Spondyloarthritis
Template:Short description Template:Redirect Template:Infobox medical condition
Spondyloarthritis (SpA), also known as spondyloarthropathy, is a collection of syndromes connected by genetic predisposition and clinical symptoms.<ref name="The Spondyloarthropathies">Template:Cite book</ref> The best-known subtypes are enteropathic arthritis (EA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and reactive arthritis (ReA).<ref name="Spondyloarthritis Lancet" /> Symptoms of spondyloarthritis include back pain, arthritis, and enthesitis, inflammation at bone-adhering ligaments, tendons, or joint capsules.
Spondyloarthritis is caused by a combination of genetic and environmental factors.<ref name="Etiology and Pathogenesis" /> It is associated with intestinal inflammation, with a connection between Crohn's disease and ankylosing spondylitis.<ref name="u788" /> Reactive arthritis is primarily caused by gastrointestinal, genitourinary, respiratory infections, and genetic factors.<ref name="Etiology and Pathogenesis" />
Spondyloarthritis is diagnosed based on symptoms and imaging. Early diagnosis criteria use genetic testing and more advanced forms of medical imaging.<ref name="Spondyloarthritis Elsevier" /> Spondyloarthritis is categorized into two groups based on the Assessment of SpondyloArthritis International Society (ASAS) criteria: primarily axial involvement and predominantly peripheral manifestations.<ref name="ASAS Axial" /><ref name="ASAS peripheral" />
Non-steroidal anti-inflammatory drugs (NSAIDs) are administered first for active axial signs of spondyloarthritis. If NSAIDs are contraindicated or cause side effects, TNF blockers are used. Traditional disease-modifying antirheumatic drugs (DMARDs) are not used for people without peripheral disease signs.<ref name="New evidence" />
Signs and symptoms
In all subtypes of spondyloarthritis, inflammatory back pain and/or asymmetrical arthritis, mainly affecting the lower limbs, are the most common symptoms.<ref name="Concepts and epidemiology">Template:Cite journal</ref> Another characteristic is enthesitis, which is inflammation at the locations where ligaments, tendons, or joint capsules adhere to bone.<ref name="Spondyloarthropathies AFP">Template:Cite journal</ref>
Inflammatory back pain associated with ankylosing 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 the sacroiliac joints and work its way up to the cervical spine over time. Spinal abnormalities such as flattening of the lumbar lordosis, exaggeration of the thoracic kyphosis, and hyperextension of the cervical spine lead to limited spinal motion. Hip and shoulder arthritis can occur in some people with ankylosing 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.<ref name="Spondyloarthropathies AFP" />
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. Inflammatory back pain and dactylitis are also prevalent.<ref name="Spondyloarthropathies AFP" />
Psoriatic arthritis is known to present in five distinct patterns: oligoarticular (affecting four or fewer joints); polyarticular (affecting five or more joints); prominent distal interphalangeal (DIP) joint involvement; arthritis mutilans; and psoriatic spondylitis. More than 70% of cases follow the oligoarticular pattern. Distal joints are frequently impacted by psoriatic arthritis, which is typically asymmetrical.<ref name="Spondyloarthropathies AFP" />
Up to 20% of people with inflammatory bowel disease (IBD) develop spondyloarthropathy. Those with Crohn's disease are more likely to have this association than those with ulcerative 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.<ref name="Spondyloarthropathies AFP" />
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 as dactylitis, enthesitis, unilateral or alternating buttock pain, inflammatory back pain, and occasionally extra-articular symptoms.<ref name="Spondyloarthropathies AFP" />
Causes
Spondyloarthritis is caused by a complicated combination of genetic polymorphisms and environment. The relative contributions of genes and environment may differ across different types of spondyloarthritis.<ref name="Etiology and Pathogenesis">Template:Cite book</ref>
Risk factors
Microscopically visible ileal inflammation is seen in about 50% of people with spondyloarthritis and ankylosing spondylitis during ileocolonoscopy.<ref name="f249">Template:Cite journal</ref><ref name="u788">Template:Cite journal</ref> There seems to be an immunological connection between the gut inflammation observed in Crohn's disease and ankylosing spondylitis.<ref name="pathogenesis and management"/> It is known that, in comparison to healthy controls, people with ankylosing spondylitis and those related to them have higher intestinal permeability.<ref name="f434">Template:Cite journal</ref>
Triggers
The majority of organisms responsible for reactive arthritis are gastrointestinal pathogens, such as Shigella flexneri, Clostridioides difficile, Yersinia enterocolitica and Yersinia pseudotuberculosis, Campylobacter jejuni and Campylobacter coli, and Salmonella spp. Genitourinary and respiratory infections, such as Chlamydia trachomatis and Chlamydia pneumoniae, have also been linked to reactive arthritis.<ref name="Etiology and Pathogenesis" />
