Risk factors for functional limitations in patients with long‐standing ankylosing spondylitis

Objective

To identify risk factors for functional limitations in patients with ankylosing spondylitis (AS) of at least 20 years' duration.

Methods

Patients with AS for ≥20 years were enrolled in the cross‐sectional component of the Prospective Study of Outcomes in AS. All patients had clinical evaluations and completed questionnaires on functional limitations and potential risk factors. Functional limitations were assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI; score range 0–100, higher scores indicate more limitations) and the Health Assessment Questionnaire for the Spondylarthropathies (HAQS). Risk factors included demographic characteristics, duration of AS, smoking status, number of comorbid medical conditions, recalled level of recreational activity in teens and twenties, occupational physical activity throughout life (rated 1 = little, 2 = moderate, 3 = heavy, and weighted by the number of years in each job), and history of AS in a first‐degree relative.

Results

The 326 patients (74% men) had a mean ± SD age of 55.0 ± 10.7 years, a mean duration of AS symptoms of 31.7 ± 10.2 years, and a mean BASFI score of 40.7 ± 25.6. BASFI scores increased with higher lifetime occupational physical activity (r = 0.31; P < 0.0001), the number of comorbid conditions (r = 0.25; P < 0.0001), and the duration of AS (r = 0.12; P = 0.04). BASFI scores were higher among current smokers compared with former/nonsmokers (55.5 versus 38.9; P = 0.0002), and among nonwhites compared with whites (49.9 versus 39.3; P = 0.02). In multivariable analyses, lifetime occupational physical activity, current smoking, education level, number of comorbid conditions, and family history were significantly associated with BASFI scores. The same risk factors were associated with the HAQS.

Conclusion

Functional limitations in patients with AS for ≥20 years are greater among those with a history of more physically demanding jobs, more comorbid conditions, and among smokers, and are less severe among those with higher levels of education and a family history of AS.

     

Relationship between the severity of enthesitis and clinical and laboratory parameters in patients with ankylosing spondylitis

In this study, we evaluated the relationship between the severity of enthesitis and outcome of measurement indices, clinical and laboratory parameters in patients with ankylosing spondylitis (AS). Thirty-three patients who fulfilled the modified New York criteria for AS were included in this study. Patients were asked to record the severity of current pain, night pain and morning stiffness on a 10-cm visual analogue scale. Stoke Enthesitis Index (SEI) was used to measure the severity of enthesitis. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) were calculated. SEI was correlated positively only with BASDAI (r = 0.370, P = 0.034). There was no relation between SEI and laboratory parameters (Erythrocyte Sedimentation Rate and C Reactive Protein). Our data suggest that using an enthesitis index such as SEI can be a valuable tool in the evaluation of disease activity in patients with AS. However, evaluation of enthesitis severity is based on information given by patient and should be combined with objective parameters such as spinal measurements when assessing disease activity.     

Atypical methotrexate dermatitis and vasculitis in a patient with ankylosing spondylitis

Reports of histologically proven low-dose methotrexate (MTX)-induced vasculitis are uncommon and mostly found for patients with rheumatoid arthritis. Herein we present a patient with ankylosing spondylitis who developed large atypical erythematopurpuric cutaneous lesions after the second oral dose of 7.5 mg MTX therapy. The histological findings of a cutaneous lesion were consistent with vasculitis. The skin lesions regressed significantly after the discontinuation of MTX therapy. As the clinical picture of the patient's rheumatological condition became progressively severe, prednisolone therapy was initiated 8 days later and the skin rash resolved completely in a couple of weeks. Received: 12 April 1999 / Accepted: 11 February 2000     

Infliximab improves productivity and reduces workday loss in patients with ankylosing spondylitis: Results from a randomized,placebo‐controlled trial

Objective

To examine whether clinical benefits observed after treatment with infliximab were accompanied by improvement in productivity and reduction in time lost from work in a randomized, double‐blind, placebo‐controlled, multicenter trial of patients with ankylosing spondylitis (AS).

Methods

Adults with active AS receiving standard antiinflammatory treatment were randomly assigned in a 3:8 ratio to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, and every 6 weeks thereafter through week 24. Physical function was measured using the Bath Ankylosing Spondylitis Functional Index. The impact of disease on productivity was measured using a visual analog scale (range 0–10). Self‐reported employment status and time lost at work before and during the trial were collected. Spearman's correlation coefficient was used to examine factors associated with productivity.

