Systemic Juvenile Rheumatoid Arthritis Research Articles

Exploration of common genomic signatures of systemic juvenile rheumatoid arthritis and type 1 diabetes

To explore the genetic characteristics of systemic juvenile rheumatoid arthritis (sJRA) and type 1 diabetes mellitus (T1D). The microarray data of sJRA and T1D from Gene Expression Omnibus (GEO) were analyzed. The shared differentially expressed genes (SDEGs) were identified by the Meta-analysis, and genes of extracellular proteins were identified. Then, transcription factors (TFs) and their target genes in SDEGs were obtained by comparing databases from HumanTFDB, and hTFtarget. After that, functional enrichment analyses of the previously identified gene sets were performed by metascape tool. Finally, immune infiltration was analysed by CIBERSORT. We found 175 up-regulated and 245 down-regulated SDEGs, and by constructing a TFs-targeted SDEGs network, 3 key TFs (ARID3A, NEF2, RUNX3) were screened. Functional enrichment analyses and immune infiltration results suggested not only the adaptive immune system but also the innate immune system, and signaling pathways like JAK-STAT are important in the pathogenesis of sJRA and T1D, involving biological processes such as CD4 T cell functions and neutrophil degranulation. This work suggests that innate immune abnormalities also play important roles in sJRA and T1D, CD4 T cell functions, neutrophil degranulation and the JAK-STAT pathway may be involved. The regulatory roles of ARID3A, NEF2, and RUNX3 in this network need to be further investigated.

A clinical case of successful treatment with an interleukin 6 receptor blocker of a systemic variant of juvenile arthritis associated with spinal injury

The article presents a clinical case of systemic juvenile idiopathic arthritis that began after a spinal injury in a 9-year-old child. The authors noted the importance of dysregulation of the innate immune system in the pathogenesis of systemic juvenile idiopathic arthritis that entitled this variant of the disease to be regarded as autoinflammatory, and not “classical” autoimmune diseases. The article emphasized the leading role played by interleukin 6 in the development of extra-articular manifestations of the disease (fever and thrombocytosis, stimulation of hepatic production of acute-phase proteins of inflammation, anaemia, inhibition of the production of adrenocorticotropic hormone and cortisol, production of growth hormone and procalcitonin, development of amyloidosis), highlighting the need for inhibition of interleukin 6 activity in patients receiving therapy for systemic juvenile rheumatoid arthritis. It stressed the importance of early initiation of therapy from the standpoint of modern understanding of the pathogenesis of this disease: the use of new biological agents, which action is directed at interleukins 1 and 6. This approach is associated with inefficiency of such drugs as corticosteroids, methotrexate, tumour necrosis factor inhibitors. Of no less importance is the fact that the use of these biological agents can significantly reduce the effect of corticosteroids. The course of the presented disease caused some difficulties in its diagnosis and selection of therapy. This is largely due to the fact that the pathology of the sacroiliac joint is extremely difficult to diagnose clinically. Inflammatory immune response associated with trauma may be accompanied by cytokine release, free radical accumulation and apoptosis, pointing to the need to exclude juvenile spondyloarthritis and other juvenile arthritis with a view to administer adequate therapy. In this case, an attempt to treat sacroiliitis as an inflammatory disease was unsuccessful. The focus on persisting fever, arthralgia, anemia, lymphadenopathy, high values of acute phase parameters in the patient, who received courses of antibiotic therapy, allowed the doctors of the surgical department to refer the patient to a specialized pediatric rheumatology department. Resistance to glucocorticoids and a tumour necrosis factor inhibitor (etanercept) was also noted. The successful result of the use of tocilizumab (interleukin 6 receptor blocker) includes: relief of visceral manifestations, normalization of laboratory activity indicators of the disease that persisted for 1.5 years.

Dyskeratosis, a characteristic histopathological feature, seen in a patient with systemic juvenile idiopathic arthritis

Dyskeratosis in the epidermis can help making the diagnosis of systemic juvenile idiopathic rheumatoid arthritis when only mild or localized lesions are present.

Treatment of Fissure Caries of Children with Severe Rheumatic Diseases with Difficulty in Opening the Mouth.

