What Is Infliximab?

Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology, mainly inflammatory synovitis. It is characterized by multiple joints, symmetry, and invasive arthritis of the small joints of the hands and feet, often accompanied by involvement of extra-articular organs and positive serum rheumatoid factor, which can lead to joint deformities and loss of function.

Basic Information

English name
rheumatoid arthritis, RA
Visiting department
Division of Rheumatology
Multiple groups
40 to 60 year old women
Common locations
Hands, feet
Common causes
May be related to heredity, infection, sex hormones, etc.
Common symptoms
Morning stiffness, arthritis of the hands, feet, wrists, ankles, temporomandibular joints, joint deformities
Contagious
no

Causes of rheumatoid arthritis

The onset of RA may be related to heredity, infection, and sex hormones. The pathologies of RA arthritis include synovial lining cell proliferation, interstitial inflammatory cell infiltration, and the formation of microvessels, the formation of vascular crests and the destruction of cartilage and bone tissue.

Clinical manifestations of rheumatoid arthritis

1. crowds
It is common in women, and the incidence is 2 to 3 times that of men. Can occur at any age, with a high incidence of 40 to 60 years.
2. Symptoms and signs
May be accompanied by systemic symptoms such as weight loss, low fever and fatigue.
(1) Morning stiffness When you wake up in the morning, the subjective feeling of inflexible joint movements is a non-specific manifestation of arthritis, and its duration is directly proportional to the severity of inflammation.
(2) manifestations of joint involvement polyarticular involvement is symmetrical polyarthritis (often 5 joints). The susceptible joints include hands, feet, wrists, ankles, and temporomandibular joints. Others include elbows, shoulders, cervical spine, hips, and knee joints. Joint malformations The deformities of the hand include fusiform swelling, ulnar deflection, swan neck deformity, button deformity, etc. The deformities of the foot include the toe deformity caused by the subluxation of the metatarsal head, the valgus deformity, the subluxation of the metatarsophalangeal joint, the curved toe and the deformity of the foot. Other carpal tunnel and sacral duct syndromes may be caused by compression of the median nerve and posterior tibial nerve. The knee joint effusion squeezes into the back of the joint to form a popliteal cyst (Baker cyst), and the cervical spine is affected (the second and third cervical spine are mostly See) There may be neck pain, neck weakness and difficulty in maintaining its normal position, atlantoaxial subluxation, and corresponding symptoms of spinal cord compression and insufficient blood supply to the vertebrobasilar artery.
(3) Extra-articular manifestations General manifestations may include fever and rheumatoid nodules (belonging to mechanized granulomas, which are related to high titer RF, severe joint destruction and RA activities, and are common in elbow and joint olecranon processes Bulges of the joints such as the iliac crests and the place where they are often under pressure), rheumatoid vasculitis (necrotizing arteritis mainly involving small arteries, which can be manifested as finger, toe necrosis, skin ulcers, peripheral neuropathy, etc.) and lymph nodes Swelling. Heart involvement may be manifested by pericarditis, pericardial effusion, epicardium, nodules of myocardium and valves, myocarditis, coronary arteritis, aortic inflammation, conduction disorders, chronic endocarditis, and heart valve fibrosis. Respiratory system involvement may include pleurisy, pleural effusion, pulmonary arteritis, interstitial lung disease, and nodular lung disease. Renal manifestations include primary glomeruli and tubulointerstitial nephritis, renal amyloidosis, and renal damage secondary to drug therapy (gold preparations, penicillamine, and NSAIDs). In addition to the symptoms of peripheral nerve compression, the nervous system can also induce neurological diseases, myelopathy, peripheral neuropathy, ischemic neuropathy secondary to vasculitis, muscle hypertrophy and neurological diseases caused by drugs. Anemia is the most common extra-articular manifestation of RA. It belongs to chronic disease anemia, which is usually mild to moderate. Digestive system can be caused by RA vasculitis, complications or medication. Young people with squint eyes may have uveitis, and scleritis in adults may be caused by vasculitis. There may also be dry conjunctival keratitis, scleral softening, scleral softening and perforation, and corneal dissolution.
(4) 1% of patients with RA with Felty syndrome may have splenomegaly, neutropenia (and thrombocytopenia, and decrease in red blood cell count), often with severe joint disease, high titer of RF and ANA, belonging to a type Severe RA.
(5) Relief sero-negative, symmetrical synovitis with depression edema syndrome (RS3PE) is more common in men. It usually develops after 55 years of age and is acute. There are symmetrical wrist joints, flexor tendon sheaths, and hand facets. Inflammation of the back of the hand may have sunken edema. Morning stiffness is long (0.5 to 1 day), but RF is negative, and most of the X-rays have no bone damage. HLA-B7 was positive in 56% of patients. The response to NSAIDs alone is poor in treatment, and the effect of low-dose glucocorticoid is significant. It usually resolves spontaneously after 1 year, and the prognosis is good.
(6) Adult Still's disease (AOSD) is a rare type of RA that alternates with acute attacks and remissions of fever, arthritis, and rash. Named for clinical manifestations similar to systemic onset juvenile rheumatoid arthritis (Still's disease). Some patients turned into typical RA after several episodes.
(7) RA at the age of onset is usually> 65 years old, with small gender differences, mostly acute onset, and develops rapidly (partially with OA as the initial manifestation, and typical RA manifestations after a few years). Hand, foot edema, carpal tunnel and sacral tunnel syndrome, and polymyalgia are prominent manifestations. Morning stiffness is obvious, 60% to 70% RF positive, but the titer is mostly low. X-rays are predominantly osteoporotic and rarely invasive. Patients often die from complications such as cardiovascular, infection, and impaired renal function. NSAIDs should be selected with caution, and low-dose hormones can be used, which respond well to slow-acting antirheumatic drugs (SAARD).

