Spondyloarthritis is caused by a combination of genetic and environmental factors.[3] It is associated with intestinal inflammation, with a connection betweenCrohn's disease andankylosing spondylitis.[4] Reactive arthritis is primarily caused by gastrointestinal, genitourinary, respiratory infections, and genetic factors.[3]
Spondyloarthritis is diagnosed based on symptoms and imaging. Early diagnosis criteria use genetic testing and more advanced forms of medical imaging.[5] Spondyloarthritis is categorized into two groups based on the Assessment of SpondyloArthritis International Society (ASAS) criteria: primarily axial involvement and predominantly peripheral manifestations.[6][7]
In all subtypes of spondyloarthritis, inflammatoryback pain and/or asymmetricalarthritis, mainly affecting the lower limbs, are the most common symptoms.[9] Another characteristic isenthesitis, which is inflammation at the locations whereligaments,tendons, orjoint capsules adhere to bone.[10]
Inflammatoryback pain associated withankylosing spondylitis usually starts slowly, has a dull feel to it, and spreads into the gluteal areas. Back pain has a nocturnal component, gets better with movement, and is worse in the morning. Axial arthritis may begin in thesacroiliac joints and work its way up to thecervical spine over time. Spinal abnormalities such as flattening of thelumbar lordosis, exaggeration of thethoracic kyphosis, and hyperextension of thecervical spine lead to limited spinal motion. Hip and shoulderarthritis can occur in some people withankylosing spondylitis, usually early in the course of the illness. Usually, the other peripheral joints start to be affected later. Most frequently, there is an asymmetrical involvement of the lower extremities.[10]
Reactive arthritis is an aseptic arthritis caused by an infectious pathogen found outside the joint. Particularly affecting the joints in the lower limbs, the arthritis is usually oligoarticular. In most cases, the condition develops quickly; two to four joints may swell and hurt in an uneven manner within a few days. Inflammatoryback pain anddactylitis are also prevalent.[10]
Psoriatic arthritis is known to present in five distinct patterns: oligoarticular (affecting four or fewer joints); polyarticular (affecting five or more joints); prominentdistal interphalangeal (DIP) joint involvement;arthritis mutilans; and psoriaticspondylitis. More than 70% of cases follow the oligoarticular pattern. Distal joints are frequently impacted by psoriatic arthritis, which is typically asymmetrical.[10]
Up to 20% of people withinflammatory bowel disease (IBD) develop spondyloarthropathy. Those withCrohn's disease are more likely to have this association than those withulcerative colitis. Arthritis may appear before bowel disease. Usually, the lower extremities are asymmetrically affected by arthritis. The arthritis typically manifests abruptly and follows a migratory pattern.[10]
In those who do not fit the criteria for any of the well-established spondyloarthropathies, the term "undifferentiated spondyloarthropathy" is used to characterize the signs of spondyloarthritis. A tiny percentage of these eventually experience a characterized spondyloarthritis, but most experience more general symptoms such asdactylitis,enthesitis, unilateral or alternating buttock pain, inflammatoryback pain, and occasionally extra-articular symptoms.[10]
Spondyloarthritis is caused by a complicated combination of geneticpolymorphisms and environment. The relative contributions of genes and environment may differ across different types of spondyloarthritis.[3]
Microscopically visibleileal inflammation is seen in about 50% of people with spondyloarthritis andankylosing spondylitis during ileocolonoscopy.[11][4] There seems to be an immunological connection between the gut inflammation observed inCrohn's disease andankylosing spondylitis.[12] It is known that, in comparison to healthy controls, people with ankylosing spondylitis and those related to them have higher intestinal permeability.[13]
Given the well-establishedfamilial aggregation and the concordance rate of up to 63% in identical twins (vs 23% in nonidentical twins), it is evident that genetic variables play a role in the susceptibility toankylosing spondylitis.[14][15] There is limited research onfamilial aggregation in other forms of spondyloarthritis.[12]
The arthritogenic-peptide theory is the classic pathophysiological paradigm for spondyloarthritis. It argues thatHLA-B27 displays self-peptides that resemble pathogen-derived peptides toCD8-restrictedT cells. Two other theories have been proposed to explain HLA-B27's function. They suggest that HLA-B27's genesis may beautoinflammatory rather thanautoimmune, as it plays a part in initiatinginnate immune responses instead of its traditional function of presenting antigens.[2]
According to the second hypothesis, the B pocket's Cys 67 residue causesHLA-B27 heavy-chain misfolding in the endoplasmic reticulum before assembling into complexes with peptide andβ2 microglobulin.[21][22] As a result, theunfolded protein response (UPR) modifies theimmune cells'cytokine output and reactivity to various innate immunological stimuli.[23][24][25]
Spondyloarthritis is primarily diagnosed, or at least first suspected, based on clinical factors. According to the current criteria forankylosing spondylitis, a person must exhibit clinical symptoms of inflammatoryback pain and limited spinal mobility together with radiologicalsacroiliitis. But many people with inflammatory back pain may have no radiographic evidence ofsacroiliitis since up to 10 years might pass between the onset of inflammatory back pain and the development of radiographic sacroiliitis.[5] Criteria for the early diagnosis of axial spondyloarthritis have been developed in light of the emergence of effective treatments. These criteria consider the added value ofHLA-B27 testing, as well as current advancements inMRI scanning.[6][26]
Magnetic resonance images ofsacroiliac joints:psoriatic arthritis. Shown are T1-weighted semi-coronal magnetic resonance images through the sacroiliac joints (a) before and (b) after intravenous contrast injection. Enhancement is seen at the right sacroiliac joint (arrow), indicating activesacroiliitis.