Background:Pediatric dentists face difficulties in treating tooth decay of children with difficulty in opening the mouth. This is especially true, as the main disease is accompanied by such symptoms as arthritis, osteoarthritis, myositis, myalgia, sclerosis, and oral atrophy.Aim:The aim was to increase the level of treatment of fissure tooth decay for children with rheumatic diseases, using the silicone key method (SKM).Materials and Methods:A dental examination of 82 children was carried out, with diagnoses: systemic lupus erythematosus, juvenile systemic scleroderma, juvenile dermatomyositis, and juvenile rheumatoid arthritis. Evaluation of the intensity of caries using indices: decayed, missing, and filled teeth (DMFT)(average). Assessment and measurement of the degree of mouth opening (MMO) by Sh. M. Batashvili. The SKM was used to treat fissure tooth decay.Results:During the dental examination of the oral cavity of all children with RD, multiple caries lesions were found. In the first age group of index indicators (DMFT) (on average) - 4.88, in the second age group DMFT (on average) - 7.58 - these values corresponded to high scores for the degree of dental caries, which requires frequent appointment to the dentist. Oral hygiene of children with difficult opening of the mouth is unsatisfactory, which leads to a rapid increase of caries. Restriction of moth opening <4 mm was found in 57 children with RD (69, 51%) that made it difficult to treat caries.Conclusion:Using SKM will improve the quality of caries treatment and provide a stable result of treatment in patients with difficulty opening the mouth in severe somatic pathologies.

Adult-onset Still's Disease: A Case Report

Adult-onset Still's Disease is a rare auto inflammatory disorder of unknown etiology characterized mainly by high spiking fever, arthritis, evanescent rash and lymphadenopathy. It is a form of systemic onset juvenile rheumatoid arthritis that is encountered in adults, typically between 15-25 years and 36-45years. We here describe a 28 years lady with fever, arthritis of multiple large joints, lymphadenopathy and rash, with negative Rheumatoid factor and evidence of past infection with Ebstein-Barr virus and Parvovirus B19. History, examination findings and investigations showed several features consistent with adult-onset Still's disease along with high ferritin level. After exclusion of probable other diagnosis and use of Yamaguchi criteria, she was diagnosed with adult-onset Still's disease. All the major and minor criteria of Yamaguchi for diagnosis were met. Her disease responded well with steroid, she achieved remission and is currently under maintenance therapy. Keywords: Adult-onset stills disease; arthritis; ferritin; fever.

An Unusual Case of Fetal/Neonatal Alloimmune Thrombocytopenia

Abstract Objectives Fetal/neonatal alloimmune thrombocytopenia (FNAIT) occurs when maternal IgG alloantibodies against paternal human platelet antigens (HPA) cross the placenta and cause the destruction of fetal platelets. The vast majority (up to 95%) of FNAIT cases are caused by antibodies against HPA-1a or HPA-5b antigens, while the remaining cases are usually due to antibodies against a variety of other HPA antigens. Cases of FNAIT due to anti-HLA antibodies are extremely uncommon and have only rarely been reported. We present a case of FNAIT suspected to be caused by anti-HLA class I alloantibodies. Methods The patient is a term infant boy born to a 32-year-old G2T2L2 mother. The mother had a previous diagnosis of Still disease (an adult form of systemic juvenile rheumatoid arthritis) but experienced complete resolution of symptoms and was off all treatment during the pregnancy. At birth, laboratory testing revealed isolated severe thrombocytopenia (platelet count 38,000/mcL) in an otherwise healthy-appearing infant. Results The infant had no evidence of bleeding, and testing for TORCH infection, sepsis, and DIC was negative. The maternal blood type was O positive. The maternal platelet count was normal. FNAIT was suspected and the infant was given two platelet transfusions from the same HPA 1a and 5b antigen-negative donor with no significant or sustained improvement in platelet count. Maternal platelet antibody testing subsequently revealed an absence of HPA antibodies, but anti-HLA class I alloantibodies were present. The infant was treated with three subsequent doses of IVIg with improvement in platelet count. No significant hemorrhage occurred. Conclusion HLA class I antibodies are commonly found in multiparous women but are not generally thought to cause significant fetal complications during subsequent pregnancies. This case suggests that, although rarely reported, HLA class I alloantibodies may be capable of causing FNAIT.

