| 1. |
- Geijer, Mats, 1957, et al.
(författare)
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Health-related quality of life in early psoriatic arthritis compared with early rheumatoid arthritis and a general population
- 2021
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Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 51:1, s. 246-252
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Both psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have a significant impact on quality of life, but few reports have compared the two diseases. The current study assessed health-related quality of life (HRQoL) in PsA at diagnosis and after five years compared with early rheumatoid arthritis (RA) and a matched general population. Methods: Patients with early PsA and early RA included in two Swedish registries with HRQoL data measured by the Medical Outcomes Study Short Form 36 (SF-36) at baseline and at five years follow-up were included. Differences in SF-36 scores compared with the general population were calculated for each patient. Physical function, disease activity, the delay before diagnosis, pain, and general wellbeing were used as explanatory variables. Statistical tests included t-tests and univariate and multivariate linear regression. Results: PsA (n = 166) and RA (n = 133) patients of both sexes had significantly reduced HRQoL at disease onset. After five years, PsA patients still had impairments in several domains of SF-36, whereas RA patients had an almost normalized HRQoL. The time from symptom onset to diagnosis, disease activity, and disability independently contributed to the reduced improvement in PsA. Conclusion: Both early PsA and RA are characterized by severely reduced HRQoL. Despite more severe disease at inclusion, normalization of HRQoL is seen in patients with RA but not PsA. This may be due to delay in the diagnosis of PsA or more powerful interventions in RA. Earlier detection, lifestyle intervention, and more aggressive management strategies may be needed for PsA. (C) 2020 Elsevier Inc. All rights reserved.
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| 2. |
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| 3. |
- Hellman, Urban, 1966-, et al.
(författare)
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Hyaluronan concentration and molecular mass in psoriatic arthritis : biomarkers of disease severity, resistance to treatment, and outcome
- 2019
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis Group. - 0300-9742 .- 1502-7732. ; 48:4, s. 284-293
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Low molecular mass hyaluronan causes inflammatory processes and can act as a pro-inflammatory cytokine in skin and other sites of activity in psoriatic arthritis (PsA). This study investigated whether the molecular mass distribution of hyaluronan (HA) in skin and the quantity of circulating HA are related to the clinical inflammatory picture in PsA with active disease and to the effect of treatment with anti-tumour necrosis factor-α (anti-TNF-α) adalimumab.Methods: Twenty patients with TNF-α-naïve active polyarticular PsA were included in this prospective clinical trial of treatment with 40 mg s.c. adalimumab according to standard procedure. Clinical activity, patients’ assessments, and skin biopsies were captured at inclusion and at the 12 week follow-up. Ten healthy individuals were recruited for comparison of HA analyses. Histochemistry of skin inflammation, serum HA, and molecular mass of HA were determined.Results: Overall improvements in clinical parameters were observed. Eight of 18 patients reached minimum disease activity after 12 weeks and disease activity was significantly reduced (p < 0.0001). Patients with elevated serum HA values were significantly older, had later onset of arthritis and more deformed joints, still had swollen joints after treatment, and had more circulating inflammatory biomarkers. More severe disease pathology showed a wide spectrum of high-molecular-mass HA accompanied by low mass HA. The treatment appears partly to normalize the HA mass distribution.Conclusion: HA concentration and mass seem to be two possible factors in the inflammatory pathology of PsA acting as biomarkers for disease severity, resistance to treatment, and worse outcome.
