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Rheumatoid arthritis, juvenile arthritis, iridocyclitis and the Epstein-Barr virus.

In order to examine the relation of Epstein-Barry virus (EBV) infection to chronic arthritis in children antibodies to EB virus capsid antigen (EBVCA) and rheumatoid arthritis nuclear antigen (RANA) were analysed in sera from 133 patients classified as juvenile rheumatoid arthritis (JRA) or pauciarticular, polyarticular, or systemic juvenile chronic arthritis. Except for an increased frequency in the systemic subgroup, the prevalence of antibodies to EBVCA and titres of anti-RANA antibodies was similar in patients and controls. These data do not support an aetiological role for EBV in chronic arthritis in children, including JRA, and suggest that the mechanisms which may account for the higher titres of anti-RANA antibodies in adult RA do not occur in children.

Adolescent↗

Juvenile rheumatoid arthritis, juvenile chronic arthritis, and juvenile spondyloarthropathies.

Immunogenetics are supporting the marked heterogeneity of chronic arthritis in children. Thus DRw13-DRw18 and DQw6-DQw18 were associated with persistent pauciarticular disease in children with an early onset of disease. Several studies have shown DPw2 as an additional susceptibility factor in this subgroup. Standardization of diagnostic criteria for juvenile onset spondyloarthropathy and psoriatic arthritis is necessary; various studies are in progress, and although HLA-B27 provides the common marker, this may only apply to a small group of juvenile psoriatics who have spondyloarthropathy. In the management of juvenile rheumatoid arthritis, methotrexate in moderate doses has been shown to be superior to lower doses of methotrexate and placebo in controlling polyarthritis. Methotrexate may be of particular value in treating the polyarthritis that follows a pauciarticular onset. The possible value of sulfasalazine in a B27 group with persistent polyarthritis has been suggested. Highlights of corticosteroid therapy were intra-articular injections, particularly in pauciarticular disease, the suggestion that deflazacort has a calcium sparing effect, and the possible role of intravenous methylprednisone in the management of severe disease.

Adrenal Cortex Hormones↗

Clinical pharmacokinetics of drugs used in juvenile arthritis.

Juvenile arthritis is defined as the occurrence of objective evidence of arthritis for a minimum of 6 weeks, in a child 16 years of age or younger. With a reported incidence of 9 to 19.6 per 100,000 children, juvenile arthritis is considered to be a rare disease. There is no known cure; however, up to 75% of patients will undergo remission by late adolescence. Drugs used in the treatment of juvenile arthritis are divided into 2 major classes: (a) the nonsteroidal anti-inflammatory drugs (NSAIDs) including salicylates, naproxen, ibuprofen, fenoprofen, ketoprofen, flurbiprofen, indomethacin, sulindac, tolmetin and diclofenac, and (b) disease modifying agents which encompass drugs such as antimalarial agents, gold, methotrexate, penicillamine and sulfasalazine. In almost all the reports dealing with the pharmacokinetics of NSAIDs, the level of disease activity has not been noted. The level of activity is important since, during a flare, the plasma albumin may fall to the point that it causes a substantial and clinically significant increase in the unbound serum concentration of highly bound drugs. The relationship between the concentration of these drugs in the systemic circulation and their efficacy is not clear. However, for many of them, therapeutic drug monitoring is recommended as a means of reducing the possibility of toxic reactions. Further pharmacokinetic and -dynamic evaluations are needed for many of these drugs in juvenile arthritis.

Adolescent↗

Delay in diagnosing juvenile arthritis.

Juvenile arthritis may present as swollen fingers or toes or joint swelling after minor trauma. The diagnosis can easily be overlooked, as small children do not complain about pain. Untreated arthritis can cause deformities or, with eye involvement, damaged vision. Three case histories are presented, as well as an audit of diagnostic delay in children with juvenile arthritis presenting to a paediatric rheumatology service over 12 months.

Adolescent↗

Prognosis in juvenile arthritis.

