Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans.

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.

Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

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.

Long-term Outcomes and Prognosis in New-Onset Psoriasis.

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.

Comorbidities in a Cohort of 66 Patients With Psoriatic Arthritis Mutilans-Results From the Nordic PAM Study.

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.

Health-related quality of life in early psoriatic arthritis compared with early rheumatoid arthritis and a general population.

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.

HLA-B*27 is significantly enriched in Nordic patients with psoriatic arthritis mutilans.

OBJECTIVES: The genetic contribution to psoriatic disease is substantial with a dominating influence of the HLA region. The profile of HLA class I 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 I and II 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. CONCLUSIONS: HLA-B*27 emerges as an important genotype marker for PAM.

Radiographic scoring systems for psoriatic arthritis are insufficient for psoriatic arthritis mutilans: results from the Nordic PAM Study.

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 (r2 = 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.

DAPSA, DAS28 and MDA predict long-term treatment regime in psoriatic arthritis. The Swedish Early Psoriatic Arthritis Cohort.

OBJECTIVES: To describe treatment patterns in the Swedish early psoriatic arthritis cohort (SwePsA) of the mono-/oligo-arthritic (M/O) and polyarthritis (P) and identify early predictive factors for treatment with disease-modifying anti-rheumatic (DMARD), non-steroidal anti-inflammatory drugs (NSAID), and tumour necrosis factor inhibition (TNFi) after 5 years. METHODS: Data for 198 M/O and P PsA were obtained within the programme for SwePsA. Multinomial and binary logistic regression analyses were used to assess the association between early predictive factors and treatment after 5 years adjusted for age at inclusion. The analysis of DMARD/NSAID was adjusted for medication at inclusion. RESULTS: After inclusion visit, DMARD was prescribed in 30% of M/O and 56% of P PsA; mainly methotrexate. TNFi was not prescribed at inclusion, but 23 patients were treated at 5-year follow-up. The adjusted OR (95% CI) for treatment with both DMARD and NSAID after 5 years was 3.65 (1.34 - 9.89) (p=0.010) for Disease Activity Score 28 (DAS28) >3.2 and 2.90 (1.20-6.99) (p=0.038) for Disease Activity Index in Psoriatic Arthritis (DAPSA) >14 at inclusion. TNFi treatment was, after adjusting for age, associated with high erythrocyte sedimentation rate (p=0.0043), high C-reactive protein (p=0.013), DAPSA (p<0.001), not reaching minimal disease activity (p=0.001) high health assessment questionnaire (p=0.001), patient's overall assessment on the visual analogue scale (VAS) (p=0.009), high pain VAS (p=0.007), and high number of tender and swollen joints (p=0.031) at inclusion. CONCLUSIONS: Disease activity in early M/O and P PsA is to be considered in deciding the level of health care assessment and future pharmacological treatment. DAS28 >3.2 and DAPSA>14 early in the disease predict subsequent treatment with DMARD. For prediction of biological treatment, not reaching MDA at onset of disease, would be the composite index of choice.

Is low molecular weight hyaluronan an early indicator of disease in avian systemic sclerosis?

AIM OF THE STUDY: To further elucidate the pathogenesis of systemic sclerosis (SSc) an experimental avian model was used. The University of California at Davis line 200 (UCD-200) chickens spontaneously develop a SSc-like disease that has most features of human SSc with vascular effects, inflammation, autoimmunity, and fibrosis. The first signs of disease in UCD-200 chickens are swelling and ischemic lesions of the comb and the presence of a tissue containing high amounts of glycosaminoglycan hyaluronan (HA). The aim of this study was to evaluate inflammatory and fibrotic processes of the disease with regard to the molecular weight of HA. MATERIAL AND METHODS: Comb biopsies from UCD-200 and healthy White Leghorn (WL) chickens, as controls, at different ages were studied with the histochemical localization of HA, hyaluronidase-1 (Hyal-1), cluster of differentiation 3, immunoglobulin Y, and collagen I and III. The molecular weight distribution of HA was estimated with gas-phase electrophoretic analysis. RESULTS: At 2 days of age, HA was visualized in UCD-200 chickens at the dermal part of the comb with no simultaneous staining of Hyal-1. In adult UCD-200 chickens, the comb skin was almost totally devoid of HA compared to WL chickens of the same age. An increase of low molecular weight (LMW) HA was detected in comb tissue from UCD-200 at the age of 1 day, 1 week, 2 weeks, and 4 weeks, in contrast to adult animals. CONCLUSIONS: An early inflammatory process involving LMW HA was confirmed as a possible profibrotic process. This indicates that HA might be an important participant in the early inflammatory events of SSc in UCD-200 chickens and that the disappearance of HA in skin predisposes to fibrosis.