Imaging is crucial to the spondyloarthritis diagnosis process. The most distinctive radiographic observation is thesacroiliac (SI) joints' erosion,ankylosis, andsclerosis.[27] There must be clear evidence ofsacroiliitis (at least grade 2 bilaterally or grade 3 unilaterally) on the radiographs to diagnoseankylosing spondylitis. When axial spondyloarthritis is suspected,sacroiliac joint radiographs are still the initial imaging approach. If radiographs clearly showsacroiliitis, then no more diagnostic imaging is required. But because structural change seen onradiographs can take months or years to emerge, normal radiographs or worrisome abnormalities only warrant additional diagnostic imaging in the context of suggestive clinical symptoms or findings.[28] Furthermore, readingsacroiliac joint radiographs can be difficult and dependent on several variables, such as the image quality, the radiological technique, the reader's background, and variations in sacroiliac anatomy.[29][30]
A challenge associated with radiographic imaging is the typical ten-year lag between the beginning of inflammatoryback pain and the development of radiographicsacroiliitis.[26]MRI imaging of the spine andentheses has made it possible to distinguish between inflammatory spinal lesions associated withankylosing spondylitis and those unrelated to it earlier than is feasible with traditional radiography. It has also allowed for accurate anatomical description of spinal components.[31] The only imaging modality that can precisely identify and evaluate spinal inflammation at this time ismagnetic resonance imaging (MRI) of the sacroiliac joints and spine. It is also being developed as a gauge of disease activity and response to treatment.[5]
When evaluating someone withreactive arthritis orpsoriatic arthritis, plain radiographs of the hands and feet are very beneficial. Seventy-five percent of those withpsoriatic arthritis have radiographic abnormalities of the peripheral joints, such as soft tissue swelling, erosions, periarticularosteopenia,periostitis, and narrowing of the joint space. Aggressive psoriatic arthritis erosions can result in the articular surface of the proximal bone of the joint being destroyed and taking on the look of a "pencil in cup."[27]
Laboratory abnormalities in spondyloarthritis are nonspecific and less effective for diagnosing a specific disease than clinical presentation. Normochromic normocyticanemia, increasedC reactive protein, anderythrocyte sedimentation rate are frequently present nonspecific indicators.[27]
Testing for thehuman leukocyte antigen (HLA) can be the most beneficial laboratory investigation. Since only 5% of those withHLA-B27 in the general population will developankylosing spondylitis, the correlation betweenHLA-B27 and the prevalence of spondyloarthritis is weak. Therefore, the illness prevalence in a particular population must be taken into account when interpreting results fromHLA-B27 testing.[27]
Spondyloarthritis is classified into two categories based on the Assessment of SpondyloArthritis International Society (ASAS) classification criteria: primarily axial involvement and predominantly peripheral manifestations.[6][7]
A person must meet two requirements to be considered for a diagnosis of axial spondyloarthritis: they must be under 45 years old and have experiencedback pain of any kind for at least three months.[6]
HLA-B27-positive people — To diagnose axial spondyloarthritis in those who test positive forHLA-B27, at least two more spondyloarthritis symptoms from the list below must be present.[6]
Sacroiliitis on imaging — When sacroiliitis is diagnosed in those with structural alterations on plain radiographs or subchondral bone marrow edema (BME) onMRI, at least one additional sign of spondyloarthritis from the list below should be present.[6]
Spondyloarthritis features:
Inflammatoryback pain[6] — Several definitions have been put forth for inflammatory back pain. Inflammatory back pain is characterized by the presence of four or more of the following five factors:[32]
If the person meets the previous requirements, they must exhibit at least one of Group A's spondyloarthritis features or two of Group B's spondyloarthritis features.[7]
Improving the persons's state (pain, functional impairment, etc.) and preventing further clinical deterioration are the goals of spondyloarthritis treatment.[2] The ASAS has issued guidelines regarding the use ofTNF blockers specifically[33] as well as the general care of spondyloarthritis.[34]Non-steroidal anti-inflammatory drugs (NSAIDs) should be administered first to those with active, primarily axial signs of spondyloarthritis. IfNSAID medication is contraindicated, does not work, or causes side effects, people are then treated withtumor necrosis factor (TNF) blockers. Because there is insufficient evidence of treatment efficacy, those withaxial spondyloarthritis who do not exhibit peripheral disease signs do not receive traditionaldisease-modifying antirheumatic drugs (DMARDs). But if peripheral arthritis is present, those with spondyloarthritis should get treatment with conventionalDMARDs beforeTNF-blocker medication and after the failure ofNSAID therapy.[8]
