Expression and Metabolomic Profiling in Axial Spondyloarthritis

Purpose of Review

The purpose of this review is to highlight recent evidence with respect to expression and metabolomic profiling in axial spondyloarthritis (axSpA) that included ankylosing spondylitis (AS).

Recent Findings

AxSpA is not only characterized by the strongest genetic contribution for any complex rheumatic disease but is also influenced by environmental and immunological factors. Large-scale association-based studies have identified over 100 genetic variants contributing to 30% of the genetic risk of ankylosing spondylitis. Recent studies in global expression and metabolomic profiling appear to highlight common themes despite differences in tissues, populations, techniques, and relative paucity of patients in many of these studies.

Summary

Expression studies support a role for immunomodulation and bone remodeling in the pathogenesis and progression of axSpA/AS, while metabolomic studies implicate the importance of the intestinal microbial metabolism as well as fat and choline metabolic pathways in AS.

     

The Epidemiology of Back Pain,Axial Spondyloarthritis and HLA-B27 in the United States

The concept of inflammatory back pain (IBP) evolved in the 1970s, coincident with the discovery of the HLA-B27 association with ankylosing spondylitis (AS), leading to the development of criteria to determine the presence of IBP. The concept of IBP and it relationship with AS and axial spondyloarthritis (AxSpA) has further evolved, and an instrument developed (the Spondylitis Association of America Back Pain Tool), which was further modified and field tested for use in the 2009 to 2010 National Health and Nutrition Examination Survey (NHANES). This has shown the frequency of chronic back pain to have risen to 19.4%, with nearly one third having IBP. The prevalence of AxSpA has been defined at 1.0% to 1.4% and AS at 0.52% to 0.55%. The national prevalence of HLA-B27 in the United States is 6.1%, and intriguing data from NHANES 2009 suggest a decreasing frequency with increasing age. From this arise new questions and a work agenda ahead.     

UROPSYCHIATRY: The Relationship Between Overactive Bladder and Psychiatric Disorders

It has been informally observed that patients attending urology clinics specializing in overactive bladder and incontinence have high rates of psychiatric conditions. Hence, the evolution of the term “uropsychiatry” that describes the association between overactive bladder and incontinence with common psychiatric conditions including depression, anxiety, and sexual abuse. Epidemiologic and case-control studies have established links between these conditions. In addition, basic science and clinical pharmacologic studies of antidepressants and atypical antipsychotics provide evidence that dysregulation of neurotransmitters including norepinephrine, serotonin, and corticotropin releasing factor may be important in the pathophysiology underlying uropsychiatric disorders. Improved understanding of these complex interactions may help in the identification of novel targets that lead to improved treatments for patients with both urologic and psychiatric conditions.     

Sarcoidosis in Israel: Clinical Outcome Status,Organ Involvement,and Long-Term Follow-Up

Purpose

Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology with heterogeneous outcomes. This study reviewed the clinical outcome status (COS) and organ involvement of Israeli sarcoidosis patients during a five-year period. Further, we compared our results to the ‘World Association of Sarcoidosis and Other Granulomatous Disease’ (WASOG) COS and the ‘A Case Control Etiologic Study of Sarcoidosis’ (ACCESS) instruments in order to evaluate their relevance to the Israeli population.

Methods

The retrospective study group consisted of 166 sarcoidosis patients for the period of 2010–2015. Data on demographic characteristics, presenting symptoms, co-morbidities, disease duration, lung function tests, treatment program, chest X-ray, and chest high-resolution computed tomography were collected.

Results

The median patient age was 62 ± 14, which was significantly higher than the WASOG and ACCESS cohorts (p < 0.0001), and the average disease duration was 9.8 ± 7.5 years. Resembling the ACCESS cohort, most patients were women (67.5%). The majority of patients suffered from constitutional symptoms (86%), as well as from respiratory symptoms (38.5%). Similarly to the ACCESS cohort, 91% of patients presented with lung involvement. However, significant differences in the involvement of other organs were noted, including lymph nodes (3 vs. 15.2%), liver (3.6 vs. 11.5%), CNS (7.2 vs. 4.6%), and joints (3.6 vs. 0.5%). In addition, significant differences were observed in the COS of the Israeli population in comparison to the WASOG data (p < 0.01).

Conclusions

Sarcoidosis in Israel is a unique and challenging disease with its clinical presentations that differ from previously reported studies.

     

Effectiveness of Adalimumab in Non-radiographic Axial Spondyloarthritis: Evaluation of Clinical and Magnetic Resonance Imaging Outcomes in a Monocentric Cohort

The primary aim of the study was to evaluate the long-term effectiveness of adalimumab (ADA) in a cohort of non-radiographic axial spondyloarthritis (nr-axSpA), and the secondary aims were to identify predictive factors of response and evaluate radiological progression.We evaluated 37 patients (male/female: 12/25; mean age 49 ± 14; mean disease duration: 6.3 ± 5.8) with active nr-axSpA (Assessment of SpondyloArthritis International Society criteria), despite the treatment with ≥1 nonsteroidal anti-inflammatory drug for at least 3 months, initiating the treatment with ADA 40 mg every other week. Patients were treated for 24 months, and evaluated at baseline, 6, 12, and 24 months. Outcome measures included Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index. Radiograph of the spine and sacroiliac joints and magnetic resonance of the sacroiliac joints were performed at baseline and according to the standard of assessment for the disease.The proportion of patients that achieved a BASDAI50 response at 6, 12 and 24 months was 51.3%, 70.3%, and 76.8%, respectively. Treatment was well tolerated with no unexpected adverse events and/or serious adverse events. All patients remained on treatment for 2 years, with a good compliance. We did not identify any predictive factor of response to therapy. Moreover, modified Stoke Ankylosing Spondylitis Spine Score and Spondyloarthritis Research Consortium of Canada scores showed a trend of improvement during the study period.ADA was effective on clinical and radiological outcomes at 2-year follow-up; thus, early treatment with ADA may prevent radiographic damage and be associated with low disease activity or remission. Moreover, data from this cohort study have confirmed safety and tolerability profile of ADA in nr-axSpA in the long term.