1.Overview
Ankylosing spondylitis (AS) is a chronic, systemic, inflammatory disease that mainly affects the sacroiliac joints and the spine, and in severe cases, spinal deformity and ankylosis can occur.
The prevalence of AS in China is about 0.3%, with a male prevalence ratio of 5-10:1, and the disease is more severe in men. The age of onset is usually from 10 to 40 years old, with a peak at 20 to 30 years old.
The etiology of AS is unknown, and there is a clear tendency of family clustering, with the probability of developing the disease in relatives of AS pre-documented individuals being 23 times higher than normal. The development of AS has been shown to be closely related to HLA-B27, which belongs to the MHC-1 class of genes. Among seronegative arthropathies, about 70% to 90% of HLA-B27-positive individuals develop AS within 10 years.
2.Clinical manifestations
2.1 Typical symptoms
Occult lower back pain is the most characteristic early symptom. Patients gradually develop low back pain and/or morning stiffness, wake up with pain in the middle of the night, have difficulty turning over, and morning stiffness is obvious when getting up in the morning or after sitting for a long time, which is reduced after activity. The disease tends to progress in an upward direction, from the lumbar spine to the thoracic and cervical spine as the disease progresses, resulting in pain, limitation of motion, or spinal deformity in the corresponding areas.
Figure 1 Appearance of a patient with AS
Some patients feel pain in the hip (sacroiliac joint), mostly intermittent or alternating pain on one side in the early stage, and after a few months the pain is mostly persistent bilaterally. One of the pathological signs and early manifestations of this disease is sacroiliac arthritis.
Red arrow shows: sacroiliac joint
Figure 2 Schematic diagram of the sacroiliac joint
Tendon attachment point lesions such as heel pain, plantar pain, and tibial tuberosity pain. Chest pain and limited chest expansion may occur when the thorax is involved.
2.2 Peripheral joint manifestations
Peripheral joint lesions may occur in 24%-75% of patients with AS at the beginning or during the course of the disease, mostly in the hip joint, but also in the knee, ankle, and shoulder joints, with occasional involvement of the elbow and small joints of the hand and foot. Hip joint involvement is characterized by localized pain, limited motion, flexion contracture and joint ankylosis.
Figure 2 X-rays of hip joint involvement in AS patients
2.3 Extra-articular manifestations
Ocular involvement is common and may even be the first symptom. Uveitis may appear, manifesting as eye redness, eye pain, photophobia, lacrimation and vision loss. In addition, upper lobe pulmonary fibrosis, IgA nephropathy, manifested by asymptomatic hematuria and renal amyloidosis, and neurological involvement may occur.
Figure 3 Uveitis in AS patients Figure 4 Upper lobe pulmonary fibrosis
3. Ancillary tests
3.1 Laboratory tests
In active patients, increased sedimentation, increased C-reactive protein and mild anemia are seen. The rate of HLA-B27 positivity is up to 90%.
3.2 Imaging
The earliest changes in AS occur in the sacroiliac joint. The degree of sacroiliac joint lesions on X-ray is usually classified into 5 grades: Grade 0: normal; Grade I: suspicious or very mild sacroiliac arthritis; Grade II: mild sacroiliac arthritis with limited erosion, sclerosis, blurring of joint margins, but no change in joint space; Grade III: moderate or progressive sacroiliac arthritis with one (or more) of the following changes: sclerosis of the proximal joint area, narrowing/widening of joint space, bone destruction or Grade IV: severe abnormalities, sacroiliac joint straightening, fusion, with or without sclerosis.
Radiographs of the spine show vertebral osteoporosis and square changes, with bone bridge formation, and the advanced stage is called “bamboo-like spine”.
Figure 4: Pelvis X-ray of AS patient Figure 5: Spine X-ray of AS patient
4.Main differentiation
Low back pain is an extremely common symptom in the general population, but most of them are mechanical low back pain, while this disease is an inflammatory low back pain, and the difference between them is as follows.
Table 1 Differentiation of inflammatory low back pain and mechanical low back pain
AS
Mechanical low back pain
Age
<40 years
Any age
Family history
Frequently
None
Type of onset
insidious
sudden
Duration
>3 months
<4 weeks
nocturnal pain
often
none
Exercise affects
improve
worsens
Pain range
diffuse
localized
ESR, CRP
may be elevated
Not elevated
5.Treatment
Treatment principles
There is no cure for AS, but patients can achieve symptom control and improve prognosis if they are diagnosed and treated reasonably in time. A combination of non-pharmacological, pharmacological and surgical treatments should be used to relieve pain and stiffness, control or reduce inflammation, maintain good posture, prevent deformation of the spine or joints, and correct deformed joints if necessary, in order to improve and enhance the quality of life of patients.
