Zahra Rezaieyazdi
- Rheumatic Disease Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Morteza Kochakzadeh
- Rheumatic Disease Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Hatef
- Rheumatic Disease Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Habibollah Esmaily
- Social Determination of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abdolreza Malek
- Department of Pediatrics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Narges Valizadeh
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Samira Tabaei
- Rheumatic Disease Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Houshang Rafatpanah
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
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Chen Y, Zou K, Sun J, Yang Y, Liu G. Associations between gene polymorphisms and treatment outcomes of methotrexate in patients with juvenile idiopathic arthritis. Pharmacogenomics 2018; 19:529-538. [PMID: 29589488 DOI: 10.2217/pgs-2017-0208] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Aim: Performance of a meta-analysis with respect to the genetic predictors of methotrexate (MTX) treatment outcomes, efficacy and toxicity, in patients with juvenile idiopathic arthritis (JIA). Methods: Databases of OVID MEDLINE and OVID EMBASE were searched to collect the studies addressing correlations between gene polymorphisms and efficacy and/or toxicity in MTX-treated JIA patients. Pooled odds ratios (ORs) with 95% CIs were estimated in allelic, recessive and/or dominant models. Results: With regards to efficacy, the C677T (rs1801133) polymorphism in MTHFR was associated with nonresponse to MTX treatment in a recessive model (OR: 0.40; 95% CI: 0.19–0.84). For associations with toxicity, the MTHFR C677T (rs1801133) polymorphism was associated with presenting overall adverse events in an allelic model (OR: 1.54; 95% CI: 1.07–2.22) and a dominant model (OR: 1.70; 95% CI: 1.08–2.68). Conclusion: C677T (rs1801133) polymorphism in MTHFR predicts nonresponse and/or adverse effects of MTX treatment in JIA patients.
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Affiliation(s)
- Yuehong Chen
- Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, PR China
| | - Kun Zou
- Department of Medical Record & Statistics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science & Technology, Chengdu, PR China
| | - Jianhong Sun
- Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, PR China
| | - Yuan Yang
- Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, PR China
| | - Gang Liu
- Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, PR China
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OLIVEIRA GN, MOHAN R, FAGBEMI A. REVIEW OF CELIAC DISEASE PRESENTATION IN A PEDIATRIC TERTIARY CENTRE. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:86-93. [DOI: 10.1590/s0004-2803.201800000-17] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 10/09/2017] [Indexed: 12/11/2022]
Abstract
ABSTRACT BACKGROUND: Celiac disease is an immune-mediated disorder with a multiform presentation and therefore a challenging diagnosis. OBJECTIVE: Our purpose is to identify the epidemiological, clinical, laboratory and histologic characteristics of children with celiac disease at diagnosis and on follow-up. METHODS: Children with previously established or newly diagnosed celiac disease, admitted in a tertiary centre in a two-year period (2014-2016) were recruited. Data was collected retrospectively from electronic medical records and clinical notes, and subsequently analysed with SPSS version 20.0. RESULTS: A total of 159 patients, out of 312, were included. Age ranged from 1 to 17 years (mean ± SD: 8.5±4.5 years, 69% girls). Disease presentation was classical in 60%, non-classical in 25%, subclinical in 10% and 5% classified as potential celiac disease. Non-classical and subclinical profiles had a higher mean age at presentation but not statistically significant (P-value 0.24). The most frequent gastrointestinal features at presentation were abdominal pain (58%), diarrhea (43%) and bloating (27%). A positive family history for celiac disease was present in 24% (n=35). We found anaemia in 23%, low ferritin in 63% and a moderate to severe deficiency of 25-hydroxyvitamin D in 62%. celiac disease -specific serologic testing and esophagogastroduodenoscopy were performed in 99%. Histology revealed modified Marsh 2 or 3 enteropathy in 94%, the remaining had normal histology but positive human leukocyte antigen typing. Clinical improvement at 12 months of gluten-free diet was complete in 51% and partial in 49%. IgA tTG normalized after 12-30 months of gluten-free diet in 45%. On growth assessment at diagnosis and after 12-28 months of gluten-free diet, 100% had height increase (mean ±SD: 7.11±4.43 cm) and 96% weight gain (mean ±SD: 5.60±4.91 kg). CONCLUSION: Our findings outline the diverse clinical presentations of pediatric celiac disease that should be considered irrespective of age. Increased clinician’s awareness will enable an early diagnosis and treatment, with subsequent symptom and nutritional status improvement.
