Summary The term axial spondyloarthritis covers both patients with non-radiographic and radiographic axial spondyloarthritis, which is also termed ankylosing spondylitis. The disease usually starts ...in the third decade of life with a male to female ratio of two to one for radiographic axial spondyloarthritis and of one to one for non-radiographic axial spondyloarthritis. More than 90% heritabilty has been estimated, the highest genetic association being with HLA-B27. The pathogenic role of HLA-B27 is still not clear although various hypotheses are available. On the basis of evidence from trials the cytokines tumour necrosis factor (TNF)-α and interleukin-17 appear to have a relevant role in pathogenesis. The mechanisms of interaction between inflammation and new bone formation is still not completely understood but clarification will be important for the prevention of long-term structural damage of the bone. The development of new criteria for classification and for screening of patients with axial spondyloarthritis have been crucial for the early indentification and treatment of such patients, with MRI being the most important existing imaging method. Non-steroidal anti-inflammatory drugs and TNF blockers are effective therapies. Blockade of interleukin-17 is a new and relevant treatment option.
The cytokines IL-23 and IL-17 have an important role in the pathogenesis of, and as a therapeutic target in, both animal models of chronic inflammation and some human chronic inflammatory diseases. ...The traditional view is that a main source of IL-17 is T cells and that IL-17 production is under the control of IL-23. IL-17 inhibition has shown good efficacy in clinical trials for ankylosing spondylitis (AS), a subtype of axial spondyloarthritis (axSpA) characterized by radiographic evidence of sacroiliitis. On the basis of data from animal models, genetic studies and the investigation of tissue and blood samples from patients with AS, IL-23 had also been predicted to be important in the pathogenesis of this disease and was therefore considered a potential therapeutic target for axSpA. However, two placebo-controlled, double-blind clinical trials in axSpA of monoclonal antibodies directed against either the p40 protein or the p19 protein of the IL-23 molecule had clear negative results. These findings indicate that IL-23 and IL-17 are at least partly uncoupled in axSpA. Reasons as to why, when and how such an uncoupling might occur are discussed in this Review, with special reference to the unique microenvironment of the subchondral bone marrow in axSpA.
Development of the Assessment in Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (SpA) was one of the major breakthroughs in the field over the past ...decade. Despite some concerns related to the specificity of the criteria, they stimulated research into the early stage of the disease. This resulted in major advances in the understanding of the course of the disease, revealing predictors of progression, improvement in early diagnosis and treatment in axial SpA. In this review, we summarize the recent developments resulting from the introduction of the ASAS classification criteria for axial SpA and the implications for research and clinical practice.
Abstract
Objectives
The objective of this study was to assess the current diagnostic delay in axial SpA (axSpA) and to analyse factors associated with it.
Methods
A stratified sample of subjects with ...a diagnosis of axSpA (International Classification of Diseases, 10th Revision code M45) was drawn from health insurance data in Germany and was questioned on disease-related, lifestyle and socio-economic characteristics. The diagnostic delay was calculated as the time from back pain onset until a diagnosis of axSpA. A multivariable linear regression analysis was performed to explore factors associated with the diagnostic delay.
Results
Among 1677 patients with axSpA included in the analysis, the mean diagnostic delay was 5.7 years (median 2.3). Of those, 407 patients were diagnosed in 1996–2005 and 484 patients in 2006–2015. The mean diagnostic delay was not substantially different in both periods: 6.3 years (median 2.6) and 7.4 (2.7), respectively. Multivariable linear regression revealed that female sex β = 1.85 (95% CI 1.06, 2.65), negative HLA-B27 status β = 3.61 (95% CI 2.07, 5.14), presence of psoriasis β = 1.40 (95% CI 0.08, 2.73) and younger age at symptom onset β = 1.91 (95% CI 1.53, 2.29) were factors associated with a longer diagnostic delay.
Conclusion
The diagnostic delay in axSpA is still unacceptably long. Patients who are female, young at symptom onset, HLA-B27 negative or have psoriasis have a longer diagnostic delay. Specific referral strategies might be necessary in order to decrease the diagnostic delay in patients presenting with these characteristics.
Uveitis in spondyloarthritis Rademacher, Judith; Poddubnyy, Denis; Pleyer, Uwe
Therapeutic Advances in Musculoskeletal Disease,
2020, Letnik:
12
Book Review, Journal Article
Recenzirano
Odprti dostop
Uveitis is the most frequent extra-articular manifestation of axial spondyloarthritis (SpA), occurring in up to one-third of the patients. In the majority of patients, uveitis is acute, anterior and ...unilateral and presents with photosensitivity, sudden onset of pain and blurred vision. Topical steroids are an effective treatment; however, recurrent or refractory cases may need conventional disease-modifying antirheumatic drugs or biological treatment with monoclonal tumor necrosis factor (TNF) inhibitors, thus also influencing treatment strategy of the underlying SpA.
