Hepatitis B vaccination in children with juvenile idiopathic arthritis

OBJECTIVES: To evaluate the responsiveness of children with juvenile idiopathic arthritis (JIA) to hepatitis B vaccination and to determine the most useful vaccination schedule. METHODS: 39 children with JIA were enrolled in the study; all were in remission and negative to serological testing for hepatitis B surface antigen (HbsAg). The control group consisted of 41 healthy children. There were two different vaccination schedules: group I was vaccinated at 0, 1, and 3 months; group II was vaccinated at 0, 1, and 6 months. Positive responsiveness to the vaccine was defined as an anti-hepatitis B antibody titre above 10 mIU/ml. RESULTS: All the children except one with systemic JIA developed an antibody response. None of the JIA patients experienced a flare up or clinical deterioration related to the vaccination. The antibody levels in children with JIA were significantly lower than in the healthy controls. Comparison of the antibody levels between the two vaccination schedules showed no statistical difference in the controls; in the JIA subjects the group II schedule resulted in a trend to a greater response than the group I schedule (p<0.07). Vaccine responsiveness was not influenced by either methotrexate or prednisolone treatment. CONCLUSIONS: Children with JIA had an adequate response to hepatitis B vaccination and the response was not affected by immunosuppressive treatment. A vaccination schedule at 0, 1, and 6 months seems to be preferable to 0, 1, and 3 months.     

Aortic incompetence in HLA B27-positive juvenile arthritis.

The early onset of isolated aortic incompetence in a male child with HLA B27 and peripheral arthritis is reported. Acute anterior uveitis and lone aortic incompetence occurred at 1 and 9 months respectively after the development of the acute inflammatory arthritis. The uveitis resolved with local therapy and the arthritis remitted 10 months after the onset. There has been no recurrence of the arthritis after 10 years of close follow-up but the aortic incompetence has persisted, though it remains haemodynamically insignificant.     

HLA B27: A prognostic factor in juvenile chronic arthritis

This study was performed to assess the frequency of HLA B27 in patients with juvenile chronic arthritis (JCA) of varying severity and outcome by studying three patient categories: those in whom cytostatic treatment with azathioprine had been started, those with secondary amyloidosis, and those with arthroplasty of the knee or hip joints. In the first category the frequency of the HLA B27 allele was compared between those who had attained remission and those who had not. In the second and third categories the rate at which amyloidosis developed and the timing for the need of arthroplasty, were compared for HLA B27-positive and-negative patients. A control group consisted of 37 patients with uncomplicated seronegative polyarthritis. Ten of the 37 patients in the control group (27%) were HLA B27 positive as opposed to 84 out of 190 (44%) in the three study groups. Of the 101 patients treated with azathioprine, two out of 15 in remission were HLA B27 positive, whereas as many as 41 out of 86 with still active disease were HLA B27 positive (p=0.013). Of the secondary amyloidosis patients, 29 out of 51 carried HLA B27. The HLA B27-positive patients contracted amyloidosis on average 5.9 (median 6.7) years earlier than the HLA B27-negative patients (p=0.038). Of the arthroplasty patients, 39 out of 91 carried HLA B27. The HLA B27-positive patients underwent arthroplasty on average 2.9 (median 3.5) years earlier than the HLA B27-negative patients (p=0.050). We conclude that HLA B27-positive cases are accumulated among the most severe cases of JCA.     

Facioskeletal changes in children with juvenile idiopathic arthritis

OBJECTIVE: To investigate the facioskeletal morphology in patients with juvenile idiopathic arthritis (JIA) with and without temporomandibular joint (TMJ) involvement. METHODS: Eighty five patients were included. TMJ involvement was defined by orthopantomogram alterations. Lateral cephalograms were used to determine linear and angular measurements and occlusion. RESULTS: Patients regardless of their TMJ status had a 67% chance for retrognathia and a 52% chance for posterior rotation of the mandible and, respectively, 82% and 58% if TMJ involvement were present. Changes were not uniformly distributed among the different subtypes. CONCLUSION: Patients with JIA have an altered facial morphology, especially in the presence of TMJ involvement.     

