Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9830883 Substance use among adolescents with juvenile rheumatoid arthritis. 1998 Oct OBJECTIVE: To determine the prevalence of substance use among adolescents with juvenile rheumatoid arthritis and to assess available opportunities for rheumatologists to identify high risk teens. METHODS: Fifty-two teens (mean age 13.9 years, 86% female) completed questionnaires regarding substance use (alcohol, tobacco, marijuana, and other illicit substances), functional disability, and frequency of health care contacts. RESULTS: Alcohol use was reported by 30.7% of teens, including 23.5% of those for whom methotrexate was prescribed; 15.4% reported tobacco use in the last year, and 13.4% reported other illicit substance use in their lifetime, although most use was experimental. No teen reported marijuana use. The majority reported regular contact with their rheumatologist but only 26.9% were ever interviewed alone. CONCLUSION: Many teens with juvenile rheumatoid arthritis, including those prescribed methotrexate, used substances, especially alcohol. When rheumatologists see adolescents, particularly in situations where methotrexate may be prescribed, a clinical setting conductive to confidentially, physician comfort in asking about sensitive topics such as substance abuse, and referral relationships with skilled adolescent health and substance abuse counseling providers are essential.
19078380 Disseminated herpes zoster and s. Aureus septic arthritis in a rheumatoid arthritis patien 1999 Jun A recalcitrant rheumatoid arthritis patient taking low dose weekly methotrexate was given oral 2-chlorodeoxyadenosine (cladribine) for 8 months in a multicenter trial. He developed dual infections over the course of the trial: disseminated herpes zoster and staphylococcal arthritis of the right elbow. His disseminated herpes zoster started with severe, unremitting abdominal pain caused by a gastric ulcer, followed by disseminated cutaneous herpes, hepatitis, pancreatitis, encephalitis, homonymous hemianopsia, the syndrome of inappropriate secretion of antidiuretic hormone (ADH), and malabsorption. Both the herpes zoster and S. aureus infections required prolonged proper chemotherapies. Serious, complicated viral, bacterial, or other unusual infections should be considered in patients with severe rheumatoid conditions treated with combination immunosuppressive therapy.
11455148 Persistent plaques and linear pigmentation in adult-onset Still's disease. 2001 A 25-year-old Japanese man presented with high spiking fever, arthralgia and a skin rash. A pruritic edematous erythema with persistent plaques was found mainly on the trunk; these lesions persisted even when the fever subsided, with prominent linear pigmentation. As marked neutrophilia and a high level of serum ferritin were detected, a diagnosis of adult-onset Still's disease (AOSD) was made, even though the persistent eruption was not characteristic of the disease. Oral prednisolone, together with low-dose methotrexate, was given with good results. In the literature, a similar atypical rash has been reported in 11 cases in Japan. All of them required high-dose administration of corticosteroids or other immunosuppressive agents. Severe systemic complications were seen in 3 patients, and 2 cases died of the disease. Persistent plaques and linear pigmentation are some of the manifestations of AOSD, which cannot be overlooked. This appearance could be an indication that suggests an increased risk of systemic complications and a prolonged time to clinical remission.
9068291 Methotrexate treatment in patients with adult onset Still's disease--retrospective study o 1997 Feb OBJECTIVE: To evaluate methotrexate treatment in patients with active adult onset Still's disease (AOSD). METHODS: Methotrexate was initially given as a single weekly oral dose of 5 mg and adjusted individually afterwards in 13 patients with active AOSD. Symptoms and laboratory findings were investigated. RESULTS: Signs of AOSD activity disappeared (remission) in eight patients between 3 and 16 weeks after starting methotrexate. In these patients, significant improvements in C reactive protein, erythrocyte sedimentation rate, white blood count, and serum ferritin were observed at 8, 12, 14, and 16 weeks after starting methotrexate, respectively. In six of these eight patients, steroids or non-steroidal anti-inflammatory drugs could be reduced or discontinued. In four patients methotrexate was not effective despite 12 or 16 weeks of treatment, and one patient discontinued treatment after 2 weeks because of severe nausea. Five patients suffered from adverse reactions, including acute interstitial pneumonia (one patient) and liver toxicity (two patients). Five out of eight patients successfully treated with methotrexate were HLA-DR4 positive (four homozygotes), and all the unsuccessfully treated patients were DR2 positive. CONCLUSIONS: Methotrexate is useful for controlling disease activity in AOSD, not only for refractory patients but also for patients who have never taken steroids or for those with steroid associated toxicity. However, serious adverse reactions can occur, as with rheumatoid arthritis. It is important to determine the critical factors, such as the immunogenetic background, that are associated with response to methotrexate treatment.