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Affiliation(s)
| | - Rajiv MOHAN
- Royal Manchester Children’s Hospital, United Kingdom
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Esmaeili Reykande S, Rezaei A, Sadr M, Shabani M, Najmi Varzaneh F, Ziaee V, Rezaei N. Association of interferon regulatory factor 5 (IRF5) gene polymorphisms with juvenile idiopathic arthritis. Clin Rheumatol 2018; 37:2661-2665. [PMID: 29423720 DOI: 10.1007/s10067-018-4010-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 01/18/2018] [Accepted: 01/29/2018] [Indexed: 11/24/2022]
Abstract
Interferon regulatory factor 5 (IRF5) is a member of IRF family which induce signaling pathways and are involved in modulation of cell growth, differentiation, apoptosis, and immune system activity. Juvenile idiopathic arthritis (JIA) is an auto-inflammatory syndrome where the inflammatory markers are believed to play a fundamental role in its pathogenesis. In this study, we aimed to assess the association of IRF5 gene polymorphisms with susceptibility of JIA in Iranian population. Three IRF5 single-nucleotide polymorphisms (rs10954213 A/G, rs2004640 G/T, and rs3807306 G/T) were genotyped using TaqMan assays in 55 patients with JIA and 63 matched healthy individuals. The frequency of the IRF5 rs2004640 T allele was significantly higher (69 vs 45%, P value = 0.0013) in JIA group as compared to control. The frequency of the IRF5 rs 2004640 G allele was significantly higher in the control group in comparison to JIA group (54 vs 32%, P value = 0.001). Allele and genotype frequencies of the rs10954213 and rs3807306 did not show any significant difference between JIA and control group. IRF5 rs 2004640 T allele can be considered as a risk factor for the development of JIA and presence of rs 2004640 G may be act as protective factor.
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Affiliation(s)
- Samira Esmaeili Reykande
- Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Arezou Rezaei
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 14194, Iran
| | - Maryam Sadr
- Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mahsima Shabani
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 14194, Iran
| | - Farnaz Najmi Varzaneh
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Baltimore, MD, USA
| | - Vahid Ziaee
- Division of Pediatric Rheumatology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 14194, Iran. .,Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. .,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, UK.
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14
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Yuwen W, Lewis FM, Walker AJ, Ward TM. Struggling in the Dark to Help My Child: Parents' Experience in Caring for a Young Child with Juvenile Idiopathic Arthritis. J Pediatr Nurs 2017; 37:e23-e29. [PMID: 28778610 PMCID: PMC5681389 DOI: 10.1016/j.pedn.2017.07.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 06/28/2017] [Accepted: 07/18/2017] [Indexed: 01/04/2023]
Abstract
PURPOSE The purpose of this study is to describe parents' experiences in caring for 2-5-year-old children with juvenile idiopathic arthritis (JIA). DESIGN AND METHODS A qualitative study using single-occasion in-depth interviews was conducted. Nine parents (eight mothers and one father) were interviewed in-person or via telephone. Data were analyzed using inductive content analysis. Methods used to protect the trustworthiness of study results included maintenance of an audit trail, peer debriefing, and member checks. RESULTS The core construct Struggling in the Dark to Help My Child explained parents' experience in six domains: not knowing, trying to reach out in the dark, feeling my child's pain, working out the kinks to stay on top to manage, feeling drained by the whole process, and being hard on the entire household. Parents struggled with the unknown, searched for resources, witnessed their child's suffering without knowing how to help, and tried every possible way to stay on top of the child's illness and treatment, even when they felt drained physically and emotionally. JIA not only consumed their lives, but also affected the entire family, including the siblings and spouse, and the relationships among family members. CONCLUSION AND IMPLICATIONS Findings highlight the day-to-day lived challenges parents face when caring for a young child with JIA. Healthcare providers including nurses need to assess the particular needs of an ill child and parents as well as the impact of the illness on the physical and psychosocial health of the entire family so that proper resources can be provided.
