Ankylosing Spondylitis (AS)

AS is perhaps the best described of the SpA conditions, being considered the most severe or potentially disabling within the group. Inflammatory back pain is the most common presenting or leading feature, with variable degrees of associated enthesopathy, peripheral arthritis and extra-articular manifestations. The association with human leucocyte antigen (HLA)-B27 is the strongest among the SpA subgroups, with over 90% of AS patients being HLA-B27 positive. The diagnosis of AS is made based on inflammatory back pain, clinical findings of restricted spinal mobility and the presence of sacroiliitis on imaging. For the last 20 years, the modified New York classification criteria have been used to define AS in population studies, requiring radiographic sacroiliitis of at least grade 2 bilaterally or grade 3 unilaterally to make the diagnosis. More recently, magnetic resonance imaging (MRI) has proven to be more sensitive for detecting early, pre-radiographic sacroiliitis , but cost and availability have to date precluded its use in epidemiological studies.

AS has traditionally been considered a predominantly male disease. Male preponderance has been varyingly reported between 2:1 and 9:1 ( Table 2 ) . The ratio, however, seems to be diminishing over time, likely due to improved awareness of the disease in women and an improvement in early diagnosis across the board. It had been thought that AS in women was a milder, less destructive disease , and therefore not diagnosed until later compared with men; more recent review would suggest a slightly different phenotype, with women having more cervical and thoracic spine involvement and less ankylosis. Disability and pain, however, are equally if not more pronounced than in men .

The incidence and prevalence of AS are closely linked to the background population frequency of HLA-B27 ( Table 3 ). The presence of HLA-B27 contributes approximately half of the genetic risk of AS , and populations with high frequencies of the HLA-B27 gene generally have a higher incidence of AS, with some exceptions. The elucidation of different HLA-B27 alleles in different populations only partly explains these discrepancies.

Psoriatic Arthritis (PsA)

Similar to AS, the diagnosis and classification of PsA have undergone an overhaul in the past few years. The development of the CASPAR (ClASsification criteria for Psoriatic ARthritis) classification criteria in 2006 has allowed a consistent case definition in clinical and epidemiological studies. Earlier studies have been difficult to compare due to different case ascertainment, different study settings and disease definitions. Although the disease has been ‘defined’ by the presence of psoriasis, skin disease and arthritis do not have to co-exist in PsA, do not have to be matched in severity and can often be separated by decades. The distribution of PsA is about equal in men and women, although a difference in phenotype has been described, with men having more axial disease and women having more classically a symmetrical polyarthritis . In general, oligoarthritis or polyarthritis is the presenting feature of PsA, with enthesitis or inflammatory back pain much less common in published studies, likely in part due to the diagnostic criteria used in older studies.

A recent retrospective population-based study has reported the overall age- and sex-adjusted annual incidence of PsA (defined using the CASPAR criteria) to be 7.2 per 100,000, higher in men than women (9.1 vs. 5.4) and increasing over the past 30 years from 3.6 per 100,000 between 1970 and 1979 to 9.8 per 100,000 between 1990 and 2000 ( p for trend <0.001). Point prevalence was 158 per 100,000 in 2000, again higher in men than in women (192 vs. 127).

Interestingly, despite the differences in methodology of earlier studies, reported prevalence rates are fairly uniform and consistent with those given by Wilson et al. (2009) . A Finnish study based on the prescription of PsA medications through the nationwide insurance scheme revealed an incidence of PsA of 6 per 100,000 adults in 1990 and 6.8 per 100,000 adults in 1995, similar to that reported in Sweden but lower than a face-to-face population study also carried out in Finland (23 per 100,000) . Shbeeb et al. (2000) identified all inflammatory joint disease associated with a definite diagnosis of psoriasis within the Rochester Epidemiology Project between 1982 and 1991, finding an age- and sex-adjusted incidence of 6.59 per 100,000 that was similar to the other studies cited. The incidence of PsA may be particularly low in Japan, reported as 0.1 case per 100,000 in just one study which was based on a self-reported patient questionnaire targeting clinics and hospitals alone for patient identification .