Rheumatoid arthritis examination

Laboratory inspection
(1) Blood, urine routine, ESR, C-reactive protein, biochemistry (liver and kidney function), immunoglobulin, protein electrophoresis, complement, etc.
(2) Autoantibodies The detection of autoantibodies in RA patients is one of the signs that RA is different from other inflammatory arthritis, such as psoriatic arthritis, reactive arthritis and osteoarthritis. At present, autoantibodies commonly used in clinical practice include rheumatoid factor (RF-IgM), anti-cyclic citrulline (CCP) antibodies, rheumatoid factor IgG and IgA, anti-perinuclear factors, anti-keratin antibodies, and anti-nuclear antibodies, anti- ENA antibodies. In addition, it also includes anti-RA33 antibody, anti-glucose-6-phosphate isomerase (GPI) antibody, anti-P68 antibody and so on.
(3) Genetic markers HLA-DR4 and HLA-DR1 subtypes.
2: Imaging examination
(1) X-ray film X-ray film shows swelling of the soft tissue, osteoporosis, and cystic changes in the articular surface, invasive bone destruction, articular surface blur, joint space narrowing, joint fusion, and dislocation. X-ray staging: Stage normal or osteoporosis; Stage osteoporosis, with mild invasion or destruction of the subarticular bone, and mildly narrow joint space; Stage obvious bone invasion and destruction, The gap was significantly narrowed and the joint was subluxated. The above-mentioned changes in stage were associated with joint fibrous or bony rigidity. Interstitial lung lesions and pleural effusions can be seen on chest X-rays.
(2) CT examination of chest CT can further suggest lung lesions, especially high-resolution CT is sensitive to changes in pulmonary interstitial disease.
(3) MRI examinations MRI examinations of the hand and wrist joints can indicate early synovitis lesions, which is very helpful for finding early joint destruction in patients with rheumatoid arthritis.
(4) Ultrasound joint ultrasound is a simple non-invasive examination, which is of differentiating significance for synovitis, joint effusion, and joint destruction. It is considered that it has good consistency with MRI.
3. Special inspection
(1) Arthrocentesis For joints with joint cavity fluid, joint fluid examination includes: joint fluid culture, rheumatoid factor detection, anti-CCP antibody detection, anti-nuclear antibody, etc., and polarized light detection to identify gout's uric acid Salt crystals.
(2) Arthroscopy and joint synovial biopsy are of great value in the diagnosis and differential diagnosis of RA, and have an adjuvant treatment effect on single joint refractory RA.

