Etiology and pathogenesis
The exact cause of the disease remains a mystery, which is why it is classified as idiopathic. The most plausible theory suggests that an unknown infectious agent (or another external factor) triggers a powerful hypersensitivity reaction with a pronounced autoimmune component. Strong emotional stress and physical trauma often act as triggering factors.
The pathogenesis of the disease unfolds in several stages:
- Immunological stage. Local blood flow increases in the joint area. Immunocompetent cells and antibodies rush there. An antigen-antibody reaction occurs, causing infiltration of the synovial membrane around the vessels, leading to the development of synovitis. The process becomes chronic due to the continuous production of cytokines and lymphokines that attract increasingly more cells.
- Destructive phase. A pannus forms in the joint—an aggressive inflammatory granulation tissue. It literally creeps onto healthy areas of bone and cartilage, destroying them. This leads to the formation of erosions, intra-articular adhesions, and finally, complete immobility—ankylosis.
- Extra-articular lesions. Systemic manifestations are caused by the deposition of immune complexes directly in the walls of blood vessels, causing systemic vasculitis.
Articular syndrome: clinical picture
The disease has a wave-like course, with periods of exacerbation alternating with remissions. In most cases, the disorder debuts with signs of small joint polyarthritis accompanied by fever. The pain has a clear circadian rhythm: it becomes most intense in the second half of the night and morning hours.
Typical localization in the early stages:
- Proximal interphalangeal joints.
- Metacarpophalangeal joints of the hands.
- Metatarsophalangeal joints of the feet.
During exacerbation, joints swell, become painful, and their mobility is severely limited. A characteristic sign is morning stiffness of movements (in pronounced cases, it lasts for more than 1 hour and subsides only after taking medication).
As it progresses, large joints (knee, ankle, wrist) and even the spine become involved. Marked atrophy of the interosseous muscles develops. Combined with anatomical deformities (such as ulnar deviation), this creates the specific appearance of a "rheumatoid hand".
Systemic (extra-articular) manifestations
In addition to the joints, the pathological process affects almost all body systems, indicating high inflammatory activity:
- Skin and soft tissues: formation of rheumatoid nodules—subcutaneous indurations, most commonly on the extensor surface of the elbow joints.
- Cardiovascular system: conduction disorders, inflammation of the heart membranes (pericarditis), and development of valve defects due to endocarditis (e.g., mitral regurgitation).
- Respiratory system: fibrosing alveolitis (appears on X-ray as "honeycomb lung", causes restrictive respiratory failure), pleurisy.
- Kidneys: development of glomerulonephritis-type nephropathy or amyloidosis, which manifests as proteinuria and ultimately leads to chronic kidney disease (CKD). Toxic kidney damage from medications is also possible.
- Organ of vision: inflammatory processes (episcleritis, keratitis, conjunctivitis).
- Nervous system: peripheral neuropathy with impaired pain sensitivity.
Of particular note is Felty's syndrome—a severe symptom complex including the classic triad: arthritis itself, enlargement of lymph nodes and the spleen (splenomegaly), and a decrease in blood leukocyte count (leukopenia).
Diagnostics and treatment principles
Comprehensive diagnosis is based on evaluating the clinical picture (ARA criteria: symmetric arthritis of 3 or more hand joints lasting longer than 6 weeks), the presence of rheumatoid nodules, and laboratory and instrumental data.
Laboratory markers: Complete blood count reveals hypochromic anemia, neutrophilic leukocytosis, and an elevated ESR. Blood chemistry shows increased fibrinogen, C-reactive protein (CRP), and dysproteinemia (elevation of $\alpha_2$- and $\gamma$-globulins). A specific marker is serum rheumatoid factor.
Radiological stages: Changes are visible after a few months. First, periarticular osteoporosis appears, followed by joint space narrowing and marginal erosions (usures). Finally, subluxations and bony ankyloses are visualized.
Therapy: The goal of treatment is to suppress inflammation and prevent deformities. Therapeutic exercise (physical therapy) is mandatory to preserve mobility. Medical support includes nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen) with monitoring of stomach and kidney status, as well as glucocorticoids for severe systemic disease. The most critical step is prescribing disease-modifying antirheumatic drugs (cytostatics, gold salts, sulfasalazine) from the very onset of the disease.
