Arthritis

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Arthritis is a term often used to mean any disorder that affects joints.[2] Symptoms generally include joint pain and stiffness.[2] Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints.[2][3] In some types other organs are also affected.[6] Onset can be gradual or sudden.[5]

There are over 100 types of arthritis.[4][5] The most common forms are osteoarthritis (degenerative joint disease) and rheumatoid arthritis.[6] Osteoarthritis usually occurs with age and affects the fingers, knees, and hips.[6] Rheumatoid arthritis is an autoimmune disorder that often affects the hands and feet.[6] Other types include gout, lupus, fibromyalgia, and septic arthritis.[6][8] They are all types of rheumatic disease.[2]

Treatment may include resting the joint and alternating between applying ice and heat.[6] Weight loss and exercise may also be useful.[6] Pain medications such as ibuprofen and paracetamol (acetaminophen) may be used.[7] In some a joint replacement may be useful.[6]

Osteoarthritis affects more than 3.8% of people while rheumatoid arthritis affects about 0.24% of people.[9] Gout affects about 1–2% of the Western population at some point in their lives.[10] In Australia about 15% of people are affected,[11] while in the United States more than 20% have a type of arthritis.[8][12] Overall the disease becomes more common with age.[8] Arthritis is a common reason that people miss work and can result in a decreased quality of life.[7] The term is derived from arthr- (meaning joint) and -itis (meaning inflammation).[13][14]

Arthritis
photograph of elderly hand depicting advanced rheumatoid arthritis
A hand affected by rheumatoid arthritis, an autoimmune form of arthritis
Pronunciation
  • /ɑːrˈθraɪtɪs/[1]
SpecialtyRheumatology
SymptomsJoint pain, stiffness, redness, swelling, decreased range of motion[2][3]
Types> 100, most common (osteoarthritis, rheumatoid arthritis)[4][5][6]
TreatmentResting, applying ice or heat, weight loss, exercise, joint replacement[6]
MedicationIbuprofen, paracetamol (acetaminophen)[7]

Classification

There are several diseases where joint pain is primary, and is considered the main feature. Generally when a person has "arthritis" it means that they have one of these diseases, which include:

Joint pain can also be a symptom of other diseases. In this case, the arthritis is considered to be secondary to the main disease; these include:

An undifferentiated arthritis is an arthritis that does not fit into well-known clinical disease categories, possibly being an early stage of a definite rheumatic disease.[19]

Signs and symptoms

Extra-articular features of joint disease[20]
Cutaneous nodules
Cutaneous vasculitis lesions
Lymphadenopathy
Oedema
Ocular inflammation
Urethritis
Tenosynovitis (tendon sheath effusions)
Bursitis (swollen bursa)
Diarrhea
Orogenital ulceration

Pain, which can vary in severity, is a common symptom in virtually all types of arthritis. Other symptoms include swelling, joint stiffness and aching around the joint(s). Arthritic disorders like lupus and rheumatoid arthritis can affect other organs in the body, leading to a variety of symptoms.[21] Symptoms may include:

It is common in advanced arthritis for significant secondary changes to occur. For example, arthritic symptoms might make it difficult for a person to move around and/or exercise, which can lead to secondary effects, such as:

These changes, in addition to the primary symptoms, can have a huge impact on quality of life.

Disability

Arthritis is the most common cause of disability in the United States. More than 20 million individuals with arthritis have severe limitations in function on a daily basis.[22] Absenteeism and frequent visits to the physician are common in individuals who have arthritis. Arthritis can make it very difficult for individuals to be physically active and some become home bound.

It is estimated that the total cost of arthritis cases is close to $100 billion of which almost 50% is from lost earnings. Each year, arthritis results in nearly 1 million hospitalizations and close to 45 million outpatient visits to health care centers.[23]

Decreased mobility, in combination with the above symptoms, can make it difficult for an individual to remain physically active, contributing to an increased risk of obesity, high cholesterol or vulnerability to heart disease.[24] People with arthritis are also at increased risk of depression, which may be a response to numerous factors, including fear of worsening symptoms.[25]

Diagnosis

Diagnosis is made by clinical examination from an appropriate health professional, and may be supported by other tests such as radiology and blood tests, depending on the type of suspected arthritis.[26] All arthritides potentially feature pain. Pain patterns may differ depending on the arthritides and the location. Rheumatoid arthritis is generally worse in the morning and associated with stiffness lasting over 30 minutes. However, in the early stages, patients may have no symptoms after a warm shower. Osteoarthritis, on the other hand, tends to be associated with morning stiffness which eases relatively quickly with movement and exercise. In the aged and children, pain might not be the main presenting feature; the aged patient simply moves less, the infantile patient refuses to use the affected limb.

