bubble_chart Overview

Ankylosing spondylitis (ankylosing sporidylitis, AS) is a chronic progressive inflammatory disease that primarily affects the spine and can involve the sacroiliac joints and peripheral joints to varying degrees. This condition is also known as Marie-Strümpell disease, Von Bechterew disease, rheumatoid spondylitis, or deformed spondylitis, but it is now uniformly referred to as AS. AS is characterized by inflammation and ossification of the spinal joints and ligaments in the lumbar, cervical, and thoracic regions, as well as the sacroiliac joints. The hip joints are often affected, and inflammation may also occur in other peripheral joints. Typically, the rheumatoid factor is negative in this disease, placing it under the category of seronegative spondyloarthropathies, along with Reiter's syndrome, psoriatic arthritis, and enteropathic arthritis.

bubble_chart Epidemiology

The incidence of this disease varies greatly across different regions and ethnic groups due to differences in survey periods and diagnostic criteria used. In 1949, West estimated the incidence of the disease in the general population to be 0.5%^[1]. Linden surveyed 2,957 people and found a prevalence rate of 1% based on self-defined criteria, while it was 2% according to the New York criteria^[2]. In China, a 1977 survey of 36,097 people at the Changchun First Automobile Manufacturing Plant showed a prevalence rate of 0.6%, while a 1987 survey of 10,647 people by Shantou University Medical College in Guangdong reported a prevalence rate of 1.97%. Through collaboration with the International Bi Disease Alliance, the recent incidence of AS in China has been determined to be 0.3%.

As is well known, the onset of AS is closely related to HLA-B₂₇. In North American Indigenous populations, the HLA-B₂₇ positivity rate is 17–50%, with an AS incidence of 27–63%; whereas in Japanese and African Black populations, the HLA-B₂₇ positivity rate is <1%, with AS incidences of 0.1% and 2%, respectively. The AS incidence ratio between White and Black Americans is 9.4:1, indicating racial and genetic differences in AS susceptibility.

Earlier, it was believed that the disease was more common in males than females, with a male-to-female ratio of about 10:1. Domestic reports suggested a ratio of 9–10:1. However, recent international reports indicate an increase in female incidence, suggesting no significant gender difference in distribution^{[4, 5]}. Some reports suggest that male AS spinal disease tends to be progressive, while female spinal involvement is generally milder, with more peripheral joint manifestations^{[6, 7]}, which may lead to misdiagnosis as seronegative rheumatoid arthritis^[8].

Carbon et al. studied the incidence of AS in the Rochester, USA, area over a 50-year period from 1935 to 1989, finding a rate of 7.3 per 100,000, with a possible declining trend. However, the age of onset or diagnosis remained unchanged, and the 28-year survival rate after diagnosis also showed no significant variation^[9].

bubble_chart Etiology

The pathogenesis of AS has not yet been fully elucidated, and it is generally believed to be related to genetic, infectious, immune, and environmental factors^{[10, 11]}.

1. Genetic factors Genetic factors play an important role in the onset of AS. According to epidemiological surveys, the HLA-B₂₇ positivity rate in AS patients is as high as 90–96%, while in the general population, the HLA-B₂₇ positivity rate is only 4–9%. The incidence of AS among HLA-B₂₇ positive individuals is approximately 10–20%, compared to 1–2% in the general population, a difference of about 100-fold. Reports indicate that the risk of AS among relatives of AS patients is 20–40 times higher than that of the general population^[12]

. Domestic surveys show that the prevalence rate among first-degree relatives of AS patients is 24.2%, which is 120 times higher than that of the general population. The probability of AS occurring in relatives of HLA-B₂₇ positive healthy individuals is much lower than that in relatives of HLA-B₂₇ positive AS patients. All of this suggests that HLA-B₂₇ is an important factor in the pathogenesis of AS.

However, it should be noted that on the one hand, not all HLA-B₂₇-positive individuals develop spondyloarthropathy, and on the other hand, about 5–20% of spondyloarthropathy patients test negative for HLA-B₂₇, suggesting that in addition to genetic factors, other factors influence the onset of AS. Therefore, HLA-B₂₇ is an important genetic factor in the expression of AS but is not the sole factor affecting the disease^{[13, 14]}. Several hypotheses can explain the association between HLA-B₂₇ and spondyloarthropathy: ①HLA-B₂₇ acts as a receptor site for an infectious agent; ②HLA-B²⁷ is a modifier of immune response genes, determining susceptibility to environmental triggers; ③HLA-B₂₇ may cross-react with foreign antigens, thereby inducing tolerance to them; ④HLA-B₂₇ increases the activity of leukocytes in priapism_[15]. Using monoclonal antibodies, cytotoxic lymphocytes, immunoelectrophoresis, and restriction fragment length polymorphism (RFLP), it has now been determined that HLA-B²⁷ has approximately 7 or 8 subtypes_[1]. Healthy individuals who are HLA-B²⁷-positive may have genetic differences from spondyloarthropathy patients. For example, all HLA-B₂₇ individuals possess a constant HLA-B₂₇ M₁ antigenic determinant, and antibodies targeting this determinant can cross-react with HLA-B₂₇

