Rheumatoid arthritis – a systemic disease of connective tissue, mainly affecting small joints of the type of erosive and destructive polyarthritis of unknown etiology with a complex autoimmune pathogenesis.
Causes of the disease on this day are unknown. Indirect data, such as increasing the number of white blood cell count and erythrocyte sedimentation rate (ESR) indicate the infectious nature of the process. It is believed that the disease develops as a result of infection, which causes a compromised immune system in genetically susceptible individuals, with formation of so-called. immune complexes (of the antibodies, viruses, etc..), which are deposited in tissues and lead to joint damage. But the ineffectiveness of antibiotic treatment of RA is likely to indicate the incorrectness of this assumption.
The disease is characterized by high disability (70%), which comes pretty early. The main causes of death from the disease are infectious complications and renal failure.
Treatment focuses primarily on relieving pain, slowing disease progression and restore damaged by surgery. Early detection of disease with the help of modern tools can significantly reduce the harm that can be inflicted joints and other tissues.
For the first time may occur after heavy physical exertion, emotional shock, fatigue, hormonal changes during the period, the impact of adverse factors or infection.
Rheumatoid arthritis is distributed worldwide and it affects all ethnic groups. Prevalence of 0,5-1% (up 5% in the elderly) ratio M: F = 1:3 peak of illness onset – 30-35 years
As with most autoimmune diseases, there are 3 main factors:
1. Hereditary susceptibility to autoimmunity.
2. Infection factor Hypothetical triggers of rheumatic diseases
Paramyxovirus – viruses, mumps, measles, respiratory syncytial infection
Hepatitis B virus
Herpes virus – herpes simplex viruses, herpes zoster, cytomegalovirus, Epstein-Barr virus (much higher in the synovial fluid of RA patients
Retroviruses – T-lymphotropic virus
3. Start-up factor (hypothermia, insolation, intoxication, mutagenic drugs, endocrinopathy, stress, etc.). For women, duration of breast-feeding reduces the risk of RA. Breastfeeding for 24 months or more reduces the risk of developing RA by half.
The course of disease
Rheumatoid arthritis progresses in three stages. In the first stage, the swelling of the synovial bags causing pain, heat and swelling around the joints. The second stage is the rapid cell division that leads to compaction of the synovial membrane. In the third stage, the inflamed cells release an enzyme that attacks the bones and cartilage, which often leads to deformation of the affected joints, increasing pain and loss of motor functions.
Typically, the disease progresses slowly at first, with the gradual deployment of clinical symptoms for several months or years, much less – subacute or acute. In about 2 / 3 of cases fever occurs, and the rest – a mono-or oligoarticular form, and articular syndrome often has no clinical specificity, which greatly complicates the differential diagnosis. Articular syndrome is characterized by morning stiffness for more than 30 minutes and similar expressions in the second half of the night – symptoms of “stiff gloves”, “corset”; ongoing spontaneous pain in the joints, increasing during active movements. The disappearance of the stiffness depends on the activity of the process: the more activity, the greater the duration of restraint. For the joint syndrome in rheumatoid arthritis is characterized by monotony, the duration, preservation of residual effects after treatment.
There may be prodromal clinical symptoms (mild transient pain, pain relationship with meteorological conditions, autonomic dysfunction). Distinguish “joint damage” and “joints exception.” Rheumatoid arthritis is often combined with other joint diseases – osteoarthritis, rheumatism, systemic connective tissue diseases.
Allocate the following options for the clinical course of rheumatoid arthritis:
The classic version of the (symmetric defeat both small and large joints
Mono-or oligoarthritis, mainly affecting the large joints, most often the knee. Severe disease onset and reversibility of all manifestations during 1-1,5 months (arthralgias are migratory in nature, radiographic changes are absent, anti-inflammatory drugs offer relatively positive effect in the latter there are all the symptoms of rheumatoid arthritis).