9361157 Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumat 1997 Nov The goal of treatment for juvenile rheumatoid arthritis (JRA) and other pediatric rheumatic disorders is to minimize joint destruction, pain, and deformity and to maximize all aspects of growth and development. Oral and injectable methotrexate are now often given early in the treatment of JRA, childhood dermatomyositis, difficult-to-control arthritis in the pediatric spondyloarthropathies, SLE, sarcoidosis, several of the vasculopathies, and idiopathic iritis. Weekly low-dose MTX has become a mainstay of long-term improved control of these disorders, and is associated with strikingly few documented long-term side effects. Dosages, pharmacology, side effects, efficacy, and treatment strategies are discussed. Although formal studies are lacking, MTX for the pediatric rheumatic disorders seems to be associated with less frequent physician visits, lower total costs, improved function, and fewer late reconstructive surgeries.
11060756 Psoriatic arthritis. 2000 Jul Psoriatic arthritis occurs in 5 - 42% of patients with psoriasis. It is an inflammatory arthritis distinct from rheumatoid, being usually sero-negative, asymmetrical and often affecting the spine, sacro-iliac and distal interphalangeal joints. It runs a very variable course, from a mild non-destructive disease to a severe rapidly progressive erosive arthropathy, producing an 'arthritis mutilans' with a combination of bone lysis and joint ankylosis. Its pathogenesis is not as well understood as rheumatoid arthritis, but is thought to be similarly immune driven, with a qualitatively similar immunomodulatory cascade and cytokine profile. Quantitatively, however, there are distinct differences in cell ratios and cytokine levels that may well impact on therapeutic strategies. Current therapies, such as methotrexate and sulphasalazine, have yet to be shown to be significantly more effective than placebo in delaying damage and produce only marginal improvements in symptoms. The newer specific biological agents, such as the anticytokine antibodies, interleukins and more specific anti-T-cell therapies, are starting to be studied in psoriatic arthritis. The rationale for their use comes mostly from extrapolation of their efficacy in rheumatoid arthritis. It has yet to be seen whether they will be efficacious in treating the osteolysis, fibrosis and new bone formation particular to psoriatic arthritis. Any treatment for the arthritis must also help the skin. Greater understanding of psoriatic arthritis, its pathogenesis and natural history is required if we are to target these exciting but expensive therapies effectively.
18020611 Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. 1998 Nov Infliximab is a chimaeric monoclonal antibody which binds to and inhibits the activity of tumour necrosis factor-alpha (TNFalpha), a cytokine which is involved in the development of both Crohn's disease and rheumatoid arthritis. In patients with treatment-resistant Crohn's disease, infliximab was significantly more effective than placebo in the relief of symptoms. 50 to 89% of patients responded to infliximab and most of them also achieved remission. Patients showed signs of relapse 8 to 12 weeks after a single infusion but responded to additional infusions of the drug. Infliximab was also effective in closing the fistulae in 68% of patients with fistulising Crohn's disease; the response rate with placebo was 26%. Infliximab achieved a clinical response in 44 to 81% of patients with refractory rheumatoid arthritis. Following a single infusion, symptom recurrence was evident after 6 to 12 weeks, but subsequent infusions re-established a clinical response. Concurrent methotrexate appeared to prolong the effects of infliximab in this patient group. Anti-infliximab and anti-double-stranded DNA antibodies developed in some patients, particularly those who received multiple infusions of infliximab. Acute adverse events consistent with hypersensitivity occurred in some patients who received multiple infusions of infliximab. Infection occurred slightly more frequently with infliximab than with placebo. CONCLUSIONS: Infliximab appears to be an effective therapy for patients with treatment-resistant or fistulising Crohn's disease or refractory rheumatoid arthritis. The tolerability, long term efficacy and optimal dosage regimen need to be further defined in comparative trials before the full potential of infliximab is realised in these patients.
18034543 Are there differences in methotrexate kinetics between responding and nonresponding patien 2000 May OBJECTIVE AND STUDY DESIGN: The purpose of this study was to investigate the presence of a correlation between methotrexate pharmacokinetics and clinical efficacy in patients with rheumatoid arthritis. PATIENTS AND METHODS: The study was carried out in 29 patients with rheumatoid arthritis. The patients received intramuscular methotrexate (MTX) 7.5mg once a week for 8 weeks. Before and 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the first administration, MTX serum concentrations were measured and pharmacokinetic investigations were carried out. The clinical status of the disease was evaluated before and after 8 weeks of therapy. In addition, before and after 2 and 8 weeks of treatment, the patients were monitored for a complete biochemical profile. After 8 weeks of treatment, on the basis of improvement in clinical parameters, the patients were designated responders or nonresponders. RESULTS: A clinical response was obtained in 62% of patients (18 patients responded and 11 did not) and was associated with a low incidence of adverse effects. There were no differences in the pharmacokinetic parameters of MTX between the 2 groups of patients (responders vs nonresponders), except that t(max) was significantly higher in nonresponders than in responders (p < 0.05). CONCLUSIONS: These data confirm the efficacy and tolerability of low dose MTX in patients with rheumatoid arthritis in the short term, but appear to exclude a relationship between MTX kinetics and clinical response.
