Comparison of greenhouse gas emissions from sheep measured using both respiration and portable accumulation chambers.

Methane (CH4) is a potent gas produced by ruminants, and new measurement techniques are required to generate large datasets suitable for genetic analysis. One such technique are portable accumulation chambers (PAC), a short-term sampling method. The objectives of the current study were to explore the relationship between CH4 and carbon dioxide (CO2) output measured using both PAC and respiration chambers (RC) in growing lambs, and separately investigate the relationship among CH4, CO2 and measured ad libitum DM intake (DMI). Methane, CO2 and DMI were measured on 30 Suffolk and 30 Texel ewe lambs (age 253 ± 12 days) using the RC and PAC sequentially. The experiment was conducted over a 14-day period, with DMI measured from days 1 to 14; measurements in RC were conducted from days 10 to 12, while measurements in PAC were taken twice, the day immediately prior to the lambs entering the RC (day 9; PAC Pre-RC) and on the day lambs exited the RC (day 13; PAC Post-RC). Greater CH4 and CO2 output was measured in the RC than in the PAC (P < 0.01); similarly mean CH4 yield was greater when measured in the RC (15.39 ± 0.452 g CH4/kg DMI) compared to PAC (8.01 ± 0.767 g CH4/kg DMI). A moderate correlation of 0.37 was found between CH4 output measured in PAC Pre-RC and the RC, the corresponding regression coefficient of CH4 output measured in the RC regressed on CH4 output measured in PAC Pre-RC was close to unity (0.74; SE 0.224). The variance of CH4 and CO2 output within the measurement technique did not differ from each other (P > 0.05). Moderate to strong correlations were found between CH4 and CO2 per kg of live weight and CH4 and CO2 yield. Results from this study highlight the suitability of PAC as a ranking tool to rank animals based on their gaseous output when compared to the RC. However, repeated measurements separated by several days may be beneficial if precise rankings are required. Given the close to unity regression coefficient of CH4 output measured in the RC regressed on CH4 output measured in PAC Pre-RC suggests that PAC could also be potentially used to estimate absolute CH4 output; however, further research is required to substantiate this claim. When DMI is unknown, CH4 and CO2 per kg of live weight are a suitable alternative to the measurement of CH4 and CO2 yield.

Modifiable risk factors and the development of psoriatic arthritis in people with psoriasis.

BACKGROUND: Psoriatic arthritis (PsA) is a progressive and often destructive joint disease affecting approximately 20% of people with psoriasis. OBJECTIVES: To investigate associations between obesity, changes in body mass index (BMI), alcohol intake and smoking status and the development of PsA in people with psoriasis. METHODS: We undertook a cohort study involving incident cases of psoriasis identified from the U.K. Clinical Practice Research Datalink between 1998 and 2014. The associations between smoking, alcohol and BMI and development of PsA were assessed using generalized additive models. Additionally, the risks associated with a change in BMI during follow-up were investigated using distributed lag nonlinear models. RESULTS: We identified 90 189 incident cases of psoriasis (42% male, mean age 51 years), of whom 1409 had a subsequent record of PsA diagnosis. BMIs of 25·0-29·9, 30·0-34·9 and ≥ 35·0 kg m-2 were significantly associated with an increased risk of developing PsA compared with BMIs < 25·0 kg m-2 : adjusted odds ratios (95% confidence intervals) 1·79 (1·46-2·19), 2·10 (1·67-2·63) and 2·68 (2·09-3·43), respectively. Reducing BMI over a 10-year period (linearly) was associated with a reduction in the risk of developing PsA compared with BMI remaining constant over the same period. Increased risks of developing PsA were associated with moderate drinking but not with former or heavy drinking or with current or past smoking status. CONCLUSIONS: In this incident psoriasis cohort, increased BMI and moderate drinking, but not heavy drinking or smoking status, were associated with an increased risk of PsA in people with psoriasis. Importantly, we have shown that reducing weight may result in a reduction in the risk of developing PsA. What's already known about this topic? There is some evidence that increased body mass index is associated with an increased risk of developing psoriatic arthritis. There are conflicting results surrounding the relationship between smoking and the development of psoriatic arthritis among patients with psoriasis. What does this study add? Using a nonlinear and lagged effect of body mass index measured over time we have shown that reducing body mass index may be associated with a reduction in the risk of developing psoriatic arthritis. We have found no evidence that smoking alters the risk of developing psoriatic arthritis in patients with psoriasis.

Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients.

OBJECTIVES: To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. METHODS: Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. RESULTS: MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2-7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p < 0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, anti-MDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. CONCLUSIONS: Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.

Expression of myxovirus-resistance protein A: a possible marker of muscle disease activity and autoantibody specificities in juvenile dermatomyositis.

