Disease Description
Spondyloarthritis (SpA), previously known as seronegative spondyloarthropathies or spondyloarthropathies (SpAs), is a group of chronic inflammatory rheumatic diseases with Inflammatory low back pain with or without peripheral arthritis, combined with certain characteristic extra-articular manifestations, are the characteristic signs and symptoms of these diseases. These diseases include: ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA), arthropathy of inflammatory bowel disease (IB), and other diseases such as ankylosing spondylitis (AS). inflammatory bowel disease (IBD), undifferentiated spondyloarthritis, and juvenile chronic arthritis. The term Reiter’s syndrome (RS) is synonymous with reactive arthritis and is now rarely used. This group of diseases often develops in young and middle-aged people, and there are more males than females with several diseases, except for psoriatic arthritis, where there is no gender difference in the onset of the disease.
Spondyloarthritis has a strong correlation with the HLA-B27 gene, which has led to a good unification of the concept. The term “seronegative spondyloarthropathies” is used to describe a related group of heterogeneous diseases with many of the same clinical, radiological, and serologic features, as well as familial and genetic relationships. These diseases have many differences and similarities, including rheumatoid factor negativity, absence of subcutaneous nodules, radiographic sacroiliac arthritis with or without inflammatory peripheral arthritis, and familial aggregation.
Causes of morbidity
B27 antigen is significantly elevated in all diseases included in spondyloarthritis. Whipple’s disease and leukoarthrosis are no longer included in the category of spondyloarthritis diseases because of the lack of association with HLA-B27 and other features. Among the non-genetic pathogenic factors, infection is more frequent. Transgenic rats living in a sterile environment did not develop ankylosing spondylitis, suggesting that environmental factors are indispensable for the development of HLA-B27-related diseases. The association of tumor necrosis factor-α (TNF-α) with the pathogenesis of ankylosing spondylitis has led to clinical trials of TNF inhibitors for the treatment of ankylosing spondylitis.
Pathological manifestations
The inflammatory process in spondyloarthritis occurs at the site where the ligaments attach to the bone at the point of origin and termination, unlike rheumatoid arthritis for which there is much clinical and radiological evidence. The primary targets of the initial inflammatory process in spondyloarthritis occur at the points of origin and termination, the cartilage and to a lesser extent the synovium. The inflammatory process has a tendency to heal itself as new bone forms over fibrous scar tissue, leading to joint ankylosis and irreversible ossification of the midshaft and peripheral joints.
Clinical manifestations
1. Mesial involvement
The spondyloarthritis spondylosis type of ankylosing spondylitis and psoriatic arthritis is dominated by mid-axis involvement. The broad range of the mid-axis should refer to the pelvis to the cervical spine, which includes the hip; narrowly defined mid-axis involvement mainly refers to the involvement of the cervical, thoracic and lumbar spine and sacroiliac joints. Medial spondylitis includes osteoarthritis, ligamentous tendon and attachment point inflammation.
The early stage mainly presents with inflammatory low back pain, but radiographically does not yet show signs of sacroiliac arthritis, which is usually easily missed or misdiagnosed clinically in this group of patients. The clinical manifestations of the late stage are very obvious, including sacroiliac arthritis, partial or full spinal involvement, changes in the patient’s body shape and posture, activity limitation, and imaging changes, which are easily diagnosed clinically, but even if they are diagnosed clinically correctly, their treatment often misses the best treatment period or the patient already has functional limitation or disability. Therefore, it is important to pay attention to the diagnosis and treatment of early mid-axis involvement in ankylosing spondylitis so that the condition can be controlled as early as possible.
(1) Alternating hip pain This is the most common early symptom in patients with ankylosing spondylitis. It is manifested as pain in one hip or buttock, which is more pronounced. In severe cases, it can lead to restricted hip movement and fear of walking, which can improve after a period of treatment, but can recur and can occur bilaterally in alternating episodes. Because the sacroiliac joint is located deep in the hip, these symptoms are the result of inflammation of the sacroiliac or hip joint. Although both patients with ankylosing spondylitis and patients with mechanical low back pain may present with hip pain, patients with ankylosing spondylitis are more specific in that they present with pain starting on one side of the hip first and progressively alternating hip pain.
