Rheumatology and orthopedics

Rheumatoid Arthirits Definition, Causes, Pathophysiology, clinical features, diagnosis and treatment

  • Clinicals
  • Rheumatology and orthopedics
  • 2021-10-09 09:57:33
  • 13 minutes, 8 seconds

Rheumatoid Arthirits Definition, Causes, Pathophysiology, clinical features, diagnosis and treatment

Arthritis is a descriptive term applied to more than 100 rheumatic diseases, ranging from localized, self-limiting conditions to those that are systemic autoimmune processes. Arthritis can affect persons of all age groups and is the second leading cause of disability.

Although the condition cannot be cured completely, much can be done to control its progress.

In systemic rheumatic diseases—those affecting body systems in addition to the musculoskeletal system, the inflammation is primary, resulting from an immune response.

In rheumatic conditions limited to a single or few diarthrodial joints, the inflammation is secondary, resulting from a degenerative process and the resulting joint irregularities that occur as the bone attempts to remodel itself

Rheumatoid arthritis is defined as a chronic systemic inflammatory disease characterized by bilateral involvement of synovial or diarthrodial joints

The initial joint changes involve the synovial cells that line the joint. In the process, the inflammatory cells accumulate and angiogenesis and pannus formation follow proceeding to cover the articular cartilage and isolate it from its nutritional synovial fluid take place.

Causes and pathogenesis of rheumatic arthritis

The exact cause of rheumatoid arthritis is idiopathic meaning it isn't exactly known. Although there is evidence of a genetic predisposition and immunologically mediated joint inflammation.

The development of rheumatoid arthritis is initiated in a genetically predisposed person by the activation of a T-cell–mediated response to an immunologic trigger, such as a microbial agent.

It has been shown that certain major histocompatibility complex (MHC) genes are expressed in a nonrandom manner in persons with RA.

An important genetic locus that predisposes to RA is present on the human leukocyte antigen (HLA) loci on the MHC class II molecules, with a specific set of HLA DR alleles (DR4, DR1, DR10, DR14) being consistently increased in persons with RA.

These HLA DR alleles form a shared epitope in the hypervariable segment of the HLA-DRB1 gene, which forms a rheumatoid pocket on the HLA molecule.

Pathogenesis of rheumatoid arthritis

The pathogenesis of RA is an aberrant immune response that leads to synovial inflammation and destruction of the normal joint architecture.  This process is usually initiated by the activation of helper T cells, the release of cytokines, and antibody formation. The majority of people suffering from rheumatoid arthritis have detectable, self-produced antibodies (IGF) known as the rheumatoid factor (RF). This rheumatoid factor reacts with a fragment of immunoglobulin G (IgG) to form immune complexes.

This Immune complexes of immunoglobulin G and immunoglobulin F (Ig RF + IgG) together with complement proteins are found in the synovium, synovial fluid, and extra-articular lesions.

When lab tests are done in patients suffering from rheumatoid factor, these individuals with RA may be seronegative without any Ig RF present in their serum.

Conversely, the presence of a high RF titer is associated with severe disease and systemic complications.

At the basic cellular level, neutrophils, macrophages, and lymphocytes are attracted to the area. These neutrophils and macrophages phagocytize the immune complexes and, in the process, they release lysosomal enzymes capable of causing destructive changes in the joint.

The inflammatory response that follows attracts additional inflammatory cells, setting into motion a chain of events that perpetuates the condition. As the inflammatory process progresses, the synovial cells and subsynovial tissues undergo reactive hyperplasia. Vasodilation and increased blood flow cause warmth and redness.
The joint swelling that occurs is the result of the increased capillary permeability that accompanies the inflammatory process.

Characteristics of rheumatoid arthritis

The characteristic of rheumatoid arthritis is the development of an extensive network of new blood vessels in the synovial membrane that contributes to the advancement of rheumatoid synovitis.

