Ankylosing Spondylitis (AS) is a chronic inflammatory disease that primarily affects the axial skeleton. The disorder causes inflammation in the joints of the spine and the sacroiliac joints, which connect the lower spine to the pelvis. Over time, this inflammation can lead to the formation of new bone, resulting in the fusion of the vertebrae and a characteristic loss of spinal mobility.
Identifying the Ancient Footprint
Skeletal remains from various ancient cultures exhibit the hallmark signs of AS, particularly the fusion of the vertebrae. For example, evidence of AS has been identified in a Bronze Age skeleton from Armenia, dated to approximately 1400–1200 BCE. Archaeological investigation has also shown that the disease was present in ancient China, with cases identified in skeletal remains from the Neolithic period. Early reports of AS found in Egyptian mummies were later re-examined using modern computed tomography (CT) scans, which revealed that the spinal fusion was actually due to Diffuse Idiopathic Skeletal Hyperostosis (DISH), a degenerative condition distinct from AS.
The First Medical Descriptions
The first clear documentation of the disease’s distinct pathological changes appeared in the late 17th century. In 1691, the Irish physician and anatomist Bernard Connor published a description of a human skeleton where the vertebrae and other bones were completely fused into a single, continuous structure. More than a century later, the focus shifted from post-mortem pathology to clinical observation in living patients. In 1818, the English surgeon Sir Benjamin Brodie documented a case of a patient suffering from chronic spinal stiffness and pain who also presented with iritis, a form of eye inflammation. This observation was significant because it linked the spinal condition with an extra-articular manifestation, suggesting a systemic illness rather than a purely mechanical problem.
Formalizing the Diagnosis and Naming
The late 19th century became the period of formal recognition, as multiple European physicians independently defined the condition as a distinct disease entity. The Russian neurologist Vladimir Bekhterev published a paper in 1893 describing a condition characterized by spinal rigidity and curvature. This description isolated the unique pattern of inflammation in the spine from other conditions, such as tuberculosis of the spine. Almost simultaneously, the German physician Adolph Strümpell provided an account of the disease in 1884, emphasizing the progressive stiffening and fusion of the spinal and hip joints. The French neurologist Pierre Marie completed this trifecta of descriptions in 1898, focusing on the ascending nature of the disorder from the sacroiliac region upward. This collective work led to the condition being known by eponyms like Marie-Strümpell disease or Bekhterev’s disease before the standardized term Ankylosing Spondylitis was widely adopted.
Advancements in Understanding the Cause
A major breakthrough in understanding the root cause of AS occurred in the early 1970s, shifting the focus from structural pathology to genetic factors. In 1973, two research groups independently discovered a remarkably strong association between AS and the human leukocyte antigen B27 (HLA-B27) gene. The HLA-B27 gene is a common variant, and its presence is found in 60% to 90% of AS patients worldwide. While this association is the strongest known for a common variant with any human disease, the gene alone contributes to only about 25% of the overall genetic risk. Subsequent research has identified over 100 other genetic risk variants involved in the disease’s development. Advances in imaging, such as magnetic resonance imaging (MRI), have also allowed for the detection of inflammation in the sacroiliac joints much earlier than traditional X-rays, aiding in the diagnosis before advanced spinal damage occurs.