19th January 2024

Ankylosing spondylitis

Background

Definition

Axial spondylitis is classified as a chronic seronegative spondyloarthropathy, primarily involving the axial skeleton. The hallmark clinical features are inflammatory back pain and spinal stiffness, which tend to respond well to non-steroidal anti-inflammatory drugs (NSAIDS). Ankylosing spondylitis (AS) is the name given to the radiological changes in the spine and sacroiliac joints, which can result from the progressive inflammatory changes. Further progression of the disease can result in spinal fusion and subsequent severe disability. HLA-B27 is found in 90% of patients with AS. It occurs most commonly between the ages of 20 and 30 years, and is more common in men than women.

Causes and pathophysiology

The aetiology of AS is unknown, but is thought to be a result of interaction between genetic and environmental factors. The heritability is estimated at 97%. The pathophysiological processes underlying AS include inflammation, erosion, and subsequent repair of cartilage. An increased number of osteoclasts are found in the axial skeleton of patients with AS.

Presentation

AS usually presents with an insidious onset before the age of 30 years. Symptoms may be mild in early stages, with inflammatory back pain being a hallmark feature of the disease. Early morning stiffness is also characteristic. Systemic features and extra-articular manifestations are common.

Symptoms

• Inflammatory back pain:
  • Worse first thing in the morning and can awaken patient from sleep
  • Often improves with physical activity but not rest
  • Originates in sacroiliac joints
  • Can be felt as diffuse, non-specific buttock pain
  • Improves with NSAIDs
  • Can cause loss of spinal mobility
• Back stiffness
  • Usually occurs in the early morning
  • Improves with exercise
• Peripheral enthesitis:
  • Inflammation at points where tendons and ligaments attach to bones
  • Commonly affected sites: Achilles tendonitis, plantar fasciitis, tibial tuberosity
  • Painful lesions, especially in the morning
  • May be associated with swelling, stiffness, and reduced mobility
• Peripheral arthritis:
  • Usually monoarticular or oligoarticular
  • Usually asymmetrical and involves hips, shoulder joints, chest wall joints and pubic symphysis
  • Temporomandibular joints can also be affected occasionally
  • More common in females
• Extra-articular manifestations:
  • Uveitis
  • Psoriasis
  • Inflammatory bowel disease
  • Osteoporosis
  • Cardiac complications: aortic regurgitation, mitral regurgitation and non-aortic valvular heart disease, heart failure, arrhythmias, cardiovascular disease, AV node block
  • Lung complications: restrictive lung disease, apical fibrosis
  • Neurological complications: vertebral fractures, cauda equina
  • Renal complications: amyloidosis, IgA nephropathy
  • Systemic features: fatigue, sleep disturbance

Signs

• Loss of lumbar lordosis and increased kyphosis (in chronic cases) 🡪 ‘question mark posture’
• Reduced spinal flexion
  • Schober test: mark is made at 5th lumbar spinous process and 10cm above with patient in erect position. Distance should increase to 15cm on bending forwards in individuals without ankylosing spondylitis
• Pelvic and chest wall tenderness
• Sacroiliac joint tenderness
• Reduced chest expansion:
  • Signifies costovertebral joint involvement
  • Less than 2.5cm on deep inspiration measured at 4th intercostal space
• Increased tragus-to-wall distance
  • Measure of kyphosis and cervical mobility
  • Measured as the distance between tragus of the ear and the wall with patient standing with heels and back against the wall and head in the neutral position

Diagnosis 

The diagnosis of AS can be challenging, as symptoms may be diverse, and patients may present with either musculoskeletal or extra-articular complaints or both. According to NICE guidelines, AS should be suspected in patients below the age of 45 years who present with lower inflammatory back pain and stiffness lasting more than 3 months. It should also be suspected in the presence of buttock, thoracic or cervical pain, asymmetric and peripheral arthritis, enthesitis, anterior uveitis, or in those with psoriasis, inflammatory bowel disease or genitourinary infections. Symptoms typically wake patients up during the night and respond to NSAIDs. There may be a family history of AS or other spondyloarthritides. As the diagnosis can be difficult, referral to a rheumatologist is recommended.

