Birgitta Nordmark

Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases

Objective: To quantify the influence of cigarette smoking on the risk of developing rheumatoid arthritis (RA). Methods: 679 cases and 847 controls included during May 1996–June 2000 in a case-control study, using incident cases, comprising the population aged 18–70 years of a defined area of Sweden, were investigated. A case was defined as a person from the study base who received for the first time a diagnosis of RA using the 1987 American College of Rheumatology criteria, and controls were randomly selected from the study base. Self reported smoking habits among cases and controls, and rheumatoid factor status among cases were registered. The incidence of RA in current smokers, ex-smokers, and ever-smokers, respectively, was compared with that of never-smokers. Results: Current smokers, ex-smokers, and ever-smokers of both sexes had an increased risk for seropositive RA (for ever-smokers the odds ratio was 1.7 (95% confidence interval (95% CI) 1.2 to 2.3) for women, and 1.9 (95% CI 1.0 to 3.5) for men), but not for seronegative RA. The increased risk was only apparent among subjects who had smoked ⩾20 years, was evident at an intensity of smoking of 6–9 cigarettes/day, and remained for up to 10–19 years after smoking cessation. The risk increased with increasing cumulative dose of smoking. Conclusion: Smokers of both sexes have an increased risk of developing seropositive, but not seronegative, RA. The increased risk occurs after a long duration, but merely a moderate intensity, of smoking and may remain for several years after smoking cessation.

Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression

Objective: To study serum levels of citrullinated protein/peptide antibodies (anti-CP) during up to 5 years’ follow up of patients with early rheumatoid arthritis (RA), and to relate serum levels to disease course and to treatments in clinical practice. Methods: 279 patients with early RA were followed up with clinical investigations, radiographs, and measurement of anti-CP at baseline and after 3 months, 1, 2, 3, and 5 years. Results: 160/279 (57.3%) patients were anti-CP positive at the first visit (mean 5 months after first symptoms). During follow up only 11/279 (3.9%) of the patients changed their anti-CP status. Anti-CP levels fell significantly during the first year, and this drop correlated with the extent of sulfasalazine treatment but not with other drugs or clinical indices. Anti-CP positive and negative patients had similar disease activities at baseline, but during follow up the anti-CP positive patients had worse clinical disease and greater radiological progression, despite at least equally intensive antirheumatic treatment. Conclusions: Anti-CP are stable during the first 5 years of RA, suggesting that events before rather than after onset of clinical manifestations of disease determine this phenotype. The presence of anti-CP at diagnosis predicts a less favourable disease course and greater radiological progression despite antirheumatic treatment, but subsequent changes in antibody levels do not reflect changes in disease activity. Taken together, these observations suggest that anti-CP positive RA is a distinct clinical and pathophysiological entity.

Somatosensory perception and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from rheumatoid arthritis.

The purpose was to investigate the influence of ongoing pain from an inflammatory nociceptive pain with two different disease durations on somatosensory functions and the effect of heterotopic noxious conditioning stimulation (HNCS) on ‘diffuse noxious inhibitory controls’ (DNIC) related mechanisms. Eleven patients with rheumatoid arthritis of a short duration (< 1 year) (RAI), and 10 patients with rheumatoid arthritis of longer duration (>5 years) (RA5) as well as 21 age‐and sex‐matched healthy controls participated. Pressure pain sensitivity, low threshold mechanoreceptive function and thermal sensitivity, including thermal pain, were assessed over a painful and inflamed joint as well as in a pain‐free area, i.e. the right thigh before HNCS (cold‐pressor test) and repeated at the thigh only during and following HNCS. In RAI and RA5 allodynia to pressure was seen over the joint (p < 0.02 and p < 0.001 respectively) in conjunction with hypoaesthesia to light touch (p < 0.02) and hyperaesthesia to innocuous cold (p < 0.05) in RA5. At the thigh, allodynia to pressure was found in RA5 (p < 0.002). During HNCS, the sensitivity to pressure pain decreased in patients and controls alike (p < 0.001). In conclusion, over an inflamed joint allodynia to pressure was found in both RA groups, with additional sensory abnormalities in RA5. In a non‐painful area, allodynia to pressure was found in RA5, suggesting altered central processing of somatosensory functions in RA5 patients. The response to HNCS was similar in both RA groups and controls, indicating preserved function of DNIC‐related mechanisms.

