Spondyloarthritis

　　1. Among all the diseases included in spondyloarthritis, B27 antigen is significantly increased. Studies have confirmed that ankylosing spondylitis and reactive arthritis have similar frequencies of B27 antigen. Peripheral arthritis in inflammatory bowel disease arthritis is evidence of extra-intestinal involvement, but its B27 antigen expression is not increased. However, 75% of patients with inflammatory bowel disease arthritis who develop spondylitis are related to B27 antigen. These findings suggest that the pathogenesis of inflammatory bowel disease arthritis is similar to that of ankylosing spondylitis, and patients with inflammatory bowel disease arthritis carrying HLA-B27 have a higher risk of developing ankylosing spondylitis. The incidence of HLA-B27 in simple psoriasis patients is not increased, and there is no evidence of increased B27 in peripheral psoriatic arthritis patients, but 45% of psoriatic spondylitis have B27 antigen, but it is significantly lower than the correlation between B27 antigen and ankylosing spondylitis and reactive arthritis. However, these studies have confirmed that psoriatic arthritis should be included in spondyloarthritis. These data suggest that there must be other factors at play in the inflammatory arthritis of the spine. Certain forms of juvenile-onset chronic arthritis should also be included in the scope of spondyloarthritis, as children with oligoarthritis have a higher frequency of B27. However, Whipple's disease and Behcet's disease are no longer included in spondyloarthritis due to the lack of correlation with HLA-B27 and their other characteristics.

　　2. The differences in onset in monozygotic twins with HLA-B27 positivity and 10% of ankylosing spondylitis patients without HLA-B27 indicate that environmental factors are also very important. Among non-genetic pathogenic factors, infection is more common. Studies on transgenic mice with HLA-B27 also found that transgenic mice living in a sterile environment do not develop ankylosing spondylitis, suggesting that environmental factors are indispensable conditions for the occurrence of HLA-B27-related diseases. However, although many studies have shown that ankylosing spondylitis is related to infection, so far, there is no definite evidence to show that the onset of ankylosing spondylitis is related to pathogenic bacteria, and the role of microorganisms in ankylosing spondylitis is still unclear. Tumor necrosis factor-α (TNF-α) is a cytokine that acts through two tumor necrosis factor receptors (TNFR1 and TNFR2) and may be related to the pathogenesis of ankylosing spondylitis. Immunohistochemical analysis found that TNF-α is an important cytokine that mediates inflammation in the sacroiliac joints of patients with ankylosing spondylitis, which also led to the first clinical trials of TNF inhibitors for the treatment of ankylosing spondylitis.

　　Ankylosing spondylitis and psoriatic arthritis spondylitis are mainly characterized by axial involvement in spondyloarthritis. As a chronic systemic inflammatory disease, spondyloarthritis often accompanied by involvement of organs such as skin and mucosa.

　　1. Axial involvement

　　Ankylosing spondylitis and psoriatic arthritis spondylitis mainly involve the axial skeleton. The broad definition of the axial range should be from the pelvis to the cervical spine, including the hip joint; the narrow definition of axial involvement mainly refers to the involvement of the neck, thoracic, lumbar, and sacroiliac joints. Axial spondylitis includes osteoarthritis, tenosynovitis, and enthesitis, etc.

　　Axial involvement includes early and late stages. The early stage is mainly manifested as inflammatory low back pain, but the radiographic manifestations of sacroiliitis have not yet appeared. These patients are often easily misdiagnosed or missed in clinical practice. The clinical manifestations in the late stage are very obvious, including sacroiliitis, partial or complete involvement of the spine, changes in the patient's body shape and posture, limited activity, and imaging changes, which are easily diagnosed in clinical practice. However, even if diagnosed correctly, the treatment is often missed the optimal treatment period, or the patient has already appeared functional limitation or disability. Therefore, it is important to pay attention to the diagnosis and treatment of early axial involvement in ankylosing spondylitis to control the condition as soon as possible.