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Affiliation(s)
- Weichao Yuwen
- Nursing and Healthcare Leadership, University of Washington Tacoma, Tacoma, WA, United States.
| | - Frances M Lewis
- Family and Child Nursing, University of Washington, Seattle, WA, United States
| | - Amy J Walker
- Family and Child Nursing, University of Washington, Seattle, WA, United States
| | - Teresa M Ward
- Family and Child Nursing, University of Washington, Seattle, WA, United States
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15
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Kolomeyer AM, Crane ES, Tu Y, Liu D, Chu DS. Adult patients with uveitis associated with juvenile idiopathic arthritis: a retrospective review. Can J Ophthalmol 2017; 52:458-462. [PMID: 28985804 DOI: 10.1016/j.jcjo.2017.01.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Revised: 12/19/2016] [Accepted: 01/12/2017] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To describe clinical characteristics and outcomes of adults with uveitis associated with juvenile idiopathic arthritis (JIA). METHODS Retrospective chart review from 2001 to 2014 of adult patients with JIA and follow-up ≥2 months. Outcome measures included visual acuity, intraocular pressure (IOP), inflammation grade, ocular findings/complications, immunosuppressive therapies, and surgeries. RESULTS Nineteen patients were included (95% female, 84% bilateral uveitis, 47% anterior uveitis). Mean (SD) ages at presentation and JIA diagnosis were 25.6 (7.8) years and 8.9 (5.6) years, respectively. Visual acuity and IOP did not significantly change throughout the study. Mean (SD) presenting inflammation grade was significantly decreased at 6 and 12 months. Fifteen (79%) patients were on topical medications, and 17 (89%) were on systemic immunosuppression. Two (12%) patients developed side effects requiring medication cessation. CONCLUSION Uveitis associated with JIA may extend into adulthood despite the use of topical medications and/or systemic immunosuppression and result in significant ocular morbidity, including the need for surgical intervention.
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Affiliation(s)
- Anton M Kolomeyer
- Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Pennsylvania
| | - Elliot S Crane
- Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark, New Jersey
| | - Yufei Tu
- Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark, New Jersey
| | - Dan Liu
- Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark, New Jersey
| | - David S Chu
- Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark, New Jersey; Metropolitan Eye Research and Surgery Institute, Palisades Park, New Jersey.
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16
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Cui A, Quon G, Rosenberg AM, Yeung RSM, Morris Q, BBOP Study Consortium. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis. PLoS One 2016; 11:e0156055. [PMID: 27244050 PMCID: PMC4887077 DOI: 10.1371/journal.pone.0156055] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 05/09/2016] [Indexed: 01/10/2023] Open
Abstract
Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction). This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples.
