Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.

The multiple comorbidities of psoriasis: The importance of a holistic approach.

BACKGROUND: Psoriasis is a common immune-mediated skin condition that affects at least 2% of the Australian population. Though psoriasis was often considered a cutaneous condition alone, more recent literature has shown other organ involvement. These comorbidities may be missed unless specifically looked for. OBJECTIVE: The aim of this article is to outline the well-recognised comorbidities associated with psoriasis to facilitate a discussion for general practitioners (GPs) to have with their patients about lifestyle changes, the need to screen for other diseases and management of comorbidities. DISCUSSION: GPs are in a prime position to screen, diagnose and manage comorbidities in a patient with psoriasis. GPs have a broad understanding of and exposure to general medicine and are in a privileged position of seeing many patients with psoriasis within the spectrum of the disease.

Subjective Health Complaints in Individuals with Psoriasis and Psoriatic Arthritis: Associations with the Severity of the Skin Condition and Illness Perceptions - A Cross-Sectional Study.

PURPOSE: High comorbidity has been reported among persons with psoriasis and psoriatic arthritis (PsA), but the occurrence of subjective health complaints (SHCs) in these patient groups is poorly understood. The study aimed to describe the prevalence of SHCs among individuals with psoriasis and PsA in Norway, and investigate whether the severity of their skin condition and their illness perceptions were associated with the number and severity of health complaints. METHOD: Participants were recruited through the Psoriasis and Eczema Association of Norway (PEF) (n = 942). The participants answered a self-administered questionnaire covering subjective health complaints, the severity of their skin condition, and their illness perceptions measured with the Brief Illness Perception Questionnaire (BIPQ-R). RESULTS: The prevalence and severity of SHCs were high. Participants with PsA reported more complaints and higher severity of complaints compared with participants with psoriasis. In both groups, the severity of the skin condition was associated with the number and severity of SHCs. Cognitive illness perceptions (consequences) and emotional illness perceptions (emotional affect) were associated with SHCs in participants with psoriasis, whereas only cognitive illness perceptions (consequences and identity) were associated with SHCs in participants with PsA. CONCLUSION: The high prevalence and severity of SHCs among individuals with psoriasis and PsA were associated with the severity of the skin condition and illness perceptions. Somatic and cognitive sensitizations are proposed as possible mechanisms. The findings suggest that holistic approaches are essential when managing these patient groups in health care institutions and clinical practice.

The effect of marine n-3 polyunsaturated fatty acids on cardiac autonomic and hemodynamic function in patients with psoriatic arthritis: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis. METHODS: The study was conducted as a randomized, double-blind, placebo-controlled trial, where 145 patients with psoriatic arthritis were supplemented with 3 g of n-3 PUFA or olive oil (control) daily for 24 weeks. Blood pressure, heart rate, heart rate variability (HRV), central blood pressure, pulse wave velocity (PWV) and fatty acid composition of granulocytes, were determined at baseline and after supplementation. RESULTS: At baseline we found a significant difference in the mean of all normal RR intervals (inverse of heart rate, vary from beat to beat) when comparing subjects with the highest vs the lowest fish intake (p = 0.03). After supplementation for 24 weeks there was a trend towards an increase in RR (p = 0.13) and decrease in heart rate (p = 0.12) comparing the n-3 PUFA group with the control group. However, per-protocol analysis showed significantly increased RR (p = 0.01) and lowered heart rate (p = 0.01) in the n-3 PUFA supplemented patients compared with controls. Blood pressure, PWV and Central blood pressure did not change after supplementation with n-3 PUFA. Adjustment for disease activity and conventional cardiovascular risk factors did not change the results. CONCLUSIONS: Marine n-3 PUFA increased RR intervals in patients with psoriatic arthritis which may suggest a protective effect of n-3 PUFA against cardiovascular disease in this population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01818804.

Emerging drugs for psoriatic arthritis.

INTRODUCTION: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. AREAS COVERED: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. EXPERT OPINION: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated.

Spotlight on ustekinumab in moderate to severe plaque psoriasis.