9890097 Systemic onset juvenile rheumatoid arthritis. 1998 May Systemic onset juvenile rheumatoid arthritis (SoJRA) accounts for 10-20% of all JRA, affecting males and females equally and occurring most frequently under the age of 5 years. It is characterized by arthritis, daily spiking fever, an evanescent rash, serositis and a variety of other extra-articular features. Exclusion of systemic infections, malignancies and connective tissue diseases is most important in establishing the diagnosis. The disease has a wide range of severity from a short monocyclic course to a prolonged chronic course with severe destructive arthritis in approximately one third of patients. Destructive arthritis, secondary amyloidosis and treatment complications including infections, osteoporosis, growth retardation and the macrophage activation syndrome account for the significant morbidity and mortality associated with the disease. Pharmacological management includes non-steroidal anti-inflammatory drugs, corticosteroids, methotrexate and an emerging role for cyclosporine A and cytotoxic drug therapy. Elucidation of the immunopathogenetic mechanisms may lead to new targeted therapy.
15758488 Animal models of rheumatoid arthritis. 2001 Jun Animal models of arthritis are used to study pathogenesis of disease and to evaluate potential anti-arthritic drugs for clinical use. Therefore morphological similarities to human disease and capacity of the model to predict efficacy in humans are important criteria in model selection. Animal models of rheumatoid arthritis (RA) with a proven track record of predictability for efficacy in humans include: rat adjuvant arthritis, rat type II collagen arthritis, mouse type II collagen arthritis and antigen-induced arthritis in several species. Agents currently in clinical use (or trials) that are active in these models include: corticosteroids, methotrexate, nonsteroidal anti-inflammatory drugs, cyclosporin A, leflunomide interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptors. For some of these agents, the models also predict that toxicities seen at higher doses for prolonged dosing periods would preclude dosing in humans at levels that might provide disease modifying effects. Data, conduct and features of the various models of these commonly utilized models of RA as well as some transgenic mouse models and less commonly utilized rodent models will be discussed with emphasis on their similarities to human disease.
10676778 Advances in the medical treatment of juvenile rheumatoid arthritis. 2000 Feb Juvenile rheumatoid arthritis (JRA) remains a challenge for clinicians. Nonsteroidal anti-inflammatory drugs and corticosteroids remain the mainstays of therapy, but concerns persist about side effects and the ability of these agents to prevent progression of bony disease. In recent years, novel treatments have been developed and quickly discarded because of unexpected toxicities or lack of efficacy. However, recent studies have shown that methotrexate and sulfasalazine are relatively safe and effective for JRA. Newly developed drugs, such as selective cyclooxygenase-2 inhibitors and soluble tumor necrosis factor receptor, whose development has stemmed from a more basic understanding of pathophysiology, may provide better disease control with fewer side effects. Finally, novel therapies, such as stem cell transplantation, may offer hope for children with JRA, especially systemic-onset JRA, whose disease has been refractory to conventional therapy.
10501775 Bone mass change during methotrexate treatment in patients with juvenile rheumatoid arthri 1999 Thirty-two children affected by juvenile rheumatoid arthritis (JRA) were studied with serial measurements of bone mass for an average of 18 months, to evaluate the effects of long-term methotrexate (MTX) treatment on bone. Bone mineral density (BMD) was measured on lumbar spine and total body. During MTX therapy some increase in BMD was observed, though this was smaller than in a control group of healthy children. Axial (spine and trunk) and appendicular (upper and lower limbs) BMD showed similar increases. BMD, either as an absolute value or as a percent variation from baseline, did not correlate with either MTX dose or length of therapy. In children treated also with corticosteroids, these drugs negatively influenced bone mass increase. The main determinant of absolute spine BMD value appeared to be weight, while height and lean mass seemed to be the determinants of total body BMD. Pubertal stage and disease activity significantly influenced the yearly change in BMD. In conclusion, our data suggest that long-term, low-dose therapy with MTX does not induce osteopenia in children with JRA.
