Comparison of different outcome measures for psoriatic arthritis in patients treated with infliximab or placebo.
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Adult↗
Biomedical subjects
H Mielants
Publications and source records attributed to H Mielants.
Altered gut transcriptome in spondyloarthropathy.
BACKGROUND: Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn's disease. Inflammation is manifested clinically in Crohn's disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn's disease. AIMS: To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn's disease and to examine global gene expression in non-inflamed colon biopsy specimens and screen patients for differentially expressed genes. METHODS: Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn's disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn's disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass-based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn's disease and 10 controls. RESULTS: 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn's disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn's disease. CONCLUSION: The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn's disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn's disease in patients with SpA can be considered.
Adult↗
An international study on starting tumour necrosis factor-blocking agents in ankylosing spondylitis.
OBJECTIVES: To determine the type and proportion of patients with ankylosing spondylitis who rheumatologists consider to be candidates for treatment with tumour necrosis factor (TNF)-blocking agents, and to what extent this is in agreement with the ASsessment in Ankylosing Spondylitis (ASAS) international working group recommendations on initiation of treatment with anti-TNF agents. METHODS: Participants were rheumatologists from 10 different countries, who were considered to be experts in treating patients with ankylosing spondylitis and in the use of anti-TNF treatment, but were unaware of the ASAS recommendations (unpublished at the time of study in 2003). The first 10 consecutive patients with ankylosing spondylitis seen by the rheumatologist were evaluated as to whether the patient was a candidate for anti-TNF treatment. Thereafter, a metrologist assessed the patient for disease activity and severity, and collected data on demographics and treatment. RESULTS: Complete data were available for 1207 of the 1284 patients and were used for analysis. Overall, the rheumatologists indicated that they would initiate TNF-blocking agents in 49.3% of patients, ranging from 37.2% patients in Canada to 78.3% in Australia. These candidates had higher disease activity, higher levels of acute-phase reactants, worse spinal mobility, worse function, more often hip involvement and a higher prevalence of sick leave. Of all patients considered to be candidates, 40% did not fulfil ASAS recommendations with respect to previous use of non-steroidal anti-inflammatory drugs (NSAIDs; at least two NSAIDs) or Bath Ankylosing Spondylitis Disease Activity Index (>or=4). Conversely, 36% of patients who did not fulfil the NSAID or BASDAI recommendations were still considered to be candidates for TNF-blocking treatment. OBJECTIVE: variables, such as C reactive protein, erythrocyte sedimentation rate or magnetic resonance activity, were considered less important than disease activity in the decision on starting TNF-blocking drugs. The only important objective criterion was rapid radiographic progression. CONCLUSION: Rheumatologists wanted to initiate TNF-blocking drugs in roughly half of the patients with ankylosing spondylitis. However, there was a wide variation across countries and doctors. Rheumatologists considered both disease activity and severity to be determinants of starting TNF blockers, but their decision was often in disagreement with ASAS recommendations.
Adult↗
Leflunomide and methotrexate combination therapy in daily clinical practice.
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Antirheumatic Agents↗
Determinants of hyperkyphosis in patients with ankylosing spondylitis.
OBJECTIVE: To determine clinical and radiographic determinants of hyperkyphosis in patients with ankylosing spondylitis. METHODS: Spinal hyperkyphosis was assessed by occiput to wall distance (OWD) in 135 patients participating in the OASIS cohort and defined as OWD >0. Disease activity was assessed by the Bath ankylosing spondylitis disease activity index (BASDAI). Wedging of the vertebrae was calculated as the Ha/Hp ratio. Structural damage of the spine was assessed by the modified Stoke ankylosing spondylitis spine score (mSASSS). Hip involvement was assessed by the Bath ankylosing spondylitis radiology index (BASRI) and defined as a score >2. Data were analysed by multiple regression analysis on van der Waerden-normal OWD values, with mean Ha/Hp ratio, mSASSS, hip involvement, and BASDAI as explanatory variables, and age, sex, and disease duration after diagnosis as covariates. RESULTS: 61 patients (45.2%) had an OWD >0 cm. Of these, 81% were male, v 57% in the group with normal OWD (p<0.001). Forty two patients had wedged thoracic vertebrae, and 27 of these (44%) had an increased OWD, compared with 15 of 74 with a normal OWD (20%) (p = 0.005). OWD was correlated with mean wedging of the thoracic spine (r = -0.45, p = 0.01), mSASSS (r = 0.56, p = 0.01), and hip involvement (r = 0.2, p = 0.05). Multivariate analysis showed that mSASSS (standardised beta (stbeta) = 0.52; p<0.001), wedging of the thoracic spine (stbeta = -0.28; p = 0.01), and BASDAI (stbeta = 0.15; p = 0.05) were independent determinants of OWD. CONCLUSIONS: Radiological damage of the cervical and lumbar spine, thoracic wedging, and disease activity are determinants of hyperkyphosis in patients with ankylosing spondylitis. These findings could be important in determining treatment goals in this disease.
