Rheumatoid arthritis

Rheumatoid arthritis (polyarthritis progressiva primaria chronica) is a chronic inflammation characterized by synovial hypertrophy with infiltration by inflammatory cells, destruction of articular cartilage and decalcification of bone (osteoporosis). Rheumatoid arthritis is characterized by the production of antibodies (RF - rheumatoid factor, ANF - antinuclear factors) and acute phase proteins. Clinically, rheumatoid arthritis can be described as a symmetrical polyarthritis that predominantly affects the small joints of the hand and radio-carpal joints, with prolonged morning stiffness.

Occurrence
Rheumatoid arthritis is 2-3 times more common in women. Symptoms develop most often between the ages of 20 and 40. However, there is also juvenile rheumatoid arthritis, which mainly affects large joints.

Etiology
Rheumatoid arthritis is an autoimmune inflammation that is often associated with the HLA-DR 4 or DR 1 immunophenotype. The initiator is thought to be a currently unknown microbial pathogen (EBV, retroviruses, parvoviruses, borrelia, etc. are being considered). It is not exactly known against which antigen the autoimmune reaction is directed - probably against type II collagen or against cartilage glycoprotein 39 (it binds to DR 4). Rheumatoid factor, the antibodies against the Fc fragment of IgG,  occurs in 80% of patients.

Pathological-anatomical changes
The first changes are in the synovium, then in the fluid, later on the cartilage and finally para-articular involvement. First, serofibrinous intra-articular inflammation occurs, then a panus develops. The panus is a villi-swollen synovial membrane in which connective tissue and blood vessels proliferate excessively. It covers the articular cartilage, separating it from the nourishing synovial fluid. As a result, the chondrocytes die and the subchondral bone mass erodes. If the panus growing from opposite sides of the joint fuse, it can further change fibrotic, ossify, and eventually ankylosis.

Another morphological manifestation of rheumatoid arthritis are rheumatic nodules, which occur mainly in the subcutaneous tissue. Histologically, they consist of three layers:


 * centrally there is necrotic tissue


 * around it is a layer of palisade fibroblasts and multinucleated cells


 * peripherally there is a layer of chronic inflammation



Symmetric polyarthritis
Initially, involvement of the joints of the hand starts from the periphery.

Proximal interphalangeal → "bottle-shaped fingers"; metacarpophalangeal; radiocarpal.

It usually does not affect the distal interphalangeal. Later, ulnar deviation of the fingers, swan- type deformities (hyperextension in the proximal interphalangeal joint and flexion in the distal interphalangeal joint) and buttonhole - type deformities are typical (flexion in the proximal interphalangeal joint and hyperextension in the distal interphalangeal joint).

The joints are painful at rest, during palpation and movement, morning stiffness occurs (agitation lasts longer than an hour). There are classic signs of inflammation on the joints, except for redness. In more severe cases, chronic inflammation can lead to volar subluxation of the wrists and rupture of the finger tendons. The activity of the process is fluctuating, often depending on the humidity.

Disability of individual joints

 * Elbow injury - flexion contractures.


 * Shoulder joints - rupture of the rotator cuff.


 * Hip joints - affected less often.


 * Knee joints - angular deformities and flexion contractures. Fluid can penetrate the popliteal bursa - Baker's cyst. Hammer toes and hallux valgus are typical findings on the foot.

Spine
Affected mainly in the neck, the atlantoaxial joint is severely affected by subluxation (neck and head pain, spinal cord compression). Sudden death can be a complication of subluxation. An X-ray should be performed prior to each intubation operation if atlantoaxial subluxation is suspected.

Temporomandibular joint involvement
It causes chewing pain.

The course of the disease
There are 3 types of the course of the disease:


 * monocyclic - one cycle of the disease followed by remission lasting more than 1 year;


 * polycyclic - gradually progressing with episodes of incomplete remissions (most common);


 * progressive - sustained progression without remissions.

