| disease | Rheumatoid Arthritis |
| alias | RA, Rheumatoid Arthritis, CategoryBi Disease |
Rheumatoid arthritis (rheumatoid arthritis) is a chronic systemic autoimmune disease characterized by synovial membrane inflammation. Persistent and recurrent synovitis can lead to the destruction of cartilage and bone within the joints, resulting in joint dysfunction or even disability. Vasculitis lesions can affect various organs throughout the body, which is why this disease is also referred to as Bi disease.
bubble_chart Etiology
It is not yet fully clear. Rheumatoid arthritis is a disease closely related to factors such as the environment, cells, viruses, genetics, sex hormones, and neuropsychiatric states.
(1) Bacterial factors: Experimental studies have shown that group A streptococci and their cell wall peptidoglycan may serve as a persistent stimulus for the onset of RA. The long-term presence of group A streptococci in the body acts as a continuous antigen, stimulating the body to produce antibodies, leading to immune-mediated pathological injury and disease. The arthritis animal model created by mycoplasma is similar to human RA but does not produce the rheumatoid factor (RF) unique to human RA. No bacteria or bacterial antigenic substances have ever been found in the joint fluid or synovial membrane tissue of RA patients, suggesting that bacteria may be related to the onset of RA, but direct evidence is lacking.
(2) Viral factors: The relationship between RA and viruses, particularly the Epstein-Barr virus (EBV), is one of the issues of interest for scholars both domestically and internationally. Studies indicate that arthritis caused by EBV infection differs from RA, and RA patients exhibit a stronger reactivity to EBV compared to healthy individuals. Persistently high levels of anti-EBV membrane antigen antibodies are found in the serum and synovial fluid of RA patients, but so far, no EBV nuclear antigen or capsid antigen antibodies have been detected in their serum.
(3) Genetic factors: The incidence of this disease is higher in certain families. Population surveys have found an association between human leukocyte antigen (HLA)-DR4 and RF-positive patients. HLA studies have revealed that DW4 is related to the onset of RA, with 70% of patients testing positive for HLA-DW4. Patients carry susceptibility genes at this locus, indicating that genetics may play a significant role in the disease's development.(4) Sex hormones: Research shows that the male-to-female ratio of RA incidence is 1:2–4. Symptoms alleviate during pregnancy, and the incidence is reduced in women taking contraceptive pills. Animal models demonstrate that LEW/n female mice are more susceptible to arthritis, while males have a lower incidence. However, castrated male mice or those treated with β-estradiol develop arthritis similarly to females, suggesting that sex hormones play a role in RA onset.
Cold, dampness, fatigue, malnutrition, trauma, and psychological factors are often triggers for the disease, though most patients have no identifiable precipitating factors prior to onset.
The exact cause is not yet fully understood, but it is widely accepted that RA is an autoimmune disease. Individuals with HLA-DR4 and DW4 type antigens exhibit heightened sensitivity to external environmental conditions, viruses, bacteria, neuropsychiatric factors, and endocrine stimuli. When these factors invade the body, they alter the antigenic determinants of HLA, turning HLA-bearing nucleated cells into targets for immune suppression. Due to the ability of HLA genes to produce T-cell antigen receptors and immune-related antigens, when external stimuli are recognized by macrophages, T-cell activation and the release of a series of immune mediators occur, triggering an immune response.
The hallmark of RF synovium is the presence of various products secreted by activated lymphocytes, macrophages, and other cells. These bioactive substances include multiple factors: T lymphocytes secrete interleukin-2 (IL-2), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha, and transforming growth factor-beta; factors derived from activated macrophages include IL-1, tumor necrosis factor-alpha, IL-6, GM-CSF, macrophage CSF, and platelet-derived growth factor; bioactive substances secreted by other cells in the synovium (fibroblasts and endothelial cells) include IL-1, IL-6, GM-CSF, and macrophage CSF. These bioactive substances account for many features of rheumatoid synovitis, including synovial tissue inflammation, synovial hyperplasia, cartilage and bone damage, and systemic manifestations of RA. The bioactive substances IL-1 and tumor necrosis factor can activate resident chondrocytes to produce collagenase and proteolytic enzymes, damaging local cartilage.
