Rheumatoid arthritis (RA) is a chronic, systemicinflammatorydisorder that may affect many tissues and organs, but principally attacksthe joints producing an inflammatory synovitisthat often progresses to destruction of the articular cartilage and ankylosis ofthe joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, pericardium,pleura, and sclera, and alsonodular lesions, most common in subcutaneous tissue under the skin.Although the cause of rheumatoid arthritis is unknown, autoimmunityplays 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 agesof 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 diagnosedchiefly on symptoms and signs, but also with blood tests(especially a test called rheumatoidfactor) and X-rays. Diagnosis and long-term management aretypically performed by a rheumatologist, an expert in the diseases of joints andconnective tissues.
Various treatments are available. Non-pharmacological treatment includes physicaltherapy, orthoses and occupational therapy. Analgesia(painkillers) and anti-inflammatory drugs, including steroids,are used to suppress the symptoms, while disease-modifying antirheumaticdrugs (DMARDs) are often required to inhibit or halt the underlying immuneprocess and prevent long-term damage. In recent times, the newer group of biologics hasincreased treatment options.
The name is based on the term "rheumaticfever", an illness which includes joint pain and is derived from theGreek word rheumatos("flowing"). The suffix -oid("resembling") gives the translation as joint inflammation that resembles rheumatic fever.
Signs and symptoms
While rheumatoid arthritis primarily affects joints, problems involvingother organs of the body are known to occur. Extra-articular ("outside thejoints") manifestations other than anemia (which is very common) areclinically evident in about 15-25% of individuals with rheumatoid arthritis. Itcan be difficult to determine whether disease manifestations are directlycaused by the rheumatoid process itself, or from side effects of themedications commonly used to treat it - for example, lung fibrosis from methotrexateor osteoporosisfrom corticosteroids.
The arthritis of joints known as synovitis isinflammation of the synovial membrane that lines joints and tendonsheaths. Joints become swollen, tender and warm, and stiffness limits theirmovement. With time RA nearly always affects multiple joints (it is a polyarthritis),most commonly small joints of the hands, feetand cervicalspine, 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 ofthe joint surface causing deformity and loss of function.
Rheumatoid arthritis typically manifests with signs of inflammation, withthe affected joints being swollen, warm, painful and stiff, particularly earlyin the morning on waking or following prolonged inactivity. Increased stiffnessearly in the morning is often a prominent feature of the disease and may lastfor more than an hour. Gentle movements may relieve symptoms in early stages ofthe disease. These signs help distinguish rheumatoid from non-inflammatoryproblems of the joints, often referred to as osteoarthritisor "wear-and-tear" arthritis. In arthritis of non-inflammatorycauses, signs of inflammation and early morning stiffness are absent, andmovements induce pain caused by the wear-and-tear. In RA, the joints are oftenaffected in a fairly symmetrical fashion, although this is not specific, andthe initial presentation may be asymmetrical.
As the pathology progresses the inflammatory activity leads to tendontethering and erosion and destruction of the joint surface, which impairs rangeof movement and leads to deformity. The fingers may suffer from almost anydeformity depending on which joints are most involved. Medical students are taughtto learn names for specific deformities, such as ulnardeviation, boutonniere deformity, swan neck deformity and "Z-thumb,"but these are of no more significance to diagnosis or disability than othervariants.
The rheumatoidnodule, which is often subcutaneous, is the feature mostcharacteristic of rheumatoid arthritis. The initial pathologic process innodule formation is unknown but may be essentially the same as the synovitis,since similar structural features occur in both. The nodule has a central areaof fibrinoid necrosis that may be fissured andwhich corresponds to the fibrin-rich necrotic material found in and around anaffected synovial space. Surrounding the necrosis is a layer of palisading macrophagesand fibroblasts,corresponding to the intimal layer in synovium and a cuff of connectivetissue containing clusters of lymphocytes and plasma cells, correspondingto the subintimal zone in synovitis. The typical rheumatoid nodule may be a fewmillimeters to a few centimeters in diameter and is usually found over bonyprominences, such as the olecranon, the calcaneal tuberosity, the metacarpophalangeal joint, or otherareas that sustain repeated mechanical stress. Nodules are associated with apositive 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 vasculitisoccur in rheumatoid arthritis. A benign form occurs as microinfarcts around thenailfolds. More severe forms include livedo reticularis, which is a network(reticulum) of erythematous to purplish discoloration of the skin caused by thepresence of an obliterative cutaneous capillaropathy.