Elements of the history of the disorder guide diagnosis. Important features are speed and time of onset, pattern of joint involvement, symmetry of symptoms, early morning stiffness, tenderness, gelling or locking with inactivity, aggravating and relieving factors, and other systemic symptoms. Physical examination may confirm the diagnosis, or may indicate systemic disease. Radiographs are often used to follow progression or help assess severity.

Blood tests and X-rays of the affected joints often are performed to make the diagnosis. Screening blood tests are indicated if certain arthritides are suspected. These might include: rheumatoid factor, antinuclear factor (ANF), extractable nuclear antigen, and specific antibodies.

Osteoarthritis

Osteoarthritis is the most common form of arthritis.[27] It can affect both the larger and the smaller joints of the body, including the hands, wrists, feet, back, hip, and knee. The disease is essentially one acquired from daily wear and tear of the joint; however, osteoarthritis can also occur as a result of injury. In recent years, some joint or limb deformities, such as knock-knee or acetabular overcoverage or dysplasia, have also been considered as a predisposing factor for knee or hip osteoarthritis. Osteoarthritis begins in the cartilage and eventually causes the two opposing bones to erode into each other. The condition starts with minor pain during physical activity, but soon the pain can be continuous and even occur while in a state of rest. The pain can be debilitating and prevent one from doing some activities. Osteoarthritis typically affects the weight-bearing joints, such as the back, knee and hip. Unlike rheumatoid arthritis, osteoarthritis is most commonly a disease of the elderly. More than 30 percent of women have some degree of osteoarthritis by age 65. Risk factors for osteoarthritis include prior joint trauma, obesity, and a sedentary lifestyle.[28]

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a disorder in which the body's own immune system starts to attack body tissues. The attack is not only directed at the joint but to many other parts of the body. In rheumatoid arthritis, most damage occurs to the joint lining and cartilage which eventually results in erosion of two opposing bones. RA often affects joints in the fingers, wrists, knees and elbows, is symmetrical (appears on both sides of the body), and can lead to severe deformity in a few years if not treated. RA occurs mostly in people aged 20 and above. In children, the disorder can present with a skin rash, fever, pain, disability, and limitations in daily activities. With earlier diagnosis and aggressive treatment, many individuals can lead a better quality of life than if going undiagnosed for long after RA's onset. The drugs to treat RA range from corticosteroids to monoclonal antibodies given intravenously. Treatments also include analgesics such as NSAIDs and disease-modifying antirheumatic drugs (DMARDs), while in rare cases, surgery may be required to replace joints, but there is no cure for the disease.[30]

Treatment with DMARDs is designed to initiate an adaptive immune response, in part by CD4+ T helper (Th) cells, specifically Th17 cells.[31] Th17 cells are present in higher quantities at the site of bone destruction in joints and produce inflammatory cytokines associated with inflammation, such as interleukin-17 (IL-17).[32]

Bone erosion is a central feature of rheumatoid arthritis. Bone continuously undergoes remodeling by actions of bone resorbing osteoclasts and bone forming osteoblasts. One of the main triggers of bone erosion in the joints in rheumatoid arthritis is inflammation of the synovium, caused in part by the production of pro-inflammatory cytokines and receptor activator of nuclear factor kappa B ligand (RANKL), a cell surface protein present in Th17 cells and osteoblasts.[32] Osteoclast activity can be directly induced by osteoblasts through the RANK/RANKL mechanism.[33]

Lupus

Lupus is a common collagen vascular disorder that can be present with severe arthritis. Other features of lupus include a skin rash, extreme photosensitivity, hair loss, kidney problems, lung fibrosis and constant joint pain.[34]

Gout

Gout is caused by deposition of uric acid crystals in the joint, causing inflammation. There is also an uncommon form of gouty arthritis caused by the formation of rhomboid crystals of calcium pyrophosphate known as pseudogout. In the early stages, the gouty arthritis usually occurs in one joint, but with time, it can occur in many joints and be quite crippling. The joints in gout can often become swollen and lose function. Gouty arthritis can become particularly painful and potentially debilitating when gout cannot successfully be treated.[35] When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of uric acid (e.g., allopurinol, febuxostat) or increase uric acid elimination from the body through the kidneys (e.g., probenecid), this can be referred to as refractory chronic gout or RCG.[36]

