('''RA''') is a chronic,
Inflammatory Autoimmune Disorder that causes the
Immune System to attack the
Joints . It is a disabling and painful
Inflammatory condition, which can lead to substantial loss of mobility due to pain and joint destruction. The disease is also systemic in that it often also affects many extra-articular tissues throughout the body including the
Skin ,
Blood Vessel s,
Heart ,
Lung s, and
Muscle s.
The name is derived from the Greek ''rheumatos'' meaning "flowing", the suffix -''oid'' meaning "in the shape of", ''arthr'' meaning "joint" and the suffix -''itis'', a "condition involving inflammation".
Rheumatoid arthritis is a chronic, inflammatory multisystem autoimmune disorder. It commonly affects the joints in a polyarticular manner (
Polyarthritis ). The symptoms that distinguish rheumatoid arthritis from other forms of
Arthritis are inflammation and soft-tissue swelling of many joints at the same time (
Polyarthritis ). The joints are generally affected in a symmetrical fashion. The pain generally improves with use of the affected joints, and there is usually stiffness of all joints in the morning that lasts over 1 hour. Thus, the pain of rheumatoid arthritis is usually worse in the morning compared to the classic pain of
Osteoarthritis where the pain worsens over the day as the joints are used.
If the arthritis has been longstanding, the inflammatory activity has led to erosion and destruction of the joint surface, which impairs their range of movement and leads to deformity. The fingers are typically deviated towards the little finger (''
Ulnar Deviation '') and can assume unnatural shapes. Classical deformities in Rheumatoid arthritis are the
Boutonniere Deformity (Hyperflexion at the
Proximal Interphalangeal Joint with hyperextension at the
Distal Interphalangeal Joint ),
Swan Neck Deformity (Hyperextension at the
Proximal Interphalangeal Joint , hyperflexion at the
Distal Interphalangeal Joint ). The thumb may develop a "Z-Thumb" deformity with fixed flexion and
Subluxation at the
Metacarpophalangeal Joint , leading to a "squared" appearance in the hand.
Subcutaneous nodules on extensor surfaces, such as the elbows, are often present.
Extra-articular manifestations also distinguish this disease from osteoarthritis (hence it is a multisystemic disease).
Haematological: Most patients also suffer of
Anemia , either as a consequence of the disease itself (Anaemia of Chronic disease) or as a consequence of
Gastrointestinal Bleeding as a side effect of drugs used in treatment, especially
NSAID s (non-steroidal anti-inflammatory drugs) used for
Analgesia .
Splenomegaly may occur with concurrent leukopaenia (
Felty's Syndrome ).
Dermatological: Subcutaneous nodules
Pulmonary: The
Lungs may become involved as a part of the primary disease process or as a consequence of therapy.
Fibrosis may occur spontaneously or as a consequence of therapy (for example
Methotrexate ).
Caplan's Nodules are found as are
Pulmonary Effusions .
Autoimmune: Vasculitic disorders, giving nail fold infarcts, neuropathies and nephropathies.
Renal:
Amyloidosis , which can also give muscular pseudohypertrophy.
Cardiovascular: Pericarditis, valvulitis and fibrosis.
Ocular: Keratoconjunctivitis sicca (dry eyes),
Episcleritis and
Scleromalacia , which can lead to fissure and leaking of eye contents.
Neurological: There can be signs of
Mononeuritis Multiplex and
Atlanto-axial Subluxation . The latter is due to erosion of the odontoid process and or/transverse ligaments in the cervical spine's connection to the skull. Such an erosion (>3mm) can give rise to vertebrae slipping over one another and compressing the spinal cord. At first the patient experiences clumsiness but with undue care this can progress to
Quadraplegia .
Rheumatoid arthritis occurs most frequently in the 20-40 age group, although can start at any age. It is strongly associated with the HLA marker DR4 (W4, W14 & W15 are associated with the disease and W10 & W13 are protective) - hence family history is an important risk factor.
The disease affects females:males in a 3:1 ratio.
The
American College Of Rheumatology has defined (
1987 ) the following criteria for the diagnosis of rheumatoid arthritis
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- Morning stiffness of >1 hour.
- Arthritis and soft-tissue swelling of >3 of 14 joints/joint groups
- Arthritis of hand joints
- Symmetric arthritis
- Subcutaneous nodules in specific places
- Rheumatoid Factor at a level above the 95th percentile
- Radiological changes suggestive of joint erosion
At least four criteria have to be met to establish the diagnosis, although many patients are treated despite not meeting the criteria.
When RA is being clinically suspected, ). A negative RF does not rule out RA; rather, the arthritis is called ''
Seronegative ''. During the first year of illness, rheumatoid factor is frequently negative. 80% patients eventually convert to seropositive status. RF is also seen in other illnesses, like
Sjögren's Syndrome , and in approximately 10% of the healthy population, therefore the test is not very specific.
Because of this low specificity, a new serological test has been developed in recent years, which tests for the presence of so called anti-
Citrullinated Protein (ACP) antibodies. Like RF, this test can detect approximately 80% of all RA patients, but is rarely positive in non-RA patients, giving it a
Specificity of around 98%. In addition, ACP antibodies can be often detected in early stages of the disease, or even before disease onset. Currently, most common test for ACP antibodies is the anti-CCP
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Also, several other can reveal
Hemochromatosis , which can mimic RA.