Population-based prevalence lies between 0.02% and 0.2% . However, in patients with existing psoriasis, the prevalence of PsA ranges between 6% and 42% in Caucasian populations, and somewhat lower in Asian populations, including 5% in China and 2% in Turkey . A cumulative incidence of joint disease of 1.7%, 3.1% and 5.1% is seen at 5, 10 and 20 years following the onset of psoriasis , giving 30-year risk for PsA at less than 10% but which does not diminish with time. Risk factors for developing PsA in patients with psoriasis include scalp psoriasis (hazard ratio (HR) 3.89), nail dystrophy (HR 2.93) and intergluteal/peri-anal psoriasis (HR 2.35).

Mortality has been reported to be increased in patients with PsA compared with the general population , related to increased rates of cardiovascular and respiratory mortality . This pattern of increased mortality is similar to that seen with other inflammatory joint diseases , raising issues of the role of chronic inflammation in particular as regards cardiovascular mortality across the spectrum.

PsA, like the other SpAs, is associated with HLA-B27 , predominantly in those individuals with axial symptoms of sacroiliitis or spondylitis (60–70% are HLA-B27 positive) . The association is much weaker in predominantly peripheral PsA (24%) , and no increase in the frequency of HLA-B27 is seen in psoriasis alone (with the exception of pustular psoriasis) .

Psoriatic Arthritis (PsA)

Similar to AS, the diagnosis and classification of PsA have undergone an overhaul in the past few years. The development of the CASPAR (ClASsification criteria for Psoriatic ARthritis) classification criteria in 2006 has allowed a consistent case definition in clinical and epidemiological studies. Earlier studies have been difficult to compare due to different case ascertainment, different study settings and disease definitions. Although the disease has been ‘defined’ by the presence of psoriasis, skin disease and arthritis do not have to co-exist in PsA, do not have to be matched in severity and can often be separated by decades. The distribution of PsA is about equal in men and women, although a difference in phenotype has been described, with men having more axial disease and women having more classically a symmetrical polyarthritis . In general, oligoarthritis or polyarthritis is the presenting feature of PsA, with enthesitis or inflammatory back pain much less common in published studies, likely in part due to the diagnostic criteria used in older studies.

A recent retrospective population-based study has reported the overall age- and sex-adjusted annual incidence of PsA (defined using the CASPAR criteria) to be 7.2 per 100,000, higher in men than women (9.1 vs. 5.4) and increasing over the past 30 years from 3.6 per 100,000 between 1970 and 1979 to 9.8 per 100,000 between 1990 and 2000 ( p for trend <0.001). Point prevalence was 158 per 100,000 in 2000, again higher in men than in women (192 vs. 127).

Interestingly, despite the differences in methodology of earlier studies, reported prevalence rates are fairly uniform and consistent with those given by Wilson et al. (2009) . A Finnish study based on the prescription of PsA medications through the nationwide insurance scheme revealed an incidence of PsA of 6 per 100,000 adults in 1990 and 6.8 per 100,000 adults in 1995, similar to that reported in Sweden but lower than a face-to-face population study also carried out in Finland (23 per 100,000) . Shbeeb et al. (2000) identified all inflammatory joint disease associated with a definite diagnosis of psoriasis within the Rochester Epidemiology Project between 1982 and 1991, finding an age- and sex-adjusted incidence of 6.59 per 100,000 that was similar to the other studies cited. The incidence of PsA may be particularly low in Japan, reported as 0.1 case per 100,000 in just one study which was based on a self-reported patient questionnaire targeting clinics and hospitals alone for patient identification .

Population-based prevalence lies between 0.02% and 0.2% . However, in patients with existing psoriasis, the prevalence of PsA ranges between 6% and 42% in Caucasian populations, and somewhat lower in Asian populations, including 5% in China and 2% in Turkey . A cumulative incidence of joint disease of 1.7%, 3.1% and 5.1% is seen at 5, 10 and 20 years following the onset of psoriasis , giving 30-year risk for PsA at less than 10% but which does not diminish with time. Risk factors for developing PsA in patients with psoriasis include scalp psoriasis (hazard ratio (HR) 3.89), nail dystrophy (HR 2.93) and intergluteal/peri-anal psoriasis (HR 2.35).