. Most HLA-B₂₇ molecules also carry the M₂ antigenic determinant. HLA-B₂₇ M₂-negative molecules appear to have a stronger association with AS than other HLA-B₂₇ subtypes, particularly in Asians, while HLA-B₂₇ M₂-positive subtypes may confer increased susceptibility to Reiter's syndrome. It has been demonstrated that both the HLA-B₂₇ M₁ and M₂ antigenic determinants can cross-react with arthritogenic factors such as Klebsiella, Shigella, and Yersinia. Individuals with a weaker immune response tend to develop AS, whereas those with a stronger response may progress to reactive arthritis or Reiter's syndrome.

2. Infection Recent studies suggest that the incidence of AS may be related to infection. Ebrimger^[16] et al. found that the detection rate of Klebsiella pneumoniae in the stool of AS patients was 79%, while in the control group it was <30%. During the active phase of AS, the carriage rate of intestinal Klebsiella pneumoniae and the serum IgA antibody titer against this bacterium were higher than in the control group and positively correlated with disease activity. Some researchers propose that Klebsiella species may share cross-reactive antigenic residues or common structures with HLA-B₂₇[17, 18]. For example, HLA-B₂₇ (host antigen residues 72 to 77) shares homologous amino acid sequences with pulmonary Klebsiella (residues 188 to 193). Whether other Gram-negative bacteria have antibodies that bind to this synthetic peptide sequence^, 29% of HLA-B₂₇-positive AS patients showed this reaction, compared to only 5% in the control group^[15]. Mason et al. reported that 83% of male AS patients had concurrent prostatitis, while some authors found that approximately 6% of ulcerative colitis cases were complicated by AS. Other reports also confirmed that the incidence of AS in patients with ulcerative colitis and regional enteritis is much higher than in the general population, suggesting a possible link between AS and infection. Romonus hypothesized that pelvic infections might spread to the sacroiliac joints via lymphatic pathways, or transmission from one meridian to the next, and then disseminate to the spine through the vertebral venous plexus, but no infectious agents (bacteria or viruses) have been identified at the lesion sites.

3. Autoimmunity Some studies found elevated blood moistening and tonifying in 60% of AS patients, with most cases showing IgA-type rheumatoid factors. Serum C₄ and IgA levels were significantly increased, and circulating immune complexes (CIC) were present in the serum, although the antigenic nature remains undetermined. These phenomena suggest that immune mechanisms are involved in the pathogenesis of the disease.

4. Other Factors Trauma, endocrine disorders, metabolic disturbances, and allergic reactions have also been suspected as disease causes. In summary, the exact cause of AS remains unclear, and no single theory can fully explain all its manifestations. It is likely that genetic predisposition, combined with environmental factors (including infections), contributes to the development of the disease.

bubble_chart Pathological Changes

The characteristic pathological changes of AS are enthesopathy, with the primary lesion site being the attachment points of ligaments and joint capsules, i.e., inflammation at the tendon ends, leading to the formation of syndesmophytes, vertebral squaring, destruction of vertebral endplates, Achilles tendonitis, and other changes. Since the tendon ends are metabolically active sites, at least during the growth period, they are a critical area for the onset of juvenile AS. However, the reason why enthesopathy predominantly occurs at tendon ends remains unclear.

The disease initially progresses from the sacroiliac joints to apophyseal arthritis and costovertebral arthritis, with other spinal joints being affected sequentially from top to bottom. The synovial membrane changes in the peripheral joints of AS are characterized by granulomatous synovitis. Around the small blood vessels of the synovial membrane, there are infiltrations of macrophages, lymphocytes, and plasma cells, along with synovial thickening. Over months or years, granulation tissue forms in the affected synovial membrane. Significant calcification and ossification occur in the periarticular soft tissues, and ligamentous attachments can develop syndesmophytes, which extend longitudinally to form bony bridges between adjacent vertebral bodies. Calcification of the paravertebral and anterior vertebral ligaments gives the spine a "bamboo-like" appearance.

