Ankylosing spondylitis (AS) is a chronic progressive disease that affects the sacroiliac joints, spondylolisthesis, paraspinal soft tissues and peripheral joints, and may be associated with extra-articular manifestations. AS is the prototype of spondyloarthropathy or primary AS; sacroiliac arthritis is secondary to other spondyloarthropathies, the former of which is usually referred to in this guideline.
The etiology of AS is not known. Genetic and environmental factors have been found to play a role in the pathogenesis of the disease from epidemiological investigations.
One of the pathological hallmarks and early manifestations of AS is sacroiliac arthritis. The typical manifestation of spinal involvement in advanced stages is a bamboo-like spine. Synovitis of peripheral joints is histologically indistinguishable from rheumatoid arthritis. Terminal tendinopathy is one of the features of the disease. Focal mesangial necrosis of the aortic root can cause annular dilatation of the aorta as well as shortening and thickening of the aortic valve cusps, leading to aortic valve closure insufficiency.
I. Clinical manifestations
1. Invisible onset: Patients gradually develop pain and/or stiffness in the low back or sacroiliac region, wake up with pain in the middle of the night, have difficulty in turning over, and the stiffness in the low back is obvious when rising in the morning or after sitting for a long time, but is reduced after activity. Some patients feel dull pain in the buttocks or severe pain in the sacroiliac region, which occasionally radiates to the periphery. The pain can be aggravated by coughing, sneezing, or sudden twisting of the back. In the early stage of the disease, the pain is mostly intermittent on one side, and after a few months, the pain is mostly persistent bilaterally. As the disease progresses from the lumbar spine to the thoracic and cervical spine, pain, limited motion, or spinal deformity may develop in the corresponding areas. 24%-75% of patients with AS develop peripheral arthropathy at the beginning or during the course of the disease, with the knee, hip, ankle, and shoulder joints predominating, and the elbow and small joints of the hand and foot occasionally being involved. Asymmetric, few-joint or single-joint arthritis and arthritis of the large joints of the lower extremities are the characteristics of peripheral arthritis in this disease. In our patients, arthritis or arthralgia of the knee and other joints, except the hip, is mostly transient and rarely or hardly causes joint destruction and disability. The hip joint is involved in 38%-66% of cases, showing localized pain, restricted movement, flexion-twisting and joint ankylosis, most of which are bilateral, and 94% of the hip symptoms start within the first 5 years after onset. Most of them are bilateral, and 94% of the hip symptoms start within the first 5 years after the onset of the disease. The young age of onset of the disease and the peripheral joints are prone to hip lesions.
Systemic manifestations are mild, but a few severe cases have fever, fatigue, emaciation, anemia or other organ involvement: plantar fasciitis, Achilles tendinitis and other areas of tendinopathy are common in this disease. 1/4 of patients develop ocular uveitis during the course of the disease, alternating unilaterally or bilaterally, which usually resolves on its own, and repeated attacks may lead to visual impairment. Neurological symptoms arise from compressive spinal neuritis or sciatica, vertebral fractures or incomplete dislocations, and cauda equina syndrome, the latter of which can cause impotence, nocturnal urinary incontinence, bladder and rectal dullness, and loss of ankle reflexes. Very few patients develop fibrosis of the upper lobe of the lung. It is sometimes accompanied by cavity formation and is considered tuberculosis, and may be exacerbated by concurrent mycobacterial infections. Aortic valve atresia and conduction disturbances are seen in 3.5-10% of patients, and AS can be complicated by IgA nephropathy and amyloidosis.
II. Diagnostic points
1.Diagnostic clues
The most common and characteristic early complaint of AS is stiffness and pain in the lower back. Since low back pain is an extremely common symptom in the general population, but most of it is mechanical non-inflammatory back pain, whereas this disease is inflammatory in nature. The following 5 items help to differentiate inflammatory back pain caused by spondylitis from non-inflammatory back pain caused by other causes.
(1) Back discomfort occurring before the age of 40.
(2) Slow onset.
(3) Symptoms persist for at least 3 months.
(4) Back pain accompanied by morning stiffness.
(5) Back discomfort decreases or disappears with activity.
If four of the above five items are met, inflammatory back pain is supported.