Results

Patients treated with infliximab had a more significant reduction in limitations of work and daily activity due to physical or emotional problems than patients treated with placebo. Of the subset of patients employed full time, patients in the infliximab group had a significantly greater improvement in productivity as early as week 6 compared with the placebo group. The median change from baseline in the productivity score at week 24 was 0.7 (median percent change 11%) in the placebo group compared with 2.1 (62%) in the infliximab group (P < 0.05). Daily productivity was significantly correlated with physical function and disease activity at baseline and week 24.

Conclusion

The daily productivity of patients with active AS was significantly associated with functional impairment and disease activity. Infliximab treatment significantly improved productivity and reduced workday loss among employed patients with AS.

     

HLA-B27阴性强直性脊柱炎一家系的心脏损害特征

目的观察 HLA-B27阴性家族性强直性脊柱炎(AS)心脏损害的特征。方法所有家系成员均采集完整病史、临床检查、常规12导联心电图、彩色多普勒超声心动图检查。并与年龄匹配的正常人对比分析。结果 33例家系成员中发生心房颤动的6例,占总心律失常人数的46%,心动过缓2例,高度房室传导阻滞1例,病态窦房结综合征1例,完全性右束支传导阻滞2例,室内差异性传导1例(排除 AS),所有传导系统异常的心律失常占 AS患者总心律失常人数的36%。因心脏原因死亡3例,其中1例死于全自动双腔起搏器(DDD)术后1年。AS 患者中 NYHA 心功能分级Ⅰ级8例。级2例,Ⅲ级1例,左心房扩大5例(45%),二尖瓣返流6例,三尖瓣返流4例。结论家族性 AS 心脏损害发生心律失常的种类有相似的趋势,主要以心房颤动为主,累及传导系统的心律失常次之,心脏损害以左心房扩大,舒张功能降低为主,可伴有二尖瓣和/或三尖瓣的返流。     

Anti-TNF therapy in the treatment of ankylosing spondylitis: the Finnish experience

Biological therapy for ankylosing spondylitis (AS) has led to improved disease control beyond that of conventional treatments. International recommendations encourage clinicians prescribing biological treatments to register patients in national registers to collect information on outcome and toxicity. Patients with AS (n = 229) from the Register of Biological Treatment in Finland (ROB-FIN) with severe disease of long duration were followed-up for up to 24 months. Due to an active disease, one or more concomitant disease-modifying antirheumatic drugs (DMARDs) were used by 86% at commencement of biological therapy. This add-on strategy with infliximab led to a rapid pain relief and improvement of patient's and physician's global assessments, C-reactive protein/erythrocyte sedimentation rate, and swollen and tender joint counts within 6 weeks. Concomitant use of NSAID and oral corticosteroid was reduced. Corresponding results were documented at 3 months with etanercept, which was more recently approved for the treatment of spondyloarthropathies. Seventy-nine percent of the patients were ASAS 20 responders. A subgroup of AS patients with only axial involvement (n = 46) responded correspondingly. The first biological drug was discontinued in only 7% due to lack of efficacy and in 6% due to adverse events. Anti-TNF agents, often used in combination with DMARDs, appeared to have persistent effectiveness and limited toxicity in a real-life clinical setting in a cohort of Finnish AS patients with severe disease and long disease duration.     

Bone and stone in ankylosing spondylitis: osteoporosis and urolithiasis

Ankylosing spondylitis (AS) has well-defined renal complications, but urolithiasis has not been studied in detail. We aimed to evaluate the relation between AS and urolithiasis presence and the effect of this coexistence on the bone mineral status of patients. By dual-energy x-ray absorptiometry measurements at the femoral neck and lumbar vertebrae, we assessed the influence of urolithiasis, disease activity, and duration on bone mineral density (BMD) at different sites. Fifty-three AS patients and 25 control subjects were enrolled in the study. Mean age was 39.49±13.01 years for the AS group and 43.80±10.69 years for the control group, with no statistically significant difference. Patients were accepted as having active disease if two of the following were present: (1) symptomatic peripheral arthritis, (2) erythrocyte sedimentation rate greater than 30 mm/h, (3) C-reactive protein greater than 5 mg/L, and (4) dorsal–lumbar morning stiffness more than 60 min. The ratios of urinary stone presence were 11.32 and 12% for AS and control groups, respectively. We observed that a statistically significant difference in femur neck BMD between AS patients with or without urolithiasis was apparent. The lumbar BMD values were also lower in the urolithiasis subgroup but could not reach the statistical significance. There were no significant BMD alterations in the control group due to stone presence. Comparison of active–inactive disease groups revealed significantly low T scores in either the femur neck or L2–4 regions of patients with higher activity indices, but this difference was more prominent in the femur neck. In the early AS group (23 patients), 18 patients (78.26%) had L2–4 T scores lower than −1 SD, and in the advanced AS population, 19 of 30 patients (63.33%) had either osteopenia or osteoporosis (OP). We conclude that severe disease and concomitant urolithiasis might increase bone loss and fracture risk especially at the femur neck.     