The Clinical Significance of Anti-cyclic Citrullinated Peptide Antibodies in Juvenile Rheumatoid Arthritis

Objective. The aim of this study was to determine the clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibody in juvenile rheumatoid arthritis (JRA). Methods. Sera for anti-CCP assay were obtained from 142 patients with arthralgia in our hospital during the period between November 2010 and October 2011. On the basis of medical records, 83 patients with JRA were designated to the study group, and 59 patients with arthralgia but were treated as transient arthritis to the control group. The values of anti-CCP were then analyzed retrospectively. We used the enzyme linked immunosorbent assay (ELISA) for detecting anti-CCP. Results. Positive anti-CCP values were found in the sera of 11 patients with JRA (13.3%), one patient presented with pauciarticular JRA and the others with polyarticular JRA. There was a statistically significant difference in the anti-CCP values between the JRA group and the control group. However, patients with systemic JRA and arthralgia without JRA had no anti-CCP. Especially, 10 out of 14 (71.4%) patients with RF-positive polyarticular JRA had anti-CCP. In addition, the rate of positive anti-CCP was significantly higher in patients with polyarticular JRA than in the control group. Conclusion. We expect that the presence of anti-CCP may help to evaluate the severity of diseases in patients with JRA. Anti-CCP can be an important biomarker for making early intensive therapeutic decision in patients with polyarticular JRA, which might have more severe course and longer disease duration.

Uveitis Prevalence and Risk Factors in Juvenile Rheumatoid Arthritis - A Prospective, Cross Sectional Study

Objective : The objective was to estimate prevalence of uveitis in children diagnosed as having Juvenile Rheumatoid Arthritis (JRA) and identify risk factors of uveitis amongst them. Methods : A cross sectional hospital based study. All newly diagnosed children of JRA attending our paediatric rheumatology clinic and uveitis clinic from Sep 2011 to January 2013 were included. JRA cases were divided into oligoarticular, polyarticular and systemic onset type. Types of uveitis seen were divided into acute anterior, recurrent anterior, chronic anterior and healed anterior type. Rheumatoid factor and ANA testing was done. Results : Out of 161 cases of JRA, 30 (18.6 %) had uveitis. Out of the cases with uveitis 80% had oligoarticular, 20% had polyarticular and none had systemic onset type JRA. Mean age of onset of JRA in cases with uveitis was 6.4yr+/-1.3. Mean age of onset of JRA in cases without uveitis was 7.8 +/-1.3. This difference was statistically significant p

Human Leukocyte Antigen-DRB1 Associations in Korean Juvenile Rheumatoid Arthritis

Objective. The aim of this study is to investigate the association of different subgroups of juvenile rheumatoid arthritis (JRA) with human leukocyte antigen (HLA) class II DR alleles. Methods. One hundred and nineteen Korean juvenile rheumatoid arthritis patients were classified as HLA-DRB1 allele. To assess the frequency, phenotype frequencies of all JRA cases and each subtypes were compared to those of 485 adult controls. Results. HLA-DRB1*01 was associated with increased risk of JRA. Furthermore, DRB1*01 was associated with polyarticular JRA and pauciarticular JRA. The frequencies of DRB1*14 and DRB1*15 were higher in systemic JRA patients than the controls. Conclusion. The data of this study on Korean children with JRA suggests that HLA-DRB1*01 was associated with the susceptibility of JRA. The study should be extended to include larger numbers of patients.

AB0695 Cyclosporine usage in resistant systemic jia-an experience from india

BackgroundThe mainstay of treatment of Systemic JIA (sJIA) are corticosteroids(1,2), with majority being well responsive to steroids. But stopping steroids is really challenging as many relapse on tapering off or...

