Update on the genetics of spondyloarthritis--ankylosing spondylitis and psoriatic arthritis

Spondyloarthritis refers to a group of inflammatory rheumatic diseases that share common clinical and genetic characteristics. Due to the rapid advances in technology and computational genetics, there is now an increasing list of well-validated genes in spondyloarthritis. The newest genetic associations are of modest magnitude and have been identified as a result of analysing thousands of samples, using genome-wide association scans or targeted candidate-gene association studies. In this article, we will highlight the genes associated with spondyloarthritis, with an emphasis on the recent candidate genes that have been identified in ankylosing spondylitis and psoriatic arthritis. If applicable, we will also discuss their potential relevance to the clinical rheumatologist.     

幼年特发性关节炎诊疗规范

幼年特发性关节炎(JIA)临床上常见亚型包括全身型JIA、少关节型/多关节型JIA和幼年脊柱关节炎。本病无特异性诊断指标, 需与感染性疾病和恶性病相鉴别。全身型JIA起病多急骤, 病情进展快, 易合并巨噬细胞活化综合征而危及生命。儿童风湿科医生对JIA的诊断及治疗经验仍不足, 规范化诊疗水平有待进一步提高。中华医学会风湿病学分会组织有关专家, 在借鉴国内外诊疗规范和分类标准的基础上, 制定本规范, 旨在规范JIA各亚型及全身型JIA合并巨噬细胞活化综合征的诊断和治疗方案, 以降低致死率和严重并发症的发生率, 从而改善患儿预后。     

ASAS classification criteria for axial spondyloarthritis: time to modify

The relationship between ankylosing spondylitis and the recently proposed entity called axial spondyloarthritis with its radiographic and non-radiographic forms that have been defined by the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis (axSpA), is currently being debated. The Food and Drug Agency (FDA) had criticized the ASAS criteria and the studies which used these criteria to enroll patients in a clinical trial of certolizumab and adalimumab for the treatment of non-radiographic axial spondyloarthritis. The primary aim of classification criteria is to create homogenous patient populations for basic and clinical research. But the multi-arm construct of the ASAS criteria is a potential source of heterogeneity reducing their utility. Criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances. We provide evidence to conclude that it is time to modify the ASAS Criteria for axSpA, and we propose some of the steps that can be taken to start moving forward in improving the validity of these criteria.     

Undifferentiated Spondyloarthritis: Recent Clinical and Therapeutic Advances

The spondyloarthropathies comprise a large clinical spectrum of disorders that include well-defined clinical disorders such as ankylosing spondylitis and less well-defined disorders such as undifferentiated spondyloarthritis, which refers to patients with inflammatory back pain not fulfilling classification criteria for ankylosing spondylitis and without radiologic evidence of sacroillitis. These disorders share clinical and genetic features and are linked by their association with HLA-B27 and by the presence of enthesitis as the basic pathologic lesion. The prevalence of the entire group ranges between 0.6% and 1.9%. This article reviews the recent advances in our understanding of the clinical spectrum, pathogenesis, genetics, and management of undifferentiated spondyloarthritis.     

Follow up and prognostic value using magnetic resonance imaging in patients with spondyloarthritis treated with biologic agents

Early diagnosis and assessment of the response to treatment in patients suffering from spondyloarthritis have always been challenging due to the lack of imaging techniques able to demonstrate spinal and sacroiliac inflammation.The last 2 years have seen important advances in the use of magnetic resonance imaging (MRI) for the study of spondyloarthritis. The possibility of quantification of inflammatory lesions using different scoring systems allows not only an early diagnosis, but the assessment of the response to several therapeutic agents, especially those known as «biological therapies».A number of randomized controlled trials of anti-tumor necrosis factor agents have been published showing regression of inflammatory lesions in MRI. This review discusses briefly the techniques and scoring systems used and all the evidences that exist about assessing treatment in spondyloarthritis.     