Classifications

Modified New York criteria for ankylosing spondylitis:

The ‘Modified New York Criteria’ or the ‘Assessment of Spondyloarthritis International Society (ASAS) Classification Criteria’ can be used by rheumatologists as an aid for the diagnosis of AS.

A diagnosis of AS can be made in the presence of criterion 4 plus any one of the other criteria:

1. Low back pain of at least 3 months’ duration that is improved by exercise and not relieved by rest.
2. Limited lumbar spinal motion in sagittal and frontal planes.
3. Chest expansion decreased relative to normal values for sex and age.
4. Bilateral sacroiliitis grade 2 to 4, or unilateral sacroiliitis grade 3 or 4.

ASAS classification criteria of axial spondyloarthritis

The Assessment of Spondyloarthritis (ASAS) International Society has developed the following criteria for the classification of AS for patients under the age of 45 years, with back pain lasting more than 3 months:

Either

• Sacroiliitis on MRI or x-ray imaging
• Plus at least 1 spondyloarthritis feature from:
  • Inflammatory back pain
  • Arthritis
  • Heel enthesitis
  • Uveitis
  • Dactylitis
  • Psoriasis
  • Crohn’s/colitis
  • Good response to NSAIDs
  • Family history of spondyloarthritis
  • HLA-B27
  • Elevated C-reactive protein

or

• HLA-B27-positive
• Plus at least 2 spondyloarthritis features

Investigations

The diagnosis of AS cannot be made reliably based on a single test, and often, a number of investigations are carried out, in addition to suggestive clinical features, in order to confirm the diagnosis.

Blood tests:

• Useful for ruling out other diagnoses mimicking AS (see differential diagnoses section below).
• FBC: could reveal normocytic normochromic anaemia of chronic disease
• ESR and CRP should be checked, and may be raised in AS, although a negative result does not rule out the disease
• HLA B-27 testing can be performed in patients presenting with highly suggestive features of AS prior to referral to rheumatology
• Rheumatoid factor and antinuclear antibodies are not necessary to make a diagnosis

Image Source: Wikimedia Commons (2020). Bamboo spine ankylosing spondylitis, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Bamboo_spine_ankylosing_spondylitis.jpg (Accessed: 30 June 2021).

If X-rays are negative for sacroiliac joint involvement, but there remains a high index of suspicion for AS, an MRI should be requested. MRI may be useful in early disease to identify sacroiliitis, which would present as bone marrow oedema.

Spirometry may be useful for diagnosing restrictive lung disease in patients with apical fibrosis, kyphosis and involvement of the costovertebral joints.

Differential diagnoses 

• Osteoarthritis – presents with mechanical pain, usually worse at the end of the day and post-activity. Radiographs may show osteophytes or evidence of degenerative disease in OA.
• Diffuse idiopathic skeletal hyperostosis (DISH) – can be asymptomatic or present with back pain and stiffness worse in the morning, in patients between the ages of 50 and 75 years. Radiographs may demonstrate flowing osteophytes along anterior margin of vertebra with normal vertebral bodies and discs.
• Psoriatic arthritis – usually presents in patients between the ages of 35 and 45 years, with no preponderance for male sex. Can get unilateral sacroiliitis, and there may be a history of psoriatic skin disease. Dactylitis is more common in psoriatic arthritis. Radiographs may show erosive disease in psoriatic arthritis.
• Reactive arthritis – symptoms may be preceded by infection. Skin manifestations and dactylitis are more common in reactive arthritis. Patients usually present with urethritis and conjunctivitis in addition to arthritis. Radiographs may reveal unilateral sacroiliitis in reactive arthritis.
• Enteric arthritis – associated with inflammatory bowel disease. Peripheral joints are commonly affected, and patients may also present with extra-articular features such as erythema nodosum or pyoderma gangrenosum. Radiographs may show unilateral sacroiliitis in enteric arthritis.
• Discitis – may be accompanied with features of systemic upset, including fever, fatigue, and reduced appetite alongside back pain. MRI or X-rays can show focal spinal abnormalities, and inflammatory markers may be raised in spinal infections.
• Vertebral fractures – can be seen in patients with ankylosing spondylitis or occur in patients without the disease. Present with spinal pain and can be identified on radiographs
• Primary bone diseases or bony metastases – patients may present with signs and symptoms of the primary malignancy or systemic features such as weight loss and night sweats. Radiographs can reveal vertebral collapse or metastatic deposits in malignancy.
• Spinal stenosis – presents with bilateral pain in the buttocks or legs, which is exacerbated by standing, walking or extension of the lumbar region and relieved by bending forwards or sitting. Can also present with neurological symptoms such as numbness and tingling in the lower limbs. Lumbar spine MRI is the investigation of choice of spinal stenosis and may show disc space narrowing.