As the disease progresses, joints and their surrounding areas show a pronounced tendency toward ossification. In the early stages, ligaments, annulus fibrosus, intervertebral discs, periosteum, and trabeculae are invaded by vascular and fibrous tissues, replaced by granulation tissue, leading to complete joint destruction and adjacent bone sclerosis. After repair, fibrous and bony ankylosis eventually occur, accompanied by vertebral osteoporosis, muscle atrophy, and thoracic kyphosis. Inflammation at the vertebral cartilage endplates and the edges of intervertebral discs ultimately results in localized ossification.

The hallmark of cardiac involvement is the invasion of the aortic valve, causing thickening and fibrosis-induced shortening of the aortic valve leaflets without fusion, along with dilation of the aortic valve ring. Sometimes fibrosis may extend below the aortic base. Occasionally, pericardial and myocardial fibrosis occur. Histologically, chronic inflammatory cell infiltration is observed in the blood vessels of the epicardium and endocarditis of the aortic valve. The elastic tissue in the middle layer of the aortic wall is destroyed and replaced by fibrous tissue. If fibrosis invades the atrioventricular bundle, it can cause atrioventricular block.

Pulmonary lesions are characterized by patchy inflammation of lung tissue with infiltration of round cells and fibroblasts, progressing to alveolar septal fibrosis with hyaline degeneration.

bubble_chart Clinical Manifestations

AS is commonly seen in young people aged 16 to 30, with a higher prevalence in males. It is rare for the first onset to occur after the age of 40, accounting for approximately 3.3%. The disease has an insidious onset and progresses slowly, with mild systemic symptoms. Early symptoms often include lower back pain and morning stiffness, which improve with activity, and may be accompanied by low-grade fever, lack of strength, loss of appetite, and weight loss. Initially, the pain is intermittent but may develop into persistent pain over months or years. Eventually, the inflammatory pain subsides, and the spine becomes partially or completely rigid from the bottom up, leading to kyphotic deformity. In women, peripheral joint involvement is more common^{[6, 7]}, with slower progression and milder spinal deformity.

1. **Manifestations of Joint Lesions** Most AS patients experience joint lesions, with the vast majority initially affecting the sacroiliac joints, followed by ascending progression to the cervical spine. A small number of patients may first exhibit cervical spine involvement or simultaneous involvement of multiple spinal segments. Peripheral joints may also be affected. In the early stages, the affected joints exhibit inflammatory pain accompanied by muscular rigidity around the joints, with pronounced stiffness in the morning. Pain may also manifest at night, relieved by activity or analgesics. As the disease progresses, joint pain diminishes, but spinal segments and joints become restricted in movement and deformed. In the advanced stage

, the entire spine and lower limbs may become rigidly arched, bending forward. (1) **Sacroiliitis**: Approximately 90% of AS patients initially present with sacroiliitis, which later ascends to the cervical spine. Symptoms include recurrent lumbago, stiffness in the lumbosacral region, intermittent or alternating pain in the lower back and buttocks, which may radiate to the thighs. No positive signs are present, and the straight-leg-raising test is negative. However, direct pressure or stretching of the sacroiliac joint can induce pain, distinguishing it from sciatica. Some patients show no symptoms of sacroiliitis, with abnormalities only detected via X-ray. About 3% of AS cases involve the cervical spine first, progressing downward to the lumbosacral region, while 7% exhibit simultaneous involvement of multiple spinal segments.

(2) **Lumbar Vertebral Lesions**: When the lumbar spine is affected, most patients experience restricted lower back and lumbar movement. Flexion, extension, lateral bending, and rotation may all be limited. Physical examination may reveal tenderness over the lumbar spinous processes and muscular rigidity in the paravertebral muscles. In the late stage

(third stage), lumbar muscle atrophy may occur. (3) **Thoracic Lesions**: Thoracic involvement manifests as back pain, anterior and lateral chest pain^{[19, 20]}, and eventually kyphotic deformity. If the costovertebral joints, sternomanubrial joints, sternoclavicular joints, or costochondral joints are affected, a band-like chest pain may occur, with restricted chest expansion. Pain worsens during inhalation, coughing, or sneezing. In severe cases, the thorax remains in an expiratory state, with chest expansion reduced by over 50% compared to normal, necessitating diaphragmatic breathing. Reduced thoracic and abdominal cavity capacity may impair cardiopulmonary and digestive functions.

