Pain interference and associated factors in young adults with juvenile idiopathic arthritis.

Objective: Pain is a common and distressing feature of juvenile idiopathic arthritis (JIA). Pain interference (PI) is underexplored in long-term conditions such as JIA. The aim of this study was to explore the factors associated with PI in young adults with JIA. Methods: All consecutive JIA patients aged 18-30 years in three tertiary rheumatology and rehabilitation centres in Finland between September 2015 and April 2016 were included. The patients completed questionnaires addressing demographics, disability, depressive symptoms, pain anxiety, pain intensity, and PI. PI was measured with a single item from the RAND-36 questionnaire. Five response categories were coded into three groups: patients reporting 'extremely', 'quite a bit' or 'moderate' were classified as having significant PI; 'a little bit' as having minor PI; and 'not at all' as having no PI. A leisure-time physical activity metabolic equivalent of task (LTPA MET) was calculated. Statistical comparisons between PI and categorical variables were made using chi-squared or Fisher-Freeman-Halton tests. Results: Of the total 195 patients, 97 (50%) patients reported PI. PI was associated with a wide spectrum of sociodemographic and disease-related variables. Pain intensity scores were higher in patients expressing greater PI (p < 0.001). Greater PI was associated with higher disability (p < 0.001), higher pain anxiety scores (p < 0.001), lower LTPA MET (p = 0.027), and poorer leisure-time activity (p < 0.001). Conclusions: PI is common in young adults with JIA. We suggest that PI should be taken into account in future outcome studies exploring the impact of pain in children and young adults with JIA.

Disability and health-related quality of life are associated with restricted social participation in young adults with juvenile idiopathic arthritis.

OBJECTIVES: To describe a cohort of Finnish juvenile idiopathic arthritis (JIA) patients, to recognize those young adults who are at risk of becoming socially restricted by their long-term rheumatic disease, and to assess which areas of self-rated health-related quality of life (HRQoL) are associated with the emergence of restricted social participation. METHODS: A total of 195 young adults with JIA completed questionnaires addressing demographics, health behaviour, physical activity, functional ability, HRQoL, depressive symptoms, and self-esteem. Patients were classified as having non-restricted social participation if they were engaged in studying, working, maternity leave, or military service, and restricted social participation if they were unemployed or on disability pension. RESULTS: Of the patients, 162 (83%) were considered as having non-restricted social participation and 33 (16%) restricted social participation. Among patients with restricted social participation, five (15%) were on disability pension and 28 (85%) were unemployed. Patients with restricted social participation participated less in leisure-time non-physical activities (p = 0.033), felt more disturbed during their leisure time (p = 0.010), had lower self-esteem (p = 0.005), and had higher disability scores (p = 0.024). HRQoL scores revealed statistically significant differences between the groups: physical functioning (p = 0.043), social functioning (p = 0.016), and emotional well-being (p = 0.049) were all lower in patients with restricted social participation. CONCLUSIONS: Socially restricted patients showed a higher degree of disability, and lower levels of physical functioning, self-esteem, emotional well-being, and social functioning. These patients should be recognized earlier and interventions provided to enhance their social participation.

Cost-effectiveness modelling of sequential biologic strategies for the treatment of moderate to severe rheumatoid arthritis in Finland.

OBJECTIVE: The main objective was to compare the cost-effectiveness of therapeutic options in moderate or severe rheumatoid arthritis (RA) when a clinical response to a first TNF-blocker, either etanercept (ETA), adalimumab (ADA), or infliximab (INF), is insufficient. METHODS: Effectiveness criteria were defined as remission (RS), low disease activity (LDAS), and moderate to high disease activity (MHDAS). Cost-effectiveness was derived as cost per day in RS and in LDAS using simulation modelling to assess six sequential biologic strategies over 2 years. Each sequential treatment strategy was composed of three biologic agents and included a first anti-TNF agent, ETA, ADA or INF, followed by either abatacept (ABA) or rituximab (RTX) as a second therapeutic option in case of an insufficient response, followed by another anti-TNF agent in case of further insufficient response. RESULTS: Over two years and taking into account biologic costs, the following estimated mean costs per day in RS and LDAS were respectively of €829 and €428 for the biologic sequence composed of ADA-ABA-ETA, €1292 and €516 for the sequence ADA-RTX-ETA, €829 and €429 for the sequence ETA-ABA-ADA, €1292 and €517 for the sequence ETARTX- ADA, €840 and €434 for the sequence INF-ABA-ETA, and €1309 and €523 for the sequence INF-RTX-ETA. CONCLUSION: The treatment sequences including ABA as the second biologic option appear more cost-effective than those including RTX in a patients with moderate to severe RA and an insufficient response to a first anti-TNF agent.

