Overview of Rheumatoid Arthritis
Rheumatoid arthritis is characterized by symmetric pain, swelling, morning stiffness, and other joint symptoms in the early stages of the disease. The cause of the disease is complex, and is mainly related to genetics, infections, sex hormones, smoking, and other factors. The mainstay of treatment is with nonsteroidal anti-inflammatory drugs (NSAIDs), traditional disease-improving antirheumatic drugs, glucocorticoids, and biologics.
Definition
Rheumatoid arthritis is a systemic autoimmune disease with multiple joint involvement as the main manifestation, and early rheumatoid arthritis usually refers to the early stage of rheumatoid arthritis disease. Patients tend to present with symptoms such as joint pain and swelling, while other systemic damage is relatively rare, usually without obvious structural destruction of the joints [1-3].
Morbidity
Since the early stage of rheumatoid arthritis is a stage in the course of rheumatoid arthritis, there is no epidemiologic study data for the early stage of rheumatoid arthritis, but a general understanding of the incidence of rheumatoid arthritis can be obtained.
The prevalence of rheumatoid arthritis varies from region to region, ranging from 0.1% to 1.9%, i.e., 1 to 19 per 1,000 people; in China, the prevalence is about 0.32% to 0.36%, i.e., about 32 to 36 per 10,000 people [1,4].
There are about 5 million rheumatoid arthritis patients in China, and the disease can occur at any age, but is more common in women of childbearing age, with a male-to-female ratio of about 1:3 [4-5].
Causes
The etiology and pathogenesis of rheumatoid arthritis is complex and involves interactions between genes and the environment. The pathogenesis is generally considered to be related to genetic factors, infectious factors, sex hormones, and smoking [1-2].
Causes
Genetic factors
The prevalence of rheumatoid arthritis in first-degree relatives has been found to be about 10%, making family history an important risk factor for the development of the disease [1-2].
Human leukocyte antigens (HLA) can be typed according to different gene loci, among which HLA-DR is often expressed on immune cells such as dendritic cells and B-lymphocytes, and participates in the process of the body’s immune response. It has been found that HLA-DR4 and DR1 alleles are associated with the development of rheumatoid arthritis [2,6-7].
In addition, the abnormal expression of genes such as PTPN22 and PADI, which have an effect on the normal function of cytokines and enzymes in the body, may also be involved in the early pathogenesis of rheumatoid arthritis [2].
Infectious factors
It is believed that pathogens such as Mycoplasma, EBV, human microvirus B19, and Porphyromonas gingivalis have been associated with rheumatoid arthritis, and potential pathogens can trigger the disease through a variety of mechanisms including direct infection of the synovium, activation of intrinsic immunity through pattern recognition receptors, or induction of an auto-responsive adaptive immune response through molecular mimicry, leading to its pathogenesis [2,4].
Sex hormones
There are significant gender differences in the development of rheumatoid arthritis, with pre-menopausal women having a significantly higher prevalence than men of the same age, and 75% of patients experience remission of the disease during pregnancy, but relapse of the disease can occur after delivery [1].
The association between sex hormones and rheumatoid arthritis is complex. Some studies have found that estrogen deficiency may cause the body to produce a large number of pro-inflammatory cytokines, affecting the normal metabolism of bone, and appropriate estrogen supplementation may improve the condition, suggesting that sex hormones may play a role in the early pathogenesis of rheumatoid arthritis [2,8].
Smoking
Smoking is a relatively clear risk factor for rheumatoid arthritis and is associated with the early onset of rheumatoid arthritis [2,9].
It is now believed that smoking is associated with the activation of intrinsic immunity and PADI in the respiratory tract, increasing the citrullination of proteins and stimulating the production of local autoantibodies such as anti-cyclic citrullinated peptide antibodies in susceptible individuals, which are involved in the pathogenesis of the disease [1-2,9].
Predisposing factors
The following factors are associated with the early onset of rheumatoid arthritis and are predisposing factors for the disease [1-3].
Women of childbearing age.
Family history of rheumatoid arthritis.
Symptoms
Main Symptoms
Patients in the early stages of rheumatoid arthritis are characterized by joint symptoms, including joint pain, joint swelling, and morning stiffness [1-2].