(4) **Cervical Spondylosis**: A minority of patients first present with cervical spine inflammation, characterized by neck pain radiating to the head and arms. Neck muscles may initially spasm and later atrophy. Disease progression may lead to kyphotic deformity of the cervicothoracic spine. Head movement becomes severely restricted, often fixed in a forward-flexed position, preventing extension, lateral bending, or rotation. Severe cases may only see a small patch of ground in front of their toes, unable to lift their heads for normal vision.

(5) **Peripheral Joint Lesions**: About half of AS patients experience transient acute peripheral arthritis, while 25% develop permanent peripheral joint damage. Large joints are more commonly affected, with the lower limbs more involved than the upper limbs. Statistics show peripheral joint involvement rates as follows: hips and shoulders (40%), knees (15.5%), ankles (10%), feet and wrists (5%), with rare hand involvement. A report from the PLA General Hospital on 80 AS cases noted hip joint involvement as a primary symptom (100%), with restricted movement (64%), flexion contracture (38%), muscle atrophy (25%), and joint ankylosis (37%) being major causes of disability. Hip symptoms appeared within 5 years of onset in 94% of cases, suggesting that if the hip joint is not affected within the first 5 years, subsequent involvement is unlikely.

When the shoulder joint is involved, limited joint movement and pain become more pronounced, restricting activities such as combing hair or raising the arm. If the knee joint is affected, compensatory bending of the joint occurs, making daily activities like walking and sitting more difficult. Involvement of the elbow, wrist, or foot joints is rare, and invasion of partial joints is even more uncommon.

In addition, the pubic symphysis can also be affected, and osteitis symptoms may occur at the upper edge of the pelvis, ischial tuberosity, greater trochanter of the femur, and heel. Early manifestations include local soft tissue swelling and pain, while the advanced stage presents with bony enlargement. Peripheral arthritis can generally occur before or after spondylitis, and local symptoms are difficult to distinguish from rheumatoid arthritis, but residual deformities are less common.

2. Extra-articular manifestations: Most extra-articular lesions of AS appear after spondylitis, though occasionally extra-articular symptoms may occur months or years before musculoskeletal symptoms. AS can affect multiple systems throughout the body and is associated with various diseases.

(1) Cardiac lesions ^{[22, 23]} : Aortic valve lesions are relatively common. Autopsy findings indicate that about 25% of AS cases involve lesions at the aortic root. Cardiac involvement may be clinically asymptomatic or exhibit significant manifestations. Approximately 1% of patients show varying degrees of aortic valve insufficiency, while about 8% develop heart block, which may coexist with aortic valve insufficiency or occur independently. Severe cases may lead to complete atrioventricular block, resulting in Adams-Stokes syndrome. When the lesion involves the coronary artery orifice, angina may occur. A few cases develop aortic aneurysm, pericarditis, and myocarditis. AS patients with cardiac complications are generally older, have a longer disease history, more severe spinal and peripheral joint lesions, and more pronounced systemic symptoms. Gould ^[24] and colleagues examined cardiac function in 21 AS patients and found it significantly lower than in the control group.

(2) Ocular lesions: Long-term follow-up shows that 25% of AS patients develop conjunctivitis, iritis, uveitis, or uveitis, the latter occasionally complicated by spontaneous anterior chamber hemorrhage ^[25] . Iritis is prone to recurrence, with higher incidence as the disease progresses, though it is unrelated to the severity of spondylitis. It is more common in patients with peripheral joint disease and may occasionally precede spondylitis. Ocular diseases are often self-limiting but may require corticosteroid treatment. In some cases, inadequate treatment can lead to glaucoma or blindness.

(3) Ear lesions: Gamilleri ^[26] and colleagues reported that among 42 AS patients, 1/2 (29%) developed chronic otitis media, four times the rate in normal controls. Moreover, AS patients with chronic otitis media had significantly more extra-articular manifestations than those without.

(4) Pulmonary lesions: A few AS patients in the late stage [third stage] may develop irregular fibrotic lesions in the upper lung lobes, presenting with cough, panting, or even hemoptysis, possibly accompanied by recurrent pneumonia or pleuritis. X-ray examination reveals diffuse fibrosis in both upper lung lobes, with possible cyst formation and parenchymal destruction, resembling subcutaneous nodules, requiring differentiation.

(5) Neurological lesions: Due to spinal rigidity and osteoporosis, cervical vertebrae dislocation and spinal fractures may occur, leading to spinal cord compression. Discitis can cause severe pain. In the late stage [third stage], AS may invade the cauda equina, resulting in cauda equina syndrome, which causes radicular pain in the lower limbs or buttocks. Sacral nerve involvement may lead to sensory loss, weakened Achilles tendon reflexes, and motor dysfunction of the bladder and rectum.

