INTRODUCTION

Seronegative inflammatory arthritis refers to a group of conditions in which clinical evidence of noninfectious, active inflammation (Box 75-1) is noted in the joints, but serum autoantibodies, such as rheumatoid factor (RF) or anticyclic citrullinated peptide antibodies (anti-CCP), are absent. RF is widely used as a diagnostic marker for rheumatoid arthritis (RA), despite its presence in other inflammatory and infectious conditions. RF can also be detected in some healthy individuals. In recent years, anti-CCP antibodies have been shown to be as sensitive as RF in the diagnosis of RA, but with greater specificity.⁹ Seventy-five to eighty percent of patients with RA are seropositive for these autoantibodies.⁹ Therefore, the term seronegative inflammatory arthritis excludes RA.

Besides their distinction from RA, the seronegative inflammatory arthridites have several clinical features in common. They present with pain, limited motion and swelling of the affected joint, in the absence of trauma. When only one joint such as the elbow is initially involved, infection needs to be excluded. However, the elbow is often not the only diarthrodial joint involved in these conditions.

For the purposes of this discussion, the seronegative inflammatory arthridites will include spondyloarthropathies, crystalline arthropathies, and adult Still’s disease (Box 75-2).

SPONDYLOARTHROPATHIES

Spondyloarthropathies (SpA) are a group of inflam-matory disorders that includes ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease, and reactive arthritis, also known as Reiter’s syndrome. They share an increased prevalence of the human leukocyte antigen class I molecule B-27. Classically, the spondyloarthropathies manifest as an inflammatory arthritis of the spine and sacroiliac joints, but an asymmetric peripheral arthritis can occur as well. A key clinical feature distinguishing SpA from RA is the presence of enthesitis. Enthesitis refers to inflammation that is located at the sites of ligamentous insertion into bone, such as the Achilles tendon or plantar fascia. Table 75-1 illustrates several clinical differences between the SpA and RA. The relative frequency of elbow involvement in the SpA is shown in Table 75-2.

TABLE 75-1 Clinical Differences Between Spondyloarthropathies and Rheumatoid Arthritis

TABLE 75-2 Elbow Involvement in Spondyloarthropathies

Aspiration of the elbow and subsequent synovial fluid (SF) analysis may be necessary to exclude infection in some cases, especially in monoarthritis. The injection of corticosteroids, such as triamcinolone and local anesthetic, into the joint space may also offer pain relief, and facilitate improvements in range of motion and overall joint function for patients with SpA.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of medical management of spondyloarthropathies. They reduce inflammatory features, and reduce joint pain and stiffness. The most common adverse events with the use of NSAIDs are gastrointestinal, and range from dyspepsia in 10% to 20% of patients to serious bleeding or gastroduodenal perforation in 7.3 to 13/1000 patients per year.¹⁰

If patients with SpA do not tolerate NSAIDs, are refractory to therapy, or have evidence of active disease or radiographic progression, the use of additional or alternative medications is indicated. These include sulfasalazine (SUSP) and methotrexate (MTX), which down-regulate the inflammatory activity that is associated with these conditions. Such medications require careful monitoring for potential adverse events, including increased risk for infection, hematologic abnormalities, and hepatotoxicity. For this reason, they should be prescribed and monitored only by physicians experienced in their administration.

If desired clinical outcomes are not achieved with NSAIDs, SUSP, or MTX, patients with spondyloarthropathies may be candidates for a new class of medications commonly referred to as biologics. Recently developed, they are monoclonal antibodies that bind to tumor necrosis factor-a, an important cytokine in the inflammatory pathway. These powerful medications can be associated with dramatic clinical improvements in patients with refractory spondyloarthropathies. Again, these medications should be administered and monitored under the guidance of a rheumatologist.