2.Physical examination
Sacroiliac joint and paravertebral muscle pressure is the positive sign in the early stage of the disease. With the progression of the disease, the anterior lumbar convexity flattens, the movement of the spine is restricted in all directions, the extension of the thorax is reduced, and the posterior protrusion of the cervical spine is seen. The following methods can be used to check the progression of sacroiliac joint pain or spinal lesions.
(1) Occipital wall test: In a normal person in a standing position with both heels pressed against the root of the wall, the posterior occiput should be close to the wall without a gap. In the case of cervical stiffness and/or thoracic segmental deformity, the gap increases to more than a few centimeters, resulting in the occipital region not being able to fit against the wall.
(2) Thoracic expansion: The normal value of the difference between the range of thoracic expansion during deep inspiration and deep expiration is not less than 2.5 cm when measured at the level of the 4th rib space, while the thoracic expansion is reduced in those with extensive involvement of the ribs and spine.
(3) Schober’s test: mark the midpoint of the posterior superior iliac spine at a vertical distance of 10 cm above and 5 cm below the midpoint of the posterior superior iliac spine, and then ask the patient to bend over (keeping both knees in an upright position) to measure the maximum forward flexion of the spine, and the normal movement increases the distance by more than 5 cm, while the spinal involvement increases the distance by less than 4 cm.(4) Pelvic pressure: the patient lies on his side, and pressure on the pelvis from the other side can cause sacroiliac joint pain.
(5) Patrick’s test (lower extremity 4-way test): The patient lies supine with one knee flexed and the heel placed on the opposite knee that is straight. The examiner presses the flexed knee with one hand (when the hip is in flexion, abduction and external rotation) and presses the contralateral pelvis with the other hand, and the pain in the contralateral sacroiliac joint is considered positive. Those with knee or hip lesions cannot complete the 4-character test either.
3.Imaging examination
The earliest changes of AS occur in the sacroiliac joint. X-rays of this area show blurred subchondral bone margins, bone erosion, blurred joint spaces, increased bone density and joint fusion. The degree of lesion of sacroiliac arthritis on X-ray is usually classified into 5 grades: grade 0 is normal, grade I is suspicious, grade II has mild sacroiliac arthritis, grade III has moderate sacroiliac arthritis, and grade IV has joint fusion ankylosis. Computed tomography (CT) should be used in clinically suspicious cases where the X-ray has not yet shown clear or grade II or higher bilateral sacroiliac arthritic changes. This technique also has the advantage of having fewer false positives. However, because the upper part of the sacroiliac joint anatomy is ligamentous, the irregularity and widening of the joint space on imaging caused by its attachment makes the judgment difficult. In addition, subchondral aging of the iliac portion of the sacroiliac joint similar to joint space narrowing and erosion is a natural phenomenon and should not be considered abnormal. Magnetic resonance imaging (MRI) is better than CT for understanding cartilage lesions, but it is prone to false positive results in determining sacroiliac arthritis, and because it is expensive, it should not be done as a routine examination at present.
Radiographs of the spine show vertebral osteoporosis and square changes, blurring of the vertebral tuberosities, calcification of the paravertebral ligaments, and bone bridge formation. Extensive and severe ossifying bridges in advanced stages are called “bamboo-like spine”. Bone erosion of the pubic symphysis, sciatic tuberosity and tendon attachment points (such as the heel bone), with reactive sclerosis and villous changes of adjacent bone, may appear new bone formation.
4.Laboratory examination
Patients with active disease may have increased blood sedimentation, increased C-reactive protein and mild anemia. Rheumatoid factor is negative and immunoglobulins are mildly elevated. Although the rate of HLA-B27 positivity in AS patients is about 90%, there is no diagnostic specificity because normal people also have HLA-B27 positivity. HLA-B27-negative patients cannot be excluded from AS as long as their clinical manifestations and imaging examinations meet the diagnostic criteria.
5. Diagnostic criteria
There are different criteria in recent years, but the New York criteria of 1966 or the revised New York criteria of 1984 are still being used. However, for those who temporarily do not meet the above criteria, reference can be made to the European preliminary diagnostic criteria for spondyloarthropathies, and those who meet them can also be included in this category for diagnosis and treatment, and follow-up observation.