(2) Inflammatory low back pain Low back pain in patients with spondyloarthritis often has an insidious onset, starting in the low back and hip area and progressing to the back, often more pronounced in the latter part of the night, with significant stiffness that can lead to difficulty turning over at night and significant stiffness in the low back when waking up in the early morning, which improves with activity. The duration of this morning stiffness is related to the severity of the patient’s condition, ranging from a few minutes in mild cases to several hours or even the whole day in severe cases. This inflammatory low back pain is an outward manifestation of inflammation of the small joints of the spinal column and attachment points. Inflammatory low back pain is one of the most hallmark features of ankylosing spondylitis and serves as a powerful tool to screen and identify those patients with chronic low back pain for spondylolisthesis with mid-axis involvement. The following 5 parameters better explain inflammatory low back pain, including.
① improvement of symptoms after activity ;
②nocturnal pain;
(iii) insidious onset;
④Onset before 40 years of age;
⑤ No improvement of symptoms after rest. Inflammatory low back pain is considered if the patient has had chronic low back pain for >3 months and meets at least 4 of the 5 items above.
(3) Anterior chest wall pain Patients with spondyloarthritis often present with pain around the anterior chest wall and, in severe cases, swelling of the sternoclavicular joint due to sternoclavicular stalk, sternoclavicular, and cribriothoracic arthritis. Progressive inflammation can lead to decreased thoracic mobility, and therefore most diagnostic criteria for the classification of ankylosing spondylitis include limited chest expansion.
(4) Spinal ankylosis Ankylosing spondylitis and the spondylotic form of psoriatic arthritis both present with spinal ankylosis in the advanced stages of the disease. It is primarily due to ossification of the vertebral ligaments, vertebral ribs and thoracic rib joints, often resulting in impaired spinal mobility and an increased risk of fracture. In the advanced stages of ankylosing spondylitis, extensive ligamentous tubercle formation results in a typical “bamboo spine”. The spondylotic form of psoriatic arthritis is often characterized by asymmetric ligamentous redundancy and paravertebral ossification, which is characterized by ligamentous ossification between the middle of adjacent vertebrae to form a bone bridge, and is asymmetrically distributed.
2, peripheral joint involvement
In addition to spondylolisthesis invading the medial (spinal) joints, peripheral joint involvement is also a common manifestation. The peripheral joints, in the usual sense, include all joints except the spine (axial joints). There is still much controversy as to whether the shoulder and hip joints of patients with ankylosing spondylitis are peripheral or axial joints. Many patients with spondyloarthritis first develop peripheral joint swelling and pain during the course of the disease, and only after several years do they develop low back pain, which can easily be misdiagnosed as other types of arthritis and not treated promptly and correctly, thus delaying treatment.
The main features of peripheral joint involvement in ankylosing spondylitis are: more lower limb joints (knees and ankles) than upper limb joints, more single/low joint involvement than multiple joint involvement, and more asymmetrical than symmetrical. Unlike rheumatoid arthritis, the symptoms of arthritis or arthralgia in the knee and other joints, except the hip joint, are mostly intermittent and mild. The serious consequences of bone erosion, destruction and joint disfigurement are rare or uncommon.
Unlike rheumatoid arthritis, which often involves the proximal interphalangeal joints of the hand, psoriatic arthritis can involve the distal interphalangeal joints of the hand, and its joints are sometimes heavily involved and can show bone erosion and destruction similar to rheumatoid arthritis, which is different from other types of spondyloarthritis.
3. Adhesion point inflammation
Adnexitis is a characteristic lesion of spondyloarthritis and is less common in other diseases. In the spine, attachment points can be found at the attachment of bursae and ligaments, as well as in the intervertebral discs, cribriform joints, and transverse cribriform joints. Pain, stiffness, and limited mobility of spinal joints are often caused by attachment points. Adnexitis also involves many extra-medial sites and manifests as localized swelling and pain in the corresponding areas, including the heel (including the plantar or Achilles tendon areas), localized swelling and pain around the knee, the sciatic tuberosity, the anterior superior iliac crest, the pubic symphysis, and the cartilaginous junction of the rib cage.