Adult↗
Healthcare consumption and direct costs of rheumatoid arthritis in Belgium.
The aim of this study was to compare the socioeconomic consequences of early and late rheumatoid arthritis in Belgium and to assess the patient out-of-pocket contributions. This multicentre longitudinal study in Belgium evaluated patients with rheumatoid arthritis. Early disease was defined as diagnosis since less than 1 year. At baseline sociodemographic and disease characteristics were assessed and during the following year patients recorded all healthcare- and non-healthcare-related direct costs and out-of-pocket contributions. The study included 48 patients with early and 85 patients with late rheumatoid arthritis. Mean disease duration was 0.5 vs 12.5 years in patients with early and late rheumatoid arthritis, respectively. The disease activity score (DAS28) was comparable between both groups (4.1 vs 4.5, p = 0.14), but physical function (Health Assessment Questionnaire, HAQ) was more impaired in patients with long-standing disease (1.0 vs 1.7, p < 0.001). Work disability had increased from 2% in patients with early to 18% in patients with late disease. The annual societal direct costs per patient were 3055 Euros (median: 1518 Euros) opposed to 9946 Euros (median: 4017 Euros) for early and late rheumatoid arthritis, respectively. The higher direct cost for patients with long-standing disease was seen for all categories, but especially for physiotherapy and need for devices and adaptations. Patients with early as well as late disease contribute out of pocket about one-third to the direct healthcare costs. Within each group, HAQ was a strong determinant of costs. In Belgium, patients with long-standing rheumatoid arthritis are nine times more likely to be work disabled than patients with less than 1 year disease duration and have a threefold increase in costs. Differences in healthcare consumption between patients could be mainly explained by differences in physical function (HAQ).
Adult↗
Measuring disease activity in ankylosing spondylitis: patient and physician have different perspectives.
OBJECTIVE: There is no "gold standard" to assess disease activity in patients with ankylosing spondylitis (AS). It is known that patients and physicians have different opinions about disease activity. The objective was therefore to investigate on which criteria patients with AS and physicians base their judgement on disease activity. METHODS: A cohort of 203 AS out-patients fulfilling the modified New York criteria included in the ongoing long-term follow-up was analysed. The Assessment in Ankylosing Spondylitis (ASAS) International Working Group has established different domains relevant for outcome in AS. Each domain includes a number of instruments for making assessments, and all these instruments are included in the Outcome in Ankylosing Spondylitis International Study and were made every 6 months for 2 yr. Disease activity from the patient perspective as well as from the physician perspective was analysed using the patient's or the physician's global assessment of disease activity [visual analogue scale (VAS): 0 (best)-10 (worst)] by dichotomizing into "high disease activity" (VAS > or = 6.0) and "low disease activity" (VAS < or = 4.0). Data reduction by principal components analysis (PCA) was performed to distinguish factors capturing correlated instruments. Discriminant analysis with the factor loadings was performed to discriminate between a low and a high disease activity state from both the patient's and the physician's perspective. Multiple regression analysis on the discriminant scores was performed to prioritize the instruments. RESULTS: PCA revealed four factors: spinal mobility, physician assessments, patient assessments and laboratory assessments (Cronbach's alpha 0.52-0.80; explained variance 61%). Discriminant function analysis showed that the factor "patient assessments" was most important (pooled correlation 0.85) in discriminating between a low and a high disease activity state as defined by the patient. The other three factors contributed marginally (pooled correlation <0.30). In contrast, the factors "physician's assessments" (pooled correlation 0.62), "spinal mobility" (pooled correlation 0.52) and "laboratory assessments" (pooled correlation 0.48) contributed most to the physician's perspective. The factor "patient assessments" did not contribute at all (pooled correlation 0.05). Multivariate analysis on the discriminant scores showed that the instruments "pain spine", "BASFI", "pain joints" and "BASDAI fatigue" explained more than 90% of variance in the case of the patient perspective. The instruments "cervical rotation", "swollen joint count", "CRP" and "intermalleolar distance" explained more than 90% of variance in case of physician perspective. CONCLUSION: AS patients rate disease activity on the basis of complaints while physicians rate disease activity on the basis of instruments related to disease severity and inflammation.