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Affiliation(s)
- Ang Cui
- Division of Engineering Science, University of Toronto, Toronto, ON, Canada
| | - Gerald Quon
- Department of Computer Science, University of Toronto, Toronto, ON, Canada
| | - Alan M. Rosenberg
- Department of Pediatrics, Division of Rheumatology, University of Saskatchewan, Saskatoon, SK, Canada
| | - Rae S. M. Yeung
- Divisions of Rheumatology and Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Departments of Paediatrics, Immunology and Medical Sciences, University of Toronto, Toronto, ON, Canada
- * E-mail: (RY); (QM)
| | - Quaid Morris
- Department of Computer Science, University of Toronto, Toronto, ON, Canada
- The Donnelly Centre, University of Toronto, Toronto, ON, Canada
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- * E-mail: (RY); (QM)
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Xu Q, Lin CS. Plasma levels of D-dimer in a 5-year-old girl with systemic juvenile idiopathic arthritis: A case report and literature review. Exp Ther Med 2016; 11:1027-1030. [PMID: 26998032 DOI: 10.3892/etm.2016.3009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 09/24/2015] [Indexed: 12/31/2022] Open
Abstract
The present study reported high levels of D-dimer associated with multiple joint pain in a 5-year-old patient with systemic juvenile idiopathic arthritis (JIA). While treatment with methotrexate (MTX), hydroxychloroquine and methylprednisolone was found to reduce the D-dimer level and alleviated joint pain, the fever was not effectively controlled. Addition of etanercept to the treatment regimen from week 2 resulted in a clinical remission. Following 4-6 months of therapy, the D-dimer level of the patient returned to the normal range, and symptoms of noticeable joint pain and fever were absent. A literature search showed that the levels of D-dimer may be associated with JIA disease severity, and can serve as a prognostic biomarker for JIA treatment. In conclusion, the present study demonstrated that, while MTX therapy effectively reduced D-dimer levels, addition of etanercept to the treatment regimen was required to achieve a long-lasting remission of clinical symptoms, including fever.
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Affiliation(s)
- Qiang Xu
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Chang-Song Lin
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
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18
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Kolomeyer AM, Tu Y, Miserocchi E, Ranjan M, Davidow A, Chu DS. Chronic Non-infectious Uveitis in Patients with Juvenile Idiopathic Arthritis. Ocul Immunol Inflamm 2016; 24:377-85. [PMID: 26902465 DOI: 10.3109/09273948.2015.1125509] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE To describe clinical findings and analyze treatment evolution of chronic, non-infectious uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS A total of 82 patients (147 eyes) with JIA-related uveitis treated for ≥2 months were included (78% females; 79% bilateral uveitis; 74% anterior uveitis). Outcome measures were visual acuity (VA), inflammation control, side-effects, and surgical procedures. RESULTS Mean ± SD age at diagnosis was 4.9 ± 3.8 years; mean ± SD follow-up time was 8.7 ± 7.8 years. Mean VA did not significantly change throughout the study. Three (2%) eyes resulted in no light perception (NLP) vision. Thirty (37%) patients underwent 69 procedures. In total, 41 (50%) patients achieved inflammation control. TNF-α inhibitors were significantly associated with inflammation control. Seven (8.5%) patients stopped treatment due to side-effects. CONCLUSIONS JIA is a cause of significant ocular morbidity. TNF-α inhibitor use was associated with inflammation control. Prospective, randomized, double blind clinical trials in this regard are warranted.
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Affiliation(s)
- Anton M Kolomeyer
- a Department of Ophthalmology , University of Pittsburgh Medical Center , Pittsburgh , Pennsylvania , USA
| | - Yufei Tu
- b Institute of Ophthalmology and Visual Science , Rutgers University , Newark , New Jersey , USA
| | - Elisabetta Miserocchi
- c Department of Ophthalmology and Visual Sciences, Scientific Institute San Raffaele , University Vita-Salute , Milan , Italy
| | - Mangala Ranjan
- d Department of Quantitative Methods , Rutgers University , Newark , New Jersey , USA
| | - Amy Davidow
- d Department of Quantitative Methods , Rutgers University , Newark , New Jersey , USA
| | - David S Chu
- b Institute of Ophthalmology and Visual Science , Rutgers University , Newark , New Jersey , USA.,e Metropolitan Eye Research and Surgery Institute , Palisades Park, New Jersey , USA
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The Effects of Orthopedic Manual Physical Therapy in the Management of Juvenile Idiopathic Arthritis: A Case Report. Pediatr Phys Ther 2016; 28:490-7. [PMID: 27661250 DOI: 10.1097/pep.0000000000000319] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Juvenile idiopathic arthritis (JIA) is a cause of disability in childhood. Little research exists concerning physical therapy management, and no evidence exists for orthopedic manual physical therapy (OMPT) for JIA. The purpose of this case report is to describe the use of OMPT in combination with therapeutic exercise in the successful treatment of a child with oligoarticular JIA. KEY POINTS A 6-year-old girl with oligoarticular JIA presented with elbow pain and stiffness interfering with function. Treatment consisted of OMPT in combination with therapeutic exercise and a home exercise program. CONCLUSIONS Improvements were demonstrated in elbow range of motion, pain, Childhood Health Assessment Questionnaire, Pediatric Outcomes Data Collection Instrument, and the Patient Specific Functional Scale. RECOMMENDATIONS FOR CLINICAL PRACTICE Orthopedic manual physical therapy may be considered as a treatment of a child with JIA. RECOMMENDATIONS We provide evidence that OMPT may be considered as a treatment of a child with JIA.