Socioeconomic status and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study

Objective: To study whether formal education and occupational class are associated with incidence of rheumatoid arthritis overall and with the incidence of the two major subgroups of rheumatoid arthritis—seropositive (RF+) and seronegative (RF−) disease. Methods: 930 cases and 1126 controls participated in a population based case–control study using incident cases of rheumatoid arthritis, carried out in Sweden during the period May 1996 to June 2001. The relative risk (RR) of developing rheumatoid arthritis with 95% confidence interval (CI) was calculated for different levels of formal education compared with university degree and for different occupational classes compared with higher non-manual employees. Results: Subjects without a university degree had an increased risk of rheumatoid arthritis compared with those with a university degree (RR = 1.4 (95% CI, 1.2 to 1.8)). For manual employees, assistant and intermediate non-manual employees together, the risk of developing rheumatoid arthritis was about 20% more than for non-manual employees. These increased risks were more pronounced for RF+ than for RF− rheumatoid arthritis and were mainly confined to women. Smoking could not of its own explain the observed associations between risk of rheumatoid arthritis in different socioeconomic groups in Sweden. Conclusions: There was an association between high socioeconomic status and lower risk of rheumatoid arthritis in a population based investigation that was representative for the Swedish population. The study shows that as yet unexplained environmental or lifestyle factors, or both, influence the risk of rheumatoid arthritis, even in the relatively egalitarian Swedish society.

The foot: still the most important reason for walking incapacity in rheumatoid arthritis: Distribution of symptomatic joints in 1,000 RA patients

Background and purpose Our knowledge of frequency of foot involvement in rheumatoid arthritis (RA) is still often based on a study from Finland in 1956. Great changes in the treatment of RA may have led to a different situation. We investigated the distribution of joint involvement in RA patients today, with special attention given to the feet and subjective walking ability. Methods 1,000 RA patients answered a questionnaire concerning joints affected, joint surgery, foot problems, and subjectively experienced reasons for walking incapacity. Results In 45% of the patients, the forefoot was involved at the start of the disease. In 17%, the hindfoot/ankle was involved at the start. Only hand symptoms were commoner. 80% of patients reported current foot problems, 86% in the forefoot and 52% in the hindfoot/ankle. Difficulty in walking due to the feet was reported by 71%. For 41% of patients, the foot was the most important part of the lower extremity causing reduced walking capacity, and for 32% it was the only part. Interpretation After the hand, the foot was the most frequently symptomatic joint complex at the start of the disease, but also during active medical treatment. The foot caused walking disability in three-quarters of the cases and—4 times as often as the knee or the hip—it was the only joint to subjectively impair gait.

Skewed distribution of proinflammatory CD4+CD28null T cells in rheumatoid arthritis.

Expanded populations of CD4+ T cells lacking the co-stimulatory molecule CD28 (CD4+CD28null T cells) have been reported in several inflammatory disorders. In rheumatoid arthritis, increased frequencies of CD4+CD28null T cells in peripheral blood have previously been associated with extra-articular manifestations and human cytomegalovirus (HCMV) infection, but their presence in and contribution to joint manifestations is not clear. In the present article we investigated the distribution of CD4+CD28null T cells in the synovial membrane, synovial fluid and peripheral blood of RA patients, and analysed the association with erosive disease and anti-citrullinated protein antibodies. CD4+CD28null T cells were infrequent in the synovial membrane and synovial fluid, despite significant frequencies in the circulation. Strikingly, the dominant TCR-Vβ subsets of CD4+CD28null T cells in peripheral blood were often absent in synovial fluid. CD4+CD28null T cells in blood and synovial fluid showed specificity for HCMV antigens, and their presence was clearly associated with HCMV seropositivity but not with anti-citrullinated protein antibodies in the serum or synovial fluid, nor with erosive disease. Together these data imply a primary role for CD4+CD28null T cells in manifestations elsewhere than in the joints of patients with HCMV-seropositive rheumatoid arthritis.