High Sensitivity Method to Estimate Distribution of Hyaluronan Molecular Sizes in Small Biological Samples Using Gas-Phase Electrophoretic Mobility Molecular Analysis.

Hyaluronan is a negatively charged polydisperse polysaccharide where both its size and tissue concentration play an important role in many physiological and pathological processes. The various functions of hyaluronan depend on its molecular size. Up to now, it has been difficult to study the role of hyaluronan in diseases with pathological changes in the extracellular matrix where availability is low or tissue samples are small. Difficulty to obtain large enough biopsies from human diseased tissue or tissue from animal models has also restricted the study of hyaluronan. In this paper, we demonstrate that gas-phase electrophoretic molecular mobility analyzer (GEMMA) can be used to estimate the distribution of hyaluronan molecular sizes in biological samples with a limited amount of hyaluronan. The low detection level of the GEMMA method allows for estimation of hyaluronan molecular sizes from different parts of small organs. Hence, the GEMMA method opens opportunity to attain a profile over the distribution of hyaluronan molecular sizes and estimate changes caused by disease or experimental conditions that has not been possible to obtain before.

The Swedish Early Psoriatic Arthritis Registry 5-year Followup: Substantial Radiographic Progression Mainly in Men with High Disease Activity and Development of Dactylitis.

OBJECTIVE: To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction. METHODS: Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol. RESULTS: Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score > 10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores > 10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men. CONCLUSION: Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs.

Radiographic development during three decades in a patient with psoriatic arthritis mutilans.

Psoriatic arthritis mutilans (PAM) is the most severe and rare form of psoriatic arthritis (PsA). We describe radiological development in a typical case of PAM covering three decades in order to elucidate the need for early diagnosis of PAM. Radiographs of hands and feet, taken from 1981 to 2010, were evaluated using the Psoriatic Arthritis Ratingen Score (PARS). When PsA was diagnosed, in 1981, gross deformity was observed in the second PIP joint of the left foot. Several pencil-in-cup deformities and gross osteolysis were present in the feet in the first decade of the disease. Over 10 years, many joints had reached maximum scores. During the follow-up, other joints became involved and the disease developed clinically. Reporting early signs suggestive of PAM, e.g. pencil-in cup deformities and gross osteolysis in any joint, should be mandatory and crucial. This would heighten our awareness of PAM, accelerate the diagnosis, and lead to improved effective treatment in order to minimize joint damages resulting in PAM.

Elevated Membrane and Soluble CD64: A Novel Marker Reflecting Altered FcγR Function and Disease in Early Rheumatoid Arthritis That Can Be Regulated by Anti-Rheumatic Treatment.

OBJECTIVES: Fc receptors (FcR) interacting with immune complexes (ICs) is a central event in the immune pathogenesis of rheumatoid arthritis (RA). Here we asked if a specific FcR is linked to RA pathogenesis and if FcR activities relate to disease and treatment outcome in early RA. MATERIAL AND METHODS: Twenty autoantibody-positive RA patients and 33 HC were included. The patients were evaluated before and after treatment with methotrexate and prednisolone. At follow-up, the EULAR response criteria were applied to determine the individual treatment outcomes. Serum immunoglobulin levels were measured and the expression of FcR for IgG (FcγR) and IgA (FcαR) on peripheral blood monocytes were determined by flow cytometry. The monocytic FcγR function was evaluated by human IgG1 and IgG3 IC-binding and TNFα stimulated release. Plasma levels of soluble FcRs (sFcRs) were determined with ELISA. RESULTS: The IgG1 and IgG3 levels were elevated in the RA sera. The RA monocytes expressed more CD64 and cell surface-bound IgG than HC monocytes, and showed an impaired FcγR function as reflected by changes in IC-binding and decreased IC-stimulated TNFα secretion. These findings correlated significantly with different disease activity markers. Furthermore, sFcRs were elevated in the patient plasma, and sCD64 was specific for RA (compared with a reference group of patients with active psoriatic arthritis). Following treatment, immunoglobulins and sFcR levels were reduced, whereas membrane CD64 was only decreased in patients with good response to treatment. CONCLUSIONS: Early RA patients display increased membrane and soluble CD64 and an impaired FcγR function correlating with joint disease activity. Beneficial responses of anti-rheumatic treatment in patients reduce CD64. These data suggest sCD64 as an important objective biomarker in RA.

