Biomedical subjects

A Calin

Publications and source records attributed to A Calin.

At least 19 recordsLinked to original sources

PubMed2006

Non-B27 MHC associations of ankylosing spondylitis.

Ankylosing spondylitis (AS) has been associated with human leukocyte antigen (HLA)-B27 for over 30 years; however, the mechanism of action has remained elusive. Although many studies have reported associations between AS and other genes in the major histocompatibility complex (MHC) in AS, no conclusive results have emerged. To investigate the contribution of non-B27 MHC genes to AS, a large cohort of AS families and controls were B27 typed and genotyped across the region. Interrogation of the data identified a region of 270 kb, lying from 31 952 649 to 32 221 738 base pairs from the p-telomere of chromosome 6 and containing 23 genes, which is likely to include genes involved with susceptibility to AS.

Case-Control Studies↗

PubMed2004

Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis.

OBJECTIVE: A double blind, randomised, placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis (AS). METHODS: Adult patients with AS at 14 European sites were randomly assigned to 25 mg injections of etanercept or placebo twice weekly for 12 weeks. The primary efficacy end point was an improvement of at least 20% in patient reported symptoms, based on the multicomponent Assessments in Ankylosing Spondylitis (ASAS) response criteria (ASAS 20). Secondary end points included ASAS 50 and ASAS 70 responses and improved scores on individual components of ASAS, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), acute phase reactants, and spinal mobility tests. Safety was evaluated during scheduled visits. RESULTS: Of 84 patients enrolled, 45 received etanercept and 39 received placebo. Significantly more etanercept patients than placebo patients responded at the ASAS 20 level as early as week 2, and sustained differences were evident up to week 12. Significantly more etanercept patients reported ASAS 50 responses at all times and ASAS 70 responses at weeks 2, 4, and 8; reported lower composite and fatigue BASDAI scores; had lower acute phase reactant levels; and had improved spinal flexion. Etanercept was well tolerated. Most adverse events were mild to moderate; the only between-group difference was injection site reactions, which occurred significantly more often in etanercept patients. CONCLUSIONS: Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of AS.

Adult↗

PubMed2004

The burden of ankylosing spondylitis and the cost-effectiveness of treatment with infliximab (Remicade).

OBJECTIVES: In the past, treatment options for ankylosing spondylitis (AS) have been limited, and the introduction of new treatments such as infliximab will have a noticeable impact on health-care budgets. The objective of this study was therefore to assess the current burden of the disease and estimate the cost-effectiveness of infliximab treatments. METHODS: A cross-sectional retrospective observational study of resource consumption and utility related to disease severity was performed in patients who had participated in a population survey between 1992 and 1994 at the University of Bath and patients regularly followed at the Royal National Hospital for Rheumatic Diseases in Bath for up to 9 years. Mean costs and utility were estimated using a regression model including age, gender, disease duration, disease activity and functional status, and disease development was expressed as annual progression of functional disability. Cost-effectiveness of infliximab was modelled using a 3-month placebo-controlled clinical trial with open 1-yr extension in 70 patients, over a total time frame of 2 yr. In the model, costs and utility controlled for disease severity and age from the observational study were assigned to individual patients. The effect of long-term treatment was evaluated in a hypothetical model over 30 yr. RESULTS: Fifty-seven per cent of patients answered the questionnaires. The mean age was 57 (s.d. 11.2) yr, 74% were male and mean disease duration was 30.2 (11.7) yr. Mean total costs were estimated at pound 6765 (s.d. pound 166). Indirect costs represented 57.9% and non-medical costs such as investments and informal care accounted for 16.5% of total costs. Mean utility was 0.67 (0.21). In the main model, mean costs for untreated patients are estimated at pound 25,128. For the infliximab group, mean costs (excluding treatment) are estimated at pound 17,240, a reduction of 31%. Thus, part of the treatment cost was offset by savings in other resources ( pound 7888), leaving an incremental cost of pound 6214. Treatment increased the number of quality-adjusted live years (QALYs) by 0.175 QALYs, leading to a cost per QALY gained of pound 35,400 for the first year of treatment. When treatment is assumed to continue for the full 2 yr, the cost per QALY is pound 32,800. When infliximab infusions are given every 8 weeks instead of every 6 weeks, the cost per QALY is reduced to pound 17,300. In the long-term model, the cost per QALY is estimated at pound 9600. CONCLUSIONS: Non-medical costs and production losses dominate costs in AS, and economic evaluation must therefore adopt a societal perspective. The cost of treatment with infliximab is partly offset by reductions in the cost of the disease and patients' quality of life is increased, leading to a cost per QALY gained in the vicinity of pound 30,000 to pound 40,000 in the short term, but potentially below pound 10,000 in the long term.

