rheumatoid arthritis



Overview of Rheumatoid Arthritis

Rheumatoid arthritis is a systemic autoimmune disease that mainly affects the peripheral joints and is characterized by joint swelling, pain, morning stiffness, joint deformity, and difficulty in movement. The specific etiology of rheumatoid arthritis is still unclear, and it may be related to genetic, environmental and other factors, with medication as the main treatment, supplemented by surgical treatment.

Definition

Rheumatoid arthritis is a chronic, systemic autoimmune disease with erosive, symmetric polyarthritis as its main clinical manifestation, mainly affecting the peripheral joints.

Incidence

According to the literature, the global prevalence of rheumatoid arthritis is 0.5% to 1%, and the prevalence in mainland China is 0.42%, with a total population of about 5 million.

Rheumatoid arthritis is most common in women aged 35 to 50, with a male-to-female ratio of about 1:4.

Causes

Causes

The cause of the disease has not yet been clarified, but a large number of studies have shown that genetic factors, environmental factors and other factors are related to the development of this disease.

Genetic factors

Human leukocyte antigen-DRB1 (HLA-DRB1) allele mutations are associated with the development of rheumatoid arthritis.

The gene locus (HLA-DQα1:160D) is another strong genetic factor associated with rheumatoid arthritis in Han Chinese.

Environmental factors

Occupational exposure: exposure to asbestos, silica, organic solvents, etc. at work may increase the risk of rheumatoid arthritis.

Smoking: increases the risk of rheumatoid arthritis-related autoantibody production, significantly increasing the risk of developing the disease.

Pathogenic microorganisms: such as bacteria, mycoplasma and viruses may promote autoantibody production and influence the onset and progression of rheumatoid arthritis.

Pathogenesis

The pathogenesis of rheumatoid arthritis is complex and has not been fully elucidated.

Currently, it is believed that rheumatoid arthritis is based on susceptibility genes, and that environmental factors initiate T-cell activation and autoimmune reactions, leading to an autoimmune system “attack” on the joint tissues, resulting in inflammatory damage to the joint tissues, synovial membrane hyperplasia, and structural damage to the bone and cartilage.

Symptoms

Clinical manifestations vary greatly from one individual to another, with joint symptoms being the most typical and systemic symptoms being more insidious, and may affect areas outside the joints, such as the heart, lungs, and blood vessels.

Main Symptoms

Joint pain

The severity of joint pain usually correlates with the degree of swelling, which may be accompanied by tenderness and brownish pigmentation of the corresponding skin.

Location of pain

It is most common in the wrist, metacarpophalangeal and proximal interphalangeal joints, followed by the toes, knees, ankles, elbows and shoulders.

Pain may also occur in the neck, buttocks and lower back.

Pain occurs in the temporomandibular joints when speaking or chewing, and in severe cases, inability to open the mouth or limited opening of the mouth.

Nature of pain: mostly symmetrical and persistent, sometimes mild and sometimes severe.

Joint swelling

Swelling of joints, symmetrical.

It is usually present at the beginning of the disease.

Typically, the proximal interphalangeal joints of the fingers are swollen in the shape of a pike.

Commonly, the area of swelling is the same as the area of joint pain.

Both active and passive movements of the joint are limited.

Morning stiffness

A feeling of stiffness and discomfort when the joints are moved in the morning.

It is noticeable in the morning and decreases after moving.

Sometimes it can last for more than 1 hour.

Joint deformity

The proximal interphalangeal joints are hyperextended and the distal interphalangeal joints are flexed, resembling the neck of a swan when viewed from the side.

The proximal interphalangeal joints lose the ability to actively straighten and remain bent, while the distal interphalangeal joints are hyperextended, which is called “button flower”-like deformity.

Knee joint internal and external deformity.

Most often occurs in the late stages of the disease.

Difficulty in joint movement

Grade I: Can carry out daily life and work as usual.

Grade II: Can carry out general daily life and certain occupational work, but limited to participate in other activities.

Grade III: Can carry out normal daily life, but participation in some occupational work or other activities is limited.

Grade IV: Limitations in self-care in daily life and participation in work.

Other symptoms

Fever

A low-grade fever that lasts for several weeks may occur early in the disease.