(6) Amyloidosis: A rare complication of AS. Among 35 reported AS cases, routine rectal mucosal biopsy revealed amyloid protein deposition in three, most without specific clinical manifestations.

(7) Renal and prostatic lesions: Compared to RA, AS rarely causes renal impairment, though cases of IgA nephropathy have been reported. The incidence of chronic prostatitis in AS is higher than in controls, but its significance remains unclear.

bubble_chart Auxiliary Examination

The white blood cell count is normal or elevated, with a slight increase in lymphocyte proportion. A few patients may have grade I anemia (normocytic hypochromic). The erythrocyte sedimentation rate may increase, but its correlation with disease activity is not significant, whereas C-reactive protein is more meaningful. Serum albumin decreases, while α₁ and γ globulins increase. Serum immunoglobulins IgG, IgA, and IgM may also increase. Blood moistening and tonifying C₃ and C₄ are often elevated. Approximately 50% of patients show elevated alkaline phosphatase, and serum creatine phosphokinase is also frequently elevated. Serum rheumatoid factor is negative. Although 90–95% or more of AS patients are LHA-B₂₇ positive, LHA-B₂₇ is generally not relied upon for diagnosing AS, and LHA-B₂₇ is not routinely tested. Diagnosis primarily relies on clinical manifestations and radiographic evidence.

X-ray examination is extremely significant for the diagnosis of AS. Approximately 98–100% of cases show early sacroiliac joint changes on X-ray, which serve as crucial diagnostic criteria.

Early X-ray findings indicate sacroiliitis, typically starting in the middle to lower part of the sacroiliac joint and affecting both sides. The iliac side is usually involved first, followed by the sacral side. Patchy or blocky bone lesions may be evident. Subsequently, the entire joint may be affected, with jagged edges, subchondral bone sclerosis, osteoproliferation, and joint space narrowing. Eventually, the joint space disappears, leading to bony ankylosis. Sacroiliitis can be classified into 5 grades based on X-ray diagnostic criteria: Grade 0 indicates normal sacroiliac joints; Grade I suggests suspected bilateral sacroiliitis; Grade II shows blurred sacroiliac joint edges, slight sclerosis, and minor erosive lesions with grade I joint space narrowing; Grade III involves bilateral sclerosis, blurred joint edges, erosive lesions with joint space disappearance; and Grade IV indicates complete fusion or ankylosis with or without residual sclerosis.

X-ray manifestations of spinal lesions include early generalized osteoporosis, blurred vertebral facet joints, and trabeculae (decalcification). Due to destructive erosions at the vertebral corners where the annulus fibrosus attaches, the vertebrae appear "squared." The normal lumbar lordosis disappears and straightens, potentially leading to compressive fractures in one or more vertebrae. As the disease progresses to the thoracic and cervical facet joints, calcification occurs in the disc spaces, along with ossification of the annulus fibrosus and anterior longitudinal ligament, forming syndesmophytes that bridge adjacent vertebrae, creating the characteristic "bamboo spine."

Primary AS and secondary spondylitis associated with inflammatory bowel disease, Reiter's syndrome, or psoriatic arthritis exhibit similar X-ray findings, but the latter is asymmetrically ankylosing. Bone spurs and enthesitis may develop at ligament, tendon, or bursa attachment sites, most commonly in the calcaneus, ischial tuberosity, and iliac crest. Similar X-ray changes may occur in other peripheral joints.

If early X-ray results are negative, radionuclide scanning, computed tomography, or magnetic resonance imaging may be performed to detect early symmetric sacroiliac joint lesions ^[27]. However, it must be noted that a simple posteroanterior X-ray is usually sufficient for diagnosing this condition.

bubble_chart Diagnosis

Based on medical history, the following manifestations should suggest inflammatory spinal disease ^[28]: ① Insidious onset of low back discomfort; ② Age <40 years; ③ Duration of more than 3 months; ④ Morning stiffness; ⑤ Symptoms improve with activity. With such a history and radiographic evidence of sacroiliitis, spinal disease is confirmed. Further exclusion of psoriasis, inflammatory bowel disease, or Reiter's syndrome arthritis allows for a diagnosis of primary AS, without waiting until obvious spinal rigidity occurs to establish the diagnosis.