Antibodies, Monoclonal↗

PubMed2003

The effect of transforming growth factor beta1 gene polymorphisms in ankylosing spondylitis.

OBJECTIVES: To determine whether genetic polymorphisms in or near the transforming growth factor beta1 (TGFB1) locus were associated with susceptibility to or severity of ankylosing spondylitis (AS). METHODS: Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). RESULTS: A weak association was noted between the rare TGFB1 +1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/+915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. CONCLUSION: This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

Adult↗

PubMed2003

Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group.

BACKGROUND: There is ample evidence of important symptomatic efficacy of tumour necrosis factor alpha (TNFalpha) inhibition in ankylosing spondylitis (AS). Moreover, studies suggest that anti-TNF could be considered as the first disease controlling antirheumatic treatment (DC-ART) for AS. OBJECTIVE: To determine precisely which patients with AS are most likely to benefit from anti-TNFalpha treatment because of the cost and possible long term side effects of such treatment. METHODS: Assessment in Ankylosing Spondylitis (ASAS) members were asked to use a Delphi technique to name the characteristics of patients with AS for whom they would start DC-ART, in three different clinical presentations (isolated axial involvement, peripheral arthritis, enthesitis). RESULTS: Among the 62 invited ASAS members, more than 50% actively participated in the four phases of definition according to the Delphi technique. For each of the three clinical presentations, a combination of five to six domains was proposed, with an evaluation instrument and a cut off point defining a minimum level of activity for each domain. CONCLUSION: This study provides a profile for a patient with AS for considering initiation of biological agents that reflects the opinion of the ASAS members, using a Delphi exercise. Further studies are required to assess their relevance and their consistency with clinical practice.

Antibodies, Monoclonal↗

PubMed2002

Prevalence of spondyloarthritis in Terceira, Azores: a population based study.

OBJECTIVE: To determine the prevalence of spondyloarthritis (SpA) in the Caucasian population of Terceira Island, Azores. METHODS: Study subjects were recruited from people over the age of 50 years from one half of the island of Terceira (n=24 561). Seventy eight men and 78 women from each five year age group were selected, giving a total of 468 men and 468 women available for study, of whom 490 agreed to take part. These subjects were assessed by dorsal, lumbar, and pelvic radiography. Radiological sacroiliitis was identified in eight patients on whom sacroiliac computed tomography scans were performed. HLA class I typing by polymerase chain reaction with sequence-specific primers was carried out in seven cases. RESULTS: SpA was present in eight subjects (1.6%, 95% CI 0.8 to 2.7%), including seven men (2.7%) and one woman (0.4%). Three (1.2% ) male patients with definite ankylosing spondylitis were HLA-B27 positive. Only one person had a previous diagnosis of SpA. CONCLUSION: These data complement previous studies in European countries on SpA prevalence and establish an estimate of the overall prevalence of SpA in a southern European population.

Adult↗

PubMed2001

Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci.

Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.

Chromosome Mapping↗

PubMed2001

Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug.

OBJECTIVE: To evaluate the short-term efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis (AS). METHODS: The study was a 6-week randomized, double-blind, placebo-controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain > or =40 mm on a 100-mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]). RESULTS: Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were -13 mm, -21 mm, and -27 mm (P = 0.006) for pain and 1, -6, and -12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively. CONCLUSION: The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage, with significant improvement of both pain and function in patients with AS.