5.1 Non-pharmacological treatment
Adhere to physical exercise to obtain and maintain the best position of the spinal joints, strengthen the paravertebral muscles and increase lung capacity, swimming is one of the good and effective exercises, but also can do some health care exercises, such as stretching, turning exercises, chest expansion exercises, etc..
In general, stand as far as possible to maintain the chest, abdomen and eyes flat in front of the posture, sitting to keep the chest upright. You should sleep on a hard bed and take more supine position to avoid positions that promote flexion deformity. The pillow should be short and should be discontinued once there is upper thoracic or cervical spine involvement.
5.2 Drug treatment
5.2.1 Non-steroidal anti-inflammatory drugs (NSAIDs)
These drugs produce rapid anti-inflammatory and pain-relieving effects by inhibiting cyclooxygenase (COX) and reducing prostaglandin synthesis, and are preferred for symptomatic treatment in patients with either early or late stage AS. Commonly used are: loxoprofen sodium tablets, meloxicam tablets, celecoxib capsules, etc. Their main adverse effects are gastrointestinal discomfort, a few can cause ulcers, liver and kidney function impairment, and cardiovascular lesions. Avoid taking two or more NSAIDs at the same time; COX-2 inhibitors, such as celecoxib capsules, are preferred in patients with gastrointestinal discomfort. NSAIDs should be used with caution in people at high cardiovascular risk or with renal insufficiency, and should be combined with disease-modifying antirheumatic drugs because NSAIDs do not control disease progression.
5.2.2 Disease modifying antirheumatic drugs (DMARDs)
Commonly used are salazosulfapyridine, methotrexate and so on. These drugs have a slow onset of action, requiring about 3 months of medication before they take effect. Application of these drugs for AS can slow or stop the progression of the disease, but there is a lack of evidence on the efficacy of these drugs for mesial joint lesions. These drugs have many side effects, including rash, leukopenia, and abnormal liver and kidney function, in addition to gastrointestinal reactions, so it is important to take the drugs strictly as prescribed and to regularly review blood tests and liver and kidney function. Allergy to sulfonamides is prohibited.
5.2.3 Glucocorticoids
Glucocorticoids as a class of drugs for AS have strong anti-inflammatory and analgesic effects, but because they cannot control the development of AS and have more side effects, they are not used as the first choice for the treatment of AS. It can be appropriately applied to AS patients with the following conditions
l) For those who cannot tolerate or have poor efficacy of NSAIDs, they can be treated with small dose prednisone instead, and the dose usually does not exceed 10mg/day.
2) If there is peripheral single joint inflammation such as knee osteoarthritis, local injection of glucocorticoids may be used.
3) In the presence of severe extra-articular manifestations such as acute iridocyclitis, cardiopulmonary involvement, etc., higher doses of glucocorticoids may be used for static dosing.
5.2.4 Biological agents
The 2008 American College of Rheumatology treatment guidelines have identified biologics as first-line agents and recommend their early use for rapid onset of action and efficacy. A large number of studies have confirmed that TNF-α plays an important role in the pathogenesis of AS. Therefore, TNF-α is regarded as the most critical cytokine among many cytokines in the immune response of AS and has become the main target for the treatment of AS, so TNF-α antagonists are the earliest and most successful to be applied. At present, enalapril and infliximab are commonly used in clinical practice in China. Among them, etanercept is administered to adults at 25 mg twice a week for rapid and stable control of inflammation in the spine and peripheral joints. Infliximab is usually given at an initial dose of 5 mg kg-1, followed by the same dose at weeks 2, 6, and every 6 weeks thereafter. There is evidence that infliximab is most effective in acute anterior uveitis in patients with AS, with a low recurrence rate and significant inhibition of spinal lesions in AS. It has few side effects, with infections and local allergic reactions being common side effects.
Other biological agents such as adalimumab and rituximab also have their irreplaceable advantages, but they are currently rare in China, so they are not introduced.
In conclusion, early detection, early treatment and regular treatment of AS can slow down joint ankylosis, improve the prognosis and enhance the quality of life.