Classification Criteria for Spondyloarthritis/HLA-B27-Associated Anterior Uveitis.

PURPOSE: The purpose of this study was to determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis DESIGN: Machine learning of cases with spondyloarthritis/HLA-B27-associated anterior uveitis and 8 other anterior uveitides. METHODS: Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated in the validation set. RESULTS: A total of 1,083 cases of anterior uveitides, including 184 cases of spondyloarthritis/HLA-B27-associated anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% CI: 92.4-98.6). Key criteria for spondyloarthritis/HLA-B27-associated anterior uveitis included 1) acute or recurrent acute unilateral or unilateral alternating anterior uveitis with either spondyloarthritis or a positive test result for HLA-B27; or 2) chronic anterior uveitis with a history of the classic course and either spondyloarthritis or HLA-B27; or 3) anterior uveitis with both spondyloarthritis and HLA-B27. The misclassification rates for spondyloarthritis/HLA-B27-associated anterior uveitis were 0% in the training set and 3.6% in the validation set. CONCLUSIONS: The criteria for spondyloarthritis/HLA-B27-associated anterior uveitis had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Axial spondyloarthritis: concept, construct, classification and implications for therapy.

The axial spondyloarthritis (axSpA) disease concept has undergone substantial change from when the entity ankylosing spondylitis was defined by the modified New York criteria in 1984. Developments in imaging, therapy and genetics have all contributed to changing the concept of axSpA from one of erosions in the sacroiliac joints to a spectrum of disease with and without changes evident on plain radiographs. Changes to the previously held concept and construct of the disease have also necessitated new classification criteria. The use of MRI, primarily of the sacroiliac joints, has substantially altered the diagnosis and differential diagnosis of axSpA. Many in the axSpA community believe that the current classification criteria lack specificity, and the CLASSIC study is underway to examine this area. Although much about the evolving axSpA disease concept is universally agreed, there remains disagreement about operationalizing aspects of it, such as the requirement for the objective demonstration of axial inflammation for the classification of axSpA. New imaging technologies, biomarkers and genetics data will probably necessitate ongoing revision of axSpA classification criteria. Advances in our knowledge of the biology of axSpA will settle some differences in opinion as to how the disease concept is applied to the classification and diagnosis of patients.

Classification vs diagnostic criteria: the challenge of diagnosing axial spondyloarthritis.

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.

The conundrum of juvenile spondyloarthritis classification: Many names for a single disease? Lesson learned from an instructive clinical case.

Pediatric rheumatic diseases are often characterized by an evolving phenotype, resulting in diagnostic dilemma for physicians involved in their management. Although several classification criteria are used in childhood to uniform patients' diagnoses, several conditions share similar clinical features and therefore their classifications may overlap or be ambiguous. This is particularly paradigmatic for the classification of juvenile spondyloarthritis (JSpA), as the currently available criteria do not encompass their complexity. The differential diagnosis of sacroiliitis is often challenging for clinicians and requires considering several conditions, which include infective, neoplastic and rheumatic diseases. We report the case of a 13-year-old boy with an evolving clinical phenotype; its progression shows the wide differential diagnosis required in pediatric rheumatic diseases and emphasizes the issues of the actual classification system.

Central reader evaluation of MRI scans of the sacroiliac joints from the ASAS classification cohort: discrepancies with local readers and impact on the performance of the ASAS criteria.

OBJECTIVES: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group conducted a multireader exercise on MRI scans from the ASAS classification cohort to assess the spectrum and evolution of lesions in the sacroiliac joint and impact of discrepancies with local readers on numbers of patients classified as axial spondyloarthritis (axSpA). METHODS: Seven readers assessed baseline scans from 278 cases and 8 readers assessed baseline and follow-up scans from 107 cases. Agreement for detection of MRI lesions between central and local readers was assessed descriptively and by the kappa statistic. We calculated the number of patients classified as axSpA by the ASAS criteria after replacing local detection of active lesions by central readers and replacing local reader radiographic sacroiliitis by central reader structural lesions on MRI. RESULTS: Structural lesions, especially erosions, were as frequent as active lesions (≈40%), the majority of patients having both types of lesions. The ASAS definitions for active MRI lesion typical of axSpA and erosion were comparatively discriminatory between axSpA and non-axSpA. Local reader overcall for active MRI lesions was about 30% but this had a minor impact on the number of patients (6.4%) classified as axSpA. Substitution of radiography with MRI structural lesions also had little impact on classification status (1.4%). CONCLUSION: Despite substantial discrepancy between central and local readers in interpretation of both types of MRI lesion, this had a minor impact on the numbers of patients classified as axSpA supporting the robustness of the ASAS criteria for differences in assessment of imaging.