Adult↗

PubMed2001

Is disease severity in ankylosing spondylitis genetically determined?

OBJECTIVE: To assess the role of genes and the environment in determining the severity of ankylosing spondylitis. METHODS: One hundred seventy-three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent-child pairs, 20 families with both first- and second-degree relatives affected, and 7 families with only second-degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance-components modeling was used to determine the genetic and environmental components contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models. RESULTS: Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10(-4)], BASFI familiality 0.68 [P = 3 x 10(-7)]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0.36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI. CONCLUSION: This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.

Adolescent↗

PubMed2001

Lessons from an international survey of paper cases of 10 real patients from an early arthritis clinic. CRI (Club Rhumatismes et Inflammation) Group.

OBJECTIVE: To determine how experts would classify 10 early-arthritis cases (7 atypical) and to study discrepancies in diagnoses relative to ACR criteria for rheumatoid arthritis (RA) or ESSG criteria for spondyloarthropathy (SpA). METHODS: Ten real cases (5 met ACR criteria for RA, 6 ESSG criteria for SpA, 3 both and 2 neither) followed for 28.5 +/- 4.8 months were sent as paper cases to 20 international and 12 French experts. Each expert selected a diagnosis among 8 possible choices and rated it on a 0-10 confidence scale. For each case, 3 analog scales (0-100 mm) were used to indicate the probability of RA, SpA or undifferentiated arthritis (UA). RESULTS: Experts often disagreed about diagnoses (up to 5 different diagnoses for a given case, with a mean of 3.9 per case). Similarly, expert opinions on probabilities for RA and SpA differed widely, with great overlap between confidence for RA, SpA and UA. Fulfilment of ACR or ESSG criteria was poorly related to the experts' diagnosis and evaluation of probabilities for RA and SpA. However, UA was a relatively infrequent choice (19%). CONCLUSIONS: There was no general consensus about the nosology of early RA and SpA. Classification of atypical early arthritis was not resolved by currently available criteria for RA and SpA. This may have implications for therapy in early disease.

Adult↗

PubMed2001

Total hip arthroplasty in ankylosing spondylitis: outcome in 340 patients.

OBJECTIVE: The longterm outcome of total hip arthroplasty (THA) in ankylosing spondylitis (AS) remains unclear. Concern has been expressed regarding joint survival, given that recipients are young and active. We present outcome data on 340 THA after a mean followup of 14 years. METHODS: The 6.7% of patients (n = 309: 237 contactable) who had undergone THA were identified from our database of 4569 subjects. Responses were received from 166 subjects (112 men, 54 women, M:F = 2:1) who were assessed for employment status and outcome [i.e., pain, mobility, satisfaction, disease activity (BASDAI), function (BASFI), and global well being (BAS-G)]. A non-THA AS control group was matched for age, sex, and disease duration. RESULTS: The mean age at AS disease onset for THA recipients was 19.5 yrs compared to 24.4 yrs for the total database (p < 0.05). The mean age at the first THA was 40.0 yrs. Of the 340 THA, 276 were primary (bilateral in 66%) and 64 were revisions. The mean followup for THA was 14.0 yrs (range 1-52). Overall, for the 340 THA, the patients considered outcome to be very good in 85%. In relation to the matched control group, THA patients were comparable for BASDAI, but had poorer function (p < 0.05) and lower global well being (p < 0.05). Of the 80 men under 60 years of age, 39 (49%) were employed compared to 49 (68%) of the control group (p < 0.01). Survival of original THA and revisions after 10, 15, and 20 yrs was 90%, 78%, 64%, respectively (originals), and 73%, 55%, 55%, respectively (revisions). CONCLUSION: The longterm outcome of THA in AS is outstanding. THA recipients have a younger age at onset than nonrecipients. The longterm survival characteristics of THA in young patients with AS is excellent.

