Espondiloartritis en la infancia

Juvenile-onset spondyloarthritis is a special group within the entities included in the concept of spondyloarthritis, and is characterized by a predominantly peripheral involvement (arthritis and enthesitis), and more frequent presentation as undifferentiated forms. However, like its adult-onset equivalent, it has the potential to develop structural damage and progress to juvenile ankylosing spondylitis, with consequent irreversible functional impairment. Many important advances have been made in the understanding of the genetics and pathophysiology of juvenile-onset spondyloarthritis, as well as in the diagnosis and treatment of this entity. These advances are summarized in this article.     

Juvenile ankylosing spondylitis—is it the same disease as adult ankylosing spondylitis?

Objectives Juvenile and adult forms of ankylosing spondylitis (AS) have been shown to have different clinical presentation and outcome in Caucasians. We did this retrospective analysis to see if similar differences exist in the Indian population.Patients and methods Case records of 210 Indian patients diagnosed with AS according to modified New York criteria were reviewed. Data were collected regarding age of onset, clinical features, drug treatment, and outcome at last follow-up. Patients with onset before 17 years of age were classified as having juvenile AS (JAS) and the rest with adult AS (AAS).Results There were 150 patients with AAS and 60 with JAS. The latter had higher male preponderance, more frequent onset with peripheral arthritis, and greater involvement of hip and knee joints. Valvular dysfunction was seen only in patients with JAS.Conclusion In this group of subjects, juvenile AS had onset more often with oligoarthritis and enthesitis than with spinal disease. Hip and knee joint involvement was more common in JAS than AAS.     

Positivity for anti-RNP antibody is a risk factor for adverse effects caused by trimethoprim–sulfamethoxazole, a prophylactic agent for P. jiroveci pneumonia, in patients with connective tissue diseases

Objectives

Trimethoprim–sulphamethoxazole (TMP–STX), an agent used for prophylaxis against pneumocystis pneumonia (PCP) in immunocompromised hosts, causes serious adverse effects (AEs) in some patients. The objective of this study was to identify the risk factors for AEs caused by TMP–STX in connective tissue disease (CTD) patients and to describe the clinical features of the AEs.

Methods

The medical records of 539 patients (CTDs 312, pulmonary diseases 227) receiving TMP–STX for prophylaxis against PCP were reviewed retrospectively. Patients with human immunodeficiency virus were excluded. Univariate and multivariate analyses were conducted to identify the risk factors.

Results

Adverse events caused by TMP–STX occurred in 22 of 312 (7.05 %) CTD patients, while only six of 227 (2.64 %) pulmonary disease patients developed AEs. The incidence of AEs was significantly higher in systemic lupus erythematosus (SLE) (11.0 %) and mixed connective tissue disease (MCTD) (33.3 %) patients than in other CTD patients. AEs occurred in 25 % of patients with anti-RNP antibody. Univariate analysis revealed that SLE, MCTD, and anti-RNP antibody were risk factors for AEs in CTD patients. Further multivariate analyses demonstrated that only anti-RNP antibody positivity was a risk factor for AEs. Systemic inflammation, including fever, was a characteristic manifestation of the AEs in CTD patients, particularly those with anti-RNP antibody.

Conclusions

Positivity for anti-RNP antibody is a risk factor for AEs caused by TMP–STX in CTD patients. Systemic inflammation, including fever, might be a characteristic feature of the AEs in CTD patients, particularly those with anti-RNP antibody.     

HLA-B27 negative reactive arthritis versus HLA-B27 positive reactive arthritis: A retrospective study

Reactive arthritis (ReA) is defined as inflammatory arthritis secondary to an extra-articular infection with a key genetic background, HLA-B27. However, to date, the diagnosis and classification remain incomplete. The study focused on the similarities and differences in clinical manifestation, imaging features, and laboratory inspection between HLA-B27 negative patients and HLA-B27 positive patients in order to provide a reference for future development of diagnostic and classification criteria. Twenty-five ReA (19 HLA-B27 negative patients and 6 HLA-B27 positive patients) were included in this retrospective study. Clinical data, including demographics, clinical symptoms, imaging features, and laboratory inspection, were collected. The chi-square test and Mann–Whitney U test were used in the analysis. HLA-B27 negative group showed more involvement of upper extremities and small joints, while HLA-B27 positive group performed more axial symptoms. No significant difference was found in imaging features (ultrasound and magnetic resonance imaging) or laboratory inspection (microbes culture and infection-related indicators) between the 2 groups. ReA patients with different genetic backgrounds show various manifestations, although they encounter similar infections.     