Sexual maturation in Egyptian boys and girls with juvenile rheumatoid arthritis

Children with juvenile rheumatoid arthritis (JRA) exhibit a compromised growth status while information concerning the pattern of their sexual maturity is scant. The aim of the current work was to study sexual maturity in boys and girls with JRA. The study included eighty JRA patients they were 45 male and 35 female and eighty age- and sex-matched normal children served as controls. Development of genitalia was evaluated as per sexual maturity rating criteria given by Tanner score. Development of hair (pubic, axillary and facial) and age of monarch to JRA females were noted The mean (±SD) age of appearance of genitalia stage G-2 in boys with systemic onset JRA (12.0 ± 0.3 years) was earlier when compared with pauciarticular (12.60 ± 0.93 years) and polyarticular (13.39 ± 0.93 years) JRA but delayed for all types of JRA when compared with controls (10.06 ± 0.63 years). In comparison with female groups, the mean (±SD) age of appearance of genitalia stage G-2 with systemic onset JRA (12.0 ± 0.4 years) was also earlier when compared with pauciarticular (12.68 ± 1.09 years) and polyarticular (13.72 ± 0.39 years). Age of menarche delayed in all JRA female patients. None of the study group reach stage G-5 of genitalia development. The timing of initiation of sexual maturity in boys and girls with JRA delayed and this delay variable according to disease subtype.

MiR‐146a polymorphism is associated with asthma but not with systemic lupus erythematosus and juvenile rheumatoid arthritis in Mexican patients

Extensive research has shown that aberrant expression of microRNAs (miRNAs) plays an important role in innate and adaptive immune responses. The rs2910164 polymorphism has been identified as a functional variant, which affects the transcription and expression level of miR-146a and, thereby, contributes to the pathogenesis of several inflammatory and autoimmune diseases. To investigate whether the rs2910164 G/C polymorphism was associated with asthma, systemic lupus erythematosus (SLE) or juvenile rheumatoid arthritis (JRA), we performed an association study in a pediatric Mexican cohort. We included 979 pediatric patients (asthma: 402, SLE: 367 and JRA: 210) and 531 control subjects without inflammatory or immune diseases. Genotyping was performed using the 5' exonuclease technique. The genotype distribution of the rs2910164 polymorphism was in Hardy-Weinberg equilibrium in each group. No significant differences were detected in the distribution of this polymorphism between cases and controls (P = 0.108, 0.609 and 0.553 for subjects with asthma, JRA and SLE, respectively). However, stratification by gender showed a statistically significant difference between asthmatic and control females, where the C allele was significantly associated with protection to asthma (odds ratio = 0.694, 95% confidence interval 0.519-0.929, P = 0.0138). Our results provide evidence that rs2910164 may play a role in the susceptibility to childhood-onset asthma, but not SLE or JRA in Mexicans. Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases.

Clinical analysis of macrophage activation syndrome in pediatric patients with autoimmune diseases

Macrophage activation syndrome (MAS) belongs to secondary hemophagocytic lymphohistiocytosis (HLH) syndrome. It is usually associated with rheumatic diseases. We retrospectively reviewed our hospital's medical records of 102 HLH/MAS patients from the past 20 years. Demographics, clinical data, treatment, and outcomes were analyzed. Among 102 patients, eight patients with underlying juvenile systemic lupus erythematous (two patients), mixed connective tissue disease (one patient), primary anti-phospholipid syndrome (one patient), and systemic type juvenile rheumatoid arthritis (sJRA; four patients) with 13 episodes of MAS were studied. Clinical manifestations of MAS included fever (100 %), hepatosplenomegaly (77 %), lymphadenopathy (38 %), skin rash (62 %), and neurological involvement (31 %). Laboratory features included leukopenia (54 %), anemia (46 %), thrombocytopenia (77 %), jaundice (27 %), hypofibrinogenemia (40 %), decreased erythrocyte sedimentation rate (67 %), and elevated liver enzymes (77 %), lactate dehydrogenase (100 %), ferritin (88 %), triglycerides (91 %), C-reactive protein (85 %), plasma D-dimer (50 %), and hemophagocytosis in bone marrow (83 %). The Epstein-Barr virus and adenovirus infection triggered MAS in two patients with sJRA. Methylprednisolone pulse therapy was effective in two out of three patients, and high-dose intravenous immunoglobulin (IVIG) was effective in two out of six patients. Patients with sJRA responded well to corticosteroids and cyclosporine. Complications included opportunistic infection with Pneumocystis jiroveci, multiple organ failure, and intensive care unit myopathy. The mortality rate was one out of eight (12.5 %). Our results showed that MAS could be fatal and complicate various pediatric autoimmune diseases. It generally has a good response to corticosteroids and IVIG. Prompt recognition and timely treatment can result in good outcomes.