　　1. Alternating hip pain

　　This is the most common early symptom in patients with ankylosing spondylitis. It manifests as pain in one hip or hip joint, which is quite pronounced, and severe cases can lead to limited hip movement and the inability to walk. After a period of treatment, it can improve, but it can recur and even occur alternately on both sides. Because the sacroiliac joint is deep in the buttocks, these symptoms are caused by inflammation of the sacroiliac joint or hip joint. Although both patients with ankylosing spondylitis and mechanical low back pain can experience hip pain, the ankylosing spondylitis patients are more specific in presenting with initial pain in one hip, which gradually alternates.

　　2. Inflammatory low back pain

　　The low back pain in patients with spondyloarthritis often starts subtly, with the initial location in the lumbar and gluteal regions, gradually extending to the back, becoming more pronounced in the latter half of the night, and accompanied by significant stiffness. This can lead to difficulties in turning over at night and noticeable stiffness in the lower back upon waking up in the morning, which improves after movement. The duration of this morning stiffness is related to the severity of the patient's condition, with mild cases improving in a few minutes, while severe cases can last for several hours or even the entire day. This inflammatory low back pain is an external manifestation of inflammation in the vertebral facet joints and enthesitis. Inflammatory low back pain is one of the most characteristic features of ankylosing spondylitis and a powerful tool for screening and distinguishing whether patients with chronic low back pain are affected by axial spondyloarthritis. The following five parameters better explain inflammatory low back pain, including: ① Improvement of symptoms after activity; ② Night pain; ③ Subtle onset; ④ Onset before the age of 40; ⑤ No improvement of symptoms after rest. If a patient has chronic low back pain for more than 3 months and meets at least four of the above five criteria, consider it as inflammatory low back pain.

　　3. Pain in the anterior chest wall

　　Patients with spondyloarthritis often experience pain around the anterior chest wall, with severe cases showing swelling in the sternoclavicular joint. This is due to inflammation of the manubrium sterni joint, sternoclavicular joint, and costochondritis, which gradually develops and can lead to decreased thoracic mobility in patients. Therefore, most classification diagnostic criteria for ankylosing spondylitis include restricted expansion of the chest.

　　4, Spinal stiffness

　　In the late stage of ankylosing spondylitis and psoriatic arthritis spondylitis, spinal stiffness will appear. This is mainly due to ossification of the ligaments, vertebral ribs, and costovertebral joints, which often leads to impaired mobility of the spine and increases the risk of fractures. In the late stage of ankylosing spondylitis, widespread calcification of paravertebral soft tissue, ligamentous ossification in strips or bands, and vertebral bone erosion often lead to bone spurs crossing the edges of intervertebral discs, known as ligamentum flavum ossification, which is the ossification of the annulus fibrosus itself. After extensive formation of ligamentum flavum ossification, a typical 'bamboo spine' appears. Psoriatic arthritis spondylitis often presents as asymmetric formation of ligamentum flavum ossification, paravertebral ossification, characterized by ossification of the middle part of adjacent vertebral bodies forming a bone bridge, and presenting an asymmetric distribution.

　　Two, Peripheral joint involvement

　　In addition to the axial (spinal) joints affected by spondyloarthritis, peripheral joint involvement is also a common manifestation. In the usual sense, peripheral joints include all joints except the spine (axial joints), and whether the shoulder and hip joints of patients with ankylosing spondylitis belong to peripheral or axial joints is still controversial. Many patients with spondyloarthritis experience peripheral joint swelling and pain first during the course of the disease, and only after several years do they develop symptoms of lower back pain. These patients are easily misdiagnosed with other types of arthritis and fail to receive timely and correct treatment, thereby delaying treatment and even causing disability. The incidence of peripheral joint involvement in spondyloarthritis is related to the age of the patient, showing the characteristics of lower age, more obvious peripheral joint involvement, and higher disability.