Rheumatoid arthritis diagnosis

Diagnosis criteria, staging, function, and activity of RA:
1. Diagnostic criteria of RA
(1) The RA classification criteria revised by the American College of Rheumatology in 1987 are as follows: 4 and exclude other arthritis can confirm the diagnosis of RA. Morning stiffness for at least 1 hour (6 weeks). 3 or more joints are involved (6 weeks). Hand joints (wrist, MCP or PIP joints) are involved (6 weeks). symmetrical arthritis (6 weeks). There are rheumatoid subcutaneous nodules. X-ray film changes. Serum rheumatoid factor is positive.
(2) ACR / EULAR's new classification criteria for RA in 2010 can be diagnosed with a total score of 6 or more.
Joint involvement
Score
(0-5 points)
Serology (requires at least 1)
Score
(0-3 points)
1 large joint
0
RF and ACPA are negative
0
2 to 10 large joints
1
RF and / or ACPA low titer positive
2
1 to 3 small joints (with or without large joint involvement)
2
RF and / or ACPA high titer (more than 3 times the normal value) positive
3
4 to 10 small joints (with or without large joint involvement)
3
> 10 joints (at least one facet joint is involved) ZA
5
Acute Phase Reactant (requires at least 1)
Score
(0-1 points)
Duration of symptoms
Score
(0-1 points)
CRP and ESR are normal
0
<6 weeks
0
Increased CRP or ESR
1
6 weeks
1
(3) Early 2012 RA (ERA) classification and diagnostic criteria
Early 2012 RA (ERA) classification diagnostic criteria:
1) Morning stiffness 30 minutes;
2) Arthritis in more than 3 joint areas;
3) hand arthritis;
4) rheumatoid factor (RF) positive;
5) Anti-CCP antibody is positive.
14 joint areas include: bilateral elbow, wrist, metacarpophalangeal, proximal interphalangeal, knee, ankle and metatarsophalangeal joint
3 can diagnose RA. The sensitivity was 84.4% and the specificity was 90.6%.
2. Stages of illness
Early synovitis without cartilage damage. The middle stage is between upper and lower (with inflammation, joint damage, extra-articular manifestations). The joint structure was damaged in the late stage, and there was no progressive synovitis.
3. Joint function classification
The functional status of class is intact, and it can be used to complete normal tasks without hindrance (free movement). Grade can engage in normal activities, but one or more joints have limited or uncomfortable movements (moderately restricted). Grade III can only be competent for general professional tasks or part of self-care (significantly restricted). Grade IV is mostly or completely incapacitated, needs to stay in bed for a long time or depends on a wheelchair, and rarely or cannot take care of themselves (bed or wheelchair).
4.RA Condition Assessment
The assessment of RA condition needs to be combined with clinical and auxiliary examinations. The items to judge the activity of rheumatoid arthritis include the severity of fatigue, the duration of morning stiffness, the degree of joint pain and swelling, the number of joint tenderness and swelling, and the degree of joint function limitation , And indicators of acute inflammation (such as ESR, C-reactive protein, and platelets).

