Rheumatoid arthritis is an autoimmune disease of unknown etiology, with chronic symmetrical progressive polyarthritis as the main manifestation. The prevalence of rheumatoid arthritis in China is about 0.32% to 0.36%. Without early standardized treatment, it is very likely to lead to disability and bring a great economic burden. Misdiagnosis and misdiagnosis of rheumatoid arthritis are serious in many places in China, so it is necessary to standardize the treatment of rheumatoid arthritis.
Studies have found that rheumatoid arthritis progresses more rapidly within one year of onset than after the second year, so the key to reducing disability is early diagnosis and treatment. Although the rheumatoid arthritis classification criteria established by the American College of Rheumatology in 1987 are still the most commonly used diagnostic criteria internationally, they were originally established to facilitate clinical epidemiological investigations, not for clinical diagnosis of a specific patient, and therefore cannot be used as an absolute basis for rheumatoid arthritis diagnosis, much less for early diagnosis. Although 60% to 80% of patients with rheumatoid arthritis have high levels of rheumatoid factor, positive rheumatoid factor is also seen in chronic infections, other connective tissue diseases and normal elderly people. Therefore, the diagnosis of rheumatoid arthritis cannot be made on the basis of a positive rheumatoid factor.
Since the 1960s, rheumatologists have identified a variety of autoantibodies with high specificity for the diagnosis of rheumatoid arthritis, such as antiperinuclear factor detected by Neinhuis and Mandema in 1964, anti-keratin antibodies detected by Young et al. in 1979, and anti-keratin antibodies detected by Hassfeld in 1989. In 1991, Menard and Despres et al. detected anti-Sa antibodies by immunoblotting, and in 1993, they confirmed that the target antigens of both perinuclear factor and anti-keratin antibodies are filaggrin, which is present in epithelial cells, and their antibodies are specific for the diagnosis of rheumatoid arthritis. The antibodies are specific for the diagnosis of rheumatoid arthritis.
In 1998, it was discovered that the antigenic determinants recognized by anti-filaggrin are peptide sequences containing citrulline, which led to the discovery of a highly specific autoantibody for rheumatoid arthritis, namely anti-cyclic citrulline peptide antibody (anti-CCP). The anti-CCP test has been carried out in China since 2000, and has been shown to be highly sensitive and specific for the diagnosis of rheumatoid arthritis, especially for early rheumatoid arthritis, and is associated with the severity of the disease and bone destruction.
The value of anti-CCP antibodies in the early diagnosis of rheumatoid arthritis has been confirmed by rheumatologists in Europe and the United States, and it has been recommended that they be included in routine testing. The combination of these early markers can help in the early diagnosis of rheumatoid arthritis.
In recent years, a large number of clinical studies have shown that plain X-rays cannot be used as a means of early diagnosis of rheumatoid arthritis, and CT (especially high-resolution CT) can be used as one of the imaging tools for early diagnosis of rheumatoid arthritis because it shows clearer and better spatial resolution than X-rays and helps to show the microstructure of lesions. MRI imaging has the advantages of being non-invasive and obtaining arbitrary cross-sectional images.
Since the severity of synovitis in rheumatoid arthritis is closely related to the occurrence of bone erosion, MRI can quantify the degree of synovitis in rheumatoid arthritis joints and detect synovitis and bone erosion changes within 4 months of the onset of rheumatoid arthritis, thus allowing a more accurate assessment of rheumatoid arthritis and the development of an appropriate treatment plan. The limitations of MRI are that the evaluation of erosive destruction of the bone cortex, periosteal reaction, calcification or ossification is not as clear as that of radiographs and CT. B-mode ultrasound of the knee is a non-invasive, easy-to-use test that, when combined with other methods, can be useful in the early diagnosis of rheumatoid arthritis.
The following 7 indices can be used to differentiate between 3 types of arthritis: self-limiting arthritis, persistent non-erosive arthritis and persistent erosive arthritis.
(1) Length of disease at the initial visit.
(2) Morning stiffness of ≥60 minutes.
(3) ≥3 arthritis.
(4) Bilateral metatarsophalangeal joint pressure pain.
(5) Positive rheumatoid factor.
(6) Positive anti-CCP antibody.
(7) Erosional destruction of the hands or feet.
Clinical practice results show that a disease duration of ≥3 months and positive anti-CCP antibody have the strongest correlation with persistent arthritis; while bilateral metatarsophalangeal joint pain and positive anti-CCP antibody have the strongest correlation with persistent erosive arthritis, and the early establishment of persistent erosive arthritis is important for the early diagnosis of rheumatoid arthritis, clinicians should pay attention to check bilateral metatarsophalangeal joints when detecting arthritis The clinician should check for pressure and swelling in the bilateral metatarsophalangeal joints when detecting arthritis.
