Spondyloarthritis

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Spondyloarthritis (SpA) is characterised by inflammation in the axial skeleton (sacroiliitis, spondylitis), peripheral joints, and entheses. Extraskeletal manifestations can occur such as anterior uveitis, psoriasis, and inflammatory bowel disease. HLA-B27 is the major genetic risk factor.

Epidemiology

The entire group of SpA has a global prevalence of 0.1% to 1.9%, with variations between countries and ethnicities. AS is the largest subgroup. The association with HLA-B27 ranges from ~50% to 95%. In the general population HLA-B27 is present in 8-10% of Caucasians. .About 5% of patients with chronic low back pain have a spondyloarthritis.

Classification

Previously SpA was viewed as consisting of interrelated subgroups that included ankylosing spondylitis (AS), reactive arthritis, or undifferentiated spondyloarthritis. The current thinking distinguishes between predominant axial SpA and predominant peripheral SpA.

Validated classification criteria exist for both axial and peripheral SpA. Sacroiliitis on MRI is an important radiological finding in classification.

The term spondyloarthritis is preferred over spondyloarthropathy due to the inflammatory nature of the condition.

Sometimes the term seronegative spondyloarthritis is used which means that the patient is negative for rheumatoid factor and anti-CCP. Unlike Rheumatoid Arthritis, the distribution of the affected peripheral joints is asymmetrical, with the large joints of the lower limbs being predominantly affected in peripheral spondyloarthritis.

Classification Criteria

Inflammatory Back Pain

The age of onset is typically under 40. They have stiffness that is worse with rest and improved with exercise. The "back" pain is typically in the buttock, and has an insidious onset. Mornings are usually the worst, and they may wake up in the second half of the night. Response to NSAIDs is the rule.

Examination findings include an abnormal Shober test, and extraarticular manifestations such as psoriasis, uveitis, and inflammatory bowel disease.

Features that aren't suggestive of inflammatory back pain are older age (>40 years), diffuse ache, abrupt onset, history of trauma, radicular symptoms, weight loss, night sweats, fever, history of cancer, worsening with exercise and in the evenings, and generalised aching. NSAID response may be moderate at best.

Criteria for Inflammatory Back Pain (IBP)
Calin criteria Berlin criteria ASAS criteria
  • Age at onset <40 yr
  • Duration of back pain >3 mo
  • Insidious onset
  • Morning stiffness
  • Improvement with exercise
  • Morning stiffness >30 min
  • Improvement with exercise, not with rest
  • Awakening at second half of the night because of pain
  • Alternating buttock pain
  • Age at onset <40 yr
  • Insidious onset
  • Improvement with exercise
  • No improvement with rest
  • Pain at night (with improvement on rising)
(at least four of five present) (at least two of four present) (at least four of five present)

Axial Spondyloarthritis

Axial spondyloarthritis is a spectrum that runs from nonradiographic axial SpA (nr-axSpA) to ankylosing spondylitis. All patients with AS start as nr-axSpA, but not all patients with nr-axSpA progress to AS.

Modified New York Criteria for AS
>1 Clinical criteria PLUS Radiographic criteria
Clinical Criteria
  • Low back pain and stiffness for >3 months which improves with exercise and not with rest
  • Limitation in spinal motion in frontal and saggitalplanes
  • Limitation of chest expansion compared to norms for age and gender
Radiographic Criteria
Radiographic sacroiliitis >Grade 2 bilaterally or >Grade 3-4 unilaterally
ASAS Classification Criteria For Axial Spondyloarthritis
In patients with back pain ≥ 3 months and age at onset < 45 years
Sacroiliitis on imaging*

plus
≥1 SpA feature†

or HLA-B27

plus
≥2 other SpA features†

SpA features†: Sacroiliitis on imaging*:
  • Inflammatory back pain
  • Arthritis
  • Enthesitis (heel)
  • Uveitis
  • Dactylitis
  • Psoriasis
  • Crohn disease or ulcerative colitis
  • Good response to NSAIDs
  • Family history of SpA
  • HLA-B27
  • Elevated CRP
  • Active (acute) inflammation on MRI highly suggestive of sacroiliitis associated with SpA

or

  • Definite radiographic sacroiliitis according to modified New York criteria
*Sensitivity 82.9%, specificity 84.4%; n = 649 patients with chronic back pain and age at onset <45 years. Imaging arm (sacroiliitis) alone has a sensitivity of 66.2% and a specificity of 97.3%.

†Elevated CRP is considered an SpA feature in the context of chronic back pain.

Peripheral Spondyloarthritis

ASAS Classification Criteria for Peripheral Spondyloarthritis
Arthritis* or enthesitis or dactylitis
Plus ≥ 1 of or Plus ≥ 2 of the remaining:
  • Psoriasis
  • Inflammatory bowel disease
  • Preceding infection
  • HLA-B27
  • Uveitis
  • Sacroiliitis on imaging (radiographs or MRI)
  • Arthritis
  • Enthesitis
  • Dactylitis
  • IBP in the past
  • Positive family history
  • of SpA
*Peripheral arthritis: usually predominantly lower limb and/or asymmetric arthritis.