　　The main characteristics of peripheral joint involvement in ankylosing spondylitis are: more involvement of lower limb joints (knee and ankle joints) than upper limb joints, more involvement of single or oligoarticular joints than polyarticular joints, and more asymmetry than symmetry. Unlike rheumatoid arthritis, the symptoms of arthritis or joint pain in the knee and other joints, except for the hip joint, are often intermittent, with mild clinical symptoms. X-ray examination mainly shows swelling of the soft tissues around the joints, and it is rarely possible to find imaging evidence of bone destruction. Under arthroscopy, varying degrees of synovial hyperplasia and inflammatory exudation can often be seen, and rarely or rarely, serious consequences such as bone erosion, destruction, and joint deformity in the involved joints.

　　Psoriatic arthritis can affect the distal interphalangeal joints of the hands, which is different from rheumatoid arthritis, which often affects the proximal interphalangeal joints of the hands. The joint involvement can sometimes be more severe, and can present with bone erosion and destruction similar to rheumatoid arthritis, which is different from other types of spondyloarthritis.

　　Three, Enthesitis

　　Ankylosing spondylitis is a characteristic lesion of spondyloarthritis, which is less common in other diseases. In the spine, enthesitis can be seen at the attachment sites of bursae and tendons, as well as in intervertebral discs, costovertebral joints, and costotransverse joints. Pain, stiffness, and limited range of motion in spinal joints often originate from enthesitis. Enthesitis also affects many extraaxial sites, presenting as local swelling and pain in the affected areas, common sites include: the heel area (including the sole or Achilles tendon), local swelling and pain around the knee joint, ischial tuberosity, anterior superior iliac spine, pubic symphysis, and costochondral junctions.

　　4. Involvement of skin and mucosa

　　As a chronic systemic inflammatory disease, spondyloarthritis often accompanied by involvement of organs such as the skin and mucosa.

　　1. Psoriasis:Psoriatic rash often appears before psoriatic arthritis, although some patients may first experience arthritis followed by a rash. Psoriatic skin lesions commonly occur on the scalp and extensor sides of the limbs, especially the elbows and knees, and are scattered or disseminated. It is important to pay attention to skin lesions in hidden areas such as hair, perineum, buttocks, and umbilicus; the rash is presented as papules or plaques, circular or irregular in shape, with abundant silvery white scales on the surface. After removing the scales, a shiny membrane is visible, and beneath the membrane, pinpoint bleeding can be seen. This feature is diagnostic of psoriasis. The presence of psoriasis is an important distinction from other inflammatory arthritides, and the severity of skin lesions is not directly related to the severity of arthritis; only 35% of the two are related.

　　2. Nail changes:About 80% of patients with psoriatic arthritis have nail plate changes, whereas the incidence of nail plate changes in patients with psoriasis without arthritis is only 20%. Therefore, nail plate changes are a characteristic of psoriatic arthritis. Common manifestations include punctate pits, multiple depressions on the nail plates of the distal interphalangeal joints, which are characteristic changes of psoriatic arthritis. Other changes include nail plate thickening, turbidity, discoloration, or white nails, with an uneven surface, transverse grooves, and longitudinal ridges. There may be subungal hyperkeratosis, and in severe cases, nail separation, sometimes forming spoon-shaped nails.

　　3. Pustular keratosis:Pustular keratosis is the excessive keratinization of the affected skin. It refers to the skin lesions that begin as vesicles on a erythematous base, which then develop into macules, papules, and nodules. They are usually painless and can coalesce into clusters. After rupture, the skin forms a very thick scab. It is mainly distributed on the sole of the foot, but can also occur on the palm, scrotum, and other parts. The appearance of the skin lesions is often difficult to distinguish from psoriasis, and patients often experience nail plate changes, such as thickening, opacity, malnutrition, subungal hyperkeratosis, and even nail loss.

　　4. Erythema nodosum:Erythema nodosum is an acute, red or purplish-red, painful inflammatory nodule that commonly occurs on the extensor side of the lower leg. The skin lesions occur suddenly, are generally bilateral and symmetrical, range in size from broad bean to walnut, and may number 10 or more. They are accompanied by pain or tenderness and have a moderate hardness. After 3-4 weeks, the nodules gradually regress, leaving temporary hyperpigmentation. The skin lesions can also occur on the extensor side of the thigh and upper arm.

