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.     

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.     

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.     

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.     

T-cell receptor Vβ chain expression in patients with juvenile rheumatoid arthritis

Summary The V chain repertoire in peripheral blood T-cells was analyzed in 23 patients with juvenile rheumatoid arthritis (JRA). Of these, 15 patients had active disease as defined by tender and swollen joints. The ESR was elevated in all but three patients, C-reactive protein (CRP) was elevated in eight. Three patients were investigated during active and inactive phases of the disease. In the active phase of the disease T-cell composition was characterized by an increased number of CD4⁺ helper cells due to a marked increase in the CD4⁺CD45RA⁺ subgroup (34.0±10.9%,P<0.001) and a decrease in CD8⁺CD29⁺ T-cells (10.3±5.6%,P<0.05) compared to controls (15.4±10.0% and 17.8±12.3%, respectively). Using the monoclonal antibodies available to determine T-cell receptor (TCR) expression, patients with active disease demonstrated a significant predominance of T-cells bearing TCRs of the V5 family as determined by flow cytometry (7.6±6.7 vs 3.4±1.3 in controls,P=0.01). In active polyarthritis, up to 24% of peripheral blood T-cells expressed TCRs of the same family. In the majority of JRA patients and especially in non-active disease, no preferential TCRs were found compared to controls. However, even defining only a part of TCRs by immunofluorescence, in certain patients a preferential or dominant expression of a single V gene family in the T-cells was found, supporting the concept of an involvement of T-cells in the autoimmune pathogenesis of JRA.     

Cloak and dagger: the case for adult onset still disease and hemophagocytic lymphohistiocytosis

Adult onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. Systemic onset juvenile idiopathic arthritis (SoJIA) is the preferred nomenclature of Still’s disease. Strong association with so-called macrophage activation syndrome (MAS) may provide a clue to the understanding of the distinctive pathogenetic features of SoJIA. MAS is a severe, potentially life-threatening complication characterized by the excessive activation of well-differentiated macrophages. It is more appropriately named autoimmune disease associated reactive hemophagocytic lymphohistiocytosis (ReHLH), a subset of a histiocytic disorder: class II histiocytosis hemophagocytic lymphohistiocytosis (HLH). The relation of SoJIA with HLH is still under debate. We propose that MAS, HLH, SoJIA, and AOSD are indeed the same disease, in different clinical presentations that may be classified based on severity and laboratory findings, but with essentially the same physiopathogenesis. We propose that the case described by Hong & Lee (Rheumatol Int 2008) was actually an AOSD-associated MAS/RHS/ReHLH fulminant disease.     

Development and preliminary validation of a Children's Arthritis Self‐Efficacy Scale

Objective

To develop a valid and reliable measure of arthritis self‐efficacy for use with school‐age children with juvenile idiopathic arthritis (JIA).

Methods

Construction of the 11‐item Children's Arthritis Self‐Efficacy Scale (CASE) was based on an existing body of knowledge and the results of focus groups with children, their parents, and health professionals. Data for validation of the CASE were collected by self‐administered questionnaires completed by 89 children and 151 caregivers.

Results

Analyses revealed a 3‐factor structure relating to self‐efficacy for managing symptoms, emotional consequences, and activities, explaining 76.5% of the total variance. The CASE demonstrated high internal consistency, concurrent validity, and construct validity.

Conclusion

Preliminary findings suggest that the CASE is worthy of further psychometric testing and may have the potential to help delineate variations in adjustment among children with JIA.

     

A case of planned pregnancy with an interruption in infliximab administration in a 27-year-old female patient with rheumatoid-factor-positive polyarthritis juvenile idiopathic arthritis which improved after restarting infliximab and methotrexate

We report a 27-year-old case of juvenile idiopathic arthritis (JIA) having been stopped infliximab during pregnancy. She was safely treated by infliximab therapy with premedications for preventing infusin reactions after her delivery, and then improved in the same manner as when she had been treated with infliximab therapy before pregnancy. As a result, it remains unclear whether or not we can use infliximab to control disease activities during pregnancy. In addition, it is also important to clarify whether or not premedications should be used when resuming infliximab treatment in such patients after pregnancy. These problems still remain controversial. More definitive data are needed in order to allow rheumatologists to better select the optimal TNF-alpha inhibitor therapy when treating pregnant JIA patients.     

Methotrexate therapy in systemic-onset juvenile rheumatoid arthritis in Saudi Arabia: A retrospective analysis

Eighteen patients (nine girls, nine boys) with systemic onset juvenile rheumatoid arthritis (SO-JRA) treated with methotrexate (MTX) for a mean period of 18 months (range 6–41 months) were analysed to evaluate the safety and efficacy of MTX in this disease subtype. The MTX dose ranged from 2.5 to 15 mg/week with a mean cumulative dose of 684.9 mg/patient at the last follow-up visit. Systemic features were severe in 10 patients before MTX was started. None of these patients showed systemic features at the last follow-up visit. Sixteen patients (89%) showed improvement in both the active joint count (from a mean of 12.0 to 1.3 joints/patient) and function class (from a mean of 3.0 to 1.3) while receiving MTX. Eleven patients (61%) showed a significant decrease in the erythrocyte sedimentation rate (>50% of the initial value), an improvement in anaemia (haemoglobin >2 g) and reduced thrombocytosis (platelets 2×10⁵). Of the patients receiving corticosteroids, three patients (20%) were able to discontinue prednisone and the dose was reduced to less than 50% of the initial dose in seven patients (47%). At these doses of MTX, no gastrointestinal, hepatic or haematological toxicity was encountered and none of the patients withdrew because of toxicity or lack of efficacy. This report suggests that MTX is an effective and safe treatment in controlling systemic and articular features in this subtype of JRA.     

Switching the therapy from etanercept to infliximab in a child with rheumatoid factor positive polyarticular juvenile idiopathic arthritis

Tumor necrosis factor α (TNFα)-blocking agents have been used increasingly in the treatment of severe refractory juvenile idiopathic arthritis (JIA). However, some patients have been forced to discontinue these agents because of the lack of efficacy or adverse events. In these situations, cases of switching from one TNF-blocking agent to another are reported in rheumatoid arthritis, but there are few cases in JIA. This report documents the case of a patient with JIA who improved following a switch from etanercept to infliximab.     

Switching the therapy from etanercept to infliximab in a child with rheumatoid factor positive polyarticular juvenile idiopathic arthritis

Abstract

Tumor necrosis factor α (TNFα)-blocking agents have been used increasingly in the treatment of severe refractory juvenile idiopathic arthritis (JIA). However, some patients have been forced to discontinue these agents because of the lack of efficacy or adverse events. In these situations, cases of switching from one TNF-blocking agent to another are reported in rheumatoid arthritis, but there are few cases in JIA. This report documents the case of a patient with JIA who improved following a switch from etanercept to infliximab.