The currently commonly used clinical diagnostic criteria for AS are the 1965 New York criteria:

1. Limitation of lumbar spine movement in all three directions—forward flexion, lateral flexion, and extension;

2. History or presence of lumbar or lumbosacral pain for more than 3 months;

3. Limited chest expansion, measured at the level of the fourth intercostal space, ≤2.5 cm.

Diagnosis is based on the above clinical criteria and radiographic grading of sacroiliitis.

(1) Definite AS is diagnosed as: ① Bilateral sacroiliitis grade III or IV, with at least one of the above clinical criteria; or ② Unilateral sacroiliitis grade III or IV, or bilateral sacroiliitis grade II, with clinical criterion 1, or with clinical criteria 2 and 3.

(2) Probable AS is diagnosed as: Bilateral sacroiliitis grade III or IV without any clinical criteria.

bubble_chart Treatment Measures

The treatment of AS is still lacking specific methods due to the unclear cause of the disease, and there is no effective therapy to halt its progression. Fortunately, in many patients, sacroiliitis does not progress beyond grade II or III^[15], and only a few may advance to complete joint ankylosis.

The goals of AS treatment are to control inflammation, alleviate or relieve symptoms, maintain normal posture and optimal functional positioning, and prevent deformities. To achieve these objectives, the key lies in early diagnosis and early treatment, adopting comprehensive measures including patient and family education, physical therapy, physiotherapy, medication, and surgical intervention.

1. Patient Education

(1) Treatment begins with educating patients and their families, helping them understand the nature of the disease, its general course, possible treatment measures, and future prognosis, to enhance their confidence and patience in fighting the disease and secure their understanding and close cooperation.

(2) Pay attention to maintaining normal posture and mobility in daily life. For example, walk, sit, and stand with the chest out and abdomen in; sleep without a pillow or use a thin pillow on a hard wooden bed, adopting a supine or prone position, lying prone for half an hour each morning and evening; engage in力所能及的 labor and physical activities; and maintain proper posture at work to prevent spinal curvature deformities.

(3) Maintain an optimistic mood, eliminate tension, anxiety, depression, and fear; quit smoking and alcohol; adhere to a regular schedule, and engage in medical physical exercise.

(4) Understand the effects and side effects of medications, learn to adjust doses and manage side effects independently, to better cooperate with treatment and achieve better outcomes.

2. Physical Therapy

Physical therapy is beneficial for various chronic diseases and is particularly important for AS. It helps maintain the physiological curvature of the spine, prevent deformities; preserve thoracic mobility, sustain normal respiratory function; maintain bone density and strength, and prevent osteoporosis and disuse muscle atrophy in limbs. Specific exercises include:

(1) Deep breathing: Perform deep breathing exercises routinely every morning, during work breaks, and before bedtime. Deep breathing maintains maximal thoracic mobility and ensures good respiratory function.

(2) Cervical exercises: Move the head and neck forward, backward, left, and right, and rotate the head to maintain normal cervical mobility.

(3) Lumbar exercises: Perform daily waist movements, including forward bending, backward arching, lateral bending, and torso rotation, to preserve normal lumbar spine mobility.

(4) Limb exercises: Engage in push-ups, inclined supports, leg flexion and extension, chest expansion exercises, and swimming. Swimming is particularly suitable for AS as it benefits limb movement, enhances lung function, and helps maintain the spine's physiological curvature, making it the most ideal full-body exercise for AS.

Patients can choose appropriate exercise types and intensities based on their individual conditions. Initial exercise may cause muscle or joint soreness or discomfort, but this usually resolves after a short rest. If new pain persists for more than 2 hours, it indicates excessive exercise, and the intensity or type should be adjusted accordingly.

3. Physiotherapy

Physiotherapy typically involves heat therapy, such as hot baths, tub baths, showers, or mineral spring baths, to improve local blood circulation, relax muscles, alleviate pain, facilitate joint movement, maintain normal function, and prevent deformities.

4. Drug Therapy

According to Gram and Husby's 1992 report^[28], drugs for AS can be divided into three categories: ① Disease-modifying drugs that suppress disease activity and influence progression, such as sulfasalazine. Suitable for active AS, AS with peripheral arthritis, and newly diagnosed AS. ② Nonsteroidal anti-inflammatory drugs (NSAIDs), suitable for patients with severe nighttime pain and stiffness, to be taken before bedtime. ③ Analgesics and muscle relaxants, such as pentazocine, fortanodyn, and mydocalm, often used for patients who do not respond to long-term NSAID use.