Prevalence of antibodies against Chlamydia trachomatis and incidence of C. trachomatis-induced reactive arthritis in an early arthritis series in Finland in 2000.

OBJECTIVE: To study the prevalence of different serotypes of Chlamydia trachomatis antibodies and the incidence of C. trachomatis-induced reactive arthritis (ReA) among patients with early arthritis in a defined population. METHODS: Serum samples were collected from a cohort of 122 adult patients in the age group 18-65 years included in the Kuopio 2000 Arthritis Survey. Antibodies against C. trachomatis serotypes C, E, and G were studied using enzyme immunoassay (EIA) tests among patients and in a control cohort of 78 adults without any joint symptoms. The incidence assessment for Chlamydia-induced ReA was based on a ligase chain reaction (LCR) test in urine and clinical symptoms and signs appropriate for ReA. RESULTS: Of 122 patients, with the baseline diagnosis of rheumatoid arthritis (RA) in 11, spondyloarthropathy (SpA) in 28, and undifferentiated arthritis (UA) in 83 cases, 42 (34%) showed immunoglobulin (Ig)G or IgA antibodies against at least one serotype C, E, or G. Among the patients with UA the prevalence was significantly increased compared with the controls (p = 0.010). C. trachomatis-induced ReA arthritis was diagnosed in only three patients with the LCR test. On this basis the incidence of C. trachomatis-induced arthritis was 5.4/100 000 [95% confidence interval (CI) 1.1-15.7] in the age group 18-65 years. CONCLUSION: Antibodies against C. trachomatis were most common in patients with UA reflecting the fact that cases with chlamydia-induced ReA are included in this subgroup.

Serum soluble CD30 in early arthritis: a sign of inflammation but not a predictor of outcome.

OBJECTIVE: To evaluate serum soluble CD30 levels (sCD30) in an early arthritis series and assess their ability to predict the outcome in patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA) at one year follow-up. METHODS: Serum sCD30 levels were measured by ELISA from 92 adult patients with RA and UA at baseline and from 60 adult controls. The patients were followed up for one year in the Kuopio 2000 Arthritis Survey. Receiver operating characteristic (ROC) curves were constructed to determine cut off points of sCD30 in RA and UA that select the inflammatory disease from controls. Sensitivity, specificity and positive likelihood ratio, and their 95 % CIs were calculated for sCD30 levels in RA and UA. RESULTS: Median serum sCD30 levels were higher in RA 25.1 (IQ range 16.3-38.6) IU/ml (p<0.001) and in UA 23.4 (15.4-35.6) IU/ml (p<0.001) than in controls 15.1 (10.7-20.8) IU/ml. No differences were recorded between RA and UA (p=0.840). Serum sCD30 levels at baseline did not predict remission at one year follow-up. CONCLUSION: Serum sCD30 levels were higher in RA and UA than in controls at baseline but they did not predict remission at one year follow-up in this series.

Sensitivity and specificity of autoantibodies binding to citrullinated carboxyterminal telopeptides of types I and II collagens in an early arthritis series.