Differential diagnosis of rheumatoid arthritis

Osteoarthritis
More common in middle-aged and elderly people, the onset process is mostly slow. Hands, knees, hips, and spine joints are susceptible, while the metacarpophalangeal, wrist, and other joints are less affected. The condition usually worsens with activity or decreases with rest. Morning stiffness is less than half an hour. Heberden and Bouchard nodules can be seen on the hands when the hands are involved, and the knee joint can touch the friction. There are no extra-articular manifestations such as subcutaneous nodules and vasculitis. Rheumatoid factor is mostly negative, and a few elderly patients may have a low titer.
2. Psoriatic arthritis
The polyarthritis type of rheumatoid arthritis is similar to that of rheumatoid arthritis. However, patients with this disease have characteristic psoriasis or nail lesions, or have a family history of psoriasis. The distal interphalangeal joints are often involved, and most of them are distributed asymmetrically in the early stage. Antibodies such as serum rheumatoid factor are negative.
3. Ankylosing spondylitis
The disease is more common in young men, mainly involving central axis joints such as sacroiliac and spinal joints. Although there are peripheral joint lesions, they are mostly large joints of the lower extremities, asymmetric swelling and pain, and often accompanied by spinous processes. , Great trochanter, Achilles tendon, spinal costal joints and other tendons and ligaments attachment points pain. Extra-articular manifestations are mostly iridocyclitis, cardiac blockade, and aortic valve insufficiency. X-ray films showed sacroiliac joint invasion, destruction, or fusion. Patients were negative for rheumatoid factor and mostly positive for HLA-B27 antigen. The disease has a more pronounced family tendency.
4. Systemic lupus erythematosus
Patients with this disease may have arthritis manifestations of the hands or wrists early in the course of the disease, but patients are often accompanied by lupus-specific, multisystemic manifestations such as fever, fatigue, oral ulcers, rashes, decreased blood cells, proteinuria, or antinuclear antibodies, Arthritis is milder than rheumatoid arthritis patients, and joint deformities do not appear. Laboratory tests can reveal a variety of autoantibodies.
5. Reactive arthritis
The onset of this disease is acute, and there is often a history of intestinal or urinary tract infections before onset. The major joints (especially the lower extremity joints) are mainly affected by asymmetry, and generally there is no symmetry involving the proximal interphalangeal joints of the fingers, small joints such as the wrist joint. May be associated with ophthalmitis, urethritis, balanitis, and fever, etc. HLA-B27 can be positive and rheumatoid factor negative, and patients can have X-ray changes in asymmetric sacroiliitis.

