Decreasing trend in the incidence of serious pneumonias in Finnish children with juvenile idiopathic arthritis.

OBJECTIVES: Children with juvenile idiopathic arthritis (JIA) may be predisposed to serious pneumonia due to modern disease-modifying anti-rheumatic treatment. In this nationwide retrospective study with clinical data, we describe the pneumonia episodes among children with JIA. METHODS: Patients under 18 years of age with JIA and pneumonia during 1998-2014 were identified in the National Hospital Discharge Register in Finland. Each individual patient record was reviewed, and detailed data on patients with JIA and pneumonia were retrieved, recorded, and analyzed. If the patient was hospitalized or received intravenous antibiotics, the pneumonia was considered serious. RESULTS: There were 157 episodes of pneumonia among 140 children with JIA; 111 episodes (71%) were serious (80% in 1998-2006 and 66% in 2007-2014). The mean age of the patients was 9 years. Forty-eight percent had active JIA and 46% had comorbidities. Disease-modifying anti-rheumatic drugs (DMARD) were used at the time of 135 episodes (86%): methotrexate (MTX) by 62% and biologic DMARDs (bDMARD) by 30%. There was no significant difference in the use of bDMARDs, MTX and glucocorticoids between the patient groups with serious and non-serious pneumonia episodes. During six of the episodes, intensive care was needed. Two patients (1.3%) died, the remaining ones recovered fully. CONCLUSIONS: Although the incidence of pneumonia and the use of immunosuppressive treatment among children with JIA increased from 1998 to 2014, the proportion of serious pneumonias in these patients decreased. There was no significant difference in the use of anti-rheumatic medication between patients with serious and non-serious pneumonia.Key Points• The incidence of serious pneumonias decreased from 1998 to 2014 among children with juvenile idiopathic arthritis (JIA).• There was no significant difference in the use of the disease-modifying anti-rheumatic medication between JIA patients with serious and non-serious pneumonias.• Active JIA, comorbidities, and combination medication were associated with nearly half of the pneumonias.

The Finnish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Finnish language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 173 JIA patients (1.2% systemic, 46.2% oligoarticular, 39.9% RF-negative polyarthritis, 12.7% other categories) and 100 healthy children, were enrolled in five paediatric rheumatology centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Finnish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Pneumonia in children with juvenile idiopathic arthritis in Finland 1999-2014: a nationwide retrospective register linkage study.

OBJECTIVES: To compare the incidence of pneumonia in children with juvenile idiopathic arthritis (JIA) to the aged-matched general population and to evaluate the use of anti-rheumatic medication among children with JIA and pneumonia. METHODS: The National Hospital Discharge Register collects data on ICD-diagnoses of hospital patients in Finland. From this register, patients with JIA under 18 years of age with pneumonia from 1999 through 2014 were identified. The control group consisted of age-matched patients derived from the general population with a diagnosis of pneumonia made in the same calendar year as the pneumonia of the JIA patients. The patient records of the children with JIA were scrutinised for the use of anti-rheumatic medication. RESULTS: We identified 223 pneumonias among the JIA patients (56,161 patient-years) and 53,058 pneumonias in the control group (17,546,609 person-years). The incidence of pneumonia in children with JIA was 386 (annual range 131-639) and in the control group 303 (annual range 225-438) per 100,000 person-years. The incidence of pneumonia increased significantly over time among JIA patients (p=0.013) and in the control group (p<0.001). Through 2007-2014 the rate of pneumonia was significantly higher among children with JIA (p<0.001) than control children. We found 150 JIA patients with pneumonia confirmed by positive chest radiograph. Altogether 47% of the JIA patients had combination medication. The use of methotrexate and biologic agents increased significantly over time (p=0.016 and p<0.001, respectively). CONCLUSIONS: The incidence of pneumonia increased in children with JIA and in the general population from 1999 to 2014. During 2007-2014 JIA patients had a significantly higher rate of pneumonia than age-matched controls. The use of active anti-rheumatic medication was common.

Fear of Injections and Needle Phobia Among Children and Adolescents: An Overview of Psychological, Behavioral, and Contextual Factors.