Gower's sign in children with juvenile idiopathic arthritis

SIR, One clinical sign assessing proximal leg muscle weaknessis Gower's sign, the most important feature of which is theadoption of a prone position before standing. This can be seenduring normal development in toddlers up to the age of 36 months;only 6.5% of healthy children over 3 yr still roll prone duringstanding, while children with neuromuscular disorders have apositive early Gower's sign that persists after the age of 3yr [1]. Previous research in our     

Macrophage activation syndrome in children with systemic onset juvenile idiopathic arthritis: clinical experience from northwest India

The objective of this study is to describe the clinical and laboratory features of macrophage activation syndrome (MAS) in systemic onset juvenile idiopathic arthritis (SOJIA) at a tertiary care center in northwest India. Review of medical records of all children with SOJIA admitted during the period January 1995–December 2008 in Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, was done. Six patients (5 boys and 1 girl) with SOJIA and MAS were identified. Mean age at time of disease onset was 6.5 years. MAS was the presenting manifestation of SOJIA in 4 patients. Clinical manifestations included fever (6/6), clinical shock (6/6), encephalopathy (5/6), generalized lymphadenopathy (4/6), hepatosplenomegaly (3/6), jaundice and abdominal tenderness (3/6), cardiac involvement (3/6), and meningeal irritation (2/6). Laboratory findings at onset of MAS included decreasing total leukocyte and platelet counts, coagulopathy, elevated transaminases, hyponatremia, and lipid abnormalities. Hemophagocytosis was demonstrable in the bone marrow in 4 patients and in the lymph node in 1. For treatment, we used intravenous methylprednisolone (4/6), oral prednisolone (2/6), and intravenous immunoglobulin (2/6). Outcome was favorable in all patients except one who died of rapidly progressive disease. This paper describes the experience of JIA-related macrophage activation syndrome in a tertiary Indian center. We have shown that MAS can be the early presenting manifestation of evolving SOJIA. Early diagnosis and aggressive management can have a significant impact on the mortality associated with this syndrome. We stress on the role of glucocorticoids in the management of this condition and believe that glucocorticoids have a far more important role in the management of this condition than what has been previously reported.     

Clinical analysis in 202 children with juvenile idiopathic arthritis

This study attempts to characterize the clinical features of various subtypes of juvenile idiopathic arthritis (JIA) and try to investigate the prognostic factors. Patients with JIA hospitalized in Nanjing Children Hospital during April 2005 to April 2010 were enrolled. Clinical manifestations and laboratory parameters were retrospectively reviewed. A total of 202 cases were included, 105 males and 97 females, with average age at onset of 7.5 years. Patients with systemic JIA were most common, accounting for 47.0 %. Fever, rash, and arthritis were the most common clinical manifestations. The most commonly involved joints were the knee and ankle. Laboratory parameters were significantly different but not specific. Time from onset to treatment, hepatomegaly, and involvement of wrist may have a significant effect on the outcome. A total of 117 cases were followed up, with an average follow-up time of 2 years. Among them, 55 cases achieved complete remission, 27 cases with partial remission, and 29 cases without remission, and six died. JIA is a heterogeneous disease with varied onset and clinical manifestations, which makes treatment a serious challenge. Receiving treatment late, hepatomegaly, and impaired wrist were early risk factors for an unfavorable outcome.     

Oral health of children with juvenile idiopathic arthritis

OBJECTIVE:s. To estimate dental disease indices and temporomandibular joint (TMJ) dysfunction in children with juvenile idiopathic arthritis (JIA). METHODS: Indices were recorded for dental caries, bacterial dental plaque, gingival inflammation, and TMJ dysfunction in children with JIA and matched controls. RESULTS: There was no significant difference in dental caries experience or the mean plaque score between children with JIA and controls. The mean gingivitis score for the permanent teeth only was significantly greater in the JIA children compared with the controls (p = 0.02). There was a significantly greater proportion of children with JIA with signs of both left and right TMJ dysfunction (p = 0.05, p = 0.02) and symptoms (p = 0.0001, p = 0.0001) compared with controls. CONCLUSION: The low caries rate was attributed to the fact that children with JIA had received preventive dental care from an early age combined with sugar free medication.     

Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.     

Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis

Objective

We have previously reported a defect in neutrophil activation in children with polyarticular juvenile idiopathic arthritis (JIA). The current study was undertaken to determine whether gene expression abnormalities persist in JIA in remission and to use systems biology analysis to elucidate pathologic pathways in polyarticular JIA.

Methods

We performed gene expression profiling on neutrophils from children with polyarticular JIA. Children were grouped according to disease status. We studied 14 children with active disease who were taking medication, 8 children with clinical remission of disease who were taking medication (CRM status), and 6 children with clinical remission of disease who were not taking medication (CR status). We also studied 13 healthy children whose age ranges overlapped those of the patients.

