Eye involvement in children's rheumatic diseases

Rheumatoid paediatric diseases are a leading cause of uveitis in childhood. Juvenile chronic arthritis (JCA), juvenile onset spondyloarthropathies as well as sarcoidosis and other systemic diseases with arthritis may include ocular manifestations that can threaten vision, and especially so in juvenile chronic arthritis. Special risk factors concerning the eye have to be considered for JCA. The diagnosis, detection, follow-up studies and treatment in children may differ significantly from adult rheumatoid diseases because of the young age of the patients and the specific features and signs of ocular involvement. Medical and surgical treatment of such ocular manifestations may be challenging. Special attention to children's ophthalmic complications must be undertaken by paediatricians and ophthalmologists.     

Antinuclear antibody and HLA-B27 positive uveitis: combination of two diseases?

AIMS/BACKGROUND: Anterior uveitis associated with juvenile chronic arthritis concerns two different clinical entities: firstly, antinuclear antibody (ANA) positive patients who have a chronic anterior uveitis with severe complications and often a poor visual prognosis; secondly, usually HLA-B27 positive children, predominantly boys, with unilateral recurrent anterior uveitis. Three patients are described who had a combination of clinical and laboratory features of both diseases. METHODS: Retrospective clinical and laboratory analysis of three patients. RESULTS: Ocular features in the three patients combined the clinical picture of ANA positive chronic anterior uveitis during early childhood with the clinical features of HLA-B27 unilateral acute anterior uveitis during adolescence. The patients fulfilled the diagnostic criteria of juvenile chronic arthritis, and they had no ankylosing spondylitis. All three patients had the HLA-B*2705 subtype. CONCLUSIONS: Whether the association of ANA positive chronic anterior uveitis and HLA-B27 unilateral acute anterior uveitis is a coincidence or represents a distinct clinical entity is not yet clear.     

Migration of the dominant pacemaker region in the rat sinoatrial node

"Early onset sarcoidosis" is a chronic granulomatous disease occurring in children younger than 5 years of age, and characterized by a classic symptom triad consisting of skin, eye and joint lesions, with on rare occasion pulmonary involvement. The disorder often goes unrecognized because of its rarity and, since polyarthritis and uveitis are the predominant symptoms, most of these children are misdiagnosed as having juvenile chronic arthritis (JCA). A child with erythema nodosum at 7 months of age, later diagnosed as JCA and definitively recognized as "early onset sarcoidosis" is reported. This case shows that, whenever possible, a biopsy showing the typical picture of sarcoid granulomas is crucial to distinguish these clinical conditions.     

Visual outcomes prognosticators in juvenile rheumatoid arthritis-associated uveitis

PURPOSE: The purpose of the study is to delineate the visual prognosticators in juvenile rheumatoid arthritis-associated uveitis. METHODS: The records of 43 patients with juvenile rheumatoid arthritis-associated uveitis who were observed for at least 6 months were studied retrospectively. Bivariate and multivariate statistical models were applied to more than 40 parameters to determine the relative odds of visual rehabilitation among patients with each characteristic. RESULTS: Thirty-seven (86%) patients were females and 6 (14%) males. The mean known age of uveitis onset was 13 years, with females having, on average, 4 years earlier onset of disease compared to males (P = 0.04). Ninety-three percent had chronic, 5% had recurrent, and 2% had an acute monophasic disease course. Of the 76 affected eyes, 93% were nongranulomatous and 97% had iridocyclitis. The mean overall duration of uveitis was 146 months, with females suffering from a significantly longer duration of active disease than did males (P < 0.001). Nineteen (44%) patients underwent cataract extraction, and 16 (37%) underwent vitrectomy. Thirty (70%) of the patients experienced visual improvement with their therapy. When controlling for potential confounders, male sex (P = 0.006), shorter duration of uveitis (P = 0.007), older age at disease onset (P = 0.02), and a shorter delay in presentation to a subspecialist (P = 0.02) were associated significantly with visual acuity improvement. Visual acuity at presentation (P = 0.001), use of systemic nonsteroidal anti-inflammatory drugs (P = 0.01), older age at disease onset (P = 0.02), absence of glaucomatous neuropathy (P = 0.02), and male sex (P = 0.03) were correlated strongly with a final visual acuity outcome of 20/40 or better. CONCLUSION: Juvenile rheumatoid arthritis-associated uveitis is a serious disease with a guarded visual prognosis. It is hoped that increased awareness of its prognosticators will lead to treatment and referral patterns that have the best chance of minimizing the likelihood of visual impairment in patients with juvenile rheumatoid arthritis.     

