| 11. |
- Bursill, D., et al.
(författare)
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Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout
- 2019
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Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X. ; 71:3, s. 427-434
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Tidskriftsartikel (refereegranskat)abstract
- Objective The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. Methods Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. Results There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (>= 80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. Conclusion Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.
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| 12. |
- Dehlin, Mats, 1968, et al.
(författare)
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Association between perinatal factors and future risk for gout-a nested case-control study
- 2022
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Increased level of urate is the strongest risk factor for gout development but since only a minority of hyperuricemics are affected by gout, other pathogenic factors must be considered. Low birth weight is associated with future morbidities causing hyperuricemia, such as diabetes and renal disease. The purpose of this study was to investigate if, and to what extent, maternal and perinatal factors, including birth weight, are associated with future risk of being diagnosed with gout. Methods A population-based retrospective nested case-control registry study based on regional and national health care registers in Sweden. All incident cases of gout born in 1973 and onward who had received >= 1 diagnosis of gout from 2000 through 2019 in the region of western Sweden were included. Up to 5 non-gout controls were matched to each case by age, sex, and county at the year of first gout diagnosis. A range of maternal, gestational, and perinatal factors were analyzed for their potential association to future gout development. This included the health of the mother, gestational length, birth weight, number of siblings, and congenital malformations. Results Maternal diabetes, any congenital malformation, and being small for gestational age were factors that significantly increased the risk for future gout development, odds ratio (95% CI) 3.1 (1.3 to 7.4) (p=0.01), 1.33 (1.04 to 1.7) (p=0.02), and 1.75 (1.3 to 2.3) (p<.0001), respectively. Conclusions In this study, maternal diabetes and being small for gestational age increased the risk for future gout development in young adults. As of today, these conditions are becoming more prevalent and may contribute to the ongoing gout epidemic. These results require both confirmation and further delineation of underlying mechanisms.
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| 13. |
- Dehlin, Mats, 1968, et al.
(författare)
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Cerebrospinal Flt3 ligand correlates to tau protein levels in primary Sjögren's syndrome.
- 2013
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Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 42:5, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting the exocrine glands and internal organs including the central nervous system (CNS). The fms-related tyrosine kinase 3 ligand (Flt3L) is a maturation factor essential for brain homeostasis. Blood levels of Flt3L are increased in inflammatory diseases including the inflamed salivary glands in pSS. The present study evaluated the role of Flt3L in the CNS of patients with pSS and in two non-autoimmune conditions, fibromyalgia (FM) and Alzheimer's disease (AD). Method: Levels of Flt3L were measured in cerebrospinal fluid (CSF) and serum of patients with pSS (n = 15), FM (n = 29), and AD (n = 39) and related to CNS symptoms and to markers of inflammation and degeneration. Results: Levels of CSF Flt3L in pSS and AD were significantly lower than in FM (p = 0.005 and p = 0.0003, respectively). Flt3L in pSS correlated to tau proteins [total tau (T-tau), r = 0.679; phosphorylated tau (P-tau), r = 0.646] and to a marker for microglia activation, monocyte chemoattractant protein 1 (MCP-1). Similar correlations were present in FM and AD patients. One-third of pSS patients had low levels of CSF Flt3L. This group had decreased levels of amyloid precursor protein metabolites (Aβ40 and Aβ42) in CSF, which was not seen in FM patients. Conclusions: This study shows a strong correlation between CSF Flt3L and tau proteins in pSS patients suggesting ongoing degradation/remodelling in the CNS. In pSS patients, low levels of Flt3L were linked to changes in amyloid turnover and may represent processes similar to those in AD.
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| 14. |
- Dehlin, Mats, 1968, et al.
(författare)
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Consequences of Gout and Hyperuricemia : Gikt och hyperurikemi starkt associerade med folksjukdomar
- 2020
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Ingår i: Läkartidningen. - 1652-7518. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Hyperuricemia (HU) and gout are strongly associated with CVD, associations that are most likely due to shared etiologies rather than causality. HU is for example causally related to the metabolic syndrome and in particular to obesity. Gout and HU can both be caused by and lead to decreased kidney function. On the other hand, there are observational data suggesting that HU may protect against neurodegenerative diseases such as Alzheimer and Parkinson's disease. Ongoing RCTs with urate and urate lowering therapy (ULT) will help to resolve some of these controversies. Nevertheless, gout is a "curable disease" by ULT, a treatment which in adequate doses may also have positive effect on several associated co-morbidities.