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| 4. |
- Henrohn, Dan
(författare)
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Pulmonary Hypertension and the Nitric Oxide System
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary hypertension (PH) is a pathophysiological state associated with several medical conditions, leading to progressive rise in pulmonary vascular resistance (PVR) and right ventricular failure. The clinical PH classification encompasses five main World Health Organization (WHO) groups; pulmonary arterial hypertension (PAH), PH due to left heart disease, PH due to lung diseases and/or hypoxia, chronic thromboembolic PH, and PH with unclear multifactorial mechanisms. Nitric oxide (NO) is a potent vasodilator. Impaired NO production via the classical L-arginine-NO synthase (NOS) pathway has been implicated in PH. Phosphodiesterase-5 (PDE5) inhibitors augment NO signalling, and are considered as one of the cornerstone treatments in PAH. The studies in this thesis aim at to explore and expand the understanding of the NO system in patients with PH.In paper I, we found that PAH patients (WHO group 1) have lower bronchial NO flux compared to healthy controls and patients with PH (WHO group 2–4). This implies reduced bronchial NO formation in PAH. Compared to healthy controls, increased alveolar NO levels were found in patients with PH (WHO group 1-4) and patients with PAH. This may reflect NO diffusion disturbances in the alveoli. PAH patients had higher plasma and salivary levels of nitrite than healthy controls, which may reflect a compensatory upregulation of NOS-independent NO generating pathways.In paper II, we observed that a single oral dose of vardenafil (a PDE5 inhibitor) causes rapid changes in cardiopulmonary haemodynamics in PH patients with PH (WHO group 1-4). We found a correlation between plasma vardenafil concentrations and the changes in mean pulmonary arterial pressure as well as PVR.In paper III, we show that a single oral dose of vardenafil to patients with PH (WHO group 1-4) alter the plasma levels of arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the arginine/ADMA ratio in a favourable manner. The increase in arginine and the arginine/ADMA ratio were associated with improved cardiac index, and the increase in the arginine/ADMA ratio at 540 min correlated with the exposure to vardenafil. Higher baseline plasma levels of ADMA and SDMA and a low arginine/ADMA ratio was associated with a more severe pulmonary haemodynamic disease state in patients with PH.In paper IV, we found that ingestion of beetroot juice, containing inorganic nitrate, increased plasma and salivary levels of nitrate and nitrite, increased exhaled NO, decreased plasma ornithine levels and increased relative arginine availability in patients with PAH compared to placebo. Higher plasma levels of nitrite after the placebo period, reflecting basal conditions, were associated with a more severe PAH phenotype. Our findings indicate that the nitrate-nitrite-NO pathway is active and upregulated in PAH patients.
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| 5. |
- Laasonen, Leena, et al.
(författare)
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Radiographic scoring systems for psoriatic arthritis are insufficient for psoriatic arthritis mutilans : results from the Nordic PAM Study
- 2020
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Ingår i: Acta Radiologica Open. - : SAGE PUBLICATIONS LTD. - 2058-4601. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis (PsA).Purpose: To describe the radiological features in PAM and explore whether existing scoring systems for radiological damage in psoriatic arthritis are applicable for PAM.Material and Methods: Radiographs were scored according to the modified Sharp-van der Heijde (mSvdH) and the Psoriatic Arthritis Ratingen Score (PARS) systems for PsA.Results: At inclusion, 55 PAM patients (49% women, mean age 58 +/- 12 years) had conventional radiographs of both hands and feet. A total of 869 PAM joints were detected and 193 joints with ankylosis. The mean total mSvdH score was 213.7 +/- 137.8 (41% of maximum) with a higher score for hands than for feet: 136.6 +/- 90.1 vs. 79.1 +/- 60.9. However, the total score was relatively higher in the feet than in the hands when compared to the highest possible scoring (47% vs. 38% of max). The mean total PARS score was 126.3 +/- 79.6 (35% of max). Scoring for joint destruction was higher than for proliferation (22% vs. 11% of max). Strong correlation was found between mSvdH and PARS (r(2) = 0.913). A significant correlation was found between scoring and duration of arthritis and the Health Assessment Questionnaire. History of smoking, BMI, and gender did not influence the scoring values.Conclusions: The two scoring systems studied may not be ideal to indicate progression of PAM in advanced disease since they reach ceiling effects rather early. Therefore, reporting early signs suggestive of PAM, e.g. signs of pencil-in-cup deformities or osteolysis, is crucial. This would reveal the presence of PAM and might lead to improved treatment in order to minimize joint damage.
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| 6. |
- Leung, Ying-Ying, et al.
(författare)
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Management of Peripheral Arthritis in Patients With Psoriatic Arthritis : An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations
- 2023
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 50:1, s. 119-130
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Forskningsöversikt (refereegranskat)abstract
- Objective We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations.Methods A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings.Results The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain.Conclusion Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.
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| 7. |
- Lindqvist, Ulla, 1948-, et al.
(författare)
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Disease activity in and quality of life of patients with psoriatic arthritis mutilans : the Nordic PAM Study
- 2017
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 46:6, s. 454-460
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries.Method: Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM.Results: Sixty-seven patients were included. Patients with PAM had a protracted disease history (3314years) and disease onset at a relatively early age (30 +/- 12years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60years of age reported the most impaired quality of life in comparison to the control group.Conclusion: PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.
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| 8. |
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| 9. |
- Lindqvist, Ulla, 1948-, et al.
(författare)
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Psoriasisartrit
- 2011. - 2. uppl
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Ingår i: Reumatologi. - Stockholm : Studentlitteratur. - 9789144055329 ; , s. 111-118
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 11. |
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| 12. |
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| 13. |
- Milosavljevic, Jugoslav, et al.