Adult↗
Anti-citrullinated peptide antibodies may occur in patients with psoriatic arthritis.
BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis. OBJECTIVE: To determine the frequency of anti-CCP antibodies in psoriatic arthritis and to describe the clinical characteristics of such patients. METHODS: Serum samples from 192 patients with psoriatic arthritis were analysed for anti-CCP antibodies. A previously defined cut off point was applied at a specificity level of > or =98.5% (42 U/ml). Antibodies against pepA and pepB (two synthetic citrullinated peptides) were determined on samples containing anti-CCP antibodies by line immune assay. The swollen joint count and the numbers of affected joints (present or past) were recorded. Clinical features were noted and if available radiographs of hands and feet were scored for erosions. Rheumatoid factor was determined in all samples. RESULTS: Anti-CCP antibodies were found in 15 patients (7.8%); 13 of 15 anti-CCP2 positive samples were also positive for anti-pepA or pepB antibodies. The prevalence of anti-CCP antibodies was higher than expected in view of the highly specific cut off applied in the test. Detailed analysis of the clinical and radiological features makes it improbable that the high prevalence of anti-CCP antibodies resulted solely from concomitant psoriasis and rheumatoid arthritis or from misclassification. CONCLUSIONS: Anti-CCP antibodies may be present in patients with psoriatic arthritis. Although some of the present cohort could have had psoriasis with concomitant rheumatoid arthritis, a proportion at least had the typical characteristics of psoriatic arthritis as the primary diagnosis.
Adolescent↗
CARD15 polymorphisms are associated with anti-Saccharomyces cerevisiae antibodies in caucasian Crohn's disease patients.
Carriage of CARD15 gene polymorphisms and the serological marker anti-Saccharomyces cerevisiae antibodies (ASCA) are two markers for Crohn's disease (CD). Similar phenotypes have been associated with both markers. In the present study we analysed whether both markers were associated with each other and, if so, whether this association could be explained by a direct link or by an indirect association with those phenotypes. Therefore, we included 156 consecutive Caucasian CD patients and assessed the prevalence of the three common single nucleotide polymorphisms in the CARD15 gene. Serum samples were analysed for IgA and IgG ASCA by ELISA. CD patients with CARD15 polymorphisms were more frequently ASCA positive (OR 2.7 (1.4-5.2); P = 0.002) and had higher titres for ASCA IgA (P = 0.005) and ASCA IgG (P < 0.001) compared to patients carrying the wild type polymorphisms. Multivariate analysis demonstrated that this association was independent from ileal disease, penetrating disease and stricturing disease, the need for resective bowel surgery, familial cases, smoking habits and early age at onset. Homozygotes or compound heterozygotes for CARD15 polymorphisms had significantly more frequent ASCA positivity compared to single heterozygotes (OR 9.1 (1.1-74.2), P(c) (corrected P-value) = 0.030). These data indicate that there is a significant association between the carriage of CARD15 polymorphisms and ASCA, independent of the described phenotypes. Moreover, ASCA positivity is more frequent in CD patients carrying 2 CARD15 polymorphisms compared to single heterozygotes.