Commonly used clinical drugs include:

⑴Non-steroidal anti-inflammatory drugs (NSAIDs) have the effects of relieving pain, reducing stiffness, and alleviating muscle rigidity. ①Phenylbutazone 0.1g taken orally three times daily was commonly used in the past, but it was later found to cause side effects such as edema and hematuria, so it is generally not recommended now. ②Indomethacin (Indocin) 25–50mg taken orally 3–4 times daily is currently the preferred first-line medication. ③Other options include naproxen 0.25g taken orally twice daily; ibuprofen 0.1g taken orally three times daily; and piroxicam 20mg taken orally once daily. ④Oxaprozin^[29]600–1200mg taken orally once daily for adults, and 10–20mg per kilogram of body weight per day for children. Side effects include gastrointestinal reactions, kidney damage, and prolonged bleeding time. For pregnant and breastfeeding women, ibuprofen is generally the first choice^[22].

⑵ Sulfasalazine (SSZ) SSZ is an azo compound of 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP). It began to be used for the treatment of AS in the 1980s. The dosage starts at 0.25g three times daily, increasing by 0.25g weekly, and is maintained at 1.0g three times daily. The efficacy increases with prolonged administration, with an effective rate of 71% at six months, 85% at one year, and 90% at two years. Patients show symptom improvement, stable or improved laboratory indicators, and radiographic signs. Side effects mainly include gastrointestinal symptoms, rash, blood count and liver function changes, but these are rare. Regular blood tests should be performed during medication.

⑶ Methotrexate (MTX) Reported efficacy is similar to SSZ. A low-dose pulse therapy is administered once weekly, starting at 0.5–5mg in the first week, then increasing by 2.5mg weekly, and maintaining at 10–15mg weekly. Oral and intravenous administration show similar efficacy. Side effects include gastrointestinal reactions, bone marrow suppression, stomatitis, alopecia areata, etc. Liver function and blood tests should be monitored regularly during treatment, and alcohol consumption should be avoided.

⑷ Corticosteroids (CS) Generally, corticosteroids are not used to treat AS. However, in cases of acute iritis or peripheral arthritis unresponsive to NSAIDs, CS may be administered via local injection or orally. Peters ^[30] et al. used methylprednisolone at doses of 1000mg/day and 375mg/day intravenously to treat 17 and 59 cases of active AS in the acute phase, respectively, unresponsive to other medications. After three consecutive days of treatment, prolonged remission was achieved. The high-dose group showed slightly better efficacy, with significant effects on pain control and spinal mobility improvement, though the difference between the two groups was not statistically significant.

⑸ Tripterygium wilfordii Hook F (T ₂ ) Initially, Tripterygium wilfordii tincture was used in China to treat AS, with anti-inflammatory and analgesic effects. The dosage was 15–30ml of 12% Tripterygium wilfordii tincture daily, taken in three divided doses after meals. After disease control (approximately 3–6 months), a maintenance dose of 5–10ml daily or every other day was used. Later, a semi-purified glycoside tablet (T ₂ ), 20mg three times daily, was used, showing better efficacy than the tincture and greater convenience. Side effects include gastrointestinal reactions, leukopenia, menstrual disorders, and reduced sperm motility, which are reversible after discontinuation.

⑹ Fengshi Kang Capsules The Navy Guilin Bi Disease Research Center used Fengshi Kang to treat 120 AS cases, with indomethacin as a control, achieving good efficacy. Fengshi Kang consists of Datura Flower, processed nux vomica, American ginseng, Epimedium, and other Chinese medicinals. Each capsule contains 0.25g of medication, with a general dosage of 8 capsules daily for 3–6 months. Recent disease control was achieved in 10.8%, marked efficacy in 40%, improvement in 44.2%, and no effect in 5%, with a total effective rate of 95%. Pain relief was the most significant effect, with an efficacy rate of 96.7%. Improvement in spinal flexion, extension, and lateral bending was also observed. Functional impairment improvement, assessed via fingertip-to-floor test, chest expansion test, and 20m walking time, was 84.2%. Along with clinical symptom improvement, ESR, C-reactive protein, and anemia improved, and body weight increased to varying degrees. However, spinal deformities and X-ray findings showed no significant changes before and after treatment. Side effects include dry mouth, blurred vision, and dizziness, which gradually diminish with prolonged medication and adaptation, requiring no intervention.

The mechanism of Fengshi Kang capsules in treating AS remains unclear. The significant decrease in serum IgA levels post-treatment suggests that this Yaodui may inhibit humoral immunity.