　　5. Conjunctivitis:Conjunctivitis is the most common ocular complication of reactive arthritis, and it is not common in other types of spondyloarthritis. Patients usually primarily present with unilateral or bilateral involvement, characterized by conjunctival congestion, tearing, and the appearance of mucopurulent discharge with papillary protrusions on the conjunctival surface. This condition can easily be confused with other types of infectious conjunctivitis or 'red eye disease', and the symptoms usually resolve within 2-7 days.

　　6. Whirlpool balanitis:It usually refers to painless superficial moist ulcers near the glans, urethral opening, and the surface is often moist, starting as small blisters, with不明显充血 symptoms around, occasionally superficial ulcers can merge into crawling spots, covering the entire glans, obviously red but without significant tenderness, sometimes the inner foreskin, penis, and scrotum can also be involved. It is more common in patients with reactive arthritis.

　　7. Oral ulcers:Mainly appear on the superficial ulcers of the buccal mucosa and tongue body, initially small blisters, scattered on the palate, gums, tongue body, and cheeks, the course of the disease is often transient, usually without pain or other discomfort symptoms, easy to be ignored. It is more common in patients with reactive arthritis and spondyloarthritis with intestinal lesions.

　　8. Enteritis:Ulcerative colitis and Crohn's disease associated with arthritis are called inflammatory bowel disease arthritis. And it is estimated that more than 6% of ankylosing spondylitis patients have overt or microscopic intestinal mucosal inflammation. The inflammatory site is mainly distributed in the ileum, and occasionally there are reports of microscopic colitis.

　　Fifth, other manifestations

　　1. General symptoms:Reactive arthritis often presents with moderate to high fever, while other types of spondyloarthritis may exhibit low to moderate fever when the disease is severe. Weight loss, anemia, and generalized weakness are also more common when the disease is severe.

　　2. Manifestations of involvement in other organs:Uveitis is the most common ocular damage associated with spondyloarthritis, with literature reports indicating that about 25% of patients may develop uveitis and other conditions. Common manifestations of heart involvement in ankylosing spondylitis include incomplete valve function (aortic valve and mitral valve regurgitation), abnormal function of the cardiac conduction system to varying degrees, and incomplete function of the left ventricle. Due to the ankylosis of the thoracic vertebrae, inflammation of the costovertebral and costosternal joints, the expansion of the thoracic cage is restricted. The most common involvement of the pleura and lung in ankylosing spondylitis is fibrosis in the upper lungs, with an incidence rate of 1.3% to 30%. Spinal fractures are not uncommon in advanced ankylosing spondylitis. The most common renal lesions in ankylosing spondylitis are secondary amyloidosis. IgA nephropathy is rare in ankylosing spondylitis. Other common renal manifestations include membranous proliferative glomerulonephritis.

　　The severity of clinical manifestations of diseases varies greatly, with some patients experiencing recurrent and persistent progression of the disease, while others remain in a relatively static state for a long time, able to work and live normally. Several types of spondyloarthritis may gradually progress to typical ankylosing spondylitis, and the disease may also be controlled after treatment. The onset age is relatively young, with early involvement of the hip joint, recurrent attacks of iridocyclitis, delayed diagnosis, inadequate and unreasonable treatment, and poor prognosis for those who do not persist in long-term functional exercise. Although the emergence of biological agents has greatly improved the prognosis of this disease, it is still a chronic progressive disease and should be followed up for a long time under the guidance of a specialist physician.

　　1. Laboratory examination

　　The positive rate of the HLA-B27 gene in patients with ankylosing spondylitis is 90% to 95%, but only about 10% of the HLA-B27 positive individuals in the population suffer from ankylosing spondylitis. Therefore, although the HLA-B27 test has high specificity and sensitivity for ankylosing spondylitis, the HLA-B27 test results cannot be used as a basis for diagnosis or predict the prognosis of the patient, but can only increase the possibility of diagnosis.

