Answer: Serum-negative spondylitis, referred to as spondylitis, refers to a group of interrelated inflammatory diseases that mainly manifest in chronic progressive inflammation of the central axis joint, peripheral joint and soft tissues around the joint, including ankylosing spo

Category：hotcomm

2025-04-17

Author:

Guo Qianyu, Zhang Liyun (Shanxi Bethune Hospital)

Liu Rui, Liu Xiangyuan (Peking University Third Hospital)

Wang Xiaofei (Second Hospital of China Medical University)

Wang Xiaojing (People's Hospital of Zunhua City, Hebei Province)

Zhao Miansong (Beijing Century Temple Hospital)

Mohanyou (Affiliated Hospital of Guilin Medical College)

Shen Haili (Second Hospital of Lanzhou University)

Basics

1. What is sero-negative Spiral arthritis ?

Answer: sero-negative spondylitis, referred to as spondylitis, refers to a group of interrelated inflammatory diseases with chronic progressive inflammation of the central axis joint, peripheral joint and soft tissues around the joint, including ankylosing spondylitis, Wright syndrome, reactive arthritis , psoriatic arthritis , inflammatory bowel disease arthritis, juvenile spondylitis and undifferentiated spondylitis. Currently, the latest classification of sero-negative spondylitis is updated to two categories: axial type (axSpA) and peripheral type.

2. What are the common characteristics of sero-negative spondylitis?

Answer: The common characteristics of diseases such as include: ① Negative serum rheumatoid factor ; ② Correlation to varying degrees with HLA-B27, ankylosing spondylitis is the closest; ③ Sacroiliac arthritis with or without spondylitis; ④ Asymmetric peripheral arthritis, lower ligament joint involvement is more common; ⑤ Diseases of tendon ligament attachment points; ⑥ It can be accompanied by various extra-articular manifestations, such as fingeritis, acute anterior uveitis, oral, intestinal and genital ulcers, urethritis, prostatitis, erythema nodular erythema, etc.; ⑦ Has a tendency to have different degrees of family aggregation.

3.What is radioactive negative axial spondylitis?

Answer: radiologically negative mid-axial spondylosis (nr-axSpA) refers to patients in mid-axial spondylitis who do not meet the New York diagnostic criteria for ankylosing spondylitis revised in 1984, but have imaging evidence - MRI suggests that sacroiliac arthritis is accompanied by 1 spondylitis characteristic or HLA-B27 positive and with more than 2 spondylitis characteristics.

4. What is the relationship between ankylosing spondylitis, sero-negative spondylitis and undifferentiated spondylitis?

Answer: sero-negative spondylitis refers to a general term for chronic inflammatory rheumatoid diseases that are mainly characterized by rheumatoid factor-negative involvement of the spine, joint ligaments and tendons, including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, inflammatory bowel disease arthritis, juvenile spondylitis and undifferentiated spondylitis. Ankylosing spondylitis and undifferentiated spondylitis are both two diseases in sero-negative spondylitis. Ankylosing spondylitis is the most typical spondylitis. Undifferentiated spondyloarthritis is suitable for patients whose clinical and radiological characteristics meet spondyloarthritis but do not meet any subtype diagnostic criteria. Undifferentiated spondylitis may have peripheral and central axial manifestations and may progress to other subtypes of spondylitis.

5.What are the causes of ankylosing spondylitis?

Answer: The cause of Ankylosing Spondylaritis (AS) is not clear yet and may be related to the interaction between genetic polymorphisms and environmental factors. In patients with ankylosing spondylitis, genetic factors are the main contribution, while environmental factors may be everywhere.

(1) Genetic factors: It is generally believed that this disease is a group of polygenic genetic diseases. In addition to being highly correlated with the MHC class I gene HLA-B27, it may also be related to other genes and certain gene polymorphisms within the HLA region and outside the HLA region. More than 28 HLA-B27 subtypes have been found so far. Epidemiological data show that ankylosing spondylitis is positively correlated with B2704, B2705 and B2702, while negatively correlated with B2709 and B2706.

(2) Infectious factors, it is generally believed that ankylosing spondylitis is related to infections of Chlamydia trachoma trachoma, certain enteric pathogens such as Shigella, Salmonella, and Yersinia colon. In recent years, it has been found that Chlamydia pneumoniae, which causes upper respiratory tract infection, can also induce reactive arthritis. It is speculated that these pathogens stimulate the body's inflammatory response and immune response, causing tissue damage and causing disease.

6. Patients with ankylosing spondylitis often experience diarrhea and urination pain. Is it the cause of the disease? How to determine whether this is the reason?

Answer: ankylosing spondylitis is the result of a complex interaction between genetic polymorphisms and environmental factors. Enteric pathogens and urinary pathogens are the main environmental factors. It is currently believed that the intestinal symbiotic microbiota is directly involved in the development of spondyloarthritis. There are as many as 100 trillion bacteria in human intestinal microorganisms, representing more than 1,000 different species. Intestinal microorganisms play a key role in the development of the immune system and maintaining the homeostasis of immune cells. However, immune inflammation will also affect the intestinal flora, and it is difficult to distinguish which one is the cause and which one is the result. It is also observed in clinical practice that up to 30% of patients with inflammatory bowel disease meet the diagnostic criteria for spondylitis, and intestinal inflammation is often seen in patients with spondylitis, and subclinical intestinal inflammation may occur in up to 60% of patients with ankylosing spondylitis. Inflammatory lesions are mostly in the ileum or ileocecal flap.

7. What is HLA-B27? What is the clinical significance?

Answer: HLA-B is the B site of human leukocyte antigen. It is the product of the expression of the I gene of the main histocompatibility complex (MHC) class I gene on the surface of leukocytes. It can be detected by serological methods. It is the first HLA allele to be related to disease and the one with the highest correlation so far. It has a very strong association with ankylosing spondylitis.

8. Does HLA-B27 positive necessarily cause ankylosing spondylitis?

Answer: Although 90% of patients with ankylosing spondylitis are positive for HLA-B27, 4% to 7% of normal people are positive for HLA-B27. People with HLA-B27 positive may not all suffer from ankylosing spondylitis.

9. Is it necessary to check the subtype in patients with ankylosing spondylitis? What is the clinical significance?

Answer: HLA-B27 is the main genetic risk factor for ankylosing spondylitis. HLA-B27 is divided into more than 100 subtypes. The incidence of ankylosing spondylitis is related to B*2702, B*2703, B*2704, B*2705, B*2708, B*2710, B*2714, B*2715 and B*2719, among which HLA-B*2704 and HLA-B*2705 are susceptible haploids of ankylosing spondylitis. If ankylosing spondylitis has been diagnosed and HLA-B27 is positive, the chais type has no additional benefit to the diagnosis, so it can not be investigated; but if only HLA-B27 is positive, the clinical diagnosis is not enough to confirm sero-negative spondylitis. It is recommended to further improve the subtype examination. If it is a negatively related subtype, it will help to excrete ankylosing spondylitis.

10. Ankylosing spondylitis has a genetic tendency. Is it an autosomal or sex chromosome inheritance?

Answer: Ankylosing spondylitis is a disease with a genetic tendency, but not a genetic disease. HLA (Human Leucocyte Antigen) is a highly polymorphic complex composed of a series of closely linked loci, located on autosome chromosome 6. There is obvious familial aggregation in ankylosing spondylitis, indicating that genetic factors play a very important role in the onset of ankylosing spondylitis. Studies have shown that HLA-B27 positive patients have much greater chance of developing ankylosing spondylitis than negative patients. The positive rate of HLA-B27 in patients with ankylosing spondylitis is as high as 90% to 96%; however, HLA-B27 positive patients are not sure of developing ankylosing spondylitis. Only about 10% to 20% of HLA-B27 positive patients will develop ankylosing spondylitis, and 5% to 20% of patients with ankylosing spondylitis are always negative. This also suggests that in addition to genetic factors, there are other factors that affect the incidence of ankylosing spondylitis.

