Longitudinal analysis of a pediatric rheumatology clinic population

OBJECTIVE: To analyze a prospectively maintained pediatric rheumatology clinic disease registry. METHODS: A total of 3269 consecutive referrals to the Pediatric Rheumatology Clinic, University of Saskatchewan, during the period 1981-2004 were analyzed. RESULTS: Among 3269 patients, a diagnosis was established in 2098 (64.2%). Within this group, 72 subjects (3.4%) were determined to be healthy. Of the remaining 2026 diagnosed patients (62.0% of the total population), 1032 (50.9%) had a rheumatic disease and 994 (49.1%) a nonrheumatic disease. A diagnosis was not established in 1171 patients (35.8%). Among the 1032 patients with a rheumatic disease, 326 (31.6%) had juvenile rheumatoid arthritis (JRA), 360 (34.9%) a spondyloarthropathy (SpA), and 225 (21.8%) a collagen vascular/connective tissue rheumatic disease. The remaining 121 patients with a rheumatic disease (11.7%) had a variety of other conditions. Of the 994 nonrheumatic disease patients, 37 (3.7%) with ocular inflammatory conditions had been referred to exclude an associated rheumatic disease. The remaining group of 957 patients comprised 345 (36.1%) with an orthopedic, mechanical or traumatic condition, 231 (24.1%) had an infection, 45 (4.7%) a hematologic or neoplastic disease, and 336 (35.1%) a variety of other conditions. Current clinic point prevalences for JRA, SpA, and collagen vascular diseases are 35.0, 16.9 and 17.7/100,000, respectively. The mean annual clinic referral incidences of JRA, SpA, and collagen vascular/connective tissue diseases were, respectively, 4.7, 5.2, and 1.7/100,000 children. CONCLUSION: Disease registries help establish the frequencies and spectrum of childhood rheumatic diseases and the role of pediatric rheumatology programs in evaluating and caring for children with a wide variety of conditions. Longitudinal disease registries aid in characterizing clinical, epidemiologic, and demographic features of childhood rheumatic diseases.     

Profile of a pediatric rheumatology practice in Israel

BACKGROUND: Several studies from Western countries have analyzed the profile of pediatric rheumatology practices. Due to differences in demography and health care systems the profile in Israel may differ from those countries. OBJECTIVE: To describe the profile of a pediatric rheumatology practice in Israel. METHODS: All new patients seen during the course of 2000 as part of my pediatric rheumatology practice in Northern Israel were registered at their initial encounter. Recorded were demographic data, referral patterns, diagnoses, and disease-related data. Diagnoses were grouped together by types of condition. RESULTS: 242 new patients were seen. 39% of the patients had a rheumatic condition, 39% had non-inflammatory conditions, 12% had periodic fever syndromes and for 10% no definitive diagnosis was determined. 14% had chronic rheumatic diseases. The time until diagnosis was significantly greater and more physicians were involved in the evaluation of periodic fever syndromes than in other disease groups. Seventeen (7%) patients had juvenile rheumatoid arthritis (JRA). The minimum estimated incidence of JRA was 8.8 per 100,000 children. CONCLUSIONS: Most patients seen did not have classic inflammatory rheumatic diseases, similar to data from other Western countries. Distinctive to Israel and the Middle East, periodic fever syndromes comprise a large proportion of the pediatric rheumatology practice. These syndromes are relatively difficult for community physicians to diagnose.     