Magnetic resonance imaging in spondyloarthritis--how to quantify findings and measure response

Sensitive and reliable tools for monitoring disease activity and damage, and for prognostication, are essential in the management of patients with spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis. Magnetic resonance imaging (MRI) allows direct visualisation of inflammation in peripheral and axial joints, and peripheral and axial entheses, and has dramatically improved the possibilities for early diagnosis and objective monitoring of the disease process in spondyloarthritis. Truthful, discriminative and feasible scoring systems are available for the assessment of inflammatory activity in the spine and sacroiliac joints in axial spondyloarthritis and in the hands of patients with peripheral psoriatic arthritis. Various systems for assessment of damage in axial and peripheral joints are available, but further studies are needed to document their value in clinical trials and clinical practice. The present article reviews key aspects of the status and recent important advances in MRI in spondyloarthritis, focussing on available MRI tools for assessing activity and damage in peripheral and, particularly, axial joints.     

Enthesitis

Enthesitis is a distinctive pathological feature of spondyloarthritis and may involve synovial joints, cartilaginous joints, syndesmoses and extra-articular entheses. This review focuses on peripheral extra-articular enthesitis, which is a clinical hallmark of spondyloarthritis. The entheses of the lower limbs are more frequently involved than those of the upper limbs, and heel enthesitis is the most frequent. Entheseal pain may be mild or moderate as well as severe and disabling. Peripheral enthesitis may be observed in all forms of spondyloarthritis, including the undifferentiated forms, and may, for a prolonged period, be the only longstanding clinical manifestation of the B27-associated disease process. The conceptual understanding of spondyloarthritis and the ability to image sites of skeletal inflammation accurately, i.e. ultrasound and magnetic resonance imaging, confirm that enthesitis is the primary lesion of spondyloarthritis. This advance has been occurring simultaneously with the therapeutic advances in spondyloarthritis due to the introduction of anti-tumour necrosis factor-alpha agents.     

Early diagnosis of spondyloarthritis

The term 'spondyloarthritis', which is preferred to 'spondyloarthropathy', refers to a group of similar diseases with distinct clinical features and a common genetic predisposition, rather than one disease with different clinical presentations. Mainly for clinical purposes, five disease subtypes are recognized: ankylosing spondylitis (AS), psoriatic spondyloarthritis, reactive spondyloarthritis, spondyloarthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. Irrespective of the disease subtype, the main clinical manifestations of spondyloarthritides are inflammatory back pain, peripheral arthritis, enthesitis and anterior uveitis, while other organ manifestations are rare. The need for a standardized, evidence-based approach to disease classification led to the development of the European Spondyloarthropathy Study Group preliminary criteria for spondyloarthritis in 1991, which confirmed the unifying concept of this group of diseases. In the past 10 years, the work of the European Spondyloarthropathy Study Group has been taken over by the Assessments in AS working group. There is still a considerable delay in diagnosis of AS and, because of the well-documented efficacy of anti-tumor-necrosis-factor therapy for all spondyloarthritis subtypes, diagnostic criteria (especially for early forms of spondyloarthritis) are needed. Diagnosis can be achieved by determination of the predominant clinical manifestation, and by the inclusion of sensitive diagnostic tools for early disease (such as HLA-B27 genotype and MRI) in the criteria set. In addition, because of the high incidence of back pain in affected individuals, the development of practical screening parameters that facilitate referral to the rheumatologist is important.     

Juvenile spondyloarthritis treatment recommendations

No specific recommendations for the treatment of juvenile spondyloarthritis have been established. Important differences exist in how spondyloarthritis begins and progresses in children and adults, supporting the need for pediatric-specific recommendations. Recently published recommendations for the treatment of juvenile arthritis consider children with sacroiliitis in a separate group and allow for more accelerated institution of a tumor necrosis factor inhibitor depending on disease activity and prognostic factors that derive primarily from studies of other forms of juvenile arthritis. There is a need to develop measures of disease activity and prognosis specific for juvenile spondyloarthritis that reflect spinal disease, as well as other major clinical features, such as enthesitis, before significant progress can be made in this area.     