RF, including IgG, IgA, and IgM, plays a significant role in the pathogenesis of systemic disease. Among these, IgG-RF itself contains both antigen and antibody binding sites, allowing it to form dimers or multimers. Immune complexes containing IgG deposit in synovial tissue, stimulating the synovium to produce IgM and IgA-type RA. IgG-RF can also bind to immune complexes containing IgG, and its ability to activate complement is greater than that of immune complexes containing IgG alone.
bubble_chart Pathological Changes
The tissue changes in wind-dampness-like joint lesions may vary slightly depending on the location, but the fundamental alterations are the same. The characteristics include: ① Diffuse or localized infiltration of lymphocytes or plasma cells in the tissue, and even the formation of lymphoid follicles. ② Vasculitis, accompanied by intimal hyperplasia leading to luminal narrowing or obstruction, or fibrinoid necrosis of the vessel wall. ③ Formation of wind-dampness-like granulomas.
1. Early changes in the joint cavity involve synovitis, with synovial congestion, edema, and extensive infiltration of mononuclear cells, plasma cells, and lymphocytes. Sometimes, lymphoid follicles form, and small areas of superficial synovial cell necrosis may lead to erosions covered with fibrin-like deposits. The latter consist of complement complexes containing small amounts of γ-globulin. The joint cavity contains exudates with neutrophils. Further progression of synovitis involves the formation of vascular pannus, where, in addition to proliferating fibroblasts and capillaries thickening the synovial villi, lymphoid follicles form, along with plasma cell and granulocyte infiltration and varying degrees of vasculitis. Synovial cells also proliferate. In these proliferating synovial cells, or in lymphocytes and plasma cells, wind-dampness-like factors, γ-globulin, or antigen-antibody complexes can be detected using fluorescent-labeled antigens.
The vascular pannus can gradually extend from the synovium at the edge of the articular cartilage to cover the cartilage surface. On one hand, this blocks contact between the cartilage and synovial fluid, affecting its nutrition. On the other hand, the release of certain hydrolytic enzymes from the vascular pannus erodes the articular cartilage, subchondral bone, ligaments, and tendons, leading to joint destruction, fusion of the upper and lower surfaces, fibrosis-induced stiffness, dislocation, or even ossification, resulting in complete loss of function. Adjacent bone tissue may also develop disuse-related osteoporosis.
2. Extracurricular lesions include wind-dampness-like nodules, seen in about 10–20% of cases. These nodules appear subcutaneously or on the periosteum in pressure or friction-prone areas. The center consists of amorphous material formed by necrotic tissue, fibrin, and immune complex deposits containing IgG, surrounded by palisading fibroblasts. Further outward, fibrogranulation tissue infiltrated by mononuclear cells is present. In a few patients, granulomatous nodules may appear in visceral organs.
3. In rheumatoid arthritis, vessels are often affected, with widespread inflammatory cell infiltration in all layers of the arterial wall. During the acute phase, immunofluorescence can detect immunoglobulin and complement deposition in the affected vessel walls. There are three manifestations: ① Severe and extensive necrotizing arteritis of large vessels, resembling polyarteritis nodosa; ② Subacute small arteritis, commonly seen in small arteries of the myocardium, skeletal muscles, and nerve sheaths, causing corresponding symptoms; ③ Intimal hyperplasia and fibrosis of terminal arteries, often leading to insufficient blood flow in digital arteries, resulting in ischemic and thrombotic lesions. The former may manifest as Raynaud's phenomenon, pulmonary hypertension, and visceral ischemia, while the latter can cause digital gangrene or, if occurring in visceral organs, may be fatal.
4. Pulmonary lesions may include: ① Chronic pleural effusion, where "RA cells" in the pleural fluid are epithelial cells containing IgG and IgM immune complexes. ② Caplan syndrome, a form of pneumoconiosis coexisting with pulmonary granulomas in rheumatoid arthritis. These granulomas have been found to contain immunoglobulin and complement deposits, with RF detected in nearby plasma cells. ③ Interstitial pulmonary fibrosis, with lymphoid cell aggregates around the lesions and occasional antibody formation.