(författare)
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Ultrasound and power Doppler evaluation of the hand and wrist in patients with psoriatic arthritis
- 2005
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 46:4, s. 374-385
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the ability of high-resolution and power Doppler sonography in detecting joint and tendon abnormalities in patients with psoriatic arthritis (PsA) of the hands and wrists compared with clinical and radiological findings. MATERIAL AND METHODS: Thirty-six patients with psoriatic arthritis of the hands and wrists and 10 healthy controls were examined with ultrasound (US). The degree of synovial proliferation, tenosynovitis, presence of joint effusion as well as the vascularity of synovial tissue was estimated. US findings were scored using a newly devised scoring system. RESULTS: Thirty-two patients had articular synovial proliferation and/or tenosynovitis/ tendinitis or joint effusion in one or more joints according to US. Twenty-two patients had tendon changes; only five had joint effusion. The synovial, Doppler, and total articular-teno scores were all significantly correlated to the number of swollen joints. The scores, however, did not correlate to other clinical or laboratory measurements of disease activity. CONCLUSION: US proved effective in demonstrating PsA involvement of the hands and wrists and was more sensitive than clinical examination in detecting pathology. Long-term follow-up studies are needed to evaluate whether this can change the traditional approach for assessing involvement of joints and tendons in PsA.
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| 14. |
- Mistegård, Josephine, et al.
(författare)
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Comorbidities in a Cohort of 66 Patients With Psoriatic Arthritis Mutilans-Results From the Nordic PAM Study
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis due to excessive bone erosion causing joint destruction and decreased functional capacity. The aim of this study was to investigate the prevalence of comorbidities among patients with PAM and the association between comorbidities and joint involvement.Methods: A total of 66 patients aged >= 18 years from the Nordic countries with past or present psoriasis along with at least one mutilated joint were included in the present study.Results: The median number of comorbid conditions per patient was 1 [interquartile range (IQR) 0-2] and 16.7% reported three or more comorbidities. The most frequent comorbidity was hypertension (36.4%). The median number of mutilated joints per patient was 3 (IQR 1-8.3; range 1-38).Conclusion: Two thirds of the patients with PAM reported comorbid conditions and the most frequent was hypertension which affected more than a third of the patients. However, this study was unable to detect any association between comorbidities and the severity of PAM.
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| 15. |
- Nikamo, P., et al.
(författare)
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HLA-B*27 is significantly enriched in Nordic patients with psoriatic arthritis mutilans
- 2021
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Ingår i: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 39:4, s. 775-780
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Tidskriftsartikel (refereegranskat)abstract
- Objective The genetic contribution to psoriatic disease is substantial with a dominating influence of the MLA region. The profile of HLA class 1 genotypes likely contributes to shaping clinical phenotypes. Herein we aimed to explore such genotypes in cohorts of closely characterised subsets of psoriatic disease with special focus on psoriatic arthritis mutilans (PAM), a severe and rare form of psoriatic arthritis (PsA). Methods Cohorts of patients with the diagnosis of psoriasis vulgaris with or without arthritis (n=1217), psoriasis without arthritis (n=534), psoriatic arthritis without mutilating disease (n=337) and psoriatic arthritis mutilans (n=63) were collected and genotyped for HLA class 1 and 11 genes, with standardised methodologies. Cases were compared with a healthy control population (n=2468). Case-only and case-control association tests were performed to address the hypothesis of genetic contribution to clinical phenotypes. Results The presence of HLA-B*27 was strikingly increased in PAM (45%) compared with PsA without mutilating disease (13%) and with healthy controls (13%). However, within the PAM population, HLA-B*27 did not correlate with clinical markers such as number of mutilating joints, radiographic scoring, disease duration and age of disease onset. Conclusion HLA-B*27 emerges as an important genotype marker for PAM.
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| 16. |
- Pasquali, L, et al.