Results

Neutrophil abnormalities persisted in children with polyarticular JIA even after disease remission was achieved. Children with active disease and those with CRM status showed no differences in expression of specific genes, although they could be separated on cluster analysis. A comparison of children with CR status and healthy control children revealed networks of pro‐ and antiinflammatory genes that suggested that remission is a state of homeostasis and balance rather than a return to normal immune function. Furthermore, gene overexpression in patients with CR status supports the hypothesis that neutrophils play a role in regulating adaptive immunity in this disease.

Conclusion

Neutrophil gene profiling in polyarticular JIA suggests important roles for neutrophils in disease pathogenesis. These findings suggest the presence of complex interactions between innate and adaptive immunity, that are not easily modeled in conventional, linear, reductionist systems.

     

Growth abnormalities in children and adolescents with juvenile idiopathic arthritis

In patients with juvenile idiopathic arthritis (JIA) growth impairment and variance in body composition are well-known long-term complications. In the active phases of the disease, particular patients with systemic and polyarticular JIA reveal growth impairment. Some experience “catch-up” growth following reduction in disease activity and lower glucocorticoid doses. Although new therapeutic options are available, there are still 10–20 % of patients with severe forms of the disease who show continuous growth disturbance. Only few studies have specifically addressed body composition in JIA. Bone mass deficits in part could be related to the deficits of muscle mass. Study data on growth hormone treatment in short children with JIA are promising in respect of growth development, final height and body composition. The major goal for physicians is optimal disease control while maintaining normal growth and body composition. Early recognition of patients who develop prolonged growth and body composition disturbances is important as these abnormalities contribute to long-term morbidity and need to be addressed both diagnostically and therapeutically.     

Aquatic fitness training for children with juvenile idiopathic arthritis

OBJECTIVE: To evaluate the effects of an aquatic training programme for JIA patients. METHODS: Fifty-four patients with JIA (age range 5 to 13 yr) participated in this study and were randomized into an experimental (n = 27) and a control (n = 27) group. The children in the experimental group received a training programme consisting of a 1 h per week supervised training programme in a local pool of approximately 20 sessions. Effects were analysed on the following domains: functional ability, health-related quality of life, joint status and physical fitness. RESULTS: Although all measures improved more in the experimental group than the control group, none of the differences was statistically significant. CONCLUSIONS: The current research found no significant effect of an aquatic fitness training programme in children with JIA. Since there were no signs of worsening in health status, one can conclude that this was a safe exercise programme.     

90K immunostimulatory glycoprotein in children with juvenile idiopathic arthritis

Objectives: To assess whether circulating levels of 90K glycoprotein are increased in children with juvenile idiopathic arthritis (JIA) at different stages of the disease, compared to healthy controls and to evaluate potential over time changes in its concentrations following treatment with the antitumor-necrosis factor (TNF) drug etanercept.

Methods: 90K glycoprotein, C-reactive protein, erythrocyte sedimentation rate, TNF, antinuclear antibodies, rheumatoid factor and the Juvenile Arthritis Disease Activity Score were assessed in 71 children: 23 with newly diagnosed JIA, 23 with established and active JIA and 25 healthy controls. Patients, eligible for anti-TNF treatment, underwent a similar clinical/laboratory assessment after 6- and 12-month etanercept therapy.

Results: At baseline, significant differences were found in 90K levels between the three study groups: JIA at onset (157.7 [131.4–241.5] μg/ml), JIA on treatment (90.0 [68.8–120.2] μg/ml) and control group (58.0 [44.5–79.0] μg/ml), (p for trend <.001), with the JIA at onset group showing the highest values. In the JIA on treatment group, following one-year etanercept treatment, a significant reduction in 90K was detected already at 6 months (74.3 [56.0–104.1] μg/ml p?=?.001) and a further decline was observed at 12 months (49.3 [46.0–67.6] μg/ml p?Conclusion: Our study showed that 90K glycoprotein levels are increased in JIA children compared to healthy controls, suggesting a potential pathogenetic role in the JIA. Besides, 12 months of therapy with etanercept can reduce 90K levels.     

Safety of anti-TNFalpha therapy in children with juvenile idiopathic arthritis

Anti-TNFalpha agents are frequently used in the treatment of severe JIA. Etanercept, a fully human soluble recombinant tumour necrosis factor p75 receptor Fc fusion protein, has been registered for the treatment of polyarticular course JIA patients who fail to respond to or do not tolerate methotrexate (MTX). Infliximab, a chimeric human-mouse monoclonal antibody to TNFalpha, is expected to be registered soon for JIA and Crohn's disease (CD) in children. As in adults, both agents are effective in controlling inflammation and inhibiting the progression of joint destruction. Despite this good clinical efficacy, the physician must remain alert for potential side effects, especially after prolonged use. This review gives an overview of the reported adverse events.