11. What are the early clinical manifestations of ankylosing spondylitis?

Answer: ① Pain or discomfort in the lumbar sacral area is the most common symptom of this disease. It occurs in concealment, which is often a hidden pain and is difficult to locate. It can also be manifested as soreness in the buttocks and groin, and the symptoms can radiate to the lower limbs similar to "scia". A few patients may have neck and chest pain as the first manifestation. Symptoms are often worsened when you are still or resting, and can be relieved after activity. Night pain can affect sleep. In severe cases, you can wake up from pain during sleep, and even get out of bed and move back to fall asleep. This is one of the indicators of the condition and activity.

② Morning stiffness is one of the common early symptoms of ankylosing spondylitis. Patients feel stiffness in their waists after getting up in the morning and relieve it after movement. In addition, hot compresses and hot water bath can also relieve morning stiffness.

③ Inflammation of the tendon ligament attachment point is also a common manifestation. Some patients may manifest pain at the thoracic rib junction, spinous process of the spinal spine, iliac crest, large trochanter, ischial tuberculosis, heel, soles of the feet and other parts.

④ About half of the patients have peripheral joint symptoms as the first symptoms, often with the main manifestations of large lower limb joints, asymmetry, and repeated arthritis, such as hips, knees, and ankles, which are rarely persistent and destructive. The pain in the early stage of the onset is mostly on one side and is intermittent, and after a few months, it is mostly on both sides, which is persistent.

12. What are the typical clinical manifestations of ankylosing spondylitis?

Answer: The typical clinical manifestations of ankylosing spondylitis are low back pain , morning stiffness, limited movement in all directions of the lumbar spine (Figure 1) and reduced thoracic mobility. The lumbar spine and thoracic mobility is reduced, and it is mostly caused by attachment inflammation in the early stage. It responds well to non-steroidal anti-inflammatory drugs, and later it is caused by spinal ankylosing, which has little response to treatment. Adhesion inflammation (Figure 2) is common manifestation of Achilles tendonitis. As the condition progresses, the entire spine may develop from bottom to top (Figure 3). First, the lumbar lordosis disappears, which then shows hunchback deformity, cervical vertebrae movement is limited, the chest ribs are connected and fused, the chest is hardened, and breathing is driven by the diaphragm.

13. Characteristics of lower back pain due to ankylosing spondylitis?

Answer: The low back pain of ankylosing spondylitis is generally inflammatory low back pain, which has the following characteristics: chronic low back pain for 3 months; onset age 40 years old; onset is hidden, accompanied by alternating buttock pain; morning stiffness lasts for 30 minutes, improves after activity, and does not improve after rest; accompanied by night pain.

14. What are the extraarticular manifestations of ankylosing spondylitis?

Answer: ① Systemic symptoms: There may be symptoms such as fever, fatigue, weight loss, anemia, etc., which are more common in the early stages. Except for a few, they are generally not serious. If the peripheral joints are affected, the systemic symptoms are more prominent.

② Ocular lesions: manifested as repeated attacks of conjunctivitis, anterior uveitis, etc. (Figure 4). However, if treatment is improper or delayed treatment, vision loss or even blindness may occur;

③Cardous lesions: rare, including ascending aortic arteritis, subaortic valve fibrosis, aortic valve insufficiency, mitral valve prolapse and mitral valve insufficiency, heart enlargement, atrioventricular block and bundle branch block, dilated cardiomyopathy and pericarditis, etc.

④ Pulmonary lesions: They can manifest as fibrosis of the upper lungs, especially the apical lung (Figure 5), cystic changes, and hollow formation, impaired lung function, and frequent opportunistic infections in the late stage. There may also be symptoms such as pleural thickening adhesion, fuzzy hilar and diaphragm, and poor striped lung swelling.

⑤ Kidney lesions: can manifest as IgA nephropathy and kidney amyloidosis.

⑥ Gastrointestinal lesions: rare. Most patients experience stomach discomfort, indigestion, etc. in clinical practice, which is mostly unrelated to the disease itself. It is caused by the gastrointestinal irritation of non-steroidal anti-inflammatory drugs; it may also be complicated by inflammatory bowel disease.

⑦Muscle nervous system: Due to spinal ankylosing and osteoporosis. Therefore, fractures are very likely to occur. The cervical spine is the most likely to occur, which is the complication with the highest mortality rate. If the patient experiences neck and back pain or limb numbness after trauma, he should be wary of the possibility of spinal fractures.

15. What are the physical examinations for ankylosing spondylitis?

Answer: Common signs of ankylosing spondylitis include sacroiliac joint tenderness, spinal flexion, posterior extension, and limited movement of the lateral curve, and reduced thoracic mobility. Commonly used tests for sacroiliac joint examination are:

Commonly used "4" tests (Figure 6). Method: The patient lies on his back, stretches one leg straight, and flexes the other leg straight on his legs (both legs are in the shape of a "4"). The examiner presses the iliac crest on the straight leg with one hand and the flexed knee with the other. If pain occurs in the sacroiliac area, it indicates that there is sacroiliac joint lesions on the flexor leg. In addition, if there is a lesion in the knee or hip , it can also be positive.
commonly used Schober test for lumbar mobility examination (Figure 7). Method: The patient was upright, with a mark of 0 at the level of the iliac crest in the midline of the dorsal, a mark of 5 cm downwards, and a mark of 10 cm upwards.The patient was bent over (keep his legs upright), and the distance between the upper and lower marks was measured. If the increase was less than 4 cm, it was positive.
thoracic mobility test (Figure 8): The patient was upright and used a soft scale to measure the 4th intercostal space level (lower edge of female breasts) and the chest circumference difference between deep breathing and inhalation is abnormal. It is less than 2.5 cm.
calculating wall distance examination (Figure 9): The patient is upright, with his heel, buttocks, and back against the wall, his chin is closed, and his eyes are looking straight. The horizontal distance between the occipital tuberculosis and the wall is measured, which is normal to 0.

16. What are the laboratory examination items for ankylosing spondylitis?

Answer: The laboratory test item has rheumatoid factors, which is often negative; about 90% of patients are positive for HLA-B27; there may be an increase in red blood cell sedimentation rate, C-reactive protein, and immunoglobulin (especially IgA) during the active period, but these indicators are not specific.

17. What are the imaging examinations for ankylosing spondylitis? What are the advantages and disadvantages of each?

Answer: Commonly used imaging methods in clinical practice include X-ray, CT, and MRI examination. These methods have their own advantages and disadvantages. Clinicians need to choose according to the situation:

X-ray examination, which is economical and simple, most widely used, and is the most commonly used imaging method. Advantages: X-ray examination of the sacroiliac joint can simultaneously understand lesions in the sacroiliac joint, hip joint, ischia, pubic joint and other parts; lumbar X-ray examination can understand whether there are ligament calcification, "shock-like" changes of the spine, square deformation of the vertebral body, and changes in physiological curvature of the vertebral facet joint and spine, and other diseases can also be excluded. Disadvantages: The sacroiliac joint surface is oblique, and X-ray examination of the sacroiliac joint is often poor due to overlapping each other.
CT examination: Advantages: High resolution, no interference at the level, slight changes in the sacroiliac joint can be found, and it is conducive to a clear diagnosis for cases that are difficult to diagnose conventional plain X-rays. Disadvantages: Cartilage lesions cannot be displayed, and there are limitations in the early stages of the disease (when there is no morphological change in the sacroiliac joint).
MRI examination: Advantages: MRI examination can show cartilage changes, bone marrow edema and osteitis, so sacroiliac arthritis can be detected earlier than CT (Figure 10). It can also estimate its activity level, which is conducive to efficacy evaluation and prognosis determination. Disadvantages: The price is relatively expensive.

