The costs of early inflammatory joint disease: a population-based study in southern Sweden

OBJECTIVE: To study the costs and use of healthcare for patients during the first months with early joint inflammation, in a population-based prospective referral study in Southern Sweden. METHODS: Adult patients with arthritis for < 3 months and with onset of symptoms between 1 May 1999 and 1 May 2000 were referred from primary health centres to rheumatologists. Four clinical assessments were performed during a 6-month follow-up period. The direct medical costs for inpatient stays, outpatient visits, visits to general practitioners, and visits to health professionals, as well as costs for medication, radiographs, and laboratory tests were recorded from the onset of the disease up to 6 months of follow-up. Indirect costs for sick leave were also recorded. RESULTS: Fifty-six of 71 referred patients agreed to participate. Thirteen (23%) had RA, 21 (38%) had reactive arthritis (ReA), 14 (25%) had undifferentiated arthritis, and eight (14%) had other arthritides. The median cost per patient in the entire group was USD 3362. The median cost per patient in the RA group was USD 4385, and USD 4085 in the ReA group. There was no statistically significant difference in the median costs per patient in the different diagnostic groups. Sick leave accounted for 44% of the total costs in the entire group, and 46% and 47%, respectively, in the RA and ReA groups. CONCLUSION: The costs of early arthritis are already considerable during the first months of the disease following the onset of the symptoms. The indirect costs due to sick leave accounted for nearly half of the costs.     

Incidence of juvenile idiopathic arthritis in children in Estonia: a prospective population-based study

OBJECTIVE: To study the incidence rate of juvenile idiopathic arthritis (JIA) and its clinical subtypes in Estonia, to follow the course of the disease in newly diagnosed patients for 2 years, and to find the frequency of human leucocyte antigens (HLA) B27, DR1 and DR4 in JIA patients. METHOD: A population-based study involving prospective registration of new cases of JIA in 1998-2000 and their clinical follow-up for 2 years. RESULTS: In 1998-2000, 162 new cases of JIA were diagnosed. The mean annual incidence rate of JIA was 21.7 per 100 000 children aged 0-15 years (22.9 in girls and 19.3 in boys). During the investigation period, the incidence rate rose 3.5-fold. Oligoarthritis was the most frequent subtype (mean annual incidence rate of 11.7 per 100 000), followed by seronegative polyarthritis (4.4 per 100 000). HLA-DR1, B27 and DR4 were found respectively in 44.4, 28.6 and 11.1% of cases in which the analysis was performed. In HLA-B27-positive patients, inflammation markers of blood remained at a high level for a longer period compared with HLA-B27-negative patients. CONCLUSIONS: This is the first population-based study on the epidemiology of juvenile arthritis in Estonia in which the new classification criteria defined by the International League of Associations for Rheumatology (ILAR) have been used. In addition to environmental factors, an increase in awareness among family doctors is a probable reason for the rise in incidence during the study period. HLA-B27 might have predictive value as a marker of chronicity of inflammation.     

Campylobacter-triggered reactive arthritis: a population-based study

OBJECTIVE: To study the incidence and clinical picture of Campylobacter-associated reactive arthritis (ReA) and other reactive musculoskeletal symptoms in the population. METHODS: A questionnaire on enteric and extraintestinal, including specifically musculoskeletal, symptoms was sent to 870 consecutive patients with Campylobacter-positive stool culture and 1440 matched controls. Analysis of self-reported musculoskeletal symptoms with clinical examination was performed. RESULTS: Forty-five of the patients (7%) had ReA and eight (1%) had reactive tendinitis, enthesopathy or bursitis. No child had ReA. The arthritis was oligo- or polyarticular, and, in most cases, mild. HLA-B27 was positive in 14% of ReA patients. Of the 45 ReA patients, 37 had C. jejuni and 8 had C. coli infection. No controls had ReA. CONCLUSION: ReA is common following Campylobacter infection, with an annual incidence of 4.3 per 100000. At the population level, acute ReA is mild, more frequent in adults, and not associated with HLA-B27. Besides C. jejuni, C. coli can trigger ReA.     

