1.Overview
Ankylosing spondylitis (ankylosingspondylitis, AS) is a chronic inflammatory disease that mainly affects the sacroiliac joints, spinal prominences, paraspinal soft tissue peripheral joints, and can be accompanied by extra-articular manifestations, serious spinal deformity and ankylosis can occur. The preliminary survey in China is about 0.3%. The ratio of men to women is about 2 to 3:1, and the onset of the disease is slow and mild in women. The age of onset is usually 13-31 years old, with a peak of 20-30 years old, and is rare after 40 years old and before 8 years old.
The etiology of AS is not known. Genetic and environmental factors have been found to play a role in the development of the disease from epidemiological investigations. It has been demonstrated that the onset of AS and human to cell antigen (HLA)~B27 are closely related, and there is a clear tendency for family aggregation. One of the pathological signs and early manifestations of AS is sacroiliac arthritis. The typical manifestation of advanced spinal involvement is “bamboo-like changes”. Synovitis of peripheral joints is histologically indistinguishable from rheumatoid arthritis (RA). Tendinopathy is one of the characteristics of this disease.
2. Clinical manifestations
The onset of the disease is insidious. Patients gradually develop pain and/or morning stiffness in the low back or sacroiliac region, wake up with pain in the middle of the night, have difficulty turning over, and morning stiffness in the low back is obvious when getting up in the morning or after sitting for a long time, but is reduced after activity. Some patients have dull pain in the buttocks or severe pain in the sacroiliac region, which occasionally radiates to the periphery. The pain may be aggravated by coughing, sneezing, or sudden twisting of the lumbar region. In the early stage of the disease, the hip pain is mostly intermittent or alternating on one side, and after a few months, the pain is mostly bilateral and persistent. In most patients, pain, restricted movement or spinal deformity occurs in the corresponding areas as the disease progresses from the lumbar spine to the thoracic and cervical spine. 24% to 75% of AS patients develop hip and peripheral joint lesions at the beginning or during the course of the disease, with the knee, ankle and shoulder joints being the majority, and the elbow, hand and foot small joints occasionally being involved. Arthritis of the large joints of the lower extremities is one of the features of peripheral arthritis in this disease.
Arthritis or arthralgia of the hip and knee, as well as other joints, is usually early in the course of the disease and causes little or no joint destruction or disability. The hip joint is involved in 38% to 66% of cases, with localized pain, limited motion, flexion contracture and joint ankylosis, most of which are bilateral, and 94% of hip symptoms begin within the first 5 years after onset. Ocular uveitis occurs in 1/4 of patients during the course of the disease, alternating unilaterally or bilaterally, and can be recurrent or even lead to visual impairment.
The systemic manifestations of the disease are mild, with a few severe cases having fever, fatigue, emaciation, anemia, or other organ involvement. Plantar fasciitis, Achilles tendinitis, and other sites of tendon telangiectasia are common in this disease. Neurologic 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 incontinence, bladder and rectal dullness of sensation, and loss of ankle reflexes. Very few patients develop fibrosis of the upper lobe of the lung, sometimes accompanied by cavity formation and mistaken for tuberculosis, or the condition may be exacerbated by concurrent mycobacterial infections. Aortic atresia and conduction disorders are seen in 3.5-10% of patients. as can be complicated by I nephropathy and amyloidosis.
3.Diagnostic points
3.1 Clinical diagnostic clues: The main clues to the diagnosis of the disease are based on the patient’s symptoms, signs, extra-articular manifestations and family history. the most common and characteristic early complaints of AS are morning 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 2009 International AS Assessment Task Force (ASAS) experts on inflammatory back pain recommended the following criteria for the diagnosis of inflammatory back pain: (1) age of onset <40 years; (2) insidious onset; (3) symptoms improve with activity; (4) worsening at rest; (5) nocturnal (5) pain at night (improves after waking up). The diagnosis of AS inflammatory back pain was made when four of the above five indicators were met. Its sensitivity is 79.6% and specificity is 72.4%.
3.2 Physical examination: Sacroiliac joint and paravertebral muscle pressure pain is a positive sign in the early stage of the disease. With the progression of the disease, the anterior convexity of the lumbar spine becomes flat, the movement of the spine in all directions is restricted, the extension of the thorax is reduced, and the cervical spine is posteriorly protruded. The following methods can be used to examine the progression of sacroiliac joint compression pain or spinal lesions.