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20
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Hu CH, Curry EJ, Matzkin EG, Todd DJ, Cai AN, Milner DA, Sparks JA. Monoarthritis in a 28‐Year‐Old Man With Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken) 2015; 67:1328-1334. [DOI: 10.1002/acr.22597] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Revised: 03/10/2015] [Accepted: 03/24/2015] [Indexed: 11/10/2022]
Affiliation(s)
- Caroline H. Hu
- Brigham and Women's Hospital, Boston, Massachusetts, and University of Minnesota Medical SchoolMinneapolis
| | | | | | - Derrick J. Todd
- Brigham and Women's Hospital and Harvard Medical SchoolBoston Massachusetts
| | - Andrew N. Cai
- Brigham and Women's Hospital, Boston, Massachusetts, and Albany Medical CollegeAlbany, New York
| | | | - Jeffrey A. Sparks
- Brigham and Women's Hospital and Harvard Medical SchoolBoston Massachusetts
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21
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Abstract
Prostaglandins, particularly PGE2, are important to adult bone and joint health, but how prostaglandins act on growth plate cartilage to affect bone growth is unclear. We show that growth plate cartilage is distinct from articular cartilage with respect to cyclooxygenase (COX)-2 mRNA expression; although articular chondrocytes express very little COX-2, COX-2 expression is high in growth plate chondrocytes and is increased by IGF-I. In bovine primary growth plate chondrocytes, ATDC5 cells, and human metatarsal explants, inhibition of COX activity with nonsteroidal antiinflammatory drugs (NSAIDs) inhibits chondrocyte proliferation and ERK activation by IGF-I. This inhibition is reversed by prostaglandin E2 and prostacyclin (PGI2) but not by prostaglandin D2 or thromboxane B2. Inhibition of COX activity in young mice by ip injections of NSAIDs causes dwarfism. In growth plate chondrocytes, inhibition of proliferation and ERK activation by NSAIDs is reversed by forskolin, 8-bromoadenosine, 3',5'-cAMP and a prostacyclin analog, iloprost. The inhibition of proliferation and ERK activation by celecoxib is also reversed by 8CPT-2Me-cAMP, an activator of Epac, implicating the small G protein Rap1 in the pathway activated by iloprost. These results imply that prostacyclin is required for proper growth plate development and bone growth.
