ankylosing spondylitis (AS)

introduction

one of the seronegative spondyloarthropathies with a strong genetic predisposition which appears to relate to the ARTS1 and IL23R genes in addition to HLA-B27
- elevated KIR2DS5 gene expression inhibits the development of endometriosis, AS and psoriasis ¹⁾
- the tumor necrosis factor (TNF) family is one of the most critical factors in the occurrence and development of AS ²⁾
- there may be an association of AS with infertile endometriosis but not with other forms of endometriosis ³⁾
men are affected more than women by a ratio of about 3:1, and the disease is generally more severe in males
- in women those with active disease tend to have lower oestrogen levels and mouse studies show elevation of estrogen levels inhibited the development of arthritis
~90% of AS patients express the HLA-B27 genotype BUT only 5% of individuals with the HLA-B27 genotype contract the disease
it mainly affects joints in the spine and the sacroiliac joint in the pelvis, and can cause eventual fusion of the spine.
onset of symptoms is usually before age 45yrs with average age of onset being 23yrs, but given the non-specific nature of early symptoms diagnosis is usually not made until ~10 years later.
in the 1st 10 yrs of the disease, it is cervical dominant in 5%, lumbar dominant in ~20% and equi-dominant or minimal in each area in 75%, while 80% have symmetric sacro-iliitis ⁴⁾

initial symptoms are chronic back pain and stiffness in the thoracic spine, often with pain referred to a buttock or back of thigh from sacro-iliac joint involvement
pain usually worst at rest improving with activity
adolescent onset may cause pain and swelling of large limb joints, particularly the knee
in prepubescent cases, the ankles and feet may be involved, where calcaneal spurs may also develop.
40% develop iritis and uveitis, causing redness, eye pain, vision loss, floaters and photophobia
4-35% of cases involve the TMJ joints
there appears to be a higher prevalence oral ulcers ⁵⁾
5-10% also have or develop inflammatory bowel disease (IBD)
a study showed that 10% also had Sjögren's syndrome (SS) ⁶⁾, while another small study of women with spondyloarthropathies showed SS was far more common in the women with SpA (31.7%) than in the controls (2.9%) ⁷⁾
symptom clusters in AS explained 58% of clinical variation in a study of AS patients ⁸⁾
- the gastrointestinal-cardiac cluster
  - constipation, intestine discomfort and diarrhea.
- the fatigue-sleep disturbance cluster
- the headache-chest pain cluster
- the mouth-eye cluster
  - patients with HLA-B27 negativity or a higher CRP value were more likely to have dry mouth

there is no specific test
Dx is usually made on clinical features, and MRI and XRay of the spine although plain XRay features are usually not present until 10yrs after onset
Schober's test is a useful clinical measure of flexion of the lumbar spine performed during examination
ESR and CRP may be raised during acute inflammatory periods
a minority are ANCA +ve

shares many features with AS but no radiographic features of the sacro-iliac involvement although this may be visible on MRI
tends to occur as chronic back pain in those 15-40yrs of age, 5-30% of cases progress to AS over 2-30yrs, esp. if male, high CRP
70% of Caucasians with nr-axSpA are HLA-B27 positive (compared with 7.5% of the general Caucasian population)
male to female ratio in nr-axSpA is close to 1:1
for some women, the neck and peripheral joints are often affected first