Analysis of a pediatric rheumatology clinic population

This analysis evaluates the role of a pediatric rheumatology clinic in assessing children with suspected rheumatic diseases and establishes relative disease frequencies in a clinic population. The study population comprised 875 children referred to a pediatric rheumatology clinic serving a population of 290,000 children. The mean annual referral rate was 113 patients. A diagnosis was established in 580 (66%) of whom 337 (58%) had a rheumatic disease. Of those with a rheumatic disease 156 (46%) had juvenile rheumatoid arthritis, 104 (31%) a spondyloarthropathy, 62 (18%) a connective tissue/collagen vascular disorder and 15 (5%) a variety of other conditions. Of the 243 diagnosed as having a nonrheumatic disease 79 (33%) had a mechanical or traumatic cause for musculoskeletal symptoms, 33 (14%) had an infection, 15 (6%) a neoplastic disorder and 71 (29%) a variety of other disorders. In addition, 45 children (19%) were evaluated because of family histories of rheumatic diseases or questionably abnormal symptoms or signs; after evaluation all these children were considered to be normal. The remaining group comprised 295 subjects (34%) for whom a definite diagnosis has not been made. In addition to diagnosing and caring for children with rheumatic disorders a pediatric rheumatology clinic serves to identify nonrheumatic conditions and provides information concerning relative frequencies and epidemiologic characteristics of childhood rheumatic diseases.     

Ethnic differences in risk for pediatric rheumatic illness in a culturally diverse population

OBJECTIVE: To analyze the differences of occurrence of pediatric rheumatic disease among various ethnic groups in a culturally diverse isolated geographic area. METHODS: A retrospective study of pediatric rheumatic diseases in a multiethnic area during a 6 year period. RESULTS: A group of 922 patients was categorized based on predominant ethnicity, and their risk of having acute rheumatic fever (ARF), juvenile rheumatoid arthritis (JRA), and systemic lupus erythematosus (SLE) was studied. Odds ratios (OR) were computed for each illness with Caucasians as the reference group. Results indicated that Polynesians were overrepresented among patients with ARF, having elevated OR that were significantly different from Caucasians (22.5-120.7, p < 0.0001). For SLE, the highest OR were obtained for Samoans, Filipinos, and Japanese. In contrast, for JRA, Filipinos and Japanese had OR less than one, and no Samoans were diagnosed with JRA, possibly indicating a protective effect against developing JRA. CONCLUSION: This unique retrospective study examined the ethnic variations of expression of certain rheumatic diseases in an isolated region. Results reveal that certain ethnic groups are at risk for ARF and SLE, but are protected against JRA. These findings suggest investigating possible immunogenetic similarities and differences in these illnesses.     

Visiting consultant clinics to study prevalence rates of juvenile rheumatoid arthritis and childhood systemic lupus erythematosus across dispersed geographic areas

OBJECTIVE: Visiting consultant clinics (VCC) may provide pediatric rheumatologic care to children in rural populations, but the clinical demands have not been studied. We studied whether these clinics could be effective in determining prevalence rates of rheumatic illness like juvenile rheumatoid arthritis (JRA) and childhood systemic lupus erythematosus (SLE) across large dispersed geographic areas. METHODS: The study population included children diagnosed with JRA or SLE at the only civilian pediatric rheumatology center in the State of Hawaii. Prevalence rates of these illnesses were then calculated for the urban and more rural neighbor island areas. VCC and prevalence data were calculated over a 10-year period. RESULTS: We found a lower prevalence of JRA in the urban area (38.3 per 100,000) when compared to the rural neighbor islands (63.2 per 100,000). However, an equivalent prevalence of SLE was found in the urban (24.0 per 100,000) and neighboring islands (21.8 per 100,000). Clinical demands increased significantly with the success of the VCC, and with an increase in pediatric rheumatologic staffing. CONCLUSION: We found an increased prevalence of JRA in rural areas when compared to urban areas. Similar prevalence rates of SLE suggested the finding was not due to referral bias alone. VCC are useful to estimate disease prevalence over large areas, and therefore make it possible to identify areas at greater risk. Further investigations are needed to elucidate the possible environmental and genetic factors that may explain the regional differences in JRA prevalence.     