① Occipital wall test: In a healthy 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 posterior convexity of the thoracic vertebral segment, the gap increases to more than a few centimeters, resulting in the occipital area not being able to fit against the wall.
②Thoracic expansion: The normal value of the difference between the range of thoracic expansion during deep inspiration and deep expiration is not less than 2.5cIll when measured at the level of the 4th rib space, while the thoracic expansion is reduced in those with extensive rib and spinal involvement.
③Schober’s test: A lobe J mark was made at a vertical distance of 1Ocm above the midpoint of the posterior superior iliac spine line, and then the patient was asked to bend over (keeping both knees in an upright position) to measure the maximum forward flexion of the spine, and the distance increased by 5cm or more for normal movement, and <4cm for spinal involvement.
④Pelvic compression: the patient lies on his side and compression of the pelvis from the other side can cause sacroiliac joint pain. ⑤Patrick’s test (lower extremity “4” 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 (at this time the hip is in flexion, abduction and external rotation) and presses the opposite pelvis with the other hand, which is considered positive if the opposite sacroiliac joint pain can be induced. Those with knee or hip lesions cannot complete the “4” test either.
The earliest change of AS occurs in the sacroiliac joint. x-ray film shows blurring of the subchondral bone margin of the sacroiliac joint, bone erosion, blurring of the joint space, increase of bone density and joint fusion. The degree of lesion of sacroiliac arthritis is usually classified into 5 grades according to x-ray: grade 0: normal; grade I: suspicious.
Grade II: with mild sacroiliac arthritis; Grade llI: with moderate sacroiliac arthritis; Grade 1V: with joint fusion ankylosis. Radiographs of the spine show vertebral osteoporosis and square changes, blurring of the vertebral tubercle, calcification of the paravertebral ligaments, and bone bridge formation. Extensive and severe ossifying bridges in the late stage are called “bamboo-like spine”. Bone erosion at the pubic symphysis, sciatic tuberosity, and tendon attachment points (e.g., heel bone), with reactive sclerosis and villous changes in adjacent bone, may result in new bone formation. For early clinical stage or suspicious cases, CT or magnetic resonance imaging (MR1) examination can be chosen. Due to the greater radiation of CT than ordinary X-ray, it should be used for diagnosis only and should not be repeatedly examined.
3.4 Laboratory tests: patients in the active phase are seen to have increased erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) t~ high, mild anemia and mildly elevated immunoglobulins. Rheumatoid factor (RF) is mostly negative, but a positive RF does not exclude the diagnosis of AS. Although the rate of HLA-B27 positivity in AS patients is about 90%, there is no diagnostic specificity because healthy people are also positive. HLA-B27-negative patients meet the diagnostic criteria as long as the clinical manifestations and imaging examinations. The possibility of AS cannot be excluded either.
4.Diagnostic criteria
In recent years, the New York criteria for AS revised in 1984 have been used more often. For those who temporarily do not meet the above criteria, reference can be made to the diagnostic criteria for spondyloarthropathies (spA), mainly including Amor, the European Spondyloarthropathy Study Group (ESSG) and the 2009 ASAS recommended classification criteria for medial spA, the latter two are described below.
4. 11984 revised AS New York criteria: ① lower back pain lasting for at least 3 months, with pain improving with activity but not relieved by rest; ② 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 to ③ respectively.
4. 2ESSG diagnostic criteria: inflammatory spinal pain or asymmetric synovitis with lower extremity joints and any 1 of the following additional items, namely: ① positive family history; ② psoriasis; ③ inflammatory bowel disease; ④ urethritis, cervicitis or acute diarrhea within 1 month before arthritis; ⑤ alternating bilateral hip pain; ⑥ tendon telangiectasia; ⑦ sacroiliac arthritis. Those who are eligible can be included in this category for diagnosis and treatment, and be followed up and observed.