Diagnosis of rheumatoid arthritis (RA) – For a long time there was no specific test that would unambiguously confirm the presence of the disease. Currently, diagnosis of disease based on biochemical analysis of blood, changes in the joints are visible on x-rays, and the use of basic clinical markers, but also in conjunction with the general clinical manifestations – fever, malaise, and weight loss
In the analysis of blood examined ESR, rheumatoid factor, platelet count, etc. The most advanced analysis is the titer of antibodies to cyclic citrulline-containing peptides – ACCP, anti-CCP, anti-CCP. The specificity of this indicator is 90%, while it is present in 79% of sera from patients with RA.
Diagnostically important clinical features are the lack of discoloration of the skin over the inflamed joints, the development of tenosynovitis flexors or extensors of the fingers and the formation of amyotrophy, typical strains of brushes, so-called “rheumatoid wrist.
The criteria for poor prognosis are:
1. Early damage of large joints and the appearance of rheumatoid nodules
2. swollen lymph nodes
3. involvement of new joints in the subsequent exacerbation;
4. systemic disease;
5. persistent disease activity with no remission for over a year;
6. persistent increase in the ESR;
7. early appearance (within the first year) and high titers of rheumatoid factor
8. early (up to four months), radiographic changes in the affected joints – a rapid progression of destructive changes;
9. Detection of antinuclear antibodies and LE-cells
10. Carrier antigens HLA-DR4
Rheumatoid arthritis can begin at any joint, but most often starts from small joints in the fingers, hands and wrists. Typically, joint damage is symmetric, for example if the sore joint on his right hand, then ill be the same joint on the left. The more joints afflicted the more advanced stages of disease.
Other common symptoms include:
Morning stiffness. Generally, the longer the constraint, the disease activity.
Flu-like symptoms, including low heat.
Pain during prolonged sitting
Outbreaks of disease activity are accompanied by remission.
Loss of appetite, depression, weight loss, anemia, cold and / or sweaty palms and feet
Violation of glands near the eyes and mouth, causing insufficient production of tears and saliva.
In the presence of infection need the appropriate antibacterial therapy. In the absence of bright extra-articular manifestations (eg, high fevers, Felty’s syndrome or polynervopathy) treatment of joint syndrome begin with the selection of non-steroidal anti-inflammatory drugs (NSAIDs). At the same time in the most inflamed joints injected corticosteroids. An important point in the treatment of rheumatoid arthritis is the prevention of osteoporosis – restoration of the calcium balance in the direction of increasing its absorption in the intestine and reduced the excretion. Sources of calcium are dairy products (especially cheese, which contains from 600 to 1000 mg of calcium per 100 g of the product, as well as cheese, to a lesser degree of cottage cheese, milk, sour cream), almonds, hazelnuts and walnuts, etc., and calcium supplements in combination with vitamin D or its active metabolite.
Importance in the treatment is therapeutic exercise, aimed at maintaining maximum joint mobility and maintaining muscle mass.
Physiotherapy (electrophoresis of nonsteroidal anti-inflammatory drugs, hydrocortisone phonophoresis) and spa treatment. With persistent mono-and oligoarthritis includes introduction of isotopes of gold, yttrium, etc., With persistent strains of joints is carried out reconstructive surgery.
Systemic drug therapy involves the use of four classes of drugs:
1. nonsteroidal anti-inflammatory drugs (NSAIDs),
2. basic drugs
3. glucocorticosteroids (GCS)
4. biological agents.
Non-steroidal anti-inflammatory drugs
NSAIDs remain the first line of therapeutic agents that are directed primarily to the relief of acute manifestations of the disease, as well as ensuring stable clinical and laboratory remission.
In the acute phase of illness use of NSAIDs, corticosteroids, pulse therapy with corticosteroids or in combination with cytotoxic immunosuppressive agents.
Current NSAIDs have a marked anti-inflammatory effect which is caused by inhibition of the activity of cyclooxygenase (COX) – a key enzyme of arachidonic acid metabolism. Of particular interest is the discovery of two isoforms of COX, which are identified as COX-1 and COX-2 and play different roles in regulating the synthesis of prostaglandins (PG). Proved that NSAIDs inhibit the activity of COX isoforms, but their anti-inflammatory activity is due to inhibition of COX-2.
Most of the known NSAIDs inhibit primarily COX-1 activity, which explains the appearance of complications such as gastropathy, renal failure, encephalopathy, hepatotoxicity.