18. What are the symptoms of X-ray examination of sacroiliac joints for ankylosing spondylitis?

Answer: The X-ray performance of sacroiliac joints is divided into grades 0~IV (Figure 11~I4):

Level 0 is normal; Level 1 is suspicious; Level 2 is mild abnormal, localized erosion and hardening can be seen, but the joint gap is normal; Level 13 is obvious abnormal, with erosion, hardening, widening of joint gap or narrowing, and partial antonymosis; Level 18 is a serious abnormal, manifested as complete joint antonymosis.

19. What are the symptoms of CT examination of sacroiliac joints in ankylosing spondylitis?

Answer: New York CT diagnostic standard classification divides sacroiliac joint CT into four levels:

Ⅰ (suspicious lesions): blurred lateral joint surface of the iliac bone, focal osteoporosis, mild erosion and erosion of subchondral bone, but the joint space and ligament joints are normal.
Grade II (Minor abnormality): blurred joint surface, small localized erosion, cystic changes, osteoporosis, hyperplasia, but not accompanied by joint space and ligamental joint changes.
Grade III (obvious abnormality): It is moderate or advanced sacroiliac arthritis, with obvious subchondral bone erosion, destruction and hyperplasia, obvious osteoporosis and cystic changes, joint edges are serrated, joint space is widened or irregularly narrow, joint part ankle, and ligament joint bone damage.
Grade IV (serious abnormalities): All joints show severe bone damage, hyperplasia and obvious osteoporosis, and the joints are completely ankle.

20. How to diagnose ankylosing spondylitis?

Answer: The current diagnosis of ankylosing spondylitis is based on the New York classification standard proposed in 1984:

(1) Clinical standard:

① Low back pain and morning stiffness for more than 3 months, activity improved, rest did not improve;

② The frontal and sagittal surface of the lumbar spine are limited;

③ Thoracic movement is lower than that of people of the corresponding age and normal gender;

(2) Radiological standard (Sacralization of sacroiliac arthritis is the same as that of the New York standard): bilateral ≥Ⅱ grade or unilateral Ⅲ-Ⅳ sacroiliac arthritis.

(3) Diagnosis:

①Acknowledge ankylosing spondylitis: those who meet the radiological standards and 1 (and above) clinical standards.
② Possible ankylosing spondylitis: those who meet 3 clinical standards or meet radiological standards without any clinical standards.

21. How to diagnose ankylosing spondylitis early?

Answer: ankylosing spondylitis often begins to develop clinical symptoms in adolescence or in young and middle-aged people. Only a few patients develop after the age of 40, so early diagnosis is critical. The early diagnosis of ankylosing spondylitis mainly relies on detailed medical history collection and physical examination. There are two key points required for the collection of medical history: ① inflammatory lower back pain and stiffness; ② positive family history of ankylosing spondylitis. In addition, young men should also be alert to the disease if they develop asymmetrical arthritis of lower limbs.

22. The patient's waist does not have ankle, which means repeated effusion in the knee joint. Why is the patient diagnosed with ankylosing spondylitis?

Answer: ankylosing spondylitis belongs to one of the major diseases such as sero-negative spondylitis. Midaxial spondylitis includes midaxial spondylitis without radiological manifestations and ankylosing spondylitis that meets the revised New York standards. Over time, the patient may develop from a radiologic-free stage to ankylosing spondylitis stage. Arthritis of lower limb asymmetry may occur in the early stages of ankylosing spondylitis. The most commonly involved joints are the hip, shoulder, and knee joints. If the knee joint is involved, it can manifest as intermittent swelling and effusion. Therefore, patients with repeated effusions in the knee joint may also be diagnosed with ankylosing spondylitis.

23. What are the classification criteria for central axial sero-negative spondylitis?

Answer: is an earlier diagnosis of ankylosing spondylitis. In 2009, the International Ankylosing Spondylitis Assessment Group (ASAS) proposed the classification criteria for axial spondylitis:

(1) Onset age 45 years old and ≥3 months of low back pain, plus one of the following criteria:

① Imaging shows sacroiliac arthritis plus ≥1 spondylitis characteristics;

② HLA-B27 positive plus ≥2 spondylitis characteristics.

(2) Imaging shows sacroiliac arthritis:

① MRI shows sacroiliac joint motility (acute) inflammation, which highly suggests sacroiliac arthritis related to spondyloarthritis;

② Clear imaging changes in sacroiliac arthritis (Revised in 1984 New York Standard).

(3) Characteristics of spondylitis:

①Inflammatory back pain; ②Artitis; ③Starting and stopping inflammation (Achilles tendon); ④Ophthalmic uveitis; ⑤Finger (toed) inflammation; ⑥Psoriasis; ⑦Crohn's disease, ulcerative colitis; ⑧ Good response to non-steroidal anti-inflammatory drug ; ⑨ Family history of spondylitis; ⑩ HLA-B27 positive; C-reactive protein elevation.

24. What diseases are generally distinguished from ankylosing spondylitis?

Answer: Chronic low back pain, stiffness, and discomfort are very common clinical symptoms and can occur at all ages and should be distinguished from a variety of diseases.

Mechanical low back pain: Young and middle-aged people have been engaged in various physical labor and physical activities, so low back pain is very common.
Disc herniation: There are some cases of disc herniation in clinical practice, which are atypical in the history, symptoms, signs and X-ray manifestations, which are not easy to distinguish from early and mild ankylosing spondylitis.
Rheumatoid Arthritis: For patients with peripheral joints as the first manifestation or the main symptoms, they should be distinguished from rheumatoid arthritis, and rheumatoid factors, CCP, HLA-B27 and related imaging examinations can be clear.
Dense osteitis: Dense osteitis is more common in young women, and the imaging manifests itself as osteosclerosis localized to the ilium bone, forming a characteristic sector-shaped distribution area on the X-ray.
diffuse idiopathic bone hypertrophy: more common in men over 50 years old, laboratory tests of radiological sedimentation and C-reactive protein are normal, HLA-B27 negative, no sacroiliac arthritis manifested, X-rays showed large and irregular osteophytes formed on the anterior and lateral side of the vertebrae, "flow-like" ossification of the anterior lateral ligament, and a translucent area exists between the vertebrae. The following thoracic segment is the most obvious, and more than 4 adjacent vertebrae ligaments can form a bone bridge after calcification.
suppurative sacroiliac arthritis, etc.

25. How to distinguish hip involvement in ankylosing spondylitis from sterile necrosis of the femoral head?

Answer: ankylosing spondylitis can affect the hip joints and is morphologically similar to the sterile necrosis of the femoral head. It needs to be distinguished. See Table 1 below for details.

26. Both rheumatoid arthritis and ankylosing spondylitis are painful. How to distinguish them?

Answer: Most of the middle-aged patients with rheumatoid arthritis are, and women are about 2 to 3 times that of men. The main characteristics are swelling and painful peripheral joints, which are manifested as symmetrical and erosive polyarthritis, especially the small joints of the hand and foot and accompanied by organ damage, while the central axis joint is less involved. As the disease progresses, peripheral joint deformities may occur and functional limitations may occur. The examination suggests that in addition to positive rheumatoid factor, other autoantibodies may appear, such as anti-cycliccitrulline polypeptide antibodies, anti-keratin antibodies and anti-perinuclear factors. Ankylosing spondylitis is more common in young and middle-aged men, and may have a family history. It mainly invades the central axis joints, such as spine and sacroiliac arthritis, and can cause sacroiliac joint destruction and spinal joint fusion. The peripheral joints can also be involved, but the knee, ankle, and hip joints are the main ones, and the hand joints are rarely involved, causing deformity and damage to the peripheral joints. Serological tests often indicate negative rheumatoid factor and positive HLA-B27. These two diseases can be identified through medical history, physical examination, serological examination and imaging examination.

