Rheumatoid arthritis simultaneously involves the area of three or more joints
Rheumatoid arthritis is a chronic systemic inflammatory disease that primarily affects the joints. However, there are also extra-articular manifestations of rheumatoid arthritis.
Rheumatoid arthritis affects 0.03-1.5% of the population, with women 2-3 times more likely than men. Life expectancy with this disease is reduced by an average of 7.5 years in men and 3.5 years in women.
To make a diagnosis of rheumatoid arthritis, at least 4 of the 7 American Rheumatological Association criteria must be present. At least one of these four criteria must be present for at least 6 weeks.
You should also know that rheumatoid factor is only one criterion; it does not have to be present to make a diagnosis of rheumatoid arthritis. In addition, there must be no evidence of another disease to which the symptoms of polyarthritis nodosa or lupus may belong.
Most patients experience slow onset of rheumatoid arthritis. However, a third of patients have a rapid onset within days or weeks. The disease may progress rapidly, causing joint destruction and other consequences, or it may progress slowly. Many patients have an unstable course with exacerbations and remissions. For 70% of women, symptoms improve during pregnancy.
The synovium is the site of the onset of inflammation with synovial proliferation and incendiary destruction of soft tissue, leading to dysfunction of ligaments and tendons. Joint destruction occurs with bone erosion. Cysts, cartilage loss, and bone erosion may be seen. Thickened synovium may be palpable around the joints; effusion from the joint may also be present. 2. The most common sites of joint damage are the MCJ and PMJ joints, as well as the hands. The disorder is symmetrical and predominantly involves the small joints.
Cervical spine. Often affected (40%). Symptoms are the same as for radiculopathy, including pain radiating to the back of the head, paresthesia, sudden loss of arm function, loss of sensation, abnormal gait, and urinary retention or incontinence.
The arm is involved in more than 85% of patients. Fusiform swelling of the fingers and joint joints, ulnar deviation of the fingers may be observed. The distal interphalangeal joints are often preserved. Ulnar deviation of the MC joints is often associated with radial deviation in the hand. Swan neck and boutonniere deformities are also common. The hip is involved in 50% of cases.
The knee is involved in 80% of patients.
The foot and ankle are involved in 80% of cases.
People with rheumatoid arthritis may experience fatigue, weight loss, muscle pain, excessive sweating, and low-grade fever. Most patients with active disease complain of morning stiffness in the affected joints for more than 1 hour.
Rheumatoid nodules are characteristic of rheumatoid arthritis and are observed in 25-50% of patients, especially with severe disease. They occur in the lungs, heart, kidneys, and dura mater, as well as on the extensor surfaces of the forearms, olecranon, Achilles tendon, and gluteal regions.
Rheumatoid vasculitis usually occurs in patients with severe deforming arthritis and high titers of rheumatoid factor. Vasculitic lesions include rheumatoid nodules, small nail bed infarcts, and purpura. Multiple mononeuritis, organ ischemia, and myocardial infarction may also occur.
Sjögren's syndrome. Keratoconjunctivitis sicca is the most common eye complication and results in dry eyes with slight redness but normal vision.
Episcleritis and scleritis. Irritation and pain in the eyes. May cause decreased vision.
Pleurocarditis or obstructive pulmonary disease, including pulmonary nodules. Widespread diffuse interstitial fibrosis with pneumonia. Chronic obstructive pulmonary disease is more common than in the general population. However, pleural diseases are usually asymptomatic; subpleural nodes and exudative pleural effusions can be observed.
Symptomatic heart disease is uncommon. The most common type is acute pericarditis, of course in seropositive individuals (does not correlate with duration of arthritis). Rheumatoid nodules may involve valves and myocardium. Therefore, myocardial infarction secondary to vasculitis may occur.
Neuropathy secondary to tissue swelling (as with carpal tunnel syndrome) may occur. Mononeuritis multiplex may occur due to ischemic neuropathy due to vasculitis.
Rheumatoid arthritis is a common cause of carpal tunnel syndrome.
It is now clear that early use of disease-modifying medications, including judicious use of steroids, reduces joint destruction. The basic treatment program consists of patient education, a balance of rest, exercise (often with physical or occupational therapy), and medication. More than 95% of seropositive patients respond to therapy, and 70% of patients achieve partial or complete remission.
Acetylsalicylic acid, NSAIDs and COX-2 inhibitors. They provide symptomatic relief, but do not reduce the rate of cartilage erosion and do not change the course of the disease. Doses should be increased to the recommended maximum over 1-2 weeks; Treatment should not be stopped until the patient has been on the maximum dose for at least 2 weeks, as these drugs may take quite a long time to achieve maximum effectiveness. If results are disappointing after 2 weeks of taking the maximum dose, you should try an alternative NSAID. Sustained-release acetylsalicylic acid preparations can make taking acetylsalicylic acid easier. Less expensive NSAIDs include naproxen 500 mg po 2/day and ibuprofen 600 mg po 3/day. Use of proton pump inhibitors with NSAIDs (and COX-2 inhibitors) reduces the occurrence of gastric and duodenal ulcers.
The COX-2 inhibitors, rofecoxib and celecoxib, are as effective as other NSAIDs but have fewer side effects. However, some patients taking COX-2 inhibitors develop ulcers (up to 12%), and these drugs are expensive. Rofecoxib also interacts with warfarin and both have renal side effects. COX-2 inhibitors do not have a direct effect on platelets.
Previous studies indicate that even one tablet of acetylsalicylic acid per day (eg, for the prevention of myocardial infarction or stroke) may negate any GI benefits of COX-2 inhibitors.
Modifying antirheumatic drugs. These agents modify the fundamental pathological process. There is no consensus on which drugs to use or in what order, but active treatment with more than one drug is becoming the standard of care. Treatment must be individualized. Today, methotrexate is most often prescribed for the treatment of rheumatoid arthritis. The use of methotrexate in combination with other medications is increasing. Combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine works better than either drug alone or sulfasalazine plus hydroxychloroquine. Another combination is methotrexate plus cyclosporine. The oral gold drug, sodium thiosulfate, is less toxic than other medications but also less effective. The injectable gold drug, sodium thiomalate, is more toxic and no more effective than hydroxychloroquine and sulfasalazine. Due to the spontaneous waxing and waning of rheumatoid arthritis, these drugs should be used for approximately 6 months. Disease-modifying drugs should be prescribed in the early stages of rheumatoid arthritis.
Corticosteroids have anti-inflammatory and immunosuppressive properties and reduce joint erosion with long-term use (for example, prednisolone 7.5 mg daily for 2 years). Low-dose corticosteroids (<10 mg prednisone/day or equivalent) may be used in combination with other drug-modifying antirheumatic drugs. They may also be useful for treating acute outbreaks with systemic symptoms. Maintain steroids at minimum effective doses due to osteopenia and other side effects, particularly thinning of the skin, increased vulnerability to infection, ecchymosis, and Cushingoid appearance. Patients chronically taking steroids should also take vitamin D, calcium, and possibly alendronate or risendronate (depending on the degree of bone demineralization). 2. Inhibitors of tumor necrotic factor. Infliximab (not FDA approved for this indication) and etanercept are disease modifiers that slow disease progression. Etanercept is registered for use in patients who have not responded to other disease-modifying drugs for rheumatoid arthritis. The long-term effectiveness of these agents is not fully understood. Use with another drug, in particular methotrexate, allows you to obtain a sustainable response. These drugs are contraindicated in patients with existing infections and cannot be used with live antiviral vaccines.
Leflunomide is a disease-modifying rheumatoid arthritis drug that has recently been approved by the FDA with similar efficacy to methotrexate and sulfasalazine. Leflunomide has been shown to reduce bone erosion. It has a long half-life (14-16 days). The recommended loading dose is 100 mg/day for 3 days and then 20 mg/day. Leflunomide requires 4-6 weeks to achieve a permanent state. Long-term safety and effectiveness have not yet been established.
Antibiotics. Minocycline 100 mg po 2/day was shown to be effective in mild to moderate rheumatoid arthritis in a double-blind, placebo-controlled study. This is likely secondary to its anti-inflammatory properties.
Antimalarials. Hydroxychloroquine 400-600 mg po q/day for 4-6 weeks followed by 200-400 mg q/day. An initial ophthalmologic examination followed by a K6 month examination may reveal early ocular changes. There may be ciliary muscle dysfunction or corneal opacification. Have the patient look at the Ansler grid daily to identify early signs of vision changes. As safe as NSAIDs.
Sulfasalazine (not FDA approved for rheumatoid arthritis) 500 mg po q/day, followed by titration to a maximum of 3000 mg q/day. Reduce to 500 mg 4/day for maintenance. Contraindications include allergy to sulfonamides. Side effects include bone marrow toxicity, hepatitis, reversible oligospermia, yellow discoloration of urine and soft contact lenses, nausea, headache and discomfort. Monitoring of PFC and liver enzymes is recommended.
Penicillamine. Start with 125-250 mg po q/day 1 hour before or 2 hours after meals and then increase the dose by 125-250 mg/day every 1-2 months to a maximum of 750-1000 mg q/day. A common problem is a metallic taste and nausea in the early stages of use, but these disappear with continued use. Skin rash, bone marrow toxicity, and proteinuria may occur. Autoimmune syndromes, including myasthenia gravis, polymyositis, pemphigus, and Goodpasture syndrome, have been reported as a result of penicillamine use. Recommended monthly urinalysis and PFC. Penicillamine should not be used in patients with kidney disease.