Genetics
Given the well-established familial 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 to ankylosing spondylitis.<ref name="r357">Template:Cite journal</ref><ref name="n421">Template:Cite journal</ref> There is limited research on familial aggregation in other forms of spondyloarthritis.<ref name="pathogenesis and management">Template:Cite journal</ref>
HLA-B27 is a polymorphic form of the HLA-B molecule found in up to 95% of people with ankylosing spondylitis of European ancestry,<ref name="n680">Template:Cite book</ref><ref name="s261">Template:Cite journal</ref> 70% with reactive arthritis,<ref name="x679">Template:Cite journal</ref> 60% with psoriatic spondylitis,<ref name="pathogenesis and management"/> 25% with peripheral psoriatic arthritis,<ref name="s261"/> and 70% with spondylitis associated with inflammatory bowel disease.<ref name="s261"/><ref name="n680"/>
Mechanism
The arthritogenic-peptide theory is the classic pathophysiological paradigm for spondyloarthritis. It argues that HLA-B27 displays self-peptides that resemble pathogen-derived peptides to CD8-restricted T cells. Two other theories have been proposed to explain HLA-B27's function. They suggest that HLA-B27's genesis may be autoinflammatory rather than autoimmune, as it plays a part in initiating innate immune responses instead of its traditional function of presenting antigens.<ref name="Spondyloarthritis Lancet">Template:Cite journal</ref>
According to the first hypothesis, HLA-B27 heavy chains devoid of β2 microglobulin can form disulphide-linked homodimers that are produced at the cell surface and can be recognized directly by KIR3DL2 killer immunoglobulin-like receptors, regardless of the associated peptide.<ref name="i916">Template:Cite journal</ref><ref name="d872">Template:Cite journal</ref>
According to the second hypothesis, the B pocket's Cys 67 residue causes HLA-B27 heavy-chain misfolding in the endoplasmic reticulum before assembling into complexes with peptide and β2 microglobulin.<ref name="g406">Template:Cite journal</ref><ref name="o546">Template:Cite journal</ref> As a result, the unfolded protein response (UPR) modifies the immune cells' cytokine output and reactivity to various innate immunological stimuli.<ref name="w906">Template:Cite journal</ref><ref name="k395">Template:Cite journal</ref><ref name="w131">Template:Cite journal</ref>
Diagnosis
Spondyloarthritis is primarily diagnosed, or at least first suspected, based on clinical factors. According to the current criteria for ankylosing spondylitis, a person must exhibit clinical symptoms of inflammatory back pain and limited spinal mobility together with radiological sacroiliitis. But many people with inflammatory back pain may have no radiographic evidence of sacroiliitis since up to 10 years might pass between the onset of inflammatory back pain and the development of radiographic sacroiliitis.<ref name="Spondyloarthritis Elsevier">Template:Cite book</ref> 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 of HLA-B27 testing, as well as current advancements in MRI scanning.<ref name="ASAS Axial" /><ref name="k089">Template:Cite journal</ref>
Imaging is crucial to the spondyloarthritis diagnosis process. The most distinctive radiographic observation is the sacroiliac (SI) joints' erosion, ankylosis, and sclerosis.<ref name="Spondyloarthritis Harper">Template:Cite journal</ref> There must be clear evidence of sacroiliitis (at least grade 2 bilaterally or grade 3 unilaterally) on the radiographs to diagnose ankylosing spondylitis. When axial spondyloarthritis is suspected, sacroiliac joint radiographs are still the initial imaging approach. If radiographs clearly show sacroiliitis, then no more diagnostic imaging is required. But because structural change seen on radiographs 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.<ref name="Early Spondyloarthritis">Template:Cite journal</ref> Furthermore, reading sacroiliac 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.<ref name="u800">Template:Cite journal</ref><ref name="n239">Template:Cite journal</ref>
A challenge associated with radiographic imaging is the typical ten-year lag between the beginning of inflammatory back pain and the development of radiographic sacroiliitis.<ref name="k089"/> MRI imaging of the spine and entheses has made it possible to distinguish between inflammatory spinal lesions associated with ankylosing spondylitis and those unrelated to it earlier than is feasible with traditional radiography. It has also allowed for accurate anatomical description of spinal components.<ref name="j089">Template:Cite journal</ref> The only imaging modality that can precisely identify and evaluate spinal inflammation at this time is magnetic resonance imaging (MRI) of the sacroiliac joints and spine. It is also being developed as a gauge of disease activity and response to treatment.<ref name="Spondyloarthritis Elsevier"/>
When evaluating someone with reactive arthritis or psoriatic arthritis, plain radiographs of the hands and feet are very beneficial. Seventy-five percent of those with psoriatic arthritis have radiographic abnormalities of the peripheral joints, such as soft tissue swelling, erosions, periarticular osteopenia, 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."<ref name="Spondyloarthritis Harper"/>
