Rheumatoid arthritis - a systemic connective tissue disease that primarily affects the small joints of the type of erosive and destructive polyarthritis of unknown etiology with a complex autoimmune pathogenesis .
The causes of the disease are unknown today. Indirect data, such as the increase in the number of counts of white blood cells and the erythrocyte sedimentation rate ( ESR) indicate the nature of the infectious process . It is believed that the disease develops following infection , which causes weakening of the immune system in genetically predisposed individuals , with the formation of the call. Immune complexes (antibodies , viruses, etc. . ) Who are deposited in tissues and cause joint damage. But the lack of effectiveness of antibiotic treatment of RA may indicate the inaccuracy of this assumption.
The disease is characterized by severe disability (70%) , which is coming very soon. The main causes of death from the disease are infectious complications and renal failure .
The treatment is primarily focused on relieving pain, slow disease progression and restore damaged by surgery . Early detection of disease using modern tools can significantly reduce the damage that can cause the joints and other tissues.
For the first time may occur after an emotional physical effort , shock, fatigue , hormonal changes during the period, the impact of adverse factors or infection.
epidemiology
Rheumatoid arthritis is distributed worldwide and affects all ethnic groups. Prevalence of 0.5-1% (up 5% in the elderly ) ratio M : F = 1:03 peak onset - 30-35 years
etiology
As with most autoimmune diseases , there are three main factors :
A . Hereditary susceptibility to autoimmunity .
Two . Hypothetical triggers infection rheumatic diseases
Paramyxovirus - viruses, mumps , measles, respiratory syncytial infection
Hepatitis B
herpes virus - the virus herpes simplex , herpes zoster , cytomegalovirus, Epstein - Barr virus ( much higher in the synovial fluid of RA patients
Retrovirus - T lymphotropic Virus
Factor 3 . Commissioning ( hypothermia , heat stroke , poisoning, mutagenic drugs, endocrine disorders , stress, etc. . ) For women, the duration of breastfeeding reduces the risk of AR . Breastfeeding for 24 months or more reduced the risk of developing RA .
The course of the disease ,
Rheumatoid arthritis progresses through three stages . In the first stage , the inflammation of the bursa causing pain , heat and swelling of the joints. The second stage is the rapid cell division leading to a compaction of the synovial membrane . In the third stage , the inflamed cells release an enzyme which attacks the bone and cartilage often leads to deformity of the joints , the increase in pain and loss of motor function .
In general, 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 two thirds of cases of fever occurs, and the rest - a mono-or oligoarticular form articular syndrome often lack clinical specificity , which greatly complicates the differential diagnosis. Articular syndrome is characterized by morning stiffness of more than 30 minutes and similar expressions in the second half of the night - symptoms of " stiff gloves ", " corset " spontaneous ongoing pain in the joints , which increases during active movements . The loss of the stiffness depends on the activity of the method : the increase in activity , over the duration of the restriction . For the joint syndrome in rheumatoid arthritis is characterized by monotony, duration, preservation of residual effects after treatment.
There may be clinical prodromal symptoms (moderate and transient pain, pain relationship with meteorological conditions, autonomic dysfunction ) . Distinguish " joint damage " and "joints exception. " Rheumatoid arthritis is often associated with other common diseases - osteoarthritis , rheumatism , diseases of connective tissue.
Assign the following to the clinical course of rheumatoid arthritis:
The classic version of defeat (small and large joints symmetrically
Mono-or oligoarthritis , mainly affecting the large joints , usually the knee. Onset of serious illness 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 on it are all symptoms rheumatoid arthritis ) .
diagnosis
The diagnosis of rheumatoid arthritis (RA ) - For a long time there was no specific evidence to confirm unambiguously 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 clinical markers base , but also as regards the general clinical manifestations - fever , malaise and weight loss
Considered in the analysis of ESR , rheumatoid factor blood platelet count , etc. The most advanced analysis is the titer of anti - citrulline -containing peptides - Cyclic - ACCP , anti -CCP , anti -CCP . The specificity of this indicator is 90 %, whereas it is present in 79 % of sera from patients with RA.