Adult↗

PubMed2001

Ankylosing spondylitis: interaction between genes, joints, age at onset, and disease expression.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disorder with symptom onset generally occurring in the late teens/mid-twenties. In women, a younger age at onset enhances disease susceptibility in the next generation. We examined the influence of age at symptom onset on phenotypic expression. METHODS: Patients were divided into cohorts according to age of symptom onset. The primary outcome measure was radiological progression (by Bath AS Radiology Index, BASRI). Secondary measures were disease activity (Bath AS Disease Activity Index, BASDAI), function (Bath AS Functional Index, BASFI), numbers undergoing AS related surgery, and percentage with secondary disorders. RESULTS: Age at onset had no significant effect on radiological progression (young onset vs late onset, 8.0, 8.6, respectively) disease activity (young vs late, 4.4, 4.4), need for non-hip surgical intervention (9%, 8%, respectively), or prevalence of secondary disorders (iritis, 40%, 41%; psoriasis, 20%, 19%; inflammatory bowel disease, 7.5%, 8.9%). By contrast, there was a striking increase in prevalence of total hip replacement in those with juvenile onset (18%, 8%, respectively; p < 0.001). Regardless of age at onset, spinal progression determined radiologically was greater in those with hip arthritis compared to those without (young onset hip involvement vs non-hip involvement, 9.7 (2.4), 7.2 (3.0) (p < 0.001); late onset hip involvement vs non-hip involvement, 10.1 (2.5), 7.1 (3.0), respectively]. Function deteriorates with age (young onset vs late onset, 3.7, 4.5, respectively; p < 0.01). CONCLUSION: (1) Hip disease (young or late onset) is a major prognostic marker for longterm severe disease (patients with hip disease have a spinal score increased by 2.5-3 points or 35-40% more change). (2) Hip involvement is more prevalent among patients with young age at onset. (3) Young onset patients without hip involvement do not have more severe disease. Thus, age at onset, itself, does not influence disease severity. (4) Since hip involvement and not age at onset is associated with worse outcome, patients with a young age at onset may be assumed to have an increased susceptibility load (i.e., genetic component or environmental trigger) rather than more severity genes. The lack of association between severity and age at onset implies that the determinants of susceptibility and severity are independent.

Adolescent↗

PubMed2001

Inflammatory eye, skin, and bowel disease in spondyloarthritis: genetic, phenotypic, and environmental factors.

OBJECTIVE: To explore the nature of the interrelationship between inflammatory disease of the spine/joints, skin, eye, and bowel [i.e., ankylosing spondylitis (AS), psoriasis, iritis, inflammatory bowel disease (IBD)]. METHODS: The study used 4 approaches: (1) analysis of the prevalence of secondary disorders within the AS individual (chi-square and matched pair analysis); (2) study of the temporal relationship between the onset of the different conditions; (3) evaluation of the prevalence of disease among first degree relatives; and (4) influence of secondary disorders on outcome of AS. RESULTS: 1. Among 3287 patients with AS, more than expected had either spondylitis associated with multiple co-disorders or pure AS (with no co-diseases); fewer than expected had AS plus a single co-disease (chi-square = 32.2, p < 0.001). In a matched pair analysis, patients with AS and a secondary disorder were more likely to have an additional concomitant disease, e.g., IBD-AS (n = 335) patients had a higher prevalence of iritis [45.4% vs 36.7%; OR 1.4 (1.1-2.0)] or psoriasis [23.9% vs 14.3%; OR 1.9 (1.3-2.8)] than controls. 2. Among our database subjects, the symptomatic onset of the spinal disease precedes or is contemporaneous with gut, skin, and eye involvement (matched pair t test, p < 0.001). 3. Patients with multiple disorders predict the highest prevalence of co-diseases (i.e., psoriasis, IBD, iritis, or AS) within family members, followed by those AS patients with only IBD, psoriasis, or iritis in descending order. 4. Both psoriasis and IBD increase severity in terrms of function and disease activity of AS in the patient. Radiological change is greatest for those AS subjects with iritis. CONCLUSION: There is a striking overlap within patients and family members of rheumatological, dermatological, and gastroenterological diseases. The susceptibility genes of these co-disorders appear to overlap with each other and with AS: 1. A patient with 2 inflammatory conditions is at an increased risk of developing an additional related inflammatory disorder. 2. Those with enteropathic spondylarthritis would appear to carry the greatest genetic load in terms of first degree relatives developing inflammatory conditions (including psoriasis and iritis that are not seen in the index IBD-AS patient). 3. The secondary disorders do not precede AS (arguing against psoriasis and IBD allowing for an environmental conduit to pathogenic triggers in AS). The susceptibility factors for these inflammatory conditions may be additive or have a synergistic effect on each other. There is evidence for a shared gene hypothesis.