Joint pain
The pain often involves the small joints of the hands and feet, such as wrist joints, metacarpophalangeal joints of the fingers, proximal interphalangeal joints, and metatarsophalangeal joints of the feet, and the pain is commonly distributed in a polyarticular and symmetrical manner, but some patients in the early stage may show less joints and asymmetry.
Joint swelling
The affected joints are often congested and edematous due to local inflammation, which may be manifested as localized pike-shaped swelling.
Morning stiffness
Most patients with rheumatoid arthritis in the early stage may have morning stiffness, i.e., the stiffness of the affected joints increases in the morning or after the joints are at rest, and can be gradually reduced after activities. The duration of morning stiffness in rheumatoid arthritis patients is longer, mostly more than one hour.
Other symptoms
As rheumatoid arthritis often has an insidious onset in the early stages, patients may also present with non-specific systemic symptoms such as fatigue, weight loss, and fever [2].
Complications
Patients with early rheumatoid arthritis may also have complications such as rheumatoid nodules and pulmonary involvement [2].
Rheumatoid nodules
Rheumatoid nodules are rarely seen in early rheumatoid arthritis and are a characteristic manifestation of the disease, suggesting that the disease is severe and may disappear in remission [2].
Rheumatoid nodules are found in friction-prone areas, such as the elbow, knee, and Achilles tendon, and are often oval or hemispherical in shape, tough, and immobile [10].
Lung involvement
Some patients in the early stage of rheumatoid arthritis may also have lung involvement, such as interstitial pneumonia and emphysema, with symptoms such as cough, chest tightness and wheezing [2].
Consultation
Department of Medicine
Rheumatology
When symptoms such as joint pain, swelling and morning stiffness occur, prompt consultation with the Department of Rheumatology and Immunology is recommended.
Respiratory Medicine
If you experience symptoms such as coughing, sputum, chest tightness, wheezing, etc., it is recommended that you consult the Department of Respiratory Medicine promptly.
Preparation
Preparation for consultation: registration, preparation of documents, common problems
Tips for the doctor
It is recommended to wear loose clothing to the clinic to facilitate the physical examination.
Record the changes and characteristics of your condition for your doctor’s reference.
Patients with severe joint symptoms or obvious weakness are recommended to be accompanied by family members.
Preparation Checklist for Doctor’s Visit
Symptom list
Particular attention should be paid to the time of onset of symptoms, special manifestations, etc.
Are there any symptoms such as joint pain, swelling, morning stiffness, etc.? When did they first appear? When did it get worse? Does it resolve on its own?
Are there symptoms such as fatigue, weight loss, fever, rheumatoid nodules? When did they first appear?
Are there any symptoms such as cough, chest tightness, chest congestion, wheezing?
List of medical history
Is there any history of infection with Mycoplasma, EBV, human microvirus B19, Porphyromonas gingivalis, etc.?
Is there a history of smoking?
Is there a family history of rheumatoid arthritis?
Checklist
Test results of the last 6 months, which can be brought to the doctor’s office
Laboratory tests: blood test, blood biochemistry, blood sedimentation, C-reactive protein, autoantibody test, rheumatoid factor, etc.
Imaging examination: ultrasonography, joint X-ray, CT examination, etc.
Other tests: lung function test, etc.
Medication List
Medications used in the last 3 months, if available in boxes or packages, bring them to the doctor’s office
Non-steroidal anti-inflammatory drugs: e.g. ibuprofen, loxoprofen, celecoxib, meloxicam, etc.
Glucocorticosteroids: e.g. prednisone, methylprednisolone, etc.
Traditional disease-modifying antirheumatic drugs: e.g. methotrexate, leflunomide, hydroxychloroquine sulfate, salazosulfapyridine, etc.
Biological agents: such as adalimumab, etanercept, infliximab, tolizumab, abatacept, etc.
Small molecule targeted synthetic drugs: e.g. tofacitib, baricitinib, upatinib, etc.
Diagnosis
Early diagnosis of rheumatoid arthritis is mainly based on clinical manifestations, laboratory tests and imaging tests.
Diagnosis is based on
Medical history
The following is not necessary for the diagnosis of the disease, but if there are the following conditions, it can provide some reference significance for the diagnosis of the disease.