Azathioprine in patients with juvenile chronic arthritis: a longterm followup study

OBJECTIVE: To evaluate drug survival, efficacy, side effects, and longterm toxicity of azathioprine treatment in patients with juvenile chronic arthritis (JCA). METHODS: In an uncontrolled, prospective study we evaluated 129 consecutive patients with JCA refractory to therapy in whom azathioprine treatment was begun during 1980-1989. In the first 29 patients, a 2 year trial was planned, while for the remaining 100 patients the protocol was to continue until remission or dropout. The median treatment period was 13 months (range 3 days-8.5 yrs). Patients were assessed every 2 months for 2 years for efficacy, side effects, growth and need for glucocorticoids, and outcome evaluated in late 1996. RESULTS: Remission without drugs was attained in 19 patients (15%); in addition, temporary remission in patients continuing treatment was attained in 18 cases (14%). Treatment was discontinued due to side effects in 18 cases (14%); in two-thirds of these cases side effects occurred during the first 2 months. Of the total number of patients, 49 (38%) completed 2 years of treatment, with significant improvement in both clinical and laboratory indices of disease activity. Treatment had no noticeable effect on iridocyclitis. One patient died of cytomegalovirus infection during azathioprine treatment. CONCLUSION: Azathioprine is a useful drug in severe JCA, with a sustained effect and acceptable side effects. Even in cases of incomplete remission, its glucocorticoid sparing effect was noteworthy.     

Autopsies in children: are they still useful?

BACKGROUND: Juvenile chronic arthritis (JCA) is the commonest autoimmune rheumatic disease in childhood and presents different clinical subtypes. Juvenile chronic arthritis is considered to be of a polygenic nature and its genetic background is still under investigation. The clinical profile of JCA in the Greek population has not been studied completely. This study retrospectively analyzed the clinical and immunological features of JCA in Greek children presented between 1989 and 1994. Human leukocyte antigen (HLA)-positive or -negative associations in the different clinical subtypes were also detected. The findings of this study were correlated with those reported from other populations. METHODS AND RESULTS: Antinuclear antibodies (ANA) anti-ds DNA and anti-extractable nuclear antigen antibodies were estimated by immunofluorescent and ELISA assays. Human leukocyte antigen typing was performed by microlymphocytotoxicity, using immunobeads. The peak ages of JCA onset were between 2 and 5 years and also between 9 and 12 years. There was a high female predominance in pauciarticular and polyarticular groups. The most common disease was pauciarticular (58.7%) followed by systemic (25%) arthritis. The incidence of eye involvement was 12.5% and presented only in the pauciarticular group. Overall, ANA positivity was 53.7%, increasing to 90% in pauciarticular cases associated with chronic uveitis. In the early onset (EOPA) pauciarticular subtype, positive-HLA associations with alleles DR11 and DR8 were shown. In the late onset pauciarticular (LOPA) group only B27 allele was increased. CONCLUSIONS: The results of this retrospective study did not reveal major differences between JCA in Greek children compared with other Caucasian series.     

Out in the real world

AIM: The trial of therapeutic effect of local therapy with dolgit cream of the joint syndrome in rheumatoid arthritis (RA), osteoarthrosis (OA) and juvenile chronic arthritis (JCA). MATERIALS AND METHODS: Cream dolgit was used locally with assessment of its effect by pains at rest, movement, palpation, swelling in 169, 98 and 102 patients with RA, OA and JCA, respectively. RESULTS: Subjective improvement was recorded in 75.6% of RA and 90% of OA patients, objective--in 80.9 and 87.2%, respectively. The cream enables a 30-50% reduction in daily dose of nonsteroid antiinflammatory drugs in 1/3 and 1/4 OA and RA patients, respectively. In JCA patients dolgit relieved symptoms of local inflammation. The response was growing in combination of dolgit with dimexide or magnetotherapy. Some of the OA patients experienced local skin itch which was not registered in children. No other side effects arose. CONCLUSION: Cream dolgit is effective in the treatment of joint syndrome in rheumatic patients, is well tolerated and may replace systemic nonsteroid antiinflammatory drugs in some patients.     

