Peter Lanyon

Modification and validation of the Birmingham Vasculitis Activity Score (version 3)

Background: Comprehensive multisystem clinical assessment using the Birmingham Vasculitis Activity score (BVAS) is widely used in therapeutic studies of systemic vasculitis. Extensive use suggested a need to revise the instrument. The previous version of BVAS has been revised, according to usage and reviewed by an expert committee. Objective: To modify and validate version 3 of the BVAS in patients with systemic vasculitis. Methods: The new version of BVAS was tested in a prospective cross-sectional study of patients with vasculitis. Results: The number of items was reduced from 66 to 56. The subscores for new/worse disease and persistent disease were unified. In 313 patients with systemic vasculitis, BVAS(v.3) correlated with treatment decision (Spearman’s rs = 0.66, 95% CI 0.59 to 0.72), BVAS1 of version 2 (rs = 0.94, 95% CI 0.92 to 0.96), BVAS2 of version 2 in patients with persistent disease (rs = 0.60, 95% CI 0.21 to 0.83), C-reactive protein levels (rs = 0.43, 95% CI 0.31 to 0.54), physician’s global assessment (rs = 0.91, 95% CI 0.89 to 0.93) and vasculitis activity index (rs = 0.88, 95% CI 0.86 to 0.91). The intraclass correlation coefficients for reproducibility and repeatability were 0.96 (95% CI 0.95 to 0.97) and 0.96 (95% CI 0.92 to 0.97), respectively. In 39 patients assessed at diagnosis and again at 3 months, the BVAS(v.3) fell by 17 (95% CI 15 to 19) units (p<0.001, paired t test). Conclusion: BVAS(v.3) demonstrates convergence with BVAS(v.2), treatment decision, physician global assessment of disease activity, vasculitis activity index and C-reactive protein. It is repeatable, reproducible and sensitive to change. The new version of BVAS is validated for assessment of systemic vasculitis.

Radiographic assessment of symptomatic knee osteoarthritis in the community: definitions and normal joint space

OBJECTIVE To evaluate radiographic features of osteoarthritis (OA) to determine which is more closely associated with knee pain and hence might be used as a radiographic definition of OA in the community. To evaluate joint space width in normal subjects. METHODS 452 subjects from a case-control community study of knee pain (294 women, 158 men, mean age 62 years, range 40–80) underwent AP standing and mid-flexion skyline radiographs. Joint space width, measured by metered calliper to 0.1 mm, and graded individual features of OA (osteophyte 0–3, narrowing 0–3, sclerosis 0–1, cysts 0–1) were assessed in all three compartments independently by two observers who were blind to clinical status. Subjects were categorised as having knee pain by a positive response to both parts of the question “Have you ever had pain in or around the knee on most days for at least a month? If so, have you experienced any pain during the last year?” RESULTS Intraobserver reproducibility for joint space width measurements was to within ±0.4 mm (95% CI for limits of agreement); κ values for grading were >0.7. One hundred and twenty five subjects were without knee pain or osteophyte. In these radiographically normal knees, mean joint space width varied according to sex but did not decrease with age. A definition based on the presence of osteophyte ⩾grade 1 in any compartment was more efficient at predicting pain than definitions based on either measurement or grading of joint space; there was no clear threshold of joint space loss at which the likelihood of pain substantially increased. The presence of osteophyte at the patellofemoral joint (PFJ) was more sensitive but less specific than at the tibiofemoral joint (TFJ); the addition of PFJ assessment improved sensitivity from 38.1% to 62.3% with a reduction in specificity from 82.7% to 58.7% for the presence of knee pain. CONCLUSION Among men and women in the community, osteophyte is the radiographic feature that associates best with knee pain. Radiographic assessment of both TFJ and PFJ should be included in all community studies. Joint space loss is not a feature of asymptomatic aging, and there is not a biological cut off for joint space width below which the likelihood of knee pain markedly increases.

Infliximab in the treatment of refractory posterior uveitis.