Subglottic stenosis in juvenile rheumatoid arthritis

Juvenile rheumatoid arthritis (JRA), now termed juvenile idiopathic arthritis (JIA), is a well-described group of arthritides in the pediatric population with known associations with airway compromise. Subclasses are based on associated symptoms and number of joints involved, namely pauciarticular, polyarticular, and systemic onset JRA. Cricoarytenoid arthritis (CA), as a cause of airway compromise, is rarely associated with JRA as compared to adult onset rheumatoid arthritis, however, there are reports of CA with JRA. Additionally, JRA is associated with other rheumatologic diseases, which include a reported case of Wegener's granulomatosis. Wegener's granulomatosis has a well-established association with subglottic stenosis. Described below is the case study of an 18 year-old African American female with a 5-year history of pauciarticular juvenile rheumatoid arthritis developed worsening shortness of breath, orthopnea, and stridor over a 1-month period. The patient had a firm circumferential subglottic mass obstructing approximately 80% of the lumen and requiring tracheostomy tube placement. Biopsies of the mass revealed only acute and chronic inflammation. There was no evidence of rheumatoid nodules, granulomas, acid fast, or fungal organisms. To our knowledge, this is the first case history reported of a patient with JRA and idiopathic subglottic stenosis; this potentially establishes an association between the two disease processes.

Clinical characteristics and disease course in children with haemophagocytic lymphohistiocytosis treated at the University children’s hospital in Belgrade

Haemophagocytic lymphohistiocytosis (HLH) is a disorder characterised by long-standing fever, splenomegaly and bicytopoenia or pancytopoenia. Lymphadenopathy, jaundice and neurological symptoms mayalsooccur. HLH may ensue in various forms of innate or acquired immunodeficiency with impaired cytotoxic lymphocyte function resulting in excessive macrophage activation. To describe and analyse clinical characteristics of patients treated for HLH at the University Children's Hospital of Belgrade from August 2000 to August 2010. Retrospective analysis of medical records. Diagnosis of HLH was established in 13 children (five boys and eight girls) aged from one month to 14 years. In six children HLH was secondary (to visceral leishmaniasis in two, Ebstein-Barr virus infection in one, Langerhans' cell histiocytosis in one and systemic juvenile rheumatoid arthritis in two). Of the remaining seven patients, genes for perforin and syntaxin 11 were examined in two and no mutations were found. Of the remaining seven patients, genes encoding perforin and syntaxin 11 were analyzed in two, but no mutations were found. All children had fever, splenomegaly, cytopoenias, hyperferritinaemia and hypertriglyceridaemia, but haemophagocytosis was seen in only six (46.1%). Six children were cured (four with secondary HLH and two with primary HLH).Two children are undergoing treatment, while five succumbed (three before treatment could be administered and two due to complications). In four of the six cured children, HLH arose in the first year of life. Cure rate in those who underwent haematopoietic stem cell transplantation was 2/3. Results underscore the importance of timely diagnosis and treatment of HLH, warranting that in all children with fever, splenomegaly and/or cytopoenias, with or without haemophagocytosis, HLH be actively sought.

A Case of Macropharge Activation Syndrome Successfully Treated with Combination Therapy Including Etanercept

Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of childhood systemic inflammatory disorder, primarily systemic onset juvenile rheumatoid arthritis (SoJRA). It is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms. The clinical manifestations are caused by the activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to cytokine overproduction including tumor necrosis factor-α (TNF-α). Methylprednisolone pulse therapy and cyclosporine A have made a considerable progress in the treatment of MAS. However, the mortality rate remains high suggesting the need of another therapeutic agent. Several cases of MAS successfully treated with TNF-α inhibitor (etanercept) have been reported. We report the first Korean case of MAS successfully treated with combination therapy of corticosteroid, cyclosporine A and etanercept.

Anti-chromatin antibodies in juvenile rheumatoid arthritis

to evaluate the prevalence and clinical significance of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA). IgG anti-chromatin Abs were detected by an enzyme-linked immunosorbent assay (ELISA), in sera of 94 children with JRA (10 children with systemic, 38 with polyarticular and 46 with oligoarticular disease onset). As control group, 33 age- and-sex-matched healthy children (HC) were also examined. Abs to chromatin were detected in 24/94 (25.5%) of children suffering from JRA. Particularly, the higher prevalence of anti-chromatin Abs has been found in children with oligoarticular (30,4%) and polyarticular (23.7%) onset JRA. In these groups Abs titers were significantly higher compared to systemic JRA and HC (p=0.003). Anti-chromatin Abs were observed more frequently in patients with oligoarticular disease and chronic uveitis (21.7%). Furthermore, higher levels of anti-chromatin Abs has been found in all the patients treated with anti-TNF-alpha therapy (p< 0.0001). our results confirm previous data about the prevalence of anti-chromatin Abs in JRA. These Abs were significantly higher in the group of patients with oligoarticular onset with past or present history of ocular involvement and in the group with polyarticular JRA treated with biologic therapy. A long-term follow-up study could be useful to evaluate the potential utility of these autoantibodies.