Circulating soluble E-selectin in early rheumatoid arthritis: a prospective five year study

BACKGROUND: Soluble E-selectin (sE-selectin) is a marker of activation of vascular endothelium. OBJECTIVE: To examine serum levels of sE-selectin in a cohort of 85 patients with early rheumatoid arthritis (RA) followed up for five years. METHODS: sE-selectin levels were assessed annually using an enzyme linked immunosorbent assay (ELISA) and related to simultaneously obtained clinical and laboratory measures. Joint inflammation was evaluated by active joint count, functional status by Health Assessment Questionnaire (HAQ), and radiographic findings in hands and feet by the Larsen method. Laboratory tests included serum C reactive protein (CRP) level, erythrocyte sedimentation rate, blood haemoglobin level, white blood cell count (WBC), and platelet count. Area under the curve (AUC) was calculated for each variable, and Jonckheere's test for ordered alternatives was applied to assess significance of association between sE-selectin AUC tertiles and other variables. Baseline sE-selectin tertiles were related to change in Larsen score and HAQ score at five years. Odds ratios (OR) with 95% confidence interval (CI) were calculated using univariate and multivariate logistic regression. RESULTS: sE-selectin levels were associated with CRP level (p=0.012), WBC (p=0.037), active joint count (p=0.019), progression of joint destruction (p=0.038), and HAQ score at five years (p=0.021), but not with extra-articular symptoms or comorbidity. Baseline sE-selectin levels in the third tertile predicted the HAQ score at five years (OR 4.18, 95% CI 1.15 to 15.22). sE-selectin levels of patients did not differ significantly from those of healthy control subjects. CONCLUSION: The degree of activation of vascular endothelium is associated with activity and outcome of early RA.     

Magnetic resonance imaging in early rheumatoid arthritis: a multicenter,prospective study

To identify the magnetic resonance imaging (MRI) features of hands and wrists in early rheumatoid arthritis (RA). A total of 129 early arthritis patients (≤1 year) were enrolled in the study. At presentation, MRI of the hands was performed, with clinical and laboratory analyses. After a 1-year follow-up, clinical diagnosis of early RA or non-RA was confirmed by two rheumatologists. The characteristics of MRI variables at baseline in RA patients not fulfilling ACR 1987 criteria [RA-87(?)] were compared with those fulfilling ACR1987 criteria [RA-87(+)] and non-RA. In the 129 early arthritis patients, 90 were diagnosed with RA in a 1-year follow-up. There were 47.8 % (43/90) of the RA patients not fulfilling ACR 1987 criteria [RA-87(?)]. The scores of synovitis in RA-87(?) patients were similar with those in RA-87(+) [Synovitis score, 14.0 (IQR, 4.0–25.0) vs. 14.0 (IQR, 10.0–25.0), p?>?0.05]. Compared with those in non-RA, RA-87(?) patients had higher synovitis scores and occurrence of synovitis in proximal interphalangeal (PIP) joints [synovitis score, 14.0 (IQR, 4.0–25.0) vs. 6.0 (IQR, 2.0–14.5), p?=?0.046; occurrence of PIP synovitis: 53.5 vs. 27.3 %, p?=?0.02]. There was no significant difference of bone marrow edema, bone erosion, and tenosynovitis between RA-87(?) and non-RA. Synovitis in PIP joints was independent predictor for RA-87(?) [OR, 3.1 (95 %CI 1.2–8.1)]. High synovitis scores and synovitis in PIP joints on MRI were important in early RA, especially those not fulfilling ACR 1987 criteria.     

Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study

OBJECTIVE: To determine prognostic factors for remission in early rheumatoid arthritis. METHODS: 191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of <1.6, was used as the outcome measure. Baseline clinical, laboratory, genetic, and radiographic data (with radiographic scores determined by Sharp's method, modified by van der Heijde) were obtained. RESULTS: 48 patients (25.1%) fulfilled the remission criteria at the three year follow up visit, and 30 (15.7%) at three and five years. On univariate analysis by Fisher's exact test, remission at three years and persistent remission at five years were closely correlated with baseline DAS values, C reactive protein level, Ritchie score, health assessment questionnaire score, duration of morning stiffness, and to a lesser extent baseline total radiological scores and rheumatoid factor negativity. No significant correlation was found with sex, age, extra-articular manifestations, erythrocyte sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline independent variables predictive of remission were low DAS, Ritchie score, morning stiffness duration, and total radiographic score. CONCLUSIONS: Baseline prognostic factors for remission in early rheumatoid arthritis were mainly clinical markers of disease activity and radiological scores.     