PURPOSE To determine the efficacy and safety of infliximab in the treatment of refractory posterior uveitis. DESIGN Noncomparative interventional case series. PARTICIPANTS Five patients with posterior uveitis were treated: 3 had Behçets syndrome, and 2 had idiopathic posterior uveitis. INTERVENTIONS Patients with sight-threatening uveitis refractory to other immunosuppressive agents were treated with infliximab. MAIN OUTCOME MEASURES Intraocular inflammation, by using binocular indirect ophthalmoscopy score, retinal vasculitis, and visual acuity. Adverse effects of infliximab were documented. RESULTS Within 2 weeks of the first infusion of infliximab, 4 of 5 patients showed marked improvement in vitreous haze and visual acuity. By the 6-month follow-up, the same four patients had achieved remission of posterior uveitis and had successfully withdrawn all other immunosuppressive therapy. Further infusions of infliximab were required in 3 patients. One patient developed ocular and systemic tuberculosis, which responded to antituberculous treatment. CONCLUSIONS Infliximab is effective in the treatment of sight-threatening refractory posterior uveitis. However, patients should be thoroughly screened for tuberculosis before treatment and followed up closely during and after therapy with infliximab.

Assessment of a genetic contribution to osteoarthritis of the hip: sibling study.

Abstract Objectives: To study the influence of genetics on the development of hip osteoarthritis as determined by structural change on plain radiographs. Design: Sibling study. Setting: Nottinghamshire, England. Participants: 392 index participants with hip osteoarthritis of sufficient severity to warrant total hip replacement, 604 siblings of the index participants, and 1718 participants who had undergone intravenous urography. Main outcome measure: Odds ratios for hip osteoarthritis in siblings. Results: The age adjusted odds ratios in siblings were 4.9 (95% confidence interval, 3.9 to 6.4) for probable hip osteoarthritis and 6.4 (4.5 to 9.1) for definite hip osteoarthritis. These values were not significantly altered by adjusting for other risk factors. Conclusion: Siblings have a high risk of hip osteoarthritis as shown by structural changes on plain radiographs. One explanation is that hip osteoarthritis is under strong genetic influence.

Development of a logically devised line drawing atlas for grading of knee osteoarthritis

OBJECTIVES To (a) develop an atlas of line drawings for the assessment and grading of narrowing and osteophyte (that is, changes of osteoarthritis) on knee radiographs, and (b) compare the performance of this atlas with that of the standard Osteoarthritis Research Society (OARS) photographic atlas of radiographs. METHODS Normal joint space widths (grade 0) for the medial and lateral tibiofemoral and medial and lateral patellofemoral compartments were obtained from a previous community study. Grades 1–3 narrowing in each compartment was calculated separately for men and women, grade 3 being bone on bone, grades 1 and 2 being two thirds and one third the value of grade 0. Maximum osteophyte size (grade 3) for each of eight sites was determined from 715 bilateral kneex ray films obtained in a knee osteoarthritis (OA) hospital clinic; grades 1–2 were calculated as two thirds and one third reductions in the area of grade 3. Drawings for narrowing and osteophyte were presented separately. 50 sets of bilateral knee x ray radiographs (standing, extended anteroposterior; flexed skyline) showing a spectrum of OA grades were scored by three observers, twice using the OARS atlas and twice using the drawn atlas. RESULTS Intraobserver and interobserver reproducibility was similar and generally good with both atlases, though varied according to site. All three observers preferred the line drawing atlas for ease and convenience of use. Higher scores for patellofemoral narrowing and lower scores for osteophyte, especially medial femoral osteophyte, were seen using the line drawing atlas, showing that the two atlases are not equivalent instruments. CONCLUSION A logically derived line drawing atlas for grading of narrowing and osteophyte at the knee has been produced. The atlas showed comparable reproducibility with the OARS atlas, but was discordant in several aspects of grading. Such a system has several theoretical and practical advantages and should be considered for use in knee OA studies.

Risk Factors for Clinical Coronary Heart Disease in Systemic Lupus Erythematosus: The Lupus and Atherosclerosis Evaluation of Risk (LASER) Study

Objective. Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting. Methods. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same “dummy-date” in controls. Results. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile. Conclusion. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

The incidence and prevalence of systemic lupus erythematosus in the UK, 1999–2012

