Acute aseptic arthritis

Need for developing a case definition and guidelines for data collection, analysis, and presentation for acute aseptic arthritis as an adverse event following immunisation (AEFI)
Acute aseptic arthritis (AAA) is commonly defined as a clinical syndrome characterized by acute onset of signs and symptoms of joint inflammation, increased white blood count (WBC) in synovial fluid and the absence of an identifiable causative organism. It is a clinical manifestation of various different inflammatory conditions directly affecting the synovium of a joint space. The term aseptic arthritis has been used to differentiate the clinical entity from infectious arthritides with a known viable infectious agent being or having been present in the synovial fluid and/or positive blood cultures [1]. However, the differential diagnosis of joint inflammation is broad [2] and a clear delineation of peri-, post- and noninfectious joint inflammation is challenging based on current literature [3]. Furthermore, arthritis may be difficult to differentiate from a periarticular process based on clinical signs and symptoms and additional investigations (e.g., imaging studies or synovial aspirates) may be required to identify the synovial space as the site of inflammation [4], [5].

In recent years, the diagnostic use of polymerase chain reaction (PCR) has become more common in addition to standard and specialized culture techniques to exclude infectious agents in synovial fluid. Other laboratory tests aiming to substantiate or exclude an existing or preceding joint infection include synovial membrane biopsy, synovial immunofluorescence microscopy or synovial fluid leucocyte investigations [6].

1.1.1. Aseptic arthritis as AEFI
An overview of the available literature on aseptic arthritis as an AEFI is provided in the systematic review in the same issue of this journal [55]. In brief, 343 articles were reviewed. 62 studies reported arthritis alone as an AEFI, 236 studies reported arthralgia alone, 14 studies reported both arthritis and arthralgia as separate outcomes, and 17 studies used arthritis and arthralgia as a composite outcome.

However, outcome definitions for arthritis or arthralgia in these studies were scarce. The large majority (n = 221) used physician-verified or patient reports based on symptom diaries to describe the outcome. 74 studies provided a description of clinical characteristics with or without laboratory, histopathology, or imaging results.

Only 5 studies reported pre-defined arthritis criteria, of whom two used the American College of Rheumatology criteria [7], [8], two used the International League of Associations for Rheumatology criteria [9], [10], and one applied the American Rheumatism Association 1956 criteria [11]. Therefore, the Brighton Collaboration Working Group set out to meet the need of developing a standardized case definition for AAA as an AEFI.

1.2. Methods for the development of the case definition and guidelines for data collection, analysis, and presentation for acute aseptic arthritis as an AEFI
Following the standard process described in the overview paper [12] as well as on the Brighton Collaboration Website,3 the Brighton Collaboration Acute Aseptic Arthritis Working Group was formed in 2015 and included members with clinical, academic, public health, regulatory, and vaccine manufacturer background.

To guide decision-making during case definition and guideline development, a literature search was performed using Medline via PubMed, Embase and the Cochrane Libraries, including terms related to “vaccine”, “immunisation”, “inoculation”, “arthralgia”, “arthritis”, and “joint pain”. The search resulted in the identification of 13,039 references after the duplicates were removed. All abstracts were screened for possible reports of arthritis or arthralgia following immunisation. Nine-hundred thirty articles with potentially relevant material were reviewed in more detail, in order to identify studies using case definitions or, in their absence, providing clinical descriptions of the case material. This review resulted in a detailed summary of 145 original articles, including information on the study type, the vaccine, the diagnostic criteria or case definition put forth, the time interval since time of immunisation, and any other symptoms [55].

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