Onset to first visit intervals in childhood rheumatic diseases

OBJECTIVE: To determine time intervals between onset of symptoms of a childhood rheumatic disease and first visit to a pediatric rheumatology clinic and to evaluate factors influencing onset to first visit intervals. METHODS: Onset to first visit intervals were analyzed in 836 children representing the 10 most common diseases in a pediatric rheumatology clinic population of 1093. RESULTS: Among 836 subjects, 469 (56.1%) could identify month of symptom onset. Among patients with juvenile rheumatoid arthritis (JRA) 125 of 195 (64.1%) with pauciarticular, 58 of 105 (55.2%) with polyarticular, and 28 of 36 (77.8%) with systemic subtypes were able to determine time interval between symptom onset and first visit. Month intervals were confidently established in 80 of 250 with a spondyloarthropathy (32.4%), 19 of 52 (36.5%) with psoriatic arthropathy, 65 of 72 (90.3%) with Henoch-Sch?nlein purpura (HSP), 50 of 56 (89.3%) with Kawasaki disease, 22 of 34 (64.7%) with systemic lupus erythematosus, 13 of 18 (72.2%) with dermatomyositis, and 9 of 18 (50%) with localized scleroderma. Determination of onset was significantly more likely in HSP than in other diagnostic categories except systemic JRA, and more likely in Kawasaki disease than other disease categories except systemic JRA and dermatomyositis. In the group of 469, 287 (61.2%) were seen within 2 months of symptom onset and 447 (95.3%) within 1 year of symptom onset. CONCLUSION: Diseases ordinarily typified by an abrupt and acute onset of symptoms were referred most promptly, suggesting that acuity of symptoms at disease onset is the factor that most influences promptness of referral. Prospective studies are required to establish how onset to first visit intervals might influence disease outcomes and to devise best practice referral guidelines.     

The influence of the hormonal system on pediatric rheumatic diseases

The role of NEI interactions in children with chronic inflammatory rheumatic disorders has not been systematically studied to the same extent as in adults. The data that are currently available suggest that NEI mechanisms are involved in the pathophysiology of some of the diseases. These include JRA, JSLE, and JAS. Prolactin has been most extensively investigated, showing interesting parallels with findings in adult rheumatologic diseases. Limited data on cortisol suggest a deficiency of production in JRA, a situation similar to that in adult RA. These findings suggest that there is a proinflammatory hormonal bias in children with JRA and JSLE. The data in children with chronic autoimmune inflammatory disorders seem to be identical to those seen in adults with RA and SLE, but a clear delineation of the role of the neuroendocrine-immune system in disease pathophysiology is still required. The neuroendocrine aspects of pediatric rheumatologic disease observed to date suggest a number of avenues for further research in the field of neuroendocrine immunology, which may open up novel therapeutic options.     

Evaluation of a recombinant antigen enzyme-linked immunosorbent assay (ELISA) in the diagnostics of antinuclear antibodies (ANA) in children with rheumatic disorders

The reliability and accuracy of ELISAs for the detection of circulating ANA in children with rheumatic diseases has recently been questioned. In this study we evaluated an allegedly superior ELISA method using recombinant antigens in a paediatric population with various rheumatic conditions and compared it to a conventional Hep-2 IFA assay. Sera from 123 children (204 blood samples) were simultaneously tested by conventional ANA immunofluorescence on Hep-2 cells (ANA-IFA) and recombinant antigen ELISA (rELISA). There were 44 children with systemic lupus erythematosus (SLE), 29 with juvenile rheumatoid arthritis (JRA), eight with mixed connective tissue disease (MCTD), eight with reactive arthritis, five with juvenile fibromyalgia syndrome, three with dermatomyositis (JDMS) and 31 with other diagnoses.  Thirty-five children (27%) had a positive Hep-2 result, which remained undetected by ELISA (P <0.002). Almost all of these children had significant IFA titres above 1:160. The major discrepancies were observed in children with JRA and SLE. There was no titre correlation between the two assays and the rELISA’s OD readings were not linear.  The ELISA using recombinant antigens was not useful for the detection of serum ANA in children with rheumatic diseases due to a high rate of false negative results. These data concur with recent reports about the lack of reliability of ELISAs using non-recombinant antigens. Received: 2 May 2001 / Accepted: 10 September 2001     