27. Lumbar disc herniation also has low back pain. How to distinguish it from low back pain in ankylosing spondylitis?

Answer: Lucking back pain is a common disease that affects human health and can be divided into acute and chronic low back pain. Lumbar disc herniation (see Figure 15) is one of the main causes of chronic low back pain. It is characterized by excessive exercise or fatigue that can easily aggravate and can be relieved after rest, which is called "mechanical low back pain". Mechanical lumbar back pain is more common in middle-aged and elderly patients. Due to the particular structure of the lumbar spine, it is prone to mechanical damage on the basis of long-term adverse posture, strain, structural lesions of the lumbar spine. Diseases that can cause mechanical lumbar back pain include degenerative lumbar spine, lumbar muscle strain, spinal stenosis, osteoporosis and compressive fractures, severe vertebral body deformities and other diseases. Corresponding to mechanical low back pain is "inflammatory low back pain", which is more common in ankylosing spondylitis. Similar clinical manifestations may occur in other types of spondylitis such as reactive arthritis, psoriatic arthritis, inflammatory bowel disease arthritis, etc.

There are 5 criteria for determining inflammatory back pain: ① Onset before the age of 40; ② Onset of concealment; ③ Symptoms improve after activity; ④ Aggravate during rest; ⑤ Night pain (recovered after getting up). If the lower back pain exceeds three months and meet 4 of the 5 criteria, it is considered inflammatory lower back pain. The importance of distinguishing inflammatory back pain from mechanical back pain lies in the early diagnosis of ankylosing spondylitis.

Figure 15 Schematic diagram of lumbar disc herniation

28. What are the evaluation indicators for ankylosing spondylitis?

Answer: The condition evaluation indicators include Bath AS disease activity index (BASDAI), Bath AS function index (BASFI), Bath AS measurement index (BASMI), patient overall evaluation VAS score (PAG1), doctor overall evaluation VAS score (PAG2), nocturnal pain VAS score, tendon end index (EI), overall swelling joint index, and chest expansion examination.

29.What are the treatment goals for ankylosing spondylitis?

Answer: There is currently a lack of radical cure for ankylosing spondylitis, but if most patients can receive early diagnosis and regular treatment, they can control symptoms and improve prognosis. The treatment goal is to control inflammation, relieve symptoms, prevent spinal and hip stiffness or maintain optimal functional position, and avoid side effects caused by treatment.

30. What are the treatment options for ankylosing spondylitis?

Answer: The treatment plans for are:

(1) General treatment: health education and functional exercise;

(2) Drug treatment: non-steroidal anti-inflammatory drugs, anti-rheumatic drugs such as sulfasalazine, thalidomide, anti-TNFα biological agents, etc.;

(3) Surgical treatment.

31. What are the non-drug treatments for ankylosing spondylitis?

Answer: health education is the key to successful treatment. Patients should be firmly determined to treat for a long time, which will help patients actively participate in treatment and cooperate with doctors. Patients are encouraged to reasonably and persist in medical physical exercises such as spine, chest, and hip joint activities; pay attention to the correct posture of standing, sitting and lying; sleep on hard beds and low pillows, avoid excessive weight bearing and strenuous exercise to obtain and maintain the best position of the spine joints, enhance paravertebral muscle strength and increase lung capacity. Swimming is one of the best effective auxiliary treatment methods. Administer the necessary physical therapy to inflammatory joints or soft tissues. Smokers are advised to quit smoking, and smoking is one of the risk factors for poor functional prognosis.

32. What are the types of drugs for treating ankylosing spondylitis?

Answer: has five types of drugs, including non-steroidal anti-inflammatory drugs, glucocorticoid , traditional anti-rheumatic drugs, biological agents, anti-rheumatic drugs, Chinese patent medicines, etc.

33. What is the mechanism of action of non-steroidal anti-inflammatory drugs? How to use it?

Answer: This type of drug has anti-inflammatory, analgesic, antipyretic and relieve joint swelling by inhibiting cyclooxidase (COX) activity and reducing prostaglandin synthesis. cyclooxidase has two isomers, namely cyclooxidase-1 (COX-1) and cyclooxidase-2 (COX-2). Compared with non-selective traditional non-steroidal anti-inflammatory drugs, the selective COX-2 inhibitor can significantly reduce serious gastrointestinal adverse reactions. The use of nonsteroidal anti-inflammatory drugs can quickly improve the symptoms of the central axis and peripheral joints in patients with ankylosing spondylitis, and should be used continuously, regularly and in full for at least 2 weeks. If the efficacy is poor for 2 to 4 weeks, you can switch to other non-steroidal anti-inflammatory drugs, but using 2 or more at the same time does not increase the efficacy, but instead increases adverse reactions. It is not recommended to use two non-steroidal anti-inflammatory drugs at the same time in clinical practice. Gastrointestinal intolerance may add gastric mucosal protective agents or switch to selective COX-2 inhibitors. Cardiovascular events should be taken with the use of selective COX-2 inhibitors.

34. What are the slow-acting drugs for the treatment of ankylosing spondylitis?

Answer: This type of drug takes effect slowly, but can control the progression of the disease, so it is called a slow-acting drug. Commonly used drugs for the treatment of ankylosing spondylitis include sulfasalazine, which can improve joint pain, swelling and stiffness in ankylosing spondylitis, and can reduce serum IgA levels and other laboratory mobility indicators. It is especially suitable for improving peripheral arthritis in patients with ankylosing spondylitis, but there is no evidence for the treatment of central axial joint lesions of ankylosing spondylitis and the effect of improving disease prognosis. The recommended dosage is usually 2.0g per day, taken in 2 to 3 times orally, and the dosage can be increased to 3.0g/d. The dosage and course of treatment should be adjusted according to the condition or the patient's response to treatment, and the dose and course will be maintained for 1 to 3 years. It has been proven that gold preparations and penicillamine are ineffective in this disease; the efficacy of methotrexate, triplodoside, leflunomide, azathioprine, cyclophosphamide, etc. is to be affirmed.

35.What are the biological agents for the treatment of ankylosing spondylitis?

Answer: Commonly used biological agents of include etanercept, infliximab, adalimumab and golimumab. They can be used effectively for 6 to 12 weeks. When one of the agents is poorly effective or cannot tolerated, another biological agent can be replaced. The adverse reactions are mainly infusion reactions or injection point reactions, respiratory infections and opportunistic infections (such as tuberculosis). In addition, demyelinating disease, lupus-like syndrome, and congestive heart failure, but the incidence is very low. All the biological preparations listed above are TNF-α inhibitors. With the development of translational medicine, biological preparations targeting other inflammatory factors have been launched one after another, such as interleukin-17 monoclonal antibody.

36.How to use glucocorticoids in patients with ankylosing spondylitis?

Answer: generally does not advocate oral or intravenous systemic applications. Resilient tendon endopathy and persistent synovitis may respond well to local corticosteroid sugar treatment. Anterior uveitis can be better controlled by dilation of mydroop and glucocorticoid local eye spot; refractory uveitis may require systemic treatment with glucocorticoids or immunosuppressants.Intra-articular peripheral arthritis (such as knee effusion or synovial hyperplasia) for intra-articular injection of glucocorticoids. Repeated injections should be intervals of 3 to 4 weeks, generally not more than 2 to 3 times per year. For patients with stubborn sacroiliac joint pain, intra-articular glucocorticoid injection can be selected under CT-guided sacroiliac joint. Tendon enditis similar to heel pain can also be treated with local injection of glucocorticoids around the tendon.