　　In the active phase, patients may show an increased erythrocyte sedimentation rate (ESR), elevated C-reactive protein (CRP), increased platelets, and mild anemia. The rheumatoid factor (RF) is negative and the immunoglobulin is slightly elevated.

　　2. Imaging examination

　　X-ray manifestations are of diagnostic significance for ankylosing spondylitis. The earliest changes in ankylosing spondylitis occur in the sacroiliac joint. The X-ray film shows blurred subchondral bone margin, bone erosion, blurred joint space, increased bone density, and joint fusion. Usually, the severity of sacroiliitis is divided into 5 grades according to the X-ray film: grade 0 is normal; grade 1 is可疑; grade 2 has mild sacroiliitis; grade 3 has moderate sacroiliitis; grade 4 is joint fusion and rigidity.

　　For clinical suspected cases where X-ray films have not yet shown clear or grade II or above bilateral sacroiliitis changes, computed tomography (CT) examination should be adopted. The advantages of this technology also lie in the low rate of false positives. However, due to the upper part of the sacroiliac joint anatomy being ligaments, the attachment causes irregular and widened joint spaces in imaging, making it difficult to judge. In addition, the subchondral aging of the iliac part of the sacroiliac joint, similar to the narrowing and erosion of the joint space, is a natural phenomenon and should not be considered abnormal.

　　Magnetic resonance imaging technology (MRI) is superior to CT in the diagnosis of sacroiliac joint inflammation and spinal inflammation. Only MRI can show grade 0 lesions of ankylosing spondylitis sacroiliitis. The advantage of MRI lies in observing the morphological and signal changes of the synovial cartilage and subarticular bone of the sacroiliac joint in ankylosing spondylitis, achieving the goal of early detection and diagnosis of ankylosing spondylitis.

　　3. Musculoskeletal ultrasound

　　Musculoskeletal ultrasound is gradually becoming a powerful imaging method for the evaluation of inflammatory arthritis. In the judgment of tendinous insertion inflammation of spondyloarthritis, synovitis, bursitis, and cysts, as well as bone and cartilage lesions, and in the assessment of disease activity, prognosis, and treatment effects of spondyloarthritis, it has its unique advantages.

　　1. It is advisable to choose foods rich in vitamins A, B2, and C.

　　2. The diet should be low in salt or salt-free, depending on whether the patient has hypertension or edema.

　　3. There is no need to limit water intake, and it is recommended to drink orange juice, watermelon juice, orange juice, fruit juice, and vegetable juice to promote diuresis and reduce edema.

　　4. The supply of protein should generally be in accordance with the normal requirement, 0.8 to 1.0 grams per kilogram of body weight per day. It is recommended to choose high-quality proteins such as eggs, milk, and meat to compensate for excretion loss, avoid, and treat edema and anemia.

　　5. If there are patients with hypertension or hyperlipidemia, it is necessary to limit the content of saturated fatty acids and cholesterol in the diet. For cases with anemia, it is recommended to choose foods rich in protein and iron, such as liver, kidneys, beef, egg yolks, and green leafy vegetables.

　　1. Non-pharmacological treatment

　　Patients with ankylosing spondylitis and those with peripheral joint lesions of spinal arthritis should pay special attention to rehabilitation exercises. It is important to exercise cautiously and continuously to achieve and maintain the best position of the spinal joints, strengthen paravertebral muscles, and increase lung capacity. When standing, it is best to keep the chest挺, abdomen tight, and eyes level forward. When sitting, the chest should also be kept upright. It is recommended to sleep on a relatively firm mattress, lie on the back as much as possible, avoid positions that promote flexion deformities, and do not use a pillow that is too high. Reduce or avoid physical activities that cause persistent pain. Necessary physical therapy should be chosen for pain in inflammatory joints or other soft tissues.

