RA Flashcards
Definition/Description
Rheumatoid arthritis (RA) is a systematic autoimmune inflammatory disease that results in persistent inflammation of synovial tissue especially of the wrists, hands and feet. RA is a long-term disease that leads to inflammation of the joints and surrounding tissues and can also affect other surrounding structures like the tendon sheath, the bursa and tendons.
This pathology causes pain, stiffness in the morning and after periods of inactivity, joint swelling, weakness, fatigue and restricted joint mobility leading to reduced function. Without treatment, RA can possibly lead to joint deformities in the later stages of the disease which then function of the joints could be lost permanently.
Thus, RA causes dramatic interference with quality of life if early diagnosis and appropriate treatment are not obtained.Individuals with RA are 8 times more likely to have the functional disability compared with adults in the general population from the same community.
The disease course typically follows three possible paths:
Monocyclic: Having one episode that does not reoccur. This usually ends within 2-5 years of initial diagnosis.
Polycyclic: The disease severity varies over the course of the progression of the condition.
Progressive: Condition continues to become more severe and non-remitting.
Clinically Relevant Anatomy
Characterizing in rheumatoid arthritis is the inflammation of the synovium also characterized is the destructive erosion of bone and loss of joint integrity what frequently leads to disability.
The synovium is a thin layer of tissue which lines the joint space where there is no cartilage. It can also be found in tendon sheaths and bursae. Under normal circumstances, the synovium consists of 2 - 3 layers of cells. In patients with rheumatoid arthritis, the synovium is strongly thickened and inflamed.
Due to the inflammation production of enzymes occurs, which breaks down the cartilage. This can cause local damage to the bone-tissue and cartilage. The cause of this inflammation in rheumatoid arthritis is unknown.
Epidemiology
There are nearly three times as many women then men with the disease. RA is found all around the world, but does tend to be more prevalent in the Native American and white population.
The risk of RA increases with age. RA most commonly begins in women between the ages of 30 and 60. It often occurs later in life for men, but can happen at any age. When RA affects the pediatric population, it is called Juvenile Idiopathic Arthritis (JIA) and usually begins before the age of 16
Etiology / risk factors
Systemic inflammation and autoimmunity in RA begin long before the onset of detectable joint inflammation. Emerging data suggest that RA-related autoimmunity may be initiated at a mucosal site years before the onset of joint symptoms. The candidate sites of origin include the oral, lung and gastrointestinal mucosa, as data consistent with this hypothesis have been generated for each location. Individual patients may undergo initiation events at unique sites but still converge on similar joint findings as the disease process evolves.
RA is typically divided into two subtypes designated “seropositive” and “seronegative” disease, with seropositivity being defined as the presence of serum elevations of the autoantibodies rheumatoid factor (RF) and the more recently described antibodies to citrullinated protein/peptide antigens (ACPAs).
Multiple genetic and environmental factors have been associated with an increased risk for rheumatoid arthritis (RA)
Genetic and Familial Risk Factors for RA
There is a generally increased prevalence of RA within families, leading to estimations of familial risk contribution of ∼40–50% of seropositive RA, with strongest risks seen in first-degree relatives (FDRs).
The strongest of the genetic risk factors is a set of alleles within the major histocompatibility complex (MHC) that encode amino acid sequences that predict structural similarities in the human leukocyte antigen (HLA) peptide-binding groove and are termed in the aggregate “shared epitope,”(SE). SE alleles are believed to contribute up to ∼40% of the genetic risk for RA, although other studies suggest less contributio
Environmental Factors
Smoking/Tobacco Exposure: Many studies have found that exposure to smoking accounts for ∼20–30% of the environmental risk for RA. Primarily, smoking is most strongly associated with antibodies to citrullinated protein/peptide antigens (ACPA) - positive RA. It has been proposed that smoking may lead to increased citrullination and in presence of the right genetic background, it may lead to the presentation of citrullinated proteins and the generation of ACPA, along with other local and systemic effects of smoking tobacco influencing the immunity.
Smoking has long been associated with the presence of RF even in the absence of RA. This suggests that there may be biologic interactions between these factors that drive the development of RA or at the very least RA-related autoimmunity.
Thus, a major unanswered question regarding the role of smoking in RA is where it acts in the natural history of RA. Specifically, does exposure to tobacco smoke act to trigger the initial autoimmunity or does it drive the propagation of autoimmunity to the point of classifiable disease? These issues need to be investigated thoroughly, especially given the potential for smoking to be a modifiable risk factor and therefore a potential preventive intervention in RA development.