Adenosine Deaminase Activity and its Isoenzyme Pattern in Patients with Juvenile Rheumatoid Arthritis and Systemic Lupus Erythematosus

Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the mechanisms of the immune system. The aim of this study was to investigate the activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in serum and peripheral blood lymphocytes (PBLs) of children with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE) in different phases of the diseases. The study comprised 34 patients with rheumatic disease, 24 with JRA and 10 with SLE, and 64 healthy controls. The tADA activity and its isoenzymes were measured in serum and PBLs of all patients by the method of Giusti and by the presence or absence of EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) during the active phase of the disease (before treatment), as well as during remission and relapse. Our data show that increased tADA activity in the serum and PBLs of patients with JRA and SLE is correlated mainly to increased levels of ADA2 activity in serum and ADA1 activity in PBLs. It also closely correlates with clinical disease activity and relapse. The cause of this increased tADA/ADA2 activity in serum and tADA/ADA1 activity in PBLs in JRA and SLE remains to be elucidated. Nevertheless, it may be noted that the measurement of tADA activity, together with ADA2 activity in serum and tADA with ADA1 activity in PBLs, could offer a biochemical approach to the assessment of the pathophysiology of JRA and SLE. Also, tADA and its isoenzymes could be used as alternative parameters representing disease activity. Received: 31 July 2000 / Accepted: 5 June 2001     

The Immunologic and Clinical Associations of the Split Products of C3 in Plasma in Juvenile Rheumatoid Arthritis

A qualitative counterimmunoelectrophoretic assay for the complement activation products C3c and C3d was used to study plasma from children with juvenile rheumatoid arthritis (JRA) and other rheumatic diseases. Positive tests for C3c,d were found in all patients with active systemic lupus erythematosus (SLE), 7 of 10 patients with active systemic JRA, 16 of 29 with active polyarticular JRA, 7 of 20 with active pauciarticular JRA, and in only 2 of 20 with inactive joint disease. The incidence of positive assays for C3c,d in JRA was increased in the presence of positive latex fixation tests, antinuclear antibody tests, or elevated values for antiglobulins as determined by affinity chromatography, but these associations were not statistically significant. Three joint fluids from children with pauciarticular JRA were negative for C3c,d. These studies show that the subgroups of JRA defined by clinical criteria are heterogeneous by current laboratory parameters and that evidence implicating antigen-antibody complexes in the pathogenesis of JRA is lacking in many patients.     

The immunologic and clinical associations of the split products of C3 in plasma in juvenile rheumatoid arthritis.

A qualitative counterimmunoelectrophoretic assay for the complement activation products C3c and C3d was used to study plasma from children with juvenile rheumatoid arthritis (JRA) and other rheumatic diseases. Positive tests for C3c,d were found in all patients with active systemic lupus erythematosus (SLE), 7 of 10 patients with active systemic JRA, 16 of 29 with active polyarticular JRA, 7 of 20 with active pauciarticular JRA, and in only 2 of 20 with inactive joint disease. The incidence of positive assays for C3c,d in JRA was increased in the presence of positive latex fixation tests, antinuclear antibody tests, or elevated values for antiglobulins as determined by affinity chromatography, but these associations were not statistically significant. Three joint fluids from children with pauciarticular JRA were negative for C3c,d. These studies show that the subgroups of JRA defined by clinical criteria are heterogeneous by current laboratory parameters and that evidence implicating antigen-antibody complexes in the pathogenesis of JRA is lacking in many patients.     

