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Objective: Our aim was to systematically review the literature on the diagnostic and prognostic value of synovial biopsy in undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating clinical practice recommendations. The results lead to multinational recommendations in the 3e Initiative in Rheumatology., Methods: We performed a systematic literature review according to the PICO strategy (Patients, Intervention, Comparator, and Outcome). Using a designed search strategy we ran literature searches using Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism. Articles fulfilling predefined inclusion criteria were reviewed, and quality appraisal was performed., Results: Six publications from a total of 3265 diagnostic and 3271 prognostic studies were included, of which 2 were review articles. Data pooling was impossible because of significant clinical and statistical heterogeneity. Three themes of outcome were identified: anti-citrullinated peptide antibody (ACPA) staining in synovium, immunohistochemistry (CD22, CD38, CD68), and vascular patterns. Prognostic and diagnostic value was poor for these themes, although diagnostic trends favoring a particular diagnosis were identified. In contrast to serological ACPA testing, ACPA staining was shown not to be specific for diagnosis of rheumatoid arthritis (RA). Synovial CD22 and CD38 positivity seem to differentiate between RA and non-RA, while synovial CD38 and CD68 positivity can differentiate among RA, spondyloarthritis (SpA), and other diagnoses. Vascular patterns in undifferentiated arthritis are insufficiently specific to differentiate between SpA and RA., Conclusion: There is sparse evidence that synovial biopsy has diagnostic or prognostic value in patients with UPIA in clinical care. We urgently need systematic studies investigating the diagnostic and prognostic potential of synovial markers. A clear, broadly accepted, and unequivocal definition of undifferentiated arthritis is required as a starting point.

Objective: To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA)., Methods: An algorithm for identification of UPIA was developed by consensus during a roundtable meeting with an expert panel. It was informed by systematic reviews of the literature used to generate 10 recommendations for the investigation and followup of UPIA through the 3e initiative. The final recommendations from the 3e UPIA Initiative were made available to the panel to guide development of the algorithm. The algorithm drew on the clinical experience of the consensus panel and evidence from the literature where available., Results: In patients presenting with joint swelling a thorough evaluation is required prior to diagnosing UPIA. After excluding trauma, the differential diagnosis should be formulated based on history and physical examination. A minimum set of investigations is suggested for all patients, with additional ones dependent on the most probable differential diagnoses. The diagnosis of UPIA can be made if, following these evaluations, a more specific diagnosis is not reached. Once a diagnosis of UPIA is established, patients should be closely followed as they may progress to a specific diagnosis, remit, or persist as UPIA, and additional investigations may be required over time., Conclusion: Our algorithm presents a diagnostic approach to identifying UPIA in patients presenting with joint swelling, incorporating the dynamic nature of the condition with the potential to evolve over time.

Objective: To review the available literature on the diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating multinational clinical practice recommendations in the 3e Initiative in Rheumatology., Methods: A systematic literature search was carried out using Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism, searching for prognostic and diagnostic markers of acute-phase reactants in adult UPIA. Articles that fulfilled predefined inclusion criteria were systematically reviewed, and the quality was appraised. Likelihood ratios (LR), sensitivity, and specificity for diagnostic and prognostic outcomes were calculated., Results: A total of 18 publications out of 3699 identified references were included in the review. Only a small number of studies with significant heterogeneity, including different outcome measures and different cutoff values, were eligible for review, so pooling data was not possible. Overall, LR showed poor diagnostic and prognostic performance for most investigated acute-phase reactants. Available data showed some value for erythrocyte sedimentation rate in establishing a diagnosis in patients with undifferentiated arthritis; some prognostic and diagnostic value for C-reactive protein; some prognostic value for plasma viscosity in predicting persistence of arthritis; and some diagnostic value for sulfhydryl levels and matrix metalloproteinase-3 in establishing a diagnosis of rheumatoid arthritis., Conclusion: There is little published evidence concerning the diagnostic and predictive value of acute-phase reactants in patients with UPIA. Studies were heterogeneous, and "undifferentiated arthritis" was not well defined or was equivocally defined. The role of acute-phase reactants in diagnosing and predicting outcome in patients presenting with undifferentiated arthritis is limited.