Methotrexate: 7.5-15 mg po weekly. Contraindications: concomitant therapy with sulfa drugs or HIV seropositivity. Alcohol consumption, overt obesity, and diabetes are factors that worsen hepatotoxicity. There may be nausea, vomiting, and cramps. Serious side effects include bone marrow toxicity, alveolitis, and hepatic fibrosis. Monthly PFC testing and liver enzyme testing every 2-3 months are recommended. Persistent elevation of liver enzymes or significant hypoalbuminemia may indicate the need for liver biopsy. Folic acid should be provided at least 5 mg/week, which reduces side effects without compromising effectiveness.
Azathioprine: 50-100 mg po q/day (1.0-1.5 mg/kg/day, dose may be increased by 0.5 mg/kg/day each week to 2.0-2.5 mg /kg/day after 3 months). Nausea is the main limiting factor. Azathioprine is more toxic than other disease-modifying rheumatoid arthritis drugs. Monthly PFC and quarterly liver function tests are recommended. Concomitant use of allopurinol increases toxicity and should be avoided. Doses should be reduced if kidney damage is present.
Cyclophosphamide. Tends to be toxic, with many patients having one or more side effects, which include nausea or vomiting (58%), alopecia (26%), dysuria (26%), hemorrhagic cystitis (14%), herpes zoster (5%) . Other adverse reactions included leukopenia, thrombocytopenia and amenorrhea in premenopausal women. Cyclosporine can be prescribed to patients with severe reversal disease. However, the potential for irreversible toxicity indicates that the use of this drug should be limited to patients who have not responded to other types of therapy.
Salts of gold. Parenteral preparations of gold salts. Gold sodium thiomalate and aurothioglucose. Intramuscular: single dose of 10 mg followed by 25 mg after 1 week for sensitivity testing. Maintenance therapy is 25-50 mg weekly. If there is no improvement with cumulative doses of 1-2 g or toxicity develops, treatment should be discontinued.
Auranofin 3-6 mg po/day. A common side effect is diarrhea. Urinalysis and PFC should be performed monthly.
Side effects. Common. Itchy skin rashes, oral ulcers, transient leukopenia, eosinophilia, diarrhea (oral medications). Sometimes treatment can be stopped temporarily and then started at low doses and side effects may not return, but the rashes should be given a chance to clear up as they can lead to exfoliative dermatitis. Transient proteinuria in 3-10% of patients. Usually requires only cessation of treatment until the urine is cleared. Less common. Thrombocytopenia, pancytopenia, agranulocytosis and aplastic anemia. Usually go away after discontinuation of the drug.
basic anti-inflammatory drugs
genetically engineered biological products
ALA – anti-drug antibodies
ACB – antibodies to cyclic citrullinated proteins
ACCP - antibodies to cyclic citrullinated peptide
DMARDs – basic anti-inflammatory drugs
VAS – visual analogue scale
GIBP – genetically engineered biological drugs
CHF - Congestive Heart Failure
IHD – coronary heart disease
ILD – interstitial lung disease
and-TNF-? – TNF inhibitors
Exercise therapy – physical therapy
MRI – magnetic resonance imaging
NSAIDs – non-steroidal anti-inflammatory drugs
ADR - adverse reaction
PBP – patient assessment of pain
GPZ – general assessment of the disease by the patient
PIP – proximal interphalangeal joint
MCP – metacarpophalangeal joint
PLF - metatarsophalangeal joint
RCTs – randomized clinical trials
RF – rheumatoid factor
SIR – standard infusion reactions
ESR - erythrocyte sedimentation rate
CRP – C-reactive protein
tsDMARDs – targeted synthetic DMARDs
TNF – tumor necrosis factor
CZP – certolizumab pegol
NBS - number of painful joints
NPV - number of swollen joints
ACR - American College of Rheumatology
CDAI - Clinical Disease Activity Index
DAS - Disease Activity Index
EULAR - European League Against Rheumatism,
HAQ - Health Assessment Questionnaire
NICE - National Institute for Health and Care Excellence
SDAI - Simplified Disease Activity Index
Undifferentiated arthritis (UDA) is an inflammatory lesion of one or more joints, which cannot be attributed to any specific nosological form, since it does not meet the classification criteria of RA or any other disease.
Early rheumatoid arthritis (RA) – duration less than 6 months (from the onset of symptoms of the disease, not the diagnosis of RA).
Full-blown RA – duration of more than 6 months, meeting the classification criteria for RA (ACR/EULAR, 2010).
Clinical remission of RA is the absence of signs of active inflammation, remission criteria: - NBS, NPP, CRP (mg/%) and TBV less than or equal to 1 or SDAI less than or equal to 3.3 (ACR/EULAR criteria, 2011).
Persistent remission of RA is clinical remission lasting 6 months or more.
Antirheumatic drugs are anti-inflammatory drugs with different structures, pharmacological characteristics and mechanisms of action, used to treat RA and other rheumatic diseases.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of synthetic drugs that have symptomatic analgesic, antipyretic and anti-inflammatory effects associated primarily with inhibition of the activity of cyclooxygen, an enzyme that regulates the synthesis of prostaglandins.
Glucocorticoids (GCs) are synthetic steroid hormones that have natural anti-inflammatory activity.
Low dose GC - less than 10 mg/day prednisone (or equivalent dose of another GC)
High doses of GC - more than 10 mg/day prednisolone (or equivalent dose of another GC).
Standard basic anti-inflammatory drugs (DMARDs) are a group of synthetic anti-inflammatory drugs of chemical origin that suppress inflammation and the progression of joint destruction.
Genetically engineered biological products (GEBPs) are a group of drugs of biological origin, including monoclonal antibodies (chimeric, humanized, fully human) and recombinant proteins (usually including the Fc fragment of human IgG), obtained using genetic engineering methods, specifically suppressing the immunoinflammatory process and slowing down the progression of joint destruction.
Rheumatoid factors (RF) are autoantibodies of IgM, less often IgA and IgG isotypes, reacting with the Fc fragment of IgG.
Antibodies to citrullinated proteins (ACP) are autoantibodies that recognize the antigenic determinants of the amino acid citrulline, formed during the post-translational modification of proteins; the most commonly identified are antibodies to cyclic citrullinated peptide (ACCP) and antibodies to modified citrullinated vimentin (AMCV).
Adverse drug reaction (AD) is any adverse event that develops during the clinical use of a drug and is not related to its obviously expected therapeutic effects.
Rheumatoid arthritis (RA) is an immunoinflammatory (autoimmune) rheumatic disease of unknown etiology, characterized by chronic erosive arthritis and systemic damage to internal organs, leading to early disability and reduced life expectancy of patients [1].
RA belongs to the group of chronic non-infectious inflammatory diseases, the etiology of which is unknown [1,2]. Most researchers are inclined to favor the multifactorial etiology of the disease, the development of which is determined by the interaction of genetic and environmental factors. The contribution of each of the components may be insignificant, and only with their accumulation is the realization of the disease possible. It is most likely that the heterogeneity of RA is due to the variability of genes that play an important role in susceptibility to RA. The most studied and established association for RA is with the HLADRB1 gene, especially with alleles encoding the amino acid sequence in the third hypervariable region of the DRB1 chain, the so-called shared-epitope (SE). There is evidence of susceptibility to the development of RA depending on the number of SE copies, which indicates to a certain extent a dose-dependent effect [1]. Residents of the European region are characterized by an association of RA with DRB1*0401 alleles. The role of hormonal factors, such as the production of sex hormones, is discussed, since estrogens have an immunostimulatory effect, including on B-cell activity, while androgens have an immunosuppressive effect. Among the environmental factors, the role of bacterial (dental) and viral infections is discussed; a certain role is assigned to chemicals, stress, and occupational hazards. It has been most reliably established that tobacco smoking is an important environmental factor in the development of RA.
The role of excess citrullination (replacement of the normal amino acid arginine with an atypical one - citrulline) of proteins, observed in response to smoking, hypoxia, oral infection (periodontitis), under the influence of the enzyme peptidyl arginine deaminase, is assumed to be a factor initiating autoimmune mechanisms. Citrullination of proteins can trigger activation of immunocompetent cells (dendritic cells, macrophages, T- and B-lymphocytes), associated with impaired tolerance to these modified proteins, caused by genetic factors (carriage of HLA-DR4), leading to an imbalance between the synthesis of “pro-inflammatory” cytokines - tumor necrosis factor (TNF)-?, interleukin (IL)-6, IL-1, IL-17 and anti-inflammatory cytokines (IL-10, soluble IL1 antagonist, soluble TNF? receptors, IL4). The development of an immune response to citrullinated proteins is manifested by the synthesis of ACB, sometimes before the clinical debut of the disease. Activated cells produce pro-inflammatory cytokines such as IL-1, TNF-?, IL-6, IL-8, activating Helper T lymphocytes type 1 (Th1) and Th17 cells. Stimulated Th1 and Th17 cells produce IL-2, TNF-?, IFN-?, IL-17, IL-21, causing activation of B lymphocytes. The latter are transformed into plasma cells that produce autoantibodies, predominantly of the IgG isotype. At the same time, mast cells are activated, secreting inflammatory mediators (heparin, serotonin, etc.). As a result, exudative-proliferative inflammation of the sionovial membrane of the joints (synovitis) occurs, characterized by the formation of lymphocytic infiltrates, the accumulation of macrophages, the development of neoangiogenesis, the proliferation of synovial membrane cells and fibroblasts with the formation of aggressive tissue - pannus. Pannus cells secrete proteolytic enzymes that destroy cartilage; at the same time, under the influence of hyperproduction of proinflammatory cytokines (TNF-β, etc.), osetoclasts are activated, which leads to osetoporosis (local and systemic) and further destruction of bone tissue with the formation of erosions (usur). With the development of extra-articular manifestations, the same cellular immunoinflammatory mechanisms play a role, as well as the occurrence of immunocomplex vasculitis associated with the production of autoantibodies (ACB, RF).