Ustekinumab (Stelara™) is a human monoclonal antibody that binds to the p40 subunit common to both interleukin (IL)-12 and IL-23. It is indicated in the US for use in adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In the EU, it is indicated for those who failed to respond to, have a contraindication to, or are intolerant of other systemic therapies or phototherapy. In well designed, randomized clinical trials, regimens of subcutaneous ustekinumab 45 or 90 mg provided a rapid and durable improvement in Psoriasis Area and Severity Index scores for patients with moderate to severe plaque psoriasis. Treatment with ustekinumab 45 or 90 mg also improved health-related quality-of-life scores from baseline. More limited data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis. Subcutaneous ustekinumab was generally well tolerated in clinical trials; most adverse events were mild in intensity and did not require dosage adjustment. A pooled analysis of clinical trial data indicated no specific patterns of infection for recipients of ustekinumab and that infection rates remained stable following cumulative exposure to the agent. Thus, subcutaneous ustekinumab provides an effective and well tolerated alternative for the symptomatic treatment of patients with moderate to severe plaque psoriasis.

Combination therapy of biologics with traditional agents in psoriasis.

Although biologics are very efficacious as monotherapy in patients with psoriasis, combination treatment with traditional systemic and topical therapies may increase the speed of onset and enhance efficacy without significant additional toxicity. In contrast, in psoriatic arthritis, the addition of methotrexate to anti-tumour necrosis factor-alpha therapy does not enhance efficacy in either the skin or joints.

Artritis psoriásica axial / Axial psoriatic arthritis

La afección espinal en la artritis psoriásica (APs) es un tema controvertido, a pesar de que no existen dudas desde el punto de vista clínico de la afectación espinal en la APs, actualmente no hay un consenso que permita definir la APs axial. En este trabajo se analizan los datos más recientes acerca de la clasificación, aspectos clínicos, de evaluación y terapia en la afección axial de la APs (AU)

Spinal involvement in PsA is a controversial issue. Currently, in spite of clinical recognition of axial involvement in axial PsA, there is a lack of consensus that impedes elaborating a definition for axial Psa. Recent advances in classification, clinical features, outcome measures and therapeutics are reviewed in this paper (AU)

Antibodies to human tissue transglutaminase and alterations of vitamin D metabolism in ankylosing spondylitis and psoriatic arthritis.

Both in ankylosing spondylitis (ASP) and psoriatic arthritis (PsA), osteopenia is present in one-third of women and men, whereas osteoporosis mainly affects men, even in their 30 s. Subclinical gut inflammation has been described in patients with AS or PsA. Joint involvement also occurs with other gastrointestinal diseases such as celiac disease. We tested the hypothesis, whether elevated serum levels of human anti-tissue-transglutaminase-IgA (htTG) are associated with changes in disease activity, vitamin D metabolism and bone mineral density (BMD) in patients with ASP and PsA. In a cross-sectional study, we evaluated both biochemical markers of bone turnover, BMD and htTG in 76 patients with ASP and 120 patients with PsA. A reduction of BMD in lumbar spine was determined both in ASP (42.7%) and in PsA (57.3%). Furthermore, a significantly higher prevalence of htTG was detected only in ASP (14/76). ASP patients with negative htTG status have significant higher 25-vitamin D3 levels. ASP patients with positive htTG status are younger. A positive htTG status entails the risk of a bad vitamin D supply, which should be considered in young patients since this constellation favors a reduction in bone density. The coincidence of ASP along with detection of htTG and clinically asymptomatic celiac disease as an accessory source of inflammation with a negative influence on the bone metabolism is also conceivable. Clinicians need to be aware of patients younger than 45 years with ASP, which have important implications for the correct treatment and vitamin D supplementation.

Efficacy and safety of etanercept in psoriasis after switching from other treatments: an observational study.

