OBJECTIVE--To assess the potential of markers of collagen metabolism to reflect disease processes in rheumatoid arthritis (RA). METHODS--Serum (S) and synovial fluid (SF) from 59 patients with RA, and a knee joint effusion and serum from 90 control subjects were studied with radioimmunoassays for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively). The breakdown of type I collagen was quantified with a radioimmunoassay for the cross linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS--About 50% of the patients had increased S-ICTP and S-PIIINP values, whereas S-PINP was increased in only 20% of the patients. The mean SF:S ratios of these markers varied between 4 (for ICTP) and 340 (for PIIINP), indicating that markers of collagen metabolism are formed locally and then released into the circulation. SF-PINP and SF-PIIINP correlated with each other (rs = 0.86, p
The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists.
Cognitive decline is commonly stated as one of the main risk factors for delirium. The aim was to assess the importance of a delirium episode as a symptom of an underlying dementia among community dwelling healthy elderly people in a prospective 2 year follow up study. The study patients consisted of 51 people living at home and older than 65 years of age, without severe underlying disorders including diagnosed dementia, admitted consecutively as emergency cases to hospital because of an acute delirious state and followed up for 2 years. The diagnosis of delirium and dementia were based on the DSM-III-R criteria. The community dwelling patients were evaluated and tested annually by a clinical investigator, a geriatric study nurse, and a neuropsychologist. The medical records of the institutionalised patients were also evaluated. Dementia was diagnosed immediately after the assurance that delirium symptoms had subsided in 14 out of 51 subjects (27%) and the additional 14 subjects were diagnosed as being demented during the 2 year follow up, 28 out of 51 patients (55%) altogether. Alzheimer's disease or mixed dementia was diagnosed in 14 out of 51 patients (27%), vascular dementia in 10 (20%), and dementia with Lewy bodies in two (4%). One case of alcoholic dementia and one case of a non-alcoholic hepatic encephalopathia were also found. A delirium episode is often the first sign of dementia requiring attention from medical and social professionals.
To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients.
322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes.
The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes.
When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.
To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).
One hundred thirty-four haplotypes from 67 Finnish RA patients and 77 control haplotypes were analyzed for HLA-DRB1 loci, associated alleles of the HLA-DQB1 locus, alleles of the type 2 transporter-associated antigen processing (TAP2) genes, and HLA-B27. In addition, a panel of microsatellite markers within the HLA class I and class III regions was studied.
The frequency of HLA-DRB1*04 in the haplotypes of RA patients was found to be 34% (45 of 134) compared with 14% (10 of 72) in control haplotypes (P = 0.004). The frequency of HLA-DRB1*13 was decreased in RA haplotypes (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72) (P = 0.000031). The decrease in DRB1*13 was not secondary to the increase in DRB1*04, since it was also found among DRB1*04-negative haplotypes (P
Monetary value of lost productivity over a five year follow up in early rheumatoid arthritis estimated on the basis of official register data on patients' sickness absence and gross income: experience from the FIN-RACo trial.
To explore the monetary value of rheumatoid arthritis related loss of productivity in patients with early active disease.
In a prospective cohort substudy of the FIN-RACo Trial, 162 patients with recent onset rheumatoid arthritis, aged 18 to 65 years and available to the workforce, were followed up for five years. Loss of work productivity in euros 2002 was estimated by data on absence for sickness and on income (human capital approach) from official databases. Treatment responses were evaluated by area under the curve (AUC) of the ACR-N measure and by increase in number of erosions in radiographs of hands and feet. The health assessment questionnaire (HAQ) at six months was linked to the International Classification of Functioning, Disability and Health (ICF).
In all, 120 (75%) patients, women more often (82%) than men (61%) (p=0.002), lost work days. The mean lost productivity per patient-year was euro7217 (95% confidence interval (CI), 5561 to 9148): for women, euro6477 (4858 to 8536) and for men, euro8443 (5389 to 12,898). There was an inverse correlation with improvement: euro1101 (323 to 2156) and euro14 952 (10,662 to 19,852) for the highest and lowest quartiles of AUC of ARC-N, respectively. Lost productivity was associated with increase in the number of erosions and with disability in "changing and maintaining body position" subcategory of the ICF.