Juvenile arthritis implies an onset of disease under 16 years with arthritis persisting in one or more joints for at least six weeks, and with the active exclusion of well defined illnesses, such as systemic lupus erythematosus. Prognosis implies the ability to predict outcome. Its accuracy depends on many factors with early recognition and appropriate care being important. However, response to treatment may be variable. In general, those with involvement of a few joints do better than those with systemic disease or seropositive juvenile rheumatoid arthritis both with regard to persistence of disease activity and complications. These include not just joint deformities, but osteoporosis, amyloidosis, alterations in growth with overall failure and local anomalies, chronic iridocyclitis and psychosocial problems. More aggressive therapy was only introduced in the 1990's, so it is important that multicentre studies are properly assessed in the context of the suggested International diagnostic criteria. One hundred years ago, George Fredric Still drew attention to the systemic form of the disease as distinct from pure polyarthritis [1], but it was only in the 1970s, as follow-up proceeded, that the separate identity of variants became clinically evident [2]. At the Park City meeting [3] and at the EULAR meeting in 1977 [4] when three subgroups (notably systemic, polyarthritis and pauci-articular onset) were defined, that subclassification became regularly used. However, since there were no absolute diagnostic tests there had to be exclusions. At that time the most common medications were aspirin and corticosteroids, although a few patients received gold or penicillamine. In their large group Wallace and Levinson (1990) [5] found that at the 10 year follow-up between 31% and 55% still had active disease. Girls appeared to have a five-fold greater risk for persistent activity than boys; disease duration was probably the most important factor influencing disease activity at follow-up as suggested previously [6]. It was not until the 1990's that the more aggressive therapy in the form of methotrexate--which Giannini had shown to be effective when given in appropriate dosage [7]--and sulphasalazine [8] and the long acting local corticosteroid triamcinolone hexatonide became regularly employed [9, 10]. At the ILAR Meeting in 1993 an international task force was set up under the chairmanship of Dr. C. Fink [11] to develop a classification for the idiopathic arthritides in children, defining childhood as up to 16 years of age. Active exclusion of well-recognised disorders such as rheumatic fever or systemic lupus erythematosus, still had to be made. The first proposed types, which are mutually exclusive, are shown in Table 1. A more recent meeting in Durban under the chairmanship of Dr. R. Petty is yet to be published, but considerable advances have been made, particularly in the definition of subgroups.

Arthritis↗

Drug therapy for juvenile arthritis.

Juvenile arthritis includes a variety of rheumatic disorders with varied articular and extraarticular manifestations. The heterogeneity of JA cannot be overemphasized in a rational approach to therapy. Fortunately, most children with JA improve significantly with first-line treatment, especially those with pauciarticular disease. Only a small number of these patients go on to require second-line treatment, usually because of the evolution of their condition into the polyarticular type. Patients with polyarticular, RF-positive disease and patients with early-onset polyarthritis in association with systemic-onset disease both have poor prognoses in terms of ultimate joint function, and should receive second-line treatment early in their therapy. Injectable gold is the drug of choice for the former patients, if an initial trial of NSAIDs has failed. Patients with polyarticular onset, RF-negative disease generally have a better prognosis than other patients with polyarticular involvement. One may wait considerably longer before introducing a second-line agent for these patients. An antimalarial agent may be a reasonable choice for these patients, especially those with limited polyarticular involvement (5 to 10 active joints). This latter principle may also be applied to patients who evolve from pauciarticular to polyarticular involvement. In all such cases, penicillamine is almost never used as first choice. If the patient is a young child, the difficulty with injecting gold and the hazards of antimalarial agents may limit the use of these treatments. In situations such as this, auranofin or sulfasalazine may be the drug of choice. Cytotoxic/antimetabolic therapy should be reserved for those children who have continued active disease despite full courses of two SAARDs, or for those who have been unable to take SAARDs because of their side effects. Corticosteroid therapy should be used only when specifically indicated, and every attempt should be made to wean the patient from it as soon as feasible. The aim of therapy is to ensure that patients enter their remission in the best condition possible. For this to be assured, a sensible approach to drug therapy is mandatory.

