Seronegative Inflammatory Arthritis

Introduction

Seronegative inflammatory arthritis refers to a group of conditions in which clinical evidence of noninfectious, active inflammation ( Box 78.1 ) is noted in the joints, but serum autoantibodies, such as rheumatoid factor (RF) or anticyclic citrullinated peptide (anti-CCP) antibodies, are absent. RFs are autoantibodies and were the first autoantibodies described in rheumatoid arthritis (RA). RF is used as a diagnostic marker for RA but can be present in a wide spectrum of both rheumatic disorders and nonrheumatic diseases. RF can be detected in some healthy individuals as well as in people with infectious diseases like hepatitis C or with malignancies. In the last two decades, the role of anti-CCP antibodies in the diagnosis of inflammatory arthritis has evolved, and they are now understood to be a critical component in initiating the inflammatory response in RA. The anti-CCP antibody test is as sensitive as the RF test in the diagnosis of RA; however, it has greater specificity and is independently associated with accelerated joint dysfunction. In the absence of both RF and anti-CCP antibodies, patients may be diagnosed with “seronegative RA” based upon findings otherwise characteristic of RA if appropriate exclusions have been met. The pathogenesis of “seronegative inflammatory arthritis” is poorly understood and remains difficult to diagnose with confidence.

For the purposes of this discussion, the inflammatory arthritides (other than seronegative RA) will include spondyloarthropathies (SpAs), crystalline arthropathies, and adult Still disease (ASD) ( Box 78.2 ). Besides their distinction from RA, the seronegative inflammatory arthritides have several clinical features in common. They present with pain, limited motion, and swelling of the affected joint, in the absence of trauma or infection. Diarthrodial joints, such as the elbow, can be affected, and seronegative arthritis can affect other synovial joints as well.