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Affiliation(s)
- Michele R Hutchison
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390
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22
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Moreno Prieto M, Carbonero Celis M, Cuadrado Caballero M. Infrecuente presentación de artritis idiopática juvenil y hepatitis autoinmune. An Pediatr (Barc) 2015; 82:e147-50. [DOI: 10.1016/j.anpedi.2014.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 05/06/2014] [Accepted: 05/14/2014] [Indexed: 11/25/2022] Open
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Präger TM, Meyer P, Rafayelyan S, Minden K, Jost-Brinkmann PG. Effect of methotrexate on the mandibular development of arthritic rabbits. Eur J Orthod 2014; 37:514-21. [PMID: 25518996 DOI: 10.1093/ejo/cju070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Juvenile idiopathic arthritis affecting the temporomandibular joint (TMJ) can cause severe disturbances of the mandibular development. Methotrexate (MTX) is often administered as a common used remission-inducing agent to treat this disease. The aim of this study was to investigate the effect of low dose MTX on the mandibular growth in arthritic rabbits. SUBJECTS AND METHODS Eighteen 10-week-old female New Zealand white rabbits were randomly assigned to three groups with six animals in each group. After being sensitized to ovalbumin (OA), the first and the second group received intra-articular injections with OA. The first group remained untreated, the second was treated by weekly injections of MTX. Cephalograms were taken from each animal at 10, 13, 16, 19, and 22 weeks of age and six mandibular distances measured. RESULTS All distances showed an increase between 10 and 20 per cent, whereas growth was more accentuated in the sagittal dimension. Significant differences in the overall growth could be observed between the arthritic and the control animals and less accentuated between the arthritic and the MTX animals. In contrast, existing differences between the groups were not significant during the intervals, but time had the greatest influence on mandibular growth. CONCLUSIONS MTX seems to have a positive impact on growth in rabbits suffering from experimental arthritis of the TMJ.
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Affiliation(s)
- Thomas Michael Präger
- *Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Charité - Universitätsmedizin Berlin and
| | - Philipp Meyer
- *Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Charité - Universitätsmedizin Berlin and
| | - Smbat Rafayelyan
- *Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Charité - Universitätsmedizin Berlin and
| | - Kirsten Minden
- German Rheumatism Research Centre Berlin (DRFZ), Berlin, Germany
| | - Paul-Georg Jost-Brinkmann
- *Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Charité - Universitätsmedizin Berlin and
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24
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Rafayelyan S, Meyer P, Radlanski RJ, Minden K, Jost-Brinkmann PG, Präger TM. Effect of methotrexate upon antigen-induced arthritis of the rabbit temporomandibular joint. J Oral Pathol Med 2014; 44:614-21. [PMID: 25243828 DOI: 10.1111/jop.12265] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/15/2014] [Indexed: 01/07/2023]
Abstract
BACKGROUND Juvenile idiopathic arthritis (JIA) of the temporomandibular joint (TMJ) can cause severe growth disturbances of the craniomandibular system. Antigen-induced arthritis (AIA) of the rabbit TMJ is simulating the inflammatory process of the TMJ in JIA. The aim of this study was to investigate the effect of a systemic administration of methotrexate (MTX) on AIA in rabbits by means of three different histological staining methods. METHODS After sensitization, a bilateral arthritis of the TMJ was induced by an intra-articular administration of ovalbumin in 12 New Zealand white rabbits aged 10 weeks. From the 13th week of age, six of the 12 rabbits received weekly intramuscular injections of MTX, and the other six animals remained without therapy. Another six animals served as controls, receiving no treatment or intra-articular injections at all. After euthanasia at the age of 22 weeks, all TMJs were retrieved en bloc. Sagittal sections were cut and stained with haematoxylin-eosin (H-E), Safranin-O for the evaluation of the Mankin score and tartrate-resistant acid phosphatase (TRAP). RESULTS In the arthritis group, a chronic inflammation with degeneration of the articular cartilage was visible. In the MTX group, the signs of cartilage degeneration were significantly reduced compared with the arthritis group. In contrast, the joints in the control group were inconspicuous. A correlation between the Mankin score and TRAP-positive cells could be found. CONCLUSIONS Systemic administration of MTX seems to have a positive effect upon the inflammatory process in the rabbit TMJ but fails to eliminate the sign of arthritis completely.
