Key Points
Disease summary:
The spondyloarthropathies (SpA) are a group of disorders causing inflammatory arthritis that typically involve the sacroiliac joints of the pelvis and usually the spine, and in which inflammation occurs at the insertion point of tendons into bone (enthesitis). They also share genetic associations notably with HLA-B27. Ankylosing spondylitis (AS) is the archetypal spondyloarthropathy; other members of this group include reactive arthritis (ReA), psoriatic arthritis (PsA), arthritis of inflammatory bowel disease (IBD), enteropathic arthritis, and axial spondyloarthritis (axial SpA). Where only peripheral joints are involved, the condition is termed peripheral SpA.
The main symptom of SpA is inflammatory back pain (IBP). This is chronic back pain that improves with activity, worsens with rest, and can cause patients to wake with back pain at night.
Inflammation in the sacroiliac joints (sacroiliitis) is universal in axial SpA.
Inflammation occurs where tendons join to bone (enthesitis). Commonly affected sites include the Achilles tendon, plantar fascia, and costal joints in SpA.
Peripheral arthritis occurs in axial SpA and usually involves large joints such as the knee, often asymmetrically.
Ankylosis, or bony fusion, of the sacroiliac joints and spinal vertebrae are the pathognomic feature of AS and other SpA.
SpA-associated conditions include skin psoriasis, IBD, and iritis.
Differential diagnosis:
The most common alternate diagnoses for chronic back pain are degenerative lumbar disc disease (spondylosis) or facet joint osteoarthritis, and lumbar disc prolapse or tear. Diffuse idiopathic skeletal hyperostosis (DISH) often resembles AS radiographically but usually does not cause marked symptoms. The differential diagnoses of sacroiliitis include DISH, osteitis condensans ilii, degenerative arthritis, and septic arthritis.
Monogenic forms:
No monogenic forms of SpA exist.
Family history:
There is often a family history of one or more of the following: spondyloarthropathy, iritis, psoriasis, or IBD.
Twin studies:
Twin studies in AS have shown that the environmental contribution to disease etiology is small; the identical twin concordance rate for the disease is greater than or equal to 60%. There is concordance among related individuals for SpA depending on the type of SpA, HLA-B27 status, and genetic relationship to the affected person (see Screening and Counseling section).
Environmental factors:
ReA is caused by an immune reaction to microbial infection. Microbial infections are also thought to underlie the development of other forms of SpA, but thus far no specific organism has been convincingly implicated. Cigarette smoking increases the severity of AS and may also increase the risk of developing the disease.
Genome-wide associations:
There have been three genome-wide association studies (GWASs) to date, one of which studied only nonsynonymous single-nucleotide polymorphisms (SNPs). These studies and other more targeted association studies have described 13 non-MHC confirmed associations. Along with the long known HLA-B association the results include SNPs in IL23R, ERAP1, CARD9, IL12B, TBKBP1, TNFR1, PTGER4, RUNX3, intergenic loci (2p15, 21q22), IL1R2, ANTXR2, and KIF21B. Some of these SNPs have also been identified in other autoimmune diseases like psoriasis and IBD.
Pharmacogenomics:
There is currently limited evidence for the role of pharmacogenomics in SpA.
Diagnostic Criteria and Clinical Characteristics
Clinical criteria
IBP
Limitation in chest expansion
Limitation in the movement of the lumbar spine
Radiographic criterion
Either bilateral grade 2 sacroiliitis or unilateral grade 3 sacroiliitis on plain film
Diagnosis requires one clinical criterion and the radiographic criterion
The Assessment of Spondyloarthritis Society (Asas) Classification Criteria for Axial Spondyloarthritis
Either
Sacroiliitis* on imaging plus one or more SpA feature**, or
HLA-B27 plus two or more SpA features**
*Sacroiliitis on imaging is defined as (a) acute (active) inflammation on magnetic resonance imaging (MRI) highly suggestive of sacroiliitis associated with SpA, or, (b) definitive radiographic sacroiliitis according to the modified New York criteria.
**SpA features are defined as 1. IBP, 2. arthritis, 3. enthesitis (heel), 4. uveitis, 5. dactylitis, 6. Psoriasis, 7. Crohn disease or ulcerative colitis, 8. good response to nonsteroidal anti-inflammatory drugs (NSAIDs), 9. family history for SpA, 10. HLA-B27, and 11. elevated C-reactive protein (CRP).
Arthritis or enthesitis or dactylitis plus
Greater than or equal to one of psoriasis, IBD, preceding infection, HLA-B27, uveitis, sacroiliitis on imaging (radiographs or MRI)
Or, two of the remaining: arthritis, enthesitis, dactylitis, IBP in the past, positive family history for SpA
Numerous sets of criteria have been published for IBP. The main features are
Morning stiffness
Improvement with exercise and not with rest
Improvement with NSAIDs
Immobility stiffness
Alternating buttock pain
Waking in the second half of the night with back pain
Diagnostic evaluation should include
History of IBP, peripheral arthritis, psoriasis, IBD, and iritis.
Physical examination, especially focused on axial spine, peripheral joints, and the skin.
Assessment of inflammatory markers included CRP and/or erythrocyte sedimentation rate (ESR).
Plain radiographs of the pelvis and spine.
HLA-B27 assessment.
There is no place for testing autoantibodies-like antinuclear antibody (ANA) or rheumatoid factor in patients with chronic back pain unless there are features suggestive of a connective tissue disease or alternate diagnosis such as rheumatoid arthritis.
Diagnostic evaluation may include
MRI of the axial spine and sacroiliac joints
Assessment and/or investigation of suspected comorbid conditions such as iritis, IBD, and psoriasis
AS is the prototypic spondyloarthritis and symptoms include IBP, peripheral enthesitis, limitation of spinal movements, and commonly a peripheral arthritis. Hip disease occurs in about 40% of AS cases, and peripheral arthritis in other joints in approximately 10% of patients; the knee is the most commonly affected, and the arthritis is usually asymmetric. Inflammation of the tendon insertions into bone (enthesitis) occurs in AS, commonly affecting the Achilles tendon, costal joints (leading to anterior chest pain), and plantar fascia of the feet. Associated conditions include iritis in approximately 40%, IBD in approximately 10%, and skin psoriasis in approximately 5%. Approximately 10% of AS patients will have clinically apparent IBD, and over 60% of SpA patients have microscopic bowel inflammation on ileocolonoscopy. Patients with AS progressively develop ankylosis of their spine and sacroiliac joints leading to a loss of movement. This loss of movement leads to a loss of function that limits activities of daily living and work. AS also commonly leads to osteoporosis, and in combination with a fused spine leads to an increased risk of spinal fracture in particular.
ReA is usually caused by either enteric or sexually transmitted infection. Chlamydia and Campylobacter are the two classic etiologic organisms, but many have been described. The actual causative organism is commonly not identified in individual patients. ReA usually manifests as an inflammatory oligoarthritis of the lower limbs. The disease course is variable with approximately one-third having a short self-limiting course of less than 6 months, one-third having a more extended course of between 6 and 24 months, and approximately one-third developing a chronic spondyloarthritis indistinguishable from AS. Having the HLA-B27 allele increases the risk of ReA to become a chronic AS-like SpA.
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