In rare cases, a high fever may develop.

Muscle pain

Generalized muscle soreness and tenderness.

Weight loss

Loss of appetite and significant weight loss.

Complications

Rheumatoid nodules

Prevalent in males, mostly with a long history of heavy smoking.

Nodules of different sizes appear on the extensor surface of the forearm, below the ulnar humerus, and in the Achilles tendon, which are hard, non-indurated, and symmetrically distributed.

Interstitial lung lesions

Presenting with shortness of breath and dry cough after activity.

Pleurisy

Often with chest pain, fever, cough, chest tightness and other symptoms.

Pulmonary hypertension

The most common first symptom is shortness of breath and weakness after activity.

Other symptoms are chest pain, hemoptysis, vertigo or fainting, and dry cough.

Rheumatoid Pneumoconiosis

Manifestations include cough, coughing up black or brown sputum, hemoptysis, and varying degrees of dyspnea and chest pain.

Pericarditis

Shortness of breath, dyspnea, retrosternal or precordial pain may occur, and in severe cases, heart failure may occur leading to death.

Anemia

Often manifested by fatigue, easy fatigue and dizziness.

Felty syndrome

Most often with joint deformities.

Generalized malaise, fever, fatigue, loss of appetite, weight loss.

Brown or black hyperpigmentation of exposed areas of the skin.

Skin or mucosal ulcers, especially calf ulcers are common.

Enlargement of lymph nodes throughout the body.

Rheumatoid vasculitis

Petechiae, ecchymosis, and reticular cyanosis appear on the skin.

Deep and large ulcers on the lower extremities.

Dry syndrome

Mainly characterized by dry mouth, dry eyes and dental caries.

Intermittent alternating parotid swelling and pain.

Weakness, skeletal muscle arthralgia, etc.

Carpal tunnel syndrome

Numbness or pain in the ends of the fingers and weakness in holding objects.

Symptoms are most severe at night or in the early morning and can be relieved by shaking the wrist appropriately.

Tarsal Tunnel Syndrome

Intermittent tingling, burning or numbness in the soles of the feet or heels.

Symptoms are worse when walking, standing or at night.

Consultation

Department of Medicine

Rheumatology

If you experience symptoms such as swollen and painful joints, stiffness and discomfort when you move your joints in the morning, deformity of the joints, or difficulty in moving them, it is recommended that you consult a doctor promptly.

Orthopedics

If you experience any of the above symptoms, you can also consult an orthopedic surgeon.

Preparation

Preparing for the consultation: registration, preparation of documents, common problems

Tips for medical treatment

Record the progress of your condition to give the doctor more reference.

It is recommended to wear clothes and shoes that are easy to put on and take off for the doctor’s examination.

Preparation Checklist

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Which part of the joint is experiencing pain, redness and swelling?

Are there any triggers for the onset of joint pain? What time of day is the pain most noticeable?

Do you experience stiffness and discomfort when you move your joints in the morning, and how long does it last?

Is there any deformation of the joint?

Is there any limitation of joint movement?

List of medical history

Has anyone in the family suffered from rheumatoid arthritis?

Are there any autoimmune diseases or other systemic diseases?

Checklist

Test results in the last six months, which can be brought to the doctor’s office

Laboratory tests: blood tests, urine tests, autoantibody tests, liver and kidney function tests

Imaging tests: joint magnetic resonance examination, X-ray examination, ultrasound examination, CT examination

Others: arthroscopy, synovial fluid examination

Medication List

Medications used in the last 3 months, if available in boxes or packages, bring them to the doctor’s office

Analgesic drugs: indomethacin, acetaminophen, diclofenac, ibuprofen

Others: methotrexate, leflunomide, salazosulfapyridine

Diagnosis

Diagnostic Basis

The diagnosis of rheumatoid arthritis relies on a thorough history, comprehensive examination, and careful differential diagnosis. Each clinical manifestation must be excluded from the corresponding systemic disease before a diagnosis can be made.

Medical history

History of autoimmune disease or systemic disease.

Relatives of patients with the disease.

Clinical manifestations

Swelling and pain in the joints, morning stiffness, joint deformity and difficulty in movement.

