Central effects of iohexol and iopamidol, non-ionic contrast media

BACKGROUND: The relationship between uveitis anterior in childhood and juvenile chronic arthritis (JCA, respectively JRA) has been known since 1950. In a review, the clinical picture of uveitis anterior, its prevalence, pathogenesis, prognosis and current therapy of ocular complications are presented. In addition, we will report our results of a clinical study. PATIENTS AND METHODS: In a cross-sectional study, 64 patients with juvenile chronic arthritis (JCA) had an ophthalmological screening for eye complications either from the disease itself or from the treatment. RESULTS: In 16% of the patients, an iridocyclitis was found, in one case acute, in 9 cases chronic. The cases of chronic uveitis anterior showed in 43% a combination with the classic risk factors (ANA-positive, oligoarticular, female). At the beginning of uveitis, the patients had a mean age of 81 months, at the beginning of JCA disease a mean age of 37 months. Four of 10 patients (= 40%) had eye complications from uveitis (cataract, posterior synechiae, glaucoma). Complications from therapy were found in 27%, mostly cataract as a complication of systemic and topical steroid treatment. Eighteen % had a visual acuity of 0.4 or less. CONCLUSIONS: Because of the often asymptomatic progression of chronic uveitis anterior, the risk of severe undetected eye complications is high. Therefore, an intensive interdisciplinary cooperation between rheumatologists, pediatrics and ophthalmologists is required.     

Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome)

OBJECTIVE: To investigate the association of polyarthritis and chromosome 22q11.2 deletions. METHODS: Eighty patients with chromosome 22q11.2 deletion syndrome followed up at The Children's Hospital of Philadelphia were examined for evidence of arthropathy or arthritis. Patients with chromosome 22q11.2 deletion syndrome and polyarthritis underwent laboratory evaluations of immunologic function to determine the relationship of their immunodeficiency to the polyarthritis. RESULTS: The prevalence of polyarthritis in patients with chromosome 22q11.2 deletion syndrome was markedly increased over the prevalence of polyarticular juvenile rheumatoid arthritis (JRA) in the general population. All 3 patients with polyarthritis had evidence of impaired T cell function. Two of the patients with polyarthritis also had IgA deficiency. CONCLUSION: The chromosome 22q11.2 deletion syndrome represents a primary T cell disorder which can be associated with a JRA-like polyarthritis. All 3 patients with polyarthritis had evidence of more extensive immunoregulatory derangements than those typically seen in patients with chromosome 22q11.2 deletion, and these derangements may have predisposed to the development of polyarthritis.     

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.     

Hypotensive effect of endothelin-1 in a rat model of pre-eclampsia

OBJECTIVE: To characterize a group of phakic patients with idiopathic intermediate uveitis as defined by vitritis, cystoid macular edema, and retinal periphlebitis. DESIGN: Cross-sectional study. PARTICIPANTS: Nineteen phakic patients (35 eyes) with vitreous inflammation, cystoid macular edema, and/or retinal periphlebitis of unknown cause. INTERVENTION: None. MAIN OUTCOME MEASURES: Best-corrected final visual acuities, standardized clinical examinations, photographic and fluorescein angiographic evaluations, and class I and II HLA analysis on all 19 patients. RESULTS: Fifteen of the 19 patients were women. The mean age was 38 years, the mean follow-up was 104 months, and the mean duration of symptoms was 154 months. All 35 affected eyes had significant vitritis; 21 eyes (60%) had cystoid macular edema, 21 eyes (60%) had retinal periphlebitis. The median initial visual acuity was 20/30. The median final visual acuity was 20/20 with 32 (91%) of 35 eyes having 20/40 or better visual acuity at the final visit. No patient developed "snow-banks" or evidence of systemic disease, including multiple sclerosis or sarcoidosis, during the follow-up period. There were no statistically significant HLA associations in these patients compared with controls from another study from Iowa, but the Iowa phakic patients with cystoid macular edema did differ from the Iowa patients with pars-planitis at loci HLA-B8, HLA-B51, and HLA-DR2. CONCLUSIONS: We describe a disease entity of idiopathic intermediate uveitis that affects primarily young to middle-aged women and usually causes bilateral vitritis, cystoid macular edema, and retinal periphlebitis. Most patients retained good vision over a prolonged follow-up period. Multiple sequential examinations and HLA associations suggest that these conditions are distinct from other syndromes of intermediate uveitis, particularly parsplanitis.     