幼年脊柱关节病的早期特征和治疗

复习近期有关幼年脊柱关节病(JSpA、早期特征和治疗的文献。肌腱端炎、关节炎、腊肠趾及血清阴性肌腱端病和关节病综合征是本病特征性表现。儿童通常出现某一临床表现，发展到某特定型脊柱关节病需要一段时间。JSpA的治疗主要为非甾体类抗炎药、甲氨蝶呤和柳氮磺吡啶。严重的肌腱端炎可用小剂量泼尼松。反应停、TNF拮抗剂和二膦酸盐对JSpA的疗效有待验证。     

Sulphasalazine in the treatment of children with chronic arthritis

The ainich of study was to investigate the efficacy and toxicity of sulphasalazine (SASP) in the treatment of children with chronic arthritis. The medical records of 36 children (25 boys, 11 girls) who received SASP for the treatment of chronic arthritis were reviewed. Twenty-one patients had juvenile spondyloarthropathies (JSA) (eight juvenile ankylosing spondylitis (JAS), 13 undifferentiated JSA (uJSA) and 15 had juvenile rheumatoid arthritis (JRA). The patients received SASP therapy for a mean of 2.5 years (range 3 weeks to 8.1 years). Clinical and laboratory data were reviewed retrospectively to determine the effects of treatment. A clinically significant response occurred in 23 (64%) children: remission in 14 (39%) (JRA 5, JSA 9) and improvement (25% reduction in joint count) in nine (25%) (JRA 4, JSA 5). There was no difference in response rate between JR and JSA patients (p=0.11), but the time to remission shorter in JSA patients (mean 5 months) JRA patients (mean 25 months) (p=0.024). Twelve of the 36 patients discontinued non-steroidal anti-inflammatory drugs, and six of eight patients discontinued prednisolone. A significant fall in erythrocyte sedimentation rate and rise in haemoglobin occurred in SASP-treated patients (p<0.005) comparing most recent results with pretreatment levels. Side-effects occurred in four of 36 patients (11%); only one patient who had persisting severe diarrhoea required discontinuation of SASP. It was concluded that SASP appears to be effective and safe in the treatment of JRA and JSA patients. As a second-line agent, SASP is the drug of first choice for patients with JSA; for JRA patients SASP may be a useful, possibly less toxic alternative to methotrexate.     

Analysis of childhood reactive arthritis and comparison with juvenile idiopathic arthritis

There is currently no agreement on how to classify and diagnose reactive arthritis (ReA) and what kind of clinical and laboratory findings are specific for the diagnosis. This study retrospectively analyzed the initial clinical manifestations and laboratory findings in children diagnosed with ReA and juvenile idiopathic arthritis (JIA). A comparison was also made between these two groups to see if there were differences. A retrospective chart review was performed and 44 patients diagnosed with ReA and 80 patients with JIA were enrolled in this study. Their initial clinical manifestations and laboratory findings were also analyzed and compared. The initial clinical manifestations in ReA were analyzed including the demographic data, the preceding infection history, the duration of the infectious episode to the onset of arthritis, the duration of arthritic symptoms, and the involved joint pattern. Comparison of the initial laboratory findings between patients with ReA and JIA showed significant differences between erythrocyte sedimentation rates (ESR) in the first hour, platelet counts (p<0.05), and ESR in the second hour (p=0.052). Further, comparing ReA with the subtypes of JIA, significant differences were noted between ReA and the systemic type in terms of hemoglobin level, platelet counts, C-reactive protein, and first and second hour ESR (p<0.05). However, if compared with the polyarticular or pauciarticular type, only the platelet counts showed any significant statistical difference (p<0.05). This study summarizes clinical experiences in ReA. The differences in laboratory findings of ReA and JIA may provide a clue in making a differential diagnosis.     

