To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP). This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001–2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively. Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31–1.82)), PsA (1.76 (1.59–1.95)) and uSpA (1.36 (1.05–1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37–0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06–1.48)) and PsA (1.34 (1.22–1.48)), and nonsignificantly increased in uSpA (1.16 (0.91–1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP. Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.

The aim of the present study was to describe prevalence and trends in the incidence of gout and patterns of urate-lowering treatment (ULT) in the Western Swedish Health Care Region (WSHCR) from 2002 to 2012. We used regional and national healthcare registers to estimate the prevalence and incidence of gout in 2012, and trends in incidence for each calendar year from 2005 to 2012. We also investigated the pattern of ULT for gout using the Swedish Prescribed Drug Register. In 2012, in the population aged 20 years and above, the prevalence of gout was 1.8 % (95 % confidence interval (CI) 1.77 to 1.82) and the incidence was 190 cases (95 % CI 180 to 200) per 100,000 person-years. Applying more strict definitions for a gout case rendered a prevalence of 1.36 % (95 % CI 1.34 to 1.38) and 0.5 (95 % CI 0.49 to 0.51) per 100,000 person-years, respectively. The incidence of gout increased steadily and significantly from 2005 to 2012, with an almost 50 % increase in the total population. There was no significant difference in the prevalence of gout in rural compared to urban areas. ULT was dispensed to only 42 % of patients with gout in 2012 who had ever been diagnosed with gout during the preceding 10-year period. Gout is the most common arthritic disease in WSHCR, Sweden, and has increased substantially over the last decade, with only a minority of prevalent cases in 2012 receiving ULT.

One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). Our findings indicate that Flt3-L is strongly expressed at the site of inflammation in human RA. It exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. Owing to these properties, treatment attempts to neutralize this molecule should be considered in RA.

Introduction: Fibromyalgia (FM) is characterized by chronic pain. Impaired growth hormone responses and reduced serum insulin-like growth factor 1 (IGF-1) are common in FM. The aim was to examine changes in serum IGF-1, cerebrospinal fluid (CSF), neuropeptides, and cytokines during aerobic exercise in FM patients. Methods: In total, 49 patients (median age, 52 years) with FM were included in the study. They were randomized to either the moderate- to high-intensity Nordic Walking (NW) program (n = 26) or the supervised low-intensity walking (LIW) program (n = 23). Patients participated in blood tests before and after 15 weeks of aerobic exercise. Changes in serum levels of free IGF-1, pain rating on a 0- to 100-mm scale, pain threshold, and 6-minute walk test (6MWT) were examined. CSF, neuropeptides, matrix metalloproteinase 3 (MMP-3), and inflammatory cytokines were determined. Nonparametric tests were used for group comparisons and correlation analyses. Results: Serum free IGF-1 levels did not change during 15 weeks of exercise between the two groups, although the 6MWT significantly improved in the NW group (p = 0.033) when compared with LIW. Pain did not significantly change in any of the groups, but tended to decrease (p = 0.052) over time in the total group. A tendency toward a correlation was noted between baseline IGF-1 and a decrease of pain in response to exercise (r = 0.278; p = 0.059). When adjusted for age, this tendency disappeared. The change in serum free IGF-1 correlated positively with an alteration in CSF substance P (SP) levels (r ^s = 0.495; p = 0.072), neuropeptide Y (NPY) (r ^s = 0.802; p = 0.001), and pain threshold (r ^s = 0.276; p = 0.058). Differing CSF SP levels correlated positively to a change in pain threshold (r ^s = 0.600; p = 0.023), whereas the shift in CSF MMP-3 inversely correlated with an altered pain threshold (r ^s = -0.569; p = 0.034). Conclusions: The baseline level of serum free IGF-1 did not change during high or low intensity of aerobic exercise. Changes in IGF-1 correlated positively with a variation in CSF SP, NPY, and pain threshold. These data indicate a beneficial role of IGF-1 during exercise in FM. Trial registration: ClinicalTrials.gov NCT00643006.

Gout is the most common inflammatory arthritic disease and is caused by crystal deposition secondary to persistent hyperuricemia. Etiological treatment with urate-lowering therapy (ULT) has been available since the 1950s but previous studies have demonstrated suboptimal degree of treatment. In recent years we have seen recommendations for ULT earlier in the course of the disease, but there are few contemporary reports reflecting the current situation. Therefore we set out to investigate proportion receiving and persisting with ULT after gout diagnosis and predictors thereof. A population-based cohort study using regional and national population-based registers. Cohort of patients (n = 7709) from western Sweden with incident gout aged 18 years and above from 2011 to 2013. An incident case of gout was defined as having been given a diagnosis of gout (ICD-10 M10, M14.0-14.1) not preceded by a gout diagnosis or a dispensation of ULT during the previous 5 years. Main outcome measures were cumulative incidence and predictors for start of, and persistence with, ULT in gout. Within the first year after first gout diagnosis, 32% received ULT. Male sex, presence of diabetes or cardiovascular comorbidity, reduced kidney function but not diagnosed “end-stage kidney failure” increased the likelihood of receiving ULT. Of those starting ULT a majority (75%) did not persist with ULT treatment within the first 2 years. Age <50 years, lack of comorbidities, and “normal kidney function” or “end-stage kidney failure” were associated with non-persistence with ULT. Only a minority of patients received ULT and a majority of these did not persist with treatment over the next 2 years. However, the older patients with renal impairment and comorbidities, possibly suffering from a more severe gout disease, were more likely to receive and persist with treatment. There is thus still room for considerable improvement with regards to management of ULT in gout.

The diagnostic golden standard for gout is to detect monosodium urate (MSU) crystals in synovial fluid. While some gout classification criteria include this variable, most gout diagnoses are based on clinical features. This discrepancy between clinical practice and classification criteria can hinder gout epidemiological studies. Here, the objective was to validate gout diagnoses (International Classification of Diseases (ICD)-10 gout codes) in primary and secondary care relative to five classification criteria (Rome, New York, ARA, Mexico, and Netherlands). The frequency with which MSU crystal identification was used to establish gout diagnosis was also determined. In total, 394 patients with ≥1 ICD-10 gout diagnosis between 2009 and 2013 were identified from the medical records of two primary care centers (n = 262) and one secondary care center (n = 132) in Gothenburg, Sweden. Medical records were assessed for all classification criteria. Primary care patients met criteria cutoffs more frequently when ≥2 gout diagnoses were made. Even then, few primary care patients met the Rome and New York cutoffs (19 % and 8 %, respectively). The ARA, Mexico, and Netherlands cutoffs were met more frequently by primary care patients with ≥2 gout diagnoses (54 %, 81 %, and 80 %, respectively). Mexico and Netherlands cutoffs were met more frequently by the rheumatology department patients (80 % and 71 %, respectively), even when patients with only 1 gout diagnosis were included. Analysis of MSU crystals served to establish gout diagnoses in only 27 % of rheumatology department and 2 % of primary care cases. If a patient was deemed to have gout at ≥2 primary care center or ≥1 rheumatology-center visits according to an ICD-10 gout code, the positive predictive value of this variable in relation with the Mexico and Netherlands classification criteria was ≥80 % for both primary care and rheumatology care settings in Sweden. MSU crystal identification was rarely used to establish gout diagnosis.