Anti‐neutrophil cytoplasmic antibody (ANCA) tests are a routine clinical assay in most UK hospitals. We examined the role of routine ANCA testing in achieving a diagnosis of systemic vasculitis in a ...routine clinical setting. From April 1996 to March 2000, 2734 samples from five hospital departments were tested for ANCA by indirect immunofluorescence (IIF) at a single laboratory. After April 1999, enzyme‐linked immunosorbent assays (ELISAs) were performed on all IIF‐positive samples. Clinical diagnosis was determined for all patients with a positive IIF ANCA, and a sample of the ANCA‐negative patients. Some 2–18% of patients with suspected ANCA‐associated systemic vasculitis (AASV) had positive IIF ANCA. The AASV diagnosis was confirmed in 0–56% of these cases. Analysis by department suggested that 88–100% of patients with a positive IIF ANCA did not have AASV, except in the Rheumatology department. The positive predictive value (PPV) of IIF ANCA for AASV was 59% and the negative predictive value (NPV) was 84%. Of the patients with proven AASV, 41% did not have ANCA on IIF. Combined ANCA testing by IIF/ELISA had a higher sensitivity and PPV but lower specificity than IIF alone for AASV. For the combined IIF/ELISA test, only the Rheumatology department had a sensitivity or PPV >0% for AASV. The PPV of ANCA by IIF/ELISA for AASV was 79% and the NPV was 63%. The ANCA test is being widely applied with very poor return. Guidelines for more effective usage are proposed.
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.
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.
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.
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.
•Myositis specific autoantibodies very rarely coexist in the one individual allowing endotypes to be more precisely defined.•The association of anti-TIF1 and cancer-associated myositis is confirmed with a cut-off age of over 58 years.•In a large combined European myositis cohort associations of anti-SRP with carditis and anti-Mi-2 with cancer have emerged.•Myositis associated autoantibodies are strongly associated with having myositis in association with another connective tissue disease.
Leg ulceration in rheumatoid arthritis (RA) without systemic vasculitis is a difficult clinical problem and a common cause of morbidity. We have assessed venous function, arterial pressures and range ...of ankle movement in 23 RA patients with a leg ulcer and compared the results with those in the non-ulcerated contralateral limb and in 25 RA patients matched for age and duration of arthritis. We found evidence of venous insufficiency in RA ulcer patients compared to disease controls. Ankle movement was more restricted in the ulcerated limb compared to the non-ulcerated contralateral leg. There was no difference in large-vessel arterial function between groups. These findings have implications for therapy and rates of healing.
Patients with rheumatoid arthritis appear to be at increased risk of developing chronic leg ulcers. This review identifies the factors that predispose these patients to leg ulceration and highlights ...how this problem can be managed and the risk of recurrence reduced.
The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data.
Cross-sectional analysis ...of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated.
Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001).Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001).ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases ('V' sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%.
This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients.
The aim of this study was to investigate HLA class II associations in polymyositis (PM) and dermatomyositis (DM), and to determine how these associations influence clinical and serological ...differences. DNA samples were obtained from 225 UK Caucasian idiopathic inflammatory myopathy patients (PM = 117, DM = 108) and compared with 537 randomly selected UK Caucasian controls. All cases had also been assessed for the presence of related malignancy and interstitial lung disease (ILD), and a number of myositis-specific/myositis-associated antibodies (MSAs/MAAs). Subjects were genotyped for HLA-DRB1, DQA1 and DQB1. HLA-DRB1*03, DQA1*05 and DQB1*02 were associated with an increased risk for both PM and DM. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype demonstrated strong association with ILD, irrespective of myositis subtype or presence of anti-aminoacyl-transfer RNA synthetase antibodies. The HLA-DRB1*07-DQA1*02-DQB1*02 haplotype was associated with risk for anti-Mi-2 antibodies, and discriminated PM from DM (odds ratio 0.3, 95% confidence interval 0.1-0.6), even in anti-Mi-2 negative patients. Other MSA/MAAs showed specific associations with other HLA class II haplotypes, irrespective of myositis subtype. There were no genotype, haplotype or serological associations with malignancy. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype associations appear to not only govern disease susceptibility in Caucasian PM/DM patients, but also phenotypic features common to PM/DM. Though strongly associated with anti-Mi-2 antibodies, the HLA-DRB1*07-DQA1*02-DQB1*02 haplotype shows differential associations with PM/DM disease susceptibility. In conclusion, these findings support the notion that myositis patients with differing myositis serology have different immunogenetic profiles, and that these profiles may define specific myositis subtypes.