10522316 [Still's disease in adults: treatment with intravenous immunoglobulins]. 1999 INTRODUCTION: Adult onset Still's disease is a rare systemic disorder of unknown etiology occurring in young adults. The diagnosis is based upon Yamaguchi criteria. Treatment is difficult and not well codified. CURRENT KNOWLEDGE AND KEY POINTS: Non steroidal anti-inflammatory drugs (salicylates, indomethacin) are used as first-line therapy but are not efficient. Steroids are needed in 80% of cases to control systemic manifestations of adult onset Still's disease. Immunosuppressive agents, such as methotrexate, are necessary when a high dose of steroids are required. The use of intravenous immunoglobulin was rarely reported, in particular in patients refractory to non steroidal anti-inflammatory drugs. Intravenous immunoglobulin was administered at 2 g/kg of body weight during two or five days. Infusion was given monthly for four-six cycles. Long-term remission was obtained in half of the patients. Precise mechanisms of action of intravenous immunoglobulin in adult onset Still's disease remain unclear. FUTURE PROSPECTS AND PROJECTS: Intravenous immunoglobulin may represent a new treatment, particularly in patients refractory to non steroidal anti-inflammatory drugs before the use of steroids. Further prospective works are needed to confirm these preliminary optimistic data.
9229181 Viral arthritis. 1997 Jul Viral infections are important in rheumatic disease not only because of the acute and subacute syndromes they cause but also because of their potential importance as etiologic factors in common chronic diseases such as rheumatoid arthritis. During 1996, the clinical spectrum of the acute polyarthritis caused by parvovirus B19 was further delineated and was shown to include carpal tunnel syndrome, hepatic dysfunction, and possibly angioedema. B19 infection can be studied using the salivary antibody response. No convincing additional data were reported regarding B19 in chronic syndromes such as rheumatoid arthritis or Behçet's syndrome. Regarding rubella as a possible cause of chronic arthropathy, more negative evidence accumulated with two additional studies in vaccinees and chronic arthritis using epidemiologic and virologic methods including the polymerase chain reaction. To define a possible link between rubella and autoimmunity in vitro, interactions of rubella RNA, ribonucleoprotein complexes including Ro and La, and calreticulin were explored. There was an avalanche of new information about hepatitis C virus infection, particularly its relationship to mixed cryoglobulinemia and related clinical syndromes. These syndromes have become much more commonly recognized, particularly in areas of high prevalence of hepatitis C virus infection such as Italy. The lymphotrophic nature of the virus is probably ultimately responsible for the rheumatic disease manifestations. Treatment is still problematic, but immunosuppressive drugs should be avoided. Epstein-Barr virus appears to have an etiologic role in the lymphomas occurring in immunosuppressed patients, including those who have had methotrexate therapy. Significant new studies regarding other viruses did not appear during the past year.
9694066 Successful methotrexate therapy for adult Still's disease with marked thrombocytopenia. 1998 A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.
9141266 Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a nationwide 1997 Apr The purpose of the present study was to investigate the incidence of juvenile rheumatoid arthritis (JRA) among Japanese children and to evaluate the clinical features of this disease. A questionnaire was sent to the department of pediatrics of 1290 hospitals in Japan, in 1994, asking for the number of rheumatic patients during the past 10 years. Subsequently, a second questionnaire was sent asking for the type of onset, clinical features, treatment, and other details. The results of 570 cases were obtained. Of these, 310 cases (54%) were the systemic onset type, 140 cases were the polyarticular onset type (25%), and 120 cases (21%) were the pauciarticular onset type. Hence, in the present series of children, the proportion of the pauciarticular type was less than the other two types of JRA. In the laboratory findings of the systemic onset type, hyperferritinemia and thrombocytosis were noted, in addition to leukocytosis, positive C- reactive protein (CRP) and accentuated erythrocyte sedimentation rate (ESR). The rheumatoid factor was positive in 50% of patients with the polyarticular onset type. Chronic uveitis was recognized in 13 cases (10.8%) of the pauciarticular onset type. In four girls, uveitis started before the onset of arthritis. Non-steroidal anti-inflammatory drugs were used in almost one-third of cases, and methotrexate (MTX) was used in 12.8% of cases. The quality of life of children with JRA was disturbed in almost 20% of cases. Therefore, for the early and definitive diagnosis of the systemic type of JRA, diagnostic procedures including thrombocyte counts and serum ferritin level, should be performed. In order to obtain good results and to avoid side effects, a protocol for the use of disease modifying anti-rheumatic drugs and immunosuppressants, especially for the use of MTX, must be established.