　　2. General medication treatment

　　1. Non-steroidal anti-inflammatory drugs (NSAIDs)

　　NSAIDs can quickly improve the pain and stiffness in the lumbar hip and back of patients, reduce joint swelling and pain, and increase the range of motion, making them the first choice for symptom treatment in both early and late stages of spinal arthritis. This class of drugs should not be simply understood as painkillers and ignored. These drugs have anti-inflammatory effects rather than just pain relief. Currently, it is advocated that patients with ankylosing spondylitis should not hesitate to use these drugs in full dose and for the full course of treatment as soon as they experience pain in the lumbar hip and back. Patients should not endure pain to prevent side effects, otherwise, long-term pain and stiffness can easily lead to spinal stiffness and hunchback deformities. The rapid onset of action of NSAIDs and the relief of symptoms are also useful tools for diagnosing ankylosing spondylitis.

　　Because ankylosing spondylitis usually causes marked pain at night, the use of such drugs before bedtime is the most ideal for efficacy. Among the adverse reactions of anti-inflammatory drugs, gastrointestinal discomfort is common, and a few can cause ulcers; other less common ones include headache, dizziness, liver and kidney damage, decreased blood cells, edema, hypertension, and allergic reactions. Physicians should select an anti-inflammatory drug based on the specific condition of each patient. Simultaneously using 2 or more anti-inflammatory drugs will not increase efficacy but will increase adverse drug reactions and even lead to serious consequences. Anti-inflammatory drugs usually need to be used for about 2 months, and the dose should be reduced after the symptoms are completely controlled, to consolidate the minimum effective dose for a period of time, and then consider discontinuation. Abrupt discontinuation can easily cause recurrence of symptoms. If a drug does not show significant efficacy after 2 to 4 weeks of treatment, other anti-inflammatory drugs of different categories should be considered. Throughout the medication process, it is always necessary to monitor adverse drug reactions and adjust them in a timely manner.

　　2. Glucocorticosteroids (glucocorticosteroids)

　　Long-term oral treatment with glucocorticosteroids not only fails to prevent the progression of the disease but also brings about more adverse reactions. For peripheral arthritis associated with the disease, long-acting corticosteroid joint cavity injections can be performed. The interval between repeated injections should be 3 to 4 weeks, generally not more than 2 to 3 times. For buttock pain that cannot be controlled by other treatments, under CT guidance, glucocorticosteroid sacroiliac joint injections can be performed, which can improve symptoms in some patients.

　　3. Sulfasalazine

　　This drug can improve joint pain, swelling, and stiffness in spondyloarthritis, and can reduce serum IgA levels and other laboratory activity indicators. It is particularly suitable for improving peripheral arthritis in patients with spondyloarthritis and has the effects of preventing recurrence and reducing lesions of this disease associated with anterior uveitis. To date, there is no evidence of the therapeutic effect of this drug on the axial joint lesions of spondyloarthritis and its effect on improving the prognosis of the disease. The recommended dosage is usually 2.0 to 3.0g, taken in 2 to 3 divided doses. This product takes effect slowly, usually 4 to 6 weeks after taking the medicine. To increase patient tolerance, it is usually started with 0.25g, three times a day, and then increased by 0.25g per week, or adjusted according to the condition or the patient's response to treatment, maintaining for more than 1 year. To compensate for the slow onset of action and insufficient anti-inflammatory effect of SSZ, a non-steroidal anti-inflammatory drug with a rapid onset of action is usually used concurrently. The adverse reactions include gastrointestinal symptoms, rash, decreased blood cells, headache, dizziness, and male sperm reduction and morphological abnormalities (most of which can recover after discontinuation). It is contraindicated in those with sulfonamide allergy.

　　4. Methotrexate (methotrexate, MTX)

　　MTX is widely used in clinical practice for the treatment of spondyloarthritis. However, comparative observations have found that this product has an improving effect on peripheral arthritis, lumbar and back pain, stiffness, and iriditis, as well as on the levels of ESR and CRP, but there is no evidence of improvement in radiographic lesions of the axial joints. It is usually administered at a dose of 7.5mg to 15mg, and for severe cases, the dose may be increased appropriately. It can be taken orally or by injection, once a week. At the same time, one non-steroidal anti-inflammatory drug can be used concurrently. Although MTX at low doses has the advantage of fewer adverse reactions, its adverse reactions are still a problem that must be paid attention to during treatment. These include gastrointestinal discomfort, liver damage, interstitial lung inflammation and fibrosis, decreased blood cells, hair loss, headache, and dizziness, etc. Therefore, regular blood routine, liver function, and other relevant tests should be reviewed before and after taking the medicine.