(författare)
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Circulating microRNAs in extracellular vesicles as potential biomarkers for psoriatic arthritis in patients with psoriasis
- 2020
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 34:6, s. 1248-1256
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psoriatic arthritis (PsA) develops in ~30% of patients with psoriasis. The diagnosis of PsA is challenging, and there are no reliable molecular markers in clinical use. MicroRNAs are short non-coding regulatory RNAs, which can be actively packaged into extracellular vesicles (EVs) and secreted to the circulation.OBJECTIVES: To explore whether plasma-derived EV microRNAs may serve as biomarkers for PsA in patients with psoriasis.METHODS: Plasma samples were obtained from patients with cutaneous-only psoriasis (PsC) and patients with psoriasis and PsA. Plasma EVs were isolated using miRCURY™ Exosome Isolation Kit. RNA sequencing was used to identify differentially expressed EV miRNAs in the discovery phase (PsC, n = 15; PsA, n = 14). In the validation phase (PsC, n = 29; PsA, n = 28), 41 selected miRNAs were analysed in plasma EVs by qPCR. The association of the identified miRNAs with PsA was assessed by logistic regression analysis.RESULTS: RNA sequencing identified 19 plasma EV miRNAs with significantly different levels between PsA and PsC in the discovery cohort. Significantly lower levels of plasma EV let-7b-5p and miR-30e-5p in PsA vs. PsC were confirmed in the validation cohort, and their decreased levels were found to be associated with the presence of PsA. ROC analysis revealed an AUC of 0.68 (95% CI 0.53-0.83) for let-7b-5p and 0.69 (95% CI 0.55-0.84) for miR-30e-5p.CONCLUSIONS: Circulating EV microRNA levels are altered in patients with PsA as compared with PsC. Findings of this exploratory study suggest that circulating EV microRNAs may serve as biomarkers for arthritis in psoriasis patients.
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| 17. |
- Svedbom, Axel, et al.
(författare)
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Long-term Outcomes and Prognosis in New-Onset Psoriasis
- 2021
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Ingår i: JAMA dermatology. - : American Medical Association (AMA). - 2168-6068 .- 2168-6084. ; 157:6, s. 684-690
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Tidskriftsartikel (refereegranskat)abstract
- Importance Psoriasis is a heterogeneous disease. Improved understanding of prognosis and long-term outcomes in new-onset psoriasis may improve care.Objective To describe the clinical course of psoriasis and identify possible indicators of long-term outcomes.Design, Setting and Participants The Stockholm Psoriasis Cohort was a noninterventional inception cohort study enrolling patients between 2001 and 2005. The present study was conducted from January 15, 2019, to February 5, 2021. At enrollment and 10 years, patients were examined by dermatologists and rheumatologists. Data from examinations were complemented by questionnaires, medical records, and registers. A total of 721 patients with recent-onset psoriasis (<12 months duration), 15 years or older were recruited using advertising and referrals from a broad range of health care settings.Main Outcomes and Measures Disease severity and psoriatic arthritis (PsA). Recursive partitioning and regression models were implemented to identify probable indicators of long-term outcomes.Results A total of 721 patients (median [interquartile range] age, 39 [27-55] years; 405 [56%] women), including 542 (75%) with plaque-onset and 174 (24%) with guttate-onset psoriasis, were enrolled. The median follow-up was 9.6 years (interquartile range, 8.8-10.4 years). The cumulative incidence of severe psoriasis at 12 years from enrollment was 21%. Among 509 patients examined clinically after 10 years, 77 of 389 patients (20%) with plaque onset and 56 of 116 (48%) with guttate onset had minimal disease activity without treatment, and 120 of 509 (24%) had PsA. Recursive partitioning identified strata with distinct risks for severe skin disease and PsA: the cumulative incidence of severe disease in patients with plaque phenotype, above-median disease activity, and scalp lesions was 52% (95% CI, 41%-64%), compared with 11% (95% CI, 8%-14%) in patients with below-median disease activity at inclusion; and 48 of 82 patients (59%) with peripheral enthesitis had PsA after 10 years compared with 37 of 304 patients (12%) without initial joint pain (P < .001). Smoking (hazard ratio, 1.70; 95% CI, 1.10-2.63) and activating genes in the interleukin-23 (IL-23) pathway (odds ratio, 1.55; 95% CI, 1.14-2.11) were also significantly associated with a severe disease course. Systemic therapy at or before enrollment was associated with a lower risk for severe disease at 10 years compared with later initiation of systemic therapy (odds ratio, 0.24; 95% CI, 0.06-0.90).Conclusions and Relevance The findings of this cohort study suggest that combinations of clinical characteristics at onset and activating genes in the IL-23 pathway are significantly associated with the clinical course of psoriasis, whereas joint pain and peripheral enthesitis may indicate the probability of PsA. Patients within those categories merit specialist referral and closer follow-up. The possibility of modifying the disease course with early systemic intervention should be tested.
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| 18. |
- Wang, Sailan, et al.
(författare)
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Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans
- 2024
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Ingår i: EMBO Molecular Medicine. - : EMBO Press. - 1757-4676 .- 1757-4684. ; 16:3, s. 596-615
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Tidskriftsartikel (refereegranskat)abstract
- Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target.
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