Comparison of types

Comparison of some major forms of arthritis[37]
Osteoarthritis Rheumatoid arthritis Gouty arthritis
Speed of onset Months Weeks-months[38] Hours for an attack[39]
Main locations Weight-bearing joints (such as knees, hips, vertebral column) and hands Hands (proximal interphalangeal and metacarpophalangeal joint) wrists, ankles, knees and hips Great toe, ankles, knees and elbows
Inflammation May occur, though often mild compared to inflammation in rheumatoid arthritis Yes Yes
Radiologic changes
  • Narrowed joint space
  • Bone erosions
  • "Punched out" bone erosions
Laboratory findings None Anemia, elevated ESR and C-reactive protein (CRP), rheumatoid factor, anti-citrullinated protein antibody Crystal in joints
Other features

Other

Infectious arthritis is another severe form of arthritis. It presents with sudden onset of chills, fever and joint pain. The condition is caused by bacteria elsewhere in the body. Infectious arthritis must be rapidly diagnosed and treated promptly to prevent irreversible joint damage.[40]

Psoriasis can develop into psoriatic arthritis. With psoriatic arthritis, most individuals develop the skin problem first and then the arthritis. The typical features are of continuous joint pains, stiffness and swelling. The disease does recur with periods of remission but there is no cure for the disorder. A small percentage develop a severe painful and destructive form of arthritis which destroys the small joints in the hands and can lead to permanent disability and loss of hand function.[41]

Treatment

There is no known cure for either rheumatoid or osteoarthritis. Treatment options vary depending on the type of arthritis and include physical therapy, lifestyle changes (including exercise and weight control), orthopedic bracing, and medications. Joint replacement surgery may be required in eroding forms of arthritis. Medications can help reduce inflammation in the joint which decreases pain. Moreover, by decreasing inflammation, the joint damage may be slowed.

Physical therapy

In general, studies have shown that physical exercise of the affected joint can noticeably improve long-term pain relief. Furthermore, exercise of the arthritic joint is encouraged to maintain the health of the particular joint and the overall body of the person.[42]

Individuals with arthritis can benefit from both physical and occupational therapy. In arthritis the joints become stiff and the range of movement can be limited. Physical therapy has been shown to significantly improve function, decrease pain, and delay need for surgical intervention in advanced cases.[43] Exercise prescribed by a physical therapist has been shown to be more effective than medications in treating osteoarthritis of the knee. Exercise often focuses on improving muscle strength, endurance and flexibility. In some cases, exercises may be designed to train balance. Occupational therapy can provide assistance with activities. Assistive technology is a tool used to aid a person's disability by reducing their physical barriers by improving the use of their damaged body part, typically after an amputation. Assistive technology devices can be customized to the patient or bought commercially. [44].

Medications

There are several types of medications that are used for the treatment of arthritis. Treatment typically begins with medications that have the fewest side effects with further medications being added if insufficiently effective.[45]

Depending on the type of arthritis, the medications that are given may be different. For example, the first-line treatment for osteoarthritis is acetaminophen (paracetamol) while for inflammatory arthritis it involves non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen. Opioids and NSAIDs are less well tolerated.[46]

Rheumatoid arthritis (RA) is autoimmune so, in addition to pain medications and anti-inflammatory drugs, is treated with another category of drug called disease-modifying antirheumatic drugs (DMARDs), which act on the immune system to slow down the progression of RA. An example of this type of drug is methotrexate.

Surgery

A number of rheumasurgical interventions have been incorporated in the treatment of arthritis since the 1950s. Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy.[47]

Alternative medicine

Further research is required to determine if transcutaneous electrical nerve stimulation (TENS) for knee osteoarthritis is effective for controlling pain.[48]

Low level laser therapy may be considered for relief of pain and stiffness associated with arthritis.[49] Evidence of benefit is tentative.[50]

Pulsed electromagnetic field therapy has tentative evidence supporting improved functioning but no evidence of improved pain in osteoarthritis.[51] The FDA has not approved PEMF for the treatment of arthritis. In Canada, PEMF devices are legally licensed by Health Canada for the treatment of pain associated with arthritic conditions.