37. Under what circumstances does ankylosing spondylitis require surgical treatment?

Answer: surgical treatment is mainly used for orthopedics in advanced patients with hip stiffness and severe spinal deformities.

38.What is the difference in the treatment of hip involvement and uninvolved ankylosing spondylitis?

Answer: Hip involvement is one of the factors of overall adverse prognosis of ankylosing spondylitis. Patients often start in childhood, experience more serious spinal structural damage and motor function impairment. Since the hip joint assumes an important function of lower limb movement, hip involvement can directly lead to impaired lower limb motor function. Studies have suggested that the overall motor function of ankylosing spondylitis patients with hip involvement is worse, so early active treatment is needed for patients with hip involvement to avoid disability. First of all, the non-steroidal anti-inflammatory drugs with sufficient treatment courses are the basic drugs for treating patients with ankylosing spondylitis with hip involvement. The effect of anti-rheumatic drugs on joint involvement is still inconclusive. Some studies have shown that methotrexate can help improve the motor function of patients with ankylosing spondylitis with hip involvement, and the effect is better than sulfasalazine. If the patient is still in a state of high disease activity after sufficient NSAID treatment, the use of biological agents should be considered. When using biological agents, it is necessary to use them actively, sufficiently and regularly, quickly control the condition, maintain the condition relief or low disease mobility and good motor function, which has a positive effect on delaying the progression of hip joint damage.

39. What are the progress in the treatment of ankylosing spondylitis? Interleukin-17 monoclonal antibody has entered the clinical stage. How to use it?

Answer: The genetic association between ankylosing spondylitis and the interleukin-23R gene and the effect of interleukin-23R gene mutation on immune system function show that drugs targeting interleukin-23 and downstream interleukin-17 have great prospects. At present, monoclonal antibodies against interleukin-17A have been launched and are used in the treatment of psoriatic arthritis, psoriasis and ankylosing spondylitis. The recommended dose is once a week at 300 mg/time for the first 5 weeks, and is administered subcutaneously, followed by 300 mg every 4 weeks. For patients weighing less than 60kg, the dose is halved or used as prescribed by the doctor.

40. What is the best treatment for ankylosing spondylitis? What are the treatment principles?

Answer: The principle of treatment of ankylosing spondylitis is to maximize the patient's quality of life by improving symptoms and controlling inflammation, preventing progressive structural destruction, protecting or improving patient's functions and ability to participate in social activities. Based on the clinical expert experience and research evidence, many suggestions are given: NSAIDs, physical therapy and patient education are first-line treatments; local injection of glucocorticoids can be considered in musculoskeletal inflammation sites; sulfasalazine can be used in patients with peripheral arthritis; for patients who are still highly active after treatment of traditional anti-rheumatic drugs, TNF-α inhibitors can be used, and for patients who are ineffective with one TNF-α inhibitor, they can be replaced with another. Recently, the entire human interleukin-17α monoclonal antibody, sekinumab, has been approved for the treatment of ankylosing spondylitis. Intractable hip pain or dysfunction occurs in the late stage of the disease and X-rays suggest that structural disruptors consider hip replacement, and patients with spinal deformities and acute vertebral fractures are considered for spinal correction. The ideal treatment option is a combination of non-pharmaceutical therapy and drug therapy.

41. Can patients with sulfasalazine be replaced by mesarazine for treatment of ankylosing spondylitis?

Answer: Although sulfasalazine and mesalazine are both aminosalicylic acid drugs, their ingredients are not the same. Sulfalazine is a conjugated compound of 5-aminosalicylic acid with anti-inflammatory effects and sulfadiazine with anti-bacterial effects, both connected by an azo bond.Although the drug has been available for more than 70 years, its principle of action in rheumatism is still not fully understood. It is currently believed that sulfasalazine has multiple anti-inflammatory effects and also shows multiple immune regulatory effects. Sulfarazine can inhibit the proinflammatory arachidonic acid cascade reaction, downregulate neutrophil chemotaxis, migration, synthesis and degranulation of proteolytic enzymes, inhibit T cell proliferation and natural killer cell activation, and in these effects, the original compound Sulfarazine is better than sulfapyridine or 5-aminosalicylic acid. Research on the active part of sulfasalazine found that sulfasalazine and sulfatazine are active ingredients in the treatment of arthritis, while 5-aminosalicylic acid is an effective group for the treatment of ulcerative colitis. The active ingredient of mesalazine is 5-aminosalicylic acid, which is not the main active ingredient in the treatment of ankylosing spondylitis, so it cannot replace sulfasalazine. Of course, for patients with ankylosing spondylitis with enteritis or ulcerative colitis, mesalazine can also be tried if sulfasalazine is allergic to it.

42. Can sulfasalazine suppository be substituted for oral treatment of ankylosing spondylitis?

Answer: orally administered sulfasalazine will be absorbed by the intestine. After most sulfasalazine reaches the colon, the intestinal bacteria here reduces its azo bond and forms two active groups - sulfadiazine and 5-aminosalicylic acid. Most sulfadiazine is absorbed through the colon and is taken orally for 4 to 6 hours in plasma (under oral dose of 2 g/d). Most 5-aminosalicylic acid stays in the intestine. Since sulfasalazine cannot be decomposed into active groups through the anal plug, it cannot be replaced by oral administration.

43. Do patients with ankylosing spondylitis need to take medication for life?

Answer: generally emphasizes that patients with ankylosing spondylitis should take medication for at least one year, and then analyze it according to the specific situation. Although the disease is a chronic disease, the treatment goal is to improve symptoms and control inflammation, prevent progressive structural damage, protect patient function, and maximize patient function. The treatment of ankylosing spondylitis should be based on the greatest care for the patient, and the patient and doctor should jointly formulate treatment plans. Currently, the study shows that there is no strong evidence that the continuous use of non-steroidal drugs can delay the radiological progress of the disease. Slow-acting drugs such as methotrexate, leflunomide, sulfasalazine are ineffective for central axis lesions, and long-term use of biological agents can cause adverse reactions such as infections and malignant tumors, and the medical expenses are expensive. Therefore, the pros and cons of the disease need to be weighed in the treatment plan, and doctors and patients jointly formulate safe and effective treatment plans. According to the 2019 ACR/SAA recommendation, it is not recommended to reduce the anti-TNFα biologics in patients with stable ankylosing spondylitis.

44. What exercises are available for ankylosing spondylitis? What auxiliary therapies can help relieve this disease?

Answer: functional exercise is one of the important measures for the treatment of ankylosing spondylitis. Regular exercise, especially for spine, chest, hip joint activities, etc., is more effective. Patients in the late stage also need to correctly stand, sit, and lie down, sleep on a hard bed, low pillow, and avoid excessive weight bearing and strenuous activities. Gymnastics, swimming, yoga, single and double bars, etc. are all good exercise methods. A spa or hot bath can be used before workout. In patients who have already experienced spinal fusion or osteoporosis, vigorous or confrontational exercise should be avoided to avoid fractures.

45.What are the factors that affect the prognosis of ankylosing spondylitis?

Answer: studies have proved that there are multiple indicators that affect the prognosis of ankylosing spondylitis, including: hip arthritis; sausage-like fingers or toes; poor efficacy of non-steroidal anti-inflammatory drugs; elevated blood sedimentation (30mm/1h); limited mobility of lumbar spine; oligoarthritis and onset age of 16 years. Other factors may also be associated with poor prognosis in patients with ankylosing spondylitis, such as smoking, radiological changes in progressively exacerbated, active lesions (assessed by disease activity index), dysfunction (self-report assessment), low education, other diseases associated with spondylitis (e.g., psoriasis, inflammatory bowel disease), male, a history of uveitis and various occupational activities involving dynamic flexibility (ability to bend, twist and stretch quickly, repeatedly) or body vibration (such as driving a truck or operating heavy equipment).In addition, those with delayed diagnosis, untimely and unreasonable treatment, and those who do not insist on long-term functional exercises have poor prognosis.

