Parity in patients with chronic inflammatory arthritides childless at time of diagnosis.

OBJECTIVE: To assess parity in women with chronic inflammatory arthritides (CIA) childless at time of diagnosis. METHODS: Patients were selected from the Norwegian Disease-Modifying Anti-Rheumatic Drug (NOR-DMARD) registry. Each patient was matched by year of birth with 100 reference women from the Norwegian Population Registry. Data linkage for patients and references with the Medical Birth Registry of Norway (MBRN) identified all offspring until time of linkage (October 2007). Patients and corresponding references childless at the time of diagnosis were included in the analyses. Kaplan-Meier curves visualized the proportion of childless women and were compared by a log rank test. RESULTS: In all, 156 rheumatoid arthritis (RA), 107 other chronic arthritides (OCA), and 75 juvenile idiopathic arthritis (JIA) patients were childless at time of diagnosis. At the time of data linkage, the proportions (%) of childless RA/OCA/JIA patients versus references were 61.5/62.6/57.3 versus 46.9/42.9/41.0, respectively, all differences statistically significant. The log rank test showed lower parity in all diagnostic groups compared with references (p < 0.001 for RA and OCA and p = 0.002 for JIA). No difference in parity was observed between RA and OCA patients, but both diagnostic groups had lower parity than JIA patients (p = 0.001). Disease characteristics were similar between childless and fertile patients. CONCLUSIONS: Reduced parity was observed in all diagnostic groups compared with references. RA and OCA patients had lower parity than JIA patients, indicating that having the disease as a young adult may influence parity more than having the disease in childhood.

The efficacy of rehabilitation for patients with rheumatoid arthritis: comparison between a 4-week rehabilitation programme in a warm and cold climate.

OBJECTIVES: To investigate the long-term effect (week 16) of a 4-week rehabilitation programme for patients with rheumatoid arthritis (RA) and to compare the effect of this intervention given in a Mediterranean or a Norwegian climate. METHODS: A randomized, controlled, parallel group design, where 124 RA patients applying for rehabilitation were randomized to a rehabilitation programme either in Norway or in a Mediterranean climate. The participants were examined clinically immediately before (week 0) and after (week 4) the rehabilitation period as well as in week 16 and answered a mailed questionnaire in week 28. The 28-Joint Disease Activity Score (DAS28), American College of Rheumatology (ACR) response and physical tests were used to measure clinical response. RESULTS: The baseline DAS28 value 4.45 (1.16) was reduced by -0.95 (1.05) in the Mediterranean climate and the baseline DAS28 value 4.18 (1.17) was reduced by -0.37 (0.92) in the Norwegian climate at week 16 (p = 0.003). An ACR20 improvement was achieved in 25% of the patients treated in the Mediterranean climate and in 15% of those treated in the Norwegian climate. Sustained improvement in all ACR core components at week 16 and in patient's assessment of health status at week 28 was found in the patients treated in the Mediterranean climate only. Tests of physical function, the 6-Minute Walk Test (6MWT) and the Timed Up and Go (TUG), showed comparable improvements in patients treated in both climates. CONCLUSIONS: RA patients showed immediate positive effects with regard to disease activity, physical function, and symptoms during a 4-week rehabilitation programme. The effects on disease activity and symptoms were larger and better maintained at least 3 months after rehabilitation in a warm rather than in a cold climate.

A Norwegian DMARD register: prescriptions of DMARDs and biological agents to patients with inflammatory rheumatic diseases.

Information concerning the effectiveness of drug therapy cannot be obtained only from randomized controlled clinical trials, due to limitations such as a short time frame and narrow inclusion and exclusion criteria. Therefore, complementary longitudinal observational studies performed in a real life setting are required. NOR-DMARD, a Norwegian 5-center register, was established in December 2000. All DMARD prescriptions to patients with inflammatory arthropathies are included, and patients are followed longitudinally with a variety of assessments. As of 2005, 4683 DMARD regimens have been included. Methotrexate is the most commonly used DMARD in rheumatoid arthritis and psoriatic arthritis. The proportions of patients who have received anti-TNF drugs in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile arthritis and other diseases have been 22.5, 21.6, 53.8, 36.9 and 9.7%, respectively. The proportion of patients receiving anti-TNF drugs is considerably higher in 2004 than earlier, and criteria for prescribing anti-TNF drugs appear to be trending toward patients with less severe and active disease. Confounding by indication or channeling bias represents a challenge for the group comparisons of longitudinal effectiveness data, but can be addressed by modern statistical techniques. The NOR-DMARD register may in the future provide comparative real life effectiveness data that may also be used in cost-effectiveness analyses.

