Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy and a chronic inflammatory disease of the axial skeleton that leads to partial or complete fusion and rigidity of the spine. It is a part of a spectrum of inflammatory spondyloarthropathies known as axial spondyloarthritis and can also be referred to as radiographic axial spondyloarthritis. Males are disproportionately affected and > 90% of patients are positive for HLA-B27, which is a predisposing factor for the disease. Pain and stiffness in the lower back and neck, caused by inflammation of the vertebral column and the sacroiliac joints, are characteristic early features of AS. Pain typically improves with activity and is particularly prominent at night. Other articular findings include restricted spine mobility and tenderness of the sacroiliac joints on provocation tests, such as the FABER test. The most common extraarticular manifestation is acute, unilateral anterior uveitis. Kyphosis and fusion of the costovertebral joints can cause restrictive lung disease. Diagnosis is primarily based on typical clinical features, elevated inflammatory markers, HLA-B27 positivity, and evidence of inflammatory changes and ankylosis of the sacroiliac ( ) and/or intervertebral joints ( ) on imaging. Typical features may be absent on imaging in early AS, but the presence of several classical clinical and laboratory features is sufficient to confirm the diagnosis and initiate treatment. There is no curative treatment for AS, but regular physiotherapy can slow disease progression. includes NSAIDs and/or TNF-α inhibitors (e.g., infliximab, adalimumab, etanercept). In severe cases, surgery (e.g., arthroplasty) may be considered to improve the patient's quality of life. Patients with AS are at an increased risk of osteoporosis and pathological fractures ( ). Axial spondyloarthritis also includes nonradiographic axial spondyloarthritis, a condition that causes similar symptoms to AS but without inflammatory changes on plain radiographs. Management of nonradiographic axial spondyloarthritis is the same as for AS.
- Axial spondyloarthritis 
- Ankylosing spondylitis (radiographic axial spondyloarthritis; AS) 
- Nonradiographic axial spondyloarthritis (nr-axSpA) 
- Genetic predisposition: 90–95% of patients are HLA-B27 positive.
- Initiation of innate immune response 
- Release of cytokines (TGF-beta and TNF-α) and interleukins (IL-17 and IL-23)
- Infiltration of paravertebral and sacroiliac entheses with macrophages, CD4 T cells, and CD8 T cells
- Chronic enthesitis leads to:
- Features of (most common presenting symptom) 
- Tenderness over the sacroiliac joints (SIJ)
- Reduced spinal mobility
- Extraspinal joint pain
- Acute, unilateral (most common extraarticular manifestation; ∼ 25% of patients)
- Constitutional symptoms such as fatigue , weakness, fever, and weight loss
- Restrictive pulmonary disease
- Gastrointestinal symptoms: due to associated chronic IBD (∼ 5–10% of patients)
- Aortic root inflammation and subsequent aortic valve insufficiency, atrioventricular blocks 
- IgA nephropathy (rare)
Positive SIJ pain provocation tests
FABER test 
- Assessed with the patient in the supine position
- The leg to be tested is placed in a figure-4 position, with the patient's ankle placed on the contralateral knee.
- Apply pressure on the patient's flexed knee.
- Pain will be felt in the ipsilateral SIJ if inflammation is present.
Mennell sign 
- Prone position: Lift the leg passively (i.e., extend the hip) with one hand while applying pressure on the ipsilateral SIJ with the other hand.
- Lateral position
- Supine position: Apply posteriorly directed pressure to the anterior superior iliac spines.
Reduced spinal mobility 
A bedside examination to assess lumbar forward flexion
- With the patient standing, the examiner marks two points on the patient's back: one at L5 and one 10 cm above. 
- The patient is asked to touch their toes without bending their knees.
- An increase of < 4 cm between the two points suggests impaired spine flexion.
- The patient is asked to stand with their back against the wall with hands by the side and flex as far as possible to one side without bending their knees.
- The distance between the tip of the patient's middle finger and the floor is measured on the ipsilateral side.
- A larger fingertip-to-floor distance indicates limited spinal mobility.
Chest expansion on deep breathing
A bedside examination to assess thoracic spine mobility 
- Measure the chest circumference after maximal expiration and again after maximal inspiration.
- A smaller difference in measurements (< 2.5 cm) indicates limited thoracic spine and costovertebral joint mobility. 
- Reduced chest expansion can also be due to concomitant pulmonary disease, chest wall deformities, or poor respiratory effort.
Kyphosis due to loss of anterior vertebral height and wedging of the thoracic vertebrae is present in up to 50% of patients, especially those with advanced AS. The extent of the deformity may be subtle and is assessed using the occiput-to-wall distance.
- Ask the patient to stand against a wall with their heels, buttocks, and shoulders pressed against the wall.
- Measure the distance between the occiput and the wall.
- In a healthy individual, the occiput should be touching the wall; the inability to do so is considered abnormal.
- Suspect AS in patients < 45 years of age who present with features of lasting > 3 months.
- Initial test in all individuals with suspected AS: x-ray of the sacroiliac joints
- HLA-B27 positive
- HLA-B27 negative
- Consider imaging of the spine in patients with pain in the cervical, thoracic, or lumbar spine.
- Further workup for associated conditions may be appropriate depending on extraarticular manifestations.
Diagnostic criteria 
There are several diagnostic criteria for AS (e.g., New York criteria, Rome criteria). The Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis, which is based on a combination of clinical features and imaging or laboratory findings, is detailed here.
- Lower back pain for > 3 months in patients < 45 years of age and one of the following:
- Clinical and laboratory findings used in the diagnostic criteria for AS include:
- Articular manifestations: dactylitis, arthritis ,
- Extraarticular manifestations: enthesitis (may present with heel pain), uveitis, IBD, psoriasis
- Patient history
- Laboratory findings: positive for HLA-B27; ↑ CRP and/or ESR
- CRP and ESR are typically elevated.