　　5. Thalidomide

　　China's Huang Feng and others observed 30 patients with refractory male ankylosing spondylitis who received thalidomide (200mg/d) for a period of one year in an open trial. The results showed that 26 patients completed the trial and found that the drug had a good therapeutic effect on most patients. At the same time, it was found that the transcription level of TNF-a in peripheral blood mononuclear cells of patients was significantly reduced. However, the adverse reactions of this drug are relatively frequent, common ones include drowsiness, dizziness, thirst, constipation, increased dandruff, and rare adverse reactions include leukopenia, elevated liver enzymes, microscopic hematuria, and tingling sensation in the fingertips. Close observation should be made for those who choose this treatment, and blood and urine routine, liver and kidney function should be checked every 2-4 weeks in the early stage of use. For long-term users, regular neurological examinations should be performed to detect peripheral neuritis in a timely manner. Women in pregnancy taking this drug can lead to fetal short limb deformity (seal fetus), so this drug should be contraindicated in pregnant women and those who plan to become pregnant in the near future (including men). The initial dose is 50mg/d, increased by 50mg every 2 weeks, maintained at 150-200mg/d, and 300mg/d is used for maintenance in some foreign countries. This drug is easy to cause drowsiness and is suitable for evening use.

　　6. Leflunomide

　　This drug has a good therapeutic effect on peripheral arthritis in ankylosing spondylitis. In addition, the drug also has a good improvement effect on other symptoms of ankylosing spondylitis, such as iritis and fever, so the drug is mainly used in the clinical treatment of extraspinal manifestations of ankylosing spondylitis. The drug is usually administered at a dose of 10mg/d, and the dose can be increased to 20mg/d for patients with severe illness. The most common side effect of this drug is liver function damage, and it is recommended to use liver-protecting drugs at the same time during the use of the drug, and liver function should be checked every 2-4 weeks in the early stage of use, and then rechecked every 3-6 months. Other symptoms such as decreased appetite, pruritic rash (often appearing after a long period of use), and weight loss may also occur during the treatment with this drug.

　　3. Treatment with biological agents

　　1. Overview

　　Biological agents refer to recombinant products of monoclonal antibodies or natural inhibitory molecules that selectively target molecules or receptors involved in immune response or inflammatory processes. Biological agents are specific for the pathogenesis of rheumatoid arthritis and are more specific than traditional immunosuppressive treatments. The emergence of this class of drugs has brought the treatment of rheumatoid diseases such as ankylosing spondylitis and rheumatoid arthritis into a new stage. More and more evidence and clinical practice have confirmed that anti-TNF-α biological agents have a good therapeutic effect on ankylosing spondylitis, and it has been found that the efficacy of this class of drugs on ankylosing spondylitis is better than that on rheumatoid arthritis.

　　2, Common TNF-α inhibitors

　　① Etanercept is a fusion protein expressed in mammalian cell lines by connecting the DNA encoding the soluble part of the human TNFp75 receptor and the DNA encoding the human IgG1Fc segment. It can reversibly bind to TNF-α, competitively inhibiting the binding of TNF-α to TNF receptor sites. The recommended dosage is: 50mg, subcutaneous injection, once a week, or 25mg, subcutaneous injection, twice a week, both dosages have similar efficacy for ankylosing spondylitis. There are three preparations, Yisaiyu, Qiangke, and Enbrel (Infliximab), available in the Chinese market.