Peripheral spondyloarthritis: a neglected entity-state of the art.

Peripheral spondyloarthritis (pSpA) refers to a number of seemingly different spondyloarthritis subsets in which psoriatic arthritis (PsA) is the most common, and symptoms of arthritis, enthesitis or dactylitis predominate the clinical presentation. Although formal classification criteria for pSpA have been introduced in 2011, only a minority of epidemiological and clinical studies addressed this clinical entity as a separate disease. Moreover, research on outcome measures and treatment modalities in pSpA has been mainly focused on PsA. Subsequently, all biological treatments are off-label in patients with non-psoriatic pSpA. Its neglected status has important implications for clinical practice since the emerging group of early-diagnosed non-psoriatic pSpA patients remains poorly characterised and lacks specific treatment recommendations. This review summarises what is currently known regarding pSpA in terms of epidemiology, clinical presentation, diagnosis and therapeutic approach.

MRI of the sacroiliac joints: what is and what is not sacroiliitis?

PURPOSE OF REVIEW: MRI has, as the only imaging modality, the ability to visualize both the inflammatory and destructive aspects of sacroiliitis and is a crucial element in the diagnosis and classification of axial spondyloarthritis (axSpA). However, the MRI appearance of several potential differential diagnoses may resemble axSpA sacroiliitis. RECENT FINDINGS: The appearances of sacroiliac joint (SIJ) MRIs of various diseased and healthy populations have recently been intensively studied. BME, the key requirement in the Assessment of Spondyloarthritis international Society (ASAS) definition of a 'MRI positive of sacroiliitis' may also be found in degenerative disease, athletes and healthy persons, and, particularly, postpartum women. Certain pattern of BME (high extent, large depth from articular surface, close relation to other lesion types) as well as the presence of structural lesions, particularly bone erosion, backfill or ankylosis increase the likelihood/specificity of being axSpA. Furthermore, old and novel MRI approaches to best distinguish the sacroiliitis of early axSpA from differential diagnoses have recently been tested and compared. SUMMARY: Significant new and clinically relevant knowledge has been gained, but further research is still needed to optimally distinguish what is and what isn't sacroiliitis.

Spondyloarthritis evolution: what is in your history?

PURPOSE OF REVIEW: This review encompasses a detailed history of spondyloarthritis (SpA) evolution as early as the 17th century, continues on to the current concept of SpA, and ends with current gaps in our understandings of SpA. RECENT FINDINGS: Until the early 1960s, ankylosing spondylitis and other SpA family members were considered to be variants of rheumatoid arthritis (RA). The formal medical community separated them from RA at that time, and shortly thereafter they were recognized to be inter-connected based on shared clinical, laboratory, and imaging features. The last two decades have witnessed the formal distinction between axial and peripheral SpA and the connections that exist between nonradiographic and radiographic axial SpA. Recent studies have revealed different microbial compositions among patients with SpA and healthy controls and also between HLA-B27 positive and negative healthy individuals. SUMMARY: Further investigation of the roles of intestinal microbiome and physical force transduction toward SpA pathogenesis, strategies to improve delay in SpA diagnosis, biomarkers to better predict radiographic progression, and modification of current classification criteria to better address the axial and peripheral groups are gaps in our understandings that pose top priorities for SpA research.

Juvenile-Versus Adult-Onset Spondyloarthritis: Similar, but Different.