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Affiliation(s)
- Smbat Rafayelyan
- Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Center for Dental and Craniofacial Sciences, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Philipp Meyer
- Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Center for Dental and Craniofacial Sciences, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Ralf J Radlanski
- Department of Oral Structural Biology, Center for Dental and Craniofacial Sciences, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Kirsten Minden
- German Rheumatism Research Centre Berlin, Berlin, Germany
| | - Paul-Georg Jost-Brinkmann
- Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Center for Dental and Craniofacial Sciences, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Thomas M Präger
- Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Center for Dental and Craniofacial Sciences, Charité - Universitätsmedizin Berlin, Berlin, Germany
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25
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Stark C, Hoyer-Kuhn H, Knoop K, Schoenau H, Schoenau E, Semler O. [Secondary forms of osteoporosis. Special features of diagnostics in childhood and adolescence]. Z Rheumatol 2014; 73:335-41. [PMID: 24714928 DOI: 10.1007/s00393-013-1326-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Rheumatic diseases in childhood and adolescence can lead to secondary osteoporosis based on various pathophysiologies. The underlying disease, medication and immobility resulting in a reduced osteoanabolic stimulus contribute to the development of a fragile skeletal system. For diagnostic purposes dual-energy X-ray absorptiometry (DXA) is the most frequently used technology. For interpretation of the areal bone mineral density, age and gender matched reference data have to be used. Particularly in the pediatric field, body height must additionally be taken into consideration. Further techniques which can provide detailed information are peripheral quantitative computed tomography and high resolution magnetic resonance imaging. Nowadays, skeletal assessments have to be interpreted in the context of the muscular system. The concept of the functional muscle-bone unit is widely accepted and uses the muscles as the dominating factor. In a second step the adaptation of the skeletal system to the applied muscle force is evaluated. This allows a differentiation between primary and secondary skeletal diseases depending on the ratio of muscles to bone. Therapeutic options for secondary osteoporosis include reduction of the causative medication, treatment of the underlying disease, antiresorptive treatment with bisphosphonates and different programs to activate the muscles. A multimodal interval rehabilitation program including alternating side vibration shows positive effects on mobility, muscle function and bone mass in children and adolescents.
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Affiliation(s)
- C Stark
- Klinik für Kinder- und Jugendmedizin, Uniklinik Köln, Kerpener Str. 62, 50931, Köln, Deutschland
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Tudur Smith C, Williamson PR, Beresford MW. Methodology of clinical trials for rare diseases. Best Pract Res Clin Rheumatol 2014; 28:247-62. [DOI: 10.1016/j.berh.2014.03.004] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Chistiakov DA, Savost’anov KV, Baranov AA. Genetic background of juvenile idiopathic arthritis. Autoimmunity 2014; 47:351-60. [DOI: 10.3109/08916934.2014.889119] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis. Pediatr Res 2014; 75:176-83. [PMID: 24213625 DOI: 10.1038/pr.2013.187] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 07/11/2013] [Indexed: 11/08/2022]
Abstract
Systemic juvenile idiopathic arthritis (s-JIA) is clinically distinct from other types of JIA. It is typified by extraarticular features such as quotidian fevers, rash, splenomegaly, lymphadenopathy, laboratory abnormalities (including leukocytosis, thrombocytosis, anemia, hyperferritinemia, and elevated inflammatory markers), and a close association with the macrophage activation syndrome. Recent investigations have highlighted dysregulation of the innate immune system as the critical pathogenic driver of s-JIA. Key innate immune mediators of s-JIA are the macrophage-derived cytokines interleukin-1 (IL-1) and IL-6. Increased understanding of the roles of IL-1 and IL-6 in the pathogenesis of s-JIA has led to major changes in therapeutic options. Until recently, the most commonly used medications included corticosteroids, methotrexate, and tumor necrosis factor (TNF) inhibitors, which are incompletely effective in most cases. Newer biologic agents targeting IL-1 and IL-6 have proven very effective in treating s-JIA and in minimizing corticosteroid exposure. Here we review recent advances in the understanding of the pathogenesis of s-JIA and the recent clinical trials that have revolutionized the care of children with s-JIA.
