Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints. The process involves an inflammatory response of the capsule around the joints (synovium) secondary to swelling (hyperplasia) of synovial cells, excess synovial fluid, and the development of fibrous tissue (pannus) in the synovium. The pathology of the disease process often leads to the destruction of articular cartilage and ankylosis (fusion) of the joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, membrane around the heart (pericardium), the membranes of the lung (pleura), and white of the eye (sclera), and also nodular lesions, most common in subcutaneous tissue. Although the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in both its chronicity and progression, and RA is considered a systemic autoimmune disease.
 
Signs and symptoms
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, 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.
Skin
The rheumatoid nodule, which is sometimes cutaneous, is the feature most characteristic of rheumatoid arthritis. It is a type of inflammatory reaction known to pathologists as a "necrotizing granuloma". 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 symptoms 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 recognized response to rheumatoid disease. It is also a rare but well recognized 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. Another complication of RA is Rheumatoid Lung Disease. It is estimated that about one quarter of Americans with RA develop Rheumatoid Lung Disease.
Kidneys
Renal amyloidosis can occur as a consequence of chronic inflammation.
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
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 caused by lymphocyte infiltration of lacrimal 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.
Hematological
Anemia is by far the most common abnormality of the blood cells.
Neurological
Peripheral neuropathy and mononeuritis multiplex may occur.
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.
 
Diagnosis Imaging

1. ultrasonography
2. magnetic resonance imaging in the second metacarpophalangeal joint in established rheumatoid arthritis.
3. X-rays of the hands and feet are generally performed in people with a polyarthritis.
4. Other medical imaging techniques such as magnetic resonance imaging (MRI) and ultrasound are also used in rheumatoid arthritis.
5. Blood tests

 Differential diagnoses

• Crystal induced arthritis (gout, and pseudogout) – usually involves particular joints (knee, MTP1, heels) and can be distinguished with aspiration of joint fluid if in doubt. Redness, asymmetric distribution of affected joints, pain occurs at night and the starting pain is less than an hour with gout.
• Osteoarthritis – distinguished with X-rays of the affected joints and blood tests, age (mostly older patients), starting pain less than an hour, a-symmetric distribution of affected joints and pain worsens when using joint for longer periods.
• Systemic lupus erythematosus (SLE) – distinguished by specific clinical symptoms and blood tests (antibodies against double-stranded DNA)
• One of the several types of psoriatic arthritis resembles RA – nail changes and skin symptoms distinguish between them
• Lyme disease causes erosive arthritis and may closely resemble RA – it may be distinguished by blood test in endemic areas
• Reactive arthritis (previously Reiter's disease) – asymmetrically involves heel, sacroiliac joints, and large joints of the leg. It is usually associated with urethritis, conjunctivitis, iritis, painless buccal ulcers, and keratoderma blennorrhagica.
• Ankylosing spondylitis – this involves the spine, although a RA-like symmetrical small-joint polyarthritis may occur in the context of this condition.
• Hepatitis C – RA-like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C may also induce Rheumatoid Factor auto-antibodies

Rarer causes that usually behave differently but may cause joint pains:^[

• Sarcoidosis, amyloidosis, and Whipple's disease can also resemble RA.
• Hemochromatosis may cause hand joint arthritis.
• Acute rheumatic fever can be differentiated from RA by a migratory pattern of joint involvement and evidence of antecedent streptococcal infection. Bacterial arthritis (such as streptococcus) is usually asymmetric, while RA usually involves both sides of the body symmetrically.
• Gonococcal arthritis (another bacterial arthritis) is also initially migratory and can involve tendons around the wrists and ankles.

 Treatment
Cortisone therapy has offered relief in the past, but its long-term effects have been deemed undesirable.
Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics.^[46][47] Treatment also includes rest and physical activity.
Disease modifying anti-rheumatic drugs (DMARDs)
Common combinations of DMARDs include methotrexate – hydroxychloroquine, methotrexate – sulfasalazine, sulfasalazine – hydroxychloroquine, and methotrexate – hydroxychloroquine – sulfasalazine.
Traditional small molecular mass drugs
Chemically synthesised DMARDs:

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

Cytotoxic drugs:

• Cyclophosphamide

Biological agents
Biological agents (biologics) include:

• tumor necrosis factor alpha (TNFα) blockers– etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi)
• Interleukin 1 (IL-1) blockers – anakinra (Kineret)
• monoclonal antibodies against B cells – rituximab (Rituxan)^[
• T cell costimulation blocker – abatacept (Orencia)
• Interleukin 6 (IL-6) blockers – tocilizumab (an anti-IL-6 receptor antibody) (RoActemra, Actemra)

Anti-inflammatory agents and analgesics
Anti-inflammatory agents include:

• glucocorticoids
• Non-steroidal anti-inflammatory drug (NSAIDs, most also act as analgesics)

Analgesics include:

• paracetamol (acetaminophen in US and Canada)
• opiates
• diproqualone
• lidocaine topical

Surgery
In early phases of the disease, an arthroscopic or open synovectomy may be performed. It consists of the removal of the inflamed synovia and prevents a quick destruction of the affected joints.
 
Prognosis
The course of the disease varies greatly. Some people 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.