The use of intravenous pulsed methylprednisolone in the treatment of systemic-onset juvenile chronic arthritis

An open prospective study using i.v. methylprednisolone in children with juvenile chronic arthritis (JCA) who had had a systemic exacerbation of disease is described. Eighteen children aged from 3 to 14 yr and 9 months (mean 9.7 yr) were treated. Ten patients (55%) had a loss of all systemic features 1 month after the pulse, and eight (45%) had a reduction in the active joint count. At this time, five of the patients on oral prednisolone had achieved a reduction in dosage. Also at 1 month, a reduction in erythrocyte sedimentation rate was observed in 11 patients (61%) and of C-reactive protein in 11 of 16 (72%). Altogether, 13 patients (72%) had a good response, while a further three (16%) went into remission. Our conclusions are that pulse methylprednisolone provides good short-term benefit in patients with systemic-onset JCA; no serious side-effects were noted. Further long-term studies are warranted.     

Bone mineral density and turnover in children with systemic juvenile chronic arthritis

OBJECTIVE: To assess bone mineral status in a group of children with systemic type juvenile chronic arthritis (JCA), which places them at high risk to develop osteoporosis. METHODS: Bone mineral density (BMD) was measured in 17 children aged 6-18 yrs (mean 14.9 +/- 4.5) with systemic JCA and in 18 matched controls by dual energy x-ray absorptiometry. Bone turnover was determined by quantitative bone scintigraphy, using quantitative single photon emission computed tomography based on skeletal uptake of methylene diphosphonates (MDP uptake). Serum concentrations of minerals, osteocalcin, and bone alkaline phosphatase were determined. Nutrient intake was assessed by a 24 hour dietary recall. RESULTS: Patients with systemic JCA who received corticosteroid therapy had significantly reduced BMD in both the lumbar spine (p < 0.05) and the femoral neck (p < 0.05) compared to controls, whereas BMD values of the non-steroid systemic JCA patients were not different from controls. Bone turnover measurement by MDP uptake showed no difference between patients with JCA and controls. Levels of calcium, phosphorus, alkaline phosphatase. and osteocalcin were within normal limits in all patients. CONCLUSION: Patients with systemic JCA receiving longterm steroid treatment may develop a significant decrease in BMD. The normal MDP uptake values together with normal osteocalcin levels that we observed in our patients indicate that their disease is not associated with enhancement of bone turnover rates. These observations might have therapeutic implications for prevention and management of osteoporosis in JCA.     

Aortic valve replacement through the transected aorta in a patient with aortic stenosis and a calcified ascending aorta

BACKGROUND: Uveitis associated with juvenile rheumatoid arthritis (JRA) is an important cause of visual impairment in children. Because uveitis is often asymptomatic in this age group, frequent ophthalmologic screening examinations are recommended. Recent reports have found a decrease in the prevalence and severity of uveitis in JRA when compared to older data. METHODS: The charts of 52 consecutive patients with JRA seen over a 30-month period were retrospectively reviewed. RESULTS: Eye examination identified uveitis in five (12%) patients. All patients with uveitis were female, ANA positive, and had pauciarticular-onset arthritis. Three patients had the onset of uveitis before the age of 2. All patients have maintained good visual acuity and have not developed serious sight-threatening ocular complications over the follow-up period. CONCLUSIONS: Although the prevalence and severity of JRA-associated uveitis may be decreasing, we strongly recommend continued strict adherence to the current screening guidelines.     

