Rheumatoid arthritis (RA) is a systemic autoimmune disease that manifests primarily as symmetric, chronic progressive polyarthritis. Chronic inflammation and hyperplasia of the synovial membrane of the joints form vascular opacities that invade the articular cartilage, subchondral bone, ligaments and tendons. It causes destruction of articular cartilage, bone and joint capsule, which eventually leads to joint deformity and loss of function. The incidence of this disease is about 0.32-0.36%, mostly seen in young and middle-aged women, with peak incidence in the age of 20-45.
I. Etiology and pathogenesis
The etiology and pathogenesis of RA are not yet clear. Infectious factors, genetic factors, T and B lymphocytes, and synovial cells may all be involved in the development of RA. It is generally believed that chronic infection or early infection initiates an immune response that acts on autoantigens through molecular mimetic factors and causes a sustained immune response. RA is associated with genetic susceptibility and has a tendency to cluster in families.
The development of RA may be caused by exogenous infectious factors (or pathogenic peptides) acting on genetically susceptible individuals, which are phagocytosed and processed by antigen-presenting cells (e.g. macrophages) and bound to HLA-DR molecules to form complexes that are recognized by self-reactive T lymphocytes through molecular mimicry mechanisms and activated by the latter. 6, IL-17, TNF-α and other cytokines, which act on synovial cells and chondrocytes to produce metalloproteinases, etc., leading to degradation of joint tissues and causing high proliferation of synovial fibroblasts and capillary endothelial cells, which constitute the characteristic vascular opacification of RA. This proliferation is repeated and eventually invades cartilage, causing cartilage and bone destruction.
Proteases are involved in the degradation of cartilage matrix molecules, with metalloproteinases being the main enzyme class for cartilage matrix degradation. In addition to synovial tissue proliferation, which is closely related to synovial cell proliferation, impairment of synovial cell apoptotic mechanism may be another important mechanism. Apoptosis of synovial fibroblasts is associated with p53, Fas, Bcl-2 and the cytokine TGF-β1. In addition, activated T-lymphocytes induce B-lymphocytes to differentiate into plasma cells and produce immunoglobulins such as RF, especially IgG-RF, which bind themselves in synovial fluid to form multimeric complexes and activate the complement system to cause and aggravate joint tissue inflammation.
Second, the clinical manifestations
(a) Onset characteristics: 60-70% of patients have an insidious onset, manifesting as fatigue, discomfort, poor weight, weight loss, peripheral muscle pain, and may have a low fever within weeks or months. Subsequently, single or symmetrical swelling of the surrounding joints appears; 20% have an acute onset of polyarthritis, with rapid onset of multi-joint redness, swelling, heat, pain and dysfunction, and severe systemic symptoms; 15-20% have an onset between the above two, but systemic symptoms are more obvious than the insidious type.
(B) Joint performance
1. Morning stiffness: It is a typical symptom of RA, that is, the affected joints become stiff and restricted after the patient wakes up in the morning or after stopping activities for a period of time. With the increase of joint activity, the morning stiffness is gradually relieved. Morning stiffness first occurs in the proximal hand joints, which are stiff and uncomfortable and cannot make a fist, and later, as the disease progresses, the stiffness of the whole body joints may appear.
Pain: The most prominent symptom of RA, often aggravated by weather changes, cold stimulation, mood swings, etc. The initial stage of RA can be manifested as wandering pain in small joints such as fingers, wrists, toes and ankles. If there is joint swelling, the pain is relatively fixed and often lasts for more than 6 weeks, with multiple joints being involved one after another. As the lesion progresses, the elbow, shoulder, knee, hip, and cervical spine may successively become painful. It may also involve the temporomandibular joint and cause pain when opening the mouth and chewing.
3, swelling: joint pyknosis is a characteristic change of RA, which is obvious in the small joints of the extremities.
4.Mobility impairment: It is a common sign of RA, which can return to normal with the improvement of pain and swelling in the early stage. With the development of the disease, muscle atrophy around the joint, joint space narrowing, joint bony fusion, and eventually complete loss of joint function, such as finger, wrist flexion and extension restrictions, which can reduce grip strength, can not be buttoned, and even can not hold things; shoulder joint dysfunction upper limb can not be lifted, resulting in hair combing difficulties; knee joint dysfunction and can not squat, walking difficulties; temporomandibular joint dysfunction can affect the mouth and mastication. Therefore, patients with RA in the middle and late stages can affect or lose the ability to work, or even unable to take care of themselves.