Class I associations and frequencies of class II HLA-DRB alleles by RFLP analysis in children with rheumatoid-factor-negative juvenile chronic arthritis

Summary A total of 94 patients with juvenile chronic arthritis (JCA) was tested for HLA class I by serology and for class II by RFLP typing. Early onset JCA (EOPA) is associated with HLA-A2, DR5 and DR8 in both males and females. The combination (joint occurrence) of these JCA associated alleles (A2, DR5, DR8) is frequently seen in patients with chronic iridocyclitis. Late onset pauciarticular disease has an increased frequency of HLA-B27, especially in males. Our data confirm that polyarticular JCA with early childhood onset (4 years) is associated with DR5 and DR8 and has a different immunogenetic background from polyarticular JCA with later childhood (>4 years) onset (associated with DR4).     

Synovial fluid RANKL and matrix metalloproteinase levels in enthesitis related arthritis subtype of juvenile idiopathic arthritis

In chronic arthritis cartilage and bone destruction occur as a consequence of synovial inflammation. It is mainly mediated by matrix metalloproteinases and RANKL-OPG pathways. Data on synovial fluid levels of these mediators in enthesitis related arthritis subtype (ERA) of JIA are not available. MMP-1, MMP-3, TIMP, sRANKL and OPG levels were measured in synovial fluid from patients with ERA and compared with other arthritides, polyarticular (Poly) JIA, RA and osteoarthritis (OA). sRANKL was detectable in 25/41 of ERA patients, 4/16 of Poly JIA patients. Median SF sRANKL level in patients with ERA was higher as compared to OA (p < 0.001) and poly JIA (p < 0.05) but were comparable to RA. The median OPG level in ERA was lower as compared to OA (p < 0.001), comparable to RA but was higher than poly JIA (p < 0.001). sRANKL/OPG ratio was significantly higher in ERA and Poly JIA compared to OA (p < 0.0001, p < 0.0001 respectively). The median MMP3 levels in ERA (74 ug/ml) was lower as compared to poly JIA (410 ug/ml; p < 0.0001) and RA (340 ug/ml; p < 0.0001) but was comparable to OA (107 ug/ml). The median level of ProMMP1 in ERA (0.70 ug/ml) was lower as compared to RA (2.9 ug/ml; p < 0.0001) and poly JIA but was elevated as compared to OA patients (0.1 ug/ml; p < 0.0001). TIMP1 levels in ERA were higher than poly JIA and RA patients. MMP3/TIMP1 ratio was lower in ERA compared to polyarticular JIA patients (p < 0.05). Ours is the first study reporting elevated sRANKL and reduced OPG levels and elevated sRANKL/OPG ratio in SF of children with JIA resulting in a mileu associated with bone loss. In addition, ERA patients had lower MMP level as well as MMP/TIMP ratio as compared to poly JIA which may partly explain lesser degree of joint damage seen in ERA as compared to poly JIA.     

Spontaneous,drug-induced,and drug-free remission in peripheral and axial spondyloarthritis

In spondyloarthritis (SpA), spontaneous remission is best described in reactive arthritis, a form of peripheral SpA. Prior SpA observational studies suggested that a significant percentage of patients reached spontaneous remission; however, these patients were followed up under older, broader European Spondyloarthropathy Study Group (ESSG) criteria or were not defined by specific criteria. In general, they were mixed populations of peripheral and axial disease, and the subsets were not differentiated when assessing end points such as remission. There are limited data on the natural history of axial SpA, in part because of the evolution of the criteria with the more recently developed Assessment of SpondyloArthritis International Society (ASAS) criteria, including the designation of non-radiographic axial SpA and peripheral SpA. Clinical trials have been conducted with various remission end points including withdrawal of therapy to determine remission maintenance. The following review addresses the potential for remission in axial and peripheral SpA based on the data from both observational studies and clinical trials.     