Access to pediatric rheumatology care in the United States

OBJECTIVE: To describe rheumatology providers, depict their availability, and determine the extent to which internist rheumatologists may expand access to care for children with rheumatic diseases. METHODS: Using data from the American College of Rheumatology and the Bureau of Health Professions Area Resource File, we generated a national map of providers' practice locations and calculated distances between each county and the nearest rheumatologist. We also performed a logit analysis to identify provider and county characteristics that were associated with internist rheumatologists' willingness to treat children. RESULTS: Approximately 50% of the under 18 population in the United States live within 50 miles of a pediatric rheumatologist and nearly 90% live within 50 miles of a pediatric rheumatologist or an internist rheumatologist who treats children. Internist rheumatologists in private practice were 3 times as likely as those in medical schools to treat children (P < 0.001). Likewise, internist rheumatologists who live 200 or more miles from a pediatric rheumatologist were more than twice as likely to treat children as those who lived within 10 miles of a pediatric rheumatologist (P < 0.001). CONCLUSIONS: Our analysis suggests that internist rheumatologists are more geographically diffuse than pediatric rheumatologists and act as substitutes for pediatric rheumatologists in those regions that lack such providers. Research is needed to understand the role of internist rheumatologists in caring for children with rheumatic diseases and the quality of the care that they provide to this population.     

Current treatment by United States and Canadian pediatric rheumatologists.

OBJECTIVE: To determine current treatment practices for 11 selected pediatric rheumatic diseases. METHODS: A questionnaire was mailed to 224 US and Canadian physicians who were listed in membership directories that included pediatric rheumatologists. RESULTS: One hundred seventy-four questionnaires (78%) were returned. Board certified pediatricians accounted for 86% of respondents. Nonsteroidal antiinflammatory drugs were the most commonly used medicines for all forms of juvenile rheumatoid arthritis (JRA), seronegative enthesopathy and arthropathy syndrome (SEA), and Henoch-Sch?nlein purpura, whereas oral corticosteroids were most frequently used for systemic lupus erythematosus (SLE), juvenile dermatomyositis, polyarteritis nodosa, and sarcoidosis. Intraarticular corticosteroid injection was the second most common therapy for pauciarticular JRA, but methotrexate (MTX) was second for polyarticular and systemic onset forms of JRA, and sulfasalazine was second for SEA. For all diseases, MTX was administered orally roughly twice as often as subcutaneously. In treating SLE, cyclophosphamide was used more frequently than azathioprine, cyclosporin A, or intravenous immunoglobulin. CONCLUSION: The results from this survey should allow individual practitioners to compare their treatment patterns to pediatric rheumatologists in the US and Canada as a whole.     

Health services in rheumatology

Studies of the costs associated with rheumatic diseases, the referral of patients to rheumatology subspecialty care, rheumatology practice patterns, and the relation between medical care and patient outcomes are reviewed. Direct medical costs in patients with rheumatoid arthritis (RA) are higher among those with more functional disability. Direct medical costs in patients with systemic lupus erythematosus (SLE) did not differ among Canadian, American, and British patients, despite substantial differences in the mechanisms by which medical care is financed and delivered in these three countries. The diagnostic accuracy of rheumatic complaints by primary care physicians may be low, and concomitant psychiatric disorders may not be uncommon among patients referred to rheumatologists. Most patient visits to rheumatologists involve patients with rheumatic diseases or musculoskeletal complaints, and few visits involve primary care. Fewer than half of elderly patients with RA or SLE are seen by a rheumatologist in a given year; access is particularly limited among black women. Early access to rheumatology subspecialty care may be associated with improved health status in patients with RA, and mortality among patients with SLE varies with the experience a hospital has in treating patients with SLE.     