Epidemiology

Arthritis is predominantly a disease of the elderly, but children can also be affected by the disease. Arthritis is more common in women than men at all ages and affects all races, ethnic groups and cultures. In the United States a CDC survey based on data from 2007–2009 showed 22.2% (49.9 million) of adults aged ≥18 years had self-reported doctor-diagnosed arthritis, and 9.4% (21.1 million or 42.4% of those with arthritis) had arthritis-attributable activity limitation (AAAL). With an aging population, this number is expected to increase.[52]

Disability due to musculoskeletal disorders increased by 45% from 1990 to 2010. Of these, osteoarthritis is the fastest increasing major health condition.[53] Among the many reports on the increased prevalence of musculoskeletal conditions, data from Africa are lacking and underestimated. A systematic review assessed the prevalence of arthritis in Africa and included twenty population-based and seven hospital-based studies.[54] The majority of studies, twelve, were from South Africa. Nine studies were well-conducted, eleven studies were of moderate quality, and seven studies were conducted poorly. The results of the systematic review were as follows:

  • Rheumatoid arthritis: 0.1% in Algeria (urban setting); 0.6% in Democratic Republic of Congo (urban setting); 2.5% and 0.07% in urban and rural settings in South Africa respectively; 0.3% in Egypt (rural setting), 0.4% in Lesotho (rural setting)
  • Osteoarthritis: 55.1% in South Africa (urban setting); ranged from 29.5 to 82.7% in South Africans aged 65 years and older
    • Knee osteoarthritis has the highest prevalence from all types of osteoarthritis, with 33.1% in rural South Africa
  • Ankylosing spondylitis: 0.1% in South Africa (rural setting)
  • Psoriatic arthritis: 4.4% in South Africa (urban setting)
  • Gout: 0.7% in South Africa (urban setting)
  • Juvenile idiopathic arthritis: 0.3% in Egypt (urban setting)

History

Evidence of osteoarthritis and potentially inflammatory arthritis has been discovered in dinosaurs.[55][56] The first known traces of human arthritis date back as far as 4500 BC. In early reports, arthritis was frequently referred to as the most common ailment of prehistoric peoples.[57] It was noted in skeletal remains of Native Americans found in Tennessee and parts of what is now Olathe, Kansas. Evidence of arthritis has been found throughout history, from Ötzi, a mummy (circa 3000 BC) found along the border of modern Italy and Austria, to the Egyptian mummies circa 2590 BC.[58]

In 1715, William Musgrave published the second edition of his most important medical work, De arthritide symptomatica, which concerned arthritis and its effects.[59]

Terminology

The term is derived from arthr- (from Ancient Greek: ἄρθρον, translit. árthron, lit. 'joint, limb') and -itis (from -ῖτις, -îtis, lit. 'pertaining to'), the latter suffix having come to be associated with inflammation.

The word 'arthritides' denotes the collective group of arthritis-like conditions.

See also

References

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  59. ^ Alick Cameron, "Musgrave, William (1655–1721)", Oxford Dictionary of National Biography, Oxford University Press, Sept 2004

External links

External resources
Adalimumab

Adalimumab, sold under the trade name Humira among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis, hidradenitis suppurativa, juvenile idiopathic arthritis, and uveitis. In rheumatoid arthritis, adalimumab has a response rate similar to methotrexate, and in combination, it nearly doubles the response rate of methotrexate alone.

Adalimumab is a TNF-inhibiting, anti-inflammatory, biologic medication. It binds to tumor necrosis factor-alpha (TNFα), which reduces the immune response. There is strong evidence that adalimumab increases the risk of life-threatening infections and cancers, particularly lymphoma.

Humira costs approximately $4370 per month (2017). From 2012 until the US patent expiry in 2016, Humira led the list of top-selling pharmaceutical products, and in 2016, it had $16 billion of global sales. In 2014, in India, the first adalimumab biosimilar came to market at a price of $200. Two years later, another Indian drugmaker, Torrent Pharmaceuticals, launched a second biosimilar. Humira's U.S. patent expired in 2016. Adalimumab biosimilars are available in Europe from late 2018.

Analgesic

An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain.

Analgesic drugs act in various ways on the peripheral and central nervous systems. They are distinct from anesthetics, which temporarily affect, and in some instances completely eliminate, sensation. Analgesics include paracetamol (known in North America as acetaminophen or simply APAP), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, and opioid drugs such as morphine and oxycodone.

When choosing analgesics, the severity and response to other medication determines the choice of agent; the World Health Organization (WHO) pain ladder specifies mild analgesics as its first step.