4. 32009 ASAS recommended classification criteria for medial s “A: patients with age of onset <45 years and low back pain for ≥3 months plus 1 of the following criteria: ① imaging suggestive of sacroiliac arthritis plus ≥1 of the following SpA features; ② HlJA-B27 positivity plus ≥2 of the following other spA features. The imaging suggestive of sacroiliac arthritis refers to: (i) MRI suggestive of active (acute) inflammation of the sacroiliac joint, highly suggestive of sacroiliac arthritis associated with SpA or (ii) definite imaging changes of sacroiliac arthritis (according to the New York criteria revised in 1984). spA features include: (i) inflammatory back pain; (ii) arthritis; (iii) onset and endpoint inflammation (Achilles tendon); (iv) oculocutaneous uveitis; (v) finger (toe) inflammation; (vi) psoriasis; ⑦ Crohn's disease/ulcerative colitis; ⑧ good response to non-steroidal anti-inflammatory drugs (NSAIDs); ⑨ family history of SpA; ⑩ HLA-B27 positive; ⑩ elevated CRP.
5. Differential diagnosis
5.1 Herniated disc: It is one of the common causes of low back pain. The disease is limited to the spine, without fatigue, wasting, fever and other manifestations of the order body, mostly acute onset, mostly limited to lumbar pain, aggravated by activity, relieved by rest; there is often lateral flexion when standing. On palpation, there were one to two painful trigger points in the spinal prominence. All laboratory tests were normal.
All laboratory tests are normal. The main difference between it and AS can be confirmed by CT, MRI or spinal canalography. Narrow or anteriorly narrowed and posteriorly wide or equal width anteriorly and posteriorly on lumbar x-ray; posterior seventh or inferior corner labral hyperplasia of the vertebral body margin or the presence of small free bone masses; CT can confirm.
5.2 Diffuse idiopathic bone hypertrophy (DISH) syndrome: the onset is mostly in men over 50 years of age, who 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 flowing calcification and ossification connecting at least four anterolateral vertebral bodies.
5.3 Iliac dense osteoarthritis: Mostly seen in middle-aged and young women, especially those who have a history of multiple pregnancies, childbirth or are engaged in long-term standing occupations. The main manifestation is chronic lumbosacral pain, aggravated by exertion, with white limit. Clinical examination has no abnormality other than muscle tension in the lumbar region. The diagnosis mainly relies on anteroposterior radiographs and typically presents in
There are obvious osteosclerotic areas along the middle and lower 2/3 of the sacroiliac joint in the iliac bone, triangular in shape with the tip upward, uniform in density, without invading the sacroiliac joint surface, without joint narrowing or erosion, with clear boundaries, and normal bone quality and joint space on the sacral side.
5.4 Others: As is the prototype of SpA, it must be differentiated from other sDA associated with sacroiliac arthritis such as psoriatic arthritis, enteropathic arthritis or Wright’s syndrome in the diagnosis. In addition, spinal osteoarthritis, RA and tuberculosis involving the sacroiliac joint or spine need to be further differentiated based on other clinical features of interest.
6. Treatment goals, protocols and principles
6.1 Treatment goals for AS patients
① Relieve symptoms and signs: Eliminate or minimize symptoms such as back pain, morning stiffness and fatigue as much as possible. ②Restoration of function: to restore the patient’s physical function, such as spinal mobility, social mobility and work ability, to the greatest extent possible. ③Prevent joint damage: To prevent new bone formation, bone destruction, bony ankylosis and spinal deformation in patients with involvement of the hip, shoulder, mid-shaft and peripheral joints. ④Improve the quality of life of patients: including socioeconomic factors, work, medical retirement, and retirement. ⑤ Prevent complications of spinal diseases: prevent spinal fractures and flexion contractures, especially in the cervical spine.
6.2 Treatment options and principles
There is no radical cure for AS. However, patients can achieve symptom control and improve prognosis if they are diagnosed and treated reasonably in a timely manner. Through a combination of non-pharmacological, pharmacological and surgical treatments, pain and stiffness should be relieved, inflammation should be controlled or reduced, good posture should be maintained, deformation of the spine or joints should be prevented, and deformed joints should be corrected if necessary, in order to improve and enhance the quality of life of patients.