Lymphadenopathy is observed in 30% of cases, with lymphoid follicle hyperplasia, and splenomegaly, particularly in Felty syndrome.
bubble_chart Clinical Manifestations
Approximately 80% of patients experience onset between the ages of 20 and 45, predominantly in young and middle-aged adults, with a male-to-female ratio of 1:2–4. The onset is initially slow, with patients exhibiting prodromal symptoms such as weeks to months of fatigue, lack of strength, weight loss, poor appetite, low-grade fever, and stabbing pain in the hands and feet. This is followed by pain and stiffness in a particular joint, with subsequent swelling and increasing pain. Initially, one or two joints may be affected, often in a migratory pattern. Later, it progresses to symmetrical polyarthritis, typically starting with the small joints of the distal limbs before involving other joints. The proximal interphalangeal joints are most commonly affected, exhibiting spindle-shaped swelling, followed by the metacarpophalangeal, toe, wrist, knee, elbow, ankle, shoulder, and hip joints. Morning joint stiffness and muscle soreness may improve with moderate activity. The severity and duration of stiffness often correlate with disease activity and can serve as an indicator of disease progression. Due to joint swelling, pain, and restricted movement, nearby muscles become increasingly stiff and atrophied. Even after acute inflammation subsides, fibrosis within the joint and surrounding tissues leads to persistent stiffness. As the disease progresses, patients may experience irregular fever, accelerated pulse, and significant anemia. Affected joints eventually become stiff and deformed, with knees, elbows, fingers, and wrists fixed in flexion. Fingers often deviate laterally at the metacarpophalangeal joints, forming a characteristic ulnar deviation deformity, requiring assistance for daily activities. Patients with extensive joint involvement may become bedridden, immobile, and suffer extreme distress.
About 10–30% of patients develop subcutaneous nodules over bony prominences, such as the olecranon process of the upper limbs, wrists, and ankles. These nodules are firm and rubbery, rarely resolve, and often indicate severe disease activity.
Additionally, a minority of patients (about 10%) may exhibit lymphadenopathy and splenomegaly during active disease. Ocular manifestations include scleritis and keratoconjunctivitis. Clinical cardiac involvement is rare, though autopsy findings suggest it affects about 35%, primarily causing mitral valve lesions. Pulmonary manifestations vary, including pleuritis, diffuse interstitial fibrosis, and pneumoconiosis-like disease. Peripheral neuropathy, chronic leg ulcers, and amyloidosis may also occur occasionally.
There is no standardized assessment for functional status in rheumatoid arthritis patients, but the following classification is widely accepted:
Class I: No limitations in performing normal activities.
Class II: Some limitations (grade II) but still manageable.
Class III: Significant limitations (grade III), unable to perform most daily tasks or activities.
Class IV: Bedridden or wheelchair-dependent, with complete loss of mobility.
bubble_chart Auxiliary Examination
1. Most patients have grade I to grade II anemia, which is normocytic and normochromic. If accompanied by iron deficiency, it may present as hypochromic microcytic anemia. The white blood cell count is mostly normal, with a slight increase during the active phase, and occasional eosinophilia and thrombocytosis. Anemia and thrombocytosis are related to disease activity. In most cases, the erythrocyte sedimentation rate (ESR) is often elevated during active sexually transmitted disease, serving as an indicator of disease activity. Serum iron and iron-binding protein levels are often reduced.
2. Serum albumin levels decrease, while globulin levels increase. Immunoprotein electrophoresis shows elevated IgG, IgA, and IgM. C-reactive protein (CRP) may rise during the active phase.
3. Rheumatoid factor (RF) and other serological tests: Rheumatoid factors include IgG-RF, IgM-RF, IgA-RF, and IgE-RF. Currently, clinical testing is mostly limited to IgM-RF. The widely used methods in China are the latex agglutination test (LAT) and the sheep red blood cell agglutination test (SCAT), both of which are highly specific and sensitive for IgM-RF, with good reproducibility. IgM-RF is positive in about 3/4 of adult RA patients. High-titer IgM-RF positivity in sexually transmitted disease patients indicates severe disease activity, rapid progression, poor remission, worse prognosis, and more severe extra-articular manifestations. A negative rheumatoid factor does not rule out the disease and must be considered in conjunction with clinical findings. Additionally, RF is an autoantibody that can also be seen in various autoimmune diseases and chronic immune-related infections, such as systemic lupus erythematosus, Sjögren's syndrome, chronic hepatitis, sarcoidosis, pestilence-related mononucleosis, leprosy, subcutaneous nodule disease, and schistosomiasis. Furthermore, temporary RF positivity may occur in healthy individuals after vaccination or blood transfusion. Relatives of RA patients may also test positive for RF. About 5% of healthy individuals, especially the elderly, may test positive, so RF positivity alone does not necessarily indicate rheumatoid arthritis. However, combined with clinical findings, it remains an important auxiliary method for diagnosing RA.