Analgesic choice is also determined by the type of pain: For neuropathic pain, traditional analgesics are less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants.

Ankylosing spondylitis

Ankylosing spondylitis (AS) is a type of arthritis in which there is long term inflammation of the joints of the spine. Typically the joints where the spine joins the pelvis are also affected. Occasionally other joints such as the shoulders or hips are involved. Eye and bowel problems may also occur. Back pain is a characteristic symptom of AS, and it often comes and goes. Stiffness of the affected joints generally worsens over time.Although the cause of ankylosing spondylitis is unknown, it is believed to involve a combination of genetic and environmental factors. More than 90% of those affected have a specific human leukocyte antigen known as the HLA-B27 antigen. The underlying mechanism is believed to be autoimmune or autoinflammatory. Diagnosis is typically based on the symptoms with support from medical imaging and blood tests. AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies. It is also within a broader category known as axial spondyloarthritis.There is no cure for ankylosing spondylitis. Treatments may improve symptoms and prevent worsening. This may include medication, exercise, and surgery. Medications used include NSAIDs, steroids, DMARDs such as sulfasalazine, and biologic agents such as infliximab.Between 0.1% and 1.8% of people are affected. Onset is typically in young adults. Males are more often affected than females. The condition was first fully described in the late 1600s by Bernard Connor, but skeletons with ankylosing spondylitis are found in Egyptian mummies. The word is from Greek ankylos meaning stiffening, spondylos meaning vertebra, and -itis meaning inflammation.

Arthralgia

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Arthralgia is a symptom of injury, infection, illnesses (in particular arthritis) or an allergic reaction to medication.According to MeSH, the term "arthralgia" should only be used when the condition is non-inflammatory, and the term "arthritis" should be used when the condition is inflammatory. The term is from Greek arthro-, joint + -algos, pain) literally means joint pain.

Disease-modifying antirheumatic drug

Disease-modifying antirheumatic drugs (DMARDs) is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to nonsteroidal anti-inflammatory drug (which refers to agents that treat the inflammation but not the underlying cause) and steroids (which blunt the immune response but are insufficient to slow down the progression of the disease).

The term "antirheumatic" can be used in similar contexts, but without making a claim about an effect on the course. Other terms that have historically been used to refer to the same group of drugs are "remission-inducing drugs" (RIDs) and "slow-acting anti-rheumatic drugs" (SAARDs).

Etanercept

Etanercept (trade name Enbrel or Benepali) is a biopharmaceutical that treats autoimmune diseases by interfering with tumor necrosis factor (TNF, a soluble inflammatory cytokine) by acting as a TNF inhibitor. It has U.S. F.D.A. approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. TNF-alpha is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.Etanercept is a fusion protein produced by recombinant DNA. It fuses the TNF receptor to the constant end of the IgG1 antibody. First, the developers isolated the DNA sequence that codes the human gene for soluble TNF receptor 2, which is a receptor that binds to tumor necrosis factor-alpha. Second, they isolated the DNA sequence that codes the human gene for the Fc end of immunoglobulin G1 (IgG1). Third, they linked the DNA for TNF receptor 2 to the DNA for IgG1 Fc. Finally, they expressed the linked DNA to produce a protein that links the protein for TNF receptor 2 to the protein for IgG1 Fc.

The prototypic fusion protein was first synthesized and shown to be highly active and unusually stable as a modality for blockade of TNF in vivo in the early 1990s by Bruce A. Beutler, an academic researcher then at the University of Texas Southwestern Medical Center at Dallas, and his colleagues.These investigators also patented the protein, selling all rights to its use to Immunex, a biotechnology company that was acquired by Amgen in 2002.It is a large molecule, with a molecular weight of 150 kDa., that binds to TNFα and decreases its role in disorders involving excess inflammation in humans and other animals, including autoimmune diseases such as ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and, potentially, in a variety of other disorders mediated by excess TNFα.