Since targeted biologic treatments have been introduced for the treatment of plaque-type psoriasis and psoriatic arthritis, switching between different medications has become necessary in selected patients, particularly after treatment failures. To evaluate the efficacy and safety of etanercept treatment in adult patients with psoriasis after failure to respond to other previous therapies. In particular, the differences in efficacy profiles after switching from traditional (cyclosporine [ciclosporin], methotrexate, retinoids, fumaric acid esters, psoralen plus UVA therapy, corticosteroids) or biologic (infliximab, efalizumab) treatments were analyzed. The study included 124 patients affected by plaque-type psoriasis who received etanercept administered subcutaneously at a dosage of 50 mg twice weekly for 12 weeks, followed by 25 mg twice weekly for an additional 12 weeks, and 110 patients affected by psoriatic arthritis who were treated with etanercept 25 mg twice weekly in a continuous regimen, after a 12-week period of treatment with etanercept 50 mg twice weekly. Efficacy results were consistent in both groups of patients (plaque-type psoriasis and psoriatic arthritis), as expressed by the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 50 and PASI 75 scores. Among psoriatic arthritis patients, the mean pain Visual Analog Scale (VAS) score showed a substantial reduction during the treatment course, from 67.2 at week 0 to 15.8 at week 24. After 24 weeks, among patients with plaque-type psoriasis who had not previously received biologic therapies, 89.9% of patients achieved PASI 50 and 75.3% achieved PASI 75, while among patients who had received biologic therapies, 69.6% of patients achieved PASI 50 and 65.2% achieved PASI 75. In addition, 92.3% of patients with psoriatic arthritis who had not previously received biologic therapies achieved PASI 50 and 73.8% achieved PASI 75, while among patients who had received biologic therapies, 45.8% of patients achieved PASI 50 and 29.2% achieved PASI 75. Our study demonstrated that etanercept was more effective in those patients who had not previously received other biologic therapies than in those who had. The results of the present study indicate that etanercept may represent a valid, effective, and well tolerated therapeutic alternative even after failure to respond to traditional and other biologic therapies.

Bone mineral density and bone turnover in patients with psoriatic arthritis.

Psoriasis is a common inflammatory skin disease, and conflicting data have been published about osteoporosis and bone turnover markers in patients with psoriatic arthritis. The aim of this study was to assess bone mineral density (BMD) and bone turnover markers in psoriatic patients with and without peripheral arthritis and to investigate the relationship between clinical parameters and markers of bone turnover. Forty-seven patients (24 women, 23 men) with psoriasis were included to the study. Demographic data and clinical characteristics were recorded. Erythrocyte sedimentation rate and C-reactive protein were assessed as disease activity parameters. BMD was determined for lumbar spine and total hip by dual X-ray absorptiometry (DXA). Serum Ca, P, alkalen phosphatase (ALP), and serum type I collagen cross-linked C telopeptide (CTX) were measured as bone turnover markers in all patients. The patients were divided into two groups according to their peripheral arthritis status. The clinical and laboratory variables, as well as bone mass status of the groups, were compared with each other. Eighteen patients had peripheral arthritis. All the female patients were premenopausal. None of the patients had radiologically assessed axial involvement. There was no significant difference between the BMD levels of psoriatic patients with and without arthropathy. One patient (5%) had osteoporosis, and nine (50%) patients had osteopenia in arthritic group, while eight (27.5%) patients had osteopenia in patients without arthritis. Serum CTX, ALP, Ca, and P levels were not significantly different in arthritic than in non-arthritic patients (p > 0.05). In patients with psoriatic arthritis, the duration of arthritis was negatively correlated with BMD values of lumbar spine and total femur and serum CTX levels, suggesting an association of increased demineralization with the duration of joint disease. In conclusion, psoriatic patients with peripheral arthritis with longer duration of joint disease may be at a risk for osteoporosis, which can require preventative treatment efforts.

The clinical spectrum of psoriasis.

The clinical picture of psoriasis is not uniform. Being one of the most common chronic inflammatory skin disorders, psoriasis may present in many different forms and may include extracutaneous manifestations. Classifications have been proposed based on disease onset or the clinical course of psoriasis. Chronic plaque psoriasis occurs in a variety of clinical forms primarily distinguished by size, distribution, and dynamics of psoriatic plaques. In addition, psoriasis inversa, localized and generalized pustular forms, erythrodermic psoriasis, as well as a number of more uncommon forms have been recognized, a distinction on clinical grounds that is relevant for the overall prognosis and impact on the patients' quality of life as well as for the choice of therapy. The broad and rather colorful clinical spectrum of psoriasis as well as implications for clinical practice will be comprehensively reviewed in this article.