AIMS: To evaluate the relationship between expression of myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis-specific autoantibodies (MSA) status in JDM patients. METHODS: 103 patients (median aged 6.3, interquartile range 0.5-15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored. Clinical data at initial presentation were collected and autoantibodies were analysed. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity, and MSA status. RESULTS: Expression of MxA protein on JDM samples was identified in 61.2%. There was a significant association between MxA scores and Childhood Myositis Assessment Scale (CMAS) (P = 0.002), and Manual Muscle Testing of Eight Muscles (MMT8) (P = 0.026). CMAS and MMT8 scores were significantly lower in the group of patients with strong MxA expression. MxA scores differed according to MSA subgroups (P = 0.002). Patients with positive nuclear matrix protein 2 autoantibodies had strong MxA expression, whereas anti-melanoma differentiation-associated gene 5 positive patients had no or weak MxA expression. CONCLUSIONS: This study reveals the significant association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients and MSA status. This confirms type I interferonopathies in muscle fibres of JDM patients which could help with improving treatment outcome in JDM patients and underscoring the distinct pathophysiological pathways in different MSA status.

Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features.

AIM: Juvenile idiopathic inflammatory myopathies have been recently reclassified into clinico-serological subgroups. Myopathological correlates of the subgroups are incompletely understood. METHODS: We studied muscle biopsies from 101 children with clinically and serologically defined juvenile idiopathic inflammatory myopathies from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review and C5b-9 complement analysis. RESULTS: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti-TIF1γ, 15/90 anti-NXP2, 11/90 anti-MDA5, 5/90 anti-Mi2 and 6/90 anti-PmScl. JDM biopsy severity scores were consistently low in the anti-MDA5 group, high in the anti-Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage-rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101) and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b-9-deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b-9 deposition. CONCLUSION: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes.

Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis.

OBJECTIVES: Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis. MATERIALS AND METHODS: Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients. INTERPRETATION: Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.

Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male athlete.

We describe the case of a 20-year-old rower presenting with an uncommon condition of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare, benign tumour infrequently developing in the upper back. Its rapid growth and firm consistency may mistake it for sarcoma at presentation. Therefore, careful multidisciplinary work-up is crucial, and should involve appropriate radiological and histopathological investigations. Here, we propose the aetiology of LD PM to be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate of progression ultimately determine the management which includes surveillance and/or conservative resection. There have been no documented cases of recurrence or malignant transformation.

Symptoms of Raynaud's phenomenon (RP) in fibromyalgia syndrome are similar to those reported in primary RP despite differences in objective assessment of digital microvascular function and morphology.

Symptoms of Raynaud's phenomenon (RP) are common in fibromyalgia syndrome (FMS). We compared symptom characteristics and objective assessment of digital microvascular function using infrared thermography (and nailfold capillaroscopy where available) in patients with FMS (reporting RP symptoms) and primary RP. We retrospectively reviewed the outcome of microvascular imaging studies and RP symptom characteristics (captured using patient-completed questionnaire at the time of assessment) for patients with FMS (reporting RP symptoms) and patients with primary RP referred for thermographic assessment of RP symptoms over a 2-year period. Of 257 patients referred for thermographic assessment of RP symptoms between 2010 and 2012, we identified 85 patients with primary RP and 43 patients with FMS. There were no differences in RP symptom characteristics between FMS and primary RP (p > 0.05 for all comparisons). In contrast, patients with FMS had higher baseline temperature of the digits (32.1 vs. 29.0 °C, p = 0.004), dorsum (31.9 vs. 30.2 °C, p = 0.005) and thermal gradient (temperature of digits minus temperature of dorsum; +0.0 vs. -0.9 °C, p = 0.03) compared with primary RP. Significant differences between groups persisted following local cold challenge. In primary RP, patient reporting "blue" digits, bi-phasic and tri-phasic RP was associated with lower digital perfusion. In contrast, no associations between skin temperature and RP digital colour changes/phases were identified in FMS. Our findings suggest that symptoms of RP in FMS may have a different aetiology to those seen in primary RP. These findings have potential implications for both the classification of RP symptoms and the management of RP symptoms in the context of FMS. Digital colour changes reported by patients might reflect the degree of digital microvascular compromise in primary RP.

Feasibility, reliability, and sensitivity to change of four radiographic scoring methods in patients with psoriatic arthritis.