The onset of the disease is usually chronic, but rarely acute.

Laboratory tests

Helps to determine the cause of the disease.

Blood tests

Purpose: To find out the changes of blood cells (red blood cells, white blood cells, platelets) and hemoglobin.

Significance: Increased platelets, normal white blood cell count and classification may be seen in patients with active disease.

Urine routine

Purpose: To find out the changes of urine components (red blood cells, white blood cells, protein, etc.).

Significance: When there is kidney damage, abnormal red blood cells may appear in the urine, and the urine protein is abnormally increased.

Precautions: When urine specimens are taken, clean mid-range urine should be selected.

Autoantibody test

Purpose: To find out whether there are autoantibodies in the body and to assist in diagnosis.

Significance: A variety of autoantibodies can be detected in the patient’s serum, mainly including rheumatoid factor, anti-cyclic citrullinated antibody, anti-keratin antibody, and anti-mutant citrullinated wave protein antibody.

Erythrocyte Sedimentation Rate and C-Reactive Protein

Purpose: To understand the changes in erythrocyte sedimentation rate and C-reactive protein.

Significance: The main indicator to reflect the activity of the disease, which is often elevated and can be reduced to normal when the disease is in remission.

Liver and Kidney Function

Purpose: To understand the state of liver and kidney function, and to determine the damage of liver and kidney function.

Significance: creatinine and urea nitrogen can be elevated when kidney function is impaired; transaminases and bilirubin can be elevated when liver function is impaired.

Precautions: Fasting is required for the examination.

Imaging

X-ray film

Purpose: To understand the condition of hands, wrist joints and other diseased joints.

Significance: Helps in the diagnosis of the disease.

Precautions

X-ray examination should be performed with caution for special groups, such as pregnant women.

Remove metal objects, such as rings and bracelets, from the examination area before the examination.

Magnetic Resonance Imaging (MRI) of Joints

Purpose: To understand the lesions of articular cartilage and surrounding soft tissues and to assist in diagnosis.

Significance

Used for early diagnosis of rheumatoid arthritis.

It is superior to methods such as X-ray plain film and CT in determining acute synovitis, vascular opacities, proliferation of synovial and other supporting structures, and articular cartilage and bone erosion.

One of the strong independent predictors of imaging progression in early rheumatoid arthritis, and can be used as one of the indicators of disease progression and outcome judgment.

Precautions

Metal or magnetic objects on the body need to be removed in advance.

People with pacemakers, metal or magnetic objects in their body cannot undergo the test.

Joint Ultrasound

Purpose: To understand the morphology, structure and surrounding lesions of the joints and to assist in diagnosis.

Significance

It is able to show bone erosion lesions that cannot be seen on X-ray films.

It can dynamically determine the amount of joint fluid and its distance from the body surface, which can be used to guide joint puncture or treatment.

Doppler ultrasound can be used to confirm the presence of synovitis, detect disease activity and progression, and assess inflammation.

Note: A coupling agent is applied to the skin surface of the joint during the examination and can be wiped off at the end of the examination.

CT

Purpose: To detect bone erosion.

Significance: Valuable for the detection of large joint lesions and lung disease; helpful in observing disease when combined with lung disease.

Precautions

Special groups, such as pregnant women, should be cautious.

Remove metal objects, such as rings and bracelets, from the body before the examination.

Other Examinations

Arthroscopy: a rod-shaped optical instrument to observe the internal structure of the joints, which helps to diagnose intra-articular lesions.

Synovial fluid examination: It can be used to confirm inflammation of the joints as well as to identify infections and crystalloid arthritis.

Diagnostic criteria

The 1987 classification criteria of the American College of Rheumatology (ACR) and the 2010 classification criteria published by the ACR and the European League Against Rheumatism (EULAR) are commonly used internationally. Both classification criteria have their own advantages in terms of sensitivity and specificity, and both are helpful for diagnosis.

1987 American College of Rheumatology (ACR) classification criteria

Rheumatoid arthritis is diagnosed when 4 or more of the following 7 criteria are met and other arthritis is excluded.

Morning stiffness: joint or peripheral morning stiffness lasting for at least 1 hour with a disease duration of ≥6 weeks.