The purpose of this clinical update is to provide an overview of the fear of needles and needle phobia in children and adolescents including characteristics and diagnosis, prevalence and epidemiology, etiological factors, and treatment options. Needle-related fear and needle phobia present as significant needle-related distress and avoidance behavior. The etiology is biopsychosocial. These challenging conditions are more common in children and adolescents than in adults. The nurse-patient relationship enables the provision of suitable preparation before injection procedures. Nurses can use exposure-based interventions and incorporate coping strategies and teaching of parents and children. Nurses play a pivotal role in noticing the need for further treatment. Procedural needle-related distress is a complex phenomenon representing a continuum ranging from needle fear to more severe needle phobia. For patients with needle fear management and training methods used by nurses can possibly prevent a progression of the condition into needle phobia. In cases of needle phobia, a correct diagnosis made by a psychiatrist is necessary and enables referral to a psychotherapist with experience in treating children and adolescents with needle phobia.

Bloodstream infections among children with juvenile idiopathic arthritis: a prospective study from the onset of disease.

OBJECTIVES: To describe the incidence and nature of bloodstream infections (BSI) among children with juvenile idiopathic arthritis (JIA) followed-up prospectively from disease onset. METHODS: The Social Insurance Institution's (SII) national register on individuals with reimbursement for medication of chronic diseases was used to identify children with JIA from 2004 through 2011 and their medications. The National Infectious Disease Register (NIDR) collects data of all blood culture positive samples from all microbiology laboratories in Finland. We combined the NIDR and SII registers to identify JIA patients with BSI. Clinical and laboratory data of each JIA-BSI patient were collected from hospital records. RESULTS: There were 1604 JIA patients and 6630 person-years of follow-up. Five patients had BSI. During the first 5 years after diagnosis the cumulative emergence of BSI was 0.38% [95% confidence interval (CI) 0.16% to 0.92%]. The incidence rates were 7.5/10 000 follow-up years for JIA (95% CI 2.4-17.6) and 2.8/10 000 follow-up years for the age-matched general population (95% CI 2.7-2.9). The standardised incidence ratio was 3.0 (95% CI 1.2 to 7.2). The causative bacteria were Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli and Fusobacterium necrophorum. Three patients were on anti-rheumatic drugs, including two on TNF inhibitors. All patients responded rapidly to antimicrobial therapy and recovered uneventfully. CONCLUSIONS: Although BSI is rare among children with JIA, the incidence is 3-fold higher than among the general population.

The frequency and outcome of uveitis in patients with newly diagnosed juvenile idiopathic arthritis in two 4-year cohorts from 1990-1993 and 2000-2003.

OBJECTIVES: To retrospectively compare the frequency and outcome of uveitis between two cohorts of patients with newly-onset juvenile idiopathic arthritis (JIA) separated by a 10 year interval. METHODS: The diagnosis of JIA was made in 239 patients in 1990-1993 and in 240 patients in 2000-2003 by paediatric rheumatologists at the Rheumatism Foundation Hospital, Heinola, Finland. An ophthalmologist examined all the patients regularly and diagnosed uveitis. The demographics of the patients, type of JIA, frequency, medical treatment and outcome of uveitis were documented. RESULTS: The main outcome measures were the frequency and outcome of uveitis, the number of complications and the best corrected visual acuity (BCVA), need of corticosteroids and other immunosuppressive treatment. The frequency of uveitis was higher (25% vs. 18%) in the earlier cohort. The visual outcome was ≥0.5 in all JIA-uveitis patients except one in the earlier cohort. Complications were fewer (21% vs. 35%) and uveitis was milder according to the Standardisation of Uveitis Nomenclature (SUN) criteria in the later cohort. Remission of uveitis (33% vs. 42%) and arthritis (20% vs. 23%) in JIA-uveitis patients was similar in both cohorts after a follow-up of 6.6 and 5.9 years, respectively. Systemic corticosteroids were more commonly used (25% vs. 7%) in JIA-uveitis patients of the earlier cohort but the use of methotrexate was equal in both cohorts (65% vs. 67%). CONCLUSIONS: In this study with early and aggressive treatment and close monitoring the outcome of JIA-uveitis patients was favourable and visual loss was avoided in most cases.

Beware of the biologicals--hospitals may die: the Rheumatism Foundation Hospital, Heinola, Finland (1951-2010).

The first patient entered the Rheumatism Foundation Hospital, Heinola, Finland in July 1951. From that point on, the hospital helped patients suffering from rheumatic disorders. Specialists in the hospital actively developed treatments and published a large number of scientific articles in international journals. The hospital was well known internationally among people working in the field. Progress in the development of disease-modifying medication (biological agents in particular) has dramatically improved the life of patients with rheumatic diseases, but all effective treatments may also have adverse effects. In this article, we briefly review the history of the Rheumatism Foundation Hospital, which was closed permanently in March 2010 due to bankruptcy. The economical difficulties were caused primarily by the progress made in disease-modifying therapy, which decreased the need of rehabilitation and operative treatment of patients with rheumatic diseases. It seems that a great success in biological agents can carry "serious adverse effects", which may kill hospitals. This is an important primary observation, which should be noticed when the future of specialised institutes is planned.

