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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 lungs, pericardium, pleura, 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) and X-rays. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in the diseases of joints and connective tissues.

Various treatments are available. Non-pharmacological treatment includes physical therapy,orthoses and occupational therapy. Analgesia (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.

The name is based on the term "rheumatic fever", an illness which includes joint pain and is derived from the Greek word rheumatos ("flowing"). The suffix -oid ("resembling") gives the translation as joint inflammation that resembles rheumatic fever. The first recognized description of rheumatoid arthritis was made in 1800 by Dr Augustin Jacob Landré-Beauvais (1772-1840) of Paris.

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. 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.

  • 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 hands, feet and cervical spine are affected, but larger joints like the shoulder and knee can also be involved, differing per individual. Synovitis can lead to tethering of tissue with loss of movement and erosion of the joint surface, causing deformity and loss of function.

    Rheumatoid arthritis typically manifests with signs of inflammation, and the affected joints are swollen, warm, painful and stiff early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the inflammatory disease which the person may experience 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 also movements aggravate pain due to the wear-and-tear. In RA, the joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical.

    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 deviation, boutonniere deformity, swan 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 joints, 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.

    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 due to the presence of an obliterative cutaneous capillaropathy.

    Other, rather rare, skin associated symtoms include:

    • pyoderma gangrenosum, a necrotizing, ulcerative, noninfectious neutrophilic dermatosis
    • Sweet's syndrome, a neutrophilic dermatosis usually associated with myeloproliferative disorders
    • drug reactions
    • erythema nodosum
    • lobular panniculitis
    • atrophy of digital skin
    • palmar erythema
    • diffuse thinning (rice paper skin), and skin fragility (often worsened by corticosteroid use)
  • Lungs

    Fibrosis of the lungs is a recognised response to rheumatoid disease. It is also a rare but well recognised consequence of therapy (for example with methotrexate and leflunomide). Caplan's syndrome describes lung nodules in individuals with rheumatoid arthritis and additional exposure to coal dust. Pleural effusions are also associated with rheumatoid arthritis.

  • Kidneys

    Renal amyloidosis can occur as a consequence of chronic inflammation. Rheumatoid arthritis may affect the kidney glomerulus directly through a vasculopathy or a mesangial infiltrate but this is less well documented. Treatment with Penicillamine and gold salts are recognized causes of membranous nephropathy.

  • Heart and blood vessels

    People with rheumatoid arthritis are more prone to atherosclerosis, and risk of myocardial infarction (heart attack) and stroke is markedly increased. Other possible complications that may arise include: pericarditis, endocarditis, left ventricular failure, valvulitis and fibrosis.

  • Other

    • Ocular: The eye is directly affected in the form of episcleritis which when severe can very rarely progress to perforating scleromalacia. Rather more common is the indirect effect of keratoconjunctivitis sicca, which is a dryness of eyes and mouth due to lymphocyte infiltration of lachrymal and salivary glands. When severe, dryness of the cornea can lead to keratitis and loss of vision. Preventive treatment of severe dryness with measures such as nasolacrimal duct occlusion is important.
    • Hepatic: Cytokine production in joints and/or hepatic Kupffer cells leads to increased activity of hepatocytes with increased production of acute-phase proteins, such as C-reactive protein, and increased release of enzymes such as alkaline phosphatase into the blood. In Felty's syndrome, Kuppfer cell activation is so marked that the resulting increase in hepatocyte activity is associated with nodular hyperplasia of the liver, which may be palpably enlarged. Because Kuppfer cells are not within the liver parenchyma, there is little or no evidence of hepatitis. Hepatic involvement in RA is essentially asymptomatic.
    • Hematological: Anemia is by far the most common abnormality of the blood cells. The red cells are of normal size and colour (normocytic). A low white blood cell count (neutropenia) or usually only occurs in patients with Felty's syndrome with an enlarged liver and spleen. The mechanism of neutropenia is complex. An increased platelet count (thrombocytosis) occurs when inflammation is uncontrolled, as does the anemia.
    • Neurological: Peripheral neuropathy and mononeuritis multiplex may occur. The most common problem is carpal tunnel syndrome due to compression of the median nerve by swelling around the wrist. Atlanto-axial subluxation can occur, owing 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. Clumsiness is initially experienced, but without due care this can progress to quadriplegia.
    • Constitutional symptoms: Constitutional symptoms including fatigue, low grade fever, malaise, morning stiffness, loss of appetite and loss of weight are common systemic manifestations seen in patients with active rheumatoid arthritis.
    • Osteoporosis: Local osteoporosis occurs in RA around inflamed joints. It is postulated to be partially caused by inflammatory cytokines. More general osteoporosis is probably contributed to by immobility, systemic cytokine effects, local cytokine release in bone marrow and corticosteroid therapy.
    • Lymphoma: The incidence of lymphoma is increased in RA, although it is still uncommon.

Treatment

There is no known cure for rheumatoid arthritis, but many different types of treatment can alleviate symptoms and/or modify the disease process.

The goal of treatment is two-fold: alleviating the current symptoms, and preventing the future destruction of the joints with the resulting handicap if the disease is left unchecked. These two goals may not always coincide: while pain relievers may achieve the first goal, they do not have any impact on the long-term consequences. For these reasons, most authorities believe that most RA should be treated by at least one specific anti-rheumatic medication, also named DMARD (see below), to which other medications and non-medical interventions can be added as needed.

Cortisone therapy has offered relief in the past, but its long-term effects have been deemed undesirable. However, cortisone injections can be valuable adjuncts to a long-term treatment plan, and using low dosages of daily cortisone (e.g., prednisone or prednisolone, 5-7.5 mg daily) can also have an important benefit if added to a proper specific anti-rheumatic treatment.

Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics. Treatment also includes rest and physical activity.

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