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Rheumatoid Arthritis

RHEUMATOID ARTHRITIS:

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks the joints producing an inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungspericardiumpleura, and sclera, and also nodular lesions, most common in subcutaneous tissue under the skin. Although the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in its chronicity and progression.

About 1% of the world’s population is afflicted by rheumatoid arthritis, women three times more often than men. Onset is most frequent between the ages of 40 and 50, but people of any age can be affected. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility. It is diagnosed chiefly on symptoms and signs, but also with blood tests (especially a test called rheumatoid factor) andX-rays. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in the diseases of joints and connective tissues.[1]

Various treatments are available. Non-pharmacological treatment includes physical therapy,orthoses and occupational therapyAnalgesia(painkillers) and anti-inflammatory drugs, including steroids, are used to suppress the symptoms, while disease-modifying antirheumatic drugs(DMARDs) are often required to inhibit or halt the underlying immune process and prevent long-term damage. In recent times, the newer group of biologics has increased treatment options.[1]

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Signs and symptoms

While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur. Extra-articular (“outside the joints”) manifestations other than anemia (which is very common) are clinically evident in about 15-25% of individuals with rheumatoid arthritis.[3] It can be difficult to determine whether disease manifestations are directly caused by the rheumatoid process itself, or from side effects of the medications commonly used to treat it – for example, lung fibrosis from methotrexate or osteoporosis from corticosteroids.

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Joints

The arthritis of joints known as synovitis is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness limits their movement. With time RA nearly always affects multiple joints (it is a polyarthritis), most commonly small joints of the handsfeet and cervical spine, but larger joints like the shoulder and knee can also be involved. Synovitis can lead to tethering of tissue with loss of movement and erosion of the joint surface causing deformity and loss of function.[1]

Rheumatoid arthritis typically manifests with signs of inflammation, with the affected joints being swollen, warm, painful and stiff, particularly early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the disease and may last for more than an hour. Gentle movements may relieve symptoms in early stages of the disease. These signs help distinguish rheumatoid from non-inflammatory problems of the joints, often referred to as osteoarthritis or “wear-and-tear” arthritis. In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are absent, and movements induce pain due to the wear-and-tear.[4]

In RA, the joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical.

File:Arthrite rhumatoide.jpg

Hands affected by RA

As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity. The fingers may suffer from almost any deformity depending on which joints are most involved. Medical students are taught to learn names for specific deformities, such as ulnar deviationboutonniere deformityswan neck deformity and “Z-thumb,” but these are of no more significance to diagnosis or disability than other variants.

Skin

The rheumatoid nodule, which is often subcutaneous, is the feature most characteristic of rheumatoid arthritis. The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both. The nodule has a central area of fibrinoid necrosis that may be fissured and which corresponds to the fibrin-rich necrotic material found in and around an affected synovial space. Surrounding the necrosis is a layer of palisading macrophages and fibroblasts, corresponding to the intimal layer in synovium and a cuff of connective tissue containing clusters of lymphocytes and plasma cells, corresponding to the subintimal zone in synovitis. The typical rheumatoid nodule may be a few millimetres to a few centimetres in diameter and is usually found over bony prominences, such as the olecranon, the calcaneal tuberosity, the metacarpophalangeal joint, or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF (rheumatoid factor) titer and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body.

Several forms of vasculitis occur in rheumatoid arthritis. A benign form occurs as microinfarcts around the nailfolds. More severe forms include livedo reticularis, which is a network (reticulum) of erythematous to purplish discoloration of the skin caused by the presence of an obliterative cutaneous capillaropathy.

Other, rather rare, skin associated symtoms include:

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Pathophysiology

Rheumatoid arthritis is a form of autoimmunity, the causes of which are still incompletely known. It is a systemic (whole body) disorder principally affecting synovial tissues.

The key pieces of evidence relating to pathogenesis are:

1. A genetic link with HLA-DR4 and related allotypes of MHC Class II and the T cell-associated protein PTPN22.

2. A link with cigarette smoking that appears to be causal.

3. A dramatic response in many cases to blockade of the cytokine TNF (alpha).

4. A similar dramatic response in many cases to depletion of B lymphocytes, but no comparable response to depletion of T lymphocytes.