RA is a common and one of the most severe human immunoinflammatory diseases, which determines the great medical and socio-economic significance of this pathology. The prevalence of RA among adults in different geographical areas of the world ranges from 0.5 to 2% [2]. According to official statistics, about 300 thousand patients with RA are registered in Russia, while according to the Russian Epidemiological Study, RA affects about 0.61% of the general population. The ratio of women to men is 3:1. The disease occurs in all age groups, but the peak incidence occurs in the most working age - 40–55 years. RA causes persistent disability in half of the patients during the first 3-5 years from the onset of the disease and leads to a significant reduction in their life expectancy, both due to the high incidence of cardiovascular pathology, severe infections, cancer, and complications characteristic of RA. with a systemic immunoinflammatory process - rheumatoid vasculitis, AA amyloidosis, interstitial lung disease, etc.
Seropositive rheumatoid arthritis (M05)
M05.0 Felty's syndrome
M05.1 - Rheumatoid lung disease (j99.0)
M05.2 - Rheumatoid vasculitis
M05.3 - Rheumatoid arthritis involving other organs and systems
M05.8 - Other seropositive rheumatoid arthritis
M05.9 - Seropositive rheumatoid arthritis, unspecified
M06.0 - Seronegative rheumatoid arthritis
M06.1 - Adult-onset Still's disease
M06.2 - Rheumatoid bursitis
M06.3 - Rheumatoid nodule
M06.4 - Inflammatory polyarthropathy
M06.8 - Other specified rheumatoid arthritis
M06.9 - Rheumatoid arthritis, unspecified
Clinical classification of rheumatoid arthritis (adopted at a meeting of the Plenum of the Board of the All-Russian public organization "Association of Rheumatologists of Russia", 2007)
Comments: Seropositivity and seronegativity of RA are determined depending on the detection of rheumatoid factor (RF) and/or antibodies to cyclic citrullinated proteins (ACP), for the determination of which it is necessary to use standardized laboratory methods.
Comments: Assessment of inflammation activity (see Appendix D1.)
4. Extra-articular (systemic) manifestations:
5. Instrumental characteristics:
I - periarticular osteoporosis
II – osteoporosis + narrowing of the joint space, there may be single erosions
III – signs of the previous stage + multiple erosions + subluxations in the joints
IV – signs of the previous stage + bone ankylosis
Comments: Detailed characteristics of radiological stages:
Stage 1. Minor periarticular osteoporosis. Single cyst-like clearings of bone tissue. Slight narrowing of the joint spaces in individual joints.
Stage 2. Moderate (severe) periarticular osteoporosis. Multiple cyst-like clearings of bone tissue. Narrowing of joint spaces. Single erosions of articular surfaces (1-4). Minor bone deformities.
Stage 3 . Moderate (severe) periarticular osteoporosis. Multiple cyst-like clearings of bone tissue. Narrowing of joint spaces. Multiple erosions of articular surfaces (5 or more). Multiple severe bone deformities. Subluxations and dislocations of joints.
Stage 4. Moderate (severe) periarticular (widespread) osteoporosis. Multiple cyst-like clearings of bone tissue. Narrowing of joint spaces. Multiple erosions of bones and articular surfaces. Multiple severe bone deformities. Subluxations and dislocations of joints. Single (multiple) bone ankylosis. Subchondral osteosclerosis. Osteophytes on the edges of the articular surfaces.
6. Additional immunological characteristic – antibodies to cyclic citrullinated peptide (ACCP):
I – fully preserved: self-service, non-professional and professional activities
II – preserved: self-service, professional activities, limited: non-professional activities
III – preserved: self-service, limited: non-professional and professional activities
IV – limited: self-service, non-professional and professional activities
Characterized by a variety of options for the onset of the disease. In most cases, the disease begins with polyarthritis; less often, manifestations of arthritis can be moderately expressed, and arthralgia, morning stiffness in the joints, deterioration in general condition, weakness, weight loss, low-grade fever, lymphadenopathy predominate, which may precede clinically significant joint damage. A number of variants of the onset of the disease have been described:
Symmetrical polyarthritis with a gradual (over several months) increase in pain and stiffness, mainly in the small joints of the hands (in half of the cases).
Acute polyarthritis with predominant damage to the joints of the hands and feet, severe morning stiffness (usually accompanied by the early appearance of RF in the blood).
Mono-oligoarthritis of the knee or shoulder joints, followed by rapid involvement of the small joints of the hands and feet.
Acute monoarthritis of large joints, resembling septic or microcrystalline arthritis.
Acute oligo- or polyarthritis with severe systemic symptoms (febrile fever, lymphadenopathy, hepatosplenomegaly) is more often observed in young patients (reminiscent of Still's disease in adults).
“Palindromic rheumatism”: multiple recurrent attacks of acute symmetrical polyarthritis of the joints of the hands, less often of the knee and elbow joints; last several hours or days and end with complete recovery.
Recurrent bursitis and tenosynovitis, especially often in the area of the wrist joints.
Acute polyarthritis in the elderly: multiple lesions of small and large joints, severe pain, diffuse swelling and limited mobility. Received the name “RS3PE syndrome” (Remitting Seronegative symmetric synovitis with Pitting Edema)
Generalized myalgia: stiffness, depression, bilateral carpal tunnel syndrome, weight loss (usually develops in old age and resembles polymyalgia rheumatica); characteristic clinical signs of RA develop later.
In a significant proportion of patients, RA debuts with uncharacteristic clinical manifestations, and therefore the diagnosis according to existing criteria cannot be established during the initial examination. This condition is usually classified as undifferentiated arthritis (UDA). Among patients with NDA, at least 30% develop typical RA during 1 year of observation. In practice, the following clinical variants of NDA are most often encountered:
• Oligoarthritis of large joints (knees, ankles, shoulders, hips)
• Asymmetrical arthritis of the joints of the hands
• RF seronegative oligoarthritis of the joints of the hands
Therapeutic approaches for NDA are close to those for RA.
The diagnosis of RA is established, first of all, on the basis of identifying the characteristic clinical signs of the disease.
Peripheral arthritis is clinically manifested by pain, swelling, and limited joint mobility. Characteristic signs are arthritis of the PJF, PJF of the joints of the hands, in some cases, damage to the PJF or large joints initially prevails.
The most characteristic manifestations at the onset of the disease:
The most characteristic manifestations in the advanced and final stages of the disease:
Extra-articular manifestations (sometimes may prevail in the clinical picture).
Special clinical forms
Level of evidence: I; strength of recommendations: A.
Level of evidence: I; strength of recommendations: A.
Level of evidence: II; strength of recommendation: B
Comment : Determining ACCP is important for diagnosing seronegative (according to RF) RA, differential diagnosis of RA with other diseases, predicting severe erosive joint damage and the risk of cardiovascular complications.
The diagnostic and clinical significance of determining RF and ACB is associated with high levels of these autoantibodies.
Comments: ESR is a highly sensitive, but nonspecific and unstable marker of systemic inflammation.
The results of determining ESR are influenced by age, gender, fibrinogen level, RF, hypergammaglobulinemia, anemia and other factors.
In early RA, an increase in ESR correlates with disease activity and the risk of progression of joint destruction.
Level of evidence: I; strength of recommendation: A
Comments: CRP is a classic acute-phase serum protein considered to be the most sensitive laboratory biomarker of inflammation, infection, and tissue damage.
Determination of CRP is used to assess the activity of inflammation, predict the rate of joint destruction and differentiate between RA and SLE.
CRP is a more stable and reproducible biomarker of inflammation than ESR.
An increase in ESR and the concentration of C-reactive protein (CRP) reflects the local and systemic inflammatory process in RA. These indicators are included in the classification criteria for RA (ACR/EULAR, 2010), and ESR and CRP are also components of RA activity indices.
Level of evidence: IV; strength of recommendation: D
Comments: These include markers (or risk factors) of chronic infections (tuberculosis, hepatitis C and C virus infections, HIV, etc.); cardiovascular diseases; renal dysfunction, alcohol intake, vaccination status, pregnancy planning; turn of the Mantoux tuberculin test.
Comments : For patients in the late stage of RA, with stages 3 and 4 of joint damage (according to Steinbrocker), the frequency of X-ray examination of the joints is determined by clinical indications.
RA is characterized by multiple and symmetrical lesions of the small joints of the hands and feet:
With acute onset and active inflammation in RA, periarticular osteoporosis and single cysts can be detected within 1 month of the disease; multiple cysts, narrowing of joint spaces and single erosions 3 to 6 months from the onset of the disease, especially in the absence of DMARD treatment
Early radiological signs of arthritis are found: in the 2nd and 3rd metacarpophalangeal joints; 3 proximal interphalangeal joints; in the joints of the wrists; wrist joints; styloid processes of the ulna bones; 5 metatarsophalangeal joints.
Typical for RA are symmetrical radiological changes in the metacarpophalangeal joints, proximal interphalangeal joints; in the joints of the wrists; metatarsophalangeal joints and 1st interphalangeal joints of the feet
With more pronounced radiological stages of RA (Steinbrocker stages 3 and 4), changes can be detected in the distal interphalangeal joints of the hands and proximal interphalangeal joints of the feet.
RA does not begin with damage to the distal interphalangeal joints of the hands and feet; proximal interphalangeal joints of the feet
Bone ankylosis in RA is detected only in the intercarpal joints; 2-5 carpometacarpal joints and, less often, in the tarsal joints.
Bone ankylosis in RA does not form in the interphalangeal, metacarpophalangeal and metatarsophalangeal joints of the hands and joints, in the 1st carpometacarpal joints. RA is characterized by ankylosis of the intercarpal, carpometacarpal joints and, less commonly, the tarsal joints.
X-ray changes characteristic of RA in large joints of the upper and lower extremities and in the joints of the axial skeleton are absent and can be detected in other rheumatic diseases.
Features of radiological changes in joints in RA in old age
Periarticular osteoporosis may be a manifestation of postmenopausal osteoporosis. Signs of osteoarthritis (narrowing of joint spaces, cysts) may be detected in the DIP and PIP joints of large joints of the hands, and less often in the PJF. To confirm the diagnosis of RA, it is necessary to identify erosions in joints typical for RA (wrist, PLF, PJF)
Comments: X-ray examination of joints is used for:
The level of certainty of evidence is IV, the level of strength of recommendations is D.
Comments: Included in the mandatory list of instrumental examination methods before prescribing DMARD and GEBD therapy
Comments: MRI signs of arthritis are nonspecific. Similar MRI changes may be present in other inflammatory joint diseases and may be detected in individuals without joint disease.
Changes detected by MRI (synovitis, tenosynovitis, bone marrow edema and bone erosion) make it possible to predict the progression of joint destruction.
MRI of the hands is indicated for patients with early RA and LDA in cases where diagnosis is difficult and to assess the prognosis.
Comments: On the “gray scale” - thickening of the synovial membrane, the presence of effusion in the joint, disruption of the contour of the articular surface (corresponding to erosion), changes in the periarticular tissues (tenosynovitis)
With a power Doppler study, the localization, extent and intensity of the signal are used, which allows us to judge the severity of inflammation.
Ultrasound of the hand joints has diagnostic and prognostic value in early RA and allows predicting the maintenance of remission during therapy with DMARDs and biologically active drugs.
Currently, there is insufficient data to consider ultrasound a more reliable method for assessing the severity of inflammation than a thorough clinical examination of the joints.
Functional impairment is assessed over time using the Health Assessment Questionnaire (HAQ) (see Appendix D3).
Level of evidence: IV; strength of recommendation: D
The goal of treatment is to achieve stable clinical remission or (an alternative goal) at least persistently low disease activity, which ensures stabilization of the patient's functional capabilities, maintaining quality of life and ability to work.
The modern treatment strategy for RA is based on the principles of “Treat to target” and implies the active administration of anti-inflammatory therapy from the moment of diagnosis, frequent (at least every 3 months until remission is achieved, every 6 months after remission is achieved). ) and objective (using quantitative methods) monitoring of the patient’s condition, changing the treatment regimen in the absence of a sufficient response to therapy until treatment goals are achieved, followed by constant follow-up [9-13].
Level of evidence is IV, level of recommendation is D
The main place in the treatment of RA is occupied by drug therapy, in which the following groups of drugs are used: non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GC) and disease-modifying anti-inflammatory drugs (DMARDs). See Appendix G4 .
Level of evidence: I; strength of recommendation: A
Comments: Patients who are in remission (or have low disease activity) have better functional status, disability, and disease prognosis (reduced risk of premature mortality) than patients who continue to have moderate or high disease activity.
The effectiveness of therapy using standardized activity indices should be assessed every 1 to 3 months until a state of remission (or low activity) is achieved, and then every 3 to 6 months. To assess remission, the ACR/EALAR (2011) criteria should be used [4] (see Appendix D2).
A decrease in RA activity during treatment during the first 3 months is associated with the development of remission after 12-24 months
Level of evidence is III, level of recommendation is C.
Comments: The functional status and prognosis of patients under the supervision of rheumatologists is better than that of general practitioners. A multidisciplinary approach to the management of patients with RA can reduce the negative impact of comorbid pathology on the course, effectiveness of pharmacotherapy and prognosis of the disease.
Comments: Smoking, obesity and periodontitis are risk factors for the development and progression of RA, a decrease in the effectiveness of treatment with DMARDs and TNF-β inhibitors, and an increase in mortality, including that caused by cardiovascular diseases (level of evidence B)
Regular physical activity improves functional status and helps patients maintain their ability to work.
The level of certainty of evidence is I, the level of strength of recommendations is A.
Comments : Since NSAIDs do not affect the activity of inflammation, the progression of joint destruction and can cause severe adverse reactions from the gastrointestinal tract, cardiovascular system, etc., their use should be limited.
The choice of NSAIDs is largely determined by their safety in relation to the development of HP rather than by their effectiveness.
— At the beginning of treatment or when increasing the dose of MT, determination of ALT/AST, creatinine, and a complete blood count must be performed every 1–1.5 months until a stable dose of MT is achieved, then every 3 months.
— Treatment with MT should be interrupted when the concentration of ALT/AST exceeds the upper limit of normal (ULN) by more than 3 times; resume treatment at a lower dose after normalization of laboratory parameters. If there is a persistent increase in AST/ALT levels >3 ULN, the dose of MT should be adjusted; If the AST/ALT level continues to increase >3 ULN after discontinuation of MT, appropriate diagnostic procedures should be performed.
— In patients with “active” RA (DAS28?5.1), who are indicated for a high dose of MTX (≥15 mg), it is recommended to begin treatment with the subcutaneous form of the drug (evidence level B).
Level of evidence is II, level of recommendation is B.
Recommendations for the prevention and treatment of ADRs associated with the use of MT are summarized in Appendix G6.
Level of evidence: I; strength of recommendation: A
Level of evidence: I; strength of recommendation: A
— The use of HCQ is recommended only as a component of combination therapy with MTX
The level of evidence is II, the level of recommendation is B.
— SULF and GC can be used during pregnancy
— During treatment with LEF, it is necessary to control blood pressure
- GK should be discontinued as quickly as possible (preferably no later than 6 months from the start of therapy).
— The use of GC in combination with MTX for RA can increase the effectiveness of therapy compared to MTX monotherapy and improve the tolerability of MTX therapy
The level of evidence is II, the level of recommendation is B.
— “Bridging” therapy, including “induction” therapy with high doses of GC
- Longer use of GC (up to 2 years), which allows for the structural-modifying effect of GC to be realized - the so-called “long bridge” therapy
- Long-term use of low or very low (<5 mg/day) doses of GCs, which may potentiate the effectiveness of therapy with MTX and other DMARDs, and possibly GEBD.
— The development of osteoporosis, insulin resistance, infectious complications and cardiovascular accidents are considered as class-specific adverse effects of GC therapy, but may be a consequence of uncontrolled “rheumatoid” inflammation.
Comments: The algorithm for using GIBP is presented in Appendix B.2 . Recommendations for prescribing ts-DMARDs (TOFA) correspond to recommendations for prescribing GEBD.
Before prescribing a GEBD, MTX (including the subcutaneous form of MTX) or MTX in combination with standard DMARDs (SULF or SULF and HCQ) should be used in adequate doses for at least 3 months [24]
The development of at least a “moderate” effect (decrease in DAS28 index>1.2 points from the initial one according to EULAR criteria) after 3 months of therapy may be the basis for continuing therapy with standard DMARDs over the next 3 months
The level of evidence is I, the level of recommendation is A.
The level of evidence is I, the level of recommendation is A.
Level of evidence is III, level of recommendation is C.
Contraindications for prescribing GIBP [30-32]
Adverse reactions of GIBP therapy [31,32]
Although, in general, treatment with GEBD is characterized by a satisfactory safety profile, various adverse reactions (often severe) may occur during their use, requiring careful monitoring.
Based on the nature of the clinical manifestations, ADRs that develop during treatment with GIBD are divided into the following main categories:
— Standard infusion reactions (SIR)
— Immediate hypersensitivity reactions (anaphylaxis)
— Reactions associated with the synthesis of anti-drug antibodies (ALA), which are caused by the immunogenicity of biologically active drugs
— Other severe bacterial infections
— Viral infections (herpes zoster, hepatitis B and C)
The most typical adverse reactions associated with the treatment of biologically active drugs are standard infusion reactions (SIR), hypersensitivity reactions (anaphylaxis) and severe infections, including reactivation of latent tuberculosis infection, post-injection reactions with subcutaneous administration of biologically active drugs (see Appendix D8 and Appendix D9).
– high: INF, ADA, GLM and TsZP
- moderate: ETC, ABC, TCZ
— Activation of latent tuberculosis infection during RTM treatment has not been proven
Level of evidence is II, level of recommendation is B.
— Presence of comorbid diseases (chronic kidney and lung diseases)
Recommendations regarding the prevention and treatment of HP during treatment with biologically active drugs are presented in Appendix G10.
Recommendations regarding additional examination of patients with RA before starting therapy with biologically active drugs are summarized in Appendix D11.
Preliminary recommendations for choosing GIBP
— Data regarding the use of TNF-inhibitors? if GIBPs with other mechanisms of action (RTM, TCZ and ABC) are ineffective, they are practically absent.
— ETC can induce the development of uveitis
Level of certainty of evidence – III, level of conviction of recommendation – C
BIBPs with a different mechanism of action (ABC, RTM), rather than TNF-? inhibitors, are preferable to be prescribed to patients with clinical and serological signs of lupus-like syndrome (arthritis, pleurisy or pericarditis, skin rash, increased ANF titers), Felty syndrome, syndrome Schöngren and stage III-IV CHF (NYHA).
Confidence level of evidence – IV, level of persuasiveness of recommendation – D
— High efficiency in RF/ABC positive variant of RA
— High efficiency in cryoglobulinemic vasculitis associated with carriage of the hepatitis C virus
— Contraindications for prescribing TNF-? inhibitors: autoimmune disorders, malignant neoplasms (within the previous 10 years), risk of reactivation of latent tuberculosis infection (contraindications for tuberculostatic therapy), demyelinating diseases of the central nervous system (multiple sclerosis).
— To maintain the effect, it is necessary to conduct repeated courses of RTM (possibly in low doses - 500 mg x 2) no earlier than 6 months after the previous course
Level of evidence – II, level of recommendation – B
— During RTM treatment, dynamic determination of serum IgG concentration is necessary, especially with low basal levels and in elderly people (over 60 years old)
— High risk of SIR (especially during the first administration of the drug), which dictates the need for premedication with GC (100 mg 6-MPRED IV, 60 minutes before RTM infusion), administration of paracetamol (1 g) and the antihistamine chlorphenamine (10 mg IV V)
— High efficiency in RF/ATS positive variant of RA
— Lower risk of infectious complications, reactivation of latent tuberculosis infection, exacerbation of ILD and cardiovascular complications than during treatment with TNF-inhibitors?
— The presence in patients of pronounced constitutional manifestations of RA (pain in many joints, prolonged morning stiffness, weakness, weight loss, insomnia, fever) and laboratory abnormalities (a significant increase in the concentration of CRP>100 mg/L, hyperferritinemia, severe anemia of chronic inflammation, detection of AA amyloidosis)
— High efficiency of TCZ monotherapy in patients with contraindications or poor tolerance to MTX
— Treatment with TCZ is effective in adult Still's disease.
— During treatment with TCZ, careful monitoring of the absolute number of neutrophils, platelets, liver enzymes, and lipid profile is necessary (every month during the first 6 months of therapy)
- If the number of neutrophils (<0.5 x 10 9 /L) and platelets (<50 x 10 3 /L) and liver enzymes (> 5 ULN) decreases, treatment with TCZ should be discontinued.
— Since TCZ reduces the severity of clinical and laboratory manifestations characteristic of an “acute-phase” inflammatory response (fever, increased ESR and CRP), careful monitoring of infectious complications is necessary, especially during emergency surgical interventions.
Treatment tactics after achieving remission (see Appendix D. 3)
Comments: The possibility of discontinuing a GEBD is more likely in patients with early RF/ACCP negative variant of RA
To maintain remission after dose reduction (or discontinuation) of GEBD, adequate MTX therapy is necessary, including the use of a subcutaneous form of the drug.
When an exacerbation of the disease develops against the background of a dose reduction (or discontinuation) of a GEBD, re-prescribing the same drugs (or other GEBD) in a standard dose leads to a rapid suppression of inflammatory activity in most patients.
In case of advanced RF/ACCP positive variant of RA, the abolition of a biological therapy usually leads to the development of an exacerbation
Arthroscopic and open synovectomy, debridement, osteotomy, osteoplasty, and joint replacement are used. Surgical correction improves the functional ability of patients in the medium term
Confidence level of evidence – IV, level of persuasiveness of recommendation – D
General recommendations regarding the treatment of patients with RA in the perioperative period are summarized in Appendix D12.
Comments: Cancellation of MT may cause exacerbation of the disease in the postoperative period and thereby worsen the results of surgical treatment
It is advisable to temporarily interrupt MTX treatment in patients with severe renal impairment
It is necessary to prescribe replacement therapy on the day of surgery (iv infusion of hydrocortisone 25-100 mg or 6-MPRED - 5-30 mg, depending on the severity of the operation).
Level of evidence is II, level of recommendation is B.
Level of evidence - I, level of recommendation - A
Level of certainty of evidence – III, level of conviction of recommendation – C
Comments: The patient must be provided with information about the disease, principles of therapy and outcomes, physical activity in everyday life. Education on joint protection strategies, energy conservation, and home strength and range of motion exercises should be used to maintain patients' functional status.
Educational programs increase the level of knowledge about RA, “self-efficacy”, social adaptation, the ability to self-control the disease, adherence to drug therapy, joint protection strategies, energy saving, the use of assistive household adaptive equipment and orthoses, regular exercise therapy, including at the early stage of the disease
Educational programs should be sure to emphasize the increased risk of cardiovascular disease in RA (B).
Support from patient organizations and training in the basic principles of “self-management” of the disease from the moment of diagnosis are needed.
Comments: Dynamic, strength, and aerobic training tailored to the patient's needs and abilities improves muscle strength, aerobic capacity, psychological well-being, and overall physical status without increasing disease activity or joint destruction in the short term.
Comments: ET has a positive effect on functional and psychological status, increases “self-efficacy”, level of everyday activity, social and professional adaptation.
Early training in joint protection techniques, energy-saving strategies, behavior modification, and the use of assistive devices improve long-term functional status.
efficiency."
The level of evidence is IV, the level of recommendation is D.
Level of certainty of evidence – III, level of conviction of recommendation – C
The nature of concomitant (comorbid) diseases is of utmost importance for the choice of treatment tactics from the point of view of both the effectiveness and safety of therapy.
Since DMARDs and biologically active drugs have the ability to suppress post-vaccination immunity, it is recommended that all RA patients begin treatment with these drugs:
Level of evidence - I, level of recommendation - A
Level of certainty of evidence – II, level of persuasiveness of recommendation – B
The diagnosis of RA should be made as early as possible, preferably within the first 1-3 months from the onset of the first symptoms of the disease [5,6]. To make a diagnosis, it is recommended to take into account the Classification Criteria for RA ACR/EULAR, 2010) [7] ( See Appendix D1).
When making a diagnosis of RA, there are three main factors to consider:
— Changes in the distal interphalangeal joints are not taken into account, the first
carpometacarpal joints and first metatarsophalangeal joints
— Shoulder, elbow, hip, knee, ankle
— Metacarpophalangeal, proximal interphalangeal, 2-5 metatarsophalangeal, interphalangeal joints of the thumbs, wrist joints
— Joints that may be affected by RA, but are not included in any of the
the groups listed above (for example, temporomandibular, acromial
clavicular, sternoclavicular, etc.)
where NBS is the number of painful joints, NPS is the number of swollen joints from the following 28: shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal, knee, which are primarily affected by RA and are well accessible for objective research.
ESR – erythrocyte sedimentation rate according to the Westergren method,
OSHA – general assessment of the patient’s health status in mm on a 100 mm visual analogue scale
Inflammatory activity in RA depending on the DSD28 index values
Low activity - DAS28 >2.6 < 3.1
Moderate activity – DAS28 >3.1 <5.1
High activity – DAS28 >5.1
Examples of formulation of clinical diagnoses:
• Rheumatoid arthritis, seropositive (M05.8), advanced stage, activity II, erosive (radiological stage II), with systemic manifestations (rheumatoid nodules), ACCP (-), FC II.
• Rheumatoid arthritis seronegative (M06.0), early stage, activity III, nonerosive (radiological stage I), ACCP (+), FC I.
• Rheumatoid arthritis, seropositive (M05.8), late stage, erosive (radiological stage III), activity II, with systemic manifestations (rheumatoid nodules, digital arteritis), ACCP (? - not studied), FC III, complications - carpal tunnel syndrome on the right, secondary amyloidosis with kidney damage.
• Probable rheumatoid arthritis (M06.9), seronegative, early stage, activity II, nonerosive (radiological stage I), ACCP (+), FC I.
An erythrocyte sedimentation rate (ESR) study was performed.
A quantitative study of C-reactive protein in blood serum was performed
The number of painful and swollen joints was assessed
Achieved a 20% reduction in the number of painful and swollen joints compared to the baseline
Treatment with DMARDs and/or tsDMARDs and/or biologically active drugs
Achieved a 20% reduction in OHB according to VAS
Nasonov EL, Karateev DE, Balabanova RM. Rheumatoid arthritis. In the book: Rheumatology. National leadership. Ed. E.L. Nasonova, V.A. Nasonova. Moscow: GEOTAR-Media; 2008.S. 290–331
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016. http//dx.doi.org/10.1016/S)140-6736(16)30173-7
Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Amer 2009;35:745-57, vii-viii. doi: 10.1016/j.rdc.2009.10.001.
Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63:573–86
Emery P, Breedveld FC, Dougados M, Kalden JR, Schiff MH, Smolen JS. Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis 2002;61:4 290-297 doi:10.1136/ard.61.4.290
Combe B, Landewe R, Lukas C, et al. EULAR recommendations for the management of early arthritis: report of task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2007; 66:34–45.
Aletaha D, Neogri T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria. An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569–81
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-24.
Smolen JS, Aletaha D, Bijlsma JW, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010;69:631–7
Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with systemic and biological disease-modifying anti-rheumatic drugs: 2013. Ann Rheum Dis. 2014; 73:492–509.
Nasonov EL, Mazurov VI, Karateev DE, etc. Draft recommendations for the treatment of rheumatoid arthritis of the All-Russian public organization “Association of Rheumatologists of Russia” - 2014 (part 1). Scientific and practical rheumatology. 2014;52:477–494.
Nasonov EL, Karateev DE, Chichasova NV. EULAR recommendations for the treatment of rheumatoid arthritis - 2013: general characteristics and controversial issues. Scientific and practical rheumatology. 2013;51:609–622.
Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheum 2016; 68:1-26. Doi: 10.1002/art.39489.
Smolen JS, van der Heijde D, Machold KP, et al. Proposal for a new nomenclature of disease-modifying anti-rheumatic drugs. Ann Rheum Dis. 2014;73:3–5
Nasonov E.L., Yakhno N.N., Karateev A.E., Alekseeva L.I., Barinov A.N., Barulin A.E., Davydov O.S., Danilov A.B., Zhuravleva M. .V., Zavodovsky B.V., Kopenkin S.S., Kukushkin M.L., Parfenov V.A., Strakhov M.A., Tyurin V.P., Chichasova N.V., Chorbinskaya S.A. . General principles for the treatment of musculoskeletal pain: an interdisciplinary consensus. Scientific and practical rheumatology. 2016;54:247-265. DOI:10.14412/1995-4484-2016-247-265
Nasonov E.L. Treatment of rheumatoid arthritis 2012: the place of methotrexate. Scientific - Practical Rheumatology 2012;51 (supplement):1-24
Nasonov EL, Karateev DE, Chichasova NV. New recommendations for the treatment of rheumatoid arthritis (EULAR, 2013): the place of methotrexate. Scientific and Practical Rheumatology 2014; 52: 8-26.
Molina JT, Garcia FJB, Alen JC, et al. Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes. Rheumatol Clin 2015;11:3-8
Visser K, Katchamart W, Losa E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systemic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis 2009; 68: 1086-1093.
Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 2009; 68:1094-1099
Singh JA, Furst D, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying anti-rheumatic drugs and biological agents in the treatment of rheumatoid arthritis. Arthritis Care Res 2012; 64: 625-639.
Nasonov EL. New recommendations for the treatment of rheumatoid arthritis (EULAR, 2013) - place of glucocorticoids. Scientific and Practical Rheumatology 2015;53:238-250
Strehl C, Bijlsma JW, de Wit M, et al. Defining conditions where long-term glucocorticoid treatment has an acceptable low level of harm to facilitate implementation of existing recommendations: view points from an EULAR task force. Ann Rheum Dis 2016; 75: 952-957. Doi:10.1136/annrheumdis-2015-208916
National Institute for Health and Care Excellence (UK). Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed [online], (2016).
Nasonov EL, editor. Genetically engineered biological drugs in the treatment of rheumatoid arthritis. Moscow: IMA-PRESS; 2013.
Nam JL, Ramiros S, Gaujoux-Viala C, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2014 73:516-28. doi: 10.1136/annrheumdis-2013-204577.
Hazlewood GS, Barnabe C, Tomilison G, Marshall D, Devoe D, Bombardier C. Methotrexate monotherapy and methotrexate combination therapy with traditional and biological disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ 2016;353:i1777. Doi:10.1136/bmj.i1777
Choy E, Aletaha D, Behrens F, Finckh A, Gomez-Reino J, Gottenberg JE, Schuch F, Rubbert-Roth A. Monotherapy with biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis. Rheumatology (Oxford) 2016 Aug 21. pii: kew271.
Nasonov EL. New approaches to pharmacotherapy of rheumatoid arthritis: tofacitinib. Scientific and practical rheumatology. 2014; 52: 209-221.
Ramiro S, Gaujoux-Viala C, Nam JL, et al. Safety of synthetic and biological DMARDs—a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73:529-535. doi10.1136/annrheumdis-2013-204575.
Woodrick RS, Ruderman EM. Safety of biological therapy in rheumatoid arthritis. Nat Rev Rheumatol 2011; 7, 639-652
Boyman O, Comte D, Spertini F. Adverse reactions to biological agents and their medical management. Nat Rev Rheumatol 2014; 10: 612-627. Doi:10.1038/nrrheuum.2014.123.
Anti-B cell therapy in rheumatology: focus on rituximab. Edited by E.L. Nasonova. Moscow. "IMA-PRESS" 2011, p. 592.
Schett G, Emery P, Tanaka Y, et al. Tapering biological and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis 2016l0:1-10. Doi.10.1136/annrheumdis-2016-209201.
Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, et al. Evidence-based recommendations for the management of comorbidities in rheumatoid arthritis, psoriasis, and psoriatic arthritis: expert opinion of the Canadian Dermatology-Rheumatology Comorbidity Initiative. J Rheumatol 2015;42:1767–80.
Richards JS, Dowell SM, Quinones ME, Kerr GS. How to use biological agents in patients with rheumatoid arthritis who have comorbid disease. BMJ 2015;17;351:h3658. doi: 10.1136/bmj.h3658.
Nasonov Evgeniy Lvovich – Academician of the Russian Academy of Sciences, chief researcher of the Federal State Budgetary Institution “Research Institute of Rheumatology named after. V.A. Nasonova”, Doctor of Medical Sciences, Professor, Moscow.
Karateev Dmitry Evgenievich – Acting Director of the Federal State Budgetary Institution “Research Institute of Rheumatology named after. V.A. Nasonova”, Head of the Department of Early Arthritis, Doctor of Medical Sciences, Moscow.
Mazurov Vadim Ivanovich - Academician of the Russian Academy of Sciences, President of the Federal State Budgetary Educational Institution of Higher Education "North-Western State Medical University named after. I.I. Mechnikov" of the Ministry of Health of Russia, head of the Research Laboratory of Rheumatology of the Federal State Budgetary Institution "Northwestern Federal Medical Research Center named after. V. A. Almazova" of the Ministry of Health of Russia, Doctor of Medical Sciences, Professor, St. Petersburg
Amirdzhanova Vera Nikolaevna – head of the laboratory for studying the quality of life and rehabilitation treatment of the Federal State Budgetary Institution “Research Institute of Rheumatology named after. V.A. Nasonova”, Doctor of Medical Sciences, Moscow.
Belov Boris Sergeevich – head of the laboratory for studying the role of infections of the Federal State Budgetary Institution “Research Institute of Rheumatology named after. V.A. Nasonova”, Doctor of Medical Sciences, Moscow.
Zhilyaev Evgeniy Valerievich, Doctor of Medical Sciences, Professor, Medical Center EMC, Moscow
Lukina Galina Viktorovna, Doctor of Medical Sciences, Professor, Moscow City Scientific Center of the Department of Health, Federal State Budgetary Institution "Research Institute of Rheumatology named after. V.A. Nasonova", Moscow.
Luchikhina Elena Lvovna – leading researcher of the department of early arthritis of the Federal State Budgetary Institution “Research Institute of Rheumatology named after. V.A. Nasonova”, Candidate of Medical Sciences, Moscow.
Muravyov Yuri Vladimirovich - head of the laboratory for studying the safety of anti-rheumatic drugs of the Federal State Budgetary Institution "Research Institute of Rheumatology named after. V.A. Nasonova”, Doctor of Medical Sciences, Professor, Moscow.
Sigidin Yakov Aleksandrovich – leading researcher of the department of early arthritis of the Federal State Budgetary Institution Research Institute of Rheumatology named after. V.A. Nasonova”, Doctor of Medical Sciences, Professor, Moscow.
Chichasova Natalya Vladimirovna – Professor of the Department of Rheumatology, First Moscow Medical University named after. THEM. Sechenov" of the Ministry of Health of Russia, Doctor of Medical Sciences, Professor, Moscow.
All members of the working group declare that there is no conflict of interest in the preparation of clinical recommendations for the management of patients with rheumatoid arthritis.
Target audience of these clinical recommendations:
Pa table. Levels of evidence, indicating the classification of levels of evidence used
High quality meta-analyses, systematic reviews of randomized controlled trials (RCTs) or RCTs with very low risk of bias
Well-conducted systematic meta-analyses or at least one RCT with low risk of bias
Conducted at least one RCT without randomization, low error rate
Well-conducted case-control or cohort studies with moderate risk of confounding effects or bias and moderate probability of causality
Non-analytical studies (eg: case reports, case series, case-control studies)
Expert opinion/clinical experience, fears
At least one meta-analysis, systematic review or RCT assessed as 1a, directly applicable to the target population and demonstrating robustness of the results
body of evidence consisting of study results rated 1b, directly applicable to the target population and demonstrating overall robustness of the results
Body of evidence that includes results from studies rated 2b, directly applicable to the target population and demonstrating overall robustness of the results
extrapolated evidence from studies rated 1a or 1b
A body of evidence that includes findings from studies rated 2a, directly applicable to the target population and demonstrating overall robustness of the results;
extrapolated evidence from studies rated 2b
Level 3 or 4 evidence;
extrapolated evidence from studies rated 2a
The procedure for updating clinical recommendations is at least once every two years.
These clinical recommendations have been developed taking into account the following regulatory documents:
Standard for the provision of primary medical care for rheumatoid arthritis (Order of the Ministry of Health of the Russian Federation No. 1470n dated December 24, 2012);
The procedure for providing medical care to the adult population in the profile “Rheumatology” (Order of the Ministry of Health of the Russian Federation No. 900n dated November 12, 2012).
Criteria for assessing the quality of medical care (Order of the Ministry of Health of the Russian Federation No. 520n dated July 15, 2016 “On approval of criteria for assessing the quality of medical care.”)
State guarantee programs for the provision of high-tech medical care in the specialty of rheumatology and dermatovenerology (Government Decree of December 19, 2015 No. 1382).
B.1. Algorithm for early diagnosis of rheumatoid arthritis at the stages of medical care
B.2. Algorithm for the use of biologically active drugs in RA.
3 mg/kg; 0, 2, 6 weeks, then every 8 weeks
40 mg; every 2 weeks
50 mg; every week
2 mg/kg; 0.4 weeks, then every 8 weeks
400 mg; 0, 2, 4 weeks, then every 4 weeks
10 mg/kg; 0, 2, 4 weeks, then every 4 weeks
125 mg; every week
4 or 8 mg/kg; every 4 weeks
162 mg; every week
Rituximab (iv) 1000 (500) mg; 2 times every 2 weeks
Timing of drug administration
Appendix B.3. Algorithm for induction of remission and maintenance antirheumatic therapy for RA.
Moderate/low activity
Rheumatoid arthritis is an autoimmune rheumatic disease characterized by chronic erosive arthritis and systemic damage to internal organs.
Rheumatoid arthritis is a fairly common disease; in Russia it affects about 1% of the population. Both children and old people can get rheumatoid arthritis, but the disease predominantly affects women of active age (women get rheumatoid arthritis 2-3 times more often than men). The peak onset of the disease is 40-55 years, according to the Institute of Rheumatology, the average age of onset is 47 years.
Doctors are still not clear what causes the disease. What is known is that some people are genetically predisposed to rheumatoid arthritis, but the disease is not transmitted directly from parents to children. In 20-30% of patients, the disease begins after an infection, most often nasopharyngeal. At the same time, many years of searching for a specific microorganism that causes rheumatoid arthritis have not led to success, so there is no reason to consider this disease to be infectious. Smoking has also been shown to increase the risk of developing rheumatoid arthritis. In about a third of patients, the first symptoms appear in full health, for no apparent reason.
Despite the fact that the true cause of rheumatoid arthritis is unknown, medical scientists have been able to uncover many deep mechanisms of the development of the disease. The essence of this serious disease is a disruption of the body's immune system. As a result, some immune cells begin to produce too many substances that cause an inflammatory response, thereby damaging their own tissues. This is a very important point that patients must understand - the basis of rheumatoid arthritis is not “lowered immunity”, but an excessive immune reaction! Therefore, the main therapeutic measures do not consist in “raising immunity,” as many people think, but in normalizing the functioning of the immune system by selectively suppressing abnormally active cells.
Rheumatoid arthritis leads to chronic inflammation of the joints, affecting the periarticular and some other tissues, organs and systems of the body, therefore rheumatoid arthritis is classified as a systemic disease (affecting the entire body, and not any specific organ) diseases. This disease, as a rule, has a progressive course, occasionally interrupted by remissions (periods of temporary improvement). After stress, colds or hypothermia, the patient's condition can worsen significantly. Over time, various complications accompany joint damage. Rheumatoid damage to the heart, lungs, blood vessels and other organs may develop. In the absence of active modern treatment, almost half of patients become disabled within the first five years after diagnosis. Rheumatoid inflammation contributes to the development of atherosclerosis and, as a result, myocardial infarction, stroke, shortening life expectancy by 8-10 years.
The main symptoms at the onset of the disease, as a rule, are pain, swelling, morning stiffness in the symmetrical joints of the hands, wrist joints, and increased skin temperature over them. Over time, the process may involve the feet, ankles, knees, and elbow joints. In some patients, on the contrary, the joints of the legs (knees, ankles) may be affected first, and only then the arms. These signs can easily be confused with symptoms of other joint diseases, so an accurate diagnosis can only be made by a rheumatologist based on a detailed clinical examination, instrumental examination and the presence of specific laboratory parameters.
Inflammation of the joint is manifested by swelling, tenderness and sometimes redness. Chronic inflammation of the joint leads to the destruction of articular cartilage and the development of joint deformation, which in turn impairs its function - pain during movement and stiffness occur.
Symptoms of rheumatoid arthritis are usually persistent and do not go away without treatment, but for a short time at the onset of the disease there may be periods of some improvement in well-being. Spontaneous remission (that is, a state of long-term significant improvement) occurs very rarely. Without treatment, an exacerbation naturally occurs, the activity of the disease increases, and the state of health worsens again. Periods of exacerbation are characterized by weakness, loss of appetite, fever, muscle and joint pain, and joint stiffness, usually most pronounced in the morning after waking up or after periods of rest.
Extra-articular (systemic) manifestations of rheumatoid arthritis usually develop in long-term ill patients, but sometimes occur from the very beginning of the disease. A specific symptom of rheumatoid arthritis is rheumatoid subcutaneous nodules, which most often form on the elbows, but can appear in other places. A rare, severe complication of rheumatoid arthritis is vasculitis (inflammation of the blood vessels). This disease disrupts the blood supply to organs and tissues; most often, vasculitis manifests itself in the formation of dark necrotic areas and ulcers on the fingers and toes. Inflammation of the glands of the eyes and mucous membranes of the mouth leads to the appearance of dryness of these organs, this disease is called “Sjögren’s syndrome.” Rheumatoid inflammation of the lining of the lungs (pleura) is called pleurisy, but is rarely clinically manifested. This is mainly detected by X-ray examination. Similar inflammation can also occur in the lining of the heart (pericarditis). The lungs themselves can also become inflamed, and rheumatoid nodules form in them.
Chronic inflammation in rheumatoid arthritis can lead to a decrease in hemoglobin in the blood - the development of anemia. There may also be an increase (during exacerbations) and a decrease in the number of leukocytes (white blood cells)
Such a variety of symptoms and variants of the disease often makes diagnosis difficult, so I would like to emphasize once again that only a qualified rheumatologist can correctly diagnose rheumatoid arthritis.
If pain and swelling of the joints develops, you should consult a rheumatologist as soon as possible.
It is well known from practice that many patients, when the first symptoms of arthritis occur, self-medicate for a long time, turning to doctors of other specialties (therapists, surgeons, traumatologists, neurologists), so an accurate diagnosis is established late - after 5-6 months, or even more. Accordingly, treatment begins late. During these six months, new joints may become involved in the inflammatory process, and irreversible changes may form in them (erosions, contractures). Therefore, early contact with a rheumatologist is a key point for successful treatment. According to current recommendations, for maximum effectiveness of therapy, it should be started within the first 6-12 weeks from the onset of the first symptoms.
A rheumatologist examines joints, skin, and other organs and systems. Then a certain range of tests is prescribed to confirm the diagnosis and determine the degree of disease activity, radiography and other research methods. Recognition of RA is carried out on the basis of a doctor’s assessment of joint damage, detection of erosions of the articular surfaces during X-ray examination, and detection of rheumatoid factor in the blood serum (a special protein that appears in most patients). ESR, levels of fibrinogen, and C-reactive protein increase in the blood.
Unfortunately, there are no absolutely specific (pathognomonic) signs of rheumatoid arthritis. Thus, a blood test for rheumatoid factor in some patients throughout their lives is persistently negative, although according to other symptoms they have obvious rheumatoid arthritis. Therefore, diagnosis is always carried out using a set of data obtained during the examination, and not using any one analysis or study.
In 30% of patients with suspected rheumatoid arthritis, the diagnosis cannot be clarified at the first visit to the doctor; repeated examinations and monitoring of the patient are required.
Currently, new immunological and instrumental research methods are increasingly being used for the early diagnosis of rheumatoid arthritis. A blood test for anticitrullinated antibodies is a new laboratory test that helps in cases where the result of a test for rheumatoid factor is negative or doubtful. Magnetic resonance imaging (MRI) of the joints can detect changes characteristic of arthritis much earlier than conventional x-rays. Ultrasound examination (ultrasound) of joints well reveals the presence of fluid in the joint and foci of inflammation in the periarticular tissues. The use of new techniques does not exclude, but rather complements, standard examination in complex cases.