Lung findings on thoracic high-resolution computed tomography in patients with ankylosing spondylitis. Correlations with disease duration,clinical findings and pulmonary function testing

The aim of this study was to identify the spectrum of abnormalities revealed on high-resolution computerized tomography (HRCT) in patients with ankylosing spondylitis (AS), to compare findings with those of plain radiography and pulmonary function testing (PFT), and to look for correlations between lung involvement and AS severity. We prospectively studied 55 consecutive patients with a diagnosis of AS according to the modified New York criteria who attended our department over a period of 2 years. All patients had a detailed rheumatological examination and underwent plain chest radiography, chest HRCT and PFT. HRCT revealed abnormalities in 29 patients (52.7%), whereas plain chest radiography was abnormal in only 2. Abnormalities consisted of interstitial lung disease (ILD) (n=4), apical fibrosis (n=5), emphysema (n=5), bronchiectasis (n=4), ground glass attenuation (n=2), and non-specific interstitial abnormalities (n=26). Only apical fibrosis and bronchiectasis were statistically more frequent with increasing disease duration (significant trend ²test, p=0.0029 and 0.028, respectively). PFT showed a restrictive process in 19 patients (34.5%). No correlation was noted between HRCT and PFT, nor with AS symptomatic and structural severity parameters. However, there was a statistically significant correlation between PFT and AS symptomatic and structural severity parameters. In conclusion,: this study confirms that the chest HRCT of patients with AS showed a great number of abnormalities undetectable by standard X-rays. The high incidence of lung abnormalities emphasizes the importance of excluding such a diagnosis in patients with AS even without respiratory symptoms.Abbreviations AF Apical fibrosis - AS Ankylosing spondylitis - FVC Forced vital capacity - FEV₁ Forced expiratory volume in 1 s - HRCT High-resolution computerized tomography - ILD Interstitial lung disease - PFT Pulmonary function tests - VC Vital capacity     

Assessment of shoulder involvement and disability in patients with ankylosing spondylitis

The purpose of the study was to evaluate the parameters which have an important role in shoulder involvement and disability in ankylosing spondylitis (AS). Ninety patients with AS were divided into two groups according to the presence of shoulder involvement. Bath AS metrology index (BASMI), ankylosing spondylitis quality of life (ASQoL) and shoulder pain and disability index (SPADI) were used. Ranges of movements of limited shoulders were measured. Mean disease duration, age, BASMI, and ASQoL were higher and hip involvement was more frequent in the shoulder-involved group. Disease duration was found to be the most significant factor in shoulder involvement. A significant relationship was found between all SPADI scores and ASQoL. The SPADI disability score was affected by flexion limitation. Patients with hip involvement and longer disease duration should be evaluated for shoulder involvement. Flexion limitation of shoulder affected shoulder disability and shoulder disability impaired quality of life.     

Physical function and health‐related quality of life of Spanish patients with ankylosing spondylitis

Objective

To determine the physical function and the quality of life (QOL) of Spanish patients with ankylosing spondylitis (AS), and to study the reliability of the Spanish version of the Bath Ankylosing Spondylitis Functional Index (BASFI).

Methods

Clinimetric variables, including Spanish BASFI (test‐retest), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), QOL instruments (Short Form 36 [SF‐36] and European Quality of Life Questionnaire [EuroQol]), Bath Ankylosing Spondylitis Metrology Index (BASMI), and chest expansion, were assessed.