Extra-articular involvement
The disease may be accompanied by extra-articular disorders:

rheumatic nodules (in the subcutaneous tissue, especially above the elbows and above the proximal edge of the ulna), mostly multiple, usually painful nodules, up to several cm in size;


 * tendonsynovitis (mainly in the hands, rupture of tendons with the development of deformities - swan neck, buttonhole);


 * osteoporosis (initially periarticular, later diffuse - pathological fractures);


 * secondary amyloidosis (AA, especially kidney damage);


 * haematological abnormalities (mainly anemia, thrombocytosis);


 * eye disorders (iritis, iridocyclitis,  keratoconjunctivitis);


 * damage to the skin, heart, blood vessels, nerves, lungs, etc.

Laboratory findings

 * Inflammatory markers: (↑ FW, CRP ).


 * Antibodies:  rheumatoid factor (RF) - antibody (mostly IgM) against Fc fragments of IgG, detection by latex-fixation test;  anti-CCP - antibody against cyclic citrullinated peptide, are more specific for RA than rheumatoid factors;  APF - antiperinuclear factors;  ANF ​​- antinuclear factors.


 * Punctate (biochemically RF, high content of polymorphonuclear cells).

X-ray changes

 * 1) Early - swelling of the soft tissues near the joints, periarticular osteoporosis, marginal bone erosion.
 * 2) Late - narrowing of the joint space, diffuse osteoporosis, deformities, bone ankylosis.

Four Steinbrocker stages were introduced for the evaluation of X-rays.

Stage	Characteristics

Stadium I	periarticular osteoporosis, no destruction

Stadium II	slight signs of destruction, without deformities

Stadium III	cartilage and bone destruction, deformities

Stadium IV	fibrous or bone ankylosis

Furthermore, scintigraphy can be used in diagnosis (it will show the distribution of disability in individual joints).

Criteria for diagnosis
The presence of 4 of 7 criteria is important for the diagnosis of rheumatoid arthritis:


 * morning stiffness


 * arthritis 3 or more areas


 * arthritis of the joints of the hand (RC, MCP, PIP)


 * symmetric arthritis


 * rheumatoid nodules


 * rheumatoid factor (RF)


 * X-ray changes

Regime measures
In the acute stage, bed rest, prevention of contractures, analgesic splints, etc.

Physical therapy and rehabilitation
Maintaining the range of motion in the joint, preventing muscle weakness.

Pharmacotherapy
The basis of pharmacological treatment is disease modifying antirheumatic drugs (DMARDs ).

Disease-modifying drugs (DMARDs)
I belong to two groups of drugs:


 * conventional


 * biological treatment

Conventional drugs


 * methotrexate : Methotrexate- the most commonly used drug, the drug of first choice,


 * leflunomide : leflunomide- a pyrimidine nucleotide inhibitor, has methotrexate-like effects,


 * sulfasalazine : sulfasalazine,


 * hydroxychloroquine : hydroxychloroquineand chloroquine : chloroquine- have the weakest effect.

Biological treatment


 * TNFα inhibitors - etanercept : etanercept, infliximab : infliximab, adalimumab : adalimumab, golimumab : golimumab, certolizumab pegol: certolizumab pegol


 * rituximab : rituximab- a chimeric monoclonal antibody against the CD20 molecule,


 * abatacept : abatacept- blocks T-cell activation by blocking the costimulatory signal,


 * tocilizumab National Drug Administration: tocilizumab- an anti-IL-6 receptor antibody,


 * anakinra : Anakinra- IL-1 receptor antagonist.

Other drugs


 * non-steroidal anti-inflammatory drugs and analgesics - only symptomatic drugs - COX 1 inhibitors - diclofenac : diclofenac, indomethacin : indomethacin, selective COX 2 inhibitors - nimesulide : nimesulide, coxibs ;


 * corticoids - systemic (prednisone : prednisone) or intraarticularly (triamcinolone : triamcinolone) - to bridge the period until the onset of action of DMARDs.

Surgical treatment

 * synovectomy (possibly also radiation application of the isotope yttrium to the joint)


 * total endoprosthesis


 * arthrodesis (fixation of the joint in an advantageous position, removal of pain, most often the radiocarpal area).