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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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The rheumatoid nodule, which is sometimes in the skin, is the most common non-joint feature and occurs in 30% of people who have RA. 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 elbow, the heel, the knuckles, or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF (rheumatoid factor) titer, ACPA, and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body.
Several forms of vasculitis occur in RA, but are mostly seen with long-standing and untreated disease. The most common presentation is due to involvement of small- and medium-sized vessels. Rheumatoid vasculitis can thus commonly present with skin ulceration and vasculitic nerve infarction known as mononeuritis multiplex.
Other, rather rare, skin associated symptoms include pyoderma gangrenosum, Sweet's syndrome, drug reactions, erythema nodosum, lobe panniculitis, atrophy of finger skin, palmar erythema, and skin fragility (often worsened by corticosteroid use).
Arthritis of joints involves inflammation of the synovial membrane. Joints become swollen, tender and warm, and stiffness limits their movement. With time, multiple joints are affected (polyarthritis). Most commonly involved are the 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.
RA 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 typically lasts 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, such as osteoarthritis. In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are less prominent with stiffness typically less than one hour, and movements induce pain caused by mechanical arthritis.
The pain associated with RA is induced at the site of inflammation and classified as nociceptive as opposed to neuropathic. 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. Specific deformities, which also occur in osteoarthritis, include ulnar deviation, boutonniere deformity (also "buttonhole deformity", flexion of proximal interphalangeal joint and extension of distal interphalangeal joint of the hand), swan neck deformity (hyperextension at proximal interphalangeal joint and flexion at distal interphalangeal joint) and "Z-thumb." "Z-thumb" or "Z-deformity" consists of hyperextension of the interphalangeal joint, fixed flexion and subluxation of the metacarpophalangeal joint and gives a "Z" appearance to the thumb. The hammer toe deformity may be seen. In the worst case, joints are known as arthritis mutilans due to the mutilating nature of the deformities.
Systemic JIA is characterized by arthritis, fever, which typically is higher than the low-grade fever associated with polyarticular and a salmon pink rash. It accounts for 10-20% of JIA and affects males and females equally, unlike the other two subtypes of JIA, and affects adolescents. It generally involves both large and small joints. Systemic JIA can be challenging to diagnose because the fever and rash come and go. Fever can occur at the same time every day or twice a day (often in late afternoon or evening) with a spontaneous rapid return to baseline (vs. septic arthritis of continuous fever). The rash often occurs with fever. It is a discrete, salmon-pink macules of different sizes. It migrates to different locations on skin, rarely persisting in one location more than one hour. The rash is commonly seen on trunk and proximal extremities or over pressure areas.
Arthritis is often absent in the first weeks or even 6–8 months into the illness.
Systemic JIA may have internal organ involvement such as hepatosplenomegaly, lymphadenopathy, serositis, hepatitis, or tenosynovitis.
A polymorphism in macrophage migration inhibitory factor has been associated with this condition.
As many as 70% of people with lupus have some skin symptoms. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with discoid lupus may exhibit thick, red scaly patches on the skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic malar rash (or "butterfly rash") associated with the disease. This rash occurs in 30 to 60% of people with SLE.
Hair loss, mouth and nasal ulcers, and lesions on the skin are other possible manifestations.
Around 30% of people have swollen, painful joints, but this is generally mild.
In some people the condition affects the lungs, and they may have a cough or difficulty breathing. If the condition affects the heart, there may be arrhythmias. If it affects the blood vessels in the stomach or intestines, which is more common in juvenile DM, the person might vomit blood, have black, tarry bowel movements, or may develop a hole somewhere in their GI tract.
SLE is one of several diseases known as "the great imitator" because it often mimics or is mistaken for other illnesses. SLE is a classical item in differential diagnosis, because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people having unexplained symptoms of SLE for years.
Common initial and chronic complaints include fever, malaise, joint pains, muscle pains, and fatigue. Because these symptoms are so often seen in association with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms (see below), however, they are considered suggestive.
While SLE can occur in both males and females, it is found far more often in women, and the symptoms associated with each sex are different. Females tend to have a greater number of relapses, a low white blood cell count, more arthritis, Raynaud's phenomenon, and psychiatric symptoms. Males tend to have more seizures, kidney disease, serositis (inflammation of tissues lining the lungs and heart), skin problems, and peripheral neuropathy.