[Medical treatment of juvenile idiopathic arthritis]. / Lastenreuman hoito kehittyy.

Although etiology of juvenile idiopathic arthritis (JIA) is currently not known, better understanding of immunologic pathways of inflammation and the development of new therapies with biologic agents have remarkably improved the treatment of JIA. However, approximately 30% of the patients with JIA do not seem to response adequately to conventional anti-rheumatic drugs but the arthritis runs a continuously active course and may lead to the evolution of erosions. Such patients benefit from biologic agents, of which the longest clinical experience comes from anti-TNF therapies. Molecules targeting IL-1, IL-6 and B- and T-lymphocytes are also used in the treatment of severe JIA.

First-year purchases of disease-modifying drugs of incident patients with chronic juvenile arthritis in Finland.

OBJECTIVES: To establish a nationwide overview on drug treatment of juvenile idiopathic arthritis (JIA), which is the most frequent form of chronic arthritis (JA) in children and adolescents. The emphasis is on the first 12 months after diagnosis, and any changes in medication practices during the early years of the present millennium are registered. METHODS: The Social Insurance Institution (SII) in Finland keeps a national register on individuals granted with a special reimbursement for medication of defined chronic diseases. From that register, we identified by the ICD-code of M08 all JA patients aged 16 years or under with an index day from 2000 through 2007. The prescription register of the SII showed the medication purchased for the patients. The register does not cover infused medications given in hospitals. We evaluated the first disease year's medication and the treatment strategy of the very first three months. RESULTS: Within our study period 2000-2007, the proportion of patients using methotrexate during the first year of treatment increased from 54 to 72% (p<0.001). The combination of two or more DMARDs became more popular (increased from 16 to 21%) as the initial treatment strategy. These changes parallel a decrease in per oral glucocorticoids. The proportion of JA patients receiving TNFα-blockers during the first year after diagnose reached the level of about 5% during the years 2004 to 007. CONCLUSIONS: The drug treatment of patients with recent onset JA has become more intensive during the course of the new millennium in Finland, a fact expected to improve the disease outcome.

Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis.

BACKGROUND: The purpose of this study was to investigate the long-term effects of adalimumab, a tumor necrosis factor alpha antagonist, in the treatment of uveitis associated with juvenile idiopathic arthritis. METHODS: Adalimumab was initiated in 94 patients with juvenile idiopathic arthritis to treat active arthritis and/or active associated uveitis. In 18 patients, therapy was discontinued after a short period because of inefficacy or side effects. The activity of uveitis (using Standardized Uveitis Nomenclature [SUN] criteria and clinical examination) and arthritis (number of swollen or active joints) was evaluated at the start and at end of the study. RESULTS: At the end of the study, uveitis was under good clinical control in two thirds of 54 patients (31% did not need any local treatment and 35% used only 1-2 corticosteroid drops a day), and one third had active uveitis (at least three corticosteroid drops a day). According to SUN criteria, adalimumab treatment for uveitis showed improved activity (a two-fold decrease in uveitis activity) in 28% of patients, with a moderate response in 16 patients, no change in a further 16 patients, and worsening activity (a two-fold increase in uveitis activity) in 13% of patients. The overall proportion of patients with active arthritis decreased. At the beginning of the study, 69% of patients with uveitis had more than two active joints, and at the end of the study only 27% had active joint disease. In 27 patients with juvenile idiopathic arthritis without uveitis on adalimumab, the number of active joints decreased from 93% to 59%. Systemic corticosteroid treatment could be stopped in 22% of patients with uveitis and in 11% of those without uveitis. Most of the patients had received methotrexate, other immunosuppressive therapy, or other biological drugs before initiating adalimumab. CONCLUSION: Adalimumab is a valuable option in the treatment of uveitis associated with active juvenile idiopathic arthritis.

An evaluation of dry eye symptoms and signs in a cohort of children with juvenile idiopathic arthritis.

OBJECTIVE: To determine the prevalence of dry eye symptoms and signs in children with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: A total of 192 children with JIA: 48 oligo-, 39 extended oligo-, 79 polyarthritis, and 26 with other types of arthritis (eight juvenile spondyloarthritis, five juvenile psoriatic arthritis, three mixed connective tissue diseases, two systemic onset arthritis, and eight undetermined arthritis) were interviewed for dry eye symptoms and tested with Schirmer test with anesthetic. Two thirds of the patients were female and the mean age of the patients was 13.1 years (range 10-16) and the mean duration of arthritis was six years (SD 4, 4). Thirty-one percent of the patients had a history of uveitis. Dry eye was defined as Schirmer test score

Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients: haplotype analysis in Finnish families.