This destructive vascular granulation tissue, which is called pannus, extends from the synovium to involve the “bare area,” which is a region of unprotected bone at the junction between cartilage and subchondral bone.

Pannus is a feature of RA that differentiates it from other forms of inflammatory arthritis.

The inflammatory cells found in the pannus have a destructive effect on the adjacent cartilage and bone. Eventually, pannus develops between the joint margins, leading to reduced joint motion and the possibility of eventual ankylosis.

With the progression of the disease, joint inflammation and the resulting structural changes lead to joint instability, muscle atrophy from disuse, stretching of the ligaments, and involvement of the tendons and muscles.

The effect of the pathologic changes on joint structure and function is related to the degree of disease activity, which can change at any time. These destructive changes in the joints are irreversible.

Signs and symptoms of rheumatoid arthritis

Classical features of rheumatoid arthritis are associated with extra-articular as well as articular manifestations.

Its onset is insidious in nature and is marked with systemic features such as excessive fatigue, loss of appetite, weight loss, and generalized body malaise and stiffness.

Rheumatoid arthritis characterized by exacerbations and remissions may involve only a few joints for brief durations, or it may become relentlessly progressive and debilitating.

Joint Manifestations.

RA has a characteristic symmetrical and polyarticular Joint involvement consisting of any diarthrodial joint.

Patients may complain of joint pain and stiffness that lasts for 30 minutes and frequently for several hours.

There is a limited joint motion that occurs early in the disease mainly as a result of joint pain; later, this limited joint motion results from fibrosis.

The commonly affected joints initially are the fingers, hands, wrists, knees, and feet. Later, other diarthrodial joints may become involved.

Spinal involvement usually is limited to the cervical region. In the hands, there usually is bilateral and symmetric involvement of the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in the early stages of RA; the distal interphalangeal (DIP) joints rarely are affected.

The fingers often take on a spindle-shaped appearance because of inflammation of the PIP joints.

Progressive joint destruction may lead to subluxation or a dislocation of the joint resulting in misalignment of the bone ends and instability of the joint and limitation of movement.

Swelling and thickening of the synovium can result in stretching of the joint capsule and ligaments. When this occurs, muscle and tendon imbalances develop, and mechanical forces applied to the joints through daily activities produce joint deformities.

In the metacarpophalangeal joints, the extensor tendons can slip to the ulnar side of the metacarpal head, causing ulnar deviation of the fingers.

Subluxation of the MCP joints may develop when this deformity is present.

Hyperextension of the PIP joint and partial flexion of the DIP joint is called a swan neck deformity.


After this condition becomes fixed, severe loss of function occurs because the person can no longer make a fist.

Flexion of the PIP joint with hyperextension of the DIP joint is called a boutonnière deformity.


The knee is one of the most commonly affected joints. Active synovitis may be apparent as visible swelling that obliterates the normal contour over the medial and lateral aspects of the patella.

The bulge sign, which involves milking fluid from the lateral to the medial side of the patella, may be used to determine the presence of excess fluid when it is not visible.
Joint contractures, instability, and genu valgus (knock-knee) deformity are other possible manifestations.

Severe quadriceps atrophy can contribute to the disability.

A Baker cyst may develop in the popliteal area behind the knee. This is caused by enlargement of the bursa but does not usually cause symptoms unless the cyst ruptures, in which case symptoms mimicking thrombophlebitis appear.

Ankle involvement can limit flexion and extension, which can create difficulty in walking. Involvement of the metatarsophalangeal joints can cause subluxation, hallux valgus, and hammertoe deformities.

Neck discomfort is common.

In rare cases, the long-standing disease can lead to neurologic complications such as occipital headaches, muscle weakness, and numbness and tingling in the upper extremities.

Extra-articular Manifestations.

Although characteristically a joint disease, RA can affect a number of other tissues. Extraarticular manifestations probably occur with a fair degree of frequency but usually are mild enough to cause few problems.

They are most likely to occur in persons who have the RF.