Adolescent↗

Juvenile arthritis.

Juvenile arthritis encompasses a group of chronic arthritides in childhood with unclear etiologies. Careful clinical observation has led to categorization and nomenclature identifying three main subtypes of the disease, each with varying natural histories and prognoses. Management centers around antiinflammatory drugs, long-term disease-modifying agents, physical and occupational therapy, joint replacement, and ongoing psychosocial assessment and care. The majority of patients achieve reasonable control of their symptoms and are able to attain independent and satisfying adult lives.

Arthritis, Juvenile↗

Novel therapies for the treatment of juvenile rheumatoid arthritis (juvenile idiopathic arthritis).

The majority of children with juvenile idiopathic arthritis respond well to conventional treatment. However, some children will have a more aggressive disease course and will be resistant to standard management. Over the past 20 years, growth in our understanding of the immunopathogenesis of juvenile idiopathic arthritis and related diseases has facilitated significant therapeutic advances. In this report, recently released antirheumatic drugs, as well as some treatments currently in development, will be discussed. Biological agents, such as antiTNF and other cytokines inhibitors, and unique drugs, such as thalidomide, provide new opportunities to suppress the inflammation found in severe cases of systemic onset juvenile idiopathic arthritis and can obtain a satisfactory outcome.

Animals↗

Outcome in juvenile arthritis.

Juvenile chronic arthritis has a number of subtypes with only seropositive juvenile rheumatoid arthritis and systemic juvenile chronic arthritis having equivalents in adult life. In 75% of patients the inflammatory disease has subsided by adulthood, leaving some with degenerative and mechanical problems. Systemic, polyarticular and pauciarticular subgroups, based on mode of presentation, have been related to prognosis. Seropositive polyarticular disease behaves as an aggressive form of adult rheumatoid arthritis. Standard methods of assessment are inappropriate in children. Active joint score is most useful. Radiographs are difficult to interpret because of growth and lack of early erosive disease. Growth and social outcome is important. Death occurs in 7% of cases and is due to infection and cardiac involvement during active systemic disease, and due to secondary amyloidosis later. Slow-acting drugs and surgical procedures may alter outcome. The aetiology of these diseases remains unknown and there is a need for diagnostic tests, particularly to identify those children who will do badly.

Adolescent↗

[Synovial cellular immune response to bacterial pathogens in patients with chronic juvenile arthritis].

Juvenile chronic arthritis is a heterogenous disease with an ill-defined pathogenesis. In our study, synovial fluid (SF) and peripheral blood (PB) of 70 children with oligoarthritis were investigated; bacteria-specific lymphocyte proliferation and antibodies to arthritogenic bacteria were determined. Specific cellular immune responses in SF but not in PB were found in 4/7 patients with either Lyme- or reactive arthritis (60%). In comparison, in subgroup JCA II (n = 45) encompassing mainly elder HLA B27 positive boys, a specific response in SF but again not in PB was detected in 10 children to Yersinia enterocolitica (YE), in four children either to Borrelia burgdorferi (BB) and Chlamydia trachomatis (CT), and in one child to Campylobacter jejuni (CJ). In contrast, in subgroup JCA I (n = 17) encompassing mainly young ANA-positive girls with chronic iridocyclitis, no specific response was found. The correlation of the synovial cellular and the humoral immune responses was 100% in the case of BB and 50% for YE; no antibodies against CT or CJ were detectable. Neither specific cellular nor humoral immune responses were detected against Salmonella or Shigella. We conclude that, in the pathogenesis of some patients with JCA, bacterial microbes have a triggering role. Mainly YE, but also BB and CT are responsible for cases of JCA in which no symptomatic infection preceded.

Adolescent↗

Radiological assessment of knees in juvenile chronic arthritis (juvenile rheumatoid arthritis).