Common vaccinations among adults do not increase the risk of developing rheumatoid arthritis: results from the Swedish EIRA study

Objective To investigate the association between vaccinations in adults and the risk of developing rheumatoid arthritis (RA). Methods Data from the Swedish population-based Epidemiological Investigation of RA case-control study encompassing 1998 incident cases of RA aged 18–70 years and 2252 randomly selected controls matched for age, sex and residency were analysed. Those vaccinated within 5 years before disease onset were compared with those not vaccinated by calculating OR with 95% CI. Results Vaccinations neither increased the risk of RA overall (OR 1.0, 95% CI 0.9 to 1.1) nor the risk of two major subgroups of RA (antibodies to citrullinated peptide-positive (ACPA-positive) and ACPA-negative disease). Furthermore, vaccinations did not increase the risk of RA in smokers or carriers of HLA-DRB1 shared epitope alleles, two groups with established risk factors for RA. Conclusions In this case-control study of incident cases of newly diagnosed RA, no increased risk of RA following immunisation was observed for vaccinations overall or for any specific vaccination. This indicates that immunological provocation of adults with commonly used vaccines in their present form carries no risk of RA. These findings should be implemented among public healthcare providers in order to encourage vaccinations according to recommended national vaccination schedules.

Incident cases of primary Sjögren’s syndrome during a 5-year period in Stockholm County: a descriptive study of the patients and their characteristics

Objectives: To define the incidence rate of primary Sjögren’s syndrome (pSS) and the prevalence of extraglandular manifestations (EGMs) at the time of diagnosis of pSS in a prospective, population-based manner. Method: This study included all consecutive patients referred to the Department of Rheumatology at Karolinska University Hospital for the investigation of incident pSS from 1 January 2007 to 31 December 2011. Investigation was according to the current criteria for pSS, and examination with a focus on the presence of EGMs was performed. Results: Of the referred individuals, 199 out of 781 were diagnosed with pSS. We found an annual incidence rate of pSS in the Karolinska University Hospital catchment area of 3.1 [95% confidence interval (CI) 2.3–4.3] cases per 100 000 adult inhabitants. The female/male ratio of incident cases was 14/1 [frequency (female) = 0.93, 95% CI 0.89–0.96]. In our cohort, we noted lower figures for severe EGMs such as lung and neurological involvement than previously reported for prevalent pSS. The frequency of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, and anti-La/SSB was also lower compared to other cohorts. In our study, autoantibody-positive patients had cytopaenia significantly more often, and in patients older than 60 years primary biliary cirrhosis (PBC) was more common. Conclusions: The incidence rate of pSS is 3.1 (95% CI 2.3–4.3) per 100 000 person-years. The prevalence of autoantibodies may be lower than previously reported, and at diagnosis, patients with pSS have few severe EGMs.

Higher pain sensitivity and lower muscle strength in postmenonpausal women with early rheumatoid arthritis compared with age-matched healthy women - a pilot study

Purpose: The purpose of the study was to examine muscle strength and pain sensitivity in postmenopausal women with and without RA. Methods: Ten women with and ten without early RA were recruited. All were postmenopausal, and did not use hormone replacement therapy. Measurements of isokinetic muscle strength in knee flexors/extensors, hand grip strength, timed standing, pressure pain thresholds (PPT), suprathreshold pressure pain, and segmental and plurisegmental endogenous pain inhibitory mechanisms during muscle contraction were assessed. Results: Participants with early RA were weaker in knee flexors, in hand grip strength and they needed more time for the timed standing. Women with early RA had higher sensitivity to threshold pain and suprathreshold pressure pain compared to women without RA. PPTs increased in the contracting muscle as well as in a distant resting muscle during static contractions in both groups. Conclusions: Our results indicate differences in muscular strength between postmenopausal women with and without RA. Furthermore, women with RA had decreased PPT and hyperalgesia, but no dysfunction of segmental or plurisegmental pain inhibitory mechanisms during static exercise compared to healthy controls. The normal function of endogenous pain inhibitory mechanisms despite chronic pain in women with RA might contribute to the good effects of physical activity previously reported. Implications for Rehabilitation Difference in muscular strength between postmenopausal women with and without (rheumatoid arthritis) RA is present in early disease despite low disease activity. Women with RA have decreased pressure pain thresholds and hyperalgesia, but no dysfunction of segmental and plurisegmental pain inhibitory mechanisms. The normal function of endogenous pain inhibitory mechanisms despite chronic pain in women with RA might contribute to the good effects of physical activity in this group of patients.