A history of infection with Mycoplasma, EBV, human microvirus B19, and Porphyromonas gingivalis.
Have a history of smoking.
There is a family history of rheumatoid arthritis.
Clinical manifestations
Symmetrical pain, swelling and morning stiffness in the small joints of the hands or feet, as well as fatigue, weight loss, fever and rheumatoid nodules.
Some patients may have symptoms of lung involvement such as cough, sputum, chest tightness and wheezing.
Laboratory Tests
Routine blood tests
Hemoglobin, white blood cell count, red blood cell count, platelet count, etc. are abnormal.
The presence of abnormal results of the above blood cell counts often suggests disease activity or severity and may guide the diagnosis and treatment of patients with early rheumatoid arthritis [1-2].
Blood biochemistry
It mainly includes liver function, kidney function and other items, which can be used to determine the patient’s liver and kidney function and so on.
If the blood creatinine and urea nitrogen are obviously elevated, it suggests that there may be impaired renal function; if the transaminase is obviously elevated, it suggests that there may be impaired liver function, which is of great significance in determining the severity of the patient’s condition.
Blood Sedimentation
Hematocrit is the sedimentation rate of erythrocytes, which is a commonly used indicator of inflammation in the acute phase, used to clarify whether there is an inflammatory reaction in the body.
If there is a significant increase in blood sedimentation, it suggests that the patient may be in the acute inflammatory phase, which can assist in the early diagnosis of rheumatoid arthritis and guide the treatment, etc. [2].
C-reactive protein
C-reactive protein is also a commonly used clinical acute phase reactive protein, which can be used to clarify the degree of inflammatory response.
If C-reactive protein is significantly elevated, it suggests that the patient may be in the acute phase of the inflammatory response, which helps to determine the extent of the disease [11].
Anti-citrullinated protein antibody (ACPA) test
ACPA is the most common autoantibody in rheumatoid arthritis, including anti-cyclic citrullinated peptide (CCP) antibody, anti-perinuclear factor (APF) antibody, anti-keratin (AKA) antibody, and mutant citrullinated wave protein (MCV) antibody.
If the test results of anti-CCP, APF, AKA, and MCV antibodies are positive, it suggests the possibility of early rheumatoid arthritis, which can help in the diagnosis and differential diagnosis of the disease [1-2].
Rheumatoid factor
Rheumatoid factor is one of the commonly used tests for rheumatoid arthritis patients.
If the rheumatoid factor results are significantly elevated or positive, it suggests the possibility of early rheumatoid arthritis, which can help in the diagnosis, differential diagnosis and prognosis of the disease [12]. However, rheumatoid factor is not only seen in rheumatoid arthritis, but also in other rheumatic diseases or some non-rheumatic diseases.
Imaging
Ultrasound.
Ultrasound, such as joint ultrasound, can be used to clarify whether a patient has synovitis, effusion, or bone destruction.
If synovitis is present on joint ultrasound, it suggests the possibility of rheumatoid arthritis disease and indicates an active phase of the disease. If irregular and discontinuous joint surfaces are found, it indicates bone erosion and suggests that the patient may have joint destruction, which helps in the diagnosis and differentiation of the disease [1].
Joint X-ray
Joint X-ray is often used to clarify whether the patient has bone destruction, joint space narrowing, etc. It is not sensitive to patients in the early stage of rheumatoid arthritis.
Arthrography may reveal periarticular soft tissue swelling, osteoporosis near the joints, periarticular bone cystic degeneration, articular surface bone erosion, gap narrowing, and joint ankylosis, which can assist in making a definitive diagnosis as well as evaluating the condition [2-3].
CT examination
CT examination is mainly used to clarify whether the patient has interstitial pneumonia, emphysema and other manifestations of lung involvement.
When the CT examination of the lungs reveals grinding glass-like changes, irregular linear shadows, reticular shadows, sparse lung texture, increased translucency of the lung field, etc., it suggests that there may be lung involvement, which is helpful for the diagnosis of the disease and the judgment of the severity of the disease [13].
Lung function tests
Pulmonary function tests include lung volume, ventilation function, diffusion function and other indicators, which can be used to clarify whether the patient has lung involvement and the degree of lung function abnormality caused by it.