Drug therapy is the main treatment for rheumatoid arthritis. This is the only way to slow down the development of the inflammatory process and maintain mobility in the joints. All other treatment methods - physiotherapy, diet, physical therapy - are only complementary and without drug treatment are not able to have a significant impact on the course of the disease.
The main goal of treatment is to slow and possibly stop the progression of the disease, preserve joint function and improve the patient's quality of life. To do this, it is necessary to suppress the inflammatory process, relieve pain, and prevent exacerbations and complications.
With early diagnosis and early initiation of drug therapy with modern antirheumatic drugs, more than 50% of patients can achieve clinical remission, that is, a state when there is no active inflammation in the joints and the patient feels practically healthy. At the same time, rheumatoid arthritis is a chronic disease prone to exacerbations, therefore, to maintain the achieved success, long-term therapy with maintenance doses of medications is required, and the question of the possibility of a complete cure still remains open.
The treatment of RA is based on the use of basic anti-inflammatory drugs. These include a large number of drugs with different chemical structures and pharmacological properties, such as methotrexate, leflunomide, sulfasalazine, etc. They are united by the ability, to a greater or lesser extent and through various mechanisms, to suppress inflammation and/or pathological activation of the immune system.
The most active of the basic anti-inflammatory drugs is methotrexate, which usually begins therapy for rheumatoid arthritis. Genetically engineered biologics are typically added to these methotrexate or other drugs (eg, leflunomide) when there is insufficient effectiveness.
The therapeutic effect of methotrexate develops slowly (over 1.5-2 months or more), but is very persistent. Maximum improvement is usually achieved by the 6th month of treatment, a good clinical effect is observed in 60-70% of patients. To improve the tolerability of treatment or to achieve the effect more quickly, the use of a subcutaneous dosage form of methotrexate is recommended. During treatment with methotrexate, it is necessary to take folic acid at least 5 mg per week, no earlier than one day after taking methotrexate.
If there are contraindications for the use of methotresate or poor tolerability of treatment, leflunomide or sulfasalazine may be prescribed.
To maintain the achieved improvement, the patient must take maintenance (low) doses of these drugs for a long time (if necessary, several years).
In general, treatment with these drugs is well tolerated, but requires monitoring regarding blood patterns and liver function.
A modern method of treating rheumatoid arthritis is the use of so-called genetically engineered biological drugs. Genetically engineered biological preparations (not to be confused with dietary supplements!) are protein molecules produced using sophisticated biotechnologies that selectively suppress the activity of substances (mediators) involved in the development of chronic inflammation. In Russia, several genetically engineered biological drugs are registered for the treatment of rheumatoid arthritis: infliximab, adalimumab, etanercept, golimumab, certolizumab, abatacept, tocilizumab, rituximab. Genetically engineered biological drugs are potent and are administered as subcutaneous injections or intravenous infusions. More recently, a new drug, tofacitinib, has appeared, which is prescribed in the form of tablets, but is close in action to genetically engineered biological drugs.
Glucocorticoid hormones can have a rapid anti-inflammatory effect. Typically, glucocorticoid drugs (prednisolone or methylprednisolone) are prescribed for high disease activity in low doses (no more than 2 tablets per day), followed by a dose reduction to 1 tablet or less, or completely discontinued when the effect is achieved. Therefore, with modern approaches to treatment, the prevailing opinion that glucocorticoid hormonal therapy is dangerous is generally unfounded. At the same time, glucocorticoid hormones require very competent handling (for example, the drug cannot be abruptly discontinued), so the decision to prescribe glucocorticoid hormonal therapy is made individually for each patient. If the disease activity is very high, pulse therapy (injection of a high dose of hormones intravenously) can be used to relieve an exacerbation.
Nonsteroidal anti-inflammatory drugs (NSAIDs for short) are an important component of the treatment of rheumatoid arthritis. The most commonly used are diclofenac, nimesulide, meloxicam, ketoprofen, and celecoxib to reduce pain and stiffness in the joints. NSAIDs are prescribed at an early stage of the disease, when the effect of treatment with basic anti-inflammatory drugs has not yet developed and it is necessary to control symptoms in order to give the patient the opportunity to move, work, and care for himself. After complete improvement has been achieved during therapy with basic anti-inflammatory drugs, NSAIDs can be discontinued in many patients. At the same time, a significant number of patients, especially those with advanced rheumatoid arthritis, are forced to continue treatment with NSAIDs for a very long time, almost constantly, due to the persistence of pain in the joints.
Often patients start taking these medications on their own and find that they help well. However, it must be borne in mind that NSAIDs do not affect the course of the disease (mainly symptomatic effect), and can cause stomach ulcers and gastrointestinal bleeding, increased blood pressure, etc.). The greatest risk of developing side effects from NSAIDs are elderly patients, smokers, and those suffering from diseases of the gastrointestinal tract and cardiovascular system. Therefore, to prescribe NSAIDs, it may also be necessary to consult a doctor.
Monitoring the patient's condition and monitoring the safety of treatment
Treatment of rheumatoid arthritis with medications can give very good results, but requires good monitoring, which should be carried out by a qualified rheumatologist.
A whole system of such control has been developed. To obtain the best results of therapy, a rheumatologist periodically evaluates its effectiveness. The patient must visit the doctor at least once every 3 months at the beginning of treatment. In addition to the examination, blood tests are prescribed, and x-rays of the joints are taken annually to assess the progression of the disease.
At each visit, depending on the activity of the inflammatory process and other indicators, the treatment regimen may change according to the decision of the rheumatologist (the dose of medications may be reduced or increased, new drugs may be added, etc.). In this case, a trusting relationship between the patient and the doctor is extremely important, as is the understanding that treatment is a complex and serious job, often requiring effort and patience. After achieving a good effect from therapy with maintenance doses of drugs, it is recommended to see a rheumatologist at least once every 6 months.
The other side of control is the assessment of indicators to ensure the safety of treatment. The safety monitoring scheme depends on which drugs are prescribed to the patient. So, when taking methotrexate or leflunomide, liver function and the number of blood cells are monitored. When prescribing genetically engineered biological drugs, their intravenous administration is carried out in a specially equipped treatment room under the supervision of a physician. All genetically engineered biologics and tofacitinib may reduce resistance to infection. For patients taking NSAIDs for a long time, gastroscopy should be performed if necessary.
There are treatment limitations. During therapy with methotrexate and leflunomide, alcohol intake is not recommended. It is advisable to avoid contact with infectious patients. Most anti-inflammatory drugs require protection against pregnancy (this is possible after discontinuation of treatment).
There are a number of methods that improve the tolerability of certain medications. To reduce the negative effect on the stomach, antiulcer drugs (most often omeprazole) can be prescribed along with non-steroidal anti-inflammatory drugs. To improve the tolerability of methotrexate, the use of a special vitamin, folic acid, is recommended. When steroid hormones are prescribed, calcium supplements and other drugs are given in parallel to prevent osteoporosis, a weakening of bone tissue that can occur with long-term hormonal therapy. Special vaccines are used to protect against infections.
Unfortunately, in many cases, patients are overly wary of drug therapy; there is an opinion that “chemistry cures one thing, cripples another.” This is fundamentally wrong for a number of reasons. Firstly, although it is possible that adverse reactions may occur, the likelihood of their development is relatively small; most patients can continue treatment for a long time without any adverse reactions. Secondly, for most medications the monitoring system is well developed (it is described in detail in reference books and package inserts) and allows for active detection of adverse reactions even before they become hazardous to health. Thirdly, the risk of developing complications of the disease itself is much more serious than the risk of developing undesirable reactions from therapy.
Non-pharmacological treatments
In addition to drug treatment, it is recommended to monitor your own diet, as well as perform therapeutic exercises.
The diet of a patient with rheumatoid arthritis should be complete, with sufficient amounts of protein and calcium. This is important for several reasons: 1) with active inflammation in the body, energy and protein consumption increases; 2) with rheumatoid arthritis, muscle atrophy quickly develops (sharp weight loss and weakening of muscles), which contribute to the appearance of joint deformities; 3) anti-inflammatory drugs can weaken the mucous membrane of the stomach and intestines, and the natural defense in this case is a sufficient amount of protein in food; 4) protein and calcium - prevention of osteoporosis (disorders of bone structure that accompany arthritis). Preference is given to proteins of animal origin: milk, lactic acid drinks, cottage cheese, cheese, eggs, meat, fish. Spicy foods should be avoided. Meat and fish dishes are boiled in water, steamed, stewed, or baked in the oven.
It is recommended to ensure the predominance of vegetable oils containing polyunsaturated fatty acids in the diet - this can contribute to a more favorable course of the inflammatory process.
A sufficient amount of vegetables, unsweetened fruits and berries is recommended
Regular exercise helps maintain joint mobility and strengthens muscles. Swimming is an optimal form of exercise because it eliminates the gravitational load on the joints.
Participation in schools for patients with rheumatoid arthritis is strongly recommended - this significantly increases the effectiveness of treatment.