Spondyloarthritis (SpA) comprises a class of inflammatory disorders of the large and small joints and the axial skeleton and local connective tissue, including ankylosing spondylosis (AS), reactive arthritis, psoriatic arthritis (PsA), non-radiographic axial (nr-ax) SpA, and nonspecific forms often referred to as “undifferentiated” SpA.1
Patients are often diagnosed with SpA on the basis of inflammatory low back pain in the lumbar, buttock, and hip area. The pain usually lasts more than 3 months, with morning stiffness of at least 30 minutes.2 SpA pain is responsive to non-steroidal anti-inflammatory drug (NSAID) therapy.
Autoimmune conditions such as inflammatory bowel disease (IBD), or anterior acute uveitis (AAU) are frequently associated with SpA, in addition to psoriasis, which can lead to an enteropathic SpA (ESpA) diagnosis. The pathophysiology of ESpA is not well understood, but the coexistence of SpA and IBD bowel symptoms in patients suggests a shared etiology.
Prevalence of overlap with gut mechanisms
An overlapping etiology between SpA and the gut has been observed in a number of studies, which could result from a lymphocytic mechanism. An estimated 70% of SpA patients demonstrate involvement of the gastrointenstinal (GI) tract, and 7-12% are diagnosed with IBD.4-8 Likewise, joint pain and swelling are reported in 16-33% of patients with IBD.5-8
In vitro studies of the binding properties of activated human intestinal immunoblasts have demonstrated efficient attachment to mucosal cells within the intestine. They also demonstrated attachment to extra-intestinal high endothelial venules (HEVs) without binding to lymph node vascular walls, conceivably providing the opportunity for intestinal lymphocytes to travel to joints.9 Once there, antigen-activated T cells may induce a synovial inflammatory response in what has been called the “gut iteropathy concept.”10
Overlapping clinical features between SpA and IBD have also pointed to mechanisms involving the human leukocyte antigen (HLA) B27 common to both conditions, which has been examined in a number of studies.4 Transgenic rats induced with HLA-B27/human B2 microglobulin rapidly progressed to inflammatory disease simultaneously in the intestines and joints with the introduction of normal intestinal bacteria, while rats that were kenervept germ-free did not develop symptoms of inflammation.11,12 This study provided the first convincing evidence a link between intestinal bacteria and joint inflammation.12
Although the prevalence of AS, the most frequent form of SpA, in IBD has only been reported in 1% to 10% of patients, this prevalence was determined using New York criteria, which prevent definitive diagnosis at disease onset, and may result in underestimation of the coexistence of the two conditions.13-15
Contradictory to previous results, one clinical study of AS patients reported that greater than 90% tested positive for HLA-B2716, while studies of IBD patients with AS have found that 25% to 78% of them are HLA-B27 positive.15,17-19 The role of HLA-B27 in inflammation is not yet clear and several theories are under investigation, involving mechanisms of altered or defective cell death and misfolding of the HLA-B27 beta pocket, as well as the possible cross-reactions with bacterial antigens that are normally restricted to HLA-B27.20-22
Another study found an overlap between SpA and Crohn’s disease (CD) in which scavenger receptor CD163+ macrophages are increased in gut mucosa, suggesting that antigen-presenting cells may contribute to both gut and joint inflammation, in addition to T-cell mechanisms.23
This article originally appeared on Rheumatology Advisor