Recently, it has been found that the positive rate of anti-rheumatoid arthritis-associated nuclear antigen antibody (anti-RANA antibody) in the serum of patients with rheumatoid arthritis (93–95%) is significantly higher than that in patients with other types of arthritis (about 19%) and healthy individuals (about 16%). This can serve as strong evidence for diagnosing rheumatoid arthritis.
The positive rate of antinuclear antibodies (ANA) in rheumatoid arthritis is about 10–20%. Blood moistening and tonifying levels are mostly normal or grade I elevated, but may decrease in severe cases or those with extra-articular manifestations.
4. Joint cavity aspiration yields opaque straw-yellow exudate, with neutrophil counts ranging from 10,000 to 50,000/mm3 or higher, and negative bacterial cultures. During active disease, leukocytes may contain rheumatoid factor and IgG-complement complex inclusions, forming phagocytic cells known as rheumatoid cells (regocytes). The relative concentration of complement in the exudate (compared to protein content) is reduced, and RF is positive.
X-ray findings: Early-stage joint X-rays in patients typically show only soft tissue swelling and joint effusion. Osteoporosis in the joint area may become evident within weeks of onset. Reduced joint space and bone erosion, indicating cartilage loss, appear only in cases lasting several months or longer. Subluxation, dislocation, and bony ankylosis are late-stage (third-stage) phenomena. When cartilage is destroyed, fusion of the articular surfaces between bones may occur, erasing signs of the original joint. Diffuse osteoporosis is common in chronic sexually transmitted disease and may worsen with hormone therapy. The incidence of avascular necrosis, particularly in the femoral head, may also increase with corticosteroid treatment.
The diagnosis of typical cases is generally not difficult, but in the early stages, especially when starting with monoarthritis and when X-ray changes are not yet obvious, follow-up observation is required to confirm the diagnosis.
Internationally, the 1985 diagnostic criteria of the American Bi Disease Society are commonly used. These criteria were revised in 1987, removing injury-related examinations and less specific joint pain and tenderness, while making the requirements for morning stiffness and joint swelling more stringent. However, rheumatoid arthritis in China tends to be milder than in Western countries, and not all patients meet the first and second criteria, so flexibility is allowed. The criteria are as follows:
1. Morning stiffness lasting at least 1 hour (≥6 weeks).
2. Swelling in 3 or more joints (≥6 weeks).
3. Swelling in the wrist, metacarpophalangeal joints, or proximal interphalangeal joints (≥6 weeks).
4. Symmetrical joint swelling (≥6 weeks).
5. Subcutaneous nodules.
6. Hand X-ray changes.
7. Positive rheumatoid factor (titer >1:32).
A diagnosis of rheumatoid arthritis requires meeting 4 or more of these criteria. The sensitivity is 93%, and the specificity is 90%, both superior to the 1958 criteria (sensitivity 92%, specificity 85%).
bubble_chart Treatment Measures
Rheumatoid arthritis currently has no specific cure and remains focused on treating inflammation and its sequelae. Comprehensive treatment is adopted, with most patients achieving certain therapeutic effects. The current treatment aims to: ① Control inflammation in joints and other tissues to alleviate symptoms; ② Preserve joint function and prevent deformities; ③ Repair damaged joints to reduce pain and restore function.
(1) General Therapy Patients with fever, joint swelling and pain, or systemic symptoms should rest in bed until symptoms largely subside. After two weeks of improvement, activity should gradually increase to avoid prolonged bed rest leading to joint disuse or even promoting joint stiffness. The diet should be rich in protein and vitamins. Patients with significant anemia may receive small blood transfusions. Chronic foci of infection, such as tonsillitis, should be removed as early as possible if the patient's health permits.
(2) Drug Therapy
1. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Used for initial or mild cases, their mechanism primarily involves inhibiting cyclooxygenase to suppress prostaglandin production, thereby achieving anti-inflammatory and analgesic effects. However, they cannot halt the natural progression of rheumatoid arthritis. Due to differing metabolic pathways in the body, these drugs may interact and are not recommended for combined use. Individualized dosing should be considered.