Results

A total of 92 patients were included: 69 males (75%), age (mean ± SD) 40.7 ± 9.1 years, and disease duration 11 ± 7.8 years. The scores (mean ± SD) were (from 0 the best to 10 the worst): BASFI 4.3 ± 2.4; BASDAI 4.5 ± 2.2; global SF‐36 5.5 ± 2.1; SF‐36 physical function 3.8 ± 2.5; SF‐36 physical scale 4.9 ± 2.7; SF‐36 mental scale 3.7 ± 2.7; SF‐36 physical role limitations 5.6 ± 4.4; SF‐36 general health 5.5 ± 2.1; SF‐36 pain 5.4 ±2.8; SF‐36 vitality 5.1 ± 2; EuroQoL rating scale 3.9±2.1; EuroQol health profile (from 0 the best to 2 the worst) 0.6 ± 0.4; and BASMI 4.7 ± 1.6. Significant association was found between BASFI and SF‐36 physical function domain (r = 0.75, R² = 0.56, P < 0.0001). BASFI Cronbach's alpha was 0.92, Spearman's rho = 0.91, P < 0.0001.

Conclusions

Physical function and QOL are deteriorated in AS. The physical domain is more impaired than the mental one. The SF‐36 and the health profile of the EuroQol may be used as generic instruments to measure health‐related QOL. Spanish BASFI index is a reliable instrument.

     

Osteopenia in men with mild and severe ankylosing spondylitis

We investigated the frequency and distribution of osteopenia according to the clinical severity in ankylosing spondylitis (AS). Bone mass was measured in men with mild (n=45) and severe AS (n=31) with dual-energy X-ray absorptiometry (DEXA). Definition of clinical severity was based on the Schobers test. Osteopenia was commonly detected (48% in mild AS and 39% severe AS) and, in mild disease, more frequently observed at the lumbar spine than any of the proximal femur sites. In severe AS, however, the frequency of osteopenia at the femoral neck and Wards triangle was as high as at the lumbar spine. Both bone mineral density and T-scores in severe disease were lower than in mild disease at the femur neck, Wards triangle, and total proximal femur, but not in the lumbar spine. The progression of osteopenia may be reflected more reliably at proximal femur sites than at the lumbar spine.     

Tocilizumab,a humanized anti-interleukin-6 receptor antibody,ameliorated clinical symptoms and MRI findings of a patient with ankylosing spondylitis

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory osteoarticular disease. Although the etiology remains unknown, proinflammatory cytokines, such as tumor necrosis factor α and interleukin-6, have been implicated in the development of AS. Here, we report that a patient with AS, whose disease had been refractory to conventional treatment regimens and who needed to receive continuous corticosteroid, responded well to tocilizumab. While further clinical evaluation is required, tocilizumab may be an optional treatment for AS.     

Hyperhomocysteinemia in ankylosing spondylitis: prevalence and association with clinical variables

We evaluated the prevalence and characteristics associated with hyperhomocysteinemia in ankylosing spondylitis (AS). Ninety-seven patients with AS were compared with 97 controls. The assessment included clinical characteristics, disease activity (BASDAI), functioning (BASFI), history of drugs, and erythrocyte sedimentation rate (ESR). Total serum homocysteine (tHcy) was determined by fluorescence polarization immunoassay. A higher frequency of hyperhomocysteinemia (>15 μmol/L) was observed in AS (12 vs. 1%, P = 0.002). In the multivariate analysis the risk for hyperhomocysteinemia was increased in patients with higher score of HAQ-S (OR = 5.27, 95% CI: 1.29–21.44) and higher ESR (OR = 1.09, 95% CI: 1.02–1.18). No statistical associations was observed between hyperhomocysteinemia with other variables including methotrexate or sulfasalazine utilization. In conclusion, this study found a significant prevalence of hyperhomocysteinemia in Mexican patients with AS mainly associated to a worst functional impairment. Further follow-up studies are required to evaluate the risk of cardiovascular disease in these patients.     

Evaluation of paravertebral muscle atrophy and fatty degeneration in ankylosing spondylitis

Aim: The purpose of this study was to assess morphological changes in the paravertebral muscles in patients with ankylosing spondylitis.

Materials and methods: Fifty-one patients diagnosed with ankylosing spondylitis and a 50 member control group were included in the study. The surface area of the multifidus and erector spinae muscles was measured at four levels between L1 and L5, and fatty degeneration in these muscles was scored. Lumbosacral and lumbar lordotic angles were determined for the patient and control groups.

Results: Loss of muscle cross-sectional area compatible with atrophy was present at all four levels in the paraspinal muscles in patients with ankylosing spondylitis. A negative correlation was observed between paravertebral muscle area and duration of disease at three levels, but not at L1-2. Although muscle area decreased with the duration of disease at the L1-2 level, this was not statistically significant (r=??0.195, p?=?0.171). Comparison of intramuscular fatty degeneration between the groups revealed increased intramuscular fat at all levels in patients with ankylosing spondylitis, with the exception of L3–4, and a positive correlation between fatty degeneration and duration of disease was determined at all levels.