Gout

Gout is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot, and swollen joint. Pain typically comes on rapidly, reaching maximal intensity in less than twelve hours. The joint at the base of the big toe is affected in about half of cases. It may also result in tophi, kidney stones, or urate nephropathy.Gout is due to persistently elevated levels of uric acid in the blood. This occurs from a combination of diet, other health problems, and genetic factors. At high levels, uric acid crystallizes and the crystals deposit in joints, tendons, and surrounding tissues, resulting in an attack of gout. Gout occurs more commonly in those who regularly eat meat or seafood, drink beer, or are overweight. Diagnosis of gout may be confirmed by the presence of crystals in the joint fluid or in a deposit outside the joint. Blood uric acid levels may be normal during an attack.Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine improves symptoms. Once the acute attack subsides, levels of uric acid can be lowered via lifestyle changes and in those with frequent attacks, allopurinol or probenecid provides long-term prevention. Taking vitamin C and eating a diet high in low-fat dairy products may be preventive.Gout affects about 1 to 2% of the Western population at some point in their lives. It has become more common in recent decades. This is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy, and changes in diet. Older males are most commonly affected. Gout was historically known as "the disease of kings" or "rich man's disease". It has been recognized at least since the time of the ancient Egyptians.

Juvenile idiopathic arthritis

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Juvenile idiopathic arthritis (JIA), also known as juvenile rheumatoid arthritis (JRA), is the most common form of arthritis in children and adolescents. ("Juvenile" in this context refers to an onset before age 16, "idiopathic" refers to a condition with no defined cause, and "arthritis" is the inflammation of the synovium of a joint.)

JIA is an autoimmune, noninfective, inflammatory joint disease of more than 6 weeks duration in children less than 16 years of age. The disease commonly occurs in children from the ages of 1 to 6, but it may develop as late as 15 years of age. It is a subset of arthritis seen in childhood, which may be transient and self-limited or chronic. It differs significantly from arthritis commonly seen in adults (osteoarthritis, rheumatoid arthritis), and other types of arthritis that can present in childhood which are chronic conditions (e.g. psoriatic arthritis and ankylosing spondylitis). Aetiopathology is similar to rheumatoid arthritis, but with less marked cartilage erosion, and joint instability and absent rheumatoid factor.

JIA affects about one in 1,000 children in any given year, with about one in 10,000 having a more severe form.

Methotrexate

Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune system suppressant. It is used to treat cancer, autoimmune diseases, ectopic pregnancy, and for medical abortions. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It acts by blocking the body's use of folic acid.Methotrexate was made in 1947 and initially came into medical use to treat cancer, as it was less toxic than the then-current treatments. In 1956 it provided the first cures of a metastatic cancer. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Methotrexate is available as a generic medication. The wholesale cost as of 2014 in the developing world is between US$0.06 and US$0.36 per day for the form taken by mouth. In the United States, a typical month of treatment costs $25 to $50.

Osteoarthritis

Osteoarthritis (OA) is a type of joint disease that results from breakdown of joint cartilage and underlying bone. The most common symptoms are joint pain and stiffness. Initially, symptoms may occur only following exercise, but over time may become constant. Other symptoms may include joint swelling, decreased range of motion, and, when the back is affected, weakness or numbness of the arms and legs. The most commonly involved joints are those near the ends of the fingers, at the base of the thumb, neck, lower back, knee, and hips. Joints on one side of the body are often more affected than those on the other. Usually the symptoms come on over years. It can affect work and normal daily activities. Unlike other types of arthritis, only the joints are typically affected.Causes include previous joint injury, abnormal joint or limb development, and inherited factors. Risk is greater in those who are overweight, have one leg of a different length, and have jobs that result in high levels of joint stress. Osteoarthritis is believed to be caused by mechanical stress on the joint and low grade inflammatory processes. It develops as cartilage is lost and the underlying bone becomes affected. As pain may make it difficult to exercise, muscle loss may occur. Diagnosis is typically based on signs and symptoms, with medical imaging and other tests occasionally used to either support or rule out other problems. In contrast to rheumatoid arthritis, which is primarily an inflammatory condition, in osteoarthritis, the joints do not become hot or red.Treatment includes exercise, efforts to decrease joint stress, support groups, and pain medications. Efforts to decrease joint stress include resting and the use of a cane. Weight loss may help in those who are overweight. Pain medications may include paracetamol (acetaminophen) as well as NSAIDs such as naproxen or ibuprofen. Long-term opioid use is generally discouraged due to lack of information on benefits as well as risks of addiction and other side effects. If pain interferes with normal life despite other treatments, joint replacement surgery may help. An artificial joint typically lasts 10 to 15 years.Osteoarthritis is the most common form of arthritis, affecting about 237 million (3.3% of the population). Among those over 60 years old, about 10% of males and 18% of females are affected. It is the cause of about 2% of years lived with disability. In Australia, about 1.9 million people are affected, and in the United States, 30 to 53 million people are affected. It becomes more common in both sexes as people become older.