[The impact of physical therapy on the quality of life of patients with rheumatoid and psoriatic arthritis].

INTRODUCTION: This open, uncontrolled study examined the effects of physical therapy and rehabilitation on the quality of life in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). MATERIAL AND METHODS: The study included a total of 109 patients (69 with RA and 40 with PsA). Patients came from Norway for a four-week rehabilitation period at the Institute of Physical Medicine, Rehabilitation & Rheumatology--Igalo from June till October, 2003. This was a self-controlled, pretest/posttest study. All patients had six days of physical therapy per week, during a four-week stay, which made a total of 24 therapy days. Basic therapy included mud packs/baths, kinesitherapy, hydrokinesitherapy and electrotherapy with analgesic effects. Quality of Life measurements were conducted two times (on admission and discharge) using questionnaire EuroQoL (EQ-5D). The research also included evaluation of ACR improvement. RESULTS: Pain/disability scale and the well being scale showed that quality of life in patients with PsA was significantly lower in comparison with RA patients. However, after 4 weeks, quality of life was much better in most dimensions of the EuroQoL questionnaire. Patients showed no improvement in self-care activities (in both group.) and daily activities (in group with PsA). Significant improvement was measured also in ACR improvement criteria (around 30%). CONCLUSIONS: Physical therapy at the Igalo Institute and good climate conditions have significantly improved the Health-Related-Quality-of-Life in both groups of patients. ACR index showed great

Psoriasis and psoriatic arthritis: clinical features and disease mechanisms.

Psoriasis is a chronic skin disorder affecting approximately 1% to 3% of the world's population. A considerable proportion of patients with psoriasis will develop a form of inflammatory arthritis known as psoriatic arthritis whose prevalence is poorly defined. Significant advances have been made in determining the pathophysiology of both of these diseases, with recent findings strongly implicating T cells and inflammatory cytokines such as tumor necrosis factor alpha in their pathogenesis. There exists an increasing array of therapies to benefit both skin and musculoskeletal manifestations. Newer therapies, such as the biologics, are providing more targeted approaches with potentially fewer systemic toxicities, providing control of disease symptoms and inhibiting progressive joint damage in those with arthritis, as well as improving long-term function and quality of life.

Subjective improvement in patients with psoriatic arthritis after short-term oral treatment with seal oil. A pilot study with double blind comparison to soy oil.

OBJECTIVE: To investigate effects of short-term oral treatment with seal oil in patients with psoriatic arthritis (PsA). METHODS: Forty-three patients with polyarticular PsA were randomized to receive oral treatment for 2 weeks with either seal oil or soy oil in a double blind controlled trial. Clinical and biochemical variables were assessed at baseline, after treatment, and 4 weeks post-treatment. Patients were allowed to continue nonsteroidal antiinflammatory drugs (NSAID) and disease modifying antirheumatic drugs (DMARD) during the study. RESULTS: Forty patients completed the study, 20 in each treatment group. Patients in the seal oil group reported a significant improvement in global assessment of the disease 4 weeks post- treatment (p < 0.01), and both groups showed a trend toward improvement in tender joint count, but the differences between the groups were not significant. There was a fall in the ratio of n-6 to n-3 fatty acids and in arachidonic acid (AA) to eicosapentaenoic acid (EPA) in serum after treatment with seal oil (p < 0.01). Twenty-one percent of all patients had elevated values of calprotectin in feces suggestive of asymptomatic colitis. CONCLUSION: Treatment with seal oil was followed by a modest improvement in patient's global assessment of the disease and a trend towards a decrease in number of tender joints. There was a shift in fatty acid composition in serum toward a putative antiinflammatory profile. Oral treatment with seal oil may have NSAID-like effects in PsA.

Current perspectives in the recognition and management of psoriatic arthritis: implications for integrated patient care.

