Seronegative spondyloarthropathy

　　Currently, research believes that environmental factors and genetic characteristics (susceptibility) are two important factors leading to the onset of SPA. Studies have found that there is a close association between seronegative spondyloarthropathy and HLA-B27, with a positive rate of HLA-B27 up to 90% to 95% in AS patients, 60% to 80% in Reiter's syndrome or reactive arthritis, 50% in psoriatic arthritis, and only 4% to 8% in the normal population. Among the first-degree relatives of AS patients with HLA-B27 positivity, 10% to 27% of HLA-B27-positive adults suffer from AS, thus it is believed that HLA-B27 is closely related to SPA. It was previously thought that HLA-B27 might be a susceptibility gene or a gene linked to other pathogenic genes in an unbalanced manner, resulting in a higher positive rate in SPA patients. However, recent studies on HLA-B27 transgenic rats have found that the spondyloarthropathy and systemic manifestations in rats after receiving the HLA-B27 gene are very similar to human SPA, which further supports the direct relationship between HLA-B27 and SPA. However, only 2% of patients with HLA-B27 positivity develop SPA, and 10% of AS patients are HLA-B27 negative, thus it is believed that HLA-B27 is not a direct pathogenic gene, but a susceptibility gene for this group of diseases. Infection is another important factor in the onset of seronegative spondyloarthropathy. Post-infection of the intestinal and urinary tracts can trigger Reiter's syndrome, infections caused by Shigella flexneri, Salmonella, Yersinia, and Helicobacter pylori can lead to reactive arthritis, and infections related to Klebsiella pneumoniae in the intestinal tract are associated with AS, all supporting this view. Chinese research has found that the 6-amino acid polypeptide structure at positions 188-193 on the surface nitrogenase of Klebsiella pneumoniae is the same as the 6-amino acid polypeptide structure at positions 72-77 of the hypermutable region of HLA-B27, suggesting that the antigen expressed by the microorganism is similar to the B27 antigen, and the microorganism antigen is considered a foreign body and causes a severe immune response, but at the same time, it can cross-react with self-tissues and cause disease. This theory is called the 'molecular mimicry mechanism'. Other theories suggest that HLA-B27 may be a receptor for pathogen antigens, and after binding to antigens, it presents them to T cells, leading to disease. In addition, the T cell receptor gene may also be involved in the pathogenic process.

　　The early stage of seronegative spondyloarthropathy is mainly manifested as inflammatory lumbar and back pain, and there are more complications due to the different parts involved, such as psoriatic rash appearing before psoriatic arthritis; nail changes are a feature of psoriatic arthritis; suppurative keratoderma is the overkeratinization of the affected skin; conjunctivitis is the most common ocular complication of reactive arthritis.

　　Typical asymmetric peripheral arthritis, mainly affecting lower limb joints, tends to involve axial joints, manifested as spondylitis, sacroiliitis, inflammation of the attachment points of tendons, ligaments, and fascia to bones, and manifested as heel pain and sole pain. The rheumatoid factor in the serum is generally negative. In addition, there is a tendency towards familial aggregation of varying degrees related to HLA-B27. Extra-articular manifestations often overlap, such as psoriatic arthritis, Reiter's syndrome, or enteropathic arthritis, although all patients may have uveitis.

　　Prevention and treatment of seronegative spondyloarthropathy: Patients with ankylosing spondylitis and those with peripheral joint lesions of spondyloarthritis should pay special attention to rehabilitation exercises. Exercise should be cautious and continuous to achieve and maintain the best position of the spinal joints, strengthen paravertebral muscles, and increase lung capacity. When standing, try to maintain a posture of挺胸、收腹 and eyes looking forward. When sitting, the chest should also be kept upright. It is recommended to sleep on a relatively firm mattress, often in a supine position, avoiding postures that promote flexion deformities, and the pillow should not be too high. Reduce or avoid physical activities that cause persistent pain.

　　1. Laboratory examination:

　　The positive rate of HLA-B27 gene in patients with ankylosing spondylitis is 90％~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 results of the HLA-B27 test cannot be used as a basis for diagnosis, nor can they predict the prognosis of patients, but only increase the possibility of diagnosis. In the active phase, patients may have an increased erythrocyte sedimentation rate (ESR), increased C-reactive protein (CRP), increased platelets, and mild anemia. The rheumatoid factor (RF) is negative and the immunoglobulin level is slightly elevated.