(1) Salicylate Preparations: These have anti-wind-dampness, anti-inflammatory, antipyretic, and analgesic effects. The dose is 2–4g daily. If the effect is unsatisfactory, the dose may be increased, sometimes requiring 4–6g daily for efficacy. They are usually taken after meals or with antacids, or enteric-coated tablets may be used to reduce gastrointestinal irritation.
(2) Indomethacin: An indole acetic acid derivative with anti-inflammatory, antipyretic, and analgesic effects. For patients intolerant to aspirin, this drug may be substituted. The usual dose is 25mg 2–3 times daily. Doses exceeding 100mg daily are prone to side effects, including nausea, vomiting, diarrhea, gastric ulcers, headache, vertigo, and depression.
(3) Propionic Acid Derivatives: A class of drugs that can replace aspirin, including ibuprofen, naproxen, and fenbufen. Their effects are similar to aspirin, with comparable efficacy and fewer gastrointestinal side effects. Common doses: ibuprofen 1.2–2.4g daily in 3–4 divided doses; naproxen 250mg twice daily. Side effects include nausea, vomiting, diarrhea, peptic ulcers, gastrointestinal bleeding, headache, and central nervous system disturbances such as irritability.
(4) Fenamate Drugs: Anthranilic acid derivatives with effects similar to aspirin. Mefenamic acid: 250mg 3–4 times daily. Clofenamic acid: 200–400mg three times daily. Side effects include gastrointestinal reactions such as nausea, vomiting, diarrhea, and loss of appetite, as well as occasional rashes, renal impairment, and headache.
2. Gold Preparations Currently recognized as effective for rheumatoid arthritis. Sodium aurothiomalate (Myochrysine) is commonly used. Dosage: 10mg intramuscularly in the first week, 25mg in the second week. If no adverse reactions occur, 50mg weekly thereafter. Most patients begin to see effects when the total dose reaches 300–700mg, with stable improvement achieved at 600–1000mg. Maintenance dose: 50mg monthly. Since relapse is possible after discontinuation, some patients abroad remain on maintenance doses for years or even lifelong. Earlier use of gold preparations yields better results. Their effects are slow, taking 3–6 months to manifest, and they should not be combined with immunosuppressants or cytotoxic drugs. If no improvement occurs after a total dose of 1000mg, treatment should be discontinued. Oral gold preparations have effects similar to injections. Side effects include increased bowel movements, rashes, stomatitis, and kidney damage, which resolve after discontinuation.
The oral gold preparation Auranofin is a hydroxyl compound of gold phosphine. The dose is 6mg once daily, with effects beginning to appear after 2-3 months. It is more effective for patients with early-stage and short disease duration. Side effects are milder than with injections, with diarrhea being the most common, but it is transient. The remission and marked effectiveness rate is 62.8%.
3. Penicillamine is an amino acid drug containing a sulfhydryl group, which has certain therapeutic effects on chronic rheumatoid arthritis. It selectively inhibits certain immune cells, reducing IgG and IgM levels. Side effects include thrombocytopenia, leukopenia, proteinuria, allergic rashes, loss of appetite, optic neuritis, muscle weakness, and elevated transaminases. The dosage is 250mg orally once daily for the first month, then 250mg twice daily in the second month. If no significant improvement is observed, the dosage is increased to 250mg three times daily in the third month. The maximum total daily dose is 750mg. Most patients show clinical improvement within three months, after which a lower maintenance dose is used. The treatment course lasts about one year.
4. Chloroquine has some anti-wind-dampness effects, but its onset of action is slow, often taking 6 weeks to 6 months to achieve maximum efficacy. It can be used as an adjunct to salicylate preparations or when tapering corticosteroid doses. The dosage is 250–500mg orally twice daily. Common gastrointestinal side effects during treatment include nausea, vomiting, and loss of appetite. Long-term use requires monitoring for retinal degeneration and optic atrophy.
5. Levamisole can alleviate pain and reduce joint stiffness duration. The dosage is 50mg once daily in the first week, 50mg twice daily in the second week, and 50mg three times daily in the third week. Side effects include vertigo, nausea, allergic rashes, blurred vision, drowsiness, granulocytopenia, thrombocytopenia, liver function impairment, and proteinuria.