Asymptomatic celiac sprue in juvenile rheumatic diseases children

Background: Celiac disease (CD) is the most frequent enteropathy in adults and its coexistence with other autoimmune diseases is frequent. Objective: To detect asymptomatic CD in children with rheumatic diseases by measuring tissue transglutaminase (tTG) antibodies and finding any relation to disease activity. Patients and methods: Setting and study design: The study included 60 children with juvenile rheumatic diseases consecutively from those attending the Rheumatology Clinics of Cairo University Hospitals: 30 juvenile rheumatoid arthritis (JRA), 10 juvenile systemic lupus erythematosus (SLE), 12 juvenile seronegative spondyloarthropathy and eight juvenile systemic sclerosis/polymyositis (SSc/PM) overlap syndrome were recruited during 2010. There were 22 male and 38 female patients. Thirty matched healthy controls were included. All children were subjected to thorough history taking, clinical examination and laboratory investigations. The body mass index (BMI) for age was used. All subjects had no gastrointestinal tract symptoms suggestive of CD and the tTG antibodies (IgA and IgG) were assessed. Results: The mean age of patients was 12.03 ± 3.3 years and disease duration 4.18 ± 3.24 years. The demographic, clinical and laboratory features of the children were studied and compared. The tTG was positive in 32 (53.3%) patients compared to 20% of the controls (P = 0.03), being higher in females. In tTG‐positive patients, the BMI was significantly lower, while white blood cell count, erythrocyte sedimentation rate and disease activity were significantly higher. Conclusions: tTG antibodies may be used as a screening test to identify asymptomatic CD associated with juvenile rheumatic diseases, especially those with active JRA or marked reduction in BMI.     

Evidence-based use of methotrexate in children with rheumatic disorders. Consensus statement of the Working Group for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and the Working Group Pediatric Rheumatology Austria

Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with nonsteroidal antiinflammatory drugs (NSAR) and physiotherapy. Still, in a significant number of cases the disease is resistant to this therapy and treatment with "second line" disease modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as "first choice second line agent" for the treatment of JIA. However, there are considerable differences among pediatric rheumatologists on how and when to use MTX. To increase drug safety, the Working Group for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and the Working Group Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words "Methotrexate" and "juvenile arthritis" limited to age 0-18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin), experience with MTX in adults with rheumatoid arthritis (RA) and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.     

上海单中心住院儿童风湿性疾病谱演变

目的:了解上海单中心风湿性疾病住院患儿疾病谱的变化趋势,提高对儿童风湿性疾病的认识。方法:回顾性分析2005—2016年复旦大学附属儿科医院5950例患者的临床资料,采用χ2检验进行发生率的比较和分析。结果:①住院例数位列前3位的分别是:川崎病2633例(44.3%),过敏性紫癜(HSP)2109例(35.4%),幼年特发性关节炎(JIA)574例(9.6%)。②除外HLP,其余病种住院人数均呈上升趋势。③近6年住院的风湿性疾病种类由原来的17种增长到目前37种。④SLE患者逐年增长(112/2348和197/3602,χ2=1.41,P=0.235),重症狼疮患者数亦较前增多(35/112和55/197,χ2=0.38,P=0.536)。⑤风湿性疾病合并巨噬细胞活化综合征(MAS)的发生率为7.2‰(43/5950),幼年型关节炎伴全身发作(sJIA)中有12.9%(26/201)出现过MAS,占风湿性疾病合并MAS总数的60.5%(26/43)。近6年风湿性疾病合并MAS(χ2=14.1,P<0.01),及sJIA合并MAS均明显增多(χ2=11.2,P<0.01)。⑥1.1%(64/5950)风湿性疾病相关肺部病变,幼年型皮肌炎(JDM)中24.4%(20/82)合并风湿性疾病相关肺部病变,占风湿性疾病相关肺部病变总人数的31.3%(20/64)。近6年风湿性疾病并发相关肺部病变及患者明显增多(χ2=5.66,P=0.017)。⑦儿童风湿性疾病病死率为3.7‰(22/5950),45.5%发生于SLE(10/22)。近6年SLE病死率有所下降(5/112和5/197,χ2=0.34,P=0.558)。结论:风湿性疾病住院患者病种及人数由多到少依次为川崎病、HSP、JIA、SLE及JDM。在每年总患者数相对稳定情况下,少见、疑难、危重病种逐年增多。虽近6年SLE仍是风湿性疾病主要死因,但病死率逐年下降。