Rheumatoid arthritis treatment

The main purpose of rheumatoid arthritis treatment is to reduce the response of arthritis, inhibit the development of lesions and irreversible bone destruction, protect the function of joints and muscles as much as possible, and finally reach the goal of complete remission or reduction of disease activity.
Treatment principles include patient education, early treatment, combined medication, individualized treatment options, and functional exercise.
Patient education
To enable patients to correctly understand the disease, build confidence and patience, and be able to cooperate with doctors for treatment.
2. General treatment
Those with obvious joint swelling and pain should emphasize rest and joint braking, and after the joint swelling and pain are relieved, attention should be paid to the early start of joint functional exercise stiffness. In addition, adjuvant treatments such as physical therapy and topical medication can quickly relieve joint symptoms.
3. Drug treatment
The plan should be individualized, and the drug treatment mainly includes non-steroidal anti-inflammatory drugs, slow-acting anti-rheumatic drugs, immunosuppressive agents, immune and biological agents, and botanical drugs.
(1) Non-steroidal anti-inflammatory drugs have anti-inflammatory, analgesic, and antipyretic effects. They are the most commonly used drugs in the treatment of rheumatoid arthritis and are suitable for patients at various stages such as the active phase. Commonly used drugs include diclofenac, nabumetone, meloxicam, celecoxib, and the like.
(2) Anti-rheumatic drugs (DMARDs) are also called second-line drugs or slow-acting anti-rheumatic drugs. Commonly used are methotrexate, orally or intravenously; sulfasalazine, starting from small doses, and gradually increasing, as well as hydroxychloroquine, leflunomide, cyclosporine, auranofin, and total glucosides of paeony.
(3) Yunke is [99Tc] methylene diphosphate injection, which is a non-excited isotope. It is effective in treating rheumatoid arthritis and has less adverse effects. Intravenous medication, a course of 10 days.
(4) Glucocorticoids are not the drug of choice for the treatment of rheumatoid arthritis. However, hormones can be used in the following four cases: Accompanying rheumatoid vasculitis includes multiple mononeuritis, rheumatoid lung and serositis, and iritis. Transition therapy In patients with severe rheumatoid arthritis, a small amount of hormones can be used to quickly alleviate the condition. Once the condition is controlled, the hormone should be reduced or stopped slowly. Patients who fail to respond to regular slow-acting antirheumatic drugs can add low-dose hormones. Local application such as intra-articular injection can effectively relieve joint inflammation. The general principle is short-term low-dose (less than 10 mg / d) application.
(5) At present, several biological agents have been approved for the treatment of rheumatoid arthritis in the treatment of rheumatoid arthritis, and have achieved certain effects, especially playing an important role in the treatment of refractory rheumatoid arthritis. Application of several biological agents in rheumatoid arthritis: Infliximab ( Infliximab ) is also called TNF- chimeric monoclonal antibody, and clinical trials have proven to be ineffective for methotrexate and other treatments in rheumatoid arthritis Patients using Infliximab can achieve satisfactory results. In recent years, it has been emphasized that the effect of early application is better. Usage: Intravenous, 3mg / kg, injected once every 0, 2, and 6 weeks, and then injected every 8 weeks, usually 3 to 6 times as a course of treatment. Need to be combined with MTX to inhibit the production of anti-antibodies. Etanercept (Etanercept) or human recombinant TNF receptor p75 and IgGFc segment fusion protein, Etanercept and human recombinant TNF receptor p75 and IgGFc segment fusion protein are effective in treating rheumatoid arthritis and AS, and are well tolerated. At present, there are two commercial dosage forms of Enli and Yisaipu in China. adalimumab (adalimumab) is a fully humanized monoclonal antibody against TNF-. The recommended therapeutic dose is 40 mg, once every 2 weeks, subcutaneously. Tocilizumab ( touzumab ), an IL-6 receptor antagonist, is mainly used for moderate to severe RA, and may be effective in patients with poor response to TNF- antagonists. The recommended usage is 4 to 10 mg / kg, intravenous infusion, once every 4 weeks. The anti-CD20 monoclonal antibody Rituximab (Rituximab) has achieved satisfactory results in the treatment of rheumatoid arthritis. Rituximab can also be used in combination with cyclophosphamide or methotrexate.
(6) Botanical medicines At present, there are many kinds of botanical medicines for rheumatoid arthritis, such as tripterygium wilfordii, total glucosides of paeony, and Sinomenine. Some drugs have a certain effect on the treatment of rheumatoid arthritis, but the mechanism of action needs further research.
4. Immune purification
Patients with rheumatoid arthritis often have high titers of autoantibodies, a large number of circulating immune complexes, and high immunoglobulins. Therefore, in addition to drug treatment, immunopurification therapy can be selected, which can quickly remove immune complexes and plasma High immunoglobulin, autoantibodies, etc. If there are too many immune-active lymphocytes, mononuclear cell removal therapy can also be used to improve the function of T, B cells and macrophages and natural killer cells, reduce blood viscosity, and achieve the purpose of improving symptoms while improving drug treatment. Efficacy. Immunopurification therapies currently in use include plasma exchange, immunoadsorption and lymphocyte / monocyte removal. The replaced pathological components may be lymphocytes, granulocytes, immunoglobulins, or plasma. The application of this method requires drug treatment.
5. Functional exercise
It must be emphasized that functional exercise is an important method for the recovery and maintenance of joint function in patients with rheumatoid arthritis. In general, joint activity should be appropriately restricted in the acute phase where joint swelling and pain are obvious. However, once the swelling and pain have improved, functional activities should be performed without increasing the patient's pain. For those who have no obvious joint swelling and pain, but with reversible joint movement limitation, they should be encouraged to perform regular functional exercises. In conditional hospitals, it should be conducted under the guidance of a rheumatologist and a rehabilitation specialist.
6. Surgical treatment
Surgery is an effective treatment for patients with rheumatoid arthritis who cannot be controlled and has severe joint dysfunction after medical treatment. Surgical treatments range from carpal tunnel syndrome release, tendon repair, synovectomy and joint replacement.

Prognosis of rheumatoid arthritis

In the past ten years, with the early combined application of slow-acting antirheumatic drugs, the treatment of extra-articular lesions and the continuous emergence of new therapies have significantly improved the prognosis of rheumatoid arthritis. The condition of most patients with rheumatoid arthritis can be well controlled or even completely relieved. The study found that the prognosis of rheumatoid arthritis can be roughly judged according to the clinical characteristics of the first year of onset of rheumatoid arthritis, and certain clinical and laboratory indicators are of great significance for disease estimation and guidance of medication. In addition, the education level of patients is also related to prognosis. Factors suggesting the severity and prognosis of rheumatoid arthritis include persistent joint swelling, high titer antibodies, HLA-DR4 / DR1 positive, associated with anemia, rheumatoid nodules, vasculitis, neuropathy, or other joints Outsider.
Rheumatoid arthritis may be life-threatening in patients with advanced, severe, or long-term bed rest due to co-infection, gastrointestinal bleeding, and heart, lung, or kidney disease.

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