4. Skin and mucous membrane involvement
(1) Psoriasis: psoriatic rash mostly appears before psoriatic arthritis, and there are a few patients who first develop arthritis and then rash. The skin psoriasis lesions are usually found on the scalp and the extremities, especially on the elbows and knees, and are disseminated or distributed in a generalized manner. Special attention should be paid to the lesions in hidden areas, such as: hair, perineum, buttocks, umbilicus, etc.; the rash is manifested as papules or plaques, round or irregular in shape, with abundant silvery-white scales on the surface, and shiny films after removing the scales, and punctate bleeding is visible after removing the films, and this feature has diagnostic significance for psoriasis. The presence of psoriasis is an important distinction from other inflammatory arthritis. There is no direct relationship between the severity of skin lesions and the severity of arthritis, and only 35% of the two are related.
(2) Nail lesions: About 80% of patients with psoriatic arthritis have finger (toe) nail lesions, while the incidence of finger (toe) nail lesions in patients with psoriasis without arthritis is only 20%, so finger (toe) nail lesions are a characteristic of psoriatic arthritis. The common manifestation is thimble-like depressions, and multiple depressions in the nails of the inflamed distal interphalangeal joints are characteristic changes of psoriatic arthritis.
(3) Pustular cutaneous keratosis: Pustular cutaneous keratosis is hyperkeratosis of the lesioned skin. The skin lesions start as vesicles on an erythematous basis and progress to macules, papules and nodules, usually without tenderness, which can fuse into clusters with each other and form a thick scab after breaking down. They are mainly found on the soles of the feet, but can also occur on the palms of the hands and scrotum. The appearance of the lesion rash is often difficult to distinguish from the psoriasis rash. In addition, patients often develop nail plate lesions, such as thickened and cloudy nails, dystrophy, hyperkeratosis under the nail, and even nail loss.
(4) Erythema nodosum: Erythema nodosum is an acute onset of red or purplish red painful inflammatory nodules easily found on the extensor side of the calf, with sudden onset of lesions, generally bilateral and symmetrical, ranging from bean to walnut size, with a number of 10 or more, self-induced pain or pressure, moderate hardness. 3 to 4 weeks later the nodules gradually fade away, leaving temporary pigmentation. The lesions can also be seen on the thighs, upper arms, etc.
(5) Conjunctivitis: Conjunctivitis is the most common ocular complication of reactive arthritis and is uncommon in other types of spondyloarthritis. Patients usually present with unilateral or bilateral involvement, with congestion, tearing, and mucopurulent discharge from the eye accompanied by papillae on the conjunctival surface, which can be easily confused with other types of infectious conjunctivitis or “pinkeye”, and the symptoms tend to resolve within 2-7 days.
(6) Swirling glans: This is usually a painless superficial moist ulcer near the glans and urethra, with a moist surface, starting as a small blister, surrounded by inconspicuous congestion, and occasionally the superficial ulcer may fuse into a runny patch covering the entire glans, which is obviously red and inconspicuous to the touch. Most often seen in patients with reactive arthritis.
(7) Oral ulcers: Superficial ulcers mainly on the buccal mucosa and tongue, initially small blisters on the palate, gums, tongue and cheeks, with a transient course, usually without pain or other discomfort and easily ignored. It is more common in patients with reactive arthritis and spondyloarthritis with combined intestinal lesions.
(8) Enterocolitis: Arthritis associated with ulcerative colitis and Crohn’s disease is called inflammatory enteropathic arthritis. In contrast, approximately 6% or more of patients with ankylosing spondylitis have a combination of mucosal inflammation of the intestines visible to the naked eye or microscopically. The site of inflammation is mainly in the ileum, with occasional reports of microscopic colitis.
5.Other manifestations
(1) Systemic symptoms: moderate to high fever is more commonly seen in reactive arthritis, while other types of spondyloarthritis often present with low to moderate fever in more severe disease. Weight loss, anemia, and generalized weakness are also common in more severe cases.