Methotrexate treatment for sarcoid-associated panuveitis

OBJECTIVE: To determine the safety and efficacy of low-dose methotrexate (MTX) for sarcoid-associated panuveitis. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty eyes from 11 patients were analyzed. Eight patients had sarcoidosis. Three patients were clinically suspected of sarcoidosis despite negative laboratory testing. All charts of patients with sarcoidosis and idiopathic uveitis seen by the Duke Uveitis Service from 1989 to 1997 were retrospectively reviewed. Those with sarcoid-associated or sarcoid-suspected panuveitis treated with MTX with a minimum of 6 months of follow-up were studied. INTERVENTION: Low-dose MTX was administered to patients weekly and patients were followed with serial ophthalmologic and medical examinations. MAIN OUTCOME MEASURES: Visual acuity, oral and topical corticosteroid requirements, anterior chamber inflammation, and ability to undergo successful cataract extraction were used to measure the efficacy of MTX therapy. RESULTS: After MTX treatment was initiated, 90% of eyes had preserved or improved visual acuity. Mean initial Snellen visual acuity was 20/62 and mean final acuity was 20/40 (P = 0.044). Of those patients initially requiring oral corticosteroids, the dosage was decreased in 100%, and they were completely discontinued in 86%. The mean initial oral corticosteroid dose was 26.6 mg and the mean final dose was 1.5 mg (P = 0.012). Topical corticosteroids were decreased in 63% of eyes. The mean initial use was once every 1.6 hours, and the mean final use was once every 3.9 hours (P = 0.001). Ninety-five percent of eyes had stabilized or decreased inflammation. The mean initial inflammation score was 1.2, and the mean final score was 0.5 (P = 0.007). Five of six eyes previously unable to have cataract extraction because of uncontrolled inflammation became quiet on MTX and underwent surgery. One hundred percent of these eyes had improved vision after surgery. Side effects were mild and transient or reversible. CONCLUSION: Low-dose MTX is an effective and safe adjunct to treat chronic sarcoid-associated panuveitis.     

Psychosocial factors in children with idiopathic musculoskeletal pain: a prospective, longitudinal study

To explore the role of psychosocial factors in the development and persistence of idiopathic musculoskeletal pain (IMP) in children, 23 children with IMP and 52 children with juvenile chronic arthritis (JCA) were compared at first admission to hospital and at 9 y follow-up. Semistructured interviews were performed at both assessments. At first admission, the prevalence of psychiatric diagnoses was high both in patients with IMP and patients with JCA, but patients with IMP more often had pain models, reported more school stress and more often lived with one biological parent. At follow-up, overall psychosocial functioning and level of chronic family difficulties were improved in both groups, but patients with IMP had a higher prevalence of psychiatric diagnoses and more chronic family difficulties and life events than patients with JCA. The persistence of IMP at follow-up was related to pain models, school stress, less parental education and more chronic family difficulties at first admission. Findings support the association between psychosocial factors and childhood IMP.     

Comparative linkage maps for the mosquitoes (Culex pipiens and Aedes aegypti) based on common RFLP loci

OBJECTIVE: To investigate the ocular complications in pediatric bone marrow transplantation (BMT) patients. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 29 pediatric BMT patients were studied. TESTING: Comprehensive ophthalmic check-up, including best-corrected visual acuity, intraocular pressure (IOP), Schirmer's test, tear breakup time, and slit-lamp and fundus examinations, was performed. MAIN OUTCOME MEASURES: Tear film instability and its related complications, IOP, cataract, and fundus lesions were measured. RESULTS: The mean age of patients was 9.1 years (range, 1.5-15 years). The mean post-BMT duration was 20.2 months (range, 3-54 months). Fifteen patients (51.7%) had tear abnormalities. Subconjunctival fibrosis was detected in two patients (6.9%). Dry and scaly skin of the eyelids was seen in one patient (3.4%). Lens opacities were found in 2 (33.3%) of 6 irradiated patients and 2 (8.7%) of 23 nonirradiated patients. Two patients (6.9%) had fundus changes, one with unilateral epiretinal membrane and the other with bilateral multiple discrete chorioretinal hypopigmented lesions in the middle to peripheral part of the retina. The overall complication rates for the anterior and posterior segments were 75.8% and 6.9%, respectively. CONCLUSION: Ocular manifestations of BMT in children are not uncommon. The most common anterior segment problem is tear dysfunction. Posterior segment complications are less common but do exist. High rate of cataract formation is reported, and this probably is the most important long-term "amblyogenic" problem in these immature eyes. Awareness and management of these problems with routine eye examination and early intervention are recommended.     