Mortality has been reported to be increased in patients with PsA compared with the general population , related to increased rates of cardiovascular and respiratory mortality . This pattern of increased mortality is similar to that seen with other inflammatory joint diseases , raising issues of the role of chronic inflammation in particular as regards cardiovascular mortality across the spectrum.

PsA, like the other SpAs, is associated with HLA-B27 , predominantly in those individuals with axial symptoms of sacroiliitis or spondylitis (60–70% are HLA-B27 positive) . The association is much weaker in predominantly peripheral PsA (24%) , and no increase in the frequency of HLA-B27 is seen in psoriasis alone (with the exception of pustular psoriasis) .

Reactive Arthritis (ReA)

ReA was first described in 1916 by Reiter as the classic triad of urethritis, conjunctivitis and arthritis after a documented enteric or urogenital infection. This condition is now considered a subgroup of the broader concept of ReA, an arthritis with a defined relationship to a preceding infection, usually enteric or urogenital, with specific pathogens implicated. There is a wide clinical spectrum including acute arthritis, inflammatory back pain, enthesopathy and characteristic extra-articular features.

The prevalence of acute ReA has been estimated to be between 1% and 7%, depending on setting and diagnostic criteria . The annual incidence of ReA is 30–40 per 100,000 with an equal distribution between men and women. A large population-based study of proven bacterial enteric infections in Minnesota and Oregon (USA) revealed an estimated incidence of ReA following proven Campylobacter, Salmonella, Shigella , Escherichia coli O157 or Yersinia infections of 0.6–3.1 cases per 100,000. Campylobacter infection was associated with the highest incidence of subsequent ReA (2.1 per 100,000), similar to other published studies .

HLA-B27 features in ReA as with the other SpAs. The risk of developing ReA has been reported to be up to 50 times higher after the exposure to a triggering infection in an HLA-B27 positive individual compared with an HLA-B27 negative patient . HLA-B27 positivity brings more severe disease, and a higher likelihood of progressing to chronic ReA . These associations are not seen in the larger population-based studies , which is likely to reflect the selection bias inherent in hospital-based studies and the more severe end of the disease spectrum. It is thought that, in the majority of cases, ReA is a mild disease, with only 20% consulting a doctor and less than 2% requiring hospital admission.

IBD-SpA

Three distinct types of arthritis are recognised as being associated with IBD . The first comprises axial disease, including AS and isolated sacroiliitis, and the others are two distinct types of peripheral arthritis . Type 1 peripheral arthritis is an acute oligoarthritis, with self-limiting disease in less than five joints, commonly in larger joints and in the lower limbs, and closely associated with IBD activity. Peripheral arthritis type 2 is described as a symmetrical small-joint polyarthritis, persistent with a median duration of 3 years, and unrelated to the activity of IBD. Both the axial group and type 1 peripheral arthritis (but not type 2) would be classified as IBD-SpA, according to the ESSG criteria, requiring inflammatory spinal pain and/or asymmetric synovitis or predominantly of the lower limbs, in the presence of IBD .

The population-based prevalence of Crohn’s disease has been reported as 75 per 100,000 and of ulcerative colitis as 50–100 per 100,000. Within this group, at least 10–15% will have clinical features of a spondyloarthritis . Furthermore, early radiographic studies have shown that up to 19% of patients with IBD will have radiographic sacroiliitis on plain X-ray and 29% on computed tomography (CT) , of which only 3% were symptomatic. In a recent review of SpA in IBD , large variations in reported frequencies of the different SpA features were seen, dependent on the populations studied. The prevalence of AS in IBD has been reported in a range of 1–25.3% , isolated sacroiliitis in 1–45.7% , peripheral arthritis in 2.8–30.6% , IBD-SpA according to the ESSG criteria in 11.5–45.7% and inflammatory back pain in 5–50% of patients with IBD . Due to changes in classification criteria and definitions of SpA over time, it is difficult to compare studies in the disease. Nevertheless, it is likely that the earliest studies have underestimated the prevalence of IBD-SpA as we now understand it.

The link between HLA-B27 and IBD-SpA is not as strong as in AS populations, with approximately 60% of IBD AS patients and 25–75% of IBD-SpA patients being HLA-B27 positive . There is an equal distribution of the disease between men and women, and axial disease is milder than in AS alone with little radiographic progression.