Because RA is a systemic disease, it may be accompanied by complaints of fatigue, weakness, anorexia, weight loss, and low-grade fever when the disease is active.
The erythrocyte sedimentation rate (ESR), which commonly is elevated during inflammatory processes, has been found to correlate with the amount of disease activity.

Anemia associated with a low serum iron level or low iron-binding capacity is common. This anemia usually is resistant to iron therapy.

Rheumatoid nodules are granulomatous lesions that develop around small blood vessels. The nodules may be tender or non-tender, movable or immovable, and small or large. Typically, they are found over pressure points such as the extensor surfaces of the ulna. The nodules may remain or resolve spontaneously.

Vasculitis, or inflammation of small and medium-sized arteries, is an uncommon manifestation of RA in persons with a long history of active arthritis and high titers of RF.

Manifestations include ischemic areas in the nail fold and digital pulp that appear as brown spots.

Ulcerations may occur in the lower extremities, particularly around the malleolar areas.

In other instances, neuropathy may be the only symptom of vasculitis.

The visceral organs, such as the heart, lungs, and gastrointestinal tract, also may be affected.

Other extra-articular manifestations include eye lesions such as episcleritis, and scleromalacia, which is due to scleral nodules and is capable of causing retinal detachment, and pulmonary and cardiac complications (pleuritis and pericarditis).

Diagnosis and Treatment

Good patient history and clinical examination combined with lab tests are sufficient to elicit the diagnosis of rheumatoid arthritis.

At the time of taking patient history, the information should be elicited regarding the duration of symptoms, systemic manifestations, stiffness, and family history.

American Rheumatism Association  criteria for diagnosis of RA

The criteria for RA developed by the American Rheumatism Association are useful in establishing the diagnosis5.

At least four of the criteria must be present to make a diagnosis of RA.

In the early stages, the disease often is difficult to diagnose.

On physical examination, the affected joints show signs of inflammation, swelling, tenderness, and possibly warmth and reduced motion.

The joints have a soft, spongy feeling because of the synovial thickening and inflammation.

Body movements may be guarded to prevent pain.

Changes in joint structure usually are not visible early in the disease.

The RF test results are not diagnostic for RA, but they can be of value in differentiating RA from other forms of arthritis.

A person can have RA without the presence of RF.

Disease severity and activity tend to correlate with RF levels; patients with high RF levels tend to have a significantly higher frequency of extra-articular.

The detection of anti-cyclic citrullinated peptide (CCP) antibodies may be more useful for diagnosing RA because of its higher specificity.

Citrulline is an unusual amino acid that is generated by the enzymatic digestion of arginine.

Anti-CPP antibodies are a good prognostic marker for the disease and discriminate between erosive and non-erosive forms of the disease.

Radiologic findings also are not diagnostic in RA because joint erosions often are not seen on radiographic images in the early stages of the disorder.

Synovial fluid analysis can be helpful in the diagnostic process. The synovial fluid has a cloudy appearance, the white blood cell count is elevated as a result of inflammation, and the complement components are decreased.

Treatment of rheumatoid arthritis

The treatment goals for a person with RA are to reduce pain, minimize stiffness and swelling, and maintain mobility.

The treatment plan includes education about the disease and its treatment, rest, therapeutic exercises, and medications.
The rest of the specific joints is recommended to relieve pain.

Emotional rest helps muscles relax and is often useful for persons who find that emotional stress increases discomfort.

Range-of-motion exercises involve the active and passive movement of joints. Isometric (muscle tensing) exercises may be used to strengthen muscles

Aerobic exercise and muscle-strengthening exercises can be an important component of the treatment regimen of selected patients.

Proper posture, positioning, and body mechanics, and the use of supportive shoes can provide further comfort.

Pharmacological therapy

The goals of pharmacologic therapy for RA are to reduce pain, decrease inflammation, maintain or restore joint function, and prevent bone and cartilage destruction.

Drugs used to achieve these goals are classified as those that provide relief of arthritis symptoms and those that have the potential for modifying the course of the disease.