Chitotriosidase activity in juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is an inflammatory joint disease of unknown etiology. The pathogenesis is driven by T and B cells. The role of macrophages remains unclear. Chitotriosidase belongs to the chitinase protein family and is secreted by activated macrophages. The chitinases are able to catalyze the hydrolysis of chitin or chitin-like substrates such as 4-methylumbelliferyl chitotrioside. Chitotriosidase activity was determined using the substrate 4-methylumbelliferyl beta-DNN'N'-triacetylchitotrioside (4-MU-TCT, SIGMA Chemical Co.). The substrate and serum were incubated with the serum in a citrate/phosphate buffer. The reaction was stopped by adding a buffer (Na(2)CO(3)). The fluorescence of 4-methylumbelliferone was evaluated by fluorimeter at excitation 360 nm and emission 450 nm. We report about chitotriosidase measurements in patients with JIA. The chitotriosidase level in synovial fluid was up to approximately 1,000 nmol/(h ml) at disease onset before therapy. The level in the sera was below 600 nmol/(h ml). Serum chitotriosidase levels could represent the activity of macrophages in the synovial fluid in JIA.     

Bone mineral density in children with juvenile chronic arthritis

The aim of this study was to evaluate bone mineral density changes in patients with juvenile chronic arthritis (JCA) and to determine the most likely causes of osteoporosis in these patients. Eighteen (11 male, 7 female) patients suffering from JCA and 14 healthy controls (10 male, four female) were included in this study. The mean age of the patients and control groups were 11.0±3.2 and 10.9±2.9 years respectively. Disease activity was determined by clinical and laboratory evaluation and Articular Disease Severity Score (ADSS). Bone mineral density (BMD) of the femoral neck and lumbar spine was measured by dual photon absorptiometry.BMD of the patients at the lumbar spine was significantly lower than the control group (p<0.05). This difference was more marked in patients treated with steroids. Femoral neck BMD was also lower in the patient group but this difference was not statistically significant. There was a negative correlation between ADSS and BMD at the spine. In conclusion, trabecular bone loss is characteristic for osteoporosis in JCA. Our results indicate that steroid treatment and disease severity are important factors in the development of osteoporosis in JCA.     

Peripheral arthritis in patients with long-term inflammatory bowel disease. Results from 20 years of follow-up in the IBSEN study

Objectives: Peripheral arthritis and related musculoskeletal manifestations, often classified as peripheral spondyloarthritis, are frequently seen in patients with inflammatory bowel disease (IBD). Few long-term studies have reported on the prevalence of these conditions. The aim of this study was to determine the prevalence of IBD-related peripheral arthritis and peripheral spondyloarthritis in IBD patients during 20 years of disease course, and to assess whether these conditions were associated with the intestinal IBD severity and activity.

Materials and methods: In an inception cohort (the IBSEN study), IBD patients were followed prospectively for 20 years. At the 5 year follow-up the patients underwent a rheumatological examination and at the 20 year follow-up they completed a questionnaire with identical questions. When peripheral arthritis was characteristic and not explained by other specific diagnoses, it was defined as IBD-related peripheral arthritis. The Assessment of Spondyloarthritis International Society criteria were used to define peripheral spondyloarthritis, including patients with peripheral arthritis, enthesitis and/or dactylitis.

Results: After 20 years of follow-up, 441 patients were included (296 ulcerative colitis and 145 Crohn’s disease). The prevalence of IBD-related peripheral arthritis was 17.2% and peripheral spondyloarthritis 27.9% during the disease course. IBD severity and activity were not different between those with a history of IBD-related peripheral arthritis or peripheral spondyloarthritis and those without. A higher proportion of women had IBD-related peripheral arthritis and peripheral spondyloarthritis.

Conclusion: During 20 years of disease course, more than every sixth patient had suffered from IBD-related peripheral arthritis and every fourth from peripheral spondyloarthritis.