Psoriasis

Psoriasis is a long-lasting autoimmune disease characterized by patches of abnormal skin. These skin patches are typically red, dry, itchy, and scaly. On people with darker skin the patches may be purple in colour. Psoriasis varies in severity from small, localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.There are five main types of psoriasis: plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90 percent of cases. It typically presents as red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. Guttate psoriasis has drop-shaped lesions. Pustular psoriasis presents as small non-infectious pus-filled blisters. Inverse psoriasis forms red patches in skin folds. Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. Fingernails and toenails are affected in most people with psoriasis at some point in time. This may include pits in the nails or changes in nail color.Psoriasis is generally thought to be a genetic disease that is triggered by environmental factors. In twin studies, identical twins are three times more likely to be affected compared to non-identical twins. This suggests that genetic factors predispose to psoriasis. Symptoms often worsen during winter and with certain medications, such as beta blockers or NSAIDs. Infections and psychological stress can also play a role. Psoriasis is not contagious. The underlying mechanism involves the immune system reacting to skin cells. Diagnosis is typically based on the signs and symptoms.There is no cure for psoriasis; however, various treatments can help control the symptoms. These treatments include steroid creams, vitamin D3 cream, ultraviolet light and immune system suppressing medications, such as methotrexate. About 75 percent of cases can be managed with creams alone. The disease affects two to four percent of the population. Men and women are affected with equal frequency. The disease may begin at any age, but typically starts in adulthood. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohn's disease and depression. Psoriatic arthritis affects up to 30 percent of individuals with psoriasis.

Psoriatic arthritis

Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis (e.g., red, scaly, and itchy plaques) frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

Genetics are thought to be strongly involved in the development of psoriatic arthritis. Obesity and certain forms of psoriasis are thought to increase the risk.Psoriatic arthritis affects up to 30% of people with psoriasis and occurs in both children and adults. Approximately 40–50% of individuals with psoriatic arthritis have the HLA-B27 genotype. The condition is less common in people of Asian or African descent and affects men and women equally.

Reactive arthritis

Reactive arthritis, formerly known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease. By the time the patient presents with symptoms, often the "trigger" infection has been cured or is in remission in chronic cases, thus making determination of the initial cause difficult.

The arthritis often is coupled with other characteristic symptoms; this was previously referred to as Reiter's syndrome, Reiter's disease or Reiter's arthritis. The term "reactive arthritis" is preferred and increasingly used as a substitute for this designation due to Hans Conrad Julius Reiter's war crimes with the Nazi Party.

The manifestations of reactive arthritis include the following triad of symptoms: an inflammatory arthritis of large joints, inflammation of the eyes in the form of conjunctivitis or uveitis, and urethritis in men or cervicitis in women. Arthritis occurring alone following sexual exposure or enteric infection is also known as reactive arthritis. Patients can also present with mucocutaneous lesions, as well as psoriasis-like skin lesions such as circinate balanitis, and keratoderma blennorrhagicum. Enthesitis can involve the Achilles tendon resulting in heel pain. Not all affected persons have all the manifestations.

The clinical pattern of reactive arthritis commonly consists of an inflammation of fewer than five joints which often includes the knee or sacroiliac joint. The arthritis may be "additive" (more joints become inflamed in addition to the primarily affected one) or "migratory" (new joints become inflamed after the initially inflamed site has already improved).Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis often precipitated by genitourinary or gastrointestinal infections. The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis).It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population. It can occur in epidemic form. Patients with HIV have an increased risk of developing reactive arthritis as well.

A large number of cases during World Wars I and II focused attention on the triad of arthritis, urethritis, and conjunctivitis (often with additional mucocutaneous lesions), which at that time was also referred to as Fiessenger-Leroy-Reiter syndrome.

Rheumatism

Rheumatism or rheumatic disorder is an umbrella term for conditions causing

chronic, often intermittent pain affecting the joints and/or connective tissue.

The study of, and therapeutic interventions in, such disorders is called rheumatology.

The term "rheumatism", however, does not designate any specific disorder, but covers at least 200 different conditions.Sources dealing with rheumatism tend to focus on arthritis, but "rheumatism" may also refer to other conditions causing chronic pain, grouped as "non-articular rheumatism", also known as "regional pain syndrome" or "soft tissue rheumatism". The term "Rheumatic Diseases" is used in MeSH to refer to connective tissue disorders.