IBP: inflammatory back pain.

Clinical Features

There is a predilection for the axial skeleton and entheses. Sacroiliitis is the cardinal sign. HLA-B27 confers a genetic risk. Clinical manifestations are inflammatory low back pain, stiffness, and a late finding of limitation of spinal range of motion.

Extraarticular manifestations are acute anterior uveitis, psoriasis, and inflammatory bowel disease.

Peripheral features include asymmetrical, oligoarticular, lower limb predominant arthritis +/- enthesitis (e.g. plantar fasciitis, insertional Achilles tendonitis). This is compared to small joint symmetrical arthritis in Rheumatoid Arthritis.

The assessment includes

  • Disease activity: BASDAI and bloods
  • Structure: X-ray/MRI and DEXA
  • Function: BASFI
  • Movement: BASMI

Imaging

Plain film radiographic features are more typical of later stage disease, however MRI can detect early disease.

Radiologic features of ankylosing spondylitis include

  • Sacroiliac joint: erosions, ankylosis, juxtaarticular osteopenia, ossification of the ligamentous attachment to the ischial tuberosity or iliac crest or the greater trochanter
  • Spine: erosions at vertebral corners (shiny corners), squaring of the vertebral bodies (Romanus lesion), syndesmophytes, ossification of the annulus fibrosus and longitudinal ligament, erosions of the discovertebral junction, calcification of the intervertebral discs, pseudoarthrosis, and bone oedema especially if juxaarticular

MRI is the gold standard for assessment of inflammatory changes in the SIJ and spine.

Definitions of what constitutes a positive MRI of the SIJ and spine have been published by ASAS.

MRI findings in the SIJ of patients with AS
Tissue Inflammatory Changes Structural Changes
Bone marrow Sacroiliitis (bone marrow edema or

osteitis) in one or both parts of

the SI joint (sacral or iliac)

Subchondral sclerosis

Erosions

Fatty deposition

Bone bridges or ankylosis

Bone marrow edema related to SpA

is located periarticularly

Synovium Synovitis: depicted only by T1/

Gd-DTPA sequences; STIR

sequences cannot differentiate

between synovitis and physiologic

joint fluid; synovitis is a rare lesion

Bone bridges or ankylosis
Joint capsule Capsulitis: comparable to synovitis;

both anterior and posterior joint

capsule can be affected

Bone bridges or ankylosis
Ligaments Enthesitis: seen in the junction of

ligaments and tendons to the bone

Degeneration of ligament
MRI findings in the spine of patients with AS
Tissue Inflammatory Changes Structural Changes
Vertebral body Inflammation (spondylitis) in the bone marrow, mainly in the corners New bone formation

(syndesmophytes, ankylosis),

eventually erosions or destruction of

the vertebral body (e.g., fracture)

Fatty degeneration

Intervertebral disc Inflammation

(spondylodiscitis)

Ossification of the disc
Facet and

costovertebral

joints

Inflammation with or

without involvement

of the vertebral body

New bone formation and ankylosis in

advanced stages

Ligaments Enthesitis, mainly of

the supraspinal and

interspinal ligaments

Degeneration of ligaments

Management

Early diagnosis is essential for good outcomes, the average delay in diagnosis is 9 years. Obstacles that cause a delay are patient behaviour, chronic low back pain being extremely common, poor awareness, reliance on plain films in early disease, non- or misuse of HLA-B27.

Physiotherapy plays a role in restoring and maintaining posture and movement. Home exercises must be continued for life. Exercise is critical at all stages and the patient should be referred early.

Medical management for both axial and peripheral spondyloarthritis includes NSAIDs, anti-TNFα drugs (adalimumab, etanercept, infliximab), and more recently IL-17 inhibitors.

The response to NSAIDs is almost 80% in AS vs ~15% in mechanical back pain, and they may reduce radiographic progression with continuous use.

For peripheral but not axial spondyloarthritis sulfasalazine and methotrexate may play a role as DMARDs, but not for axial disease. Local corticosteroid injections can be useful in oligoarticular forms of arthritis.

Core Readings

  • Ehrenfeld. Spondyloarthropathies. Best practice & research. Clinical rheumatology 2012. 26:135-45. PMID: 22424199. DOI.
  • Dougados & Baeten. Spondyloarthritis. Lancet (London, England) 2011. 377:2127-37. PMID: 21684383. DOI.
  • Taurog et al.. Ankylosing Spondylitis and Axial Spondyloarthritis. The New England journal of medicine 2016. 374:2563-74. PMID: 27355535. DOI.
  • Sieper. Developments in therapies for spondyloarthritis. Nature reviews. Rheumatology 2012. 8:280-7. PMID: 22487798. DOI.
  • Braun et al.. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Annals of the rheumatic diseases 2011. 70:896-904. PMID: 21540199. DOI. Full Text.