Dysregulated Fc receptor function in active rheumatoid arthritis.

Given the critical role of Fc gamma receptors (FcγR) as primary targets for autoantibody-mediated effects an important issue is how the FcγR pathway is affected in autoimmune disorders. Here we investigated the FcγR function in monocytes from rheumatoid arthritis (RA) patients in relation to immunoglobulin levels and disease activity. Peripheral blood was obtained from 30 RA patients with clinical acute joint synovitis (active RA), 28 RA patients with no clinical signs of acute joint synovitis (non-active RA) and 34 healthy controls. Prior the functional studies the monocytes were characterized of their FcγRI (CD64), II (CD32), IIb (CD32b) and III (CD16) expression as well as their cell surface bound IgG. The monocytic FcγR function was assessed by binding of human IgG1 and IgG3 immune complexes (IC) and TNF secretion in vitro. IgG anti-citrullinated peptide antibodies (ACPA) were analyzed in the plasma. We found that monocytes from active RA patients had increased levels of FcγRI, II and cell surface IgG concurrently with impaired FcγR function. This was evident by reduced IgG1-IC binding and decreased TNF secretion in response to IgG3-IC. In contrast, monocytes from non-active RA patients displayed a normal FcγR function and had increased FcγRIIb expression together with elevated FcγRI, II and cell surface IgG. The ACPA levels did not differ in active and non-active RA patients but correlated with the monocytic FcγRIII expression in the patients. In conclusion, active RA patients display a dysregulated FcγR function that may represent a novel phenotypic and likely pathogenetic marker for active RA. A disease and FcγR function controlling effect is suggested by the increased inhibitory FcγRIIb in non-active RA.

Early psoriatic arthritis: short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish Early Psoriatic Arthritis Register (SwePsA).

OBJECTIVE: The Swedish Early Psoriatic Arthritis Register describes the course of early psoriatic arthritis (PsA) in a real life clinical setting in Sweden. The aim of this study was to obtain information on predictors of clinical outcomes over a 5-year period with special focus on effects of gender, joint patterns, diagnostic delay and initial disease activity. METHODS: In six centres, patients with signs suggestive of PsA were included in the Swedish Early Psoriatic Arthritis Register within 2 years of symptom onset. CASPAR (classification for psoriatic arthritis) criteria were fulfilled by 197 patients who had passed the 5-year follow-up. Disease activity was measured by the Disease Activity Score including 28 joints (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). Remission and minimal disease activity (MDA) were used as outcome measures. RESULTS: Mean age at inclusion was 46 years, younger in male than female patients (43 vs 48 years). Mean DAS28 was 3.7 and 3.0 at inclusion and 2.8 and 2.1 at follow-up for women and men, respectively-significantly higher in women at both visits. Likewise, DAPSA scores were significantly higher in women. The degree of improvement (change in DAS28 and DAPSA) was similar. Men achieved MDA or remission (50% vs 33%, 25% vs 13%, respectively) more often, and women had significantly more polyarthritis at inclusion (49% vs 27%) and after 5 years (25% vs 15%). Axial or mono/oligoarticular disease was predominant in men. Independent predictors of MDA at the 5-year follow-up were: shorter symptom duration; greater general well-being (global visual analogue scale); and low Health Assessment Questionnaire at inclusion. CONCLUSIONS: In early PsA, short delay between onset of symptoms and diagnosis, preserved function, and male gender are the most important predictors of favourable clinical outcome at the 5-year follow-up. Early recognition of PsA and active treatment may be important, particularly in women with polyarticular disease.