Age of Onset↗

PubMed2000

Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common and highly familial rheumatic disorder. The sibling recurrence risk ratio for the disease is 63 and heritability assessed in twins >90%. Although MHC genes, including HLA-B27, contribute only 20-50% of the genetic risk for the disease, no non-MHC gene has yet been convincingly demonstrated to influence either susceptibility to the disease or its phenotypic expression. Previous linkage and association studies have suggested the presence of a susceptibility gene for AS close to, or within, the cytochrome P450 2D6 gene (CYP2D6, debrisoquine hydroxylase) located at chromosome 22q13.1. We performed a linkage study of chromosome 22 in 200 families with AS affected sibling-pairs. Association of alleles of the CYP2D6 gene was examined by both case-control and within-family means. For case-control studies, 617 unrelated individuals with AS (361 probands from sibling-pair and parent-case trio families and 256 unrelated non-familial sporadic cases) and 402 healthy ethnically matched controls were employed. For within-family association studies, 361 families including 161 parent-case trios and 200 affected sibling-pair families were employed. Homozygosity for poor metabolizer alleles was found to be associated with AS. Heterozygosity for the most frequent poor metabolizer allele (CYP2D6*4) was not associated with increased susceptibility to AS. Significant within-family association of CYP2D6*4 alleles and AS was demonstrated. Weak linkage was also demonstrated between CYP2D6 and AS. We postulate that altered metabolism of a natural toxin or antigen by the CYP2D6 gene may increase susceptibility to AS.

Alleles↗

PubMed2000

The X-chromosome and susceptibility to ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) affects 0.25-1.0% of the population, and its etiology is incompletely understood. Susceptibility to this highly familial disease (lambda(s) = 58) is primarily genetically determined. There is a significant sex bias in AS, and there are differences in recurrence risk to the offspring of affected mothers and fathers, suggesting that there may be an X-linked recessive effect. We undertook an X-chromosome linkage study to determine any contribution of the X-chromosome to AS susceptibility. METHODS: A linkage study of the X-chromosome using 234 affected sibling pairs was performed to investigate this hypothesis. RESULTS: No linkage of the X-chromosome with susceptibility to AS was found. Model-free multipoint linkage analysis strongly excluded any significant genetic contribution (lambda > or = 1.5) to AS susceptibility encoded on the X-chromosome (logarithm of odds [LOD] <-2.0). Smaller genetic effects (lambda > or = 1.3) were also found to be unlikely (LOD <-1.0). CONCLUSION: The sex bias in AS is not explained by X-chromosome-encoded genetic effects. The disease model best explaining the sex bias in occurrence and transmission of AS is a polygenic model with a higher susceptibility threshold in females.

Genetic Linkage↗

PubMed2000

Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis.