46. What are the differences in the clinical manifestations of patients with HLA-B27-positive and HLA-B27-negative ankylosing spondylitis?

Answer: ①HLA-B27 positive people are more likely to have central axis joint involvement. ②People with HLA-B27 positive are more likely to experience hip pain and hip joint lesions. ③People with HLA-B27 positive are more likely to develop acute iriditis. ④ HLA-B27 positive patients have more severe inflammatory changes, such as higher levels of erythrocyte sedimentation and C-reactive protein. ⑤The tendency of family aggregation among HLA-B27 positive people is more obvious. ⑥ The age of onset of HLA-B27 negative patients is relatively late and the age of diagnosis is relatively late.

47. Can ankylosing spondylitis be eradicated?

Answer: ankylosing spondylitis is a chronic disease and cannot be cured or cured. However, as long as it is discovered early and treated early, on the basis of effective treatment plans and active cooperation between doctors and patients, patients can maintain normal spinal and joint functions and ensure quality of life.

48. Will you be in danger of life if you have ankylosing spondylitis?

Answer: This disease generally does not affect life span, but it will affect the patient's normal life and work, and even disability. Timely and correct treatment can reduce the risk of severe spinal and joint deformities. Hip involvement, HLA-B27 positive, persistent erectal sedimentation and increased C-reactive protein, juvenile onset, smoking, etc. are usually related factors for poor prognosis.

49. Will all patients with ankylosing spondylitis eventually suffer from hunchback, straight spine and bent?

Answer: is not certain, some patients will experience hunchback, straight spine and bent down (see Figure 16). The course of ankylosing spondylitis is characterized by self-relieving and aggravating, and the prognosis varies greatly between patients. It is generally believed that the disease presents a mild or self-limiting process and has a good prognosis. Patients who have lost their ability to work mostly occur after 10 years of disease course, and those who have lost their function can reach 10% to 30% after 10 years of disease course. Older age of onset, low physical labor and education are high-risk factors for inability to work. Therefore, the first 10 years of the disease are crucial to the prognosis. If you actively treat it, grasping the treatment opportunity can prevent spinal deformities and protect your work ability.

Figure 16 The process of hunchback in patients with ankylosing spondylitis

50. I had ankylosing spondylitis when I was a child. Will this disease affect the growth of the body?

Answer: Ankylosing spondylitis mainly invades the spine and can lead to bone ankylosing and deformities. In patients with younger ankylosing spondylitis, if spinal ankylosing or hip joint involvement occurs, it will affect the patient's height. After adulthood, you suffer from ankylosing spondylitis. As the condition worsens, the spine will undergo a bamboo joint change, and the physiological curve of the spine will cause height changes. The more severe the damage, the greater the change in height, and the height will become shorter and shorter. In severe cases, hunchback or even lifelong disability may occur.

Fertility chapter

51. Will ankylosing spondylitis be hereditary?

Answer: ankylosing spondylitis has a genetic tendency. There is obvious family aggregation in ankylosing spondylitis. Studies have found that the positive rate of HLA-B27 in first-degree relatives of patients with HLA-B27-positive ankylosing spondylitis is higher, and about 10% to 30% of them may have symptoms or signs of ankylosing spondylitis. Compared with HLA-B27 heterozygote, HLA-B27 homozygote has a 2-fold risk of ankylosing spondylitis.

52. What is the relationship between the onset of ankylosing spondylitis and gender?

Answer: Most men suffer from ankylosing spondylitis, and it is reported that the ratio of men and women is 2~3:1. However, an epidemiological survey on the diagnosis prevalence of male and female ankylosing spondylitis patients in the United States shows that the incidence of ankylosing spondylitis in women has gradually increased in the past 10 years, and the male-female ratio can even reach 1:1, but the condition in men is more serious. Studies have also found that radionegative axial spinal arthritis is more feminine and that women are more likely to misdiagnose or delay diagnosis.

53.What are the characteristics of ankylosing spondylitis in women?

Answer: ①The disease form and condition are different: male patients have acute onset, early onset, severe symptoms, rapid progression, poor prognosis, and more systemic symptoms such as fever, fatigue, and weight loss. Women are the opposite.② Different involved joints: Men are more likely to be affected by lumbosacral, cervical vertebra, hip joint and long spine, while women are more likely to be swollen and painful in peripheral joints such as wrist, elbow, and knee, especially in the knee joint and pubic joint involvement than men. Studies have shown that male patients have more spinal imaging changes and hip involvement than women, and overall, men seem to be more serious than women.

54. Will ankylosing spondylitis affect sexual function?

Answer: will affect. Studies have found that this disease will have a great impact on the sexual function of patients with ankylosing spondylitis, both men and women. Joint spinal function, pain, depression, disease activity, unemployment and lack of self-confidence are all independent factors that affect sexual life. Studies have also shown that the sexual function index of ankylosing spondylitis in women is associated with higher depression levels, while sexual function in men is associated with cumulative exposure to smoking and dependence on smoking.

55. The most common use of sulfasalazine in female patients with ankylosing spondylitis. In order to reduce its side effects, do I need to supplement folic acid during pregnancy? How to use it? Same as an ordinary pregnant woman?

Answer: sulfasalazine can be used to control the activity of ankylosing spondylitis. In the study, no newborn deformity rate in patients with pregnancy stage 3 who took this drug was higher than that of normal people. Therefore, if the disease requires sulfasalazine, you can use it. Since sulfasalazine can degrade folic acid in the body, interfere with folic acid metabolism, and women's demand for folic acid has increased significantly since 3 months before pregnancy, patients are advised to supplement folic acid. Oral dose of sulfasalazine 2g/d can be supplemented with folic acid, and 2mg/d is appropriate.

56. Will ankylosing spondylitis affect the patient's fertility?

Answer: Since ankylosing spondylitis is mostly caused by young and middle-aged people, fertility is worthy of attention. Many studies have shown that the fertility function of patients with ankylosing spondylitis is not affected. A survey of 939 female ankylosing spondylitis patients from the United States, Canada and 11 European countries by the International Ankylosing Spondylitis Association showed that ankylosing spondylitis has no adverse effect on women's fertility, with an average of 2.4 pregnancy times per patient, of which 1.4 were during the disease activity. For men, studies have shown that there is no significant difference in sperm quality in male patients with ankylosing spondylitis and the normal population, but the incidence of varicocele increases.

57. What impact does pregnancy affect the condition of female patients with ankylosing spondylitis?

Answer: About ~ 60% of patients with ankylosing spondylitis have stable or improved during pregnancy, and a small number of them may experience disease activity. Studies have shown that about 33.2% of patients have no change in their condition during pregnancy, 30.9% have improved, and 32.5% have active conditions. At about 20 weeks of pregnancy, morning stiffness and low back pain may worsen, especially at night, which can be relieved for several days or weeks. There are also studies that have observed that patients with ankylosing spondylitis who are pregnant with girls have more symptoms of remission during pregnancy than those who are pregnant with boys. About 50% of patients relapse within six months after childbirth, and being in disease activity during conception is a predictor of postpartum disease recurrence.

58. What impact does ankylosing spondylitis have on the pregnancy outcomes and newborns in female patients?

Answer: Most previous studies have shown that there is no adverse effect on pregnancy outcomes of ankylosing spondylitis in women or newborns. The study shows that about 93.2% of patients can give birth in full term, while most newborns are healthy, with an average birth weight of 3339 g. A recent study in South Korea that included 1,293 delivery cases of 996 patients with ankylosing spondylitis showed that compared with those matching age and year of delivery, there were no significant differences in maternal complications and fetal outcomes, including growth restriction, fetal malformations and Apgar scores, indicating that the pregnancy outcomes of patients with ankylosing spondylitis were consistent with healthy people; however, a study from Sweden that included 388 patients with ankylosing spondylitis showed that women had high incidence of emergency or elective cesarean section, and offspring were more likely to have premature births and less than gestational age, and fewer fetal loss. Therefore, although most studies show that the fetal prognosis of ankylosing spondylitis is not affected, considering that patients with this disease may have potential high risks in each pregnancy, it requires close cooperation between rheumatologists and obstetricians.