This article provides an overview of juvenile spondyloarthritis and important differences in the classification criteria, clinical presentation, outcomes, and pathology in juvenile versus adult-onset disease. Key differences in classification criteria between children and adults with spondyloarthritis are important to understand, as they can make transition from pediatric to adult care challenging. MRI and ultrasonography are increasingly relied on for the assessment of adult-onset disease activity and change over time in the pediatric population. The unique features of the maturing axial and peripheral skeleton are described for each modality, as they are key to understand for accurate interpretation of pathology in the pediatric population.

Classification Criteria in Axial Spondyloarthritis: What Have We Learned; Where Are We Going?

Spondyloarthritis (SpA) is a chronic inflammatory condition that can have a predominately peripheral or axial presentation. Axial SpA (axSpA) affects the axial skeleton with either radiographic (r-axSpA) or nonradiographic (nr-axSpA) changes. Radiographic changes are a late disease feature and earlier disease stages can be identified by incorporating other imaging methods. The diagnosis of axSpA is a clinical diagnosis and classification criteria are not aimed to be diagnostic tools. The split between r-axSpA and nr-axSpA is artificial and we should move toward the unifying concept of axSpA. Our understanding of genetics, biomarkers, and immunopathophenotypes will drive further refinement of classification criteria.

Can Imaging Be a Proxy for Remission in Axial Spondyloarthritis?

Targeting clinical remission is currently the focus of the treat-to-target strategy. Defining clinical outcomes as the main achievable treatment goal questions whether imaging remission should also be considered in the treat-to-target concept. Imaging has gained a pivotal role in diagnosing and classifying axial spondyloarthritis at the earliest phase of the disease. Its importance has been expanded to monitoring and prognosticating spondyloarthritis. This article summarizes current evidence on the use of imaging for monitoring disease activity and predicting treatment response in axial spondyloarthritis, and discusses the concept of imaging-driven treat-to-target strategy with a highlight on the newest imaging modalities in spondyloarthritis.

Psoriatic arthritis in childhood: A commentary on the controversy.

Approximately 5% of children with juvenile idiopathic arthritis (JIA) are diagnosed with the psoriatic form of the disease. In recent years, there has been substantial scholarship demonstrating both heterogeneity within the disease as well as similarities with other forms of JIA, culminating in a recent proposal for the categorization of JIA that excluded the psoriatic form altogether. The purpose of the review is to summarize the clinical, epidemiologic, and genetic features of psoriatic JIA (PsJIA), comparing it with other categories of JIA including spondyloarthritis. We conclude that there are sufficient unique clinical and genetic features within PsJIA as well as similarities with its adult counterpart that warrant including it within the JIA paradigm.

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis - 2019.

Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013.A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed.These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

What is axial spondyloarthritis? A latent class and transition analysis in the SPACE and DESIR cohorts.

OBJECTIVES: To gain expert-judgement-free insight into the Gestalt of axial spondyloarthritis (axSpA), by investigating its 'latent constructs' and to test how well these latent constructs fit the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. METHODS: Two independent cohorts of patients with early onset chronic back pain (SPondyloArthritis Caught Early (SPACE)) or inflammatory back pain (IBP) (DEvenir des Spondylarthopathies Indifférenciées Récentes (DESIR)) were analysed. Latent class analysis (LCA) was used to estimate the (unobserved) potential classes underlying axSpA. The best LCA model groups patients into clinically meaningful classes with best fit. Each class was labelled based on most prominent features. Percentage fulfilment of ASAS axSpA, peripheral SpA (pSpA) (ignoring IBP) or both classification criteria was calculated. Five-year data from DESIR were used to perform latent transition analysis (LTA) to examine if patients change classes over time. RESULTS: SPACE (n=465) yielded four discernible classes: 'axial' with highest likelihood of abnormal imaging and HLA-B27 positivity; 'IBP+peripheral' with 100% IBP and dominant peripheral symptoms; 'at risk' with positive family history and HLA-B27 and 'no SpA' with low likelihood for each SpA feature. LCA in DESIR (n=576) yielded similar classes, except for the 'no-SpA'. The ASAS axSpA criteria captured almost all (SPACE: 98%; DESIR: 93%) 'axial' patients, but the 'IBP+peripheral' class was only captured well by combining the axSpA and pSpA criteria (SPACE: 78%; DESIR: 89%). Only 4% of 'no SpA' patients fulfilled the axSpA criteria in SPACE. LTA suggested that 5-year transitions across classes were unlikely (11%). CONCLUSION: The Gestalt of axSpA comprises three discernible entities, only appropriately captured by combining the ASAS axSpA and pSpA classification criteria. It is questionable whether some patients with 'axSpA at risk' will ever develop axSpA.

