A comprehensive, full-body evaluation should be performed in patients suspected of having AS due to the pervasive nature of the disease and susceptibility to multi-organ system involvement. Almost all patients will complain of back pain to some degree. The characteristic type of back pain in AS is "inflammatory" in nature. Inflammatory back pain typically exhibits at least four of the five following characteristics: age of onset less than 40 years, insidious onset, improvement with exercise, no improvement with rest, and pain at night with an improvement upon arising. Spinal stiffness, immobility, and postural changes, especially hyperkyphosis, are also commonly seen. History and physical exam should address all systems, as AS can have several axial and peripheral musculoskeletal manifestations, as well as extra-articular features. A detailed medical history should be obtained to rule in/out any correlated conditions (e.g., psoriasis, IBD, uveitis, among others).

Laboratory findings in AS are generally nonspecific but may help assist with diagnosis. About 50% to 70% of patients with active AS have elevated acute phase reactants, such as erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP). A normal ESR and CRP, however, should not exclude the disease.[7][8][9]

A number of imaging abnormalities, especially those affecting the spine and sacroiliac joints, are characteristic of AS. In fact, according to the Assessment of Spondyloarthritis International Society (ASAS) 2009 axial SpA criteria, evidence of sacroiliitis on imaging (radiographic or MRI) is a major inclusion criteria for AS. A standardized plain radiographic grading scale exists for sacroiliitis, which ranges from normal (0) to most severe (IV), as detailed below.

• 0: Normal SI joint width, sharp joint margins
• I: Suspicious
• II: Sclerosis, some erosions
• III: Severe erosions, pseudo dilation of the joint space, partial ankylosis
• IV: Complete ankylosis

In the first few years of AS, plain radiographic changes in the SI joints can be very subtle, but within the first decade will usually become more obvious. Subchondral erosions, sclerosis, and joint fusion are the most obvious abnormalities, and these radiographic changes are typically symmetric.

A series of plain radiographic changes characteristic of AS can progressively develop over the course of the disease. An early sign is "squaring" of the vertebral bodies, best seen on lateral x-ray. This is seen as a loss of normal concavity of the anterior and posterior borders of the vertebral body due to inflammation and bone deposition. Romanus lesions, or the "shiny corner sign," can also be seen on this radiographic view in early stages. These lesions are characterized by small erosions and reactive sclerosis at the corners of the vertebral bodies. Late-stage findings include ankylosis (fusion) of the facet joints of the spine, syndesmophytes, and calcification of the anterior longitudinal ligament, supraspinous ligaments, and interspinous ligaments. This calcification may be seen on imaging as the "dagger sign," which is represented as a single radiodense line running vertically down the spine on frontal radiographs. The classic radiographic finding in late-stage AS is the "bamboo spine sign," which refers to the vertebral body fusion by syndesmophytes. A bamboo spine typically involves the thoracolumbar and/or lumbosacral junctions. It is this fusion of the spine that predisposes the patient to progressive back stiffness.

While plain radiography is the first-line imaging modality in AS, MRI may be needed to reveal more subtle abnormalities such as fatty changes and/or inflammatory changes. Active SI joint inflammatory lesions appear as bone marrow edema (BME) on short tau inversion recovery (STIR) and T2-weighted images with fat suppression. It should be noted that the presence of BME on MRI can also be seen in up to 23% of patients with mechanical back pain and 7% of healthy people.[10]

Treatment goals should focus on relieving pain and stiffness, maintaining axial spine motion and functional ability, and preventing spinal complications. Non-pharmacologic interventions should include regular exercise, postural training, and physical therapy. First-line medication therapy is with long-term, daily non-steroidal anti-inflammatory drugs (NSAIDs). Should NSAIDs not provide adequate relief, they can be combined with or substituted for tumor necrosis factor inhibitors (TNF-Is) such as adalimumab, infliximab, or etanercept. Response to NSAIDs should be assessed 4 to 6 weeks after initiation and 12 weeks following initiation of TNF-Is. Systemic glucocorticoids are not recommended, but local steroid injections may be considered. Specialist referrals may be warranted based on the patient's clinical picture, potential complications, and/or extra-articular manifestations of the disease. Rheumatologists may assist in a formal diagnosis, management, and monitoring, while dermatologists, ophthalmologists, and gastroenterologists may assist with associated non-musculoskeletal features of AS.[11][1][12]

Certain diseases and conditions can mimic AS and must be ruled out. These include, but are not limited to, mechanical low back pain, lumbar spinal stenosis, rheumatoid arthritis, and diffuse idiopathic skeletal hyperostosis (DISH). Each of these diagnoses has similarities with AS, but their differences should be ruled in or out for accurate diagnosis. 