59. Do female patients with ankylosing spondylitis need a cesarean section when giving birth?

Answer: is not. Studies have shown that sacroiliac arthritis, including complete ankinetic sacroiliac joints, is not a contraindication for vaginal delivery. There are also studies showing that there is no clear correlation between the severity of sacroiliac arthritis and cesarean section. Studies have shown that compared with normal populations, the rate of cesarean section in women with ankylosing spondylitis is higher, but the success rate of transvaginal delivery patients with ankylosing spondylitis excluding selective cesarean section is not different from that in the control group. For patients who do require cesarean section, epidural anesthesia is generally performed because most patients have a short course of disease and are not affected by spinal ligaments.

60. What drugs can be used during pregnancy for rheumatic diseases?

Answer: According to the British Society of Rheumatology (BSR) and the European Union for Anti-Rheumatism (EULAR), patients with rheumatoid diseases during pregnancy can use low-dose glucocorticoids, and non-steroidal anti-inflammatory drugs can be used within 32 weeks of pregnancy. The recommended non-steroidal anti-inflammatory drugs are ibuprofen (use with caution in the early pregnancy); some slow-acting anti-rheumatoid drugs such as hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus (required for blood concentration monitoring) and cyclosporine (required for blood concentration monitoring) can also be used during pregnancy; biological agents that can be used include pecelizumab (available throughout pregnancy), adalimumab, golimumab, etanercept (available for early and middle pregnancy) and infliximab (available before 16 weeks of pregnancy). For anticoagulants, low-dose aspirin and low-molecular heparin or common heparin can be used during pregnancy.

61. What drugs are not recommended during pregnancy for rheumatic diseases?

Answer: According to the British Society of Rheumatology and the European Anti-Rheumatology Alliance, COX-2 inhibitors are not recommended for patients with rheumatoid diseases during pregnancy; slow-acting anti-rheumatoid drugs such as methotrexate, cyclophosphamide, mycophenolate and leflunomide; biological agents such as rituximab, belimuzumab and urinumumab; and anticoagulants such as warfarin, apixaban, rivaroxaban and dabigatran.

62. During pregnancy, do you have to take medication for the treatment of ankylosing spondylitis? What effect will take medications for ankylosing spondylitis play in adverse pregnancy?

Answer: is not necessarily. The treatment of ankylosing spondylitis needs to be individualized. During pregnancy, most patients' condition remains stable or improved, and a few patients' condition worsens. If the condition worsens, safe and effective treatment measures can be selected according to the condition.

63. It has been reported that non-steroidal anti-inflammatory drugs can cause difficulties in implanting fertilized eggs in early pregnancy. Which type of non-steroidal anti-inflammatory drugs are more obvious?

Answer: studies show that whether it is a non-selective non-steroidal anti-inflammatory drug or a selective COX-2 inhibitor, it can affect the implantation of the embryo and ovulation of women, so it is recommended to avoid using it during pregnancy preparation.

64. Women with ankylosing spondylitis must not use thalidomide during pregnancy. So, should my husband stop taking it? Will thalidomide cause oligospermia and sperm malformation?

Answer: thalidomide is a glutamate derivative. Under physiological PH conditions, there are two optical isomers - R (right-order) and S (left-order). The R configuration - has a sedation effect, and the S configuration - is related to teratogenicity.

The effects of thalidomide include: ① Central nervous system inhibitory effect (sedation effect): hypnosis, analgesia, antiemetic, anti-anxiety, and anti-anxiety. Thalidomide has a piperidine ring structure that induces sleep, so itchy effect has a sedative effect; ② Immunomodulation and anti-inflammatory effect: Thalidomide can regulate the secretion of other cytokines induced by TNF-α, thereby regulating the body's immune state; inhibit the migration and adhesion of white blood cells, thereby reducing the inflammatory response; ③ Anti-angiogenic effect: used for the treatment of anti-tumor and hematologic diseases. Thalidomide has a clear teratogenic effect on pregnant women, so it is an absolute taboo for women during pregnancy. Currently, studies on potential teratogenicity of drugs focus on the exposure of pregnant women before and during pregnancy, and there are few similar studies in men.

The pathogenesis of male teratogenicity is mainly two aspects: ① The direct effect of drugs on sperm development, leading to genetic changes or epigenetic changes; ② Semen transfer, that is, drug metabolites in the semen during sexual intercourse caused by the exposure of vaginal mucosa. This mechanism depends on the concentration of the drug in the semen and the absorption of the drug in the vagina. Although many drugs are transferred to semen, the drug concentration is usually low and the amount of further dilution of drugs in the vagina is negligible. Thalidomide can be detected in the semen of male patients who take oral thalidomide, but the concentration is very low. Considering the high teratogenic risk of mothers' exposure to thalidomide and the hypothetical risk of semen transfer, as well as the study on the effect of thalidomide on male sperm quality, it is recommended that male patients avoid using this drug within the first three months of pregnancy.

65. Female patients with ankylosing spondylitis have sexual frigidity, but want to get pregnant earlier. Can Viagra be used? If it cannot be used, which drugs are better?

Answer: (1) "Viagra" is sildenafil citrate, which is mainly used for male erectile dysfunction due to dilatation of blood vessels, but is ineffective for female patients with sexual frigidity.

(2) Treatment of female sexual frigidity can start from the cause, remove the cause, learn some reading materials about sexual knowledge, care for each other between husband and wife, and eliminate negative psychological factors. There are many factors that cause sexual indifference in women, mainly as follows: ① Physical diseases: Gynecological diseases such as ovarian cysts and ovarian tumors lead to low estrogen levels, which can make women lack sexual desire and have no sexual impulses; any chronic disease can cause sexual indifference due to neuroendocrine disorders; ② Mental factors, chronic fatigue, high work pressure, affect advanced neurological functions; different sexual concepts, excessive suppression of one's own needs, not allowing one to enjoy a pleasant sexual life, or even disgust sexual intercourse; couples (partners) have dissonance in their relationship, and women feel resentful or pessimistic, negative or even despair, suppressing their own sexual needs. ③Special drugs: such as antihistamines, androgens, reseral, etc.

(3) In 2015, the US FDA approved the "female Viagra" - flibanserin to be launched, which increases the sexual desire of women by increasing neurotransmitters (dopamine and norepinephrine) in the brain that help stimulate sexual desire, but it cannot be immediate and will take several weeks to take effect. Long-term use may cause nausea, drowsiness, dizziness, hypotension and fainting, especially when used with alcohol, which increases the risk of fainting and accidental injury. It is not clear whether it can be used before pregnancy.