Incorporating natural language processing to improve classification of axial spondyloarthritis using electronic health records.

OBJECTIVES: To develop classification algorithms that accurately identify axial SpA (axSpA) patients in electronic health records, and compare the performance of algorithms incorporating free-text data against approaches using only International Classification of Diseases (ICD) codes. METHODS: An enriched cohort of 7853 eligible patients was created from electronic health records of two large hospitals using automated searches (⩾1 ICD codes combined with simple text searches). Key disease concepts from free-text data were extracted using NLP and combined with ICD codes to develop algorithms. We created both supervised regression-based algorithms-on a training set of 127 axSpA cases and 423 non-cases-and unsupervised algorithms to identify patients with high probability of having axSpA from the enriched cohort. Their performance was compared against classifications using ICD codes only. RESULTS: NLP extracted four disease concepts of high predictive value: ankylosing spondylitis, sacroiliitis, HLA-B27 and spondylitis. The unsupervised algorithm, incorporating both the NLP concept and ICD code for AS, identified the greatest number of patients. By setting the probability threshold to attain 80% positive predictive value, it identified 1509 axSpA patients (mean age 53 years, 71% male). Sensitivity was 0.78, specificity 0.94 and area under the curve 0.93. The two supervised algorithms performed similarly but identified fewer patients. All three outperformed traditional approaches using ICD codes alone (area under the curve 0.80-0.87). CONCLUSION: Algorithms incorporating free-text data can accurately identify axSpA patients in electronic health records. Large cohorts identified using these novel methods offer exciting opportunities for future clinical research.

Assessment of SpondyloArthritis International Society (ASAS) Consensus on Spanish Nomenclature for Spondyloarthritis. / Consenso ASAS en nomenclatura en español para las espondiloartritis.

OBJECTIVE: To develop a consensus to standardize the use of Spanish terms, abbreviations and acronyms in the field of spondyloarthritis (SpA). METHODS: An international task force comprising all native Spanish-speaking Assessment of SpondyloArthritis International Society (ASAS) members, the executive committee of Grupo para el estudio de la Espondiloartritis de la Sociedad Española de Reumatología (GRESSER), two methodologists, two linguists from the Real Academia Nacional de Medicina de España (RANM) and two patients from the Spanish Coordinator of Spondylitis Associations (CEADE) was established. A literature review was performed to identify the conflicting terms/abbreviations/acronyms in SpA. This review examined written sources in Spanish including manuscripts, ICF and ICD, guidelines, recommendations and consensuses. This was followed by a nominal group meeting and a three-round Delphi. The recommendations from the RANM based on the Panhispanic dictionary were followed throughout the process. RESULTS: Consensus was reached for 46 terms, abbreviations or acronyms related to the field of SpA. A Spanish translation was accepted for 6 terms and 6 abbreviations to name or classify the disease, and for 6 terms and 4 abbreviations related to SpA. It was agreed not to translate 15 acronyms into Spanish. However, when mentioning them, it was recommended to follow this structure: type of acronym in Spanish and acronym and expanded form in English. With regard to 7 terms or abbreviations attached to acronyms, it was agreed to translate only the expanded form and a translation was also selected for each of them. CONCLUSIONS: Through this standardization, it is expected to establish a common use of the Spanish nomenclature for SpA. The implementation of this consensus across the community will be of substantial benefit, avoiding misunderstandings and time-consuming processes.

