Imaging X-ray of the hand in<unk> . Appearance of synovial fluid from a joint with inflammatory<unk> . Closeup of bone erosions in<unk> . X-rays of the hands and feet are generally performed when many joints affected. In<unk> , there may be no changes in the early stages of the disease or the x-ray may show osteopenia near the joint, soft tissue swelling, and a smaller than normal joint space. As the disease advances, there may be bony erosions and subluxation. Other medical imaging techniques such as magnetic resonance imaging (MRI) and ultrasound are also used in<unk> . Technical advances in ultrasonography like high-frequency transducers (10 MHz or higher) have improved the spatial resolution of ultrasound images depicting 20% more erosions than conventional<unk> diography. Color Doppler and power Doppler ultrasound are useful in assessing the degree of synovial inflammation as they can show vascular signals of active synovitis. This is important, since in the early stages of<unk> , the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage. Blood tests When<unk>  is clinically suspected, a physician may test for<unk>  factor (RF) and anti-citrullinated protein antibodies (ACPAs measured as anti-CCP antibodies). It is positive in 75–85%, but a negative RF or CCP antibody does not rule out<unk> ,<unk> ther, the<unk>  is called seronegative, which is in about 15–25% of people with<unk> . During the first year of illness,<unk>  factor is more likely to be negative with some individuals becoming seropositive over time. RF is a non-specific antibody and seen in about 10% of healthy people, in many other chronic infections like hepatitis C, and chronic autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus. Therefore, the test is not specific for<unk> . Hence, new serological tests check for anti-citrullinated protein antibodies ACPAs. These tests are again positive in 61–75% of all<unk>  cases, but with a specificity of around 95%. As with RF, ACPAs are many times present before symptoms have started. The by far most common clinical test for ACPAs is the anti-cyclic citrullinated peptide (anti CCP) ELISA. In 2008 a serological point-of-care test for the early detection of<unk>  combined the detection of RF and anti-MCV with a sensitivity of 72% and specificity of 99.7%. Other blood tests are usually done to differentiate from other causes of<unk> , like the erythrocyte sedimentation<unk> te (ESR), C-reactive protein, full blood count, kidney function, liver enzymes and other immunological tests (e.g., antinuclear antibody/ANA) are all performed at this stage. Elevated ferritin levels can reveal hemochromatosis, a mimic of<unk> , or be a sign of Still's disease, a seronegative, usually juvenile, variant of<unk> . Classification criteria In 2010, the 2010 ACR / EULAR<unk>  Classification Criteria were introduced. The new criterion is not a diagnostic criterion but a classification criterion to identify disease with a high likelihood of developing a chronic form. However a score of 6 or greater unequivocally classifies a person with a diagnosis of<unk> . These new classification criteria overruled the "old" ACR criteria of 1987 and are adapted for early<unk>  diagnosis. The "new" classification criteria, jointly published by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) establish a point value between 0 and 10. Four areas are covered in the diagnosis: * joint involvement, designating the metacarpophalangeal joints, proximal interphalangeal joints, the interphalangeal joint of the thumb, second through fifth metatarsophalangeal joint and wrist as small joints, and shoulders, elbows, hip joints, knees, and ankles as large joints: * Involvement of 1 large joint gives 0 points * Involvement of 2–10 large joints gives 1 point * Involvement of 1–3 small joints (with or without involvement of large joints) gives 2 points * Involvement of 4–10 small joints (with or without involvement of large joints) gives 3 points * Involvement of more than 10 joints (with involvement of at least 1 small joint) gives 5 points * serological parameters – including the<unk>  factor as well as ACPA – "ACPA" stands for "anti-citrullinated protein antibody": * Negative RF and negative ACPA gives 0 points * Low-positive RF or low-positive ACPA gives 2 points * High-positive RF or high-positive ACPA gives 3 points * acute phase reactants: 1 point for elevated erythrocyte sedimentation<unk> te, ESR, or elevated CRP value (c-reactive protein) * duration of<unk> : 1 point for symptoms