The Cochrane Library and Medline were searched from 2000–2006. The search terms “ankylosing spondylitis” and “spondyloarthritis” were used in combination with the terms “epidemiology”, “pathogenesis”, “genetics”, “diagnosis”, “management”, and “therapy”. Publications from the past 6 years were preferentially selected but important ones from the past millennium were also included according to our judgment.
SeminarAnkylosing spondylitis
Section snippets
Epidemiology
Ankylosing spondylitis is a disease that affects young people, who generally present at around 26 years of age. Men are more often affected than are women, with a ratio of roughly 2 to 1.1 About 80% of patients develop the first symptoms at an age younger than 30 years, and less than 5% of patients present at older than 45 years.1 There is a rough correlation between the prevalence of HLA B27 and the incidence and prevalence of this disease in a specific population.2 HLA B27 is most prevalent
Clinical features
Irrespective of the spondyloarthritis subtype, the main clinical features of this group are inflammatory back pain (panel 1) caused by sacroiliitis and inflammation at other locations in the axial skeleton, peripheral arthritis, enthesitis,11 and anterior uveitis,12 whereas manifestations in other organs, such as the heart, are rare.13 Characteristic symptoms of ankylosing spondylitis are spinal stiffness and loss of spinal mobility, which are explained by spinal inflammation, structural
Pathogenesis
The cause of ankylosing spondylitis and other spondyloarthritides is unknown. The two central features that deserve explanation are inflammation and new bone formation, especially in the spine. Although inflammation is assumed to trigger new bone formation, there is no close correlation between inflammation and osteoproliferation. There is a strong genetic effect in spondyloarthritides, especially in ankylosing spondylitis. About a third of this effect is explained by HLA B27; the remainder, as
Genetics
Although HLA B27 itself is the most important gene predisposing to ankylosing spondylitis, there is clear evidence of association of other genes with susceptibility to this disease. Studies (in twins)25 suggest a contribution of HLA B27 of only about 20–30% of the total genetic risk in this disease, whereas the whole MHC contributes about 40–50%. The concordance rate is 63% for B27-positive monozygotic twin pairs, and 23% for dizygotic twin pairs. Furthermore, HLA B27-positive individuals with
Radiography
Sacroiliitis is a hallmark of ankylosing spondylitis, especially in earlier disease stages. It has become a major means for the development of classification criteria because of its very high prevalence in patients with ankylosing spondylitis. The first criteria set for classification, developed in 1961 in Rome, Italy,68 did not need radiographs of the sacroiliac joints to make a diagnosis, but in the 1966 New York (USA) criteria radiographic evidence of sacroiliac joint changes were included.69
Management
Ten main recommendations for the management of ankylosing spondylitis have been proposed by a combined ASsessment in Ankylosing Spondylitis working group (ASAS) and European League Against Rheumatism (EULAR) task force (figure 4).98 Briefly, the treatment of ankylosing spondylitis should be tailored according to the manifestations of the disease at presentation, severity of symptoms, and several other features that include the wishes and expectations of the patient. The disease monitoring of
Socioeconomics
Cost-effectiveness is an issue when expensive treatments are discussed. Despite the high costs, the clinical benefits118 and improvements in quality of life in patients with ankylosing spondylitis given infliximab result in lower disease-associated costs than does standard care, which translates to a short-term cost of about US$70 000 (GB£35 000) per quality-adjusted life year (QALY) gained144—an amount societies might be willing to pay. However, the calculated costs were higher than this
Search strategy and selection criteria
References (146)
- et al.
Classification of inflammatory arthritis by enthesitis
Lancet
(1998) - et al.
Ankylosing spondylitis and HL-A 27
Lancet
(1973) - et al.
Ileocolonoscopy in seronegative spondylarthropathy
Gastroenterology
(1989) Animal models of inflammatory spinal and sacroiliac joint diseases
Rheum Dis Clin North Am
(2003)- et al.
Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci
Am J Hum Genet
(2001) - et al.
Ankylosing spondylitis. Clinical features
Rheum Dis Clin North Am
(1998) - et al.
Refining clinical diagnosis with likelihood ratios
Lancet
(2005) - et al.
Radiologic diagnosis and pathology of the spondyloarthropathies
Rheum Dis Clin North Am
(1998) - et al.
Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis
Rheumatol Int
(2003) Epidemiology of HLA-B27 and arthritis
Clin Rheumatol
(1996)