5. A more or less random pattern of whether and when predisposed individuals are affected.

6. The presence of autoantibodies to IgGFc, known as rheumatoid factors (RF), and antibodies to citrullinated peptides (ACPA).

These data suggest that the disease involves abnormal B cell – T cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting T cell help and consequent production of RF and ACPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. The process may be facilitated by an effect of smoking on citrullination but the stochastic (random) epidemiology suggests that the rate limiting step in genesis of disease in predisposed individuals may be an inherent stochastic process within the immune response such as immunoglobulin or T cell receptor gene recombination and mutation. (See entry under autoimmunity for general mechanisms.)

If TNF release is stimulated by B cell products in the form of RF or ACPA – containing immune complexes, through activation of immunoglobulin Fc receptors, then RA can be seen as a form of Type III hypersensitivity.[13] [14] If TNF release is stimulated by T cell products such as interleukin-17 it might be considered closer to type IV hypersensitivity although this terminology may be getting somewhat dated and unhelpful.[15] The debate on the relative roles of immune complexes and T cell products in inflammation in RA has continued for 30 years. There is little doubt that both B and T cells are essential to the disease. However, there is good evidence for neither cell being necessary at the site of inflammation. This tends to favour immune complexes (based on antibody synthesised elsewhere) as the initiators, even if not the sole perpetuators of inflammation. Moreover, work by Thurlings and others in Paul-Peter Tak’s group and also by Arthur Kavanagh’s group suggest that if any immune cells are relevant locally they are the plasma cells, which derive from B cells and produce in bulk the antibodies selected at the B cell stage.[citation needed]

Although TNF appears to be the dominant, other cytokines (chemical mediators) are likely to be involved in inflammation in RA. Blockade of TNF does not benefit all patients or all tissues (lung disease and nodules may get worse). Blockade of IL-1, IL-15 and IL-6 also have beneficial effects and IL-17 may be important. Constitutional symptoms such as fever, malaise, loss of appetite and weight loss are also caused by cytokines released in to the blood stream.

As with most autoimmune diseases, it is important to distinguish between the cause(s) that trigger the process, and those that may permit it to persist and progress.

See also

References

  1. a b c Majithia V, Geraci SA (2007). “Rheumatoid arthritis: diagnosis and management”. Am. J. Med. 120 (11): 936–9. doi:10.1016/j.amjmed.2007.04.005PMID 17976416.
  2. a b Landré-Beauvais AJ (1800). La goutte asthénique primitive (doctoral thesis). Paris. reproduced in Landré-Beauvais AJ (March 2001). “The first description of rheumatoid arthritis. Unabridged text of the doctoral dissertation presented in 1800”.Joint Bone Spine 68 (2): 130–43. doi:10.1016/S1297-319X(00)00247-5PMID 11324929.
  3. ^ Turesson C, O’Fallon WM, Crowson CS, Gabriel SE, Matteson EL (2003). “Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years”Ann. Rheum. Dis. 62 (8): 722–7. doi:10.1136/ard.62.8.722.PMID 12860726.
  4. ^ Jijith Krishnan,Document on Rhuematoid arthritis
  5. ^ de Groot K (August 2007). “[Renal manifestations in rheumatic diseases]”. Internist (Berl) 48 (8): 779–85. doi:10.1007/s00108-007-1887-9PMID 17571244.
  6. ^ Wolfe F, Mitchell DM, Sibley JT, et al (April 1994). “The mortality of rheumatoid arthritis”. Arthritis Rheum. 37 (4): 481–94. doi:10.1002/art.1780370408PMID 8147925.
  7. ^ Westwood OM, Nelson PN, Hay FC (April 2006). “Rheumatoid factors: what’s new?”Rheumatology (Oxford) 45 (4): 379–85. doi:10.1093/rheumatology/kei228PMID 16418203.
  8. a b Nishimura K, Sugiyama D, Kogata Y, et al (June 2007). “Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis” (PDF). Ann. Intern. Med. 146 (11): 797–808. PMID17548411.

January 27, 2010 - Posted by | Blood, Cells, Muscles, Thyroid

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