One form the rashes take is called "heliotrope" (a purplish color) or lilac, but may also be red. It can occur around the eyes along with swelling, but also occurs on the upper chest or back what is called the "shawl" (around the neck) or "V-sign" above the breasts and may also occur on the face, upper arms, thighs, or hands. Another form the rash takes is called "Gottron's sign" which are red, sometimes scaly, papules that erupt on any of the finger joints (the metacarpophalangeal joints or the interphalangeal joints). All these rashes are made worse by exposure to sunlight, and are often very itchy, painful, and may bleed.
If a person exhibits only skin findings characteristic of DM, without weakness or abnormal muscle enzymes, then he or she may be experiencing amyopathic dermatomyositis (ADM, formerly known as "dermatomyositis sine myositis".
There are five main types of psoriatic arthritis:
- Oligoarticular: This type affects around 70% of patients and is generally mild. This type does not occur in the same joints on both sides of the body and usually only involves fewer than 3 joints.
- Polyarticular: This type accounts for around 25% of cases, and affects five or more joints on both sides of the body simultaneously. This type is most similar to rheumatoid arthritis and is disabling in around 50% of all cases.
- Arthritis mutilans (): Affects less than 5% of patients and is a severe, deforming and destructive arthritis. This condition can progress over months or years causing severe joint damage. Arthritis mutilans has also been called chronic absorptive arthritis, and may be seen in rheumatoid arthritis as well.
- Spondyloarthritis (): This type is characterized by stiffness of the neck or the sacroiliac joint of the spine, but can also affect the hands and feet, in a similar fashion to symmetric arthritis.
- Distal interphalangeal predominant (): This type of psoriatic arthritis is found in about 5% of patients, and is characterized by inflammation and stiffness in the joints nearest to the ends of the fingers and toes. Nail changes are often marked.
Treatments for inflammatory arthritis vary by subtype, though they may include drugs like DMARDs (disease-modifying anti-rheumatic drugs) and tumor necrosis factor inhibitors.
Systemic-onset juvenile idiopathic arthritis (also known as systemic juvenile idiopathic arthritis (sJIA) or the juvenile onset form of Still's disease) is a type of juvenile idiopathic arthritis (JIA) with extra-articular manifestations like fever and rash apart from arthritis. It was originally called systemic-onset juvenile rheumatoid arthritis or Still's disease.
Predominantly extra-articular manifestations like high fevers, rheumatic rash, enlargement of the liver and spleen, enlargement of the lymph nodes, and anemia. Others manifestations include inflammation of the pleura, inflammation of the pericardium, inflammation of the heart's muscular tissue, and inflammation of the peritoneum are also seen.
It is sometimes called "juvenile-onset Still's disease", to distinguish it from adult-onset Still's disease. However, there is some evidence that the two conditions are closely related.
Symptoms of inflammatory arthritis include stiffness, pain, and swelling of the joints, restricted motions, and reduced physical strength. Other symptoms may include systemic complaints including fatigue.
Three types of juvenile arthritis exist—juvenile rheumatoid arthritis (JRA), juvenile chronic arthritis (JCA), and juvenile idiopathic arthritis (JIA), of which JRA is the most common.
JRA again can be divided into three main forms: The classification is based upon symptoms, number of joints involved and the presence of certain antibodies in the blood.
1. Polyarticular arthritis is the first type of arthritis, which affects about 30–40% of children with arthritis and is more common in girls than boys. Typically five or more joints are affected (usually smaller joints such as the hands and feet but many also affect the hips, neck, shoulders and jaw).
2. Oligoarticular (aka pauciarticular) arthritis can be early or late onset and is the second type of arthritis, affecting about 50% of children with juvenile arthritis. This type affects fewer than four joints (usually the large joints such as knees, ankles or wrists) and may cause eye inflammation in girls with positive anti-nuclear antibodies (ANA). Girls younger than eight are more likely to develop this type of arthritis.
3. Systemic disease is the least common form, with 10–20% of children (boys and girls equally) being affected with limited movement, swelling and pain in at least one joint. A common symptom of this type is a high, spiking fever of or higher, lasting for weeks or months, and a rash of pale red spots on the chest, thighs or other parts of the body may be visible.
