Israel Medical Association Journal

Background: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Background: Patients with rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS), encounter significantly higher rates of cardiovascular morbidity and mortality. The renin-angiotensin-aldosterone system maintains hemodynamic stability through blood pressure regulation. When dysregulated, this system has been implicated in various pathological conditions, including cardiovascular events.

Objectives: To investigate the levels of renin and aldosterone in RA and AS patients.

Methods: Three groups were recruited: patients with RA, patients with AS, and healthy controls. Subjects were excluded if they had a diagnosis of hypertension, hyperaldosteronism, or renal artery stenosis, or were taking drugs that might have affected renin levels. Renin and aldosterone levels were measured using commercially available kits. Data were analyzed using univariate analyses and multivariate regression analyses.

Results: Fifty-one subjects were enrolled in the study: 15 with RA, 4 with AS, and 32 healthy controls. At the univariate analysis, the three groups differed in age (P = 0.005), renin levels (P = 0.013), and aldosterone-to-renin ratio (P = 0.019). At the post-hoc tests, both AS and RA patients differed from controls for renin levels and the aldosterone-to-renin ratio. At the multivariate regression analysis, AS patients had lower renin values than controls (beta standardized regression coefficient -0.323, P = 0.022).

Conclusion: Patients with RA tended to have lower levels of plasma renin compared to healthy subjects. This finding indicates that the renin-angiotensin-aldosterone system might not be directly involved in the process that results in increased cardiovascular events in rheumatoid arthritis.

Background: Enthesopathy may lead to calcification of the stylohyoid ligament and can cause elongation of the styloid process (SP).

Objectives: To evaluate whether SP elongation is associated with two common enthesitis-related diseases: ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH).

Methods: Cervical spine computed tomography (CT) examinations of patients with DISH (n=64, Resnick criteria), AS (n=24, New York criteria) and a controls (no radiological signs of DISH or AS, n=54) were retrospectively evaluated. The DISH group was further divided into patients with and without cervical DISH. The length of right and left SP was measured independently by two readers on coronal and sagittal curved reformats. The average right and left styloid length and average length per person were compared among the groups.

Results: Demographic characteristics were similar between the DISH and control groups (average age 68.2 ± 15.7, 69.2 ± 12.7 years, male:female ratio 48:16 and 35:19, respectively, P > 0.05), whereas age was significantly lower (average age: 53 ± 15 years, P < 0.0001) in the AS group, which was also composed mainly of men. The AS and DISH groups had significantly longer SP compared to controls (AS 37.9 ± 9.6 mm, DISH 34.4 ± 9 mm, control 30.3 ± 10.1 mm, P < 0.05). There was no correlation between age and SP length. Inter-reader reliability of SP measurements was excellent in all groups (ICC = 0.998, P < 0.0001).

Conclusions: SP elongation is associated with both AS and DISH substantiating the enthesopathy-related pathophysiology of this finding.

Background: Magnetic resonance imaging (MRI), which has recently become the leading imaging modality in the study of ankylosing spondylitis (AS), has not been evaluated in the assessment of disease-specific changes at the craniocervical junction (CCJ) in patients with AS.

Objectives: To describe the spectrum of active inflammatory lesions at the CCJ using MRI in a cohort of patients with AS and neck pain.

Methods: The study included 18 patients with AS presenting with neck pain and a control group of 9 fibromyalgia patients matched for age and levels of neck pain. All patients underwent a focused rheumatologic examination, X-ray of the cervical spine, and a 3T MRI study, which included STIR, CUBE T2, FSE and FSE FAT SAT sequences before and after administration of gadolinium.

Results: The median age of AS patients was 43 years with a median disease duration of 7 years. Fifteen of 18 patients were under biologic treatment. Seven of 18 AS patients had evidence of cervical syndesmophytes on X-ray films. Active inflammatory lesions of atlanto-occipital joints and apical and alar ligaments were detected in MRIs in 2 out of the 18 patients with AS and in none of the patients with fibromyalgia. Both AS patients with active inflammation of CCJ detected on MRI received treatment with biological agents prior to and during the study.

Conclusions: Active inflammation of both entheses and joints of the CCJ can be demonstrated by MRI in patients with AS.

Lung involvement is a well-recognized extra-articular manifestation of ankylosing spondylitis (AS). Anecdotal reports suggest that the use of anti-TNF drugs may be related to lung disease and pulmonary fibrosis. To examine the association between anti-TNF drugs and the development of lung disease in patients with AS or  psoriatic arthritis (PsA) we conducted a systematic review. Of the 670 papers identified by means of key word and hand search, only one full-text paper was considered potentially relevant but had to be discarded as it did not meet the eligibility criteria. Although no conclusion was reached, this is the first systematic review to examine this problem which is becoming increasingly important as these drugs are widely prescribed in patients with spondyloarthritis.

The term non-radiographic axial spondyloarthritis (nrAxSpA) was coined for patients who have a clinical picture of ankylosing spondylitis (AS) but do not exhibit radiographic sacroiliitis. The ASAS classification criteria for nrAxSpA, ensuring the recruitment of homogenous study cohorts, were accepted in 2009, although the respective diagnostic criteria for daily clinical practice have not yet been developed. The clinical diagnosis should be based on the composite of clinical symptoms and signs of the disease, HLA B27 status, and magnetic resonance imaging (MRI) of sacroiliac joints. Notably, a negative MRI or HLA B27 does not exclude the diagnosis in patients with a high clinical suspicion for nrAxSpA. The prevalence of nrAxSpA is similar to that of AS, but the former has a higher female preponderance. The rate of progression of nrAxSpA to the radiographic stage of disease (AS) ranges from 10% to 20% over 2 years. Current treatment strategies for nrAxSpA are the same as for AS and include non-steroidal anti-inflammatory drugs and inhibitors of tumor necrosis factor-alpha. While this review summarizes the current achievements in the field of nrAxSpA, further understanding of the epidemiology and natural history of the disease and, particularly, mechanisms of inflammation and subsequent new bone formation is essential for the development of new treatment strategies for nrAxSpA patients.