OBJECTIVES: It has long been suspected that susceptibility to ankylosing spondylitis (AS) is influenced by genes lying distant to the major histocompatibility complex. This study compares genetic models of AS to assess the most likely mode of inheritance, using recurrence risk ratios in relatives of affected subjects. METHODS: Recurrence risk ratios in different degrees of relatives were determined using published data from studies specifically designed to address the question. The methods of Risch were used to determine the expected recurrence risk ratios in different degrees of relatives, assuming equal first degree relative recurrence risk between models. Goodness of fit was determined by chi(2) comparison of the expected number of affected subjects with the observed number, given equal numbers of each type of relative studied. RESULTS: The recurrence risks in different degrees of relatives were: monozygotic (MZ) twins 63% (17/27), first degree relatives 8.2% (441/5390), second degree relatives 1.0% (8/834), and third degree relatives 0. 7% (7/997). Parent-child recurrence risk (7.9%, 37/466) was not significantly different from the sibling recurrence risk (8.2%, 404/4924), excluding a significant dominance genetic component to susceptibility. Poor fitting models included single gene, genetic heterogeneity, additive, two locus multiplicative, and one locus and residual polygenes (chi(2) >32 (two degrees of freedom), p<10(-6) for all models). The best fitting model studied was a five locus model with multiplicative interaction between loci (chi(2)=1.4 (two degrees of freedom), p=0.5). Oligogenic multiplicative models were the best fitting over a range of population prevalences and first degree recurrence risk rates. CONCLUSIONS: This study suggests that of the genetic models tested, the most likely model operating in AS is an oligogenic model with predominantly multiplicative interaction between loci.

Female↗

PubMed2000

Ankylosing spondylitis and the shoulder: commonly involved but infrequently disabling.

OBJECTIVE: To undertake 2 independent studies of shoulder involvement in patients with ankylosing spondylitis (AS) and assess the frequency of shoulder pain, stiffness, and loss of movement and function. To evaluate and correlate shoulder symptoms, function, range of movement, and radiology. METHODS: A cross sectional design was used in both studies. In Study A, a self-administered questionnaire was sent to members of the National Ankylosing Spondylitis Society of the UK and patients attending the Royal National Hospital for Rheumatic Diseases. In Study B, a clinical assessment of 88 patients with AS was undertaken that included a radiological assessment of 26 consecutive patients. RESULTS: In Study A, 15.2% and 13.8% of subjects had severe/very severe shoulder pain or stiffness, respectively. In Study B the corresponding findings were 9.6% and 17.6%. Patient reported disability associated with shoulder involvement was uncommon. Study A revealed that patients with severe/very severe shoulder pain were more likely to have significant hip and knee involvement. Significant shoulder involvement appears to be as common as involvement of the hip joint. In Study B radiological changes were common, being present in 31% of patients, but were often minor. There was a significant correlation between the sum of the stiffness, abduction, and flexion scores for both shoulders and the total radiological score (r = 0.87; p<0.001). CONCLUSION: The results suggest that shoulder symptoms and loss of shoulder mobility are common in patients with AS, and correlate with higher pain scores and influence of AS on their lives as assessed by the Arthritis Impact Measurement Scale, but are rarely disabling. Involvement of the shoulder joint in AS correlates with involvement of other peripheral joints as well as the extent of radiographic change on shoulder radiographs.

Adult↗

PubMed2000

The development and validation of a radiographic grading system for the hip in ankylosing spondylitis: the bath ankylosing spondylitis radiology hip index.

OBJECTIVE: To develop a simple but reproducible radiological scoring system for the hip in ankylosing spondylitis (AS). METHODS: A consensus approach was used to develop a grading system whereby hip radiographs of 470 patients with AS were scored from 0 to 4 (normal, suspicious, mild, moderate, and severe), producing the Bath Ankylosing Spondylitis Radiology Hip Index ( BASRI-hip or BASRI-h). The system was designed to be specific for AS radiographic change at the hip and includes circumferential joint space narrowing, osteophytes, erosions, and protrusio acetabulae. This score can then be added to the BASRI-spine, forming the grading system BASRI-total, scored 2-16. Radiographs of 134 patients were used to test reproducibility. Blinded radiographs of 100 non-AS patients were included randomly to assess disease specificity. Sensitivity to change was determined using 438 radiographs from 122 patients, over 219 time intervals. RESULTS: Inter and intraobserver variation for the right and left hip showed 83-84% and 94-96% complete agreement, respectively. Disease specificity was 0.76. If non-AS patients with a total hip replacement were excluded, disease specificity was 0.83. Sensitivity to change became apparent at one year (p < 0.001). Grading the hips using a single radiograph takes seconds. CONCLUSION: BASRI-h is a reliable method for grading hip radiographic change in AS. It is disease-specific, sensitive to change, simple to use, and rapid to perform.

Female↗