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves the body's immune system attacking the joints. This results in inflammation and thickening of the joint capsule. It also affects the underlying bone and cartilage. The diagnosis is made mostly on the basis of a person's signs and symptoms. X-rays and laboratory testing may support a diagnosis or exclude other diseases with similar symptoms. Other diseases that may present similarly include systemic lupus erythematosus, psoriatic arthritis, and fibromyalgia among others.The goals of treatment are to reduce pain, decrease inflammation, and improve a person's overall functioning. This may be helped by balancing rest and exercise, the use of splints and braces, or the use of assistive devices. Pain medications, steroids, and NSAIDs are frequently used to help with symptoms. Disease-modifying antirheumatic drugs (DMARDs), such as hydroxychloroquine and methotrexate, may be used to try to slow the progression of disease. Biological DMARDs may be used when disease does not respond to other treatments. However, they may have a greater rate of adverse effects. Surgery to repair, replace, or fuse joints may help in certain situations. Most alternative medicine treatments are not supported by evidence.RA affects about 24.5 million people as of 2015. This is between 0.5 and 1% of adults in the developed world with 5 and 50 per 100,000 people newly developing the condition each year. Onset is most frequent during middle age and women are affected 2.5 times as frequently as men. In 2013, it resulted in 38,000 deaths up from 28,000 deaths in 1990. The first recognized description of RA was made in 1800 by Dr. Augustin Jacob Landré-Beauvais (1772–1840) of Paris. The term rheumatoid arthritis is based on the Greek for watery and inflamed joints.

Rheumatology

Rheumatology (Greek ῥεῦμα, rheûma, flowing current) is a branch of medicine devoted to the diagnosis and therapy of rheumatic diseases. Physicians who have undergone formal training in rheumatology are called rheumatologists. Rheumatologists deal mainly with immune-mediated disorders of the musculoskeletal system, soft tissues, autoimmune diseases, vasculitides, and heritable connective tissue disorders.

Many of these diseases are now known to be disorders of the immune system. Rheumatology is considered to be the study and practice of medical immunology.

Beginning in the 2000s, the incorporation of drugs called the biologics (which include inhibitors of TNF-alpha, certain interleukins, and the JAK-STAT signaling pathway) into standards of care is one of the paramount developments in modern rheumatology.

Septic arthritis

Septic arthritis, also known as joint infection or infectious arthritis, is the invasion of a joint by an infectious agent resulting in joint inflammation. Symptoms typically include redness, heat, and pain in a single joint associated with a decreased ability to move the joint. Onset is usually rapid. Other symptoms may include fever, weakness, and headache. Occasionally, more than one joint may be involved.Causes include bacteria, viruses, fungi, and parasites. Risk factors include an artificial joint, prior arthritis, diabetes, and poor immune function. Most commonly joints becomes infected via the blood but may also become infected via trauma or an infection around the joint. Diagnosis is generally based on aspirating joint fluid and culturing it. White blood cells of greater than 50,000 mm3 or lactate greater than 10 mmol/l in the joint fluid also makes the diagnosis likely.Initial treatment typically include antibiotics such as vancomycin, ceftriaxone, or ceftazidime. Surgery may also be done to clean out the joint. Without early treatment long term joint problems may occur. Septic arthritis occurs in about 5 people per 100,000 each year. It occurs more commonly in older people. With treatment about 15% of people die while without 66% die.

Tendinopathy

Tendinopathy, also known as tendinitis or tendinosis, is a type of tendon disorder that results in pain, swelling, and impaired function. The pain is typically worse with movement. It most common occurs around the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elbow, golfer's elbow), wrist, hip, knee (jumper's knee), or ankle (Achilles tendinitis).Causes may include an injury or repetitive activities. Groups at risk include people who do manual labor, musicians, and athletes. Less common causes include infection, arthritis, gout, thyroid disease, and diabetes. Diagnosis is typically based on symptoms, examination, and occasionally medical imaging. A few weeks following an injury little inflammation remains, with the underlying problem related to weak or disrupted tendon fibrils.Treatment may include rest, NSAIDs, splinting, and physiotherapy. Less commonly steroid injections or surgery may be done. About 80% of people get better within 6 months. Tendinopathy is relatively common. Older people are more commonly affected. It results in a large amount of missed work.

Tocilizumab

Tocilizumab, also known as atlizumab, is an immunosuppressive drug, mainly for the treatment of rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis, a severe form of arthritis in children. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. It was developed by Hoffmann–La Roche and Chugai.

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