Dietary factors: Lower intake of vitamin D and antioxidants and higher intake of sugar, sodium, red meats, protein, iron and certain medications are associated with increased risk of RA
Characteristics/Clinical Presentation
There is typically a period of circulating autoantibody elevations that may last several years prior to the first appearance of inflammatory arthritis. This period can be termed “Preclinical RA,” and its presence has raised the issue that a subset of the genetic and environmental factors that drive RA , are likely acting years prior to the first appearance of arthritis. This process of disease progression is not universal, although some studies have identified a small percentage of patients where inflammatory arthritis presents prior to the appearance of circulating autoantibodies
In rheumatoid arthritis, joint complaints are in the foreground.
Typically in a first stage, there is:
a chronic, symmetrical inflammation of the joints of the hands and the feet, especially the metatarsophalangeal joints (MTP), the wrists, the metacarpophalangeal joints (MCP) and the proximal interphalangeal joints (PIP).
Softening of the ligaments can lead to deformation of the fingers, like subluxations of the metacarpophalangeal joints.
Rheumatoid arthritis causes deformity, pain, weakness and restricted mobility and will result in loss of function.
The three most important complaints are the pain, morning stiffness and fatigue.
In 80-90% of the patients with rheumatoid arthritis the cervical spine is involved, which can lead to instability, caused by the ligamentous laxity. Usually, the instability occurs between the first and second cervical vertebrae. This instability can lead to pain and neurological symptoms, like a headache and tingling in the fingers
the increased mortality in RA patients is mostly associated with cardiovascular disease. Accelerated atherosclerosis is of growing concern in these patients. There is increasing evidence that atherosclerotic disease is driven by inflammatory mechanisms similar to those in RA. Cardiovascular morbidity correlates with inflammatory activity in RA.
Signs and Symptoms of RA
Joint Pain: warmth, redness, tenderness, swelling
Joint Stiffness: increased in the mornings
Fatigue throughout the body
Fever
Weight Loss
Rheumatoid Nodules: small lumps of tissue felt under the skin
Symmetrical Patterns of affected joints
Most common joints: wrist, hand, fingers, cervical spine, shoulder, elbow, knee, hip, foot, and ankle
Prolong symptoms
Anemia
Neck Pain
Dry Eyes
Dry Mouth
Classification Of Progression of Rheumatoid Arthritis
Stage I
Mild
No destructive changes on radiographic examination
Radiographic evidence of osteoporosis may be present
Stage II
Moderate
Radiographic evidence of osteoporosis, with or without slight subchondral bone destruction; slight cartilage destruction may be present
No joint deformities, although limitation of joint mobility may be present
Adjacent muscle atrophy
Extra-articular soft tissue lesions, such as nodules and tenosynovitis may be present
Stage III
Severe
Radiographic evidence of cartilage and bone destruction in addition to osteoporosis
Joint deformity, such as subluxation, ulnar deviation, or hyperextension, without fibrous or bony ankylosis Extensive muscle atrophy Extra-articular soft tissue lesions, such as nodules and tenosynovitis may be present
Stage IV
Terminal
Fibrous or bony ankylosis
Stage III criteria
Differential Diagnosis
Osteoarthritis: best differentiated from RA by a careful history and examination. Two factors to distinguish the two disorders: the absence of systemic inflammatory signs and symptoms, onset in later life, and the pattern of joint involvement.
Infectious arthropathies: the important consideration in the setting of fever and polyarthritis. If bacterial arthritis is suspected, joint aspiration and synovial fluid cultures and blood cultures are often helpful in establishing the diagnosis.
Lyme disease: also associated with negative synovial fluid cultures. When a patient has been in an endemic region where tick exposure was likely, it should be considered.
Seronegative spon
dyloarthropathies (reactive arthritis, ankylosing spondylitis, inflammatory bowel disease–associated arthropathy): muscle weakness and antibodies associated with these disorders most often readily distinguish these disorders from RA.
Fibromyalgia (FMS): diffuse symmetrical arthralgias and stiffness at rest, but an absence of synovitis, the lack of pain on motion, and normal laboratory and imaging studies
Diagnostic Procedures
The American College of Rheumatology has defined 7 criteria, where a patient has to correspond with at least 4 of these 7 criteria for the diagnosis of rheumatoid arthritis.The first 4 of these criteria are only valid if they persist for at least 6 weeks. These 7 criteria are:
Morning stiffness
Arthritis in 3 or more joints
Arthritis in the joints of the hands (wrist, MCP, PIP)
Symmetrical arthritis
Rheumatoid nodules over bony prominences or extensor surfaces
Positive serum rheumatoid factor
Radiographic changes including erosion or bony decalcifications localized in or adjacent to joints.