Arthritis in ≥3 joint areas: soft tissue swelling or effusion (not just bone augmentation) in at least 3 of 14 joint areas (proximal interphalangeal joints, metacarpophalangeal joints, wrists, elbows, knees, ankles, and metatarsophalangeal joints on both sides) with a disease duration of ≥6 weeks.

Arthritis of the hand: swelling in at least one of the wrist, metacarpophalangeal, or proximal interphalangeal joint areas with a duration of ≥6 weeks.

Symmetric arthritis: simultaneous involvement of the left and right joints (not necessarily absolutely symmetric when bilateral proximal interphalangeal joints, metacarpophalangeal joints, and metatarsophalangeal joints are involved) with a duration of ≥6 weeks.

Rheumatoid nodules: subcutaneous nodules on the bony prominences, extensor surfaces or around the joints.

Positive serum rheumatoid factor: elevated serum levels of rheumatoid factor as evidenced by any test.

Imaging changes: definite osteoporosis or bone erosion on hand and wrist radiographs.

Classification criteria published by ACR/EULAR 2010

Serologic index score (0 to 3 points)

Rheumatoid factor (RF) and anti-cyclic citrulline (CCP) antibodies are both negative 0 points

Rheumatoid factor (RF) and anti-cyclic citrulline (CCP) antibodies are both negative

0 points

Low titer positive RF or anti-CCP antibody 2 points

Low titer positive RF or anti-CCP antibody.

2 points

RF or anti-CCP antibody high titer positive (3 times the upper limit of normal) 3 points

RF or anti-CCP antibody high titer positive (3 times upper limit of normal)

3 points

Duration of synovitis score (0 to 1 point)

<6 weeks 0 points

<6 weeks

0 points

≥6 weeks 1 point

≥6 weeks

1 point

Acute temporal reactant score (0 to 1 point)

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are both normal0 points

Both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are normal

0 points

CRP or ESR abnormal 1 point

CRP or ESR abnormal

1 point

Rheumatoid arthritis is diagnosed when the patient has synovitis in at least 1 joint that cannot be explained by other diseases and when the scores in the above 4 areas add up to ≥ 6 points (maximum 10 points).

Differential Diagnosis

The clinical manifestations of rheumatoid arthritis are complex and varied. Doctors will differentiate rheumatoid arthritis from other diseases according to different clinical manifestations.

Osteoarthritis

Similarities: joint pain, swelling and fluid accumulation.

Differences: Osteoarthritis is more common in middle-aged and old people, belongs to the degenerative joints, and mainly involves weight-bearing joints such as knees and spine.

Ankylosing spondylitis

Similarities: Both have morning sickness.

Differences: Ankylosing spondylitis mainly affects the sacroiliac and spinal joints, mostly seen in young and middle-aged men; joint involvement is mainly asymmetric large arthritis of the lower limbs, and rarely involves the joints of the hands; rheumatoid factor test is negative, and HLA-B27 can be positive.

Psoriatic arthritis

Similarities: Both present with symmetric polyarthritis.

Differences: psoriatic arthritis involves the distal phalangeal joints more obviously, and manifests as adhesive telangiectasia and phalangitis of the joints, and sacroiliac arthritis and spondylitis at the same time; Rheumatoid factor test is mostly negative, and HLA-B27 can be positive.

Gout

Similarities: both have joint pain and swelling.

Differences: Gout occurs mostly in men, with an acute onset, preferably in the 1st metatarsophalangeal joints, with localized redness, swelling, heat and pain, and often recurrent attacks. Acute attacks usually have increased blood uric acid levels, and sometimes gout stones may appear in the joints and ears.

Systemic Lupus Erythematosus

Similarities: Joint pain, swelling and morning stiffness.

Differences: SLE is often accompanied by fever, facial erythema, photosensitivity, recurrent mouth ulcers, hair loss, etc. Tests may reveal decreased blood counts, proteinuria, and positivity of antinuclear antibody, anti-Sm antibody, and anti-cardiolipin antibody.

Treatment

Treatment principle: early and standardized treatment, regular monitoring of disease changes, and timely review.

Treatment goal: to achieve remission or low disease activity (i.e., standardized treatment), control the disease, reduce the disability rate, and improve the quality of life.