Clinical features for diagnosis are important no discoloration of the skin over the inflamed joints , the development of flexor or extensor tenosynovitis of the fingers and the formation of a muscular , typical strains of brushes, the " wrist arthritis.
The criteria for poor prognosis are :
A . Damage at the beginning of large joints and the appearance of rheumatoid nodules
Two . Swollen lymph nodes
3 new joint participation in the subsequent exacerbation. ;
4 systemic disease. ;
. Five activity of persistent disease without remission for over a year;
. June persistent increase ESR ;
7 . Early onset ( first year) and high titers of rheumatoid factor
8 early (up to four months), radiographic changes of the affected joints - a rapid increase in destructive changes . ;
9. Detection of antinuclear antibodies and LE- cells
10. Carrier HLA -DR4
symptoms
Rheumatoid arthritis can start in any joint , but most commonly begins in the small joints of the fingers , hands and wrists. Usually , the articular damage is symmetric , for example , swollen joint in his right hand , and the patient is left joint itself . Most joints suffer the most advanced stages of the disease .
Other common symptoms include:
fatigue
Morning stiffness . Generally, the higher the stress , the disease activity .
weakness
flu-like symptoms , including a low heat.
Pain during prolonged sitting
Outbreaks of disease activity are accompanied by reference.
muscle aches
Loss of appetite , depression, weight loss, anemia , cold palms and / or sweaty feet
Violation of glands near the eyes and mouth , causing insufficient production of tears and saliva.
treatment
In the presence of infection need appropriate antibacterial therapy . In the absence of strong extra -articular manifestations (eg , high fever , or Felty's syndrome polynervopathy ) joint syndrome treatment begins with the selection of non-steroidal anti -inflammatory drugs ( NSAIDs). At the same time , more inflamed joints injected corticosteroids. A major problem in the treatment of rheumatoid arthritis is the prevention of osteoporosis item - restoring calcium balance in the direction of increase of the absorption in the gut and reduce shedding . Sources of calcium include dairy products ( in particular cheese , which contains 600 to 1000 mg of calcium per 100 g product , and cheese, to a lesser extent of cottage cheese , milk , cream ) , almonds, hazelnuts and walnuts, etc. , and calcium supplements in combination with vitamin D or its active metabolite.
Importance in the treatment is a therapeutic exercise , for maintaining maximum joint mobility and maintaining muscle mass .
Physiotherapy (electrophoresis nonsteroidal anti- inflammatory drugs , hydrocortisone phonophoresis) and spa treatments . With persistent mono-and oligoarthritis includes introduction of isotopes of gold, yttrium , etc. , with persistent strains of joints is performed reconstructive surgery.
modern therapy
Systemic drug therapy involves the use of four types of drugs :
A . Nonsteroidal anti- inflammatory drugs ( NSAIDs) ,
Two . Basic medicines
Three . Glucocorticosteroids (GCS)
April. Biological agents.
NSAIDs
NSAIDs remain the first line of therapeutic agents that are primarily directed towards the relief of acute manifestations of the disease and to ensure a stable clinical remission and laboratory.
In the acute phase of the disease from the use of NSAIDs , corticosteroids, pulse therapy with corticosteroids in combination with cytotoxic or immunosuppressive agents .
Common NSAIDs have marked anti- inflammatory effect which is caused by the inhibition of the activity of cyclooxygenase ( COX) - a key enzyme in the metabolism of arachidonic acid . Of particular interest is the discovery of two isoforms of COX, which is identified as COX - 1 and COX - 2 and play different roles in regulating the synthesis of prostaglandins (PG) . Shown that NSAIDs inhibit the activity of the isoforms of COX, but their anti - inflammatory activity is due to inhibition of COX - 2 .
Most NSAIDs inhibit primarily known activity COX-1 , which explains the occurrence of complications such as gastropathy , renal failure , encephalopathy , hepatotoxicity .