Efficacy of methylprednisolone pulse therapy versus infliximab in the treatment of severe flares of chronic polyarthritis.

BACKGROUND: To compare short term efficacy of pulse intravenous (iv) Methylprednisolone (MP) versus Infiximab in flares of polyarthritis. PATIENTS-METHODS: Observational study of consecutive patients admitted with flares of chronic polyarthritis. Treatment consisted of three iv doses of MP 1000mg on alternate days (MP-group, n = 10) or of Infliximab will be 3 mg/kg at baseline, two, and six weeks later (I-group, n=9). DMARD therapy was initiated/continued in all patients. Disease parameters at baseline (t=0), two weeks (t=1) and twelve weeks (t=2) were compared by non-parametric testing. RESULTS: Reductions in disease parameters at both t=1 and t=2, the occurrence of side effects and the proportion of patients reaching ACR 20, 50 or 70% response criteria were similar in both groups. CONCLUSION: Pulse MP resulted in a symptomatic response similar to Infliximab in our patients. The benefit of MP was observed for up to 3 months.

[Referrals from general practitioners to rheumatologists]. / Henvisninger fra primaerleger til revmatologisk poliklinikk.

BACKGROUND: The study is an analysis of referrals of new patients from general practitioners to an outpatient clinic of rheumatology. MATERIAL AND METHODS: All referrals from general practitioners during a 12 months period were evaluated. RESULTS: The annual incidence of referrals of new patients was 423 per 100,000. The main cause of referral was diagnosis, and more than half of the diagnoses suggested were changed at the visit. Few of the referred patients had severe disease. INTERPRETATION: The selection of patients for specialist consultation in rheumatology should be changed in favour of patients with severe disease at the expense of those with long-standing non-debiliating disorders.

Referrals from general practice to an outpatient rheumatology clinic: disease spectrum and analysis of referral letters.

Our objective was to study the demographic characteristics of patients referred from general practitioners to a rheumatology outpatient clinic and to analyse the content and quality of the referral letters. During a 12-month period 346 randomly chosen referral letters of new patients from GPs to a rheumatology outpatient clinic were evaluated. The mean age of the 346 referred patients (73.1% females and 26.9% males) was 45.5 years and 17.8% were 60 or older. Mean disease duration at the time of referral was 50.9 months (1-432 months). Only about 10% of the patients referred had a disease duration of 1 month or less. The current clinical problem was appropriately presented in 95% of the referral letters. In only 0.9% of referrals had there been a prior phone consultation. Altogether, 95.1% of the referrals were as a result of diagnosis or treatment, and in nearly half the cases a diagnosis of inflammatory rheumatic disease was suggested. In 23% of the letters the result of clinical examinations were missing. Laboratory tests such as serum rheumatoid factor, antinuclear antibodies and HLA-B27 were used by GPs to screen for rheumatic disease in general. A lack of correlation between clinical manifestations and subsequently requested laboratory examinations was frequently found in the referral letters, exemplified by the use of HLA-B27 in rheumatoid arthritis and serum rheumatoid factors in ankylosing spondylitis. These results show that among GPs the threshold for referring patients to a rheumatology outpatient clinic appears rather high, and that patients are subjected to long observation periods before referral. A more frequent use of phone consultations and an improvement in the diagnostic skills of GPs may positively influence the selection of patients for referral and shorten the long waiting lists in rheumatology. This need for improvement was further strengthened by GPs' inappropriate use of laboratory tests.

[Myalgia and high sedimentation rate in adults]. / Myalgi og høy senkning hos voksne.

The polymyalgic syndrome may be the presenting clinical feature for several diseases such as polymyalgia rheumatica, temporal arteritis, malignancy, rheumatoid arthritis, virus infections, connective tissue diseases, and myositis. In this review we present the various diagnostic options seen from a rheumatological point of view, with emphasis on polymyalgia rheumatica, temporal arteritis and the paraneoplastic syndrome. We are of the opinion that polymyalgia rheumatica is overdiagnosed in general practice, and steroid treatment may delay diagnosis and treatment of other differential diagnosis presenting as the polymyalgic syndrome. Several recently published Norwegian epidemiological studies offer new information on various aspects of the polymyalgic syndrome, which will be discussed.