OBJECTIVE: To assess the specificity and sensitivity of autoantibodies binding to citrullinated carboxyterminal telopeptides of types I and II collagens in an early arthritis series. METHODS: A cohort of 146 patients from the Kuopio 2000 Arthritis Survey having RA, AS, PsA, ReA, uSpA or undifferentiated arthritis were studied. Autoantibodies binding citrullinated types I and II carboxytelopeptides were measured in two different inhibition ELISA assays. Sera from 135 adult persons were used as controls. RESULTS: In RA, the sensitivities were 0.83 with long type I telopeptide and 0.78 with long type II telopeptide and the respective specificities were 0.94 and 0.93, while the corresponding values in other inflammatory joint diseases were much lower. The likelihood ratio in RA increased with longer peptides from 4.20 to 14.06 for type I telopeptide and from 2.74 to 11.67 for type II telopeptide. CONCLUSION: The antibody assay using long telopeptide from type I collagen was the most specific and sensitive method in every diagnostic category, although in the arthritides other than RA, binding was much less abundant and possibly citrulline-independent.

Change of diagnoses and outcome of patients with early inflammatory joint diseases during a mean 13-month follow-up.

OBJECTIVE: To assess the state of the disease and verify the diagnoses during a 7-24-month follow-up of adult patients with newly diagnosed inflammatory joint diseases in a defined population. METHODS: Patients with previously undiagnosed synovitis in at least one peripheral joint or signs of inflammation in sacroiliac, glenohumeral or hip joints were enrolled on their first hospital visit in 2000 and followed-up for up to 24 months in Kuopio. RESULTS: A total of 138/173 adult patients completed a mean 13-month follow-up. During the follow-up the diagnosis was specified for 15/81 (19%) patients previously classified as undifferentiated arthritis (UA). Eight patients developed rheumatoid arthritis (RA). Of 28 patients with RA, 92% were on disease-modifying anti-rheumatic drugs (DMARDs) and 75% had a combination treatment with two or more DMARDs. According to the diagnosis at baseline, 75% of cases with RA, 38% with spondyloarthropathies (SpAs) and 42% with UA had active synovitis or arthralgia at follow-up. In multivariate analysis, older patients at disease onset were less likely to be in remission (p = 0.011). CONCLUSION: The diagnosis could be specified for 19% of patients with UA. Fifteen of 20 patients with RA had an active disease despite treatment with DMARDs. Patients with SpAs and UA had a better short-term outcome. Patients with active disease need aggressive therapy in all age groups.

Assessing the intra- and inter-reader reliability of dynamic ultrasound images in power Doppler ultrasonography.

OBJECTIVE: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. METHOD: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. RESULTS: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (kappa = 0.52-0.82). CONCLUSIONS: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry.

OBJECTIVE: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. METHODS: Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). RESULTS: Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). CONCLUSION: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.

Joint symptoms and diseases associated with moisture damage in a health center.

Rheumatic diseases do not usually cluster in time and space. It has been proposed that environmental exposures may initiate autoimmune responses. We describe a cluster of rheumatic diseases among a group of health center employees who began to complain of symptoms typically related to moldy houses, including mucocutaneous symptoms, nausea and fatigue, within a year of moving into a new building. Dampness was found in the insulation space of the concrete floor below ground level. Microbes indicating mold damage and actinobacteria were found in the flooring material and in the outer wall insulation. The case histories of the personnel involved were examined. All 34 subjects working at the health center had at least some rheumatic complaints. Two fell ill with a typical rheumatoid factor (RF)-positive rheumatoid arthritis (RA), and 10 had arthritis that did not conform to any definite arthritic syndrome (three met the classification criteria for RA). Prior to moving into the problem building one subject had suffered reactive arthritis, which had then recurred. Another employee had undiagnosed ankylosing spondylitis and later developed psoriatic arthritis, and another developed undifferentiated vasculitis. A total of 16 subjects developed joint pains, 11 of these after beginning work at the health center. Three subjects developed Raynaud's symptom. Fourteen cases had elevated levels of circulating immune complexes in 1998, 17 in 1999, but there were only three cases in 2001, when the health center had been closed for 18 months. The high incidence of joint problems among these employees suggests a common triggering factor for most of the cases. As some of the symptoms had tended to subside while the health center was closed, the underlying causes are probably related to the building itself and possibly to the abnormal microbial growth in its structures.

Comparison of low-dose rofecoxib versus 1000 mg naproxen in patients with osteoarthritis. Results of two randomized treatment trials of six weeks duration.