Therefore , depending on the nature of the inhibition of COX , NSAIDs are divided into non- selective and selective COX - 2 .
Representatives of selective COX - 2 are meloxicam , nimesulide , celecoxib . These drugs have minimal side effects and retain high anti - inflammatory and analgesic . COX - 2 may be used in all programs of treatment of rheumatoid arthritis, which require the use of NSAIDs. Meloxicam (Mobic) in the early treatment of inflammatory activity assigned to 15 mg / day and then transferred to 7.5 mg / day maintenance therapy. Nimesulide is given at a dose of 100 mg twice daily .
Celecoxib ( Celebrex ) - a specific inhibitor of COX - 2 - assigned to 100-200 mg twice daily . No selection for the elderly dosage of the drug is required. However, patients with a lower median weight (50 kg) is desirable to start treatment with the lowest recommended dose.
You should avoid the combination of two or more NSAIDs, remain unchanged for its effectiveness , and the risk of adverse effects increases .
Basic preparations
Essential medicines continue to play a key role in the treatment of rheumatoid arthritis, but now there was a new approach to your destination. Unlike the well-known treatment of progressive rheumatoid arthritis (" Pyramid Principle " ) tactic , which is now advocated early aggressive treatment of basic drugs immediately after diagnosis , the purpose of which - has changed the flow rheumatoid arthritis and maintaining remission . the reason for this lack of deformation of the early rheumatoid arthritis, osteopenia , and serious complications , formed by autoimmune mechanisms , the likelihood of remission .
The main drug -based therapy of rheumatoid arthritis include methotrexate , sulfasalazine , gold preparations , D- penicillamine . Thanks to the reserve include cyclophosphamide, azathioprine , cyclosporine A. The new group consisted of the following medications: Remicade.
1.5 to 3 months inefficiency basic drugs , should be replaced or used in combination with low dose corticosteroids , which reduces the activity of rheumatoid arthritis , before the start of the first . Six months - a critical period , by adjusting the basic therapy effective.
The best preparation for the start of the basic therapy in severe rheumatoid arthritis and RF- positivity, the presence of extra -articular manifestations of methotrexate is considered - cytotoxic immunosuppressive agent that is well tolerated for prolonged use and has fewer side effects side than the other drugs in this group.
In the treatment of basic drugs carefully monitor the activities of the effects of the disease and side.
corticosteroids
A new approach is the use of high doses of corticosteroids ( pulse therapy ) in combination with slow-acting tools that can enhance the effectiveness thereof ; combinations of methotrexate with gold salts, sulfasalazine , and selective immunosuppressive agent cyclosporin A.
With a high degree of inflammatory activity of corticosteroids are used, and if systemic manifestations of RA a form of pulse therapy is used. Cyclophosphamide - alone or in combination with cytostatic drugs corticosteroids. SCS support for anti -inflammatory therapy after failure of other drugs used as well .
In some cases , the corticosteroids are used as local therapy . The indications for use are mainly mono-or oligo- arthritis of large joints ,
Biological agents
In rheumatoid arthritis , the synovium , for unclear reasons , secrete large amounts of the dehydrogenase, glucose -6 - phosphate , which also destroyed the disulfide bonds of the enzyme in the cell membrane. In this case , there is no " leak " of proteolytic enzymes in the lysosomes of cells, which causes damage to the bone and the surrounding cartilage . The body responds to this cytokine , including also a tumor necrosis factor TNF . Cascade of these reactions in the cells are activated by cytokines , which further aggravates the symptoms . Inflammation associated with rheumatoid arthritis TNF - α , often causing damage to the cartilage and joints , leading to physical disability .
The treatment uses a monoclonal antibody against the cytokine TNF - A, which is effective with a high affinity for binding to TNF , both in its soluble and transmembrane forms of the resulting TNF - neutralizing activity .
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 bone erosion in the joint space . Clinical trials of monoclonal antibodies have shown that the use of slow erosion and reduction of the space between the bones .