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.     

Autoreactivity to human heat-shock protein 60 predicts disease remission in oligoarticular juvenile rheumatoid arthritis

OBJECTIVE: To determine whether T lymphocyte reactivity to endogenous human hsp60 plays a regulatory role in the course of oligoarticular juvenile rheumatoid arthritis (JRA). METHODS: A prospective, longitudinal study of T cell reactivity to HSP in 15 patients with newly diagnosed HLA-B27 negative oligoarticular JRA was performed. Results were compared with those in a group of 20 patients with newly diagnosed polyarticular or systemic JRA or with acute arthritis caused by other systemic diseases or viral infections, as well as with those in a group of 9 healthy control subjects. RESULTS: In 86% of the patients with oligoarticular JRA (13 of 15), significant T lymphocyte proliferative responses to hsp60 were found in peripheral blood mononuclear cells and/or synovial fluid mononuclear cells within 3 months after the onset of arthritis. Only 5% of the patients in the rheumatologic disease control group (1 of 20) showed such positivity. All patients with oligoarticular JRA and positive responses to human hsp60 developed a remission of their disease within 12 weeks. During this period of remission, blood samples were taken from 8 patients and showed significantly lower and even negative responses to hsp60, compared with active disease, when all 8 patients had good responses. CONCLUSION: The results show that significant proliferative responses to human hsp60 can be found early in the course of oligoarticular JRA. Furthermore, these responses correlate with disease activity in such a manner that T cell reactivity to human hsp60 seems to be associated with disease remission.     

Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.     

Association of methotrexate treatment with a decrease of double negative (CD4-CD8-) and gamma/delta T cell levels in patients with juvenile rheumatoid arthritis

OBJECTIVE: It has been suggested that double negative (CD4-CD8-) (DN) and gamma/delta T cells may be involved in some autoimmune diseases. We investigated peripheral blood DN and gamma/delta T cell levels in patients with active juvenile rheumatoid arthritis (JRA). METHODS: DN and gamma/delta T cell levels were measured in 42 patients with active JRA and in 10 healthy controls comparable for age by an immunofluorescence double staining procedure. RESULTS: All 3 JRA onset types had DN and gamma/delta T cell levels not significantly different from those of controls, although a wide scattering of data was present. No correlation was found between DN or gamma/delta T cell levels and erythrocyte sedimentation rate values or the number of active joints. When patients were divided according to treatment, we found that DN and gamma/delta T cell levels were significantly lower (p = 0.001, p = 0.02, respectively) in patients receiving methotrexate (MTX) than in patients not receiving MTX. The association of MTX treatment with a decrease in DN and gamma/delta T cell levels was also confirmed in a followup study of individual patients. Among patients not receiving MTX, patients with systemic JRA presented DN T cell levels significantly higher than those of controls. In 5 patients with pauciarticular JRA DN and gamma/delta T cell levels were higher in synovial fluid than in the peripheral blood. CONCLUSIONS: We found an increase in peripheral blood DN T cell levels in systemic JRA; treatment with MTX appears to be associated with a decrease in DN and gamma/delta T cell levels.     

Clinical and biological markers of secondary uveitis: results of a discriminant analysis

BACKGROUND: The association of uveitis and systemic disease is well known. Patients suffering from uveitis often undergo a extensive battery of tests in order to detect underlying disease, but the efficiency of such screening is uncertain. The aim of this study was to investigate useful clinical data for recognizing secondary uveitis. PATIENTS AND METHODS: We conducted a prospective analysis of 115 patients with uveitis of unknown etiology. All of them were included in an extensive protocol study. Four groups were considered: specific ocular disease (SOD), idiopathic uveitis, HLA-B27 associated uveitis without arthritis (HLA-B27-AU) and secondary uveitis. Groups were compared by analysis of variance for continuous variables, and chi 2 test or Student's t-test for discrete variables. A stepwise multiple discriminant analysis was performed for ranking the variables in order of their usefulness for distinguishing idiopathic and secondary uveitis. RESULTS: We diagnosed 11 SOD (9.6%), 54 idiopathic uveitis (47%), 6 HLA-B27-AU (5.2%) and 41 secondary uveitis (35.7%). The discriminant analysis showed that age, an elevated erythrocyte sedimentation rate, presence of cutaneous lesion, joint pain and genital ulcers are the strongest predictors of secondary uveitis. This model classification functions detected 92.5% of idiopathic uveitis and 72% of secondary uveitis. The global percentage of patients with a correct diagnosis was 84.6%. CONCLUSIONS: Anamnesis, physical examination and basic laboratory tests are sufficient tools for the diagnostic approach of the majority of patients with uveitis. Subsequent diagnostic procedures must be planned in each patient to confirm a specific disease.     