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| 15. |
- Dehlin, Mats, 1968
(författare)
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Differentiation factor Fms-like tyrosine kinase 3 ligand is a modulator of cell responses in autoimmune diseases
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fms-like tyrosine kinase 3 (Flt3) is a receptor on common stem cell progenitors and has a crucial role in hematopoesis, regulating cell proliferation and differentiation in man and mice. The growth factor Flt3 is activated by its soluble ligand, Flt3-L, leading to differentiation of multipotent stem cells and lymphoid progenitors. Flt3-L functions as a differentiation factor for dendritic cells (DC) in the periphery. These properties of the Flt3/Flt3-L system lead us to further investigate the role of the growth factor Flt3-L in rheumatic disease. In paper I, Flt3-L was found to be strongly expressed at the site of inflammation in human RA, the joint. Levels of Flt3-L were significantly higher in the synovial fluid compared to serum in RA patients and levels of Flt3-L in RA synovial fluid were significantly higher compared to synovial fluid from non-inflammatory joint diseases. Furthermore, intra-articular administration of a B-cell line overexpressing Flt3-L resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and caused arthritis in a minority of cases. Thus, Flt3-L is expressed at the site of inflammation in human RA and facilitates tissue destructive properites in the joint cavity. In paper II, mice with antigen-induced arthritis, mBSA-arthritis, were treated with the Flt3-inhibitor sunitinib. Treatment was started together with mBSA immunization or together with the induction of arthritis. Abrogation of Flt3 signalling reduced the intensity of synovitis and the frequency of bone destruction. Inhibition of Flt3 reduced also the number of differentiated (mature) dendritic cells concomitant with reduction of antibody production and bone metabolism. In addition to this, we investigated the ability of mouse bone marrow cells to migrate towards Flt3-L in a migration assay. Flt3-L was found to be a potent chemoattractant facilitating mobilization of Flt3+ cells from the bone marrow. Thus, the processes of antigen presentation, influx of leukocytes into synovial tissue and bone remodelling are mediated by Flt3 signalling in antigen-induced arthritis. In paper III, Flt3-L in CSF correlated to levels of Tau and pTau of patients with Sjögrens syndrome, fibromyalgia and Alzheimers disease, implying involvement of Flt3L in brain homeostasis. Furthermore, CSF Flt3-L in pSS correlated to a marker for microglia activation, MCP-1. Levels of Flt3-L in CSF were significantly decreased in pSS, and AD, compared to FM. Low levels of Flt3-L were associated to low levels of amyloid degradation peptides in pSS and AD patients. Thus, in CNS of patients with pSS Flt3-L is strongly correlated to neuroaxonal plasticity and microglia activation and reduced levels of CSF-Flt3-L in pSS are linked to changes in tau and amyloid turnover resembling processes ongoing in AD patients. Taken together, these results indicate that Flt3-L is involved in the inflammatory and tissue remodelling processes in joints and neuroaxonal structures of the brain. Flt3/Flt3-L signalling is an essential regulator of antigen-induced processes in autoimmune diseases.
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| 16. |
- Dehlin, Mats, 1968, et al.
(författare)
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Factors associated with initiation and persistence of urate-lowering therapy
- 2017
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Ingår i: Arthritis Resarch and Therapy. - 1478-6354. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: 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. Method: 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. Results: 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. Conclusions: 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.
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| 17. |
- Dehlin, Mats, 1968, et al.
(författare)
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Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors
- 2020
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Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4790 .- 1759-4804. ; 16, s. 380-390
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Tidskriftsartikel (refereegranskat)abstract
- Gout is a chronic crystal deposition disorder in which sustained hyperuricaemia leads to formation and deposition of monosodium urate crystals in the joints. The prevalence and incidence of gout are increasing globally, which may be related to changes in the prevalence of gout risk factors (such as obesity) and comorbidities. Gout is the most common inflammatory arthritis and occurs when hyperuricaemia, sustained elevation of serum urate levels resulting in supersaturation of body tissues with urate, leads to the formation and deposition of monosodium urate crystals in and around the joints. Recent reports of the prevalence and incidence of gout vary widely according to the population studied and methods employed but range from a prevalence of <1% to 6.8% and an incidence of 0.58-2.89 per 1,000 person-years. Gout is more prevalent in men than in women, with increasing age, and in some ethnic groups. Despite rising prevalence and incidence, suboptimal management of gout continues in many countries. Typically, only a third to half of patients with gout receive urate-lowering therapy, which is a definitive, curative treatment, and fewer than a half of patients adhere to treatment. Many gout risk factors exist, including obesity, dietary factors and comorbid conditions. As well as a firmly established increased risk of cardiovascular disease and chronic kidney disease in those with gout, novel associations of gout with other comorbidities have been reported, including erectile dysfunction, atrial fibrillation, obstructive sleep apnoea, osteoporosis and venous thromboembolism. Discrete patterns of comorbidity clustering in individuals with gout have been described. Increasing prevalence and incidence of obesity and comorbidities are likely to contribute substantially to the rising burden of gout.