Adolescent↗
Association between radiographic damage of the spine and spinal mobility for individual patients with ankylosing spondylitis: can assessment of spinal mobility be a proxy for radiographic evaluation?
OBJECTIVE: To demonstrate the association between various measures of spinal mobility and radiographic damage of the spine in individual patients with ankylosing spondylitis, and to determine whether the assessment of spinal mobility can be a proxy for the assessment of radiographic damage. METHODS: Radiographic damage was assessed by the mSASSS. Cumulative probability plots combined the radiographic damage score of an individual patient with the corresponding score for nine spinal mobility measures. Receiver operating characteristic analysis was performed to determine the cut off level of every spinal mobility measure that discriminates best between the presence and absence of radiographic damage. Three arbitrary cut off levels for radiographic damage were investigated. Likelihood ratios were calculated to explore further the diagnostic properties of the spinal mobility measures. RESULTS: Cumulative probability plots showed an association between spinal mobility measures and radiographic damage for the individual patient. Irrespective of the chosen cut off level for radiographic progression, lateral spinal flexion and BASMI discriminated best between patients with and those without structural damage. Even the best discriminatory spinal mobility assessments misclassified a considerable proportion of patients (up to 20%). Intermalleolar distance performed worst (up to 30% misclassifications). Lateral spinal flexion best predicted the absence of radiographic damage, and a modified Schober test best predicted the presence of radiographic damage. CONCLUSION: This study unequivocally demonstrated a relationship between spinal mobility and radiographic damage. However, spinal mobility cannot be used as a proxy for radiographic evaluation in an individual patient.
Adult↗
CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease.
BACKGROUND: The association between spondyloarthropathy and Crohn's disease is well known. A risk for evolution to Crohn's disease has already been shown in the subgroup of patients with spondyloarthropathy associated with chronic gut inflammation. OBJECTIVE: To investigate whether the reported polymorphisms in the CARD15 gene, a susceptibility gene for Crohn's disease, are associated with the presence of preclinical intestinal inflammation observed in spondyloarthropathies. METHODS: 104 patients with spondyloarthropathies were studied. All underwent ileocolonoscopy with biopsies between 1983 and 2004. The prevalence of three single nucleotide polymorphisms in the CARD15 gene (R702W, G908R, and 1007fs) was assessed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR); the patients were compared with an ethnically matched Crohn's disease population and a control population. RESULTS: The carrier frequency of R702W, G908R, or 1007fs variants in the spondyloarthropathy populations (20%) was similar to the control population (17%), but increased to 38% in the spondyloarthropathy subgroup with chronic gut inflammation. This frequency was significantly higher than in the other spondyloarthropathy subgroups (p = 0.001) or the control group (p = 0.006), but not different from the Crohn's disease group (49%) (NS). This indicates that CARD15 polymorphisms are associated with a higher risk for development of chronic gut inflammation. CONCLUSIONS: CARD15 gene polymorphisms clearly identify a subgroup of patients with spondyloarthropathies associated with chronic intestinal inflammation.
Adolescent↗
Histological evidence that infliximab treatment leads to downregulation of inflammation and tissue remodelling of the synovial membrane in spondyloarthropathy.
OBJECTIVE: To confirm and extend the immunopathological evidence of effects of infliximab on the synovium in active spondyloarthropathy. METHODS: Synovial biopsies obtained in patients with spondyloarthropathy at baseline and week 12 were stained and scored by two independent observers. Two study populations were evaluated: I, a cohort of 10 patients treated with 5 mg/kg infliximab at week 0, 2, and 6, plus three placebo treated patients; and II, a pooled cohort of 20 patients fulfilling identical inclusion and exclusion criteria and treated with the same loading dose regimen. RESULTS: In study population I, treatment with infliximab induced reduction in synovial lining layer thickness (p = 0.015), endothelial activation (E-selectin, p = 0.034), and inflammatory cell infiltration with neutrophils (p = 0.041), macrophages (p = 0.034), and T cells (p = 0.026), but not with B cells and plasma cells; no such trends were observed in the placebo treated patients. Besides confirming the highly significant downregulation of inflammation, analysis of cohort II showed structural changes such as normalisation of lining layer thickness (p = 0.030), reduction in the number of blood vessels (p = 0.039), and downregulation of follicular organisation (p = 0.050). No differences in histopathological response were observed between spondyloarthropathy subtypes. CONCLUSIONS: Profound immunomodulatory changes in the synovium parallel the clinical benefit in patients with spondyloarthropathy treated with infliximab, independently of the subtype. The study provides histological evidence that TNF alpha blockade not only downregulates inflammation but also leads to tissue remodelling.