6.2.1 Non-pharmacological treatment
①Education of patients and their families about the disease is an integral part of the overall treatment plan, which helps patients to actively participate in treatment and cooperate with physicians. The long-term plan should also include the patient’s psychosocial and rehabilitation needs. ② Advise patients to be reasonably and consistently physically active 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 adjuncts to treatment. ③Standing should try to maintain the posture of chest up, abdomen in and eyes flat in front. The sitting position should also keep the chest upright. One should sleep on a hard bed and take more supine positions to avoid positions that promote flexion deformity. Pillows should be short and should be discontinued once there is upper thoracic or cervical spine involvement. ④Give necessary physical therapy for painful or inflamed joints or soft tissues. ⑤ Advise smokers to quit smoking; patient smoking is a functional
One of the risk factors for poor prognosis.
6.2.2 Medication
6.2.2.1 NSAIDs: They can rapidly improve patients’ low back pain and morning stiffness, reduce joint swelling and pain and increase activity van weeks, and are preferred for symptomatic treatment of patients with early or late AS. The most common adverse effects of NSAIDs are gastrointestinal discomfort and a few can cause ulcers; other less common are cardiovascular disease such as hypertension, which can be accompanied by headache, dizziness, liver and kidney damage, hematocrit, edema and allergic reactions. Physicians should select one NSAIDs drug for each patient’s specific case. The use of ≥2 NSAIDs at the same time will not increase the efficacy, but will increase the adverse drug reactions and even bring serious consequences. Regardless of the NSAIDs used, not only to achieve symptomatic improvement, but also to delay or control progression, it is usually recommended to continue using them for a longer period of time at the appropriate drug dose. To assess whether a particular NSAID is effective, the same dose should be used consistently and regularly for at least 2 weeks. If one drug is not effective for 24 weeks, it should be switched to another NSAID of a different class, and adverse drug reactions should be monitored and adjusted promptly during the course of drug administration.
6.2.2.2 Biologics: Anti-tumor necrosis factor (TNF) ~ antagonists include: etanercept, infliximab and adalimumab. The treatment of AS has been evaluated in several randomized double-blind placebo-controlled trials with an overall efficacy rate of 50%-75%. Patients who are not satisfied with or cannot tolerate one TNF-d antagonist may be better treated with another. The patients who are not satisfied with the efficacy of one TNF-d antagonist or cannot tolerate it may have better efficacy with another agent. However, its long-term efficacy and effect on axial joint x-ray lesions in AS remain to be studied. Studies suggest that patients with good initial response appear to sustain efficacy for at least 2 years. The use of TNF-antagonists may also reduce the frequency of recurrence of uveitis. Although TNF-antagonists are recommended only for patients with AS who are “diagnosed” according to classification criteria, studies suggest that they may also be used in patients who lack typical clinical radiological changes and meet the “probable” or sDA criteria of the As classification criteria in the following cases The most significant adverse reactions to TNF-OL antagonists are infusion or point-of-injection reactions, ranging from nausea, headache, pruritus, and dizziness to hypotension, dyspnea, and chest pain. These range from nausea, headache, pruritus, dizziness to hypotension, dyspnea, chest pain. Other adverse reactions were an increased chance of infection, including common respiratory infections and opportunistic infections (e.g., tuberculosis), but the difference was not statistically significant compared with placebo. Pretreatment screening for tuberculosis significantly reduces the incidence of tuberculosis associated with TNF-antagonist therapy and is now routine. Demyelinating disease, lupus-like syndrome, and congestive
exacerbations of congestive heart failure have also been reported, but the incidence is low. Routine blood, urine, liver and kidney functions should be reviewed regularly during drug administration.
6.2.2.3 Salicyclovir: It can improve joint pain, swelling and stiffness in AS and reduce serum IgA levels and other laboratory activity indicators, especially for improving peripheral arthritis in AS patients. To date, there is a lack of evidence on the therapeutic effect of this product on the mesial joint lesions of AS and on improving the prognosis of the disease. The usual recommended dosage is 2.0g/day, divided into 2-3 oral doses. Increasing the dosage to 3.0g/a may increase the efficacy, but also significantly increase the adverse effects. The effect of this product is slow, usually in 4-6 weeks after the drug. In order to increase the tolerance of patients. Generally start with 0.25g, 3 times a day. The dose and duration of treatment can also be adjusted according to the condition or the patient’s response to treatment and maintained for 1 to 3 years. To compensate for the slow onset of action of salazosulfapyridine and the lack of anti-inflammatory effect, one fast-acting NSAIDs are usually used in combination with it. Adverse reactions include gastrointestinal symptoms, rash, hematocrit, headache, dizziness, and reduced spermatozoa and abnormal morphology in men (reversible with discontinuation of the drug). It is contraindicated in patients with sulfonamide hypersensitivity.