(2) Manifestations of other organ involvement.
Uveitis is the most common combination of ocular damage in spondyloarthritis, and the literature reports that ocular uveitis can occur in about 25% of patients. Common manifestations of cardiac involvement in ankylosing spondylitis include cardiac valvular insufficiency (aortic and mitral regurgitation), varying degrees of cardiac conduction system abnormalities, and left ventricular insufficiency. Thoracic expansion is limited due to ankylosis of the thoracic spine and inflammation of the rib cage and thoracic rib joints. The most common pulmonary pleural involvement in ankylosing spondylitis is fibrotic lesions of both upper lungs, with an incidence of 1.3% to 30%. It is not uncommon to develop spinal fractures in progressive ankylosing spondylitis.
Ancillary tests
1. Laboratory tests
The rate of HLA-B27 gene positivity in patients with ankylosing spondylitis is 90% to 95%, but only about 10% of the population with HLA-B27 positivity has ankylosing spondylitis. Therefore, although the HLA-B27 test is highly specific and sensitive for ankylosing spondylitis, the HLA-B27 test results can neither be used as a basis for diagnosis nor predict the prognosis of the patient, but only increase the the possibility of diagnosis.
In active patients, increased ESR, increased C-reactive protein (CRP), thrombocytosis, and mild anemia are seen. Rheumatoid factor (RF) is negative and immunoglobulin is mildly elevated.
2. Imaging tests: X-ray, CT, MRI
X-ray manifestations have diagnostic significance for ankylosing spondylitis. The earliest changes in ankylosing spondylitis 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. Usually, the degree of sacroiliac arthritis on X-ray is divided into 5 grades: grade 0 is normal; grade I is suspicious; grade II has mild sacroiliac arthritis; grade III has moderate sacroiliac arthritis; grade IV has joint fusion and ankylosis. Figure 1 shows a grade III lesion of the sacroiliac joint.
For clinically suspicious cases, and X-rays have not yet shown clear or grade II or higher bilateral sacroiliac arthritic changes, computed tomography (CT) should be used, and the technique also has the advantage of fewer false positives. Magnetic resonance imaging (MRI) is superior to CT in determining the value of inflammation of the sacroiliac joint as well as inflammation of the spine. Only MRI examination can show grade 0 lesions of sacroiliac arthritis in ankylosing spondylitis, and the advantage of MRI is the early detection and diagnosis of ankylosing spondylitis by observing the morphology and signal changes of the synovial cartilage and subsurface bone of the sacroiliac joint in ankylosing spondylitis. Because positive x-ray signs of sacroiliac arthritis are often detected months or even years after the onset of ankylosing spondylitis, high-resolution CT or MRI scans are usually used for the detection of early sacroiliac joint lesions, and MRI of the lumbar spine can be performed at the same time.
X-rays of the spine show osteoporosis and squareness of the vertebral body, blurring of the vertebral tuberosities, calcification of the paravertebral ligaments, and formation of bony bridges. Extensive and severe ossifying bridges in the late stage are called “bamboo-like spine”, see Figure 4. Bone erosion at the pubic symphysis, sciatic tuberosity and tendon attachment points (e.g., heel bone), with reactive sclerosis and villous changes in the adjacent bone, and new bone formation may occur, which are mainly radiological manifestations of attachment pointitis.
3. Musculoskeletal ultrasound
Musculoskeletal ultrasound is becoming a powerful imaging method for the assessment of inflammatory arthritis, and has unique advantages in the determination of spondyloarthritis tendonitis, synovitis, bursitis and cysts, bone and cartilage lesions, as well as in the assessment of spondyloarthritis disease activity, prognosis and treatment outcome.
Diagnosis
(1) In 1991, the European Spondyloarthropathy Study Group (ESSG) proposed a set of classification criteria for the entire group of spondyloarthritis, which, although not intended to be clinically diagnostic, do provide some clinical guidance in identifying atypical or undifferentiated spondyloarthritis. A diagnosis of spondyloarthritis is made when one of the other conditions is added.