Management 

All patients with suspected AS should be referred to a rheumatologist for confirmation of diagnosis and initiation of management. The main outcomes of treatment are prevention of disease progression and control of symptoms to maintain a good quality of life for patients. The management plans should be tailored to each individual patient and take into consideration the patient’s disease activity level and degree of functional impairment. A combination of non-pharmacological and pharmacological therapies is recommended.

Non-pharmacological management

All patients should be provided with specific information regarding their disease, prognosis, likely symptoms, potential extra-articular features, and management options. Physiotherapy is essential for patients to optimise their posture, flexibility and motility and can include stretching and strengthening, spinal extension and deep-breathing exercises. Hydrotherapy can also be beneficial in pain management. Patients with AS are more prone to develop cardiovascular disease; therefore, should be routinely assessed for modifiable risk factors. Smoking has been shown to be a key predictor of spinal radiological disease progression; therefore, smoking cessation advice must be offered to patients.

Pharmacological management

• Non-steroidal anti-inflammatory drugs (NSAIDS): NSAIDs are first-line treatment for patients with pain and stiffness in active AS. The lowest effective dose should be used in conjunction with a proton pump inhibitor to minimise the risk of side effects. If NSAIDs are contraindicated, paracetamol and/or codeine can be trialled. If NSAIDs are taken at the maximum tolerated dose for 2-4 weeks and fail to provide adequate control of symptoms, NICE guidelines recommend switching to another NSAID or seeking specialist advice.
• Corticosteroid injections: Steroid injections may be offered to patients with localised inflammation, e.g. peripheral enthesitis.
• Conventional disease-modifying anti-rheumatic drugs (DMARDs): DMARDS such as Sulfasalazine and Methotrexate can be used in the presence of peripheral joint involvement but have not been shown to be effective in treating axial disease
• Biological disease-modifying anti-rheumatic drugs (DMARDs): The European League against Rheumatism (EULAR) recommends the use of anti-tumour necrosis factor (Anti-TNF) therapy for patients with persistently high disease activity, despite the optimal use of conventional therapy such as physiotherapy and NSAIDs. It can also be considered in patients with severe disease who cannot tolerate NSAIDs. Patients do not need to have received a trial of DMARDs before progressing to anti-TNF therapy. Examples of anti-TNF drugs which can be used are Adalimumab, Certolizumab pegol, Etanercept, Golimumab and Infliximab. NSAIDs should be taken in conjunction with anti-TNF inhibitors upon initiation of treatment. Treatment should be assessed after 12 weeks of initiation and only be continued if there is clear evidence of response. In patients who do not receive an adequate response to an anti-TNF medication, NICE recommends switching to another anti-TNF drug. Potential complications of anti-TNF therapy include increased risk of serious infections, malignancy such as lymphoma, worsening of heart failure and increased incidence of demyelinating disease. A baseline chest x-ray and hepatitis B and tuberculosis status should be checked before commencing treatment.

Complications

Patients with AS are at an increased risk of developing spinal fractures, cauda equina syndrome and cardiovascular disease. Patients can also suffer from adverse effects from treatment, e.g., infection, immunosuppression and malignancy resulting from long-term use of biological DMARDs.

References 

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