Pathology of rheumatoid arthritis

2021-01-26 12:00 AM

Standard of American Low School Association 1987: Including 7 points, in which standard from 1-4 must have time at least 6 weeks, positive diagnosis needs at least 4 criteria.



Rheumatoid arthritis (VKDT) is an autoimmune, chronic rheumatoid arthritis, mainly in women.


The most common disease among joint diseases. In Vietnam, the incidence rate is 0.5% among people and 20% of joint diseases are treated in hospitals. The disease is found everywhere in the world, accounting for 0.5% -3% of the population in adults.

70 - 80% are female and 60-70% are over 30 years old.

Some cases are of a family nature.

Causes and mechanisms


Is it an autoimmune disease involving many factors?

Pathogens: Could it be bacteria, viruses, allergens? but has not been verified with certainty.

Location: The disease is clearly related to gender and age.

Genetics: The disease is familial and 60-70% of patients carry HLA-DR4 (while in normal people it is 30%).

Favorable factors: after trauma, weak body, childbirth, prolonged cold, and humidity.

Mechanism of pathogenesis

Initially, the pathogen acts as an antigen, until now it is not known what antigens are, causing the expansion of the antigen-stimulated T-cell line in genetically susceptible organisms in the early stages of the disease. A subgroup of activated T cells in the synovial membrane produced various cytokines including Interferon γ (IFN-γ), interleukin 2 (IL2), IL6, and tumor necrosis factor (TNF -α), which the effect causing chronic inflammation of the synovial membrane, characteristic of VKDT. Additional stimulation of other cells in the synovial membrane (monocytes, B cells, fibroblast-like synovial cells), either by cytokines or in direct contact with activated T cells, leads to the second is more destructive. Activated mononuclear leukocytes and fibroblast-like synovial cells not only produce various, proinflammatory cytokines (especially IL. 1 and TNF-a) and growth factors can complicate inflammation but also stimulate the production of substrate metalloproteinases and other proteases. It is these agents that mediate the destruction of the substrate of the joint tissue characteristic of the destruction phase in VKDT.

Clinical symptoms


Onset: 85% gradual, progressive, 15% sudden with acute inflammatory markers; most of it is arthritis, which is one of the hand joints (wrists, fingers, fingers), knees. Lasts from a few weeks to a few months then moves into full play.

Full play: Polyarthritis.

Location: Early are the joints in the limbs, dominant at the base.

Upper limbs: Wrist, finger table, the nearest finger is finger 2 and 3.

Lower extremities: Pillows, ankles, toes, and toes.

Late are the joints: the elbows, shoulders, groin, neck vertebrae, temples, and brisket.

Characteristics: Tend to spread to the sides and symmetry:

Swelling, pain and limited mobility, less hot redness, possible water in the knee joint.

Pain increases at night near morning, morning stiffness.

The fingers are rhombohedral, especially the 2 and 3 fingers.

Characteristic joint deformations appear more slowly: wind hand blows, camel backhand.

Out of joint symptoms

Body as a whole: Mild fever, pale skin, poor appetite, thinness, and neurological disorders.

Paraplegic manifestations:

Subcutaneous seeds: Floating out of the skin surface, firm, painless d: 0.5-2 cm is common on the pillar near the elbow joint, on the tibia near the knee joint, the number is from one to a few seeds.

Dry atrophy, edema 1 limb, erythema palms.

Muscle atrophy: evident in the area around arthritis, tendinitis: often met Achille's tendons.

Very rare in clinical:

Heart: Discreet myocardial damage, possibly with pericarditis.

Lung: Mild pleurisy, alveolar fibrosis.

Spleen: enlarged spleen and leukopenia in Felty's syndrome

Bone: loss of lime, natural fracture.

There are also: keratitis, iritis, compression of the peripheral nerves, hypo chromatic anemia, neurophysics disorders, Amyloid infection mainly manifest in the kidney, usually appear very late.


Includes X-ray, biopsy, and biopsy

X-ray: In the first stage, there is a loss of lime in the bone head. Then there is a bone defect or erosive bone in the part adjacent to the joint cartilage, then the cleft joint. Finally, the destruction of joint cartilage and bone head causes joint adhesion and deformation.

Biology: Including inflammatory markers, immune disorders, joint fluid.

The rate of blood sedimentation increases, α2 globulin increases, red blood cells decrease.

Waaler Rose: Low serum factor detection. The reaction is positive when agglutination with patient serum dilution from 1/32.

Joint fluid: Reduce mucus, increase leukocytes, grape-shaped cells 10% of synovial fluid. Grape-shaped cells are polymorphonuclear leukocytes that have swallowed up immune complexes.

Biopsy: Synovial membrane or subcutaneous seed.

Biopsy of synovial membrane shows five lesions: the proliferation of hair-shaped membranes of the synovial membrane, the proliferation of coat-shaped coatings, the appearance of fibrotic necrotic clusters, neovascular proliferation, extensive penetration of inflammatory cells around the blood vessels. When there are three or more lesions it is possible to lead to a definitive diagnosis.

Subcutaneous granular biopsy: In the middle is a fibrotic necrosis cluster surrounded by many Lymphocytes and cytoplasm.


Definite diagnosis

It should be early for the treatment to work.

Standard of American Low School Association 1987: Including 7 points, in which standard from 1-4 must have time at least 6 weeks, positive diagnosis needs at least 4 standards, that is:

Morning stiffness: lasts at least 1 hour.

Painful swelling at least 3 joint groups out of 14 groups: proximal fingers, fingers, wrists, elbows, knees, ankles, toes (2 sides = 14).

Painful swelling in 1 of 3 joints of the hand: near finger, fingertip, wrist.

Swelling of symmetrical joints.

There are particles under the skin.

The reaction found a positive serum low factor (Waaler-Rose +).