Conclusion: Chronic inflammation, cytokine-mediated fibrosis, immobilization, and postural changes in ankylosing spondylitis contribute to fatty degeneration and atrophy in the paravertebral muscles.     

Responsiveness and discriminative capacity of the assessments in ankylosing spondylitis disease‐controlling antirheumatic therapy core set and other outcome measures in a trial of etanercept in ankylosing spondylitis

Objective

To investigate the responsiveness and discriminative capacity, and the relationship between both, of instruments selected for the disease‐controlling antirheumatic therapy (DC‐ART) core set by the Assessments in Ankylosing Spondylitis Working Group (ASAS).

Methods

Responsiveness and discriminative capacity of different measures reflecting disease activity and function, either included in the ASAS DC‐ART core set or not, were evaluated in a randomized controlled clinical trial comparing etanercept with placebo in patients with ankylosing spondylitis. Guyatt's method was used as the primary analysis for responsiveness, and Student's t‐test for discriminative capacity.

Results

At day 28 of therapy, almost all measures indicated moderate to large responsiveness in the etanercept group (Guyatt 0.60–3.11). Some scales of the Short Form 36 (general health, mental component summary, and role emotional), the modified Schober's test, and the Fatigue Severity Scale were not responsive. The results were similar if analyzed at day 112 of therapy. Peripheral joint counts, joint scores, and occiput‐to‐wall distance could not be evaluated due to a floor effect. In general, the relation between responsiveness and discriminative capacity was strong: Measures that demonstrated high responsiveness also showed high between‐group t values.

Conclusion

Measures included in the ASAS DC‐ART core set, except modified Schober's test, have good responsiveness and good discriminatory capacity. Some measures could not be evaluated due to a floor effect.

     

New insights toward the pathogenesis of ankylosing spondylitis; genetic variations and epigenetic modifications

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, characterized by typically an axial arthritis. AS is the prototype of a group of disorders called spondyloarthropathies, which is believed to have common clinical manifestations and genetic predisposition. To date, the exact etiology of AS remains unclear. Over the past few years, however, the role of genetic susceptibility and epigenetic modifications caused through environmental factors have been extensively surveyed with respect to the pathogenesis of AS, resulted in important advances. This review article focuses on the recent advances in the field of AS research, including HLA and non-HLA susceptibility genes identified in genome-wide association studies (GWAS), and aberrant epigenetic modifications of gene loci associated with AS. HLA genes most significantly linked with AS susceptibility include HLA-B27 and its subtypes. Numerous non-HLA genes such as those in ubiquitination, aminopeptidases and MHC class I presentation molecules like ERAP-1 were also reported. Moreover, epigenetic modifications occurred in AS has been summarized. Taken together, the findings presented in this review attempt to explain the circumstance by which both genetic variations and epigenetic modifications are involved in triggering and development of AS. Nonetheless, several unanswered dark sides continue to clog our exhaustive understanding of AS. Future researches in the field of epigenetics should be carried out to extend our vision of AS etiopathogenesis.     

Identification of acute phase reactants and cytokines useful for monitoring infliximab therapy in ankylosing spondylitis

Although most ankylosing spondylitis patients show an apparent clinical response to infliximab therapy, there is considerable individual variation. Because current clinical assessment relies heavily on subjective patient self-evaluation, biomarkers of high sensitivity and specificity are much needed. Here, we assessed potential biomarkers in 47 ankylosing spondylitis patients who received three standard pulses of infliximab. Before each infusion and at week 10, the following were measured: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count, serum levels of metalloproteinase-3 (MMP-3), and 22 different cytokines. We discovered that, 2 weeks after the first infusion, the combination of ESR, CRP, and platelet count distinguished responders from non-responders with 81.3% sensitivity and 72.7% specificity. The distinguishing power was much less when each acute phase reactant was used alone. Among the 22 cytokines, serum IL-1α was able to distinguish responders from non-responders at week 6, with sensitivity of 84.9% and specificity of 53.8%. Serum IL-1α was probably generated from the joint compartments, as synovial fluid levels were much higher than corresponding serum levels. Although infliximab infusions led to rapid and significant suppression of serum MMP-3 levels, serum MMP-3 levels did not distinguish responders from non-responders. Besides identifying potential biomarkers, our results also demonstrate the usefulness of using sensitivity and specificity to assess usefulness of potential biomarkers.