66. If ankylosing spondylitis suffers from worsening inflammatory low back pain during pregnancy, how to treat it?

Answer, about 30% of patients with ankylosing spondylitis may develop disease activity during pregnancy. The following measures can be taken when inflammatory back pain worsens during pregnancy:

(1) General treatment: Appropriate functional exercise and physical therapy, such as exercise, physical therapy, etc. It is necessary to pay attention to the movements during exercise to avoid violent running, jumping, bending, etc.;

(2) Local medication: Nonsteroidal plasters or patches with single local ingredients can also relieve symptoms, which are safe during pregnancy. Patients who are allergic to tape should pay attention;

(3) Nonsteroidal anti-inflammatory drugs: Patients with severe inflammatory back pain can take oral Nsteroidal anti-inflammatory drugs. Nsteroidal anti-inflammatory drugs are classified as B or C by the FDA and can be applied within the first 32 weeks of pregnancy. Nonsteroidal anti-inflammatory drugs are divided into nonselective COX inhibitors and selective COX inhibitors. Two U.S. and two European population-based case-control clinical studies have shown that exposure to nonselective COX inhibitors (including aspirin) in early pregnancy does not increase the incidence of congenital malformations in neonates and can be continued in early and middle pregnancy. However, the guidelines recommended by the British Society of Rheumatology still recommend caution in early pregnancy (the risk of miscarriage and malformations cannot be ruled out). Since such drugs are detected in milk in small amounts, they can be considered during breastfeeding. Nonselective COX inhibitor drugs available include ibuprofen and naproxen; for selective COX-2 inhibitors such as celecoxib and etocoxib, studies have shown that the miscarriage rate caused by such drugs is 15.5%, and the congenital malformation rate is 7.9%, which is significantly higher than that of the control group. Therefore, the EULAR expert group recommends avoiding use during pregnancy.

(4) Biologics: Currently, TNF-α inhibitors used in the treatment of ankylosing spondylitis in China mainly include etanercept (ETA) and its biosimilars (trade names: Ambenau, Yisep, Junker), infliximab (IFX) and adalimumab (ADA). When selecting TNF-α inhibitors for women of childbearing age, differences in placental metastasis related to molecular structure and half-life need to be considered. TNF-α inhibitors are divided into two categories: monoclonal antibody and receptor fusion protein. The anti-TNF-α structure that can be transported by the placenta after 16 weeks of pregnancy contains the IgG1-Fc segment. Therefore, it is theoretically safe to use anti-TNF-α before 16 weeks of pregnancy, and many studies have also supported this view. Because infliximab has a high bioavailability and placental transport rate, it is recommended to avoid use after 16 weeks of pregnancy. If infliximab is required for disease activity, live vaccines should be avoided within 7 months of the baby's birth. Therefore, it should be avoided in the third trimester. The molecular weight of monoclonal antibodies in breast milk is relatively large and is decomposed in the infant's digestive tract. Therefore, the infant absorbs very few drugs through breast milk, and biological agents can be used during breastfeeding.

(5)Sulaxanthin: It is relatively safe to use sulfasalhin during pregnancy. This drug can be used in patients with ankylosing spondylitis with peripheral joint involvement, and is not recommended for patients with pure axial spondylitis. Studies have found that this drug and metabolites can pass through the placenta, but they have not shown their teratogenicity, so most rheumatologists believe that this drug can continue to be used during pregnancy. Since sulfasalazine can degrade folic acid in the body, interfere with folic acid metabolism, and women's demand for folic acid has increased significantly since 3 months before pregnancy, patients are advised to supplement folic acid. Oral dose of sulfasalazine can be supplemented with folic acid, which is suitable for 2mg/d; although it is clinically believed that this drug can be used in lactation, since the active metabolite of sulfasalazine can replace bilirubin, breastfeeding should be avoided for premature infants, hyperbilirubinemia, and neonatal mothers with lack of glucose-6-phosphate dehydrogenase. For male patients, since this drug can cause reversible sperm reduction, it is necessary to stop taking the drug for more than 3 months to consider preparing for pregnancy.

67. Both couples are patients with ankylosing spondylitis and are both positive for HLA-B27. In order to prevent offspring from getting this disease, can you do a third-generation test tube and transplant an embryo that does not carry the B27 gene and is a female, so as to reduce the incidence of offspring?

Answer: is not recommended to do third-generation test tubes. Although ankylosing spondylitis is affected by genetic factors, the disease is not a genetic disease, but a result of the combined action of genetic and environmental factors. It has been observed in clinical practice that the positive rate of HLA-B27 in patients with ankylosing spondylitis is as high as 90% to 96% of patients with ankylosing spondylitis; those with HLA-B27 are not sure to suffer from ankylosing spondylitis, and only about 10% to 20% of patients with ankylosing spondylitis will develop ankylosing spondylitis, and HLA-B27 is always negative in 5% to 20% of patients with ankylosing spondylitis. Therefore, this disease is not an indication for third-generation IVF. Even if an HLA-B27-negative embryo is transplanted, it cannot guarantee that the disease will not occur in the future.

68. What drugs are available during lactation of ankylosing spondylitis?

Answer: According to the British Society of Rheumatology (BSR) and the European Anti-Rheumatology Alliance EULAR, the small dose of glucocorticoids, non-steroidal anti-inflammatory drugs, hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, adalimumab, etanercept, golimumab, infliximab and other drugs that can be used during pregnancy. In terms of anticoagulant drugs, in addition to using small doses of aspirin and heparin during breastfeeding, warfarin can also be selected if long-term anticoagulation is required.

69. Will the use of biological agents for male ankylosing spondylitis affect fertility?

Answer: TNFα inhibitor is one of the important drugs for ankylosing spondylitis. The study found that during the preconception phase, exposure of fathers to TNF-α inhibitors may be safe for pregnancy outcomes. Studies have also shown that male patients who gave birth to healthy newborns during the treatment of the drug still need to further expand the sample size due to the small sample size. Studies have shown that men with ankylosing spondylitis did not have an adverse effect on sperm quality after using TNFα antagonist for 3 to 6 months, but the current data are limited.

70. Male, 32 years old, suffered from ankylosing spondylitis for 5 years, took Lessom (60mg, 3 times/day), sulfasalazine (1.0g, 2 times/day) and thalidomide (75mg, 1 time/night). He is now married for 2 years. His wife plans to get pregnant and have a child. Should the medicine be stopped? How long does it take to disable the use to have a child? What other medicines should I change?

Answer: leson can be used without stopping, and the lowest effective amount should be taken, while sulfasalazine and thalidomide should be discontinued 3 months in advance. Anti-TNFα biological agents such as etanercept or adalimumab can be replaced.

71. Female, 35 years old, suffered from ankylosing spondylitis for 12 years, has been treated with Siloborg (0.2g, 2 times/day), sulfasalazine (1.0g, 2 times/day) and thalidomide (50mg, 1 time/night), intermittent use of Yisep (25mg, subcutaneous injection, 1 time/month). I have been married for 4 years and am preparing to get pregnant and have children. Should the medicine be discontinued? How long does it take to disable the use to have a child? What other medicines should I change?

Answer: (1) Xilebao is a selective COX-2 non-steroidal anti-inflammatory drug, which can affect implantation of fertilized eggs. It is recommended to stop taking the pregnancy for 1 to 3 months. If the pain worsens in the early and middle stages of pregnancy, ibuprofen or loxolophen can be replaced, but it will not be used after 32 weeks of pregnancy;

(2) Sulfarazine can continue to be used during pregnancy preparation and pregnancy, but folic acid must be supplemented, 2 mg per day. If the child has premature birth, the use will be stopped during breastfeeding and normal delivery can be continued.

(3) Thalidomide cannot be used during pregnancy preparation, pregnancy and breastfeeding.

(4) Yisaipu is an anti-TNFα biological agent and can be used during pregnancy preparation, pregnancy and breastfeeding. If the patient is active, the injection frequency can be increased to 1 to 2 times a week.

Author:

Guo Qianyu, Zhang Liyun (Shanxi Bethune Hospital)

Liu Rui, Liu Xiangyuan (Peking University Third Hospital)

Wang Xiaofei (Second Hospital of China Medical University)

Wang Xiaojing (People's Hospital of Zunhua City, Hebei Province)

Zhao Miansong (Beijing Century Temple Hospital)

Mohanyou (Affiliated Hospital of Guilin Medical College)

Shen Haili (Second Hospital of Lanzhou University)