lasting six weeks or longer The new criteria accommodate to the growing understanding of<unk>  and the improvements in diagnosing<unk>  and disease treatment. In the "new" criteria serology and autoimmune diagnostics carries major weight, as ACPA detection is appropriate to diagnose the disease in an early state, before joints destructions occur. Destruction of the joints viewed in<unk> diological images was a significant point of the ACR criteria from 1987. This criterion no longer is regarded to be relevant, as this is just the type of damage that treatment is meant to avoid. Differential diagnoses Several other medical conditions can resemble<unk> , and need to be distinguished from it at the time of diagnosis: * Crystal induced<unk>  (gout, and pseudogout) – usually involves particular joints (knee, MTP1, heels) and can be distinguished with an 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, older age, starting pain less than an hour, asymmetric 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<unk>  resembles<unk>  – nail changes and skin symptoms distinguish between them * Lyme disease causes erosive<unk>  and may closely resemble<unk>  – it may be distinguished by blood test in endemic areas * Reactive<unk>  – 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. * Axial spondyloarthritis (including ankylosing spondylitis) – this involves the spine, although an<unk> -like symmetrical small-joint polyarthritis may occur in the context of this condition. * Hepatitis C –<unk> -like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C may also induce<unk>  factor auto-antibodies.<unk> rer causes which usually behave differently but may cause joint pains: * Sarcoidosis, amyloidosis, and Whipple's disease can also resemble<unk> . * Hemochromatosis may cause hand joint<unk> . * Acute rheumatic fever can be differentiated by a migratory pattern of joint involvement and evidence of antecedent streptococcal infection. * Bacterial<unk>  (such as by Streptococcus) is usually asymmetric, while<unk>  usually involves both sides of the body symmetrically. * Gonococcal<unk>  (a bacterial<unk>  is also initially migratory and can involve tendons around the wrists and ankles. Sometimes<unk>  is in an undifferentiated stage (i.e. none of the above criteria is positive), even if synovitis is witnessed and assessed with ultrasound imaging. Difficult-to-treat<unk>  (D2T<unk>  is a specific classification<unk>  by the European League against Rheumatism (EULAR). Signs of illness: # Persistence of signs and symptoms # Drug resistance # Does not respond on two or more biological treatments # Does not respond on anti-rheumatic drugs with different mechanism of action Factors contributing to difficult-to-treat disease: # Genetic risk factors # Environmental factors (diet, smoking, physical activity) # Overweight and obese Genetic factors Genetic factors such as HLA-DR1B1, TRAF1, PSORS1C1 and microRNA 146a are associated with difficult to treat<unk> , other gene polymorphisms seem to be correlated with response to biologic modifying anti-rheumatic drugs (bDMARDs). Next one is FOXO3A gene region been reported as associated with worst disorder. The minor allele at FOXO3A summon a differential response of monocytes in<unk>  patients. FOXO3A can provide an increase of pro-inflammatory cytokines, including TNFα. Possible gene polymorphism: STAT4, PTPN2, PSORS1C1 and TRAF3IP2 genes had been correlated with response to TNF inhibitors. HLA-DR1 and HLA-DRB1 gene The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex is the human version of the major histocompatibility complex (MHC). Currently, have been identified at least 2479 different versions of the HLA-DRB1 gene. The presence of HLA-DRB1 alleles seems to predict<unk> diographic damage, which may be partially mediated by ACPA development, and also elevated sera inflammatory levels and high swollen joint count. HLA-DR1 is encoded by the most risk allele HLA-DRB1 which share a conserved 5-aminoacid sequence that is correlated with the development of anti-citrullinated protein antibodies. HLA-DRB1 gene have more strong correlation with disease development. Susceptibility to and outcome for<unk>  <unk>  may associate with particular HLA-DR alleles, but these alleles vary among ethnic groups and geographic areas. MicroRNAs MicroRNAs are a factor in the development of that type of disease. MicroRNAs usually operate as a negative regulator of the expression of target proteins
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