Investigations showed a pancytopaenia with renal impairment (Hb 4.1 g/dl, mean cell volume 89.5 fl, white cell count 3.1 x 109/l, neutrophils 2.0 x 109/l, lymphocytes 0.5 x 109/l, platelets 31 x ...109/l, serum urea 20.8 mmol/l, and creatinine 148 μmol/l). Oral folinic acid 15 mg four times daily was substituted for folic acid and five days later her full blood count and renal function had returned to normal (Hb 10.5 g/dl, white cell count 6.1 x 109/l, platelets 268 x 109/l, serum urea 2.8 mmol/l, and creatinine 90 μmol/l).
OBJECTIVES: To review the outcome of surgery undertaken to stabilise the neck in patients with rheumatoid arthritis performed over a five year period, to compare the results with those of previous ...reports, and to identify factors that may predict surgical outcome. METHODS: Outcome was assessed at time of discharge from hospital after surgery by review of patients' notes, and at follow up by patient interview, clinical examination, anonymous questionnaire, and cervical spine radiograph. The Ranawat classification of neurological impairment and Steinbrocker functional classification were used. RESULTS: Thirty nine patients underwent 44 procedures; 28 patients were available for review after a mean period of 29.8 months (range 12-65 months). Fourteen patients had preoperative neurological impairment and were available for follow up; 13 returned the questionnaire. Four (29%) had improved Ranawat class, nine were unchanged, and one had deteriorated. Nine (69%) reported a subjective improvement in neurological symptoms by questionnaire, even though the Ranawat class was unchanged in five. Twenty five of the patients reviewed had pain before operation; 21 returned the questionnaire. Pain relief was reported by direct questioning and questionnaire in 76% and 67% of patients, respectively. Overall, 67% felt that surgery had been successful. Surgery was more successful in producing symptomatic relief in patients with neck or radicular pain than in those with neurological deficit, but did prevent progression of neurological symptoms. CONCLUSIONS: Our results are similar to those from other centres. Overall patient satisfaction with surgery was good. Surgery was more likely to produce symptomatic relief in patients with neck or radicular pain before operation than in those with neurological deficit. The greater subjective improvement in neurological symptoms as judged by questionnaire probably reflects the relative insensitivity of the Ranawat classification in detecting change in neurological status; previous reports of poor outcome for patients with neurological symptoms who undergo surgery may in part be a reflection of the insensitivity of this method of assessment. No clear factors emerged which allowed prediction of those patients at greatest risk of operative mortality. In particular, an increased risk of neurological compromise appeared to confer no additional risk of immediate perioperative death. Our data support the suggestion that early surgery to correct symptomatic atlantoaxial subluxation may prevent progression of instability.
To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations, and malignancy, between adults with anti-synthetase syndrome (ASyS) and dermatomyositis (DM).
...Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1ɣ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash).
In total 1,054 patients were included (DM, n = 405; ASyS, n = 649). In ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease, and cardiac involvement differentiated ASyS-DMskin from DM (all p< 0.001), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%) differentiated DM from ASyS-DMskin (all p< 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both p< 0.001).
DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.
To test hypotheses about the universality of personality traits, college students in 50 cultures identified an adult or college-aged man or woman whom they knew well and rated the 11,985 targets ...using the 3rd-person version of the Revised NEO Personality Inventory. Factor analyses within cultures showed that the normative American self-report structure was clearly replicated in most cultures and was recognizable in all. Sex differences replicated earlier self-report results, with the most pronounced differences in Western cultures. Cross-sectional age differences for 3 factors followed the pattern identified in self-reports, with moderate rates of change during college age and slower changes after age 40. With a few exceptions, these data support the hypothesis that features of personality traits are common to all human groups.
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