The most common hand deformities in RA are gooseneck deformity, buttonhole deformity, flipper hand, and lateral ulnar deviation. Severe joint deformity is an important reason for affecting labor and life ability.
(C) extra-articular manifestations
1, subcutaneous nodules: about 20% of patients can be seen, mostly in the joint bulge, such as the elbow joint hawk, wrist and finger extension, but also visible bursa and tendon sheath area. The nodules are round and oval in shape, generally 2-3 mm in diameter, hard, non-tender, and can move freely under the skin or adhere to deeper tissues.
2, secondary vasculitis: incidence of about 25%, can involve large, medium and small vessels, small vasculitis manifested as rash, skin infarction, gangrene of finger ends, leg ulcers; heart, lung, kidney and eye vessels can be involved, respectively, manifested as pericarditis, alveolitis or pleurisy, nephritis or even renal failure, sclerositis or corneal lysis. Sudden mononeuropathy is a more specific manifestation of vasculitis, but the incidence is low.
3, respiratory system: pulmonary fibrosis can occur, the incidence of about 11%, there can be pleural effusion, rheumatoid nodules in the lungs, etc.
4, cardiac lesions: pericardial damage is the most common, RA with clinical manifestations of pericardial damage accounted for about 10%, the heart valve and myocardium can also be involved.
5, hematological system: anemia is more common in RA patients, thrombocytosis and eosinophilia are seen in the active phase, and trilineage reduction can occur after certain drug therapy and Felty syndrome.
6, renal lesions: renal damage is dominated by amyloidosis, vasculitis and drug factors. There may be glomerulonephritis, interstitial nephritis, and renal failure in severe cases.
7, other: the disease can involve the digestive tract when active, clinical indigestion, peptic ulcers, perforation, liver enzymes increase when the liver is damaged; RA can also be accompanied by secondary amyloidosis, which can involve all organs including the above, such as the spleen, various glands, etc.
Auxiliary examinations
(A) General examination
Routine blood tests commonly show mild to moderate anemia, high platelet count, increased sedimentation, and increased C-reactive protein, which often parallels the activity of the disease.
(B) Serological examination
About 70-80% of rheumatoid factor (RF) positive reactions and increased serum IgG. Anti-perinuclear factor (APF), anti-RA3, anti-keratin antibody (AKA), anti-Sa antibody, anti-cyclic citrullinated peptide antibody (anti-CCP antibody), anti-serotonin antibody (AFA), type II collagen antibody have high specificity in RA patients and are important for early diagnosis of RA, among which anti-CCP antibody has high diagnostic specificity of more than 98% and sensitivity of The sensitivity of anti-CCP antibody is about 30-40%.
(C) X-ray examination
It is of high value for the diagnosis of typical RA, and can determine the degree of destruction of cartilage and subchondral bone tissue in RA patients to estimate the disease. X-rays are performed differently as the disease progresses and are staged according to their performance as follows.
1.Stage I (early stage).
(1) X-ray examination without destructive changes;
(2) Osteomalacia is visible.
2.Stage II (middle stage).
(1) Osteoporosis, there may be mild cartilage destruction, with or without mild subchondral bone destruction;
(2) Restricted joint movement is seen, but no joint deformity;
(3) Atrophy of adjacent muscles;
(4) There are extra-articular soft tissue lesions, such as nodules and tenosynovitis.
3.Stage III (severe stage).
(1) Osteoporosis plus cartilage or bone destruction;
(2) Joint deformity, such as joint dislocation, ulnar deviation without fibrous or bony ankylosis;
(3) Extensive muscle atrophy;
(4) extra-articular soft tissue lesions, such as nodules or tenosynovitis.
4. Stage IV (terminal).
(1) Fibrous or bony ankylosis;
(2) Each article within the criteria of stage III.
(D) CT examination: It can understand the integrity of the bone, especially the bone cortex, and is more ideal than X-ray for bone destruction of the joint surface, bone sclerosis, and joint space narrowing. In recent years, the application of MRI can accurately describe the damage of soft tissues and joints, which has a high diagnostic value for patients with early RA or suspected RA and is the best criterion for judging clinical inflammation indicators.
(V) Others
Arthroscopy can observe the pathological changes such as vascular opacity formation and synovial hyperplasia in early RA. Ultrasound of knee joint can detect early RA synovial and periarticular soft tissue lesions, which helps in the early diagnosis of RA is the future development direction.