Disease-modifying antirheumatic drug therapy should be used when the diagnosis of RA is established and before erosive changes appear on radiography.

Early treatment is based on the theory that T-cell–dependent pathways, which manifest early in the inflammatory process, are more responsive to treatment than later in the process when disease progression is controlled by activated fibroblasts and macrophages, and the disease may be more resistant to treatment.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used early in the treatment of RA. They inhibit cyclooxygenase (COX)-mediated synthesis of prostaglandins, which have a damaging effect on joint structures.

NSAIDs, including salicylates (e.g., aspirin), provide analgesic and anti-inflammatory effects.

The selective COX-2 inhibitors (e.g., celecoxib) were developed with the goal of decreasing gastrointestinal adverse effects.

There are two COX isomers—COX-1 and COX-2. COX-1 is continuously expressed in many cells and is responsible for the general effects of prostaglandins, including protection of the gastric mucosa; whereas COX-2 is induced by cytokines and mainly expressed in inflammatory tissues.

Early treatment also includes disease-modifying antirheumatic drugs (DMARDs). DMARDs include gold salts, hydroxychloroquine, sulfasalazine, methotrexate, and azathioprine.

Methotrexate has become the drug of choice because of its potency, and it is relatively fast-acting compared with the slower-acting DMARDs, which can take 3 to 4 months to work.

Methotrexate is thought to interfere with purine metabolism, leading to the release of adenosine, a potent anti-inflammatory compound.

All of the DMARDs can be toxic and require close monitoring for adverse effects, especially those related to bone marrow suppression.

Corticosteroid drugs may be used to reduce discomfort. These agents interrupt the inflammatory and immune cascade at several levels, such as interfering with inflammatory cell adhesion and migration, impairing prostaglandin synthesis, and inhibiting neutrophil superoxide production.  

Intra-articular corticosteroid injections can provide rapid relief of acute or subacute inflammatory synovitis (after infection is excluded) in a few joints.

Second-line antirheumatic drugs include leflunomide, etanercept, infliximab, and adalimumab.

Leflunomide is a pyrimidine synthesis inhibitor that blocks the expansion of T cells. Its efficacy is equal to that of methotrexate. Infliximab, etanercept, and adalimumab are biologic response–modifying agents that block TNF-α, one of the key proinflammatory cytokines in rheumatoid arthritis.

Another approach to RA treatment is combination DMARD therapy. Individual drugs with different mechanisms of action are given simultaneously to control the disease.

The individual drugs are then tapered as symptoms subside and clinical remission is achieved.

Newer biologic response modifiers, abatacept, and rituximab have recently become available for the treatment of persons with RA who have had an inadequate response to one or more of the DMARDs.

Abatacept, a T-cell modulator, binds to CD80/CD86 on antigen-presenting cells, preventing the costimulatory signal that results in full T-cell activation.

Rituximab is a chimeric antibody that binds to the antigen CD20 on pre-B and mature B lymphocytes, causing their destruction. B-cell depletion is associated with the reduction of markers of inflammation, including IL-6, C-reactive protein, antiCCP, and RF.

Surgery also may be a part of the treatment of RA.

Synovectomy may be indicated to reduce pain and joint damage when synovitis does not respond to medical treatment.

The most common soft tissue surgery is tenosynovectomy (i.e., repair of damaged tendons) of the hand to release nerve entrapments.

Total joint replacements (i.e., arthroplasty) may be indicated to reduce pain and increase motion. Arthrodesis (i.e., joint fusion) is indicated only in extreme cases when there is so much soft tissue damage and scarring or infection that a replacement is impossible.


References: NCBI
author

Daniel Ogera

Medical educator, passionate about simplifying difficult medical concepts for easier understanding and mastery by nursing and medical students.

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  • Topic:Clinicals
  • Duration:13 minutes, 8 seconds
  • Subtopic:Rheumatology and orthopedics

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