Clinical manifestations, disease activity and disease burden of radiographic versus non-radiographic axial spondyloarthritis over 5 years of follow-up in the DESIR cohort.

OBJECTIVES: To compare the clinical manifestations, disease activity and disease burden between patients with radiographic (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) over a 5-year follow-up period in the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort. METHODS: Patients from the DESIR cohort who had X-ray images of the sacroiliac joints available at baseline and did not leave the study during the 5-year follow-up period because of a diagnosis other than axSpA were included. A unilateral rating of 'obvious sacroiliitis' by the local reader was considered sufficient for classification as r-axSpA. The incidence of first episodes of peripheral and extra-rheumatic manifestations was compared between the two groups using the incidence rate ratio and Cox regressions adjusted for sex, age and tumour necrosis factor blocker (TNFb) intake. Mean values of patient-reported outcomes (PROs) and days of sick leave over 5 years of follow-up were compared using mixed models adjusted for sex, age, TNFb intake and baseline values. RESULTS: In total, 669 patients were included, of whom 185 (27.7%) and 484 (72.3%) were classified as r-axSpA and nr-axSpA, respectively. At baseline, the r-axSpA patients showed a significantly higher prevalence of males. After adjusting for age, sex and TNFb intake, Cox regressions for peripheral and extra-rheumatic manifestations did not show any significant differences between groups. Mixed models also showed similar mean levels in PROs and days of sick leave between groups over time. CONCLUSION: The incidence of peripheral and extra-rheumatic manifestations as well as the disease burden over time remained similar between r-axSpA and nr-axSpA groups after adjusting for intermediate variables. TRIAL REGISTRATION NUMBER: NCT01648907.

The impact of sex and disease classification on patient-reported outcome measures in axial spondyloarthritis: a descriptive prospective cross-sectional study.

BACKGROUND: The aim of this study was to explore the impact of sex and disease classification on outcomes in axial spondyloarthritis (axSpA) patients, including both radiographic (r-) axSpA and non-radiographic (nr-) axSpA, in males and females, respectively. METHODS: AxSpA patients were consecutively recruited from two rheumatology outpatient university clinics. We explored how sex and axSpA disease classification affected patient-reported outcome measures (PROMs). General linear models were used to investigate if there was an association between the continuous variables and each of the main effects of interest (sex and axSpA classification), as well as the possible interaction between them. Categorical outcome measures were analyzed with the use of logistic regression with the same fixed effects. We analyzed the relationship between tender point count (TPC) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The prevalence of extra-articular manifestations (EAMs) and the Charlson Comorbidity Index (CCI) were determined. RESULTS: According to the protocol, a total of 100 outpatients with axSpA were enrolled (r-axSpA males 30, r-axSpA females 10, nr-axSpA males 25, nr-axSpA females 35). The BASDAI scores appeared higher among nr-axSpA females (median [Q1; Q3], 47 [21; 60]) compared with the combined median for the 3 other subgroups 25 [12; 25]. Female sex was associated with a higher number of tender point count (TPC, P < 0.001). TPC and BASDAI were correlated for female nr-axSpA patients (r = 0.44, P = 0.008) and male nr-axSpA patients (r = 0.56, P = 0.003). Being classified as nr-axSpA was associated with a lower SF-36 Mental Component Summary (median for the 4 subgroups: nr-axSpa females 46.7, nr-axSpA males 52.3 vs. r-axSpA males 56.9 and r-axSpA females 50.4). EAMs were frequent (up to 50%). The CCI was low in all 4 subgroups, and no difference in the CCI between the subgroups was observed (P = 0.14). However, male sex had a significant impact on the CCI (P = 0.03). CONCLUSIONS: In summary, patients with r-axSpA, regardless of sex, appeared less affected on most PROMs compared with nr-axSpA patients. However, female sex was associated with a higher number of TPC. TPC could possibly confound disease activity outcomes such as BASDAI, and one can consider different thresholds for defining high disease activity depending on the patient's sex. TRIAL REGISTRATION: The trial is registered and approved by the Region of Southern Denmark's Ethics Committee ( S-20150219 ). Registered 19 February 2015.