Objectives To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in the UK over the period 1999–2012. Methods A retrospective cohort study using the Clinical Practice Research Datalink (CPRD). The incidence was calculated per 100 000 person-years and the prevalence was calculated per 100 000 people for the period 1999–2012 and stratified by year, age group, gender, region and ethnicity. Three definitions of SLE were explored: (1) systemic lupus, (2) a fully comprehensive definition of lupus including cutaneous only lupus and (3) requiring supporting evidence of SLE in the medical record. Results Using our primary definition of SLE, the incidence during the study period was 4.91/100 000 person-years (95% CI 4.73 to 5.09), with an annual 1.8% decline (p<0.001). In contrast, the prevalence increased from 64.99/100 000 in 1999 (95% CI 62.04 to 67.93) (0.065%) to 97.04/100 000 in 2012 (95% CI 94.18 to 99.90) (0.097%). SLE was six times more common in women. The peak age of incidence was 50–59 years. There was regional variation in both incidence and prevalence. People of Black Caribbean ethnicity had the highest incidence and prevalence. Alternative definitions of SLE increased (definition 2) or decreased (definition 3) estimates of incidence and prevalence, but similar trends were found. Conclusions The incidence of SLE has been declining but the prevalence has been increasing in the UK in recent years. Age, gender, region and ethnicity are risk factors for SLE. This is the first study to report ethnic differences on the incidence and prevalence of SLE using the CPRD.

Characterisation of size and direction of osteophyte in knee osteoarthritis: a radiographic study

Objectives: To examine the size and direction of osteophyte in knee osteoarthritis (OA) and to determine associations between osteophyte size and other radiographic features. Methods: Knee radiographs (standing extended anteroposterior and 30 degrees flexion skyline views) were examined from 204 patients referred to hospital with symptomatic knee OA (155 women, 49 men; mean age 70, range 34–91 years). A single observer assessed films for osteophyte size and direction at eight sites; narrowing in each compartment; varus/valgus angulation; patellofemoral subluxation; attrition; and chondrocalcinosis using a standard atlas, direct measurement, or visual assessment. For analysis, one OA knee was selected at random from each subject. Results: Osteophyte direction at the eight sites was divisible into five categories. At all sites, except for the lateral tibial plateau and the medial patella, osteophyte direction varied according to (a) the size of osteophyte and (b) the degree of local narrowing. At the medial femur, medial tibia, and lateral femur osteophyte direction changed from being predominantly horizontal to predominantly vertical with increasing size. The size of osteophyte correlated positively with the severity of local narrowing, except for the medial patellofemoral compartment where osteophyte size correlated positively with the severity of narrowing in the medial tibiofemoral compartment. Logistic regression analysis showed that osteophyte size was associated not only with local narrowing but also with local malalignment and bone attrition, and that chondrocalcinosis was positively associated with osteophyte size at multiple sites. Conclusion: In patients referred to hospital with knee OA different patterns of osteophyte direction are discernible. Osteophyte size is associated with local compartmental narrowing but also local alignment and attrition. Chondrocalcinosis is associated with osteophytosis throughout the joint. These data suggest that both local biomechanical and constitutional factors influence the size and direction of osteophyte formation in knee OA.

Health-related utility values of patients with primary Sjögren's syndrome and its predictors

Objectives EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjögrens syndrome (PSS) in the UK. Methods Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. Results The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587–0.796, range −0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for <5% in variability. Conclusions This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.

Assessing progression of patellofemoral osteoarthritis: a comparison between two radiographic methods.

OBJECTIVE: To compare two plain radiographic methods for sensitivity to detect progression of patellofemoral osteoarthritis. METHODS: Two sets of paired skyline and lateral knee radiographs from 54 hospital referred patients (108 knees) with knee osteoarthritis were taken an average of 31 months apart (range 12-40). Films were examined separately in random order by a single observer blind to patient identity and time order. Minimum joint space was measured by metered caliper; individual features of osteoarthritis were graded 0-3 using an atlas. RESULTS: Intraobserver reproducibility assessed on 40 knees was to within +/- 0.5 mm for skyline lateral facet and +/- 0.7 mm for medial facet and lateral views. On the lateral view measured joint space decreased in 51% of knees but increased in 43%, with overall no significant mean group change with time (-0.2 mm, 95% confidence interval, 0.1 to -0.5). By contrast on the skyline view joint space decreased in at least one facet in 71% of knees, with significant decrease in mean joint space for both lateral facets (-0.4 mm, 95% CI, -0.2 to -0.6) and medial facets (-0.5 mm, 95% CI, -0.1 to -0.8). CONCLUSIONS: It is possible to detect significant joint space loss with time on the skyline view that is not apparent on the lateral view. The skyline view should be the method of choice to detect progression of patellofemoral osteoarthritis.