OBJECTIVE: We set out to assess the feasibility, reliability, and sensitivity to change of 4 radiographic scoring methods in psoriatic arthritis (PsA). METHODS: Hand and feet radiographs from 50 patients with PsA were scored at 2 time points by 2 assessors with each of the following methods: modified Steinbrocker score, modified Sharp score (MSS), modified Sharp/van der Heijde score (SHS), and the Ratingen score for PsA. The radiographs of 10 patients were scored by both assessors to assess reliability using intraclass correlation coefficients (ICCs). Sensitivity to change was estimated using a standardized response mean (SRM) and smallest detectable change (SDC). RESULTS: The patients' mean ± SD age at baseline was 50 ± 12.1 years, the mean ± SD disease duration was 10 ± 8.4 years, and the mean ± SD followup period was 25 ± 9.6 months. Intrarater reliability was excellent for all methods (ICC >0.97). Interrater reliability was highest for the SHS (ICC 0.95-0.99). The percentage SDC for the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 2.9%, 2.1%, 1.4%, and 1.2%, respectively, and the SRMs were 0.46, 0.44, 0.77, and 0.79, respectively. The mean time to score each of the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 6.2, 10.5, 14.6, and 14.4 minutes, respectively. CONCLUSION: The SHS method was the most reliable and sensitive to change but took longer to perform. The Steinbrocker method is the most feasible but lacks the sensitivity of the SHS. The SDC of the Ratingen method is close to that of the SHS and MSS, but is quicker to perform.

Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis (CONTEST study).

BACKGROUND: Multiple questionnaires to screen for psoriatic arthritis (PsA) have been developed but the optimal screening questionnaire is unknown. OBJECTIVES: To compare three PsA screening questionnaires in a head-to-head study using CASPAR (the Classification Criteria for Psoriatic Arthritis) as the gold standard. METHODS: This study recruited from 10 U.K. secondary care dermatology clinics. Patients with a diagnosis of psoriasis, not previously diagnosed with PsA, were given all three questionnaires. All patients who were positive on any questionnaire were invited for a rheumatological assessment. Receiver operating characteristic (ROC) curves were used to compare the sensitivity, specificity and area under the curve of the three questionnaires according to CASPAR criteria. RESULTS: In total, 938 patients with psoriasis were invited to participate and 657 (70%) patients returned the questionnaires. One or more questionnaires were positive in 314 patients (48%) and 195 (62%) of these patients attended for assessment. Of these, 47 patients (24%) were diagnosed with PsA according to the CASPAR criteria. The proportion of patients with PsA increased with the number of positive questionnaires (one questionnaire, 19·1%; two, 34·0%; three, 46·8%). Sensitivities and specificities for the three questionnaires, and areas under the ROC curve were, respectively: Psoriatic Arthritis Screening Evaluation (PASE), 74·5%, 38·5%, 0·594; Psoriasis Epidemiology Screening Tool (PEST), 76·6%, 37·2%, 0·610; Toronto Psoriatic Arthritis Screen (ToPAS), 76·6%, 29·7%, 0·554. The majority of patients with a false positive response had degenerative or osteoarthritis. CONCLUSION: Although the PEST and ToPAS questionnaires performed slightly better than the PASE questionnaire at identifying PsA, there is little difference between these instruments. These screening tools identify many cases of musculoskeletal disease other than PsA.

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.

BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.

Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study.

OBJECTIVES: HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. This study examined whether smoking was associated with the development of anti-Jo-1 antibodies in HLA-DRB1*03-positive IIM. METHODS: IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation. RESULTS: 557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strong association between HLA-DRB1*03 and anti-Jo-1 status was observed across all four cohorts (DRB1*03 frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR 5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency of HLA-DRB1*03 was increased in smokers. The frequency of anti-Jo-1 was increased in DRB1*03-positive smokers vs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75, 95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positive non-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers and non-smokers was not significantly different. No significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure. CONCLUSION: Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.

A modified Sharp score demonstrates disease progression in established psoriatic arthritis.

OBJECTIVE: To use a modified Sharp score (MSS) to measure radiologic progression and to assess its relationship to other radiologic features, peripheral joint disease, and physical function in psoriatic arthritis (PsA). METHODS: Two sets of hand radiographs (median interval 5.75 years) in 139 patients with established PsA were scored using an MSS. Seventy-four patients had standardized clinical joint and Health Assessment Questionnaire (HAQ) scores and other radiologic features of PsA documented at baseline and followup (median interval 5 years). RESULTS: Radiologic damage was present in 58% of patients at baseline and 74% at followup. The median MSS and its components, erosion score and joint space abnormality score, were significantly greater at followup (P < 0.001). The median MSS progression was +1.08 units/year. There was strong correlation between MSS and clinical joint scores at baseline and followup (r = 0.72 and r = 0.81, respectively). There was weak correlation between MSS and HAQ at baseline (r = 0.29), but stronger correlation at followup (r = 0.48). There was a strong association between MSS and other characteristic radiologic features of PsA (bony proliferation, periostitis, bony ankylosis) at baseline and followup (P < 0.001). However, the presence of soft-tissue swelling on radiographs at baseline was the only radiologic parameter associated with an increased rate of change of MSS (corrected P < 0.006). CONCLUSION: The MSS shows good construct validity with measures of peripheral joint involvement such as clinical joint scores and other radiologic features of PsA, and is able to demonstrate that radiologic damage is progressive beyond early disease.

Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions.

OBJECTIVES: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions. METHODS: Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: > or =50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a > or =3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a > or =50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%). RESULTS: Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear" increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria. CONCLUSIONS: Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis.

OBJECTIVE: The identification of novel autoantibodies in juvenile dermatomyositis (DM) may have etiologic and clinical implications. The aim of this study was to describe autoantibodies to a 140-kd protein in children recruited to the Juvenile DM National Registry and Repository for UK and Ireland. METHODS: Clinical data and sera were collected from children with juvenile myositis. Sera that recognized a 140-kd protein by immunoprecipitation were identified. The identity of the p140 autoantigen was investigated by immunoprecipitation/immunodepletion, using commercial monoclonal antibodies to NXP-2, reference anti-p140, and anti-p155/140, the other autoantibody recently described in juvenile DM. DNA samples from 100 Caucasian children with myositis were genotyped for HLA class II haplotype associations and compared with those from 864 randomly selected UK Caucasian control subjects. RESULTS: Sera from 37 (23%) of 162 patients with juvenile myositis were positive for anti-p140 autoantibodies, which were detected exclusively in patients with juvenile DM and not in patients with juvenile DM-overlap syndrome or control subjects. No anti-p140 antibody-positive patients were positive for other recognized autoantibodies. Immunodepletion suggested that the identity of p140 was consistent with NXP-2 (the previously identified MJ autoantigen). In children with anti-p140 antibodies, the association with calcinosis was significant compared with the rest of the cohort (corrected P < 0.005, odds ratio 7.0, 95% confidence interval 3.0-16.1). The clinical features of patients with anti-p140 autoantibodies were different from those of children with anti-p155/140 autoantibodies. The presence of HLA-DRB1*08 was a possible risk factor for anti-p140 autoantibody positivity. CONCLUSION: This study has established that anti-p140 autoantibodies represent a major autoantibody subset in juvenile DM. This specificity may identify a further immunogenetic and clinical phenotype within the juvenile myositis spectrum that includes an association with calcinosis.

Treatment recommendations for psoriatic arthritis.

OBJECTIVE: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. METHODS: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. RESULTS: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. CONCLUSIONS: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.

Conventional therapy of psoriatic arthritis: evidence-based review.

Psoriatic arthritis is a heterogeneous condition, the pattern of which is determined by any combination of pathology affecting peripheral joints, the enthesis and the spine. There is a paucity of evidence for most of the conventional agents used to treat psoriatic arthritis, with many of them being used on the basis of experience in rheumatoid arthritis. Herein, we summarise the evidence compiled relating to effectiveness of treatment for various manifestation of PsA. For those patients with progressive forms of arthritis who may benefit from intervention of newer biological therapies, the continued use of conventional therapy needs ever increasing scrutiny.

Improvement in patient-reported outcomes for patients with ankylosing spondylitis treated with etanercept 50 mg once-weekly and 25 mg twice-weekly.

OBJECTIVES: The objective of this study was to assess the humanistic impact of ankylosing spondylitis (AS), and compare the effect of etanercept 50 mg once-weekly (QW), etanercept 25 mg twice-weekly (BIW) and placebo on patient-reported outcomes (PROs). METHODS: In a 12-week, double-blind, placebo-controlled multicenter study, 356 patients with active AS received etanercept 50 mg QW, etanercept 25 mg BIW or placebo (3:3:1 randomization, respectively). PROs were assessed using Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Activity Index fatigue item, EuroQOL-5D (EQ-5D) utility, EQ-5D visual analog scale and the Medical Outcomes Short Form Questionnaire (SF-36) scores at baseline and at regular intervals. Mean changes from baseline in PROs were analysed using analysis of covariance to assess differences between etanercept and placebo, or between the two etanercept groups. RESULTS: Consistent with earlier reports, AS was associated with quality of life (QOL) impairment and functional limitations, similar to or worse than cancer, congestive heart failure, diabetes or depression. Treatment with etanercept 50 mg QW or 25 mg BIW significantly improved QOL and functional status compared with placebo. High proportions of patients achieved clinically meaningful improvements in all PRO measures, including physical function, fatigue, pain, psychosocial domains and general health status. Improvements were similar with the two etanercept dose regimens. CONCLUSIONS: The more convenient etanercept 50 mg QW dose regimen significantly improves function and QOL in patients with AS, similarly to the standard dosing of 25 mg BIW, supporting its use for AS therapy.