Psoriatic arthritis (PsA), a chronic and debilitating spondyloarthropathy, is believed to affect as many as 30% of those with psoriasis. The use of tumor necrosis factor (TNF) inhibitors shows promise in the treatment of PsA and psoriasis. Etanercept, the first TNF inhibitor to be approved for use in PsA, inhibits the proinflammatory cytokine TNF in both conditions, making it possible for the clinician to prescribe a single agent to manage both the joint manifestations of PsA and the cutaneous manifestations of psoriasis. Etanercept has been shown to be well tolerated, even for long-term use, and is potentially superior to disease-modifying antirheumatic drugs.

The effect of low dose methotrexate on bone density.

OBJECTIVE: High dose methotrexate (MTX) has been linked with bone loss in oncology patients. However, it is unclear whether longterm low dose MTX used in the treatment of inflammatory arthritis is associated with bone loss. We compared the effect of low dose MTX on bone density in prospectively recruited patients with rheumatoid arthritis (RA) and psoriasis/psoriatic arthritis (Ps/PsA). METHODS: Thirty RA patients and 30 Ps/PsA patients taking MTX were compared to controls not taking MTX (30 with RA, 27 Ps/PsA). Bone mineral density (BMD) of the radius, lumbar spine, trochanter, and femoral neck was measured using Lunar dual energy x-ray absorptiometry. Student t tests were used to detect differences in bone density (using Z scores) of the MTX group versus controls for both the RA and Ps/PsA groups. Analysis of covariance was used to examine for confounders including disease duration, disease activity, age, and sex. RESULTS: BMD of the radius/femoral neck/trochanter did not differ significantly between the MTX treated groups and controls when analyzed by Z scores. The mean difference between the MTX group and controls of the femoral neck was 0.040 (95% CI -0.40, 0.12) and 0.060 (95% CI -0.30, 0.15) for the RA and Ps/PsA groups, respectively. The absolute BMD of the lumbar spine (L2-L4) was higher in the RA MTX group than in controls. Analysis of covariance did not reveal an effect of study group on bone density. CONCLUSION: This study suggests that low dose MTX does not have a negative effect on bone density, at either cortical or trabecular sites.

Immediate and delayed effects of treatment at the Dead Sea in patients with psoriatic arthritis.

The purpose of this study was to evaluate the immediate and delayed effects of balneotherapy at the Dead Sea on patients with psoriatic arthritis (PsA). A total of 42 patients with PsA were treated at the Dead Sea for 4 weeks. Patients were randomly allocated into two groups: group 1 (23 patients) and group 2 (19 patients). Both groups received daily exposure to sun ultraviolet rays and regular bathing at the Dead Sea. Group 1 was also treated with mud packs and sulfur baths. Patients were assessed by a dermatologist and a rheumatologist 3 days before arrival, at the end of treatment, and at weeks 8, 16, and 28 from the start of treatment. The clinical indices assessed were morning stiffness, right and left hand grip, number of tender joints, number of swollen joints, Schober test, distance from finger to floor when bending forward, patient's self-assessment of disease severity, inflammatory neck and back pain and psoriasis area and severity index (PASI) score. Comparison between groups disclosed a similar statistically significant improvement for variables such as PASI, morning stiffness, patient self-assessment, right and left grip, Schober test and distance from finger to floor when bending forward. For variables such as tender and swollen joints, and inflammatory neck and back pain, improvement over time was statistically significant in group 1. Addition of mud packs and sulfur baths to sun ultraviolet exposure and Dead Sea baths seems to prolong beneficial effects and improves inflammatory back pain.

Four cases of pustulotic arthro-osteitis.

We describe four cases of pustulotic arthro-osteitis. All of them suffered from anterior chest wall symptoms, such as swelling and pain on the sternoclavicular joint, sternal angle area, sternocostal joint, and costochondral junction. Although chest X-ray findings were all normal, 99mTc-scintigraphy revealed increased uptake in the affected areas in all cases. Laboratory examinations including rheumatoid factor were negative or normal except for elevation of the erythrocyte sedimentation rate and C-reactive protein in 2 cases. After treatment with non-steroidal anti-inflammatory drugs and etretinate or topical PUVA, the skin lesions on the palms and soles and the arthro-osteitis were moderately improved. Pustulotic arthro-osteitis should be considered when a patient with pustulosis palmoplantaris complains of anterior chest wall pain and other joint pain.