According to a recent Cochrane systematic review of published work, supervised groupphysiotherapy is superior to home exercises, individual home-based or supervised exercise programs are preferable to no intervention, and in-patient spondyloarthritis exercise therapy combined with follow-up group physiotherapy is superior to group physiotherapy alone.[35] Recreational exercise, whether performed in a group setting or alone, helps people withankylosing spondylitis feel less stiff and in pain. Back exercise also helps these people function better, but the effects vary depending on how long the disease has been present. People's health improves when they engage in back exercises five days a week and recreational activity for at least half an hour each day.[36][35]
NSAIDs continue to be the first line of treatment forspondylitis, and many people will get adequate symptom relief on their own with just these medications. The best NSAID for treating those with ankylosing spondylitis appears to betolmetin orindomethacin, although there is insufficient evidence to support this theory in rheumatologic practice. The majority of those with establishedpeptic ulcer disease should take selectiveCOX-2 antagonists.[12]
When peripheral arthritis coexists with axial illness, conventionalDMARDs suchmethotrexate,[37]sulfasalazine,[38] orleflunomide may be useful in treating peripheral spondyloarthritis.[39] These drugs are typically ineffective in treating axial symptoms of spondyloarthritis.[40]
The lives of people withankylosing spondylitis are profoundly affected.[5] According to recent statistics, people withankylosing spondylitis, particularly those who are older and have had the condition longer, may be more likely than population controls to be work handicapped or not engage in the labor market. Additionally, those with ankylosing spondylitis were more likely to have never married or been divorced. Compared to expectations, women withankylosing spondylitis were less likely to have had children.[31] People withankylosing spondylitis experience up to 50% more sick leave episodes, an overall 8% loss of productivity, and a thrice higher rate of disability than the general population. Their overall frequency of disability and economic costs are comparable to those ofrheumatoid arthritis.[48] Furthermore, increasing evidence indicates thatcardiovascular illness puts those with ankylosing spondylitis at risk for early death.[49]
Early research on the course ofreactive arthritis indicated a poor prognosis.[5] But more recent research has shown that the prognosis forreactive arthritis is generally favourable.[50] Within six months of onset, the majority of cases seem to resolve.[5]
The prognosis forpsoriatic arthritis is worse than previously thought, according to recent research.[51][52] It has also been demonstrated that those withpsoriatic arthritis have a higher mortality rate, which is linked to higherythrocyte sedimentation rate, high usage of medications, and early radiographic damage.[5]
While not well researched, the prognosis forjuvenile spondyloarthritisis is unknown.[53] According to the data available, children who have had a condition for longer than five years are more likely to be impaired. After five years of the illness, the chance of remission was only 17 percent. After ten years of the condition, moderate to severe restriction affects around 60% of children with juvenile spondyloarthritis.[5]
The prevalence ofankylosing spondylitis and spondyloarthritis, in particular, varies across populations and is similar to that ofHLA-B27.[5] The incidence of spondyloarthritis as a disease entity was recorded in only four investigations, and ranged from 0.48/100,000 inJapan[54] to 62.5/100,000 inSpain.[55][56] Data on the prevalence of spondyloarthritis were reported from 16 investigations; the results ranged from 0.01% inJapan[54] to 2.5% inAlaska.[57][56]
Those with European heritage have a 0.2% to 0.7% prevalence ofankylosing spondylitis.[58][59][60]Reactive arthritis prevalence is unknown and likely varies with time based on endemic rates of the enteric (Shigella,Salmonella,Campylobacter) and sexually acquired (chlamydia) infections that cause it.[5] In the general community, 1–3% of people havepsoriasis.[60] It is less known how commonpsoriatic arthritis is, and it is more common in people with more severe disease; population studies in Caucasians suggest that the prevalence is about 0.1%.[58]Inflammatory bowel disease about 400 Caucasians per 100,000 people, with a male–to–female ratio of 1:1.[59][58] People of Asian and African ancestry rarely experience it. Varying reports have varying risks forspondylitis and peripheral arthritis, which may be related to the observer's specialty. 15% to 20% of people withinflammatory bowel disease have spondylitis.[5] Peripheral arthritis is generally less common in those withulcerative colitis (up to 10%) than in those withCrohn's disease (up to 20%), but it is more common in cases where arheumatologist served as the assessor.[59][58]
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