Cardiovascular death in rheumatoid arthritis: a population-based study

OBJECTIVE: To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities. METHODS: Using the population-based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death. RESULTS: This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of >or=60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45-2.83), RA vasculitis (HR 2.41, 95% CI 1.00-5.81), and RA lung disease (HR 2.32, 95% CI 1.11-4.84). CONCLUSION: These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.     

The diagnostic value of streptococcal serology in early arthritis: a prospective cohort study

OBJECTIVE: To evaluate the diagnostic value of streptococcal serology in adult early arthritis patients in discriminating between post-streptococcal reactive arthritis (PSRA) and arthritis with other causes. METHODS: The antistreptolysin-O (ASO) and anti-DNase B tests were performed at baseline in 366 consecutive, newly referred early arthritis patients. After 1 yr of follow-up the patients were classified according to international classification criteria and were evaluated for the presence of persistent arthritis. The outcome measures were the predictive value of streptococcal serology for the diagnosis of PSRA and the ability of this serology to discriminate at the first visit between the self-limiting and persistent forms of arthritis. RESULTS: With a positive serological result, the probability of having PSRA increased from 2 to 9%, whereas the probabilities of having rheumatoid arthritis or undifferentiated arthritis continued to be high (23 and 29%). The serological tests did not discriminate between the self-limiting and persistent forms of arthritis. The major Jones criteria apart from arthritis were not observed. CONCLUSION: Streptococcal serology has no diagnostic value in adult early arthritis patients in whom major Jones criteria other than arthritis are not present.     

Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study

OBJECTIVE: To determine prognostic factors of radiologic damage and radiologic progression in early rheumatoid arthritis (RA). METHODS: A cohort of 191 patients with RA whose disease duration was shorter than 1 year were prospectively followed up for 3 years. Radiologic scores (as determined by Sharp's method, modified by van der Heijde) and radiologic progression were used as outcome measures. Numerous baseline clinical, laboratory, genetic, and radiographic data were obtained. RESULTS: The change in the total radiologic score for the patients followed up over 3 years was a mean +/- SD increase of 6.1 +/- 6.2. Radiologic progression was observed in 71 of the 172 patients for whom there were data at the end of the study. By univariate analysis with Fisher's exact test, radiologic scores and progression at followup were closely correlated with the baseline values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM and IgA rheumatoid factor positivity, antiperinuclear antibody positivity, radiologic scores, duration of morning stiffness, and RA-associated HLA-DRB1*04 genes. No correlation was demonstrated with sex, age, Disease Activity Score, swollen or tender joint counts, extraarticular manifestations, Health Assessment Questionnaire score, Ritchie Articular Index, patient's assessment of pain, positivity for anti-heat-shock protein 90-kd antibodies, anticalpastatin antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin antibodies, and HLA-DRB1*01 genes. The logistic regression analysis revealed that the only baseline values that were predictive of the 3-year radiologic scores were IgM rheumatoid factor positivity, DRB1*04 genes, pain score, and total radiologic score. Progression of joint damage was predicted by the ESR, IgM rheumatoid factor positivity, DRB1*04 genes, and erosions score at baseline. CONCLUSION: Prognostic factors for radiographic damage in early RA were identified. A combination of these baseline values allowed us to draw up a predictive arithmetic score that could be used to predict radiologic damage at 3 years and radiologic progression in individual patients.     

Quality of life and economic burden of illness in very early arthritis. A population based study in southern Sweden