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Makay B, Unsal E, Kasapcopur O. Juvenile idiopathic arthritis. World J Rheumatol 2013; 3:16-24. [DOI: 10.5499/wjr.v3.i3.16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 07/22/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease in childhood, which represents a nonhomogeneous group of disorders that share the clinical manifestation of arthritis lasting at least 6 wk under the age of 16. The exact diagnosis requires exclusion of other diseases that cause arthritis. The exact etiopathogenesis of JIA is still unknown. The interactions between genetic factors, environmental exposures and immune mechanisms are thought to contribute to pathogenesis of the disease. The “International League Against Rheumatism” classification divides JIA into 7 subtypes: oligoarticular JIA, rheumatoid factor (RF) positive polyarticular JIA, RF negative polyarticular JIA, systemic-onset JIA, enthesitis-related arthritis, juvenile psoriatic arthritis and undifferentiated JIA. Each subgroup of JIA is characterized by a different mode of presentation, disease course and outcome. The improvements in treatment of JIA in the last 2 decades, such as the early introduction of intraarticular corticosteroids, methotrexate and biologic agents, have dramatically upgraded the prognosis of the disease. If untreated, JIA may cause devastating results, such as disability from joint destruction, growth retardation, blindness from chronic iridocyclitis, and even multiple organ failure and death in systemic-onset JIA. The aim of treatment is the induction of remission and control the disease activity to minimize the pain and loss of function, and to maximize quality of life. JIA is a disease having a chronic course, which involves active and inactive cycles over the course of years. Recent studies showed that nearly half of the patients with JIA enter adulthood with their ongoing active disease. This review elucidates how recent advances have impacted diagnosis, pathogenesis and current treatment.
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Abstract
PURPOSE OF REVIEW Pediatric uveitis is relatively uncommon, accounting for only 5-10% of all patients with uveitis. However, owing to high prevalence of complications and devastating outcomes, its lifetime burden can be significant. RECENT FINDINGS Immunomodulatory therapy has been associated with better outcomes in noninfectious pediatric uveitis. However, effective treatments are limited by medication-related complications, including multiorgan toxicities and systemic side effects. SUMMARY We review the current therapies available to treat pediatric uveitis, discuss novel and future therapies, and provide clinical recommendations utilizing these new agents. The consideration for treatment regimens in noninfectious pediatric uveitis is multifactorial. Understanding past, present, and future technology will aid in treatment of a complex and refractory disease.
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Hu-Torres S, Foster CS. Disease of the Year: Juvenile Idiopathic Arthritis—Differential Diagnosis. Ocul Immunol Inflamm 2013; 22:42-55. [DOI: 10.3109/09273948.2013.835430] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Lovell DJ, Ruperto N, Giannini EH, Martini A. Advances from clinical trials in juvenile idiopathic arthritis. Nat Rev Rheumatol 2013; 9:557-63. [PMID: 23838613 DOI: 10.1038/nrrheum.2013.105] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Treatments available to children with juvenile idiopathic arthritis (JIA) have improved dramatically in the past 15 years, largely because of the development of powerful new biologic treatments. However, the seeds of this development were sewed over 40 years ago with the formation of a group of paediatric rheumatologists who understood the necessity of performing clinical trials in children with JIA. From there, international paediatric rheumatology networks have grown, and are dedicated to and highly experienced in performing such clinical trials. Development of validated outcomes and methodologies has also been critical. The ability to perform these trials stems from legislation enabling the FDA and the European Medicines Agency to require studies to be performed in children before they can be licensed for use in children. Current efforts to enhance the understanding of treatment options for patients with JIA include the development of disease-specific rather than drug-specific consolidated registries, studies in personalized predictive medicine and the development of treatment protocols for regular clinical care of these patients.
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Affiliation(s)
- Daniel J Lovell
- Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
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