[Hereditary amyloid cardiomyopathy related to a mutation at transthyretin protein number 111. A clinical, genetic and echocardiographic study of an affected Danish family]. / Hereditaer amyloid kardiomyopati relateret til en mutation på plads nr. 111 i transthyretinproteinet. En klinisk, genetisk og ekkokardiografisk undersøgelse af en afficeret dansk familie.

Amyloidosis is a group of diseases characterized by amyloid deposition in various tissues. The diseases can roughly be divided into hereditary and non-hereditary forms. The hereditary forms are related to a mutation in the serum protein transthyretin which is produced mainly in the liver. The inheritance is autosomal dominant. A family in Denmark has earlier been described as having inherited cardiac amyloidosis with a mutation at amino acid number 111 in the transthyretin protein. The family now has been re-examined because of new diagnostic and therapeutic possibilities. The aims of the study were to identify carriers and non-carriers of the mutant transthyretin methionine 111 linked familial amyloid disease, to detect early signs of the restrictive cardiomyopathy and other clinical manifestations of this disease. Clinical, echocardiographic and genetic examination was carried out. Out of 125 living family members, 99 were available for examination. Twenty-five persons were heterozygous carriers of the mutant transthyretin methionine 111 genotype, while 74 were non-carriers. Eight carriers, all above the age of 35, showed echocardiographic abnormalities suggestive of developing or manifest restrictive cardiomyopathy. Nine carriers had carpal tunnel syndrome as opposed to none of the non-carriers. It is concluded that for early detection of familial amyloid cardiomyopathy, echocardiography is the investigation of choice. The first sign is diastolic dysfunction detected as an abnormal relaxation pattern. Carpal tunnel syndrome appears to be the earliest presenting clinical symptom. Early liver transplantation seems to be curative.

An overlap syndrome with features of atypical Cogan syndrome and Wegener's granulomatosis.

A 48 year old women developed serous otitis, scleritis, myalgia, vertigo, polyneuropathy, crescentic glomerulonephritis, general cerebral dysrythmia, hilar adenopathy, and retroorbital granulomatous inflammation. Pulmonary manifestations were absent and antibodies against neutrophilic cytoplasmic antigens (ANCA) could not be detected. The clinical picture was classified as an overlap syndrome with features of both atypical Cogan syndrome and Wegener's granulomatosis. The patient responded to treatment with high dose corticosteroids and pulse cyclophosphamide.

A clinical, echocardiographic and genetic characterization of a Danish kindred with familial amyloid transthyretin methionine 111 linked cardiomyopathy.

AIMS: To identify carriers and non-carriers of the mutant transthyretin methionine 111 linked familial amyloid disease, to detect early signs of the restrictive cardiomyopathy and other clinical manifestations characteristic of this inheritable disease. METHODS AND RESULTS: Out of 125 living family members 99 were available for clinical, echocardiographic and genetic examination. Twenty-five family members were heterozygous carriers of the mutant transthyretin methionine 111 genotype, while 74 were non-carriers. Among the 25 carriers, none had overt clinical signs of heart disease. Eight carriers, all above the age of 35, showed echocardiographic abnormalities suggestive of developing or manifest restrictive cardiomyopathy. Three had biopsy-verified transthyretin-related amyloid cardiomyopathy. None of the 15 carriers in the younger age group exhibited aberrant echocardiographic patterns. Nine carriers had carpal tunnel syndrome as opposed to none of the non-carriers. CONCLUSION: For early detection of familial amyloid cardiomyopathy, echocardiography is the investigation of choice. The first sign is diastolic dysfunction detected as an abnormal relaxation pattern. The appearance of echocardiographic aberrations solely in the older age group suggests that the cardiomyopathy is a late onset disease. Carpal tunnel syndrome appears to be the earliest presenting clinical symptom. A curative treatment seems to be an early liver transplantation.

Interaction between circulating amyloid fibril protein precursors and extracellular tissue matrix components in the pathogenesis of systemic amyloidosis.