6. Immunosuppressants are suitable for severe rheumatoid arthritis patients unresponsive to other medications or those tapering off corticosteroids. Common agents include azathioprine (50mg 2–3 times daily) and cyclophosphamide (50mg twice daily). Once symptoms or lab tests improve, the dose is gradually reduced to a maintenance level of 1/2 to 2/3 of the original dose, continued for 3–6 months. Side effects include bone marrow suppression, leukopenia, thrombocytopenia, hepatotoxicity, gastrointestinal reactions, alopecia areata, amenorrhea, and hemorrhagic cystitis.
Methotrexate (MTX) has immunosuppressive and anti-inflammatory effects, reducing ESR and improving bone erosion. The dosage is 5–15mg weekly via intramuscular injection or oral administration, with a treatment course of 3 months. Side effects include anorexia, nausea, vomiting, stomatitis, alopecia areata, leukopenia, thrombocytopenia, drug-induced interstitial pneumonitis, and rashes. It may become an alternative disease-modifying drug after gold and penicillamine.
7. Adrenal corticosteroids provide rapid relief for joint swelling, pain, and inflammation, but their effects are not sustained and do not influence the disease cause or pathogenesis. Relapse occurs shortly after discontinuation. They do not improve RF, ESR, or anemia. Long-term use leads to severe side effects, so they are not routine treatments. They are reserved for severe vasculitis causing extra-articular organ damage (e.g., ocular complications risking blindness, CNS lesions, heart block, or persistent active synovitis) or cases unresponsive to NSAIDs or penicillamine. A low-dose corticosteroid may be added to existing therapy, with gradual tapering to the minimal maintenance dose after symptom control.
Hydrocortisone acetate suspension can be injected intra-articularly for refractory monoarthritis, with 25–50mg per injection, while strictly preventing joint infection and bone destruction. Triamcinolone acetonide is a long-acting corticosteroid suitable for intra-articular administration, with doses of 10mg (or 30mg for the knee joint).
8.Root Leaf or Flower of Common Threewingnut After years of clinical application and experimental research in China, it has shown good therapeutic effects. It exhibits non-steroidal anti-inflammatory effects, as well as immunosuppressive or cytotoxic effects, which can improve symptoms and reduce erythrocyte sedimentation rate and RF titer. Common Threewingnut glycosides at 60mg/d can produce clinical effects within 1 to 4 weeks. Side effects include menstrual irregularities and amenorrhea in women, reduced sperm count in men, rash, leukopenia and thrombocytopenia, abdominal pain, diarrhea, etc. These effects can be eliminated after discontinuation of the medication.
Kunming Mountain Begonia, with effects similar to Root Leaf or Flower of Common Threewingnut, is taken 2–3 tablets each time, three times daily. The treatment course lasts 3–6 months or longer. Side effects include dizziness, dry mouth, sore throat, loss of appetite, abdominal pain, and amenorrhea.
9. Other Treatments Thymosin, plasmapheresis, and other therapies remain under exploration.
(3) Physical Therapy The goal is to use thermotherapy to enhance local blood circulation, relax muscles, and achieve anti-inflammatory, anti-swelling, and analgesic effects, while incorporating exercises to maintain and improve joint function. Physical therapy methods include hot water bags, hot baths, wax baths, infrared therapy, etc. Post-therapy, tuina may be combined to improve local circulation and relieve muscular rigidity and spasms.
The purpose of exercise is to preserve joint mobility and strengthen muscle power and endurance. After acute symptoms subside, as long as the patient can tolerate it, early and regular active or passive joint exercises should be initiated.
(4) Surgical Treatment Previously, surgery was considered only for advanced-stage deformities. Currently, early synovectomy may be attempted for cases with severe damage limited to 1–2 joints and unresponsive to salicylate therapy. For late-stage (third-stage) cases with static lesions and significant deformities, osteotomy correction may be performed. Joint ankylosis or destruction may warrant arthroplasty or artificial joint replacement. Weight-bearing joints may undergo arthrodesis.