ESSG classification criteria for spondyloarthritis
Inflammatory spinal pain or synovitis (asymmetric or predominantly lower extremity joints) plus at least 1 of the following.
Positive family history of
psoriasis
Inflammatory bowel disease
Urethritis, cervicitis or acute diarrhea
alternating hip area pain
Tendon attachment site inflammation
Sacroiliac arthritis
(2) In 2004, the Association for the International Evaluation of Spondyloarthritis (ASAS) initiated an international collaboration to develop criteria for the classification of medial and peripheral spondyloarthritis, and in 2009 completed criteria for medial spondyloarthritis, in which the revised New York criteria required x-ray sacroiliitis only as part of, but not a mandatory condition for, imaging sacroiliitis, for those without The inflammation of the sacroiliac joint as shown by MRI in patients without radiographic sacroiliitis is also an important reference indicator, and it also combines various clinical manifestations (e.g., inflammatory low back pain, arthritis, Achilles tendonitis, etc.) and laboratory tests (HLA-B27 and CRP), which are more useful for the early diagnosis of the disease.
a) ASAS classification criteria for medial spondyloarthritis (for patients with chronic low back pain, age of onset <45 years)
Imaging sacroiliac arthritis plus at least 1 feature of spondyloarthritis or HLA-B27 positive plus at least 2 other features of spondyloarthritis
Features of spondyloarthritis: inflammatory low back pain; arthritis; Achilles tendonitis; uveitis; toe inflammation; psoriasis; Crohn’s disease/colitis; effective treatment for NSAIDS; family history of spondyloarthritis; HLA-B27 positive; elevated CRP;
Imaging sacroiliac arthritis: active (acute) inflammation on MRI highly suggestive of sacroiliac arthritis associated with spondyloarthritis; x-ray showing definite sacroiliac arthritis meeting the revised New York criteria.
b) ASAS classification criteria for peripheral spondyloarthritis (for patients with chronic low back pain, age of onset <45 years) Arthritis or tendonitis or phalangitis plus ≥ 1 spondyloarthritis Clinical features or ≥ 2 other spondyloarthritis Clinical features Uveitis, arthritis psoriasis, tendonitis, Crohn's disease/colitis , phalangitis History of previous infection, inflammatory back pain (history) HLA -B27 Family history of spondyloarthritis , imaging shows sacroiliac arthritis.
Differential diagnosis
1. rheumatoid arthritis
In the early stages of ankylosing spondylitis, it is particularly important to differentiate from rheumatoid arthritis when peripheral arthritis alone is the main manifestation.
(1) Ankylosing spondylitis is more common in men, while rheumatoid arthritis is more common in women.
Ankylosing spondylitis invariably has sacroiliac joint involvement, whereas rheumatoid arthritis rarely has sacroiliac joint lesions.
Ankylosing spondylitis involves the entire spine from the bottom up, whereas rheumatoid arthritis only affects the cervical spine.
In ankylosing spondylitis, the peripheral arthritis is few-joint, asymmetric, and predominantly in the joints of the lower extremities, and often associated with tendonitis; in rheumatoid arthritis, it is multi-joint, symmetric, and can develop in both large and small joints of the extremities.
⑤ Ankylosing spondylitis without rheumatoid nodules visible in rheumatoid arthritis.
(6) Ankylosing spondylitis is negative for rheumatoid factor, while rheumatoid arthritis is positive in 60% to 95% of cases.
(7) HLA-B27 positivity is predominant in ankylosing spondylitis, while rheumatoid arthritis is associated with HLA-DR4.
2. Gouty arthritis
Some patients with this disease have long-lasting arthritic episodes in the lower extremities, and sometimes the blood uric acid does not appear to be elevated during the onset of the disease, which often requires differentiation from peripheral arthritis caused by ankylosing spondylitis. In this case, the clinical characteristics of the two diseases need to be carefully differentiated.
3.Non-specific low back pain
This type of low back pain is the most common in clinical practice, including: lumbar muscle strain, lumbar muscle spasm, spinal osteoarthritis, cold-irritated low back pain, etc. These low back pain diseases do not have the inflammatory low back pain characteristics of ankylosing spondylitis, and are easily identified by sacroiliac joint X-ray or CT examination, as well as by performing relevant laboratory tests such as erythrocyte sedimentation rate and C-reactive protein.