The goal of treatment for rheumatoid arthritis is to prevent joint destruction, protect joint function, and maximize the patient’s quality of life; therefore, it is important to seize the opportunity for treatment. Standardized treatment for rheumatoid arthritis should include medication, surgery and psychological rehabilitation. For refractory rheumatoid arthritis, biological agents, plasma replacement and hematopoietic stem cell transplantation are available. Although non-steroidal anti-inflammatory drugs and glucocorticoids can reduce symptoms, synovial inflammation and joint destruction can still occur and progress, so early and active use of anti-rheumatic drugs to improve the condition is the key to reducing disability.
Once rheumatoid arthritis is diagnosed, it is treated with disease-modifying anti-rheumatic drugs, with methotrexate as the first choice, but also with leflunomide, salazosulfapyridine and hydroxychloroquine. For example, methotrexate 5-25mg/week, leflunomide 10-20mg/d, salazosulfapyridine 1.0-3.0 g/d, hydroxychloroquine 0.2-0.4g/d. Combination of two or more disease-modifying antirheumatic drugs can be used depending on the condition.
Generally, patients with progressive or poor prognosis or severe or refractory disease are treated with different mechanisms of disease-modifying antirheumatic drugs. When combining drugs, the dose of each of these drugs can be reduced appropriately to reduce adverse effects. Currently, the following combination regimens are commonly used.
(1) Methotrexate + lorazepam.
(2) Methotrexate + hydroxychloroquine (or chloroquine).
(3) Methotrexate + leflunomide.
(4) Methotrexate + Ginuphen.
(5) Methotrexate + salazosulfapyridine + hydroxychloroquine.
(6) Salazosulfapyridine + hydroxychloroquine.
(7) Methotrexate + ryanodine.
Biological agents, immunopurification therapy, high-dose chemotherapy, and peripheral blood hematopoietic stem cell transplantation offer new options for patients with rheumatoid arthritis for whom conventional treatment has failed. New biologic agents can reduce joint erosion in rheumatoid arthritis, but they cannot cure rheumatoid arthritis. Current biologic agents used in rheumatoid arthritis include.
(1) TNF inhibitors: e.g. human/mouse chimeric anti-TNF monoclonal antibodies (class g), fusion proteins of TNF receptors with IgG-Fc region and (Ixab) human anti-TNF monoclonal antibodies (adalimumab).
(2) Interleukin 2 receptor antagonists.
(3) Anti-B cell CD20 monoclonal antibody: Rituxan (Meroval).
A total of 125 centers in North America and Europe conducted the ASPIRE trial in 1049 patients with early rheumatoid arthritis. The trial used classical gram plus methotrexate in the experimental group and methotrexate plus placebo in the control group for 54 weeks and showed that patients in the experimental group had better symptom improvement, prevention of progressive joint destruction, and relief of joint disability than the control group.
It was found that the combination of Ixepro and interleukin 2 receptor antagonist did not improve the efficacy but led to more serious infections, so the combination is not recommended.
The most frequent side effects of biologic agents are infections, including bronchitis, sinusitis, and activity of old tuberculosis, and autoimmune diseases (multiple sclerosis, lupus-like manifestations) and non-Hodgkin’s lymphoma have also been reported. Therefore, patients applying biologic agents should be routinely excluded from TB prior to treatment and monitored annually for TB-related indicators after treatment.
In addition, ANA (antinuclear antibodies) and anti-dsDNA (anti-double-stranded DNA antibodies) should be tested before use and monitored yearly. Immunosorbent therapy, single nucleus cell clearance, and plasma exchange have been shown to be effective in critical and refractory rheumatoid arthritis, and can be used in patients with rheumatoid arthritis who have high titers of autoantibodies in the serum and have failed to respond to regular therapy. High-dose chemotherapy and peripheral blood stem cell transplantation have been used in China for refractory rheumatoid arthritis.
Regardless of which treatment option is chosen, it is important to emphasize that
(1) X-rays of both hands, including the wrist and/or symmetrical X-rays of the affected joints, should be taken before treatment, and X-rays should be repeated yearly after treatment to compare efficacy.
(2) During the course of treatment, disease activity should be monitored and treatment response should be evaluated periodically, and the type and dose of medication should be changed according to the condition. The evaluation should include the number and degree of painful joints, the number and degree of swollen joints, the radiology of affected joints, the functional status of joints, and the overall assessment of disease activity by doctors and patients before and after treatment.
(3) In order to avoid adverse drug reactions, individualization should be emphasized in treatment, and blood and urine routine, liver and kidney function should be closely observed, and the type or dose of drugs should be adjusted when appropriate.
(4) Patients in the early, acute phase or with persistent activity should be closely followed up until the disease is controlled. Patients in remission can be followed up once every six months, but the corresponding indexes should still be tested regularly and the damage to internal organs other than joints should be observed.
(5) Symptom relief after treatment is not the same as cure of the disease, and disease-modifying drugs and biological agents can improve and delay the progression of the disease, but they cannot cure rheumatoid arthritis. Therefore, in order to prevent relapse of the disease, in principle, the drug should not be stopped, but the dosage can be gradually reduced to maintain the treatment according to the condition until it is eventually discontinued.