Adult↗
Scoring of radiographic progression in randomised clinical trials in ankylosing spondylitis: a preference for paired reading order.
OBJECTIVES: To describe the influence of the reading order (chronological v paired) on radiographic scoring results in ankylosing spondylitis. To investigate whether this method is sufficiently sensitive to change because paired reading is requested for establishing drug efficacy in clinical trials. METHODS: Films obtained from 166 patients (at baseline, 1 year, and 2 years) were scored by one observer, using the modified Stoke Ankylosing Spondylitis Spinal Score. Films were first scored chronologically, and were scored paired 6 months later. RESULTS: Chronological reading showed significantly more progression than paired reading both at 1 year (mean (SD) progression 1.3 (2.6) v 0.5 (2.4) units) and at 2 years (2.1 (3.9) v 1.0 (2.9) units); between-method difference: p<0.001 at 1 year, and p<0.001 at 2 years. After 1 year, progression (>0 units) was found in 35/166 (21%) patients after paired reading and in 55/166 (33%) after chronological reading. After 2 years, these figures were 50/166 (30%) and 68/166 (41%), respectively. Sample size calculations showed that 94 patients in each treatment arm are required in a randomised clinical trial (RCT) to provide sufficient statistical power to detect a difference in 2 year progression if films are scored paired. CONCLUSION: Reading with chronological time order is more sensitive to change than reading with paired time order, but paired reading is sufficiently sensitive to pick up change with a follow up of 2 years, resulting in an acceptable sample size for RCTs.
Adult↗
Colon mucosa of patients both with spondyloarthritis and Crohn's disease is enriched with macrophages expressing the scavenger receptor CD163.
BACKGROUND: Crohn's disease is associated with an increased number of macrophages in ileal and colonic mucosa. Data on macrophages in gut mucosa of patients with spondyloarthritis (SpA) are scarce. OBJECTIVE: To investigate macrophages and other antigen presenting cells in gut mucosa from patients with SpA and Crohn's disease, given the relationship between both entities. METHODS: Biopsy specimens from patients with SpA, Crohn's disease, ulcerative colitis, and from controls were immunohistochemically stained with different markers for macrophages and dendritic cells. Slides were scored semiquantitatively on a four point scale. RESULTS: SpA and Crohn's disease were associated with large numbers of CD68+ macrophages. Colon mucosa of both patients with SpA and Crohn's disease, but not ulcerative colitis, showed increased numbers of macrophages expressing the scavenger receptor CD163. CONCLUSIONS: Macrophages expressing the scavenger receptor CD163 are increased in colonic mucosa in SpA and in Crohn's disease, highlighting the relationship between these entities. The increased number of CD163+ macrophages in colon mucosa of patients with SpA suggests this is another argument for a role of macrophage scavenger receptors in this group of diseases.
Adolescent↗
A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis.
OBJECTIVES: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. METHODS: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. RESULTS: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. CONCLUSIONS: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.
Adult↗
Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations.