6.2.2.4 Glucocorticoids: Oral or intravenous systemic application of corticosteroids is generally not advocated for the treatment of AS because of the large adverse effects and the inability to stop the course of AS. Persistent tendon telangiectasia and persistent synovitis may respond well to topical corticosteroid therapy.
well. Anterior uveitis can be better controlled by pupil dilation and hormonal spotting. Refractory iritis may require systemic hormonal or immunosuppressive therapy. Intra-articular injections of glucocorticoids for intractable peripheral arthritis (e.g., knee) effusions that do not respond well to systemic medications are feasible, and repeated injections should be given at 3-4 week intervals, usually no more than 2-3 times a year. Similarly, CT-guided intra-sacroiliac joint glucocorticoid injections are an option for patients with intractable sacroiliac joint pain. Similar heel pain-like tendon telangiectasia can also be treated with local glucocorticoid injections.
6.2.2.5 Other drugs: Some male patients with refractory AS showed significant improvement in clinical symptoms, ESR and CRP after the application of thalidomide (thalidomide). The initial dose of 50mg/night, every 1014d increments of 50mg, to 150200m night maintenance, foreign useful 300mg / d maintenance. Insufficient dosage is not effective, and the symptoms are likely to recur rapidly after discontinuation. The adverse effects of this product include drowsiness, thirst, decreased blood cells, increased liver enzymes, microscopic hematuria and tingling sensation at the fingertips. Therefore, routine blood, urine and liver and kidney functions should be checked regularly during the initial period of use. Regular neurological examination should be done for long-term drug users to detect possible peripheral neuritis in time. For patients who lack the efficacy of the above treatments, methotrexate and anti-rheumatic phytochemicals can be used for AS peripheral joint involvement (see RA diagnosis and treatment guidelines), etc. However, their efficacy on medial joint lesions is uncertain and needs further study.
6.2.3 Surgical treatment
Joint space narrowing, ankylosis and deformity caused by hip joint involvement are the main causes of disability in this disease. Artificial total hip arthroplasty is the best choice. After the replacement, the joint pain of most patients is controlled, the function of some patients is normalized or close to normal, and the life expectancy of the replaced joint is 90% over 10 years.
7. Course and prognosis
It should be emphasized that the severity of the disease varies greatly in clinical manifestations, with some patients experiencing repeated and continuous progression and others in a relatively stable state over time. Patients with mild AS with only localized involvement can maintain almost full function and employability. However, some patients develop severe limitations in skeletal activity or life-threatening extramusculoskeletal complications. There is usually individual variation in disease activity. Symptoms usually persist for decades. A small number may experience a “bum-out” period of disease activity followed by long-term remission. The risk of developing lymphoma in AS does not appear to be significantly increased.
Several indicators have been shown to be informative in determining the prognosis of AS, including: hip osteoarthritis; salami-like fingers or toes; poor efficacy of NSAIDs; elevated ESR (>30 mm portal h); limited lumbar spine mobility; oligoarthritis and age of onset <16 years. Several other factors may also be associated with poor prognosis in patients with AS, such as smoking, progressively worsening radiographic changes, active lesions (as rated by the Disease Activity Index), functional impairment (as assessed by self-report), lower educational attainment, presence of other SpA-related conditions (e.g., psoriasis, inflammatory bowel disease), male gender, history of uveitis, and a variety of conditions involving dynamic flexibility (ability to bend rapidly, repeatedly , twisting and stretching) or occupational activities that involve body vibration (e.g., driving a truck or operating heavy equipment). In addition, the prognosis is poor for delayed diagnosis, untimely and unreasonable treatment, and non-adherence to long-term functional exercise. Long-term follow-up under the supervision of a specialist should be emphasized.