When pulmonary function tests show the presence of pulmonary ventilation dysfunction, reduced diffusion function, small airway lesions, etc., it suggests that there may be lung involvement, which is of great significance in judging the condition and guiding treatment [14].
Differential diagnosis
Gouty arthritis
Similarities: Gouty arthritis and rheumatoid arthritis in the early stages of the disease may both present with joint pain and swelling.
Differences: Gouty arthritis often starts suddenly and involves a single joint, usually the first metatarsophalangeal joint. The affected joints may show redness of the skin and increased skin temperature. Laboratory tests show elevated blood uric acid level, joint ultrasound, dual-energy CT and other manifestations of urate crystal deposition, but generally there is no ACPA antibody, rheumatoid factor positive and other changes.
Psoriatic arthritis
Similarity: Psoriatic arthritis and rheumatoid arthritis in the early stage of patients can appear pain, swelling and other manifestations of the small joints of the hands and feet.
Differences: Patients with psoriatic arthritis have a clear history of psoriasis or a family history of psoriasis, and the affected joints include the distal interphalangeal joints, accompanied by sacroiliac arthritis. Laboratory tests for rheumatoid factor and ACPA antibodies are mostly negative [3].
Treatment
Aim of treatment: through early and standardized treatment, to achieve the purpose of controlling the disease and delaying the progress.
Treatment principle: The disease is mainly treated by relieving symptoms, controlling the condition, preventing joint disability and preventing internal organ damage, with drug treatment as the main treatment, supplemented by general treatment.
General treatment
Patients with rheumatoid arthritis in the early stage of the disease, such as joint pain and swelling are obvious, should pay attention to rest, avoid joint labor and pay attention to joint warmth.
When the symptoms improve, appropriate joint function exercise can be carried out under the guidance of the doctor, such as palm training, grasping exercises.
Medication
Non-steroidal anti-inflammatory drugs
Commonly used drugs such as ibuprofen, loxoprofen, celecoxib, meloxicam and so on.
NSAIDs can exert analgesic and anti-inflammatory effects by inhibiting the synthesis and release of cyclo-oxygenase and prostaglandins, and are commonly used to relieve the symptoms of patients in the early stages of rheumatoid arthritis.
Adverse effects of this class of drugs include gastrointestinal reactions (e.g., peptic ulcer, upper gastrointestinal bleeding), renal impairment, cardiovascular disease, and allergic reactions (e.g., asthma, urticaria) [15].
Glucocorticoids.
Commonly used drugs such as prednisone and methylprednisolone.
Glucocorticosteroids have anti-inflammatory and immunosuppressive effects, which can rapidly relieve symptoms, and are mainly applied to patients who are in the active stage of the disease and ineffective in the treatment of non-steroidal anti-inflammatory drugs, and patients with obvious lung involvement, rheumatoid nodules and other extra-articular manifestations [1].
Glucocorticoids have more adverse effects, and their long-term application can lead to side effects such as infection, osteoporosis, hypertension, drug-induced diabetes mellitus, and in severe cases, aseptic necrosis of the femoral head [15].
Traditional disease-improving antirheumatic drugs
Commonly used drugs such as methotrexate, leflunomide, hydroxychloroquine sulfate, salazosulfapyridine, and elamod.
They can play the role of improving and delaying the progression of the disease by inhibiting intracellular dihydrofolate reductase, etc., and can block bone destruction. Patients in the early stages of rheumatoid arthritis should be treated with disease-improving antirheumatic drugs as soon as they are diagnosed [1,15].
Common adverse reactions to this class of drugs include allergy, abdominal pain, diarrhea, nausea, ulcerative stomatitis, alopecia, myelosuppression, liver damage, etc. The specific choice of drugs should be based on the patient’s specific condition and physical condition. [2,15].
Biological agents
Commonly used drugs such as adalimumab, etanercept, infliximab, tolizumab, abatacept and so on.
Biological agents can act directly on cells important in the pathogenesis of rheumatoid arthritis such as T cells, or important cytokines such as tumor necrosis factor-α and interleukin-6. Biological agents can quickly and effectively control the disease, delay the progress, and block bone destruction, and are commonly used to improve the condition of patients with poor antirheumatic drug treatment and high early activity [15-17].