Generally, early and aggressive comprehensive treatment yields better recovery outcomes. Acute-onset cases fare better than chronic ones, males better than females. Cases involving only a few joints with mild systemic symptoms or non-symmetrical joint involvement often have a shorter course. About 10–20% of patients become disabled due to inadequate treatment. The disease does not directly cause death, but severe advanced-stage cases may succumb to secondary infections.
The disease manifests with a rapid onset, and the course of progression is relatively short. After one episode, symptoms may be absent for several months or years, remaining dormant for a period before recurring. In cases with an insidious onset, the disease progresses slowly and gradually, with the entire course lasting several years, characterized by alternating periods of remission and relapse. Approximately 10–20% of patients experience complete remission after each episode. With each recurrence, the affected joints become increasingly stiff and less flexible, eventually fixing the joints in abnormal positions and leading to deformities. According to foreign statistics, about 10% of patients lose their ability to work entirely within a few years of onset.
Factors associated with a poor prognosis include: ① typical lesions (symmetrical polyarthritis accompanied by subcutaneous nodules and high titers of wind-dampness factors); ② disease activity persisting for over a year; ③ onset before the age of 30; and ④ the presence of extra-articular manifestations of wind-dampness sexually transmitted disease.
This disease must be differentiated from the following conditions:
(1) **Hyperplastic Osteoarthritis** The onset age is usually over 40, with no systemic disease. There is no local redness or swelling in the joints, and the commonly affected joints are weight-bearing ones such as the knees and spine. There is no migratory phenomenon. Muscle atrophy and joint deformities present with lip-like hyperplasia or osteophyte formation. The erythrocyte sedimentation rate (ESR) is normal, and rheumatoid factor (RF) is negative.
(2) **Wind-Dampness Arthritis** This condition is particularly prone to confusion with rheumatoid arthritis (RA) at onset. The following points can aid differentiation: ① The onset is generally acute, with sore throat, fever, and elevated white blood cell count. ② Large joints of the limbs are more commonly affected, with migratory joint swelling and pain, and no permanent damage after joint symptoms resolve. ③ Cardiac inflammation often occurs simultaneously. ④ Serum anti-streptolysin O (ASO), anti-streptokinase, and anti-hyaluronidase are all positive, while RF is negative. ⑤ Salicylate preparations often produce rapid and significant therapeutic effects.
(3) **Subcutaneous Node Arthritis** When rheumatoid arthritis is limited to a single joint or a few joints, it should be differentiated from this condition. This disease may be accompanied by subcutaneous node lesions in other areas, such as paravertebral abscesses in spinal subcutaneous nodes. Simultaneous involvement of more than two joints is rare. Early X-ray findings are difficult to distinguish, but localized bone destruction or paravertebral abscess shadows can aid diagnosis. Joint effusion cultures for subcutaneous node bacteria are often positive. Anti-subcutaneous node therapy is effective.
(4) **Other Connective Tissue Diseases (Involving Polyarthritis)**
1. **Systemic Lupus Erythematosus (SLE)** Early-stage wind-dampness arthritis is difficult to distinguish from SLE. The latter mostly occurs in young women and may also involve synovitis of the proximal interphalangeal and metacarpophalangeal joints, but joint symptoms are generally mild, with no cartilage or bone destruction. Systemic symptoms are prominent, with multi-organ damage. Typical cases present with butterfly or discoid facial rashes. Lupus cells, anti-dsDNA antibodies, Sm antibodies, and positive lupus band tests aid in diagnosis.
2. **Scleroderma** This condition predominantly affects women aged 20–50. In the early edema stage, symmetric hand stiffness, finger and knee joint pain, and periarticular soft tissue swelling due to synovitis can mimic RA. However, the early stage is self-limiting, often resolving suddenly after weeks. The presence of Raynaud’s phenomenon supports the diagnosis. In the sclerotic-atrophic stage, skin hardening and a "mask-like" facial expression facilitate differentiation.
3. **Mixed Connective Tissue Disease (MCTD)** Clinical symptoms resemble RA, but high-titer speckled antinuclear antibodies (ANA) and high-titer anti-ribonucleoprotein (RNP) antibodies are positive, while Sm antibodies are negative.
4. **Dermatomyositis** Muscle pain and edema are not limited to joints, and cardiac or renal involvement is common, whereas joint damage is rare. ANA is positive, and anti-PM-1 and anti-Jo-1 antibodies are often positive.