4.Lumbar disc prolapse
Disc prolapse is one of the common causes of inflammatory low back pain. The disease is limited to the spine, without systemic manifestations such as fatigue, wasting, fever, etc. All laboratory tests including blood sedimentation are normal. The main difference between it and ankylosing spondylitis can be confirmed by CT, MRI or spinal canal imaging.
5. Iliac dense osteitis
The main manifestation is chronic lumbosacral pain and stiffness. There is no abnormality in clinical examination except for muscle tension in the lumbar region. The diagnosis mainly relies on anteroposterior x-ray or CT of sacroiliac joint, which typically shows obvious osteosclerotic area along the middle and lower 2/3 of sacroiliac joint in the iliac bone, 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 ankylosing spondylitis. The disease is not characterized by significant sitting or lying pain, and is not as effective as ankylosing spondylitis when treated with NSAIDs. Some women with early ankylosing spondylitis are more difficult to differentiate from this disease. MRI of the sacroiliac joint may be helpful, but still requires comprehensive clinical judgment, and follow-up observation is recommended for patients who are more difficult to identify.
Treatment
1.Non-pharmacological treatment
Patients with ankylosing spondylitis and patients with spondyloarthritis with peripheral joint lesions should pay particular attention to rehabilitation exercises. Physical exercise should be performed carefully and without interruption to obtain and maintain the best position of the spinal joints, strengthen the paravertebral muscles and increase lung capacity. When standing, you should try to maintain a posture with the chest up, abdomen tucked in and eyes level in front of you. The sitting position should also keep the chest upright. Should sleep on a relatively hard mattress, more supine position, avoid positions that promote flexion deformity, the pillow should not be too high.
2.General drug treatment
(1) Non-steroidal anti-inflammatory drug (NSAIDs)
NSAIDs can rapidly improve the patient’s back and hip pain and stiffness, reduce joint swelling and pain and increase the range of motion, whether early or late spondyloarthritis patients are preferred for symptomatic treatment. This class of drugs should not be interpreted simply as pain medications and ignore their application, this class of drugs have anti-inflammatory effects rather than simple pain relief, currently advocate that patients with ankylosing spondylitis as long as the emergence of low back pain should not hesitate to apply such drugs in full amount, full course of treatment, should not prevent the emergence of side effects and pain, otherwise long-term pain, stiffness is easy to gradually appear stiff spine, hunchback and other deformities. Rapid onset of NSAIDs and relief of symptoms is also a useful tool in the diagnosis of ankylosing spondylitis.
Because most ankylosing spondylitis is characterized by significant pain at night, bedtime application of such drugs is most effective. The more frequent adverse effects of anti-inflammatory drugs are gastrointestinal discomfort and a few can cause ulcers; other less common ones are headache, dizziness, liver and kidney damage, hematocrit, edema, hypertension and allergic reactions. The physician should select an anti-inflammatory drug for each patient. Anti-inflammatory drugs usually need to be used for about 2 months, after the symptoms are completely controlled, the dose is reduced and consolidated for a period of time with the minimum effective amount before considering stopping the drug, too quickly stopping the drug may cause recurrence of symptoms. If a drug is not effective for 2-4 weeks of treatment, it should be switched to other anti-inflammatory drugs of a different class. In the process of drug use, attention should always be paid to monitoring adverse drug reactions and timely adjustment.
(2) Glucocorticosteroid
For peripheral arthritis associated with this disease, long-acting corticosteroid injections into the joint cavity are feasible. Repeated injections should be given at intervals of 3~4 weeks, generally no more than 2~3 times. Long-term oral treatment with hormones not only fails to stop the development of the disease, but also brings more adverse effects.