OBJECTIVE: To compare the efficacy and safety of rofecoxib 12.5 mg once daily to naproxen 500 mg twice daily in patients > or = 40 years of age with knee or hip osteoarthritis (OA). METHOD: Two identical 6-week, randomized, double-blind studies were conducted (1 in Africa, Australia, Europe, Canada, Mexico, & South America; 1 in Asia). Primary endpoints were pain walking on a flat surface, patient global assessment of response to therapy, and investigator global assessment of disease status. RESULTS: Overall, 944 patients participated. For all efficacy endpoints, treatment effects for rofecoxib and naproxen were comparable and seen at the first measures of efficacy. Both compounds were generally well-tolerated, with an improved gastrointestinal safety profile for rofecoxib versus naproxen. CONCLUSIONS In these studies, rofecoxib 12.5 mg once daily (the lowest indicated dose) and naproxen 500 mg twice daily showed similar treatment effects in OA patients. Rofecoxib and naproxen were generally well tolerated.

Current features of peptic ulcer disease in Finland: incidence of surgery, hospital admissions and mortality for the disease during the past twenty-five years.

BACKGROUND: Medical therapy of peptic ulcer disease (PUD) has improved dramatically during the past 20 years with the introduction of modern antisecretory drugs as well as eradication therapy of Helicobacter pylori. During the 1990s, there has been a 3-fold increase in the consumption of histamine-2-receptor antagonists and proton-pump inhibitors, but also an 8-fold increase in the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) in Finland. METHODS: The incidence of surgery, hospital admissions and mortality for PUD was analysed between 1972 and 1999; the data were collected from the National Research and Development Centre for Welfare and Health and from the National Centre for Statistics. In the analysis, the codes of the Intemational Statistical Classification of Diseases 8-10 were used. RESULTS: In 1987, 11.9 elective operations (per 10(5) inhabitants) were performed (mean of 2 consecutive years), but only 1.3 in 1997, a reduction of 89%. In 1987, 5.2 emergency operations for ulcer perforation or bleeding were performed, whereas there were 7.5 in 1997, an increase of 44%. The annual hospital admission rate increased from 38.3 admissions (per 10(5) inhabitants) in 1972 (mean +/- s (standard deviation) of 5 consecutive years) to 68.7 in 1992. This 79% increase was mainly due to bleeding from gastric ulcer in elderly women. The overall annual mortality rate increased between 1972 and 1992 from 6.4 to 8.4 deaths (per 10(5) inhabitants), i.e. by 31%. The mortality rate from ulcer perforation and haemorrhage increased from 4.2 deaths in 1972 to 7.3 deaths in 1992, i.e. by 74%. CONCLUSIONS: The increasing incidence rates of emergency surgery, hospital admissions and mortality for PUD in the 1980s and 1990s have started to decrease in the most recent years in Finland. This epidemiologic change probably reflects both the demographic change and an increased consumption of NSAIDs, among the elderly people, in particular. The most recent epidemiologic change may reflect an increased consciousness about the harmful effects of conventional NSAIDs. Regardless of the constantly occurring emergency surgery, elective surgery for PUD is hardly ever required today.

A cluster of inflammatory rheumatic diseases in a moisture-damaged office.

OBJECTIVE: To describe a cluster of inflammatory rheumatic diseases in an office workplace that suggests the presence of an environmental trigger. METHODS: There had been an indoor air problem in the workplace since the early 1990s. Large areas of the outer walls of the building were found to be moisture-damaged and contaminated by microbial growth. Case histories of the personnel were studied, and their working areas were related to the areas with highest microbial contamination. The incidence of inflammatory rheumatic diseases was compared with the statistics of the same geographic area. RESULTS: Ten patients with inflammatory rheumatic diseases (3 rheumatoid arthritis, 4 ankylosing spondylitis, 2 Sjögren's syndrome, and one of psoriatic arthritis) entitled to specially reimbursed medication were diagnosed in 1987-2000 (seven cases in 1995-1998). The incidence density ratio computed for the period 1987-2000 was 6.8 (95% confidence interval 3.6-13.0) for all office personnel and 13.2 (6.0-29.0) for those working close to the wall sustaining the worst damage. CONCLUSION: The accumulation of chronic inflammatory rheumatic diseases in a single workplace suggests that some environmental exposure in this damp office had triggered the diseases.

Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders.

Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building. Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-alpha in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure. The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 microg x mL(-1), range 0-206.5 microg x mL(-1)), as compared to that during vacation (0.4 microng x mL(-1) range 0-3.7 pg x mL(-1)) (p = 0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p = 0.028). In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.

Mortality associated with cervical spine disorders: a population-based study of 1666 patients with rheumatoid arthritis who died in Finland in 1989.

OBJECTIVE: To evaluate the mortality associated with cervical spine deformities in rheumatoid arthritis (RA) based on national data. METHODS: The role of rheumatoid disorders of the cervical spine as a cause of death was studied in 1666 subjects who died in Finland in 1989 and had been entitled under the national sickness insurance scheme to receive reimbursed medication for RA. Death certificates and certificates for drug reimbursement of these 1666 patients and the clinical files of 853 patients were examined for the mention of cervical spine disorders. Thereafter, the cervical spine radiographs and detailed clinical histories of patients with diagnosed cervical spine disorder were evaluated separately. RESULTS: According to the official death certificates, cervical spine disorder was not an underlying, contributory or immediate cause of death in any of these patients. Cervical spine abnormalities had been diagnosed only in 38/853 (4.5%) patients. Cervical spine radiographs from 33 patients were available for examination, and in 17 patients cervical spine deformities were found to be severe enough to be a potential cause of fatal complications. Among these 17 cases, four sudden and four postoperative deaths were recorded (one after cervical spine operation) and three patients were suffering from quadriparesis or paraparesis at the time of death. Among the other 16 patients with cervical spine radiographs, the cervical deformities were less severe and their death histories differed from those of the group with more severe deformities. CONCLUSIONS: Cervical spine disorders in RA should be diagnosed early and treated actively to prevent severe and potentially fatal complications. Deaths caused by these disorders are rare, but they should be remembered when the death certificates are written.

Autologous peripheral blood stem cell transplantation in a patient with severe mixed connective tissue disease.

A 65-year old man with mixed connective tissue disease (MCTD) and severe therapy resistant polymyositis was considered for high-dose cyclophosphamide (200 mg/kg) supported by autologous stem cell transplantation (ASCT). During a 21 months follow-up there has been a significant subjective, but objectively only a slight improvement in muscle strength. Initially the levels of serum creatine kinase and serum aldolase normalised, but are at 21 months at about the same level as before ASCT. Based on histopathological examination there is still active myositis. Our case would suggests that this treatment may have some efficacy in MCTD with severe polymyositis although longer follow-up is needed.

Intensive treatment of rheumatoid arthritis reduces need for dialysis due to secondary amyloidosis.

We have analysed changes in the intensity of treatment of patients with rheumatoid arthritis (RA) and its influence on the number of patients with RA and secondary amyloidosis (SA) admitted to dialysis due to end-stage renal disease. The number of visits and patients at the rheumatological outpatient clinic because of RA, the type of medication used in 1988-1997, and the number of patients with RA and SA on dialysis from 1989 to 1999 were extracted from the data set of Kuopio University Hospital. The intensity of treatment could be evaluated as the treated number of patients with RA and the number of visits at the outpatient clinic. Both the numbers increased from 1988 to 1996, patients under treatment from 201 to 550 and visits from 1091 to 2198, respectively. In 1997, the number of patients still increased (n=637), although the number of visits started to decline (n=2054), partly due to better collaboration of health centres. A marked shift from use of only symptomatic treatment or one disease-modifying antirheumatic drug (DMARD) to more common use of immunosuppressants and/or combinations of at least two DMARDs occurred in the five years from 1992 to 1997. In 1988, the figures for only nonsteroidal anti-inflammatory drugs or only glucocorticoids or one immunosuppressive drug were 24%, 8%, and 9%, and in 1997, 4%, 3%, and 22%, respectively. In 1997, 43% of the patients were treated with combinations of two or more DMARDs. The number of patients with RA on dialysis treatment and the number of new admissions each year due to SA decreased from 11 to 2 and from 5 to none, respectively. At the beginning of year 2000 there was only one patient with RA and SA on dialysis.