BACKGROUND: Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein antibodies can be detected in rheumatoid arthritis (RA) sera. OBJECTIVE: To determine the diagnostic values of RF, anticitrullinated protein antibodies, and the shared epitope (SE), and their associations with radiological progression rates and extra-articular manifestations. METHODS: Population 1 consisted of sera from 315 patients, consecutively sent for detection of anticitrullinated protein antibodies, of which 264 were used to determine the sensitivity and specificity of RF and of antibodies against three synthetic citrullinated peptides: peptide A (pepA), peptide B (pepB), and CCP2. Population 2 consisted of sera from 180 longstanding RA patients and was used to determine associations of RA associated antibodies and the SE with radiological progression rates and extra-articular manifestations. Antibodies to pepA and pepB were detected by line immunoassay, and antibodies to CCP2 by ELISA. HLA Class II typing was performed by LiPA. RESULTS: In population 1, we defined adapted cut offs corresponding to a specificity of >/=98.5%. This yielded the following sensitivities: RF 12.8%; anti-pepA antibodies 63.6%; anti-pepB antibodies 54.2%; and anti-CCP2 antibodies 73.7%. In population 2, significant differences in radiological progression rates were found between positive and negative patients for different RA antibodies and the SE. RF, but not anticitrullinated protein antibodies or the SE, were more frequent in patients with extra-articular manifestations. CONCLUSION: A valid comparison of RA associated antibodies shows superior sensitivity of the anticitrullinated protein antibodies compared with RF. The presence of RA associated antibodies and the SE are indicative for poorer radiological outcome, and presence of extra-articular manifestations is associated with RF but not with anticitrullinated protein antibodies.
Adult↗
Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease.
BACKGROUND: Sacroiliitis is a common extraintestinal manifestation of Crohn's disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn's disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases. OBJECTIVES: To investigate whether the presence of sacroiliitis in patients with Crohn's disease is linked to the carriage of CARD15 polymorphisms. METHODS: 102 consecutive patients with Crohn's disease were clinically evaluated by a rheumatologist. Radiographs of the sacroiliac joints were taken and assessed blindly by two investigators. The RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms (SNP) in the CARD15 gene. Every SNP was verified by direct sequencing. The HLA-B27 phenotype was determined. RESULTS: Radiological evidence of sacroiliitis with or without ankylosing spondylitis was found in 23 patients (23%), of whom only three were HLA-B27 positive. In contrast, 78% of patients with sacroiliitis carried a CARD15 variant v 48% of those without sacroiliitis (p = 0.01; odds ratio 3.8 (95% confidence interval, 1.3 to 11.5)). Multivariate analysis (logistic regression) showed that the association between sacroiliitis and CARD15 polymorphisms was independent of other CARD15 related phenotypes (ileal and fibrostenosing disease, young age at onset of disease, familial Crohn's disease) (p = 0.039). CONCLUSIONS: CARD15 variants were identified as genetic predictors of Crohn's disease related sacroiliitis. An association was demonstrated between these polymorphisms and an extraintestinal manifestation of Crohn's disease.
Adolescent↗
Assessment of enthesitis in ankylosing spondylitis.
OBJECTIVE: To assess, firstly, the validity of the enthesis index published by Mander (Mander enthesis index (MEI)) and, secondly, to investigate whether it is possible to define a new enthesis index that is less time consuming to perform with at least similar or better properties. METHODS: Data from the OASIS cohort, an international, longitudinal, observational study on outcome in ankylosing spondylitis, were used. In this study, measures of disease activity, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the MEI, were assessed regularly in 217 patients. With the MEI, for each measurement period independently, a process of data reduction was performed to identify the entheses most commonly reported as painful by the patients. A more concise enthesis index was constructed with aid of the entheses found in this way. Correlations with measures of disease activity were used to test the validity of several entheses indices. RESULTS: Reduction of the number of entheses from 66 to 13 and omitting grading of the intensity of pain resulted in an index which was named the "Maastricht Ankylosing Spondylitis Enthesitis Score" (MASES). The MASES (range 0-13) has much greater feasibility than the MEI (range 0-90). However, up to 21% of patients with a score >0 on the MEI were not identified by a score on the MASES >0. Only 2.1% of the patients with an original enthesis score >0 had an original score on the MEI >3 (range 0-90) and it can be questioned whether a low score on the MEI index represents clinically important enthesitis. The Spearman correlation coefficient between the MASES score and the MEI was 0.90 and between the MASES and the BASDAI was 0.53 compared with a correlation of 0.59 between the MEI and the BASDAI. CONCLUSIONS: MASES seems to be a good alternative to the MEI with much better feasibility.
Adult↗