Thomas J. Learch

The Impact of Tumor Necrosis Factor α Inhibitors on Radiographic Progression in Ankylosing Spondylitis

OBJECTIVEnTo study the effect of tumor necrosis factor α (TNFα) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS).nnnMETHODSnAll AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n=334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNFα inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA-B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model.nnnRESULTSnTNFα inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30-0.88, P=0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09-5.3], P=0.03). In the ZINB model, the use of TNFα inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNFα inhibitors was stronger after propensity score matching.nnnCONCLUSIONnTreatment with TNFα inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup.

Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis

OBJECTIVEnTo improve prognostic ability in ankylosing spondylitis (AS), we sought to identify demographic, clinical, and immunogenetic characteristics associated with radiographic severity in a large cohort of patients.nnnMETHODSnPatients with AS for > or =20 years were enrolled in a cross-sectional study (n = 398). Pelvic and spinal radiographs were scored using the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s), and radiographic severity was measured as the BASRI-s/duration of AS. Clinical factors and HLA-B, DR, DQ, and DP alleles associated with the highest quartile of the distribution of radiographic severity were identified by first using random forests and then using multivariable logistic regression modeling. Similar procedures were used to identify factors associated with the lowest quartile of radiographic severity.nnnRESULTSnRadiographic severity (being in the top quartile of BASRI-s/duration of AS) was associated with older age at onset of AS (odds ratio [OR] 1.10 per year), male sex (OR 1.90), current smoker (OR 4.72), and the presence of HLA-B*4100 (OR 11.73), DRB1*0804 (OR 12.32), DQA1*0401 (OR 5.24), DQB1*0603 (OR 3.42), and DPB1*0202 (OR 23.36), whereas the presence of DRB1*0801 was strongly negatively associated (OR 0.03). Being in the lowest quartile of BASRI-s/duration of AS was also less likely among those with an older age at onset of AS (OR 0.94 per year), men (OR 0.28), and current smokers (OR 0.29).nnnCONCLUSIONnThe accuracy of the prognosis of radiographic severity in AS is improved by knowing the age at disease onset, sex, smoking history, and the presence of HLA-B*4100, DRB1*0804, DQA1*0401, DQB1*0603, DRB1*0801, and DPB1*0202 alleles.

Ankylosing Spondylitis: Patterns of Radiographic Involvement—A Re-examination of Accepted Principles in a Cohort of 769 Patients

PURPOSEnTo re-examine the patterns of radiographic involvement in ankylosing spondylitis (AS).nnnMATERIALS AND METHODSnThis prospective study had institutional review board approval, and 769 patients with AS (556 men, 213 women; mean age, 47.1 years; age range, 18-87 years) provided written informed consent. Radiographs of the cervical spine, lumbar spine, pelvis, and hips were scored by using the Bath Ankylosing Spondylitis Radiology Index (BASRI) by an experienced radiologist. Differences in sacroiliitis grade between right and left sacroiliac joints, frequency of cervical- and lumbar-predominant involvement by sex, frequency of progression to complete spinal fusion, and association between hip arthritis and spinal involvement were computed for the cohort overall and for subgroups defined according to duration of AS in 10-year increments.nnnRESULTSnSymmetric sacroiliitis was seen in 86.1% of patients. Lumbar predominance was more common during the first 20 years of the disease, after which the cervical spine and lumbar spine were equally involved. Men and women were equally likely to have cervical-predominant involvement. Complete spinal fusion was observed in 27.9% of patients with AS for more than 30 years and in 42.6% of patients with AS for more than 40 years. Patients with BASRI hip scores of 2 or greater had significantly higher BASRI spine scores.nnnCONCLUSIONnThere were no sex differences in cervical-predominant involvement in AS. Hip arthritis was strongly associated with worse spinal involvement.

Psychological correlates of self-reported functional limitation in patients with ankylosing spondylitis

IntroductionFunctional status is an integral component of health-related quality of life in patients with ankylosing spondylitis (AS). The purpose of this study was to investigate the role of psychological variables in self-reported functional limitation in patients with AS, while controlling for demographic and medical variables.Methods294 AS patients meeting modified New York Criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality and helplessness at the baseline visit. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of correlation of psychological variables with functional limitation, as measured by the Bath AS Functional Index (BASFI).ResultsIn the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASFI scores, adding an additional 24% to the overall R-square beyond that accounted by demographic and medical variables (R-square 32%), resulting in a final R-square of 56%. Specifically, arthritis helplessness, depression and passive coping beside age, ESR and the Bath AS Radiograph Index accounted for a significant portion of the variance in BASFI scores in the final model.ConclusionsArthritis helplessness, depression, and passive coping accounted for significant variability in self-reported functional limitation beyond demographic and clinical variables in patients with AS. Psychological health should be examined and accounted for when assessing functional status in the AS patients.

Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis

Objective To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). Method We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon–intron boundaries, and 5u2005kb flanking DNA in the 5′ and 3′ UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into ‘mild’ and ‘severe’ groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. Results Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10−5), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10−3). There was no observed association between radiographic severity and HLA-B*27. Conclusions These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

REGIONAL RADIOGRAPHIC DAMAGE AND FUNCTIONAL LIMITATIONS IN PATIENTS WITH ANKYLOSING SPONDYLITIS: DIFFERENCES IN EARLY AND LATE DISEASE

Both radiographic damage and functional limitations increase with the duration of ankylosing spondylitis (AS). We examined whether radiographic damage contributed more to functional limitations in late AS than in early AS, and if the strength of association varied with the anatomic region of damage.

