Article: Rheumatoid arthritis

Rheumatoid arthritis (RA) is traditionally considered 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 vessels, heart, lungs, and muscles.

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".

Features

Rheumatoid arthritis is a chronic, inflammatory, multisystem, autoimmune disorder. It commonly affects the joints in a polyarticular manner. 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 usually affected initially asymmetrically and then in a symmetrical fashion as the disease progresses. 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.

As the pathology progresses the inflammatory activity leads 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.

Extra-articular manifestations also distinguish this disease from osteoarthritis (hence it is a multisystemic disease). For example, 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 NSAIDs (non-steroidal anti-inflammatory drugs) used for analgesia. Splenomegaly may occur with concurrent leukopaenia (Felty's syndrome), and lymphocytic infiltration may affect the salivary and lacrimal glands (Sjögren's syndrome).

Dermatological: Subcutaneous nodules on extensor surfaces, such as the elbows, are often present.

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 without due care this can progress to quadraplegia.

Epidemiology

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 is 3 times more common in women than men and up to 4 times more common in smokers than non-smokers.

Diagnosis

Diagnostic criteria

The American College of Rheumatology has defined (1987) the following criteria for the diagnosis of rheumatoid arthritis [1].

  • 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.

Blood tests

When RA is being clinically suspected, immunological studies are required, such as rheumatoid factor [2] (RF, a specific antibody). 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% of 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[3] (cyclic citrulinated peptide) test.

Also, several other blood tests are usually done to allow for other causes of arthritis, such as lupus erythematosus. The erythrocyte sedimentation rate (ESR), C-reactive protein[4], full blood count, renal function, liver enzymes and immunological tests (e.g. antinuclear antibody/ANA)[5] are all performed at this stage. Ferritin can reveal hemochromatosis, which can mimic RA.

Pathophysiology

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Joint abnormalities in rheumatoid arthritis

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 B19 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.

But physical and emotional effects, stress and inproper diet could play role in the disease.

Autoimmune diseases require that the affected individual have a defect in the ability to distinguish self from foreign molecules. 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 unaffected controls do. Thus, in theory, RA requires susceptibility to the disease through genetic endowment with specific markers and 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), interleukins 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.

Bacteria/antibiotic hypothesis

Thomas McPherson Brown along with other researchers and patient groups believe that it can be demonstrated that RA is caused by a bacterial infection, in particular mycoplasma that localizes to joints.[1] However it seems that, at least in part, tetracycline antibiotics also "exhibit immunomodulatory properties, which may contribute significantly to their beneficial effects in rheumatoid arthritis".[2]

Treatment

Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics [3][4]. DMARDs have been found to produce durable remissions and delay or halt disease progression. This is not true of anti-inflammatories and analgesics.

Disease modifying anti-rheumatic drugs (DMARDs)

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

Xenobiotics include:

  • azathioprine
  • ciclosporin (cyclosporine A)
  • D-penicillamine
  • gold salts
  • hydroxychloroquine
  • leflunomide
  • methotrexate (MTX)
  • minocycline
  • sulfasalazine (SSZ)

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

Biological agents include:

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 and analgesics

Anti-inflammatory agents include:

Analgesics include:

  • acetaminophen
  • opiates
  • lidocaine topical

Other therapies

Other therapies are weight loss, occupational therapy, physiotherapy, joint injections, and special tools to improve hard movements (e.g. special tin-openers).

Severely affected joints may require joint replacement surgery, such as knee replacement.

Many natural healing practitioners attribute rheumatoid arthritis to toxemia, which can be caused by several things, including, among several other things, the many poisons that enter our systems through food, air, and skin; the effect of accumulated poisons and hard-to-digest food on the liver and other digestive organs; and intestinal permeability, a.k.a. LGS (Leaky Gut Syndrome), where the lining of the stomach, small intestine, and or large intestine become porous, allowing undigested substances to cross the intestinal wall and enter the bloodstream. Toxicity is believed to trigger the inflammation characteristic of rheumatoid arthritis because the immune system creates antibodies for toxins. In rheumatoid arthritis, certain instances of these antibodies are believed to attack not just the antigen but also synovium and, eventually, other tissue. Hence, to reduce or cure rheumatoid arthritis without drugs, an effort is made to eliminate the toxin(s) that cause the auto-immume system to attack the afflicted person's own tissue. The body is detoxified by various means, including eliminating/reducing stress and unpleasant emotions (which affect the health of the bowels and digestive system), sleeping as long and often as necessary, eating less (professionally supervised fasts are sometimes employed), eating highly digestible foods and foods high in oxygen and chlorophyll (like raw vegetables and wheat grass juice), eating friendly-bacteria foods (like acidophilus, plain yogurt, and other probiotics), eating foods that are unfriendly to dysbiotic bacteria (like coconut oil, garlic, and raw vegetables), taking a tablespoon of cod liver oil every day to reduce inflammation, completely eliminating sugar and other anti-biotic foods and medications, drinking sufficient amounts of high-quality water (half the number of pounds of body-weight in ounces), and consequently cleansing and healing the blood, digestive organs, and intestines. These dietary and lifestyle modifications have not been studied in clinical trials, and therefore, your physician should be consulted before making such changes to your treatment regimen.

Epidemiology

The incidence of RA is 30 cases per 10,000 population. The peak incidence is between the ages of 40 and 60. 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 twins is approximately 15-20%.

Prognosis

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.

Disability

  • 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.

Prognostic factors

  • 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 [ESR], C-reactive protein [CRP]), and increased clinical severity.

Mortality

  • Life expectancy for patients with RA is shortened by 5-10 years, although those who respond to therapy may have lower mortality rates.

Prevention

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.

History

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 symptoms very similar to rheumatoid arthritis. In 1859 the disease got its current name.