OBJECTIVE: To measure health related quality of life (HRQOL) in patients with very early arthritis in a population based study in southern Sweden, and to compare HRQOL at baseline between the different diagnostic groups. Further, we investigated whether HRQOL at baseline correlated with the costs the patients incurred during the study. METHODS: Seventy-one adult patients with arthritis of less than 3 months' duration were referred from primary health care centers to rheumatologists. HRQOL was measured with the Arthritis Impact Measurement Scales (AIMS) and EuroQol at baseline. A comparison of HRQOL measures at baseline and the costs the patients incurred during the study was conducted in 56 of the patients. RESULTS: Twenty-seven (38%) patients had reactive arthritis (ReA), 17 (24%) undifferentiated arthritis, 15 (21%) rheumatoid arthritis (RA), 4 (6%) psoriatic arthritis, and the rest (11%) other diagnoses. Statistically significant differences were found between the 4 patient groups concerning the AIMS subscales of dexterity, household activity, activities of daily living (ADL) and pain, the patients with RA being most severely affected. There were no statistically significant differences between the 4 diagnosis groups concerning the EuroQol utility and EuroQol visual analog scale (VAS) scores. Of the AIMS subscales, the mobility, physical activity, household activity, ADL, and pain subscales correlated significantly with the incurred costs. Also the EuroQol utility scores and EuroQol VAS scores correlated significantly with the costs. Only the AIMS household activity subscale predicted the costs in the regression analysis. CONCLUSION: Patients with RA had significantly worse scores in the AIMS dexterity, household activities, ADL, and pain subscales compared to patients with other arthritides very early in the disease. The EuroQol generic quality of life instrument was less sensitive in detecting differences between patients with early arthritis than the disease-specific AIMS instrument. There was a correlation between the costs and the EuroQol utility scores and EuroQol VAS scores during the very first months of the disease, as well as with costs and the AIMS subscales of mobility, physical activity, household activity, ADL, and pain.     

Survivin improves the early recognition of rheumatoid arthritis among patients with arthralgia: A population-based study within two university cities of Sweden

ObjectivesThe aim of this study was to validate the use of survivin for preclinical recognition of rheumatoid arthritis (RA) among patients with unexplained arthralgia.MethodsSerum levels of survivin and the arthritis-specific autoantibodies RF and ACPA were measured in total of 5046 patients with musculoskeletal complains during 12 consecutive months in Gothenburg and in Umeå. Among them, 303 arthralgia patients were identified and prospectively followed.ResultsAfter 48 months, 12.2% of the arthralgia patients developed RA. Most of RA cases had high serum survivin, which increased the relative risk for RA (RR = 5.90, p = 3 × 10⁻⁷). Combination of survivin with autoantibodies was present in only 4.6% of the arthralgia patients and increased further the risk of RA and shortened time to RA development. Presence of any single autoantibody in the survivin-negative patients was associated with a minor risk for RA and had RA-free survival similar to the reference group.ConclusionThis study shows that measurement of survivin in serum improves estimation of RA risk and prospectively predicts RA development in patients with arthralgia. Survivin may indicate a phase preceding autoantibody production.     

Nursing home utilization in adults: a prospective population-based study

Rates of nursing home utilization between 1972 and 1986 were determined for 1,302 men and women living in an upper-middle-class community in Southern California. Leading diagnostic reasons for admission were dementia, cancer, and stroke, and the leading nondiagnostic reason for admission was an inability to carry out activities of daily living. In this cohort, rates of nursing home utilization increased with age. Women at all ages used nursing homes at a higher rate than men, although their probability of survival once admitted was greater. Admission rates were higher over time or prior to death than when observed cross-sectionally. Rates were highest in the year prior to death but declined at time of death.     

Incidence and prevalence of juvenile arthritis in an urban population of southern Germany: a prospective study

OBJECTIVE: To ascertain the incidence and prevalence of juvenile arthritis in a German urban population. METHODS: All 766 paediatricians, orthopaedists, and rheumatologists working in practices or outpatient clinics in 12 south German towns were asked to report all patients who consulted them for juvenile arthritis during the year 1995. Patients with continuing symptoms were followed up for 9-12 months to obtain a final diagnosis. Extended measures of quality control were taken to control for known biases. RESULTS: Of 457 reported cases, 294 were diagnosed with para-/postinfectious arthritis (PPA), 78 with juvenile chronic arthritis (JCA), and 18 with other forms of arthritis. Half of the PPA cases were classified as transient synovitis of the hip (SH). For JCA the reported annual incidence was 6.6 and the prevalence 14.8 per 100 000 subjects under 16 years of age. For PPA the reported incidence was 76 and the prevalence 4.4 per 100 000 subjects under 16. The incidence of rheumatic fever was clearly below 1 per 100 000 people under 16. A correction model was used to control for known biases and to adjust the estimates accordingly. CONCLUSIONS: The results of this first prospective study on the incidence and prevalence of juvenile arthritis in Germany are consistent with a retrospective study performed in the Berlin area. Based on these results it was estimated that the annual frequency of juvenile arthritis in Germany is as follows: 750-900 incident JCA cases, 21 000 incident SH cases, and 21 000 incidence cases of other forms of PPA a year. The number of incidence cases of rheumatic fever is expected to be markedly lower than 150 a year. The total prevalence is expected to be 3600-4350 JCA cases, 2250-3000 SH cases, and the same number of other forms of PPA.     

Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity

The present series comprises all families (n = 77) with haemophilia B in Sweden and may be considered to be representative for the purposes of a population-based study of mutational heterogeneity. The 77 families (38 severe, 10 moderate, 29 mild) had 51 different mutations in total. Thirteen families had total, partial or small deletions, two had mutations in the promoter, eight families had splice site mutations, 14 had nonsense and the remaining 41 had missense mutations. Ten of the mutations, all C-->T or G-->A, recurred in 1--6 other families. Using haplotype analysis of seven polymorphisms in the factor IX (FIX) gene, we found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate haemophilia, 23 (48%) had a sporadic case of haemophilia compared with 31 families out of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations, 11 out of 23 of the mothers were proven carriers and, in the remaining seven families, it was not possible to determine carriership. Eleven of the 48 patients (23%) with severe haemophilia B developed inhibitors and all of them had deletions or nonsense mutations. Thus, 11 out of 37 (30%) patients with severe haemophilia B as a result of deletion/nonsense mutations developed inhibitors compared with 0 out of 11 patients with missense mutations. The ratio of male to female mutation rates was 5.3 and the overall mutation rate was 5.4 x 10(-6) per gamete per generation.     

Fractures after rheumatoid arthritis a population-based study

In a population-based study, the incidence of osteoporotic fractures in patients who have been diagnosed as having rheumatoid arthritis was investigated. This incidence was found to be increased, though not dramatically so: the relative risk for hip fracture, for example, was 1.5. Univariate analyses generally indicated increased risk associated with increasing age, earlier age at diagnosis of rheumatoid arthritis, disability, impaired ambulation, steroid use, and thinness, and decreased risk associated with obesity and estrogen use. In multivariate analyses, only aging, impaired ambulation, and thinness were identified as independent risk factors.     

Infections in outpatients with systemic lupus erythematosus: a prospective study

The objective of this study was to assess the incidence and risk factors of infections in 200 SLE outpatients. All outpatients with active or inactive SLE without infections in the previous month were included. They were assessed every 3 months. Major infections were those requiring hospitalization and parental antibiotic therapy; minor infections required oral or topical therapy. Sociodemographic, disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), therapy and laboratory variables were evaluated. After a follow-up of 22+/-7 months, 65 (32%) patients had infections; 35% of those were major. The most common sites for infection were urinary (26%), skin (23%), systemic (12%), and vaginal (9%). At infection onset, 50 of 65 patients (77%) had disease activity, with a mean SLEDAI score of 6.1. The variables significantly associated with infection in the univariate analyses were the presence of disease activity, SLEDAI score, renal activity, prednisone dose, and IV cyclophosphamide. The only variable associated with infection in the multivariate analyses was a SLEDAI score of 4 or higher. Most infections in SLE outpatients were single, minor, non-life threatening, and associated with disease activity independently of sociodemographic and therapeutic factors.     

Reinfection with Lyme borreliosis: a retrospective follow-up study in southern Sweden

In a 5-y retrospective follow-up study in southern Sweden that initially included > 1000 individuals with previously diagnosed erythema migrans, factors that influenced the risk of reinfection with Lyme borreliosis were elucidated. The total frequency of reinfection was 4% and the number of tick bites influenced the risk of reinfection: those bitten > 10 times during the observation period had a 4-8-fold increased risk compared with those bitten <5 times. Women manifested to a greater extent than men although both genders were bitten equally by ticks, thus indicating that women may be more susceptible to reinfection. All reinfected women were > 44 y old. The county of Kalmar including Oland was found to be highly endemic for reinfection with Lyme borreliosis. Thus the number of tick bites, gender, age and study area influenced the risk of reinfection.     

Rheumatoid arthritis and pyoderma gangrenosum: a population-based case-control study

Clinical Rheumatology - The association between pyoderma gangrenosum (PG) and rheumatoid arthritis (RA) was not investigated in the setting of controlled studies. The risk of PG among patients with...