Application of blood purification of critical disease with non-renal indications in PICU

Objective To investigate the application of blood purification for critical disease with non-renal indications in PICU. Methods We retrospectively analyzed the clinical data of 10 critical disease cases with non-renal indications in PICU admitted from Jan to Dec 2009. Five cases were with acute liver failure,2 with autoimmune disease (1 with Guillaln-Barre syndrome, 1 with systemic juvenile rheumatoid arthritis with macrophage activation syndrome) ,2 with severe sepsis,one with metabolic diseases. Results Four cases were treated with plasma exchange combined with continuous veno-venous hemmofiltration. Three cases were treated with continuous veno-venous hemmofiltration. Three cases were treated with plasma exchange.Conclusion CBP is an effective and safe method in the treatment of critical diseases with non-renal indications in PICU. Key words: Blood purification; PICU; Liver failure; Autoimmune disease

Sexual maturation in boys with juvenile rheumatoid arthritis

This paper aimed to study sexual maturation of boys with juvenile rheumatoid arthritis (JRA) during adolescence. This study was carried out in the Department of Pediatrics, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A total of 70 boys (between 9 and 17 years of age) diagnosed as cases of JRA comprised the sample for this study. Every child was examined for the development of genitalia as per criteria given by Tanner (Growth at adolescence, 2nd edn, Blackwell, Oxford, 1962) at half-yearly age intervals. However, with regard to development of hair (pubic, axillary and facial) mere presence or absence was noted. Mean (±SD) age of attainment of different stages of genitalia development as well as for eruption of hair was ascertained amongst boys who entered puberty using conventional statistics. Initiation of genitalia development (i.e. appearance of G-2 stage) was earliest among boys with systemic onset JRA (10.8 ± 1.3 years). None of the boys with JRA could attain final stage (G-5) of genitalia development by the age of 17 years, as compared with normal Chandigarh boys who had attained this by 15.2 years. Age of appearance of axillary, pubic, and facial hair was also earlier in systemic onset type of disease as compared with those with pauciarticular and polyarticular JRA. The timing of initiation of sexual maturity in boys with different types of JRA remains variably affected, and appears to experience substantial delay in completion of puberty.

Mortality outcomes in pediatric rheumatology in the US

To describe mortality rates, causes of death, and potential mortality risk factors in pediatric rheumatic diseases in the US. We used the Indianapolis Pediatric Rheumatology Disease Registry, which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were determined. After excluding patients with malignancy, 110 deaths among 48,885 patients (0.23%) were confirmed. Patients had been followed up for a mean +/- SD of 7.9 +/- 2.7 years. The SMR of the entire cohort was significantly decreased (0.65 [95% CI 0.53-0.78]), with differences in patients followed up for > or =9 years. The SMR was significantly greater for systemic lupus erythematosus (3.06 [95% CI 1.78-4.90]) and dermatomyositis (2.64 [95% CI 0.86-6.17]) but not for systemic juvenile rheumatoid arthritis (1.8 [95% CI 0.66-3.92]). The SMR was significantly decreased in pain syndromes (0.41 [95% CI 0.21-0.72]). Causes of death were related to the rheumatic diagnosis (including complications) in 39 patients (35%), treatment complications in 11 (10%), non-natural causes in 25 (23%), background disease in 23 (21%), and were unknown in 12 patients (11%). Rheumatic diagnoses, age at diagnosis, sex, and early use of systemic steroids and methotrexate were significantly associated with the risk of death. Our findings indicate that the overall mortality rate for pediatric rheumatic diseases was not increased. Even for the diseases and conditions associated with increased mortality, mortality rates were significantly lower than those reported in previous studies.