IV. Diagnosis
(I) Diagnostic criteria: 1987 American Rheumatism Association (ARA) rheumatoid arthritis classification criteria.
1.Morning stiffness: stiffness in and around joints lasting at least 1h (duration of disease ≥ 6 weeks);
2, 3 or more areas of arthritis: the physician observed the following 14 areas (left or right proximal interphalangeal joints, metacarpophalangeal joints, wrist, elbow, knee, ankle and metatarsophalangeal joints) involved in 3, and at the same time soft tissue swelling or fluid accumulation (not simple bone augmentation) (duration of disease ≥ 6 weeks);
3, hand arthritis: wrist, metacarpophalangeal or proximal interphalangeal arthritis, at least one joint swelling (duration of disease ≥ 6 weeks);
4, symmetric arthritis: both joints are involved at the same time (bilateral proximal interphalangeal joints, metacarpophalangeal joints and metatarsophalangeal joints may not be absolutely symmetrical) (duration of disease ≥ 6 weeks);
5, rheumatoid nodules: The doctor observed subcutaneous nodules at the site of the bony prominence, on the surface of the extensor muscle or around the joint;
6, rheumatoid factor positive: any test method to prove that the serum rheumatoid factor level is abnormal, and the positive rate of the method in the normal population is less than 5%;
7, radiological changes: typical radiological changes of rheumatoid arthritis in the posterior-anterior phase of the hand and wrist, which must include bone erosion or definite bone decalcification in the involved joint and its adjacent areas.
RA can be diagnosed by satisfying 4 or more of the above 7 items and excluding other arthritis.
V. Differential diagnosis
(A) Ankylosing spondylitis (AS): The disease mainly affects the spine, but peripheral joints can also be involved, especially in those with hip and knee hip joints as the first symptoms.
(1) It is more common in young men;
(2) mainly invade the sacroiliac joint and spine, peripheral joint involvement is mostly asymmetric in the lower extremities, often with tendonitis, ligamentous attachment pointitis;
(3) RF is mostly negative; (4) 90% to 95% of patients are HLA-B27 positive; (5) X-rays have sacroiliac arthritis or changes in the spine.
(B) Osteoarthritis (OA): the disease is degenerative osteoarthritis, mostly occurring over 40 years of age, often involving weight-bearing joints such as the knee and spine, and a few appear in the distal interphalangeal joints of the fingers. The pain is aggravated by activity, and there are specific Heberden and Bonchard nodes; there may be joint pain, joint swelling and effusion, joint stiffness, difficulty in going up and down stairs and squatting, and in severe cases, joint deformity. x-ray examination shows specific radiological changes such as bone spurs and bone redundancy.
(C) Systemic lupus erythematosus (SLE): It is mostly seen in young women and may have swelling and pain in multiple joints of the extremities and may involve multiple organs of the body. There is no erosive joint destruction. The manifestations of facial pteroid erythema, photosensitivity, oral ulcers, proteinuria, hemocytopenia, plasmacytitis and central nervous system damage are predominant, with positive ANA high titer and positive anti-ds-DNA.
(iv) Rheumatic fever: the onset of the disease is preceded by symptoms of sore throat, characterized by painful swelling of the knees, wrists, ankles and other large joints of the extremities, increased heart rate and prolonged P-R interval on ECG may occur; annular erythema and subcutaneous nodules may appear; anti-“O” is often increased.
(E) Gouty arthritis: mostly seen in middle-aged and elderly men, often with recurrent attacks, sudden onset, waking up at night or in the early morning due to cutting pain in the toes, the preferred site is the unilateral first metatarsophalangeal joint, there may be redness, swelling, heat and pain in the joint. Often a single attack, blood uric acid is elevated, colchicine treatment is effective.
(VI) Dry syndrome (SS): It mainly invades the lacrimal gland and salivary gland, and may involve the joints and many systems of the body, such as respiratory, digestive, urinary and nervous, etc. It also has dry mouth, dry eyes, dental caries and repeated parotid enlargement, and mostly shows pain in the peripheral joints, but it does not cause joint space narrowing and erosion-like changes of bone, with positive serum anti-SSA and SSB antibodies.
VI. Treatment
The treatment principle of RA is to control the disease, relieve the symptoms, treat the complications, stop the progress of the disease, reduce the recurrence, prevent the deformity, and restore the joint function as much as possible.