　　2. Imaging examination:

　　X-ray, CT, MRI. X-ray findings 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. The severity of sacroiliitis on X-ray films is usually divided into 5 grades: 0 grade is normal; Ⅰ grade is可疑; Ⅱ grade has mild sacroiliitis; Ⅲ grade has moderate sacroiliitis; Ⅳ grade is joint fusion and ankylosis.

　　1. Avoid eating too much meat bones:If a large amount of meat bones is consumed after a fracture, it will promote an increase in inorganic components in the bone, leading to a disorder in the proportion of organic matter in the bone, which will hinder the early healing of the fracture.

　　2. Avoid faddy eating:Fracture patients often have local edema, congestion, hemorrhage, and muscle tissue damage, and the body itself has resistance and repair ability for these conditions. The body's repair of tissue and swelling mainly relies on various nutrients.

　　First, general treatment

　　1. Education:

　　Patients should be educated about the disease, so that they understand the chronic process of the disease, the necessity of long-term treatment, and the possible adverse reactions that may occur during medication, and actively cooperate with the doctor's treatment.

　　2. Exercise and rest:

　　In addition to rest during the acute attack or severe damage to important organs such as the heart and lungs, it is necessary to strengthen the exercise of spinal and joint functions, perform more chest expansion exercises to increase lung capacity, and it is advisable to sleep on a hard bed during rest.

　　3. Physical therapy:

　　It is beneficial for eliminating local inflammation, reducing pain, and improving joint mobility.

　　Secondly, NSAIDs drugs

　　NSAIDs drugs can inhibit the inflammatory process, alleviate joint pain, swelling and morning stiffness. Commonly used drugs include indomethacin, diclofenac, naproxen, sulindac, etc. Indomethacin should be administered in sustained-release formulations, with a daily dose of 1-2 mg/kg. Phenylbutazone has definite efficacy, but due to the possibility of causing aplastic anemia, it is only used in refractory cases. In the selection of NSAIDs, there is a tendency to use selective COX-2 inhibitors to reduce the toxic and side effects of these drugs on the gastrointestinal tract and kidneys.

　　3. Glucocorticoids

　　SpA rarely requires systemic use of glucocorticoids, but they can be used for intra-articular injection. When acute iridocyclitis occurs, they can be instilled into the eyes or subconjunctival injection. When myositis ossificans occurs, local injection can be performed. Only a few patients with severe diseases or severe involvement of内脏 organs, or those allergic to NSAIDs or unable to control symptoms, may require low-dose glucocorticoid treatment. Generally less than 1mg, some patients may need higher doses, even shock therapy.

　　4. Disease-modifying Drugs

　　DMARDs can be used for chronic patients or those who are ineffective with NSAIDs treatment. The common preparation is sulphasalazine, 2-4g/day, or methotrexate (MTX) 7-15mg per week, but it takes 2-6 months to take effect. SASP has a good effect on peripheral joint and附着端 inflammation, but the efficacy of spinal lesions is uncertain. MTX is effective for many SpA patients, especially for psoriatic arthritis patients with skin and joint lesions, but large doses and long-term use are prone to cause liver damage, which limits the use of this drug. When the above drugs are ineffective, azathioprine (AZA) can be used, 1-2mg/kg per day. In addition, gold preparations, antimalarial drugs, and cyclosporin all have certain efficacy.

　　5. Traditional Chinese Medicine Raifukuangen

　　It has achieved good efficacy in the treatment of SLE and rheumatoid arthritis and can also be used for the treatment of SpA. The common dose is 20mg, tid, and after the symptoms improve, it can be changed to 10mg, Lid for maintenance treatment. Attention should be paid to the toxic effects of the drug on the gonads, hematopoietic system, liver, and kidneys.

　　6. Antibiotics Reiter's Syndrome, Reactive Arthritis

　　Patients can appropriately use antibacterial drugs to eliminate the pathogenic bacteria causing the prodromal infection.

　　7. Surgical Treatment

　　When joint deformities, rigidity, and functional disorders occur in the late stage of the disease, such as: scoliosis, kyphosis, severe compression of the cervical spine, joint deformities, fixation, necrosis, etc., orthopedic corrective surgery can be performed, such as: 91 joint arthroplasty, total hip arthroplasty, total knee arthroplasty, spinal correction, etc., which can alleviate joint pain, increase joint mobility, and significantly improve the quality of life of patients.