Despite remission targeted treatment with disease modifying antirheumatic drugs, early rheumatoid arthritis results in substantial loss of productivity. A good improvement in the disease reduces the loss markedly.
Cites: J Occup Environ Med. 2003 Dec;45(12):1303-1114665817
To study whether enterobacteria and Gram-positive bacterial cell walls (BCW) derivedfrom normal intestinal microbiota are involved in the etiopathogenesis of early rheumatoid arthritis (RA).
Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were isolatedfrom patients with early RA (the average duration of 5 months) and the controls (other types of inflammatory arthritis). The mononuclear cell proliferation and tumor necrosis factor-alpha (TNF-alpha) responses to heat-killed Salmonella enteritidis (SE). Yersinia enterocolitica (YE), and Escherichia coli (EC), and to Gram-positive BCW derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (EA), Eubacterium limosum (EL), Lactobacillus casei (LC), and Lactobacillus fermentum (LF), and a BCW derived from a pathogen, Streptococcus pyogenes (SP) were investigated.
39% or 56% of patients with early RA showed significant proliferation responses by PBMC or SFMC against enterobacteria, respectively. In other types of arthritis, corresponding figures were 59% or 66%. When BCW were used as antigens, 8.1% or 23% of patients with early RA showed proliferation responses by PBMC or SFMC, respectively. In other types of arthritis the corresponding figures were 7.5% or 35%, respectively. However, TNF-alpha production by SFMC stimulated by EA BCW, SE, YE or EC, was significantly higher in early RA than in other types of arthritis.
These results suggest that SFMC reacting with enterobacteria or BCW exist in some patients with early RA, but also in other types of inflammatory arthritis. Intestinal bacterial agents may play a role in the etiopathogenesis of RA, but the effect appears to be non-specific.
To study the occurrence of Sindbis-related (Pogosta) disease in Finland by serological means.
A total of 2250 serum samples from five different areas were included in the study. Four hundred samples were collected from healthy blood donors and 1850 samples from patients who were suspected to have some viral infection. Antibodies of IgG and IgM classes against Pogosta virus were measured.
Eleven per cent of 2250 samples were positive for IgG and 0.6% were positive for IgM class antibodies against Pogosta virus. The antibody prevalence in Finland was almost equally distributed, being highest in western Finland (17%) and lowest in southern and northern Finland (9%). Of all samples with IgG class antibodies, 25% were taken from children under 10 yr of age.
The prevalence of antibodies against Pogosta virus was much higher than we expected. Additionally, they were detected from all locations studied and not only in eastern Finland, which has been thought to be the main endemic area for this disease. Pogosta disease has been considered to affect mainly middle-aged persons, but our results indicate a high prevalence also among children.
A follow-up study of musculoskeletal symptoms after Pogosta virus infection.
Twenty-six patients with earlier serologically confirmed Pogosta disease were examined. Ultrasonography of affected joints was performed in patients who had chronic musculoskeletal symptoms. Serum antibodies against Sindbis virus were determined. The patients were typed for HLA-DR and B27. Efforts were made using the polymerase chain reaction to demonstrate the virus.
Only 50% of the patients were symptomless 2.5 yr after onset of Pogosta disease. Three patients had fibromyalgia, six had occasional arthralgia and two had chronic arthritis.
The epidemiology of Pogosta disease is changing and practitioners should be better aware of it. Pogosta virus infection may lead to chronic musculoskeletal discomfort and arthritis.
Amongst the arthritis-causing arboviruses, i.e. those spread by insects, the alphavirus group is of special interest. These viruses occasionally cause vast outbreaks, such as O'nyong-nyong in Africa in 1959. In Fennoscandia, Sindbis-related Ockelbo, Pogosta, or Karelian fever viruses have been found to cause significant morbidity. The major symptoms in addition to joint inflammation are fever, fatigue, headache and rash. The joint symptoms may persist for weeks, even months. The diagnosis is based on the clinical picture and serology. The causative viruses are closely related but not identical. It appears that at least in Finland the Pogosta disease is more common than thought, and the symptoms may often be overlooked. Several factors related to the viruses, their hosts, and global environmental changes may affect the spread of these viruses. All over the world arbovirus-caused diseases have increased, because of global changes.