Serial backcross mapping of multiple loci associated with resistance to Leishmania major in mice

PURPOSE: Cataract surgery is often followed by a posterior capsule opacification, usually treated with YAG laser capsulotomy, however, there are huge variations in the incidence figures available in the literature, from 18 to 50% (Sterling & Wood 1986). We have therefore analyzed the incidence of secondary cataracts in a population-based cohort of patients, as revealed by the number of YAG laser capsulotomies performed postoperatively. METHODS: Data for all patients undergoing cataract surgery from 1986 up to and including 1990 in the Lund Health Care District were prospectively recorded, and 4722 patients were retrieved for analysis, using only one eye per patient. The patients had been operated on with extracapsular extraction (phacoemulsification or planned large incision procedure) or a combined trabeculectomy and cataract extraction procedure leaving an intact capsule after surgery. Death dates for each patient were obtained from the Swedish Bureau of Census up to and including 1991. Different risk factors were considered such as sex, age, preoperative axial length, preoperative average keratometry, preoperative intraocular pressure, glaucoma history, diabetes history, uveitis history (including both anterior and posterior uveitis), history of age related macular degeneration and a history of rheumatoid arthritis. We also considered the influence of factors connected to the operation itself on the incidence of secondary capsular haze: extraction mode (ordinary ECCE versus phacoemulsification or trabeculectomy) and the type of implant and the surgeon's surgical activity. RESULTS: Besides age, four variables significantly influenced the risk of having postoperative YAG laser treatment. They were gender, iris sphincterotomy, operation date, and whether the patient came from a rural or an urban region. After about four to five years, the percentage of patients not having had a YAG laser capsulotomy was reduced to around 50% for women and 60% for men. These percentages were based on a survival analysis, minimizing the confounding effect of the limited life span of these elderly patients. CONCLUSIONS: In this material, the most important predisposing factors for YAG laser capsulotomy after extracapsular cataract surgery are: young age, female gender, if the patient was operated late in the period observed, and if the patient came from an urban area.     

Diagnostic anterior chamber paracentesis in uveitis: a safe procedure?

BACKGROUND: Differentiation between infectious and non-infectious uveitis is of crucial value for accurate management of patients with uveitis. Tests performed on aqueous humour yield more relevant information than those done in serum. The objective of this study was to evaluate whether the aqueous humour tap for diagnostic purposes is a safe procedure to perform in uveitis patients. METHODS: In this retrospective study 361 patients with uveitis, who underwent a diagnostic anterior chamber paracentesis in an outpatient clinic, were investigated. 72 of the 361 patients were examined 30 minutes after the puncture. The site of the paracentesis, the depth of the anterior chamber, and cells in the anterior chamber were examined. All 361 patients were evaluated within 2 weeks after the paracentesis was performed. The final follow up period varied from 6 months to more than 3 years. The clinical data were analysed with the emphasis on the occurrence of cataract and a history of corneal infections or endophthalmitis. RESULTS: In this series no serious side effects such as cataract, keratitis, or endophthalmitis were observed. The depth of the anterior chamber of all evaluated patients was restored after 30 minutes. In five out of 72 cases (three AIDS patients with cytomegalovirus retinitis and two patients with anterior uveitis due to herpes simplex virus) a small hyphaema was observed 30 minutes after the paracentesis took place. CONCLUSION: Anterior chamber paracentesis appears to be a safe procedure in the hands of an experienced ophthalmologist.     

Intraarticular hip treatment with triamcinolonehexacetonide in juvenile chronic arthritis

To evaluate the effect and tolerance of intraarticular Triamcinolonehexacetonide (TCH) in the course of chronic coxitis in juvenile chronic arthritis (JCA) in an open uncontrolled study. Since 1990 we treated patients < 16 years of age suffering from chronic coxitis with 1 mg/TCH/KG body weight. The patients were checked again 4-8 weeks after the treatment. Clinical and ultrasound courses were recorded with the help of ultrasound and joint scores. The evaluation took place 6, 12, 24 and 36 months after the treatment. At that time we give a report on the 12 months follow-up of 37 hip joints and the 24 months follow-up of 20 hip joints. The immediate effect of TCH influencing mobility, pain sensitivity and joint effusions of the patients is impressing. The long term effect of TCH has to be evaluated by regular check ups for at least 2 years. An individual comparison with the not treated contralateral joint would be desired if ethically justifiable. Most patients suffering from polyarticular diseases with a long course of coxitis needed more than one injection of TCH (mean reinjection time 5.8 months). Any avascular necrosis of the femoral heads or other complications were not observed.     

Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study

OBJECTIVE: To investigate the prevalence of juvenile chronic arthritis (JCA), familial Mediterranean fever (FMF), and Beh?et's disease in Turkish children through a field survey. METHODS: The field survey was based on cluster centering with 2 level strata. A total of 46,813 children were screened. For the diagnosis of chronic arthritis and Beh?et's previously suggested criteria were used. We have developed criteria for the diagnosis of probable FMF. Children previously diagnosed to have these diseases were also defined and included. RESULTS: JCA was found in 6.4/10,000. 2.8/10,000 children were previously diagnosed as FMF (minimum phenotype frequency). Together with the probable diagnosis of FMF, the prevalence increased to 9.3/10,000. The findings were also compared with those of our center. None of the 46,813 children had Beh?et's disease. CONCLUSION: The prevalence of chronic arthritis is similar to the other childhood populations reported. However, FMF has a very high prevalence.     

Impact of genetics on disease resistance

PURPOSE: To evaluate the safety and efficacy of phacoemulsification, primary posterior capsulorhexis (PCCC), and primary intraocular lens (IOL) implantation for uveitic cataracts. SETTING: Institutional practice. METHODS: Fifteen consecutive eyes of 13 patients with various causes of uveitis received anterior capsulorhexis, phacoemulsification, PCCC, and in-the-bag implantation of a heparin-surface-modified IOL for visually disabling cataract. The safety and efficacy of the combined operation were studied prospectively. RESULTS: At a mean follow-up of 16.9 months (range 8 to 30 months), all eyes had a clear central visual area. Fourteen of 15 eyes (93.3%) had good visual improvement after surgery. Eight eyes (53%) achieved a best corrected visual acuity (BCVA) of 20/30 or better and 6 (40%), 20/20 or better. Seventy-three percent of eyes attained a BCVA of 20/80 or better. The mean improvement in visual acuity was 5.2 Snellen lines (range 0 to 11 lines). No cases of uveitis flare-up or other major complications related to the cataract surgery occurred. CONCLUSIONS: The study's preliminary results are encouraging and indicate that phacoemulsification, PCCC, and IOL implantation can be considered in patients with visually disabling uveitic cataract.     

Involvement of macrophage scavenger receptors in protection against murine malaria

OBJECTIVE: This study aimed to determine whether heparin surface-modified (HSM) intraocular lenses (IOLs) with a hydrophilic surface would reduce cell adherence and other postoperative changes compared with the conventional polymethylmethacrylate (PMMA) IOLs in patients with either diabetes mellitus or inactive uveitis. DESIGN: The study design was a randomized, double-masked, clinical trial. PARTICIPANTS: Twenty-five patients with bilateral cataracts, 14 with inactive anterior uveitis and 11 with diabetes, with an age range of 11 to 81 years (mean, 52.8 years) participated. INTERVENTION: Bilateral cataract extraction with posterior chamber IOL implantation was measured, each patient receiving an HSM lens in one eye and a PMMA lens in the other. Pharmacia one-piece HSM and PMMA IOLs were used. Postoperative ocular changes were evaluated at regular intervals for 24 months in patients with inactive uveitis and for 6 months in patients with diabetes. Patients and physicians alike were unaware of which eye contained which lens until postoperative results were compiled. Records were kept by a study coordinator. MAIN OUTCOME MEASURES: Comparisons of posterior synechiae, IOL cellular deposits, and posterior capsular fibrosis between PMMA and HSM IOLs were measured. RESULTS: Using the chi-square test, no statistically significant difference was found between the HSM and PMMA IOLs in the number of cellular deposits found on the anterior IOL surface, the number of adhesions between the iris and IOL, or the incidence of capsular opacification. CONCLUSION: The HSM and PMMA IOLs showed similar postoperative results in patients with inactive uveitis or diabetes mellitus.     

Albendazole treatment of human hydatid tissue

Current treatment of children with juvenile chronic arthritis (JCA) has been changed significantly by the results of randomized controlled trials (RCTs). However, due to low market appeal of JCA, few RCTs are being funded by drug companies and none in the more rare childhood rheumatic diseases. In addition, RCTs have several limitations when used for a chronic illness such as JCA. To deal with this situation, the Pediatric Rheumatology International Trials Organization (PRINTO) is being organized to perform effectiveness trials in addition to efficacy trials in a variety of paediatric rheumatic illnesses.