Amyloidosis is a heterogeneous group of diseases characterized by deposition of a fibrillar, proteinaceous material, amyloid, in various tissues and organs. Increasing knowledge about the different proteins that constitute the amyloid fibrils has made it possible to classify amyloidosis by the fibril protein, which appears more rational than the traditional classification by its clinical expression. A serum protein is the precursor of the amyloid fibril protein in the various systemic forms of amyloidosis. Although the chemical composition of amyloid is presently well known, the pathogenetic processes that convert such proteins into a fibrillar form and lay them down in the tissues are far from clarified. We suggest some pathogenetic mechanisms for amyloid deposition, involving different types of fibril protein, their precursors, the extra-fibrillar amyloid P component, glycosaminoglycans, proteoglycans, and calcium with special reference to experimental work from our research group.

Retrospective molecular detection of Transthyretin Met 111 mutation in a Danish kindred with familial amyloid cardiomyopathy, using DNA from formalin-fixed and paraffin-embedded tissues.

Severe familial amyloid cardiomyopathy (FAC) in a Danish kindred is associated with a specific mutation (Met for Leu 111) in the transthyretin (TTR) gene. The mutation causes the loss of a DdeI restriction site in the gene, allowing molecular diagnostic studies. We studied formalin-fixed, paraffin-embedded tissues, up to 39 years old, from 29 family members of this kindred. DNA was partially purified from deparaffinized tissue sections and a DNA sequence of the TTR gene flanking the mutation site was amplified by the polymerase chain reaction (PCR), followed by restriction enzyme analysis. Amplified DNA was obtained from tissues representing 23 of the 29 persons. Ten out of the 23 family members were found to carry the TTR Met 111 mutation, whereas 13 were not affected. The results were consistent with known clinical data and with corresponding serum TTR examinations. This retrospective study shows that archival tissues can be used to confirm the diagnosis and disease pattern in members of families affected by hereditary diseases.

Molecular diagnosis of the transthyretin (TTR) Met111 mutation in familial amyloid cardiomyopathy of Danish origin.

Familial amyloid cardiomyopathy in a Danish kindred is associated with a specific mutation (Met for Leu111) in the transthyretin (TTR) gene, causing the loss of a recognition site for the restriction enzyme DdeI in the gene. We describe a diagnostic test for the molecular detection of this mutation. A sequence of the TTR gene containing the mutation was amplified by the polymerase chain reaction from isolated genomic DNA of two affected patients and several controls. DdeI digestion of the amplified DNA from the patients revealed 3 bands by gel-electrophoresis, whereas amplified DNA of the controls showed only 2 bands, consistent with complete digestion. Thus, the assumed heterozygous TTR Met111 mutation was confirmed in the affected patients.

Direct PCR of washed blood cells.

We report a simple and rapid method for direct DNA amplification of washed blood cells by PCR. Small samples (2-100 microliters) of blood were washed, the cells resuspended in a buffer and used directly for PCR after boiling. Amplification of a specific DNA sequence of the human transthyretin gene, directed by the primers, was successfully performed. The method gives comparable results to amplifications made by purified DNA from blood.

Diet and disease symptoms in rheumatic diseases--results of a questionnaire based survey.

Experiences with food intake, diet manipulations and fast were registered in rheumatic patients. The study was a questionnaire-based survey in which 742 patients participated. It comprised 290 patients with rheumatoid arthritis, 51 patients with juvenile rheumatoid arthritis, 87 patients with ankylosing spondylitis, 51 patients with psoriatic arthropathy, 65 patients with primary fibromyalgia and 34 patients with osteoarthritis. One third of the patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthropathy reported aggravation of disease symptoms after intake of certain foods while 43% of the patients with juvenile rheumatoid arthritis and 42% of the patients with primary fibromyalgia stated the same. Twenty-six percent of the patients with juvenile rheumatoid arthritis and 23% of the patients with rheumatoid arthritis, ankylosing spondylitis and primary fibromyalgia had previously tried certain diets in the attempt to alleviate disease symptoms, whereas 13% of the patients with psoriatic arthropathy and 10% with osteoarthritis had tried diet therapy. Less pain and stiffness were reported by 46% of the patients and 36% reported reduced joint swelling. Similar beneficial effects of diet were also reported in other rheumatic disease groups. Fifteen percent of the patients with rheumatoid arthritis and ankylosing spondylitis had been through a fasting period. Less pain and stiffness were reported by 2/3 of the patients in both groups and half of the patients in both groups reported a reduced number of swollen joints.