Newer therapeutic approaches: spondyloarthritis and uveitis

Over the last 5 years considerable progress has taken place in the therapeutic approach to spondyloarthritis (SpA). This progress is due in large part to the development of effective biologic therapies and to improved clinical trial design and implementation. This article summarizes treatment advances in SpA with emphasis on the efficacy and safety of biologic agents in the treatment of psoriatic arthritis, ankylosing spondylitis, undifferentiated spondyloarthropathy, and uveitis.     

How to investigate: Early axial spondyloarthritis

Axial spondyloarthritis (axSpA) is a chronic inflammatory condition of the axial skeleton that encompasses radiographic and non-radiographic axSpA and that can lead to chronic pain, structural damage, disability, and loss of quality of life. Scientific advances, including the role of MRI assessment, have led to new diagnostic insights and the creation of a new set of classification criteria for axial and peripheral SpA. New criteria allow the identification of SpA patients with early disease and their enrolment in clinical studies. In this chapter, we discuss the difference between diagnostic and classification criteria, the diagnostic approach to patients with suspected axSpA, the limitations of MRI assessment, and the importance of early identification of this condition. A practical algorithm to investigate axSpA, based on the current evidence, is also proposed. Clinical judgement should always be kept as the mainstay in the diagnosis of axSpA.     

Cutaneous polyarteritis nodosa associated with HLA-B39-positive undifferentiated spondyloarthritis in a Japanese patient

We present the case of a 43-year-old man diagnosed with HLA-B39-positive spondyloarthritis who developed cutaneous lesions consistent with cutaneous polyarteritis nodosa (CPN). Previous studies indicated an elevated incidence of HLA-B39 in HLA-B27-negative Japanese patients with spondyloarthritis. This case suggested that CPN may also occur in association with forms of HLA-B39-positive spondyloarthritis. The rarity of this association is emphasized. Therapy with corticosteroid and methotrexate improved both the cutaneous lesions and the clinical symptoms of spondyloarthritis.     

Are current available therapies disease-modifying in spondyloarthritis?

Disease modification in spondyloarthritis should target the improvement of symptoms and preservation of function. Therefore, inhibition of structural damage caused by the disease processes appears essential. In spondyloarthritis, structural damage results mainly in progressive ankylosis of the spine and peripheral joint destruction. Currently available therapies for the treatment of spondyloarthritis appear effective at inhibiting tissue destruction but, with the exception of celecoxib, do not appear to affect new tissue formation leading to ankylosis. In this article, we discuss clinical and pathophysiological concepts of disease modification in spondyloarthritis, challenges in its evaluation, recent clinical data and new concepts that may help explain structural damage as well as the onset and progression of disease.     

Cutaneous polyarteritis nodosa associated with HLA-B39-positive undifferentiated spondyloarthritis in a Japanese patient

Abstract

We present the case of a 43-year-old man diagnosed with HLA-B39-positive spondyloarthritis who developed cutaneous lesions consistent with cutaneous polyarteritis nodosa (CPN). Previous studies indicated an elevated incidence of HLA-B39 in HLA-B27-negative Japanese patients with spondyloarthritis. This case suggested that CPN may also occur in association with forms of HLA-B39-positive spondyloarthritis. The rarity of this association is emphasized. Therapy with corticosteroid and methotrexate improved both the cutaneous lesions and the clinical symptoms of spondyloarthritis.     

Update on Biologic Therapy in the Management of Axial Spondyloarthritis

Axial spondyloarthritis, which includes ankylosing spondylitis and psoriatic spondyloarthritis, is an important subtype of the spondyloarthritides. Tumor necrosis factor (TNF) antagonists are effective therapies for this partially heterogeneous group of rheumatic diseases in terms of signs, symptoms, and functioning, but they do not seem to substantially inhibit radiographic progression, which is mainly new bone formation in ankylosing spondylitis. However, they clearly reduce inflammation, as shown by MRI. TNF blockers are also efficacious in the treatment of extraspinal features of spondyloarthritis. In addition, evidence indicates that anti-TNF therapy works well in early axial disease. Other biologics are currently being investigated, as alternatives are needed for patients who fail anti-TNF therapy.     