Though the exact pathogenesis of SpA and uveitis remains unknown, both seem to result from the interaction of a specific, mostly shared genetical background (among other HLA-B27 positivity), external influences such as microbiome, bacterial infection or mechanical stress and activation of the immune system resulting in inflammation. Up to 40% of patients presenting with acute anterior uveitis (AAU) have an undiagnosed SpA. Therefore, an effective referral strategy for AAU patients is needed to shorten the diagnostic delay of SpA and enable an early effective treatment. Further, the risk for ophthalmological manifestations increases with the disease duration in SpA; and patients presenting with ocular symptoms should be referred to an ophthalmologist. Thus, a close collaboration between patient, rheumatologist and ophthalmologist is needed to optimally manage ocular inflammation in SpA.
Degeneration of the sacroiliac joints (SIJs) is a common finding, while its underlying cause and development remain incompletely understood. The aim of this investigation was to describe the spatial ...distribution of degenerative SIJ changes across age groups and to investigate for the first time their relationship to anatomical form and sex. For this IRB-approved investigation, demographic data of 818 patients without SIJ disease were retrieved from electronic patient records. High-resolution computed tomography (CT) datasets of all patients were analysed retrospectively for seven predefined age groups (ten-year increments, from < 25 to ≥ 75). A structured scoring system was applied to assess sclerosis, osteophytes, joint space alterations, and anatomical form. Chi-square tests were used to compare frequencies of degenerative lesions, and logistic regression analyses were performed to investigate associations between demographic data, anatomical form, and the presence of structural lesions. Sclerosis and osteophytes were common findings, with an overall prevalence of 45.7% and 46.8%, respectively. Female sex had an odds ratio (OR) of 0.15 (95% CI: 0.08-0.27) for the presence of ventral osteophytes and of 4.42 (95% CI: 2.77-7.04) for dorsal osteophytes. Atypical joint forms were significantly more prevalent in women with 62.1% vs. 14.1% in men (p < 0.001). Accessory joints increased the likelihood of dorsal sclerosis (OR 2.735; 95% CI 1.376-5.436) while a typical joint form decreased its likelihood (OR 0.174; 95% CI 0.104-0.293). Sex and anatomical joint form have a major impact on the development of degenerative lesions of the SIJs and their spatial distribution.
In recent years, significant progress has been made in improving the early diagnosis of spondyloarthritides (SpA), including axial SpA. Nonetheless, there are still issues related to the application ...of classification criteria for making the primary diagnosis of SpA in the daily practice. There are substantial conceptional and operational differences between the diagnostic vs classification approach. Although it is not possible to develop true diagnostic criteria for natural reasons as discussed in this review, the main principles of the diagnostic approach can be clearly defined: consider the pre-test probability of the disease, evaluate positive and negative results of the diagnostic test, exclude other entities, and estimate the probability of the disease at the end. Classification criteria should only be applied to patients with an established diagnosis and aimed at the identification of a rather homogeneous group of patients for the conduction of clinical research.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). Nonradiographic axSpA (axSpA without radiographic ...sacroiliitis) and ankylosing spondylitis (AS; radiographic form of axSpA) are considered nowadays as two consecutive stages of one disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective against the major symptoms of axSpA (pain and stiffness) and may have disease-modifying properties including retarding progression of structural damage in the spine. Therefore, NSAIDs, unless contraindicated, are the treatment of choice for the majority of patients with axSpA. Beyond NSAIDs, only tumour necrosis factor (TNF) α blockers are effective and approved for the treatment of active axSpA. Several novel drugs (i.e. monoclonal antibodies targeting interleukin-17, interleukin-12/23, inhibitors of phosphodiesterase-4 and kinases), which might be effective in axSpA, are currently under investigation. Pharmacological therapy of axSpA should always be combined with nonpharmacological treatment including education and regular exercise/physiotherapy.
•Pancytopenia is a possible side effect of interferon-gamma (IFN-γ) treatment.•Pancytopenia may limit adjuvant IFN-γ treatment for disseminated nocardiosis.•First clinical report of pancytopenia ...following IFN-γ treatment.•Basic research supports the causative role of IFN-γ treatment for pancytopenia.
A patient with disseminated nocardiosis developed pancytopenia after treatment with recombinant interferon-gamma (IFN-γ). While no previous clinical reports link pancytopenia to IFN-γ, our observations align with basic research on myelosuppressive effects of IFN-γ. Adjunctive IFN-γ may improve standard nocardiosis therapy, but vigilant monitoring of its hematologic effects is necessary.
To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA).
The Assessment in SpondyloArthritis International Society (ASAS) MRI working group ...conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership.
The clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition.
The definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of 'active sacroiliitis' until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes.
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