Juvenile rheumatoid arthritis in African Americans

OBJECTIVE: To examine racial differences in disease expression in African American and Caucasian children with pauciarticular and polyarticular juvenile rheumatoid arthritis (JRA). METHODS: A retrospective chart review was conducted of 35 African American and 137 Caucasian children with pauciarticular and polyarticular JRA. RESULTS: African American children were significantly older than Caucasian children at the time of presentation. This was true both for the group as a whole and for each of the disease onset subtypes. African American children were less likely to have positive antinuclear antibody tests than Caucasian children. This finding paralleled a low incidence of uveitis in African American children. African American children were also more likely to have IgM rheumatoid factors (detected by latex agglutination) than Caucasian children. This was true even for African American children with pauciarticular JRA. CONCLUSION: There are significant phenotypic differences between African American and Caucasian children with JRA.     

Evaluation of a patient file folder to improve the dissemination of written information materials for cancer patients

OBJECTIVE: To study the prevalence of coagulation abnormalities in children with systemic juvenile rheumatoid arthritis (JRA) using a sensitive marker of fibrin degradation, and to determine whether serial levels of this variable parallel disease activity or predict response to medications in this disease. METHODS: Levels of d-dimer were determined in 24 consecutive patients with systemic JRA in conjunction with complete blood counts, erythrocyte sedimentation rate, maximum fever, duration of morning stiffness, and swollen joint count. Serial levels were then obtained in 11 patients. Linear regression analyses were done to determine any correlations between d-dimer and the other variables; and paired t test was used to compare levels before and after treatment interventions. Levels of d-dimer were also compared against concurrent clinical events such as pericarditis. RESULTS: Elevated levels of d-dimer were found in 23/24 of the patients (96%). When serial levels were analyzed, there were correlations between levels of d-dimer and fever (p = 0.03) and total leukocyte count (p = 0.04), but not with other variables. There was a significant reduction in levels before and after treatment in patients deemed to be clinical responders to immunomodulatory agents (p = 0.02). Elevated levels were also indicative of severe disease over the remainder of followup; lack of d-dimer indicated a benign disease course. CONCLUSION: With the use of a sensitive and specific marker of fibrinolysis known as d-dimer, coagulation abnormalities were more prevalent in children with systemic JRA than previously reported, and are frequently found during periods of active disease. Furthermore, serial levels of d-dimer appear to parallel response to disease modifying agents, and may predict outcome over a short followup period. Fibrin d-dimer may represent a novel marker that, when used in combination with known variables, could enhance that assessment of disease activity and response to medications in children with systemic onset JRA.     

Intraarticular corticosteroid injection in the management of children with chronic arthritis