- HLA-B27: Positive in 90–95% of patients with axial spondyloarthritis 
- Autoantibodies (e.g., rheumatoid factor, antinuclear antibodies) are negative
- CBC: may show anemia 
Sacroiliac joints (PA view) 
- Indication: best initial test to confirm the diagnosis of AS and evaluate disease severity
- Characteristic findings (usually symmetrical)
- Loss of lumbar lordosis: abnormal straightening of the spine
- Ankylosis of costosternal and costovertebral joints
- Dagger sign
- Bamboo spine: seen in later stages and is caused by the following
- Shiny corners sign: reactive sclerosis of the superior and inferior margins of vertebrae
Early stages of AS may be unidentifiable on x-ray (low sensitivity for early-stage). Hence, a patient with several classical clinical and laboratory findings fulfills the diagnostic criteria for AS even if x-ray findings are inconclusive. 
MRI is the most sensitive method for early detection of inflammatory changes of AS. However, MRI is not routinely required to confirm a diagnosis of AS as specialized MRI techniques and radiology expertise is required to accurately identify AS findings. 
Sacroiliac joints with gadolinium contrast
- Indication: negative or equivocal radiographs of sacroiliac joints in a patient with some classical features of AS 
- Characteristic findings
Spine without contrast
- Indications: suspected AS in a patient with any of the following
- Characteristic findings 
CT sacroiliac joints and/or spine
- Findings: bone erosions, reparative changes
Further evaluation for extraarticular disease
|Symptom-based workup for extraarticular manifestations|
|Extraarticular complication||Characteristic clinical features||Recommended diagnostic studies and characteristic findings|
|Restrictive lung disease|
|Inflammatory bowel disease|
|Aortic root and valve disease |
|Atrioventricular blocks |
|IgA nephropathy|| |
- Other (e.g., reactive arthritis, psoriasis arthritis, arthritis associated with inflammatory bowel disease)
- Mechanical low back pain
- Disk prolapse
- Vertebral osteomyelitis
- Osteophytes of the spine 
- See also “ .”
Diffuse idiopathic skeletal hyperostosis (DISH; also called Forestier's disease or hyperostotic spondylosis): degenerative disease of the vertebral column (especially the thoracic and lumbar spine), which is characterized by calcification and ossification of spinal ligaments and entheses
- Not related to HLA-B27 
- May be asymptomatic or present with limited spinal mobility
- Back pain may be absent or mild
- Mostly affects men and is more common in patients with diabetes
- X-ray of the spine : osteophytes may be present (see table below); no evidence of sacroiliitis
- Treatment is primarily symptomatic
|Syndesmophytes vs. osteophytes|
The differential diagnoses listed here are not exhaustive.
- Early referral to rheumatology is recommended in all patients with suspected or confirmed AS.
- Ensure all patients receive supportive therapy.
- Assess symptom severity.
- Manage extraarticular complications and associated diseases accordingly.
- The management of Nr-axSpA is similar to AS.
All patients with AS, regardless of the disease stage, should receive appropriate supportive therapy to improve their mobility and prevent complications.
- Provide regular physical therapy to maintain range of motion and posture 
- Refer patients for:
- Fall evaluation and counseling
- Group or individual patient education on self-management
- Encourage smoking cessation. 
- Screen and treat patients for osteoporosis. 
- Advise patients with severe osteoporosis or spinal fusion to avoid spinal manipulation.
Management of active disease
- First-line pharmacotherapy in most patients: NSAIDs
- Second-line : TNF-α inhibitors (e.g., etanercept, adalimumab).
- Alternative therapies (e.g., DMARDs such as sulfasalazine, intraarticular glucocorticoids): Consider in patients with significant peripheral disease or insufficient response to first-line therapies.
|Pharmacological therapy in ankylosing spondylitis |
|Medication class||Indications||Dosage and administration||Cautions|
|NSAIDs|| || || |
|Local parenteral glucocorticoids|| |
Advanced therapeutic options 
- Tofacitinib ( ): Consider in patients who do not respond to NSAIDs, TNF-α inhibitors, or antiinterleukin-17 antibodies.
Management of stable disease 
Patients with AS may have stable disease at diagnosis or following management of active disease.
- NSAIDs as needed for pain relief (see “Oral analgesics” for agents and dosages)
- Biological agents may need to be continued indefinitely if there is adequate symptom control.
Monitoring treatment response 
- Treatment efficacy should be assessed by a physician.
- Treatment response can be assessed based on the impact of symptoms on quality of life and the trend of inflammatory markers and imaging findings.
- In patients with stable AS, regular follow-up imaging is not recommended.
Management of acute pain 
Spinal fractures can occur following minor trauma, e.g., a fall from standing, or even spontaneously.
- Initiate spinal precautions; however, avoid cervical collars and maintain the patient's preinjury spinal alignment.
- Perform a full neurovascular examination.
- Order imaging to assess for fractures; consider CT or MRI as the initial modality.
- If a fracture is confirmed, consult a spinal surgeon urgently; stabilization via spinal fusion is typically required.
- Complete fusion of the spine → severely limited mobility
- Increased risk of osteoporosis; → pathological fractures and possibly spinal cord injury
- Chalk stick fractures: transverse fractures through the fused spinal column caused by reduced flexibility due to a fused spine and osteoporosis
- Restricted chest expansion and spine mobility → breathing difficulties
- Lungs: fibrosis of upper lobes (apical fibrosis) 
We list the most important complications. The selection is not exhaustive.