(3) Sulfasalazine
This drug can improve joint pain, swelling and stiffness in spondyloarthritis, and reduce serum IgA levels and other laboratory activity indicators. It is particularly suitable for improving peripheral arthritis in patients with spondyloarthritis, and has the effect of preventing recurrence and reducing the lesions of anterior uveitis complicated by this disease. To date, there is a lack of evidence for the therapeutic effect of this drug on the mesial arthropathy of spondyloarthritis and for improving the prognosis of the disease. The usual recommended dosage is 2.0 to 3.0 g, divided into 2 to 3 oral doses. The onset of action of this product is slow, usually 4-6 weeks after dosing. Adverse reactions include gastrointestinal symptoms, rash, hematocrit, headache, dizziness, and reduced spermatozoa and abnormal morphology in males (mostly reversible with discontinuation of the drug). It is contraindicated in patients with sulfonamide hypersensitivity.
(4) Methotrexate (MTX)
This product only improves the manifestations of peripheral arthritis, low back pain, stiffness and iritis, as well as ESR and CRP levels, while there is no evidence of improvement in radiographic lesions of the mid-axis joints. It is usually administered at 7.5mg to 15mg, with individual doses increased as appropriate in severe cases, orally or by injection, once a week. Its adverse effects are a must in treatment, these include gastrointestinal discomfort, liver damage, interstitial inflammation and fibrosis of the lung, hematocrit, alopecia, headache and dizziness, so blood routine, liver function and other related items should be reviewed regularly before and after the drug.
(5) Thalidomide
Huang Feng et al. observed 30 cases of refractory male ankylosing spondylitis patients receiving thalidomide (200 mg/d) in an open trial for one year. 26 patients completed the trial and found that the drug was effective in most patients. A significant reduction in transcript levels of TNF-a in peripheral blood individual nucleated cells was also found in patients. However, the adverse effects of this drug are relatively frequent, including drowsiness, dizziness, thirst, constipation, and increased dandruff, and the rare adverse effects include decreased white blood cells, elevated liver enzymes, microscopic hematuria, and tingling sensation at the fingertips, etc. Those who choose this treatment should be closely monitored, and blood and urine routine, liver and kidney functions should be checked every 2-4 weeks during the initial period of use. For long-term users, regular neurological examination should be done to detect possible peripheral neuritis in time. The drug may cause short limb malformation (seal fetus) in pregnant women and should be contraindicated in pregnant women and in patients (including men) who intend to have children in the near future. The initial dose of 50 mg/d is increased by 50 mg every 2 weeks to 150-200 mg/d for maintenance, and 300 mg/d for maintenance in foreign countries. This drug tends to cause drowsiness and is suitable for taking at night.
(6) Leflunomide (leflunomide)
This drug is more effective in the peripheral arthritis of ankylosing spondylitis, in addition, this drug has a better effect on other symptoms of ankylosing spondylitis, such as: iritis, fever, etc. Therefore, this drug is mainly used in the clinical treatment of the extraspinal manifestations of ankylosing spondylitis. The most common side effect of this drug is liver function impairment, so it is recommended to use liver protection medication at the same time, and liver function should be checked every 2 to 4 weeks at the beginning of the drug, and then every 3 to 6 months. Loss of appetite, pruritic rash (often appearing after a longer period of time), weight loss, etc. can also occur during the course of the drug treatment.
3.Biological agent treatment
(1) Overview
The so-called biologics are monoclonal antibodies or recombinant products of natural inhibitory molecules that selectively target molecules or receptors involved in the immune response or inflammatory process, and biologics target the pathogenesis of rheumatic diseases and are more specific than traditional immunosuppressive therapy. There is increasing evidence and clinical practice that anti-TNF-α biologics are highly effective in spondyloarthritis, and they are found to be more effective in spondyloarthritis than in rheumatoid arthritis.