Imaging in Spondyloarthritis: Controversies in Recognition of Early Disease

Advanced imaging has become essential for recognition of clinically suspected early spondyloarthritis. This report summarizes recent progress towards a data-driven comprehensive definition of a positive sacroiliac joint MRI in axial spondyloarthritis, which incorporates contextual information provided by structural lesions alongside with active changes. A focus is on emerging limitations and challenges with increasing use of imaging in spondyloarthritis. We discuss the ongoing controversy as to whether sacroiliac joint MRI due to its superior reliability and ability to depict both structural and active lesions should be the preferred imaging modality in early disease over the traditional approach with pelvic radiographs. Another challenge is transferring the expanding knowledge about imaging evaluation in spondyloarthritis to the community of rheumatologists and radiologists. Advanced imaging modalities will not become the gold standard for diagnosis of spondyloarthritis, which remains a process of composite deduction based on complementary information obtained from clinical, laboratory, and imaging assessment.     

Anti-CD74 antibodies in spondyloarthritis: A systematic review and meta-analysis

ObjectiveThere is still an unmet need for a simple and reliable biomarker for the diagnosis of spondyloarthritis. Recent studies indicated that anti-CD74 antibody could act as a biomarker for spondyloarthritis. Therefore, this review aims to evaluate the levels of anti-CD74 IgG and IgA antibodies in spondyloarthritis and the diagnostic value of anti-CD74 antibodies.MethodsPubMed, Web of Science and Medline were comprehensively searched from inception to August 7th, 2019. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to estimate the differences of the levels of anti-CD74 IgG and IgA antibodies between spondyloarthritis patients and controls. Sensitivity, specificity and summary receiver operating characteristics (SROC) curve were used for evaluating the diagnostic value of anti-CD74 antibodies. The use of fixed-effect or random-effects model depended on heterogeneity.ResultsAmong 55 searched studies, 9 studies were finally included for analysis. Anti-CD74 IgG and IgA antibodies were both significantly increased in spondyloarthritis patients compared with matched controls (IgG: SMD = 0.88, 95% CI = 0.55 to 1.21; IgA: SMD = 0.98, 95% CI = 0.68 to 1.28). The pooled sensitivity, specificity and area under the SROC curve of anti-CD74 IgG antibodies were 0.61, 0.90 and 0.8881, while these indicators of anti-CD74 IgA antibodies were 0.59, 0.95 and 0.8671, respectively.ConclusionAnti-CD74 IgG and IgA antibodies were significantly increased in spondyloarthritis patients and suggest a high diagnostic specificity of spondyloarthritis. Anti-CD74 antibody could potentially be a biomarker for the diagnosis of spondyloarthritis, but many open questions remain.     

Advances in classification,basic mechanisms and clinical science in ankylosing spondylitis and axial spondyloarthritis

The field of spondyloarthritis (SpA) has seen huge advances over the past 5 years. The classification of axial disease has been redefined by the axial SpA criteria that incorporate disease captured before radiographic damage is evident as well as established erosive sacroiliac joint disease. Our knowledge of genetics and basic immunological pathways has progressed significantly. In addition, revolutionary progress has been achieved with the availability of tumour necrosis factor inhibitors for treating patients with moderate to severe disease. In parallel, several of novel biomarkers have been identified that show significant promise for the future. Advances in magnetic resonance imaging have helped define positive disease. We have identified that T1 and short tau inversion recovery sequences are best for the diagnosis of axial SpA, and gadolinium contrast is not additive for diagnosis. Progress has been made in identifying potential agents and strategies that reduce radiographic progression. Several referral strategies aimed at appropriate identification of patients have been trialled and found to be effective. There is still substantial work ahead, but the advances of the last 5 years have made a huge and tangible difference at the clinical coalface, and we suggest that this trend will continue.