• The history of ankylosing spondylitis (AS) dates back to the discovery of 5000-year-old skeletons with characteristic spinal changes.
• Numerous cases of AS have featured in medical literature since the 16th century.
• The disease was further defined by correlating pathological and clinical features, and the development of clinical radiology.
• Subsequent epidemiological and familial studies highlighted the association with other conditions as part of the spondyloarthritides. The discovery of HLA-B27 confirmed this association.
• Over the past two decades, genome-wide association studies, and advances in imaging and immunology have yielded dramatic insights into the disease and the development of highly effective therapies.
The earliest evidence of ankylosing spondylitis (AS) may date back to ancient Egypt, where paleopathological analysis of the skeletons of 5000-year-old mummified pharaohs showed spinal osteophyte formation and ‘bamboo spines’ suggestive of the disease. However, this still remains controversial as definitive distinction from diffuse idiopathic skeletal hyperostosis (DISH) is difficult.
The first published cases in medical literature were in 1559 when Realdo Colombo, an assistant to Andreas Vesalius at the University of Padua, described two skeletons with spinal disease suggestive of AS. In his excellent review, Bywaters called this the ‘fossil stage’ in the development of the history of AS (Bywaters, 1979). Several other pathological descriptions of medieval skeletons described changes typical of AS, but, the first definite description of AS is attributed to Bernard Connor (1666–1695), an Irish physician studying at the University of Rheims. While demonstrating anatomy, he noted a male skeleton in which complete bone fusion had occurred from the lower ribcage and thoracic spine to the sacrum. In his thesis (1691), he postulated the man probably had difficulty breathing due to fused rib joints, and trouble turning and bending due to the spinal fusion. In the mid-1800s, several clinical cases were described in Europe for the first time, with clinical and post-mortem pathology correlation suggesting links between the spinal and extra-spinal manifestations (including iritis) in the patients.
In 1893, Vladimir von Bekhterev, a Russian neurologist and psychologist, described a series of three patients, including a mother and daughter, who had previous back trauma and developed a form of spondylitis deformans. He postulated that a chronic inflammatory process of the vertebrae had led to rigidity, bone fusion, and myelopathy, and that it had a hereditary component. Adolph Strümpell (1897) and Pierre Marie (1898), neurologists from Germany and France, respectively, characterized further cases and independently delineated the disease as being primarily rheumatological. These descriptions, together with the development of radiology in the late 1800s, facilitated the ability to diagnose the disease prior to the development of severe ankylosis. For these reasons, AS was previously also known as Bechterew’s Disease (the transliteration of Bekhterev) or Marie-Strümpell Disease, terms which are still used in some countries.
The x-ray changes of AS were characterized in the early 1900s by Forestier, Scott, Krebs and others who described sacroiliac joint arthritis early in the disease, with later syndesmophyte formation. The disease appeared to be familial and epidemiological studies were carried out to investigate inheritance patterns. However, many rheumatologists at the time believed this disease to be a clinical subset of rheumatoid arthritis (RA) affecting the spine, which was occasionally triggered by factors such as psoriasis, colitis, and urethritis. While many ‘lumped’ AS as a subset of RA, the striking difference in x-ray findings and lack of rheumatoid factor prompted others to ‘split’ it into a completely different disease category of seronegative arthritis.
From the 1930s until the mid-1950s radiation therapy was widely used for the treatment of AS. While this was often very effective, it was subsequently abandoned due to the concern about secondary malignancies as a result of this treatment. A follow-up study in the United Kingdom of 14,000 patients with AS who had received at least one x-ray course revealed a threefold increase in mortality for leukaemia and a 28% increase in mortality from neoplasms other than leukaemia or colon cancer, compared to the general population.
By the 1950s, not only was the distinction with RA indisputable, but association with the other seronegative arthritides was increasingly recognized. Marche (1954) and Oates (1959) (both cited in Zeidler, 2011) suggested that AS and Reiter’s syndrome (now called reactive arthritis) were associated and may share the same origin, while Amor (1968; also cited in cited in Zeidler, 2011) postulated a common genetic background after noting the frequent development of AS in those with Reiter’s syndrome.
A year after Moll and Wright proposed their seminal classification for psoriatic arthritis, they also proposed a unifying concept for a group of related seronegative arthritides which included AS, psoriatic arthritis, Reiter’s disease, intestinal arthropathies, and Behcet’s syndrome. This group of conditions, termed spondyloarthritides, share common characteristics including negative rheumatoid factor, absence of ‘rheumatoid’ nodules, peripheral inflammatory arthritis, radiologic sacroiliitis, tendency to familial aggregation, and related clinical features such as psoriasis, uveitis, conjunctivitis, intestinal inflammation, and genitourinary infections.
While the familial tendency in AS had been recognized in the 19th century, and a genetic link between the various seronegative diseases was postulated, this remained unproven until the 1970s. In 1973, two groups independently described the HLA-B27 association with AS, representing one of the strongest genetic associations ever reported in a polygenic disease (see Chapter 4). Of interest, HLA-B27 sequences were subsequently detected in the skeletal remains of presumed AS cases from the Middle Ages. Subsequent studies also indicated the association of HLA-B27 with Reiter’s syndrome and psoriatic arthritis, supporting the concept of spondyloarthritides as a family of diseases sharing similar pathogenetic manifestations. The concept of spondyloarthritis (SpA) was subsequently incorporated into disease classification criteria and remains important in clinical practice (covered in Chapter 12).
Following the discovery of the association with HLA-B27, progress in genetics largely stalled and the treatment of AS remained largely limited to physiotherapy and non-steroidal anti-inflammatory drugs throughout the late twentieth century (see Chapter 15). However, over the past two decades, large genome-wide association studies, advances in imaging, and increased understanding of immunology (see Chapters 4, 5, and 11) have led to novel insights into the disease processes and the development of both new classification criteria and therapies, transforming the lives of patients with this condition.
Key References and further reading:
Bywaters, EG. Historical aspects of ankylosing spondylitis. Rheumatol Rehabil. 1979;18(4):197–203. doi: 10.1093/rheumatology/18.4.197Find this resource:
Moll JM, Haslock I, Macrae IF, Wright V. Associations between ankylosing spondylitis, psoriatic arthritis, Reiter’s disease, the intestinal arthropathies, and Behcet’s syndrome. Medicine. 1974;53(5):343–64. PMID: 4604133Find this resource:
Sieper J, Braun J, Rudwaleit M, et al. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002;61(Suppl 3):iii8–18. doi: 10.1136/ard.61.suppl_3.iii8Find this resource:
Zeidler H, Calin A, Amor B. A historical perspective of the spondyloarthritis. Curr Opin Rheumatol. 2011;23(4):327–333. doi: 10.1097/BOR.0b013e3283470ecdFind this resource: