Ankylosing spondylitis (AS) is a chronic inflammatory disease that belongs to the spondyloarthritis family (Table 1). It mainly affects the sacroiliac joints, spinal prominences, paraspinal soft tissues and peripheral joints, and may be accompanied by extra-articular manifestations, and in severe cases, spinal deformity and ankylosis.
AS imposes a tremendous burden on both patients and society. For most patients, osteoporosis can cause vertebral fractures or hunchbacks, and inflammation of the sacroiliac joints and spine can eventually lead to bone ankylosis, both of which result in decreased function of the patient’s body and can be combined with psychological disorders such as anxiety and depression. These further result in the need for assistance at work, increased sick leave, and even loss of ability to work. In addition to this, patients are also required to spend high amounts of medical resources. It is important to note that the burden of the disease increases with the duration of the disease. Therefore, early diagnosis and treatment are essential to improve the prognosis.
Sacroiliac joint imaging changes are the hallmark of AS and occur in 90% of patients. In clinical practice, patients with a clinical diagnosis of AS often require further confirmation of the diagnosis supported by abnormal sacroiliac joint radiographs. In fact, many people consider AS to be symptomatic sacroiliac arthritis. However, although sacroiliac joint radiographic abnormalities are common, they are not an early manifestation. Other conditions in the classification criteria (Table 2) (e.g., limited lumbar motion, decreased thoracic mobility) also do not occur early in the disease. Therefore, most patients start in their 20s, but the average time to diagnosis takes 6-8 years.
Acute sacroiliac joint inflammatory manifestations on MRI can predict sacroiliac arthritis on late radiographs. Patients with early typical AS presentation may not have clear radiographic sacroiliac joint abnormalities, and therefore this population may be excluded from the diagnosis of AS. However, further MRI performed may reveal sacroiliac joint inflammation. Based on these clinical findings, the Assessment of SpondyloArthritis International Society (ASAS) proposed nonradiographic axial spondyloarthritis, The criteria for the classification of axial spondyloarthritis are detailed in Table 3. nr-axSpA covers patients with inflammatory low back pain for 3 months and an age of onset <45 years who meet both imaging abnormalities (MRI or X-ray) and ≥1 SpA feature or HLA- B27 positive and ≥2 SpA features. the study of ASAS found that 30% of patients with a definite diagnosis of mid-axis SpA were diagnosed with AS due to abnormal sacroiliac joint X-rays, and the remaining 2/3 of patients were diagnosed with nr-axSpA. interestingly, the pain level and disease burden of nr-axSpA were comparable to AS, and the earlier the patient received biologic therapy, the better the clinical outcome, and early axSpA has a lower relapse rate after drug discontinuation than patients with long disease duration. Therefore, AS and nr-axSpA currently follow the same treatment process and principles.
Low back pain is an extremely common clinical manifestation in daily practice, occurring in 80% of the population. The inflammatory low back pain of AS is different from the mechanical low back pain, which is not well recognized in clinical practice. Some of the features of inflammatory low back pain are shown in Table 4, which should be more alarming in HLA-B27-positive patients with a family history of AS disease. The ASPECT study (Ankylosing Spondylitis Patients Epidemiological Cross-section Trial) found that only 58% of patients with AS had no extra-articular manifestations, and 22% had combined uveitis, which can involve the lungs, bones, and kidneys. Uveitis, in particular, is prone to recurrence, as conventional treatment only controls symptoms and does not suppress the underlying inflammation. If not adequately treated, the disease may progress to anterior chamber pus accumulation, iris adhesions, cataracts, glaucoma, and even blindness.
Intervention in the first 10 years of disease onset is critical for prognosis. The following 7 areas are indicative of severe disease if present within 2 years of follow-up: hip osteoarthritis, ESR >30 mm/H, poor response to NSAIDs, lumbar spine restriction, waxy fingers (toes), monoarthritis, and onset <16 y. The goal of AS treatment is to reduce pain, morning stiffness, and fatigue; maintain good posture, physical function, and psychological function. Patient education (a comprehensive description of the disease) is the basis for patient compliance. Prone lying for 15-30 min several times a day can reverse the tendency to hunchback. Sleeping on a hard bed with a low pillow on the head is required during the day. Exercise is the key to treatment and 3 hours of hydrotherapy, exercise and physical activity twice a week is recommended. Hot water baths are best. Patients should avoid strenuous or impact sports, as there is a high risk of fracture if the spine is fused or osteoporotic. It is important to note that home exercise is preferable to no exercise and guided group exercise is preferable to individual exercise. Patient associations and self-help groups can provide important information and social support.
Long-term administration of NSAIDs improves spinal mobility, acute chronotropic protein, and radiographic progression. There is no evidence to suggest who is better or worse. If adequate treatment is not effective, switch, but do not use 2 or more NSAIDs in the same period. Selective COX-2 inhibitors may be used in patients at risk for gastrointestinal bleeding who require long-term dosing. There is no evidence to support the effectiveness of DMARDs drugs in mid-axis joint involvement, including salazosulfapyridine and methotrexate, of which salazosulfapyridine may be used as a treatment for peripheral arthritis. If NSAIDs are ineffective, anti-TNF inhibitors should be added for significant mid-axis joint involvement, and local glucocorticoid injections and DMARDs (recommended for salbutamol) should be adequately treated for predominant peripheral joint involvement; if still ineffective, anti-TNF inhibitors should be considered. Monoclonal anti-TNF inhibitors should be preferred for severe extra-articular manifestations such as recurrent iritis, otherwise there is no advantage or disadvantage. One biologic agent is ineffective and may be switched to another. Vigilance against infection, especially the risk of tuberculosis, is required during use. Acute uveitis can be treated with hormonal spotting to reduce inflammation and pupil dilation, and atropine to prevent and reduce iris adhesions. patients need to be informed at the onset of AS that acute uveitis can occur at any stage of the disease. Hip involvement is a poor prognostic indication, and total hip replacement is feasible in advanced stages without consideration of age and with good surgical results.
In conclusion, paying attention to early clinical symptoms such as inflammatory low back pain, performing sacroiliac joint MRI in suspected patients, and raising awareness of nr-axSpA are the basis for timely diagnosis and early treatment of AS patients. In addition to pharmacological treatment, patient education and reasonable functional exercise should be emphasized, and long-term follow-up by rheumatologists is needed to improve patients’ prognosis and quality of life.
Appendix.
Table 1. spectrum of spondyloarthritis diseases.
Medial spondyloarthropathy; peripheral spondyloarthropathy; ankylosing spondylitis; medial spondyloarthropathy without radiological changes; reactive arthritis; psoriatic arthritis; inflammatory bowel disease arthritis; undifferentiated spondyloarthropathy.
Table 2. revised New York criteria for ankylosing spondylitis (1984).
Clinical criteria.
1, Low back pain for at least 3 months, relieved by activity but not by rest.
2. Restricted lumbar spine motion in the frontal and sagittal planes.
3. Thoracic mobility is lower than that of a normal person of corresponding age and sex.
4. Bilateral sacroiliac arthritis grade 2 to 4.
5. Unilateral sacroiliac arthritis grade 3 or 4.
Definite ankylosing spondylitis.
Unilateral grade 3 or 4, or bilateral grade 2 to 4 x-ray sacroiliac arthritis, plus at least 1 clinical criterion.
Table 3. New criteria for ASAS diagnosis of mid-axis SpA: low back pain for ≥3 months, age of onset <45 years.
Imaging evidence of sacroiliac arthritis.
≥1 SpA feature or HLA-B27 positivity.
≥2 SpA features.
SpA features.
1, inflammatory low back pain.
2, arthritis.
3.Tendonitis (heel).
4.Finger/toe inflammation.
5.Ocular uveitis.
6.Psoriatic rash.
7, Crohn’s disease/ulcerative colitis.
8, Good response to NSAIDs.
9, Family history of SpA.
10, HLA-B27 positive.
11, Elevated CRP levels.
Imaging sacroiliac arthritis.
MR shows active (acute) inflammation, highly suggestive of SpA-related sacroiliac arthritis, or definite X-ray sacroiliac arthritis as defined by the Revised New York Criteria.
Sensitivity 82.9%, specificity 84.4%, number of cases studied 649.
Table 4. Characteristics of inflammatory low back pain in ankylosing spondylitis and medial spondyloarthropathies 1, Onset before 45 years of age.
2, Chronic low back pain (symptoms persist for >3 months).
3.The pain is located in the lower back.
4, Alternating hip area pain.
5.Waking up with pain at night.
6.Morning stiffness greater than 30 minutes.
7.Incognito onset.
8.Relievable after activity.
9.No improvement after rest.
10.Effective for NSAIDs drugs.
Other features that contribute to the diagnosis of AS: synovitis (lower extremity, asymmetrical); attachment pointitis (heel, sole); acute anterior uveitis, etc.
Table 5. Treatment recommendations for ankylosing spondylitis.
Overall goals of AS treatment: control of inflammation, delay of radiological changes (structural destruction), improvement and enhancement of patient quality of life.
The clinical presentation is diverse and requires multidisciplinary collaboration.
The treatment strategy should be based on a joint decision of the patient and the rheumatologist, with a combination of pharmacological and non-pharmacological treatments.
1. General treatment.
The treatment plan should be tailored to the patient’s
Current disease manifestations (mesial joints, peripheral joints, attachment points, extra-articular symptoms and signs), extent of lesions and factors affecting prognosis.
General clinical characteristics (age, gender, comorbidities, combined medications, and psychiatric factors)
2. Disease monitoring.
Including medical history, clinical indicators, laboratory indicators and imaging examinations (all with reference to clinical manifestations and ASAS core indicators), the frequency of monitoring should be individualized based on disease progression, severity and treatment options.
3. Non-pharmacological treatment.
The cornerstones of nonpharmacologic treatment are patient education and regular exercise; home exercise is preferable to no exercise, guided group exercise is preferable to individual exercise, and patient associations and self-help groups may be helpful.
4. Extra-articular manifestations and comorbidities.
Extra-articular manifestations need to be treated in cooperation with the appropriate specialist (e.g., iritis, etc.), and increased cardiovascular and osteoporosis risks need to be guarded against.
5. NSAIDs drugs.
First-line treatment for joint pain and morning stiffness in patients with AS, should be used long-term for patients with active AS and on-demand for patients with stable AS.
Cardiovascular, gastrointestinal and renal related risks need to be considered.
6. Analgesics.
Paracetamol and opioids may be used as alternative analgesics in cases where the recommended regimen is ineffective or contraindicated or difficult to tolerate.
7. Glucocorticoids.
Local inflammation of musculoskeletal can be considered glucocorticoid local injection, there is no evidence to support the systemic use of hormones.
8. DMARDs drugs.
There is no evidence to support the effectiveness of DMARDs drugs in medial joint involvement, including salazosulfapyridine and methotrexate. Salicyclovir can be used as a treatment for peripheral arthritis.
9. Anti-TNF inhibitors.
Anti-TNF inhibitors should be added for those who fail to respond to treatment with NSAIDs*.
Patients with no evidence to support a mid-axis lesion should be treated with DMARDs before or concurrently with anti-TNF therapy.
There is no current priority for medication for mid-axis arthritis, peripheral arthritis, and adhesions, but those with extra-articular manifestations of involvement (e.g., recurrent iritis) may be interchanged when mono-antibiotics are superior to receptor fusion proteins are ineffective.
10. Surgical treatment.
Total hip arthroplasty should be considered for those with intractable pain or dysfunction and structural damage on imaging, without age consideration.
Severe deformities such as severe kyphosis can be treated with selective spinal osteotomy.
Patients with AS who present with vertebral fractures need to be consulted by a spine surgeon.
Determination of ineffectiveness of NSAIDs treatment*: 1 NSAIDs full dose for 4 weeks or 2 NSAIDs full dose successively for a total of 4 weeks is ineffective or intolerable, or contraindicated. Ineffective: Failure to meet ASAS20 remission criteria and <50% improvement in pain as judged by the physician.