Salmonella spondylodiscitis associated with a mycotic abdominal aortic aneurysm and paravertebral abscess

Each year, 1.4 million people in the United States are infected with Salmonella (Beneson et al. [23] Am J Med, 110:60–63, 2001). The most common clinical presentation of Salmonella infection is gastroenteritis which is usually self-limited, lasting between one to four days (Black et al. [24] N Engl J Med, 261:811–816, 1960). Although most infections are mild-to-moderate, serious disease, and death does occur (Voetsch et al. [25] CID, 38:S127–S132, 2004). A rare but increasing number of patients present with Salmonellosis spondylodiscitis resulting from contiguous spread of infection from the adjacent abdominal aorta. Concurrent infection of these structures exacerbates morbidity, necessitating an elevated clinical suspicion in patients with appropriate risk factors, clinical signs and symptoms. Furthermore, an overall mortality rate of 67% makes mycotic abdominal aortic aneurysms highly lethal (Gonda et al. [26] Radiology, 168:343–346, 1988). Thus, early diagnosis is crucial, allowing for prompt antibiotic and surgical management. Laboratory and imaging tests obtained at the initial suspicion for infection of the spine and aorta facilitates diagnosis while minimizing or preventing more serious complications like paresis and aortic rupture. We present a patient with a mycotic abdominal aortic aneurysm infected with Salmonella enteritides that spread to the adjacent lumbar vertebra and left psoas muscle.

Spine fractures in ankylosing spondylitis: A case report and review of imaging as well as predisposing factors to falls and fractures

BACKGROUNDnAnkylosing spondylitis (AS), an inflammatory arthritis that affects the axial skeleton, predisposes patients with severe disease to falls and spinal fractures. Advanced imaging has improved the process of fracture detection. In spite of increased knowledge about early diagnosis and management of AS, little attention is being paid to the environmental hazards that pose a risk for patient outcome.nnnOBJECTIVESnTo identify risk factors for falls and fractures and evaluate imaging modalities in the detection of fractures in AS patients.nnnMETHODSnA case report and review of the literature using PubMed for English articles from 2000 to 2013 regarding AS patients׳ risk factors for falls and fractures and imaging modalities used to diagnose fracture in this population.nnnRESULTSnPotential impairments in balance and coordination in the AS population include vestibular dysfunction, thoracolumbar kyphosis, and deficits in proprioception. A common and significant environmental risk factor for falls includes the use of a tub-shower arrangement. Furthermore, osteoporosis is a well-known complication of AS, which can predispose to a fracture. Lastly, there are no comprehensive studies that have evaluated the ability of advanced imaging modalities to identify an acute spine fracture in this patient population.nnnCONCLUSIONSnAS patients with advanced disease are at an increased risk of falls and fractures due to many factors including but not limited to a rigid spine and difficulty with peripheral vision. A tub-shower arrangement commonly found in homes and hotel rooms is a major hazard. A consistent approach to diagnosis of fractures involving advanced imaging recommendations should be considered.

Opioid Analgesic Use in Patients with Ankylosing Spondylitis: An Analysis of the Prospective Study of Outcomes in an Ankylosing Spondylitis Cohort

Objective. Opioid analgesics may be prescribed to ankylosing spondylitis (AS) patients with pain that is unresponsive to antirheumatic treatment. Our study assessed factors associated with opioid usage in AS. Methods. A prospective cohort of 706 patients with AS meeting modified New York criteria followed at least 2 years underwent comprehensive clinical evaluation of disease activity and functional impairment. These were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). Radiographic severity was assessed by the Bath Ankylosing Spondylitis Radiology Index and modified Stokes Ankylosing Spondylitis Scoring System. Medications taken concurrently with opioids, as well as C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), were determined at each study visit, performed every 6 months. Analyses were carried out at baseline, and longitudinal multivariable models were developed to identify factors independently associated with chronic and intermittent opioid usage over time. Results. Factors significantly associated with opioid usage, especially chronic opioid use, included longer disease duration, smoking, lack of exercise, higher disease activity (BASDAI) and functional impairment (BASFI), depression, radiographic severity, and cardiovascular disease. Patients taking opioids were more likely to be using anxiolytic, hypnotic, antidepressant, and muscle relaxant medications. Multivariable analysis underscored the association with smoking, older age, antitumor necrosis factor agent use, and psychoactive drugs, as well as with subjective but not objective determinants of disease activity. Conclusion. Opioid usage was more likely to be associated with subjective measures (depression, BASDAI, BASFI) than objective measures (CRP, ESR), suggesting that pain in AS may derive from sources other than spinal inflammation alone.

Functional Limitations Due to Axial and Peripheral Joint Impairments in Patients With Ankylosing Spondylitis: Are Focused Measures More Informative?

Functional limitations in ankylosing spondylitis (AS) may be due to peripheral joint or axial involvement. To determine if the Bath Ankylosing Spondylitis Functional Index (BASFI), an axial‐focused measure, can detect limitations related to peripheral joint involvement equally as well as the Health Assessment Questionnaire modified for the spondyloarthropathies (HAQ‐S), a peripheral arthritis–focused measure, and vice versa, we compared associations of each questionnaire with spinal and hip range of motion, peripheral arthritis, and enthesitis in patients with AS.