Adverse effects of this class of drugs include infections, abnormal liver function, hematopenia, skin erythema, and elevated cholesterol [15].
Small molecule targeted synthetic drugs
mainly refer to JAK inhibitors, such as tofacitib, baricitinib, and upatinib.
By inhibiting intracellular JAK molecules, they block the activity of the JAK-STAT pathway, thereby inhibiting the effects of multiple inflammatory factors.
Adverse effects of this class of drugs include infections, thrombosis, elevated blood lipids, tumors, and hematopenia.
Prognosis
Cure
At present, rheumatoid arthritis cannot be completely cured, and the prognosis varies among patients due to the different progress of their diseases [17]. Early diagnosis and treatment is the key.
Patients with early rheumatoid arthritis who have severe joint symptoms at the onset of the disease, or who have combined lung and other internal organ function involvement, generally have faster disease progression and require more aggressive treatment. Early and standardized treatment can significantly improve the prognosis of patients and reduce the possibility of disability [1].
Hazards
In the early stage of rheumatoid arthritis, patients may experience pain, swelling, and morning stiffness in the affected joints, resulting in limited activities and affecting normal work and life.
Some patients may suffer from delayed treatment due to inaccurate diagnosis and untimely treatment, or some patients may suffer from unstandardized treatment after diagnosis, which may eventually lead to joint deformity and disability. In addition to joints, patients may also have multiple organ involvement, such as impaired lung function, the occurrence of cardiovascular and cerebrovascular diseases, which seriously affects the quality of life of patients and reduces the survival rate.
Daily
Daily Management
Dietary management
Diet should pay attention to balanced nutrition, and consume food rich in high quality protein, such as eggs, lean meat, etc., and food rich in calcium and vitamin D, such as milk, shrimp skin, etc..
Reduce the intake of spicy and irritating foods such as chili peppers and peppers, etc. Avoid cold and raw foods to avoid increasing the risk of gastrointestinal infections.
Life management
Pay attention to cold protection and warmth; quit smoking [1-2].
Pay attention to personal hygiene, clean and disinfect the living environment regularly, open windows more often for ventilation, and actively prevent infections.
Appropriate aerobic activities, such as jogging, swimming, walking, pedaling, tai chi, etc., can be performed as prescribed by the doctor.
Psychological support
Some early rheumatoid arthritis patients may experience anxiety, depression and other negative emotions during the diagnosis and treatment of recurrent disease. In case of emotional instability and psychological depression, relatives and friends can increase companionship and support, and psychological intervention can be carried out if necessary.
Disease monitoring
Patients with fever should have their temperature measured and recorded daily.
Observe whether the joint symptoms change, such as whether the pain and swelling worsen, whether the site increases, whether morning stiffness occurs and the duration of morning stiffness.
Pay attention to observe whether there are signs of weakness, cough, sputum, chest tightness, wheezing, pain in the precordial area, etc. If there is dyspnea, chest tightness, etc., it is necessary to consult a doctor promptly.
In case of adverse drug reactions (e.g. itchy skin, nausea, abdominal pain, hepatic impairment, infection, etc.), timely medical consultation or follow-up is required.
Follow-up examination
As rheumatoid arthritis progresses in the early stages and the disease is prone to recurrence during the process, regular review can help relieve symptoms and adjust treatment in time.
Regular checkups should be conducted according to the doctor’s instructions, and the cycle of checkups usually lasts for one to three months.
Tests that may be needed during the review include routine blood tests, blood biochemistry, rheumatoid factor, CCP antibody, immunoglobulin, joint ultrasound, X-ray, chest CT, and so on.
Prevention
The causes of rheumatoid arthritis in its early stages are complex and varied, and it is generally difficult to prevent effectively, but you can help to reduce the risk of developing the disease by, for example, following healthy lifestyles or behaviors.
Pay attention to personal hygiene and actively prevent infections.
Do not smoke or quit smoking if you are a smoker, and stay away from second-hand smoke.
People with a family history of rheumatoid arthritis should have regular medical checkups and seek prompt medical attention if they have any uncomfortable symptoms.