Dermal distribution of hyaluronan in psoriatic arthritis; coexistence of CD44, MMP3 and MMP9.

Psoriatic arthritis is a chronic systemic disease in which patients develop persistent inflammation of the skin and joints, leading to disability and joint damage. The extracellular component hyaluronan (HA) plays an important role in regulatory processes such as inflammation, wound healing and tumour progression. At any site of inflammation HA can be depolymerized to low-molecular weight fragments, which, in turn, induce an array of inflammatory mediators that can lead to chronic inflammation. This study describes the serum concentration and dermal distribution of HA, its receptor CD44 and the metalloproteinases 3 and 9 in skin biopsies from patients with different types of psoriatic arthritis. Fifty-one patients with psoriatic arthritis were included in the study and classified as oligo- or poly-arthritic PsA with and without treatment. Biopsies were obtained from both involved and non-involved skin and compared with biopsies from healthy individuals. Serum HA was analysed for estimation of the total turnover of HA. The main findings were an overall redistribution of HA in both involved and non-involved psoriatic skin and an epidermal imbalance between HA and CD44. The structurally and functionally important basement membrane zone was found to be disintegrated and devoid of HA irrespective of the type of articular involvement, treatment or skin affection.

Down regulation of Fc and complement receptors on B cells in rheumatoid arthritis.

B cell tolerance is regulated by receptors that modulate B cell receptor signaling, such as Fc gamma receptor IIb (FcγRIIb; CD32b) and complement receptors (CR) 1 and 2. Deficiency in these receptors may contribute to autoimmunity. To address this we have investigated the receptor expression in healthy individuals in comparison with rheumatoid arthritis (RA) patients. In healthy subjects we found that women had overall lower FcγRIIb expression on B cells than men that significantly decreased with age. RA patients had fewer FcγRIIb, CR1 and CR2 positive B cells and decreased receptor expressions compared to healthy subjects. Further, the RA B cells displayed a significantly increased proliferative response when cultured with interleukin-2 in vitro. In summary, the dysregulated B cells in RA are associated with lower FcγRIIb, CR1 and CR2 levels. The reduced FcγRIIb expression on B cells in women may influence the increased frequency of autoimmunity in women.

Physical activity and quality of life in subjects with chronic disease: chronic obstructive pulmonary disease compared with rheumatoid arthritis and diabetes mellitus.

OBJECTIVE: Chronic diseases interfere with the life situation of the affected person in different ways. The aim was to compare the burden of disease in three chronic diseases - chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), diabetes mellitus (DM) - and in healthy subjects, with a particular interest in physical activity, quality of life, and psychological health. DESIGN: Cross-sectional, observational study. SETTING AND SUBJECTS: Postal survey questionnaire to a stratified, random population of 68 460 subjects aged 18-84 years in Sweden. The subjects included were 40-84 years old (n = 43 589) and data were analysed for COPD (n = 526), RA (n = 1120), DM (n = 2149) and healthy subjects (n = 6960). RESULT: Some 84% of subjects with COPD, 74% (RA), 72% (DM), and 60% in healthy subjects (p < 0.001, COPD versus RA, DM, and healthy subjects) had a physical activity level considered too low to maintain good health according to guidelines. Quality of life (EuroQol five-dimension questionnaire, EQ-5D) was lower in COPD and RA than in DM. Anxiety/depression was more common in subjects with COPD (53%) than in those with RA (48%) and DM (35%) (p < 0.001, COPD versus RA and DM), whereas mobility problems were more common in RA (55%) than COPD (48%) and DM (36%) (p < 0.001, RA versus COPD and DM). All differences between groups remained significant after adjusting for age, sex, and socioeconomic background factors. CONCLUSION: Subjects with chronic diseases had a low level of physical activity, most evident in subjects with COPD. COPD and RA had a higher negative impact on quality of life than DM. Our results indicate that increased attention regarding physical inactivity in subjects with chronic diseases is needed to minimize the burden of disease.