Thus, depending on the nature of blocking COX, NSAIDs are divided into selective and nonselective COX-2 inhibitors.
Representatives of the selective COX-2 inhibitors are meloxicam, nimesulide, celecoxib. These drugs have minimal side effects and retain high anti-inflammatory and analgesic activity. COX-2 inhibitors can be used in all programs of the treatment of rheumatoid arthritis, which require the use of NSAIDs. Meloxicam (Movalis) in the early treatment of inflammatory activity assigned to 15 mg / day and subsequently transferred to 7.5 mg / day as maintenance therapy. Nimesulide is assigned a dose of 100 mg twice a day.
Celecoxib (Celebrex) – a specific inhibitor of COX-2 – is assigned to 100-200 mg twice a day. Selection for the elderly dosage of the drug is not required. However, patients with body weight below the median (50 kg) it is desirable to begin treatment with the lowest recommended dose.
You should avoid combining two or more NSAIDs, because of their effectiveness remain unchanged, and the risk of side effects increases.
Basic drugs continue to play a pivotal role in the treatment of rheumatoid arthritis, but now there has been a new approach to their destination. In contrast to the well-known tactic of gradual treatment of rheumatoid arthritis (“principle of the pyramid”), is now advocated early aggressive treatment of basic drugs immediately after diagnosis, the purpose of which – changed the flow of rheumatoid arthritis and remission maintenance. The reason for this are the lack of early rheumatoid arthritis deformities, osteopenia, and severe complications, formed by autoimmune mechanisms, the high likelihood of remission.
The main drugs of basic therapy of rheumatoid arthritis include: methotrexate, sulfasalazine, gold preparations, D-penicillamine,. By means of the reserve include cyclophosphamide, azathioprine, cyclosporine A. The new group consisted of the following drugs: Remicade.
Ineffective for 1.5-3 months of basic drugs should be replaced or used in combination with corticosteroids in low doses, thus reducing the activity of rheumatoid arthritis before the start of the first. Six months – a critical period, no later than that should be adjusted effective basic therapy.
The best preparation for the start of basic therapy in severe rheumatoid arthritis and RF-positivity, presence of extraarticular manifestations of methotrexate is considered – cytotoxic immunosuppressive agent, which is well tolerated for prolonged use and has fewer side effects than other drugs of this group.
In the treatment of basic drugs carefully monitored the activity of the disease and side effects.
A new approach is the use of high doses of corticosteroids (pulse therapy) in combination with slow acting tools that can improve the efficiency of the latter; combinations of methotrexate with salts of gold, sulfasalazine, as well as a selective immunosuppressive agent cyclosporin A.
With a high degree of inflammatory activity are used corticosteroids, and in cases of systemic manifestations of rheumatoid arthritis a form of pulse therapy is used. Corticosteroids only or in combination with cytostatic drugs – cyclophosphamide. SCS is also used as supporting anti-inflammatory therapy after failure of other medicines.
In some cases, corticosteroids are used as local therapy. The indications for their use are: mostly mono-or oligoarthritis of large joints,
In rheumatoid arthritis the synovial membrane, for unclear reasons, secrete a large amount of the enzyme glucose-6-phosphate dehydrogenase that also destroys the disulfide bonds in the cell membrane. In this case, there is “leakage” of proteolytic enzymes from the cell lysosomes, which cause damage to surrounding bones and cartilage. The body responds to this by making cytokines, among which also has a tumor necrosis factor -the A TNF. Cascade of these reactions in cells are triggered by cytokines, further aggravating the symptoms of the disease. Chronic rheumatoid inflammation associated with TNF-α, often causing damage to the cartilage and joints, leading to physical disability.
The treatment uses a monoclonal antibody to the cytokine TNF-the A, which is effective with high affinity in binding to TNF, both in its soluble and transmembrane forms resulting in neutralizing activity of TNF.
During the progression of rheumatoid arthritis, Joint damage in patients with rheumatoid arthritis is observed as a narrowing of the joint space between bones and erosion of bone in the articular space. Clinical trials of monoclonal antibody showed its use as a slow erosion and narrowing of the space between the bones.