Mechanical back pain can be differentiated from AS by the onset of symptoms, as mechanical back pain can present at any age, while AS typically presents before age 40. Unlike AS, pain improves with rest, and morning stiffness is mild and short-lived. Mechanical back pain is also not associated with peripheral arthritis or extraskeletal manifestations, as AS is.

Lumbar spinal stenosis (LSS) is a narrowing of the spinal canal that exerts pressure on the spinal cord. Like AS, it may present with chronic back pain and morning stiffness. Unlike AS, however, LSS usually presents in patients older than 60 years, is not associated with peripheral arthritis or extraskeletal features, and response to NSAIDs is variable.

Rheumatoid arthritis (RA) is another chronic inflammatory disorder of the joints that often presents with progressive back pain and morning stiffness in patients 40 or younger, similar to AS. However, peripheral arthritis is extremely common in RA, unlike in AS. In addition, rheumatoid nodules are pathognomonic for RA but are not usually present with AS.

Diffuse idiopathic skeletal hyperostosis (DISH) is a degenerative disorder characterized by ossification in the spine occurring primarily in the anterior longitudinal ligament, paravertebral tissues, and peripheral aspect of the annulus fibrosus. Similar to AS, the DISH may present with a history of postural changes and back pain. Unlike AS, which is an inflammatory disorder, the DISH does not have inflammatory characteristics such as morning stiffness or improvement with exercise but not with rest. DISH also shows no evidence of sacroiliitis on radiographs.

While the younger age of onset in AS patients is associated with poorer function outcomes, severe physical disability is uncommon. Most patients remain fully functional and able to work. Patients with severe, long-standing disease have greater mortality compared with the general population, predominantly due to cardiovascular complications.

• Chronic pain
• Disability
• Aortic regurgitation
• Pulmonary fibrosis
• Cauda Equina syndrome
• Mood disorders

To remain functional, physical therapy is highly recommended. Both water therapy and swimming are known to help maintain fitness and lower the morbidity.

Pitfalls: The possibility of vertebral fracture should always be considered in patients with AS, even after minor trauma. Patients with AS are at increased risk of vertebral fracture and subluxation, especially of the cervical spine. Therefore, these patients are more susceptible to neurologic compromise.

Prevention of disease morbidity can be achieved with exercise, physical therapy, tailored pharmacologic intervention, and regimented follow-up appointments with physicians.

Ankylosing spondylitis is a systemic disorder that can affect many organ systems and hence an interprofessional team approach is recommended to avoid the morbidity. 

• Rheumatologist to evaluate and manage the acute symptoms and address any coexisting spondyloarthropathies.
• Gastroenterologist to assess for inflammatory bowel disease
• Ophthalmologist to assess for anterior uveitis
• Cardiologist to assess for heart block or valvular involvement
• Physical therapy to help with function
• Neurologist to assess for nerve compression syndromes
• Pharmacist to monitor for drug interactions and dependence on analgesics
• Nurse to educate the patient on the management of daily living activities

There are many reports indicating that an interprofessional approach to ankylosing spondylitis can improve function, lower pain and increase the quality of life. [13][14] (Level II)

Evidence-based Medicine

Meta-analysis of many studies has revealed that those who participate in an exercise program have a much better outcome than those who lead a sedentary lifestyle. (Level II) Unfortunately, those patients with large symptom burden at the time of diagnosis usually have poor response rates and are often lost to follow up. One way to retain these patients is by starting an education program early in the disease.  [15][16][17](Level V)