5. Surgical Treatment Severe kyphosis deformity can undergo corrective surgery after the condition stabilizes. For lumbar deformity, spinal osteotomy can be performed to correct the kyphosis; for cervical ₇ thoracic ₁ osteotomy can correct severe cervical deformity. Rowed ^[31] reported 21 cases of AS patients with cervical spine injuries due to falls, half of whom had good prognosis after conservative treatment; the other half underwent decompression and internal fixation surgery due to recurrent cervical dislocation or spinal nerve compression worsening symptoms, also achieving good results. Severe hip flexion deformity may be treated with total hip replacement or hip arthroplasty, but the outcomes are less satisfactory, as postoperative re-ankylosis is prone to occur.

6. Other Treatments Deep X-ray and ²²⁴ radium radiation therapy have certain effects in alleviating symptoms and improving function in early-stage AS patients, with a short-term remission rate reaching 80–96%. However, they cannot halt disease progression and carry the risk of inducing aplastic anemia, leukemia, and transverse myelitis, and are no longer used. Antimalarial drugs, gold preparations, penicillamine, and azathioprine are ineffective for AS and are no longer employed.

For pulmonary lesions, treatment is primarily symptomatic, with active prevention and management of secondary infections. For severe cardiac valve insufficiency caused by AS, valve surgery may be performed. Patients with severe conduction block may be fitted with an artificial cardiac pacemaker.

bubble_chart Differentiation

1. Lumbosacral joint strain: Chronic lumbosacral joint strain presents as persistent, diffuse lumbago, most severe in the lumbosacral region, with no restriction in spinal movement and no special changes on X-ray. Acute lumbosacral joint strain causes pain that worsens with activity and alleviates with rest.
2. Osteoarthritis often occurs in the elderly, characterized by degeneration and hypertrophy of bones and cartilage, thickening of the synovial membrane, with commonly affected joints including weight-bearing spine and knee joints. When the spine is involved, chronic back pain is the main symptom, easily confused with AS; however, this condition does not cause joint stiffness or muscle atrophy, lacks systemic symptoms, and X-ray shows osteophyte formation and narrowing of intervertebral spaces.
3. Forestier's disease (senile ankylosing hyperostosis): The spine also develops continuous osteophytes, similar to the bamboo spine appearance of AS, but the sacroiliac joints remain normal, and the facet joints are not affected.
4. Subcutaneous nodule spondylitis: Clinical symptoms such as spinal pain, tenderness, stiffness, muscle atrophy, kyphotic deformity, fever, and elevated ESR resemble AS, but X-ray can differentiate. In subcutaneous nodule spondylitis, the spinal margins are blurred, intervertebral spaces narrow, anterior wedging occurs, without ligament calcification, and sometimes paravertebral subcutaneous nodule abscess shadows are present, with unilateral sacroiliac joint involvement.
5. Rheumatoid arthritis: It is now confirmed that AS is not a special type of RA, and the two can be differentiated by many differences. See Table 1. RA is more common in women, typically first affecting small joints of the hands and feet bilaterally and symmetrically, with sacroiliac joints generally unaffected. If the spine is involved, it is usually limited to the cervical spine, without paravertebral ligament calcification, and presents with rheumatoid subcutaneous nodules, often positive serum RF, and HLA-B₂₇ antigen usually negative.
   
6. Enteropathic arthropathy: Ulcerative colitis, regional enteritis, or intestinal lipodystrophy (Whipple's disease) can all cause spondylitis, and the affected joints and X-ray changes in enteropathic arthropathy are similar to AS and difficult to distinguish, thus requiring identification of intestinal symptoms and signs for differentiation. Ulcerative colitis presents with colonic mucosal ulcers, edema, and bloody diarrhea; regional enteritis with abdominal pain, nutritional disorders, and fistula formation; Whipple's disease with steatorrhea and rapid weight loss, all aiding in the diagnosis of the primary disease. Enteropathic arthropathy has a low HLA-B₂₇ positivity rate, and Crohn's disease patients have increased IgG in intestinal perfusion fluid^[17], whereas AS patients have essentially normal IgG levels in intestinal perfusion fluid.
7. Reiter's syndrome and psoriatic arthritis: Both can cause spondylitis and sacroiliitis, but spondylitis generally occurs later and is milder, with less paravertebral tissue calcification, and ligamentous osteophytes mainly of the non-marginal type (calcification of outer fibrous tissue of the annulus fibrosus), forming partial bony bridges between adjacent vertebrae, differing from the bamboo spine of AS; sacroiliitis is usually unilateral or bilateral asymmetric damage, while psoriatic arthritis has skin psoriasis lesions for differentiation.
8. Tumors: Tumors can also cause progressive pain, requiring comprehensive examination for accurate diagnosis to avoid misdiagnosis.