The cause of RA is still unknown to this day, but has long been suspected to be infectious. It could be due to food allergies or external organisms. ''
Mycoplasma '', ''
Erysipelothrix '',
Epstein-Barr Virus ,
Parvovirus and
Rubella have been suspected but never supported in epidemiological studies. As in other autoimmune diseases, the "mistaken identity" theory suggests that an offending organism causes an immune response that leaves behind antibodies that are specific to that organism. The antibodies are not specific enough, though. They begin an immune attack against, in this case, the
Synovium , because some molecule in the synovium "looks like" a molecule on the offending organism that created the initial immune reaction - this phenomenon is called molecular mimicry.
Autoimmune diseases require that the affected individual have a defect in the ability to distinguish self from foreign molecules. This ability is acquired in the first year of life. There are markers on many cells that confer this self-identifying feature. However, some classes of markers allow for RA to happen. 90% of patients with RA have the cluster of markers known as the HLA-DR4/DR1 cluster, whereas only 40% of controls do. Thus, in theory, RA requires susceptibility to the disease through genetic endowment with specific markers an infectious event that triggers an autoimmune response.
Once triggered, the immune response causes inflammation of the synovium. Early and intermediate molecular mediators of inflammation include
Tumor Necrosis Factor alpha (TNF-α),
Interleukin s
IL-1 ,
IL-6 ,
IL-8 and
IL-15 ,
Transforming Growth Factor beta,
Fibroblast Growth Factor and
Platelet-derived Growth Factor . Modern pharmacological treatments of RA target these mediators. Once the inflammatory reaction is established, the synovium thickens, the cartilage and the underlying bone begins to disintegrate and evidence of joint destruction accrues.
Pharmacological treatment of RA can be divided into
Disease-modifying Antirheumatic Drug s (DMARDs),
Anti-inflammatory agents and
Analgesic s O'Dell JR. Therapeutic strategies for rheumatoid arthritis. ''N Engl J Med.'' 2004;350(25):2591-602 PMID 15201416. DMARDs have been found to produce durable remissions and delay or halt disease progression. This is not true of anti-inflammatories and analgesics.
DMARDs can be further subdivided into
Xenobiotic agents and biological agents. Xenobiotic agents are those DMARDs that do not occur naturally in the body, as opposed to biologicals.
Xenobiotics include:
The most important and most common adverse events relate to
Liver and
Bone Marrow toxicity (MTX, SSZ, leflunomide, azathioprine, gold compounds, D-penicillamine), renal toxicity (cyclosporine A, parenteral gold salts, D-penicillamine), pneumonitis (MTX), allergic
Skin reactions (gold compounds, SSZ), autoimmunity (D-penicillamine, SSZ, minocycline) and infections (azathioprine, cyclosporine A). Hydroxychloroquine may cause ocular toxicity.
Biological agents include:
- Tumor Necrosis Factor (TNFα) blockers - Etanercept (Enbrel), Infliximab (Remicade), Adalimumab (Humira)
- Interleukin -1 blockers - Anakinra
Bristol-Myers Squibb Company announced on December 23, 2005, that the US Food and Drug Administration (FDA) has approved Orencia (abatacept), the first selective modulator of a costimulatory signal required for full T-cell activation, for the treatment of rheumatoid arthritis.
Orencia is expected to be available for initial commercial use by the end of February 2006.
Anti-inflammatory agents include:
Analgesics include:
Other therapies are
Weight Loss , occupational therapy,
Physiotherapy ,
Joint Injection s, and special tools to improve hard movements (e.g. special tin-openers).
Severely affected joints may require
Joint Replacement surgery, such as knee replacement.
The
Incidence of RA is 30 cases per 10,000 population. The peak incidence is between the ages of 20 and 40. The
Prevalence rate is 1%, with women affected three to five times as often as men. Some
Native American groups have higher prevalence rates (5-6%) and black persons from the
Caribbean region have lower prevalence rates. First-degree relatives prevalence rate is 2-3% and disease concordance in monozygotic
Twin s is approximately 15-20%.
The course of the disease varies greatly from patient to patient. Some patients have mild short-term symptoms, but in most the disease is progressive for life. Around 20%-30% will have subcutaneous nodules (known as rheumatoid nodules) this is associated with a poor prognosis.
- Daily living activities are impaired in most patients.
- After 5 years of disease, approximately 33% of patients will not be working
- After 10 years, approximately half will have substantial functional disability.
- Poor prognostic factors include persistent synovitis, early erosive disease, extra-articular findings (including subcutaneous rheumatoid nodules), positive serum RF findings, positive serum anti-CCP autoantibodies, carriership of HLA-DR4 "Shared Epitope" alleles, family history of RA, poor functional status, socioeconomic factors, elevated acute phase response (erythrocyte sedimentation rate C-reactive protein [CRP ), and increased clinical severity.
- Life expectancy for patients with RA is shortened by 5-10 years, although those who respond to therapy may have lower mortality rates.
Regular exercise and carefully controlled diet can usually help lessen the pain and stiffness associated with arthritic flare-ups.
Cold can increase the pain and stiffness.
Also see Eastern and Naturopathic Approaches in this article.
The first known traces of arthritis date back as far as
4500 BC . It was noted in skeletal remains of
Indians found in
Tennessee . A text dated
123 AD first describes
Symptom s very similar to rheumatoid arthritis. In
1859 the disease got its current name.