Briefly: answers to topical questions
What radiological stages (Steinbrocker classification) are distinguished in rheumatoid arthritis?
Four radiological stages according to Steinbrocker (modified) are distinguished in rheumatoid arthritis.
- Stage 1—periarticular osteoporosis, isolated cystic radiolucencies of the bone tissue, and minor joint space narrowing.
- Stage 2—osteoporosis combined with joint space narrowing, possible isolated erosions.
- Stage 3—joined by multiple erosions and joint subluxations.
- Stage 4—all signs of the previous stage, plus the formation of bony ankylosis.
Which drugs are used as disease-modifying therapy for rheumatoid arthritis?
Synthetic disease-modifying antirheumatic drugs are used as disease-modifying therapy for rheumatoid arthritis.
Sources indicate the following groups of csDMARDs:
- folic acid analogues;
- intestinal anti-inflammatory drugs: aminosalicylic acid and analogues;
- selective immunosuppressants;
- antimalarial drugs.
Sources name the following specific drugs and agents for disease-modifying therapy of rheumatoid arthritis:
- methotrexate;
- sulfasalazine;
- penicillamine;
- gold preparations;
- chloroquine or hydroxychloroquine;
- azathioprine.
Which antibodies, in addition to rheumatoid factor, are used for the specific diagnosis of rheumatoid arthritis?
For the specific diagnosis of rheumatoid arthritis, in addition to rheumatoid factor, antibodies to citrullinated proteins (anti-CCP) are determined.
The most frequently detected types include:
- Antibodies to cyclic citrullinated peptide—anti-CCP.
- Antibodies to modified citrullinated vimentin—anti-MCV.
These autoantibodies recognize antigenic determinants of the amino acid citrulline, which is formed during the post-translational modification of proteins.
Which diseases require differential diagnosis with rheumatoid arthritis?
According to the provided sources, the differential diagnosis of rheumatoid arthritis includes diseases and conditions that may present with a similar articular syndrome:
- osteoarthritis, including polyarthrosis and gonarthrosis;
- crystalline and microcrystalline arthritides, including gouty arthritis and chronic tophaceous gout;
- septic arthritis;
- spondyloarthropathies;
- psoriatic arthritis;
- reactive arthritides;
- chronic liver diseases, including active hepatitis and cirrhosis, which can mimic systemic connective tissue diseases, including rheumatoid arthritis.
What criteria are used by modern rheumatological communities (ACR/EULAR) to diagnose rheumatoid arthritis?
To establish a diagnosis using the ACR/EULAR classification criteria, a point-based scoring system evaluating four domains of features is used.
- Clinical joint involvement — number and type of involved joints (from 0 to 5 points).
- Specific autoantibodies — presence and titer of rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (anti-CCP) (from 0 to 3 points).
- Acute-phase reactants — elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) (0 or 1 point).
- Duration of synovitis — less than 6 weeks or 6 weeks or more (0 or 1 point).
Felty's syndrome triad: Arthritis + Lymphadenopathy/Splenomegaly + Leukopenia.
Class and exam questions
What is pannus and why is it dangerous?
Pannus is an inflammatory granulation tissue that forms within the joint. It aggressively invades healthy areas of cartilage and bone, causing their destruction, erosion formation, and subsequent fusion (ankylosis).
Which joints are affected at the very onset of the disease?
At onset, small joints are most commonly and symmetrically affected: the proximal interphalangeal and metacarpophalangeal joints of the hands, as well as the metatarsophalangeal joints of the feet.
When is it appropriate to initiate disease-modifying therapy?
Disease-modifying antirheumatic drugs (DMARDs) (such as methotrexate or gold salts) must be prescribed in the earliest stages of the disease to halt the progression of joint destruction.
What else to study on this topic
- Pathogenesis of immune complex formation and systemic vasculitis development
- Mechanisms of specific hand deformity development
- Differential diagnosis of articular syndrome
- Inflammatory activity criteria based on laboratory tests
- Iatrogenic complications: NSAID-induced gastropathy and renal toxicity
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