(1) New York criteria (1966): bilateral or unilateral sacroiliac arthritis (graded according to the aforementioned grades 0-IV) confirmed by X-rays, with one or two of the following clinical manifestations, respectively, namely
① limitation of motion of the lumbar spine in all 3 directions of anterior flexion, lateral flexion and posterior extension.
② history or existing symptoms of low back pain.
③ thoracic extension less than 2.5 cm.
Based on the above points, the diagnosis is positive.
AS requires either: X-ray confirmed grade III-IV bilateral sacroiliac arthritis with at least 1 of the above clinical manifestations attached; or X-ray confirmed grade III-IV unilateral sacroiliac arthritis or grade II bilateral sacroiliac arthritis with 1 or 2 of the above clinical manifestations attached, respectively.
(2) Revised New York criteria (1984).
(i) The duration of lower back pain lasting at least 3 months, with pain improving with activity but not relieved by rest.
(ii) Restricted movement of the lumbar spine in the anterior-posterior and lateral flexion directions.
③ thoracic extension less than the normal value for the same age and sex.
④ bilateral sacroiliac arthritis grade II-IV, or unilateral sacroiliac arthritis grade III-IV.
The diagnosis of AS can be confirmed if the patient has ④ and any 1 of ①-③ respectively.
(3) European Spondyloarthropathy Study Group criteria: inflammatory spondylodynia or asymmetric synovitis predominantly of the lower extremity joints with any of the following additional items, namely
①positive family history.
(ii) psoriasis.
(iii) Inflammatory bowel disease.
④Urethritis, cervicitis or acute diarrhea within 1 month prior to arthritis.
⑤ alternating bilateral hip pain.
(vi) tendon terminal disease.
(vii) Sacroiliac arthritis.
III. Differential diagnosis
AS should be differentiated from the following diseases.
1, rheumatoid arthritis (RA): the main differences between AS and RA are.
(1) AS is more prevalent in men while RA is more prevalent in women.
(2) AS invariably has sacroiliac joint involvement, while RA rarely has sacroiliac joint lesions.
(3) AS involves the entire spine from the bottom up, while RA only affects the cervical spine.
(4) Peripheral arthritis in AS is few-joint, asymmetric, and predominantly in the joints of the lower extremities; in RA, it is multi-joint, symmetric, and can develop in both large and small joints of the extremities.
(5) There are no rheumatoid nodules visible in AS and RA.
(6) RF is negative in AS, while the positive rate of RA is 60%-95%.
(7) AS is mostly HLA-B27 positive, while RA is associated with HLA-DR4. The chance of AS and RA occurring in the same patient is 1/10,000-200,000.
2, herniated disc: disc prolapse is a common cause of inflammatory low back pain. The disease is limited to the spine, with no systemic manifestations such as fatigue, wasting, fever, etc. All laboratory tests, including blood sedimentation, are normal. The main difference between it and AS can be confirmed by CT, MRI or vertebral canal angiography.
3, tuberculosis: for unilateral sacroiliac joint lesions, it should be distinguished from tuberculosis or other infectious arthritis.
4, diffuse idiopathic bone hypertrophy (DISH) syndrome: the onset of this disease is mostly in men over 50 years of age, and patients also have spinal pain, stiffness and gradually increasing spinal motion limitation. The clinical presentation and x-ray findings are often similar to those of AS. However, calcification of the ligaments, often involving the cervical and low thoracic vertebrae, is often seen on X-ray, with no erosion of the sacroiliac and spondylolisthesis joints, no increased stiffness in the morning, normal blood sedimentation and negative HLA-B27. Based on the above characteristics, the disease can be distinguished from AS.
5, iliac dense osteitis: this disease is mostly seen in young women, and its main manifestation is chronic lumbosacral pain and stiffness. The clinical examination is not abnormal except for the lumbar muscle tension. The diagnosis mainly relies on X-ray anteroposterior radiographs, and its typical manifestation is an obvious osteosclerotic area in the iliac bone along the middle and lower 2/3 of the sacroiliac joint, triangular in shape with the tip upward, uniform in density, not invading the sacroiliac joint surface, without joint stenosis or erosion, so it is different from AS.
6, other: AS is the prototype of seronegative spondyloarthropathy, in the diagnosis must be differentiated from other spondyloarthropathies associated with sacroiliac arthritis such as psoriatic arthritis, enteropathic arthritis or Wright’s syndrome.