OBJECTIVE: The SLC11A1 (formerly called NRAMP1) gene is important in natural resistance to a variety of intracellular infections mediated by macrophages and has been proposed as a candidate gene for autoimmune disease susceptibility. The aim of this study was to examine susceptibility in Finnish patients with persistent oligoarticular and polyarticular rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) due to the presence of the SLC11A1 locus on chromosome 2. METHODS: A total of 234 Finnish JIA nuclear families and 639 elderly Finnish controls without a history of JIA were evaluated for association with JIA at 3 intragenic single-nucleotide polymorphisms: an intragenic insertion/deletion, a promoter microsatellite (NRAMP1), and a 3' microsatellite (D2S1471). RESULTS: Analysis of marker haplotypes demonstrated a strong association of Finnish JIA with 6-marker, 4-marker, and 2-marker haplotypes. Most impressively, 1 of the 6-marker haplotypes showed an odds ratio (OR) of 4.0 (95% confidence interval [95% CI] 2.6-6.2) in all JIA patients, 3.5 (95% CI 1.9-6.5) in those with persistent oligoarticular JIA, and 4.1 (95% CI 2.5-6.7) in those with polyarticular RF-negative JIA. Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well-characterized strong susceptibility to DRB1*08 and *11 alleles. This SLC11A1 haplotype also had an additive effect with DRB1*JIASE in those with polyarticular, but not those with persistent oligoarticular, disease (P = 0.06, OR 2.9 [95% CI 0.9-9.2] versus P = 0.5, OR 1.6 [95% CI 0.4-6.0]). CONCLUSION: Taken together, these data provide support for the existence of a locus at or near SLC11A1 that is a strong susceptibility factor for JIA in Finnish patients.

HLA and susceptibility to juvenile idiopathic arthritis: a study of affected sibpairs in an isolated Finnish population.

OBJECTIVE: To determine the effects of class I (A, B, and C) and II (DRB1 and DQB1) HLA loci alleles and DRB1-DQB1 haplotypes on genetic susceptibility to juvenile idiopathic arthritis (JIA) in families with 2 or more affected siblings. METHODS: A total of 83 affected siblings belonging to 38 families and corresponding to 50 affected sibpairs, their parents, and 45 healthy sibs were typed for HLA in A, C, B, DRB1, and DQB1 loci. Two study designs were used to explore linkage and association: a case-population control design and a family design using the linkage method: identical-by-descent (IBD) allele-sharing and the association analysis methods. Associations in family data were analyzed using the independent transmission disequilibrium test (TDT) for linkage in the presence of association. This was supplemented by the family-based association test (FBAT) to look for association in the presence of linkage, and is robust for population stratification and phenotype-based selection of data. RESULTS: Significantly increased HLA allele frequencies among the affected siblings compared to Finnish bone marrow donors were observed for HLA alleles Cw4 (odds ratio, OR, 1.7), B27 (1.8), B35 (1.7), and DR8 (3.7). The observed ratio of sharing 0, 1, and 2 HLA haplotypes (A, C, B, DRB1, and DQB1) among affected sibpairs (ASP) was 10:23:17, significantly different from expected (p < 0.001), using a formula that takes into account disease prevalence and the sibling recurrence risk. In the univariate association analysis, both independent TDT and FBAT found significantly increased transmission of the DRB1*0801 and DQB1*0402 alleles and Cw*0401. Independent positive allele effects of Cw*0401, DRB1*0801, and DQB1*0402 as well as negative effects of Cw*0701 and DQB1*0302 were shown by the family-based association analysis of the joint allele main effects. Multi-allelic test for association of each locus confirmed significant associations of the DRB1 and DQB1 loci in the risk of JIA. We found DRB1*0801/DQB1*0402 haplotype to be strongly associated (p < 0.001) with JIA, supporting findings of the haplotype associations-based ASP design. CONCLUSION: Both linkage analysis of the affected sibpairs and association analysis of nuclear families with JIA provided overwhelming evidence of the major contribution of HLA to genetic susceptibility to JIA. The association analysis of HLA-A, C, B, DRB1, and DQB1 alleles by both TDT and FBAT tests confirmed in the Finnish population that the most significant associations prevailed for DRB1*0801, DQB1*0402, as expected from previous observations, and supported the independent role of Cw*0401.