Radiological changes in the knees were assessed in those patients with juvenile chronic arthritis who still had evidence of knee involvement 5 years after onset of the disease. The patients were grouped according to age and mode of onset. Osteoporosis, modelling abnormalities, growth arrest lines and joint narrowing were found, but erosive change was less common. Tables are given correlating age of onset of disease with radiologic changes.

Adolescent↗

Radiological findings in seropositive juvenile chronic arthritis (juvenile rheumatoid arthritis) with particular reference to progression.

The radiological effects of peripheral joint disease in 81 patients with seropositive juvenile chronic arthritis were studied retrospectively with an average length of follow up of 11 years. The patients comprised 63 girls and 18 boys with average ages of onset being 10.7 years and 12.1 years respectively. All had developed positive serology within the first year of the disease. X-rays available in 70 of these patients at five years from onset of the disease showed erosive change to be present in all but three. The sites most commonly affected included the carpus, the metacarpal, the metatarsal, and interphalangeal joints, though a third of the patients also showed erosive change in large joints such as hips, knees, or shoulders. Between five and 10 years after disease onset progression of x-ray changes was evident in most patients, with additional joints becoming involved in about one third, though the distribution of joints was similar. After 15 years or more of disease the radiological changes tended to be more stable, but various mechanical difficulties often secondary to poor growth and degenerative change and to primary destructive inflammatory arthritis were evident. No specific drug regimen was found to have been universally effective in suppressing disease, and the frequency of side effects was a significant factor in preventing treatment schedules being maintained for long enough to be effective.

Adolescent↗

Epidemiology of rheumatoid arthritis, juvenile idiopathic arthritis and gout in two regions of the Czech Republic in a descriptive population-based survey in 2002-2003.

OBJECTIVE: To estimate the annual incidence and prevalence of rheumatoid arthritis (RA), juvenile arthritis (JIA) and gout in a population based study in two regions of the Czech Republic with total population of 186,000 inhabitants. METHODS: The study was conducted in the Town of Ceske Budejovice and district of Cheb in the Czech Republic (with a total population of 186,000 inhabitants) in the years 2002 and 2003. Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. Prevalence was studied on the basis of identification of established diagnosis from registers of patients of participating rheumatologists and other specialists. They were asked to report all living patients who had been diagnosed before 1st March 2002. Patients were only included in the study if their permanent address was in the selected study area. RESULTS: Overall, we found 48 incident and 947 prevalent cases of RA among adults (16+ years), 4 incident and 43 prevalent cases of JIA among children (less than 16 years old), and 64 incident and 425 prevalent cases of gout among adults (16+ years). The total annual incidence of RA was 31/100,000 in the adult population aged 16 years and more (95% CI 20 to 42/100,000). The prevalence of RA was 610/100,000 (95% CI 561 to 658/100,000) in the adult population. An annual incidence of gout in adults was 41/100,000 (95% CI 28 to 53/100,000). The prevalence of gout was 300/100,000 (95% CI 266 to 334/100,000). The annual incidence of JIA was 13/100,000 in children less than 16 years old (95%CI 1 to 20/100,000). The prevalence of JIA in children was 140/100,000 (95% CI 117 to 280/100,000). CONCLUSION: This study estimates the annual incidence and prevalence rates of RA, gout and JIA in the first population-based survey in the Czech Republic. The rates of RA and JIA compare well with figures reported from other countries; figures in gout seem to be lower than reported elsewhere.

Adolescent↗

[Personal experience with the comprehensive care of children with chronic juvenile arthritis].

Juvenile chronic arthritis implies in almost one third of the patients a disease with permanent sequelae--deformities of the joints with subsequent disability or the affection of various organs. To prevent the development of such changes, comprehensive treatment of these patients is necessary comprising coordinated medicamentous rehabilitation and physical therapy as well as psychosocial care. Collaboration of the doctor, patient, parents and social worker is one of the prerequisites of an optimal perspective.

Arthritis, Juvenile↗