Pain, swelling, or stiffness in one or more joints is commonly present in psoriatic arthritis. Psoriatic arthritis is inflammatory, and affected joints are generally red or warm to the touch. Asymmetrical oligoarthritis, defined as inflammation affecting one to four joints during the first six months of disease, is present in 70% of cases. However, in 15% of cases, the arthritis is symmetrical. The joints of the hand that is involved in psoriasis are the proximal interphalangeal (PIP), the distal interphalangeal (DIP), the metacarpophalangeal (MCP), and the wrist. Involvement of the distal interphalangeal joints (DIP) is a characteristic feature and is present in 15% of cases.
In addition to affecting the joints of the hands and wrists, psoriatic arthritis may affect the fingers, nails, and skin. Sausage-like swelling in the fingers or toes, known as dactylitis, may occur. Psoriasis can also cause changes to the nails, such as pitting or separation from the nail bed, onycholysis, hyperkeratosis under the nails, and horizontal ridging. Psoriasis classically presents with scaly skin lesions, which are most commonly seen over extensor surfaces such as the scalp, natal cleft and umbilicus.
In psoriatic arthritis, pain can occur in the area of the sacrum (the lower back, above the tailbone), as a result of sacroiliitis or spondylitis, which is present in 40% of cases. Pain can occur in and around the feet and ankles, especially enthesitis in the Achilles tendon (inflammation of the Achilles tendon where it inserts into the bone) or plantar fasciitis in the sole of the foot.
Along with the above-noted pain and inflammation, there is extreme exhaustion that does not go away with adequate rest. The exhaustion may last for days or weeks without abatement. Psoriatic arthritis may remain mild or may progress to more destructive joint disease. Periods of active disease, or flares, will typically alternate with periods of remission. In severe forms, psoriatic arthritis may progress to arthritis mutilans which on X-ray gives a "pencil-in-cup" appearance.
Because prolonged inflammation can lead to joint damage, early diagnosis and treatment to slow or prevent joint damage is recommended.
Juvenile arthritis, also known as Childhood arthritis (JA) is any form of chronic arthritis or arthritis-related conditions which affects individuals under the age of 16.
Juvenile arthritis is a chronic autoimmune disease.
Symptoms of JIA are often nonspecific initially, and include lethargy, reduced physical activity, and poor appetite. The first manifestation, particularly in young children, may be limping. Children may also become quite ill, presenting with flu-like symptoms that persist. The cardinal clinical feature is persistent swelling of the affected joint(s), which commonly include the knee, ankle, wrist, and small joints of the hands and feet. Swelling may be difficult to detect clinically, especially for joints such as those of the spine, sacroiliac joints, shoulder, hip, and jaw, where imaging techniques such as ultrasound or MRI are very useful.
Pain is an important symptom. Morning stiffness that improves later in the day is a common feature (this implies inflammatory-type joint pain versus mechanical-type joint pain). Late effects of arthritis include joint contracture (stiff, bent joint due to fibrosis) and joint damage. Children with JIA vary in the degree to which they are affected by particular symptoms. Symptoms may also differ between sexes, affecting girls and boys differently among different geographic locations. This is predicted to be due to biological differences in different geographic regions. Children may also have swollen joints (inflammatory swelling, or in chronic arthritis due to synovial proliferation and thickening, and periarticular soft-tissue swelling).
The three major types of JIA are oligoarticular, polyarticular, and systemic.
Disease presentation varies widely from patient to patient, as UCTD is by definition nonspecific. Symptoms typically include constitutional complaints that are common to connective tissue diseases such as fatigue, a general sense of feeling unwell, and fever.
Other symptoms associated with UCTD include:
- dry eyes
- dry mouth
- hair loss
- joint inflammation
- joint pain
- oral ulcers
- positive ANA test
- raynaud's phenomenon
- sun sensitive rash
Lung involvement, such as nonspecific interstitial pneumonia, is a possible disease complication.
It may be associated with bilateral edema in lower limbs, pain and joint swelling. Sometimes there is previous history of inflammatory joint problems and bilateral edema of lower limbs.
Alphavirus Polyarthritis Syndrome has an incubation period of 3–21 days, depending on the specific virus, with either a gradual or sudden onset of fever, arthralgias, headache, and lymphadenitis and conjunctivitis in some forms. A maculopapular rash may present 4–8 days post symptom onset and may be accompanied by an increase in fever. Joint pains associated with this condition may recur for many months after initial illness for up to a year.
