Spondyloarthritis (SpA) is a family of chronic inflammatory diseases that primarily affect the joints and the spine. These conditions cause pain, stiffness, and structural damage that can impact mobility. The classification of SpA is complex, requiring a closer look at how the immune system malfunctions to cause inflammation, as its mechanisms differ from classic autoimmune disorders.
Defining Spondyloarthritis
Spondyloarthritis is an umbrella term for several related forms of chronic inflammatory arthritis. These diseases primarily affect the spine and the sacroiliac joints, which connect the lower spine to the pelvis. Inflammation in these areas causes chronic lower back pain and stiffness, often worsening after rest, such as in the morning. SpA also frequently involves enthesitis—painful inflammation at the entheses, where tendons or ligaments attach directly to the bone (e.g., the Achilles tendon). Chronic inflammation can eventually lead to structural damage and new bone formation, potentially causing sections of the spine to fuse together, a process called ankylosis.
The Distinction Between Autoimmune and Autoinflammatory
The classification of SpA requires understanding immune-mediated diseases. Autoimmune diseases, like Rheumatoid Arthritis or Lupus, are driven by the adaptive immune system, which learns to recognize specific invaders. A hallmark is the production of autoantibodies—proteins that mistakenly attack the body’s own specific self-antigens.
In contrast, autoinflammatory diseases are linked to the innate immune system, the body’s first and general line of defense. This response is rapid, non-specific, and not mediated by autoantibodies. Autoinflammatory conditions involve generalized inflammation without a clear self-antigen trigger.
SpA is generally classified as an immune-mediated or autoinflammatory disease rather than a classic autoimmune disorder, primarily due to the absence of typical autoantibodies. The inflammatory response in SpA is driven by the aberrant activation of innate immune cells, such as macrophages and neutrophils.
The involvement of cytokines like Interleukin-23 (IL-23) and Interleukin-17 (IL-17) further supports the autoinflammatory classification. While SpA has features suggesting an adaptive component (like T-cell involvement and the HLA-B27 association), the lack of autoantibodies shifts the understanding toward a predominantly autoinflammatory process. The field acknowledges that SpA often blurs the lines, possessing features of both classifications.
Genetic and Environmental Triggers
The development of Spondyloarthritis is strongly influenced by genetic predisposition and external factors. The most significant known genetic risk factor is the presence of the human leukocyte antigen B27 (HLA-B27). This gene is found in a large majority of people with Ankylosing Spondylitis, the most recognizable form of SpA.
The presence of HLA-B27 does not guarantee disease development; most people with this gene never show symptoms. This suggests the gene is a necessary but not sufficient component, requiring other factors to initiate the disease process. The HLA-B27 protein’s function is related to presenting antigens to the immune system, and its involvement in SpA may stem from its tendency to misfold or interact with other immune pathways.
Environmental triggers are thought to play a role in initiating the inflammatory cascade in genetically susceptible individuals. Infections, particularly those affecting the gastrointestinal or genitourinary tracts, are strongly implicated. For example, Reactive Arthritis, a subtype of SpA, often occurs following an infection with specific bacteria like Salmonella or Yersinia. This link suggests that an infection may confuse the immune system, causing it to misdirect its attack toward the body’s own tissues, especially in those with the HLA-B27 gene.
Major Types of Spondyloarthritis
Spondyloarthritis encompasses a spectrum of related diseases that share core features but have distinct primary sites of inflammation.
Ankylosing Spondylitis (AS)
This is the most widely known type, characterized by chronic inflammation primarily in the spine and sacroiliac joints, which can eventually lead to bone fusion. AS is sometimes referred to as radiographic axial spondyloarthritis because the structural damage is visible on X-rays.
Non-Radiographic Axial Spondyloarthritis (nr-AxSpA)
This condition presents with the same inflammatory symptoms in the spine and sacroiliac joints as AS but without visible damage on conventional X-rays.
Psoriatic Arthritis (PsA)
PsA affects individuals who also have the skin condition psoriasis, causing inflammation in peripheral joints (such as the hands and feet) and often involving the spine and entheses.
Enteropathic Arthritis (EnA)
This form of SpA occurs in people with Inflammatory Bowel Diseases (IBD), such as Crohn’s disease or ulcerative colitis. EnA inflammation can affect the spine and peripheral joints, linking joint disease with intestinal inflammation.
Reactive Arthritis
This type typically follows an infection and affects the joints in the lower limbs.