Other, rather rare, skin associated symptoms include:
Fibrosisof the lungs is arecognised response to rheumatoid disease. It is also a rare but wellrecognised consequence of therapy (for example with methotrexate and leflunomide).Caplan's syndrome describes lung nodules inindividuals with rheumatoid arthritis and additional exposure to coal dust. Pleuraleffusions are also associated with rheumatoid arthritis.
Renal amyloidosiscan occur as a consequence of chronic inflammation. Rheumatoid arthritis mayaffect the kidney glomerulus directly through a vasculopathy or a mesangialinfiltrate but this is less well documented. Treatment with Penicillamineand goldsalts 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 markedlyincreased.Other possible complications that may arise include: pericarditis,endocarditis,left ventricular failure, valvulitis and fibrosis. Manypeople with rheumatoid arthritis do not experience the same chest pain thatothers feel when they have angina or myocardial infarction. To reducecardiovascular risk, it is crucial to maintain optimal control of the inflammationcaused by rheumatoid arthritis (which may be involved in causing thecardiovascular risk), and to use exercise and medications appropriately toreduce other cardiovascular risk factors such as blood lipids and bloodpressure. Doctors who treat rheumatoid arthritis patients should be sensitiveto cardiovascular risk when prescribing anti-inflammatory medications, and maywant to consider prescribing routine use of low doses of aspirin if thegastrointestinal effects are tolerable.
The eye is directly affected in theform of episcleritiswhich when severe can very rarely progress to perforating scleromalacia. Rather morecommon is the indirect effect of keratoconjunctivitis sicca, which is adryness of eyes and mouth caused by lymphocyte infiltration of lachrymal andsalivary glands. When severe, dryness of the cornea can lead to keratitis andloss of vision. Preventive treatment of severe dryness with measures such as nasolacrimalduct occlusion is important.
Cytokine production in joints and/orhepatic Kupffer cells leads to increased activity ofhepatocytes with increased production of acute-phase proteins, such asC-reactive protein, and increased release of enzymes such as alkalinephosphatase into the blood. In Felty'ssyndrome, Kuppfer cell activation is so marked that the resulting increasein hepatocyte activity is associated with nodular hyperplasia of the liver,which may be palpably enlarged. Because Kuppfer cells are not within the liverparenchyma, there is little or no evidence of hepatitis. Hepatic involvement inRA is essentially asymptomatic.
Anemia is by farthe most common abnormality of the blood cells. The red cells are of normalsize and colour (normocytic). A low white blood cell count (neutropenia)usually only occurs in patients with Felty's syndrome with an enlarged liverand spleen. The mechanism of neutropenia is complex. An increased plateletcount (thrombocytosis) occurs when inflammation isuncontrolled, as does the anemia.
Peripheral neuropathy and mononeuritis multiplex may occur. The mostcommon problem is carpal tunnel syndrome caused by compression of the mediannerve by swelling around the wrist. Atlanto-axialsubluxation can occur, owing to erosion of the odontoid process andor/transverse ligaments in the cervical spine's connection to the skull. Suchan erosion (>3mm) can give rise to vertebrae slipping over one another andcompressing the spinal cord. Clumsiness is initially experienced, but withoutdue care this can progress to quadriplegia.
Constitutional symptoms including fatigue,low grade fever, malaise, morningstiffness, loss of appetite and loss ofweight are common systemic manifestations seen in patients withactive rheumatoid arthritis.
Local osteoporosisoccurs in RA around inflamed joints. It is postulated to be partially caused byinflammatory cytokines. More general osteoporosis is probably contributed to byimmobility, systemic cytokine effects, and local cytokine release in bonemarrow and corticosteroid therapy.
The incidence of lymphoma isincreased in RA, although it is still uncommon.