General treatment

During the acute active phase of the disease, bed rest should be provided to reduce physical exertion and protect joint function.

Functional joint exercises can be carried out under doctor’s supervision to maintain or restore joint function during the recovery period.

Medication

During drug treatment, you should insist on following the doctor’s instruction strictly, and should not change the drug dosage without authorization or stop the drug suddenly to ensure that the treatment plan is implemented.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Effects: With analgesic and anti-inflammatory effects, they can relieve arthritis symptoms such as redness, swelling, heat and pain in the joints during the acute active period.

Commonly used drugs: Ibuprofen, Indomethacin, Loxoprofen, Celecoxib, Naproxen, Meloxicam, Diclofenac, and so on.

Precautions

May be at risk for gastrointestinal ulcers, bleeding, and perforation.

Avoid taking two or more NSAIDs together.

Relieve only the symptoms of pain, redness, and swelling; do not control or prevent exacerbation of the condition.

Synthetic disease-modifying antirheumatic drugs (DMARDs)

Once a diagnosis of rheumatoid arthritis has been made, treatment with DMARDs should be started as early as possible to slow or control the progression of the disease.

Traditional synthetic DMARDs

Methotrexate alone is generally preferred.

When methotrexate is ineffective or intolerant, other DMARDs, such as leflunomide, salazosulfapyridine, antimalarials (including hydroxychloroquine and chloroquine), azathioprine, cyclophosphamide, cyclosporine A, and gold preparations (kinnofen) may be chosen.

If the effect of single drug treatment is not good, DMARDs combination therapy can be used according to the specific condition.

Note: While taking methotrexate, folic acid should be supplemented under the guidance of a doctor.

Targeted synthetic DMARDs

Currently only refers to JAK inhibitors, including tofacitib and baricitinib.

If the combination of traditional synthetic DMARDs is not effective, one traditional synthetic DMARDs combined with one biological DMARDs can be applied for treatment; or one traditional synthetic DMARDs combined with one targeted synthetic DMARDs for treatment.

Biological DMARDs

Effects: Effective in controlling joint inflammation, reducing bone destruction, reducing glucocorticoid dosage and osteoporosis.

Commonly used drugs

Tumor necrosis factor (TNF)-α inhibitors: e.g. etanercept, infliximab, adalimumab, golimumab, etc.

Interleukin (IL)-1 inhibitors: e.g. anabolic acid.

IL-6 antagonists: e.g. tolizumab, etc.

Anti-CD20 monoclonal antibodies: e.g. rituximab, etc.

T-cell co-stimulatory signaling inhibitors, etc.: e.g. Abatacept, etc.

Precautions: After achieving the standard of treatment with the combination of drugs, a gradual reduction of the dosage can be considered, and the dosage reduction process needs to be closely monitored in order to prevent relapse.

Glucocorticoid

Apply to the active stage of severe disease.

Effects: Rapid improvement of joint swelling and pain and systemic symptoms.

Principle: small dose, short course of treatment.

Commonly used drugs: prednisone, etc. DMARDs should be used in combination at the same time, avoiding single use.

Precautions: In the course of glucocorticoid treatment, attention should be paid to the prevention of osteoporosis and infection.

Supplement calcium and vitamin D to prevent osteoporosis.

Closely observe the presence of infections and promptly carry out appropriate anti-infection treatment.

Botanical preparations

Effects: Helps to relieve joint swelling and pain, morning stiffness and other symptoms.

Commonly used drugs: Lei Gong Teng, Paeonia lactiflora total glycosides, Qing Feng Teng, etc.

Precautions: Close monitoring and evaluation of adverse effects such as gonadal suppression, bone marrow suppression, liver damage, etc. are required in the course of use.

Surgical treatment

If the condition cannot be controlled after active and regular treatment, surgery can be considered to correct the deformity and improve the quality of life.

Synovectomy

It can reduce the exudation of joint fluid, prevent the formation of vascular cataract, protect the cartilage and subchondral bone tissue, and improve the joint function.

Conventional synthetic DMARDs should be applied at the same time to prevent recurrence.

Arthroplasty

Suitable for joints with deformity and loss of function in more advanced stages.