(2) Commonly used TNF-α inhibitors
a) Etanercept is a fusion protein expressed in mammalian cell lines by linking DNA encoding the soluble portion of the human TNF p75 receptor to DNA encoding the human IgG1Fc segment molecule. It binds reversibly to TNF-α and competitively inhibits the binding of TNF-α to the TNF receptor site. The recommended use is 50 mg subcutaneously once a week or 25 mg subcutaneously twice a week, both of which have similar efficacy in ankylosing spondylitis. Enbrel is available on the domestic market in three formulations: Lexapro, Qiangke and Enbrel.
b) Adalimumab (Xumel) is a fully humanized anti-TNF-α specific IgG1 monoclonal antibody. In vivo and in vitro experiments have shown that it binds to soluble TNF and thereby inhibits TNF binding to TNF receptors on the cell surface to achieve its anti-TNF effect. The recommended use is 40 mg subcutaneously once every 2 weeks.
c) Infliximab (gram-like) is a human/mouse chimeric anti-TNF-α specific IgG1 monoclonal antibody. Its recommended use for the treatment of ankylosing spondylitis is 5 mg/kg intravenously, with the same dose repeated at weeks 2 and 6 after the initial injection and every 6 weeks thereafter.
Currently, all three of these agents are approved by the FDA and SFDA for the treatment of ankylosing spondylitis. These drugs have a rapid onset of action (a few hours to 24 hours) and good efficacy, and most patients can rapidly achieve significant improvement in their condition. After a period of application, patients’ physical function and health-related quality of life are significantly improved, especially some newly emerged spinal mobility disorders can be restored. However, its long-term efficacy and effect on radiographic changes of the median joint remain to be observed. After 2-3 months of disease control with adequate doses of these agents, the interval between doses can be gradually lengthened, and many patients do not experience significant relapse with NSAIDs and other disease-modifying antirheumatic drugs.
(3) Adverse effects of TNF-α inhibitors
The application of this class of agents can reduce the body’s resistance to tuberculosis bacteria, so patients must be screened for tuberculosis infection before preparation for use, including inquiries about a history of tuberculosis, pulmonary imaging and tuberculin pure protein derivative testing (PPD test), and TB-SPOT testing if available. Close contact with patients with active tuberculosis should be avoided during treatment with this class of drugs, and patients with symptoms suggestive of tuberculosis infection, such as persistent cough, weight loss, and fever, should be aware of the presence of tuberculosis infection.
Other types of adverse reactions may result from this class of agents, including skin reactions at the injection site, increased risk of infection, exacerbation of active or active viral hepatitis B in patients with latent infection, exacerbation of pre-existing congestive heart failure, and neurological demyelination in some patients, and infusion reactions to infliximab in a small number of patients, who should be monitored closely when using the drug for the first time. .
4.Arthroscopic treatment
Arthroscopic access to the diseased joint, removal of synovial tissue with a rotary planing knife and aspiration can effectively relieve the refractory synovial inflammation of spondyloarthritis. The minimally invasive nature of arthroscopic operation significantly reduces the damage to the joint and its surrounding tissues caused by traditional open surgery, resulting in a much shorter postoperative recovery period for the patient. Arthroscopy can also be used to examine articular cartilage and obtain synovial tissue.
5.Surgical treatment
For patients with ankylosing spondylitis who have a more severe deformity of the spine in forward flexion or scoliosis that causes significant life impairment, such as the inability to see the road a few meters ahead when walking, such patients can consider spinal vertebral osteotomy to correct the deformity, but this type of surgery is risky, so surgery is not recommended for those whose deformity is not very serious. For patients with significant narrowing of the hip joint space or deformation of the femoral head, artificial total hip replacement can be considered.
6.Psychotherapy
Patients with ankylosing spondylitis may experience anxiety, depression, fear and other adverse emotions, and some patients may experience fatigue, narrative disorders, etc. A treatment plan combining somatic and psychological treatment should be used, and antidepressants may be applied if necessary.
Prognosis
The severity of clinical manifestations of these diseases varies widely, with some patients experiencing repeated and continuous progression and others remaining relatively quiescent for long periods of time, allowing them to work and live normally. Several types of spondyloarthritis progress gradually and all may develop into typical ankylosing spondylitis, which may also be controlled with treatment. The prognosis is poorer for younger age of onset, earlier involvement of the hip, recurrent episodes of iridocyclitis, delayed diagnosis, untimely and unreasonable treatment, and non-adherence to long-term functional exercise. Although the prognosis of the disease has improved with the advent of biologics, it is still a chronic progressive disease and should be followed for a long time under the guidance of a specialist.