OBJECTIVE: Intraarticular (IA) corticosteroid injection is a common therapeutic approach in the management of adult rheumatoid arthritis. This study examined the safety and efficacy of IA corticosteroid injection in 71 patients with juvenile arthritis who were being seen at the Sheba Medical Center during the years 1991-1996. METHODS: Sixty-one patients fulfilled the American College of Rheumatology revised criteria for the diagnosis of juvenile rheumatoid arthritis (JRA), 6 patients had reactive arthritis, and 4 patients had various other arthritic conditions. The mean +/- SD age was 9.4 +/- 5.6 years (range 0.5-18 years); 47 were female (mean age 8.1 +/- 5.5 years) and 24 were male (mean age 10.8 +/- 5.4 years). A total of 300 joints were injected with triamcinolone hexacetonide. The most common sites of injection were the knees (124 injections), ankles (71 injections), wrists (46 injections), shoulders (10 injections), and elbows (7 injections). Children under the age of 6 (n = 17), or older children who received more than 4 joint injections at one time (n = 10) were sedated with either ketamine HCI or propofol. All other children received their joint injections under local anesthesia. RESULTS: Full remission of the joint inflammation lasting >6 months following injection was achieved in 246 of the 300 injections (82.0%). In 54 (18.0%) of the injected joints, the inflammation recurred within 6 months of injection. In patients with pauciarticular arthritis, 115 of 141 injections (81.6%) resulted in full remission. Discontinuation of all oral medications was accomplished in 43 patients (60.6%) of the total group of 71 patients and in 32 of the 43 patients with pauciarticular disease (74.4%). Correction of joint contraction was achieved in 42 children (55 joints). In all 11 patients with Baker's cyst and in 12 patients with tenosynovitis, complete remission was achieved following injection. No infection or other serious complications occurred in any of the patients following the procedure. CONCLUSION: IA corticosteroid joint injection in children with juvenile arthritis is a safe and effective mode of therapy. It may be the only therapy needed in patients with pauciarticular JRA, obviating the need for prolonged oral medications, and is effective in correcting joint contractions and deformities.     

Prothrombin gene G20210-->A transition is a risk factor for cerebral venous thrombosis

OBJECTIVE: The objective of the study was to determine the long-term outcome of patients with uveitis who underwent extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PCIOL) implantation. DESIGN: Retrospective review. PARTICIPANTS: Twenty-eight patients (36 eyes). INTERVENTION: Extracapsular cataract extraction and PCIOL implantation. MAIN OUTCOME MEASURES: Level of best-corrected Snellen visual acuity, change in visual acuity, length of follow-up, long-term findings, and complications. RESULTS: In long-term follow-up (mean, 81.4 months), 94% of eyes had visual acuity improvement compared with preoperative levels. Average change in visual acuity for all eyes was an improvement of 6.4 Snellen lines; 75% of eyes were 20/40 or better. The prevalences of cystoid macular edema (CME), epiretinal membrane (ERM), and posterior capsule opacification (PCO) were 56%, 56%, and 58%, respectively. CONCLUSIONS: Patients with uveitis who are treated with ECCE with PCIOL implantation can have successful visual results in long-term follow-up despite the prevalence of PCO or macular abnormalities such as CME and ERM.     

Late onset undifferentiated seronegative spondyloarthropathy

OBJECTIVE: To define the clinical spectrum of late onset undifferentiated seronegative spondyloarthropathy (uSpA) based on a large number of patients. METHODS: All consecutive patients older than 45 years at the onset of SpA and not meeting criteria for any of the definite categories of the SpA complex seen in the 1988-1993 period were entered in a special register and were followed prospectively. RESULTS: Twenty-three patients (mean age at onset 56.9, range 46-72; mean age at the last visit 61.7, range 48-79) were studied. Of these, 12 had 3 or more clinical and/or radiological manifestations of SpA, while 7 showed only 2, and 4 only one. Of the 10 patients with peripheral arthritis, only 3 had the large pitting edema of the lower limbs described by Dubost and Sauvezie. Of the 4 patients with only one manifestation, 2 had peripheral enthesitis and 2 acute anterior uveitis. CONCLUSION: The clinical spectrum of late onset uSpA is as wide as in children and young and middle aged adults.     

Diagnosis of systemic causes of uveitis; a matter of ophthalmologist and internist

OBJECTIVE: To assess how often the aetiology is established in patients with uveitis, what systemic disease are found and what is the contribution of the internist to the diagnostic process. DESIGN: Retrospective study. SETTING: University Hospital Leiden, the Netherlands. METHOD: From January 1987 to April 1992, 342 patients presented with uveitis. All patients underwent a standard ophthalmological examination. Referral to an internist and individualised laboratory screening followed in patients with recurrent, chronic, bilateral or panuveitis. Recorded were: ophthalmological data, results of laboratory screening, results of analysis by the internist, final diagnosis and presence of systemic disease. RESULTS: 149 (44%) patients were examined by the internist, 18 (5.2%) were seen by another specialist. In 169 (49%) patients a specific diagnosis was made. 74 (22%) had a systemic disease, 74 a primary ocular disease. In 28 (8%) a systemic disease was presumed (5% were HLA-B27 positive, 3% had abnormal laboratory results); 5 (1%) patients had endophthalmitis as a complication of a septic process. CONCLUSION: In approximately 1/3 of the patients with uveitis a systemic disease was found. Examination by the internist tailored to the individual patient is essential in the evaluation of uveitis patients.     