Traditional Chinese Medicine (TCM)

Doctors will choose targeted treatments according to the condition (Diagnostic Therapy).

Tonics: Qiang Wu Sheng Dampness Tang Plus Reduction, Wu Tou Tang Plus Reduction, Shuang He Tang Plus Reduction, etc. may be used.

Acupuncture point plasters: San Fu Paste, San Jiu Paste, Spring and Autumn Equinox Acupuncture Points Paste, as well as poultices and other treatments can improve the symptoms and reduce the recurrence of the disease.

Tui na massage: Tui na massage therapy with traditional Chinese medicine can improve symptoms such as joint pain and morning stiffness.

TCM treatment should be carried out in regular hospitals under the guidance of or by a doctor, and do not believe in undetermined treatments such as local remedies, secret prescriptions, and biased prescriptions.

Other treatments

Physiotherapy methods such as wax therapy, hydrotherapy, magnetotherapy, ultra-short wave, infrared ray, etc. can be used to relieve pain under the guidance of a doctor according to the condition, and muscles can also be massaged and joints can be moved to prevent and control muscle contracture and joint mobility disorders.

Prognosis

Cure

Cannot be cured or eradicated.

With early diagnosis and standardized treatment, the progression of the disease can be slowed down, the occurrence of joint deformity and disability can be prevented, and the quality of life can be significantly improved.

Harmfulness

Joint pain, swelling and limitation of joint movement often occur, seriously affecting normal work and life. With the gradual progression of the disease, it eventually leads to joint deformity and loss of function, which is highly disabling.

According to the literature, the disability rates of rheumatoid arthritis in China are 18.6%, 43.5%, 48.1% and 61.3% for the disease duration of 1 to 5 years, 5 to 10 years, 10 to 15 years and more than 15 years, respectively.

As the disease progresses, it can also lead to damage to multiple organs such as the heart, lungs, brain, kidneys, blood vessels, eyes, etc., which further affects physical health and brings greater psychological and economic burdens to oneself and one’s family. In serious cases, it may be life-threatening.

If glucocorticoids are taken for a long period of time, serious adverse effects such as infection, osteoporosis, hypokalemia, hypertension, hyperglycemia, hyperlipidemia, etc. are likely to occur, further affecting physical health and quality of life.

Daily

Daily Management

Dietary management

No vital organs affected by disease

Choose foods rich in protein and vitamins, such as lean meat, milk, beans, fresh vegetables and fruits.

Avoid spicy and stimulating foods such as alcohol, strong tea, coffee, raw garlic, ginger, chili peppers and curry.

Reduce refined carbohydrate intake (e.g. white flour, white rice, sucrose, etc.) and increase the intake of whole grains as appropriate.

Avoid high-sugar diets such as beverages, candies, and snacks to avoid blood sugar fluctuations and increased inflammation.

Combined hyperlipidemia, cardiac insufficiency and other conditions

Refrain from eating high-calorie foods such as fried foods, fast foods, chocolates, and sweets.

Vegetable oil should be used for stir-frying, not exceeding the amount of two white porcelain spoons per day.

Do not eat high cholesterol food such as animal offal, crab roe, shrimp roe, fish roe, etc. Animal meat should be eaten without skin.

Long-term application of glucocorticoids

To avoid osteoporosis, calcium-rich foods such as milk (300 ml per day), tofu, shrimp skin, etc. are recommended, but should be avoided together with dark green vegetables.

Get plenty of sunshine and take vitamin D supplements under doctor’s supervision.

Exercise management

During the acute active phase of the disease, appropriate bed rest should be provided.

After the symptoms are basically controlled, you should get out of bed and move around as early as possible.

Train manual dexterity and coordination under doctor’s guidance, and strengthen the training of daily living activities to improve proficiency and skill.

Perform touching, stretching, kicking and other whole-body stretching exercises.

Exercise should be gradual and avoid strenuous exercise.

It is normal to feel pain for a short period of time during activities. If the pain persists for several hours after the activity, it means that the activity is too much and the amount of activity should be adjusted.

Psychological support

Face the disease with a positive and optimistic mindset and build up confidence in overcoming the disease.

Talk to your family and friends about your inner feelings.