9309197 Clinical aspects of juvenile rheumatoid arthritis. 1997 Sep This paper reviews studies in epidemiology, differential diagnosis, clinical manifestations, and treatment of juvenile rheumatoid arthritis (JRA) that have appeared during the past year. One epidemiologic study suggested a decreased incidence recently; however, changes over time in the ethnic and racial characteristics of the patients studied may also have played a role. Findings from an Australian study suggested that some studies may underestimate the true incidence of JRA if visits of physicians are the only basis for the studies. Finally, a Canadian study of incidence showed no seasonal correlations--except for the Prairie region--raising the possibility that the disease varies by region because of environmental factors or variations in ethnic background. Differential diagnostic issues were covered in several reports. One study suggested that elevations in lactate dehydrogenase levels identified children with malignancies who presented with musculoskeletal symptoms. Another study of children with Lyme disease failed to find any patients with asymmetric joint involvement, in contrast to JRA patients. Two studies from Europe reached opposite conclusions regarding whether the incidence of celiac disease was increased in JRA patients. Clinical studies included a French study showing increased production of interleukin-6 and interleukin-1-Ra during fever spikes in children with systemic JRA. An Italian study explored the potential role of interleukin-6 in the anemia of JRA patients. An American study confirmed decreases in markers of bone formation in JRA patients. Two treatment studies addressed the use of intravenous gamma globulin in JRA. Another report described two JRA patients who developed nodules while receiving methotrexate. Finally, a report added confirmation to the successful use of cyclosporine for macrophage activation syndrome in JRA.
10599320 Prognosis in juvenile arthritis. 1999 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.
18031184 How does leflunomide modulate the immune response in rheumatoid arthritis? 1999 Oct Leflunomide has recently been approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis. This approval was based on data from double-blind multicentre trials in the US (US 301; leflunomide versus methotrexate versus placebo) and multicentre European trials (leflunomide versus sulfasalazine versus placebo, and leflunomide versus methotrexate versus placebo). In these trials, leflunomide was superior to placebo and similar to methotrexate or sulfasalazine in efficacy and adverse effects. Both methotrexate and leflunomide retarded the rate of radiological progression, entitling them to qualify as disease-modifying agents (DMARDs). Leflunomide is an immunomodulatory drug that may exert its effects by inhibiting the mitochondrial enzyme dihydro-orotate dehydrogenase (DHO-DH), which plays a key role in the de novo synthesis of the pyrimidine ribonucleotide uridine monophosphate (rUMP). The inhibition of human DHO-DH by A77-1726, the active metabolite of leflunomide, occurs at concentrations (approximately 600 nmol/L) that are achieved during treatment of rheumatoid arthritis. We propose that leflunomide prevents the expansion of activated and autoimmune lymphocytes by interfering with cell cycle progression. This is mediated by inadequate production of rUMP and utilises mechanisms involving the sensor protein p53. The relative lack of toxicity of A77-1726 on nonlymphoid cells may be due to the ability of these cells to fulfil their ribonucleotide requirements by use of the salvage pyrimidine pathway, which makes them less dependent on de novo synthesis.
11346232 Renal involvement in juvenile rheumatoid arthritis: report of two cases. 2001 Renal involvement is a rare occurrence in juvenile rheumatoid arthritis (JRA). We report on two JRA patients with kidney disease. The first was a 14-year-old African-American female with a 12-month history of polyarthritis. On presentation she was found to have an ESR of 127 mm/h and a positive ANA, rheumatoid factor (RF), perinuclear antineutrophil cytoplasmic antibodies (pANCA), haematuria, proteinuria with normal BUN and creatinine. Renal biopsy showed focal segmental glomerulosclerosis. Her renal function deteriorated to end-stage renal failure requiring dialysis within a few months, despite aggressive treatment with steorids and monthly i.v. pulses of cyclophosphamide. The second patient presented with a 6-week history of polyarthritis and intermittent fever, and had a salmon-coloured evanescent rash. On presentation his laboratory evaluation was significant for elevated ESR and negative ANA, RF and ANCA tests. Within 8 months the patient had developed a persistent microscopic haematuria. Renal biopsy showed mild mesangial glomerulonephritis. On low-dose methotrexate therapy his JRA went into remission and his renal function remained normal. The haematuria persisted for 1 year and then resolved spontaneously. This is the first time that focal segmental glomerulosclerosis and mesangial glomerulonephritis have been described in JRA. Although the association may be just coincidental, further studies are needed to define the role of JRA in these renal conditions. In patients with JRA, urinalysis and renal function should be routinely monitored.