Interleukin 8 and monocyte chemoattractant protein-1 in patients with juvenile rheumatoid arthritis. Relation to onset types, disease activity, and synovial fluid leukocytes

OBJECTIVE: To measure serum and synovial fluid (SF) levels of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in patients with juvenile rheumatoid arthritis (JRA) and to compare them with adult rheumatoid factor-positive rheumatoid arthritis (RA). METHODS: IL-8 and MCP-1 were measured by immunoassay (1) in sera obtained from 55 children with JRA and from 16 adults with RA, and (2) in SF obtained from 30 children with JRA and 11 adults with RA. RESULTS: Patients with active systemic JRA had serum levels of IL-8 and MCP-1 higher than in controls (p<0.01) and in patients with active polyarticular or pauciarticular JRA (p<0.05). In patients with RA serum MCP-1 levels were higher than in patients with the 3 JRA onset types, while no difference was found for IL-8 levels. Patients with systemic JRA and with current systemic features had serum levels of IL-8 and MCP-1 higher (p = 0.03 and p = 0.04, respectively) than patients in which systemic features had subsided. No significant differences in SF IL-8 or MCP-1 levels were found among the 3 JRA onset types or adults with RA. In patients with JRA SF leukocyte counts were correlated with SF IL-8 levels (p = 0.002), but not with MCP-1 levels. Moreover, SF levels of both IL-8 and MCP-1 were correlated with those of IL-1beta (p<0.001) and IL-6 (p<0.01), but not with those of TNF-alpha. CONCLUSION: Elevated serum levels of IL-8 and MCP-1 in patients with systemic JRA with current systemic features at sampling suggest systemic production of the 2 chemokines during systemic phases of the disease. Similar SF levels of IL-8 and MCP-1 among the 3 JRA onset-types and RA suggest comparable local production of the 2 chemokines.     

Characteristics of ANP-binding sites in the adrenal capsules of term-pregnant rats

Magnetic resonance imaging (MRI) of the cervical spine was performed on 20 patients (mean age 10 years) with a preliminary diagnosis of juvenile rheumatoid arthritis (JRA). In all patients conventional x-rays of the cervical spine were obtained, and the relationship between clinical status and MRI findings were evaluated. Two patients with clinical manifestations, including neck pain and diminished range of motion, exhibited significant pathologic features on radiogram and MRI, the latter providing more detailed information. Among 18 patients who had no complaints about their cervical spines, 3 patients (65%) had either soft tissue involvement, pannus formation or erosions on the surface of atlantoaxial joints; only four patients (20%) had erosions on plain x-ray views. Since the early diagnostic ability of MRI in JRA allows early therapeutic intervention, every patient with a probable diagnosis of JRA would benefit from MRI.     

Chlorella virus NY-2A encodes at least 12 DNA endonuclease/methyltransferase genes

OBJECTIVE: To describe outcome and determine predictive factors in juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthopathy (JSpA). METHODS: Seventy-two children with chronic arthritis were studied on first admission to the pediatric rheumatology clinic and after a mean of 9.7 +/- 1.8 yrs of disease duration. RESULTS: At followup, 53 patients had JRA and 19 had JSpA. Eleven (21%) of the patients with JRA did not meet the criteria for JRA on first admission, and 12 (22%) of 54 children diagnosed as having JRA on first admission were later reclassified as having another disease. Remission occurred in 43 (60%) of the 72 patients with JRA and JSpA. Forty-four patients (60%) reported no disability by the childhood or adult Health Assessment Questionnaire and 18 patients (25%) had developed joint erosions. Disease modifying antirheumatic drugs (DMARD) were given to 49 patients (68%) after a median of 0.8 yrs (range 0.2-10.8) disease duration. The patients who developed erosions and disability tended to have started treatment later than those who did not (NS). Active disease 5 years after onset was a predictor of disability in JRA and JSpA (OR 4.5, 95% CI 1.6-12.5). Predictors of joint erosions were long duration of elevated erythrocyte sedimentation rate (ESR) (OR 3.7/yr of elevated ESR, 95% CI 1.9-7.2), long disease duration before first admission (OR 1.5/yr of duration, 95% CI 1.1-2.1), long disease duration before treatment with DMARD (OR 1.8, 95% CI 1.0-3.3), and IgM rheumatoid factor (OR 12 x 10(4), 95% CI 0-1.2 x 10[52]). CONCLUSION: The longterm outcome in JRA and JSpA was more favorable than previously reported. This may be explained by less selection in favor of severely diseased patients and by the use of early aggressive treatment regimes.     