The vasculitis caused by JDMS manifests itself predominantly in two ways:
One is a distinctive rash. The rash often affects the face, eyelids, and hands, and sometimes the skin above joints, including the knuckles, knees, elbows, etc. The color of the rash is a pinkish purple, and is called heliotrope (after a flower of the same name with approximately this color). On the hands and face, the rash very closely resembles allergies, eczema, fifth disease, or other more common skin condition, but the heliotrope color is unique to the inflammatory process of JDMS. Some children develop calcinosis, which are calcium deposits under the skin. The rash is the source of the "dermato-" part of the name of the disease.
The second symptom caused by vasculitis is muscle inflammation. This symptom is the source of the "-myositis" part of the name of the disease ("myo" = muscle, "-itis" = inflammation of). Muscle Inflammation causes muscle weakness, which can cause fatigue, clumsiness, not keeping up physically with peers, and eventually inability to perform tasks like climbing stairs, lifting objects, and performing other manual tasks. Other signs may include falling, dysphonia, or dysphagia. The muscle weakness often causes a medical misdiagnosis of muscular dystrophy or other muscle disease. Some patients develop contractures, when the muscle shortens and causes joints to stay bent; exercise, occupational therapy, and physical therapy can prevent this. The muscles first affected tend to be proximal (i.e., neck, shoulders, back, and abdominal). About half of children with JDMS also have pain in their muscles.
Other symptoms may include irritability, weight loss, and mouth ulcers. When a child becomes irritable, fatigued, reluctant to socialize, and the face becomes flushed easily, physicians refer to this constellation of symptoms as "misery."
The speed of the progression of JDMS is highly variable. Nearly all JDM patients have some skin involvement. The JDMS rash usually occurs as the initial symptom. Sometimes it is so slight as not to be recognized for what it is until muscle symptoms appear. Sometimes muscle symptoms never appear at all or occur very gradually over the course of months, and sometimes going from normal strength to being unable to walk within days. Usually, muscle symptoms appear weeks to months after the onset of the rash.
These symptoms could consist of asthenia, fever, anorexia, and weight loss. It mostly occurs during a severe disease flare.
The involvement of the kidney can be caused by primary renal parenchymal lesions, or an underlying vasculitis, or another associated autoimmune disease. Actual kidney involvement is quite rare, elevated creatinine levels are reported in approximately 10% of people with RP, and abnormalities in urinalysis in 26%. Involvement of the kidney often indicates a worse prognosis, with a 10-year survival rate of 30%.
The most common histopathologic finding is mild mesangial proliferation, that is followed by focal and segmental necrotizing glomerulonephritis with crescents. Other abnormalities that are found include glomerulosclerosis, IgA nephropathy and interstitial nephritis. Immunofluorescence studies most often reveal faint deposists of C3, IgG or IgM in the primarily mesangium.
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. Symptoms may include:
- Inability to use the hand or walk
- Stiffness, which may be worse in the morning, or after use
- Malaise and fatigue
- Weight loss
- Poor sleep
- Muscle aches and pains
- Tenderness
- Difficulty moving the joint
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:
- Muscle weakness
- Loss of flexibility
- Decreased aerobic fitness
These changes, in addition to the primary symptoms, can have a huge impact on quality of life.
Undifferentiated connective tissue disease (UCTD) is a disease in which the body mistakenly attacks its own tissues. It is diagnosed when there is evidence of an existing autoimmune condition which does not meet the criteria for any specific autoimmune disease, such as systemic lupus erythematosus or scleroderma. Latent lupus and incomplete lupus are alternative terms that have been used to describe this condition.
The term is sometimes used interchangeably with mixed connective tissue disease, an overlap syndrome. However, MCTD is thought by some researchers to be a clinically distinct entity and is strongly associated with the presence of high titers of ribonucleoprotein (RNP) antibodies.
It is estimated that up to 25 percent of people with systemic autoimmune disease could be considered to have UCTD.
Palindromic rheumatism is a rare type of inflammatory arthritis which causes sudden inflammation in one or several joints, lasts a few hours or up to a few days, and then goes away completely. The problem usually involves 2 or 3 joints, which have onset over hours and last days to weeks, before subsiding. However episodes of recurrence form a pattern, with symptom-free periods between attacks lasting for weeks to months. The large joints are most commonly involved. Constitutionally, there may or may not be a fever, and swelling of the joints. The soft tissues are involved with swelling of the periarticular tissues, especially heel pads and finger pads. Nodules may be found in the subcutaneous tissues.Attacks may become more frequent with time but there is no joint damage after attacks.
It typically affects people between the ages of 20 and 50. One study showed an average age of onset of 49.