　　② Adalimumab (Humira) is a fully humanized anti-TNF-α specific IgG1 monoclonal antibody. In vitro and in vivo experiments have observed that the drug binds to soluble TNF to inhibit the binding of TNF to TNF receptors on cell surfaces, thereby achieving its anti-TNF effect. The recommended dosage is subcutaneous injection of 40mg, once every 2 weeks.

　　③ Infliximab (Remicade) is a human/mouse chimeric anti-TNF-α specific IgG1 monoclonal antibody. The recommended dosage for the treatment of ankylosing spondylitis is: 5mg/kg, intravenous infusion, and the same dose is repeated after the first injection at the 2nd and 6th weeks, and the same dose is injected every 6 weeks thereafter.

　　Currently, the above three preparations have been approved by the US FDA and China's SFDA for the treatment of ankylosing spondylitis. This class of drugs has the characteristics of rapid onset (within a few hours to 24 hours) and good efficacy, and the condition of most patients can be significantly improved rapidly. After a period of application, the physical function and health-related quality of life of patients are significantly improved, especially some newly appeared spinal mobility disorders can be restored. However, its long-term efficacy and the impact on X-ray changes of the axial joints are yet to be observed. After the condition is controlled by using a sufficient amount of this type of preparation for 2 to 3 months, the interval between doses can be gradually extended, and NSAIDs and other anti-rheumatic drugs that improve the condition can be used simultaneously. Many patients' conditions will not show significant recurrence.

　　3, Adverse reactions of TNF-α inhibitors

　　The application of this type of preparation can reduce the body's resistance to tuberculosis bacteria, therefore, it is necessary to screen for tuberculosis infection in patients before use, including inquiring about a history of tuberculosis, pulmonary imaging examination, and purified protein derivative test (PPD test), and those with conditions can undergo TB-SPOT examination. It is advisable to avoid close contact with active tuberculosis patients during the treatment with this type of drug. If symptoms suggestive of tuberculosis infection such as persistent cough, weight loss, and fever occur, it is important to be aware of tuberculosis infection.

　　These preparations may also cause other types of adverse reactions, including skin reactions at the injection site, increased risk of infection, exacerbation of latent infection or active hepatitis B virus infection in patients with latent infection, exacerbation of pre-existing congestive heart failure, and some patients may develop demyelinating neurological lesions. In addition, a few patients may experience infusion reactions to infliximab, and it is recommended to closely observe the patient during the first use of the drug.

　　Fourth, Arthroscopic Treatment

　　By entering the diseased joint through the arthroscope, using a rotating shaver to remove synovial tissue and aspirate it, it can effectively alleviate the refractory synovitis of spondyloarthropathy. The minimally invasive nature of arthroscopic surgery significantly reduces the damage to the joint and surrounding tissues from traditional open surgery, greatly shortening the postoperative recovery period. Arthroscopic examination can also be used to examine joint cartilage and obtain synovial tissue.

　　Fifth, Surgical Treatment

　　For patients with severe anterior or lateral curvature deformities of the ankylosing spondylitis spine, which causes significant life difficulties, such as not being able to see the road a few meters ahead when walking, such patients may consider spinal vertebral osteotomy to correct the deformity. However, this type of surgery has a high risk, which may cause spinal cord injury and lead to paraplegia of the lower limbs. Therefore, it is not recommended to correct the deformity by surgery for those with not very severe deformities. Physical therapy and rehabilitation exercises should be carried out under the active treatment of internal medicine, which can also slow down or suppress the development of deformity to some extent. For patients with明显 narrowing of the hip joint space or deformation of the femoral head due to necrosis, total hip arthroplasty can be considered to improve the joint function and quality of life of the patients. After the replacement surgery, the joint pain of the vast majority of patients is controlled, and the function of some patients returns to normal or nearly normal. The lifespan of the implanted joint reaches 90% for more than 10 years.

　　Sixth, Psychological Treatment

　　Patients with ankylosing spondylitis may experience negative emotions such as anxiety, depression, and fear, and some patients may also experience fatigue and affective disorders. A combined treatment plan of somatic therapy and psychological therapy should be adopted, and antidepressant drugs may be used when necessary.

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