Juvenile rheumatoid arthritis in affected sibpairs

OBJECTIVE: To describe the demographics and clinical disease in affected sibpairs (ASPs) with juvenile rheumatoid arthritis (JRA), and to compare JRA as it occurs in ASPs with that from non-ASP JRA populations described in the literature. METHODS: A rare disease research registry was established with a focus on JRA ASPs to facilitate accrual of patients for genetic, epidemiologic, and clinical studies. Physicians likely to care for patients with JRA were made aware of the registry and its goals by a variety of methods and asked to refer patients for entry. RESULTS: To date, 71 ASPs have been registered and complete information has been obtained. These affected sibs differed in age by a mean of 4.1 years (SD 3.4) and in age at disease onset by 2.8 years (SD 3.0). The actual time difference between onset in sib 1 versus sib 2 averaged 4.4 years (SD 4.2). Sixty-three percent of the sibpairs were concordant for sex, and 76% for JRA onset type. Onset type within sibpairs did not appear to be random, based upon comparisons with non-ASP populations. Greater than expected concordance was seen among those with pauciarticular-onset and polyarticular-onset JRA. Seventy-nine percent of the pairs were concordant for course type. Seven sets of twins were included (approximately 10% of the total), all were concordant for onset and course type (6 sets with pauciarticular, 1 set with polyarticular), and disease onset was separated by a mean of only 3.3 months. Within the onset and course types, the clinical disease, such as the female:male ratio, age at onset, and serologic findings, in ASPs resembled that which has been described in the literature. CONCLUSION: A higher than expected degree of concordance for onset type of JRA exists between sibpairs, indicating that genetic influences play a role. Affected sibs do not tend to develop their disease at approximately the same point in time, except for the twin sets. Clinical features of the disease within the various subtypes appear similar to those in non-ASP populations.     

Expression of macrophage markers by a population of T cells obtained from synovial fluid of a subgroup of patients with juvenile rheumatoid arthritis

OBJECTIVE: To characterize distinctive lymphoid cell populations in the synovial fluid (SF) of patients with juvenile rheumatoid arthritis (JRA) that have the specific ability to display monocytic markers when cultured in vitro. METHODS: Mononuclear cells obtained from SF of patients with JRA and depleted of adherent macrophages were cultured in vitro in RPMI 1640 medium supplemented with only fetal calf serum (FCS). Phenotypic evaluation of these cells was by flow cytometry and immunohistochemical analysis was by specific fluorochrome labeled antibodies. RESULTS: T cells from a JRA subgroup displayed some typical macrophage attributes, i.e., abundant cytoplasm, adherence to plastic, and phagocytosis of latex beads when cultured in vitro. These cells have the ability to survive in culture for several weeks in RPMI 1640 medium containing only 10% FCS. The macrophage-like T cells rosetted with sheep red blood cells and proliferated when stimulated with phytohemagglutinin or anti-CD3, indicating functional T cell responses. CONCLUSION: Our data indicate that a population of T cells obtained from the SF of a subgroup of patients with JRA exhibited characteristics of macrophages, yet retained their CD3 and T cell receptor expression. Whether this promiscuous behavior is caused by malignant transformation of lymphoid precursor cells or is induced by the concerted effect of a myriad of cytokines and growth factors present in the SF remains unknown. The presence of these cells in the SF of 2 patients with JRA with different onset types raises the question of their function and significance in an autoimmune disorder such as JRA.