Typical X-ray image.

The baseline lacks subclinical: diagnosis can be based on the following points:

Women 30-50 years old.

Inflammation of many joints far from the base of the limb.

Start slowly, progressing for at least 6 weeks.

Nocturnal pain and morning stiffness.

Differential diagnosis

The first stage (<6 weeks):

Rheumatoid arthritis: based on age, inflammatory properties ...

Reactive rheumatism: after infectious diseases, asymmetry.

Reiter's syndrome: Arthritis, urethritis, and eye conjunctiva.

The following period (> 6 weeks):

Arthritis: older, no signs of inflammation.

Arthralgia in colloid disease is lupus erythematosus.

Ankylosing spondylitis: men, spine pain, lumbar and pelvic pain.

Gout: uric acid increases in the blood.


Combining many measures: internal, external, physical, orthopedic.

Light form

The number of arthritic joints is small, the movement is almost normal (stage I)

Aspirin: 1-2g / day in divided doses.

Chloroquine: 0.2-0.4g / day, inhibiting the effect of digestive enzymes.

Traditional medicine:  sigesbeckia orientalist, leaf guise.

Exercise, physical therapy, electricity, ultrasound, mineral water ...

Medium form

Many joints are inflamed, with limited movement (stage II).

Like as light but requires:

Using one of the nonsteroid anti-inflammatory drugs: Indomethacin 50 - 100mg / day, Diclofenac: 100 - 150mg / day; Piroxicam 20mg / day.

Moderate doses of corticosteroids can be used.

Heavy form

Not being able to walk, have little or no movement (stage III).

High dose corticosteroids: Short-term, oral or IV.

Use one of the following therapies: Gold salt: total dose 1500-2000mg; D- Penicillamine: 300mg / day; Methotrexate: 7.5-10mg / week; Cyclophosphamide: 1- 2mg / kg / day. Other measures as above.

New treatment

The following new drugs introduced to treat VKDT can be classified into 3 types:

Cyclooxygenase type 2 inhibitors (Cox 2).

Biological agents.

Anti-rheumatic drugs that change disease progress (DMARD: Disease Modifying Anti - Rheumatic Drugs).

Cox 2 inhibitors:

At least two isoforms of cyclooxygenase (Cox) have been identified recently: Cox - 1 is an ontological enzyme, present in many tissues and is mainly involved in the production of prostaglandins needed for the normal homeostasis process. In contrast, cox -2 is an inductive enzyme found in healthy tissues at low concentrations, but is markedly increased in inflamed tissues and is involved in PGE2 biosynthesis at the site of inflammation. Because nonsteroidal anti-inflammatory drugs (AINS) normally suppress inflammation, they have many side effects. Therefore, the new AINS drugs that are either preferentially or selectively inhibited on cox-2 have anti-inflammatory effects and very few side effects, which is the advantage of the new drugs.

MELOXICAM (Mobic): 7.5mg and 15mg inflammation, 15mg tube. Daily dose: 15 mg/day, once a day.

CELECOXIB (CELEBREX) inflammation 100mg and 200mg. Daily dose: 100mg x 2 times / day.

Side effects of the above drugs include the general side effects of AINS, but their rates and severity are much lower than those of classic AINS.

In general, AINS do not delay joint destruction progression in VKDT.

Biological agents:

Attention is focused on anti-TNF agents - α, inflammatory 1cytokine, mainly released by synovial membrane macrophages, acting as a very important molecule that commands other types of cells in Synovial membrane releases pro-inflammatory molecules and destroys joints. Two such substances have been recognized for the treatment of VKDT.

ETANERCEPT: A dimer consisting of the extracellular part of two soluble TNF receptors (75kDa) fused with the Fc part on human immune -globulin G1 (IgG1). Etanercept specifically binds to 2 cyclic TNF-α or TNF- molecules, thus blocking their interaction with the TNF receptor on the cell surface.

Indications: Moderate to severe VKDT in patients who do not respond adequately to 1 or more DMARD.

Dosage and administration: 25mg subcutaneously x 2 times/week for several months.

Side effects: Mild reactions at the injection site.

INFLIXIMAB: A monoclonal antibody composed of (the constant region of human antibodies and the mouse changing regions, administered by the intravascular route and specifically binding the soluble and transmembrane TNF-A) .

Designation: VKDT works.

Dosage and administration: 10 mg/kg IV dose, or split IV 2 times a week.

Side effects: Pneumonia when taking low doses. The inconvenience of using the two drugs above, namely subcutaneous injection and IV infusion, can limit adherence to treatment.

New DMARD drug:

LEFLUNOMIDE: A derivative of isoxazole, is the newest DMARD recognized for treating VKDT. During the onset of disease, activated, rapidly proliferating CD4 T cells of leflunomide inhibit such proliferation by preventing T cells from producing the pyrimidines necessary for new DNA synthesis before cell division.

Presentation: 100mg inflammation and 20 mg tablets.

Dosage and administration: first 3 days: 100mg / day.

From day 4 onwards: 10 - 20mg / day.

Side effects: Gastrointestinal symptoms, skin rash, and hair loss, reversible when stopping the drug.

The full clinical benefit of leflunomide, when used alone to treat VKDT, is evident only after annual use.

How to use DMARD effectively:

In the traditional pyramid approach, DMARD is started relatively late in the course of the disease and then is not used consistently. The current treatment model uses the serrated method: Accordingly, the DMARD is used early after the onset of VKDT and continued throughout the course of the disease with the aim of keeping the patient's loss of health close to the average level. often. When the effects of DMARD are reduced, the regimen is changed by adding a new drug to the current regimen or by changing the drug. The aim of the serrated method is to achieve a fundamental improvement in long-term outcomes for patients with rheumatoid arthritis.