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| 18. |
- Dehlin, Mats, 1968, et al.
(författare)
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Impact of psoriasis disease activity and other risk factors on serum urate levels in patients with psoriasis and psoriatic arthritis-a post-hoc analysis of pooled data from three phase 3 trials with secukinumab
- 2021
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Ingår i: Rheumatology Advances in Practice. - : Oxford University Press (OUP). - 2514-1775. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Our aims were to determine if the Psoriasis Area Severity Index (PASI) score and serum urate (SU) levels were associated at baseline and whether the change in PASI score during 12 weeks of treatment resulted in a significant change in SU, adjusted for relevant confounders. Methods. Data from patients with psoriasis/PsA (n = 1042/204) in three phase 3 randomized control trials treated with secukinumab (dose 300 mg, n = 628) or placebo (n = 414) were pooled. At baseline, values for SU, PASI and the following covariates were assessed: age, sex, BMI, estimated glomerular filtration rate, and medication with diuretics. To assess the changes in PASI (DPASI) and SU (Durate), the differences (week 12 minus baseline) in patients receiving the active drug were used. Multivariable linear regression, adjusting for covariates, was used to assess the association between PASI and SU at baseline with all patients pooled and to assess the association between Durate and DPASI over 12 weeks of treatment with secukinumab. Results. The degree of skin involvement of psoriasis showed a statistically significant, albeit modest, association with SU (R-2 = 0.014, P < 0.0001 univariately), whereas known risk factors for hyperuricaemia had a much larger impact cross-sectionally at baseline (R-2 = 0.33, P < 0.0001). Furthermore, a substantial improvement in PASI score resulted in only a modest decrease of SU over 12 weeks of treatment with secukinumab (R-2 = 0.014, P < 0.0001 univariately). Conclusions. There is a statistically significant, albeit modest, association with both extent and change in PASI score and SU in patients with psoriasis, compatible with a potential pathophysiological relationship between urate and psoriasis.
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| 19. |
- Dehlin, Mats, 1968, et al.
(författare)
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Incidence and prevalence of gout in Western Sweden
- 2016
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: 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. Methods: 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. Results: 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. Conclusions: 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.
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| 20. |
- Dehlin, Mats, 1968, et al.
(författare)
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Incident Gout: Risk of Death and Cause-Specific Mortality in Western Sweden: A Prospective, Controlled Inception Cohort Study
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundExcess mortality in gout has been attributed to cardiovascular diseases (CVD). Considering the decline in CVD mortality in the general population, we wanted to evaluate overall mortality in gout and cause-specific contributions to mortality beyond CVD and temporal trends. MethodsAll incident cases of gout between 2006 and 2015 in western Sweden and 5 population controls per case matched for age, sex, and county were identified. Comorbidities were identified for 5 years preceding the index date. Follow-up ended at death, migration, or end of study on December 2017. Effect of gout on death risk was calculated using COX regression on the whole population and stratified by sex, adjusted for demographics, and comorbidities. Death incidence rates were compared between the two time periods, 2006-2010 and 2011-2015. ResultsWe identified 22,055 cases of incident gout and 98,946 controls, median age (Q1, Q3) 69-68 (57, 79/56, 78) years and 67.6-66.5% males. Except for dementia, all comorbidities were significantly more common at baseline among gout cases. Overall, the risk for death in incident gout was neither increased overall nor in men, but women had a 10% elevated risk. In adjusted models for cause-specific mortality, death from CVD, renal disease, and digestive system diseases were significantly increased in the total gout population while death from dementia, cancer, and lung diseases were significantly decreased. There were no significant differences in overall incident death rate ratios between cases and controls in the two time periods examined. ConclusionsAn increased risk for CVD, renal disease, and diseases of the digestive system in patients with gout highlights the importance of addressing CVD risk factors in gout management. Gout was associated with reduced mortality from dementia, which may have implications on urate lowering therapy and possible effects on dementia risk.
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