Laboratory abnormalities in spondyloarthritis are nonspecific and less effective for diagnosing a specific disease than clinical presentation. Normochromic normocytic anemia, increased C reactive protein, and erythrocyte sedimentation rate are frequently present nonspecific indicators.<ref name="Spondyloarthritis Harper"/>
Testing for the human leukocyte antigen (HLA) can be the most beneficial laboratory investigation. Since only 5% of those with HLA-B27 in the general population will develop ankylosing spondylitis, the correlation between HLA-B27 and the prevalence of spondyloarthritis is weak. Therefore, the illness prevalence in a particular population must be taken into account when interpreting results from HLA-B27 testing.<ref name="Spondyloarthritis Harper"/>
Classification
Spondyloarthritis is classified into two categories based on the Assessment of SpondyloArthritis International Society (ASAS) classification criteria: primarily axial involvement and predominantly peripheral manifestations.<ref name="ASAS Axial">Template:Cite journal</ref><ref name="ASAS peripheral">Template:Cite journal</ref>
Axial spondyloarthritis
Template:Main A person must meet two requirements to be considered for a diagnosis of axial spondyloarthritis: they must be under 45 years old and have experienced back pain of any kind for at least three months.<ref name="ASAS Axial" />
The second step comprises two sections that are assessed independently according to the existence of either sacroiliitis on imaging or human leukocyte antigen (HLA) B27:<ref name="ASAS Axial" />
- HLA-B27-positive people — To diagnose axial spondyloarthritis in those who test positive for HLA-B27, at least two more spondyloarthritis symptoms from the list below must be present.<ref name="ASAS Axial" />
- Sacroiliitis on imaging — When sacroiliitis is diagnosed in those with structural alterations on plain radiographs or subchondral bone marrow edema (BME) on MRI, at least one additional sign of spondyloarthritis from the list below should be present.<ref name="ASAS Axial" />
Spondyloarthritis features:
- Inflammatory back pain<ref name="ASAS Axial" /> — 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:<ref name="ASAS inflammatory back pain">Template:Cite journal</ref>
- Onset at <40 years old.<ref name="ASAS inflammatory back pain"/>
- Insidious onset.<ref name="ASAS inflammatory back pain"/>
- Improved with exercise.<ref name="ASAS inflammatory back pain"/>
- Not improved by rest.<ref name="ASAS inflammatory back pain"/>
- Pain at night.<ref name="ASAS inflammatory back pain"/>
- Arthritis.<ref name="ASAS Axial" />
- Heel enthesitis.<ref name="ASAS Axial" />
- Uveitis.<ref name="ASAS Axial" />
- Dactylitis.<ref name="ASAS Axial" />
- Psoriasis.<ref name="ASAS Axial" />
- Inflammatory bowel disease.<ref name="ASAS Axial" />
- Good response to nonsteroidal anti-inflammatory drugs (NSAIDs).<ref name="ASAS Axial" />
- Family history of spondyloarthritis.<ref name="ASAS Axial" />
- Elevated C-reactive protein (CRP).<ref name="ASAS Axial" />
Peripheral spondyloarthritis
The initial requirement is that a person have at least one of the following three findings:<ref name="ASAS peripheral" />
- Arthritis.<ref name="ASAS peripheral" />
- Enthesitis.<ref name="ASAS peripheral" />
- Dactylitis.<ref name="ASAS peripheral" />
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.<ref name="ASAS peripheral" />
Group A spondyloarthritis features:<ref name="ASAS peripheral" />
- Uveitis.<ref name="ASAS peripheral" />
- Psoriasis.<ref name="ASAS peripheral" />
- Inflammatory bowel disease.<ref name="ASAS peripheral" />
- Preceding infection.<ref name="ASAS peripheral" />
- HLA-B27.<ref name="ASAS peripheral" />
- Sacroiliitis on imaging.<ref name="ASAS peripheral" />
Group B spondyloarthritis features:<ref name="ASAS peripheral" />
- Arthritis.<ref name="ASAS peripheral" />
- Enthesitis.<ref name="ASAS peripheral" />
- Dactylitis.<ref name="ASAS peripheral" />
- Inflammatory back pain in the past.<ref name="ASAS peripheral" />
- Family history of spondyloarthritis.<ref name="ASAS peripheral" />
Treatment
Improving the persons's state (pain, functional impairment, etc.) and preventing further clinical deterioration are the goals of spondyloarthritis treatment.<ref name="Spondyloarthritis Lancet" /> The ASAS has issued guidelines regarding the use of TNF blockers specifically<ref name="ASAS anti-TNF">Template:Cite journal</ref> as well as the general care of spondyloarthritis.<ref name="ASAS/EULAR">Template:Cite journal</ref> Non-steroidal anti-inflammatory drugs (NSAIDs) should be administered first to those with active, primarily axial signs of spondyloarthritis. If NSAID medication is contraindicated, does not work, or causes side effects, people are then treated with tumor necrosis factor (TNF) blockers. Because there is insufficient evidence of treatment efficacy, those with axial spondyloarthritis who do not exhibit peripheral disease signs do not receive traditional disease-modifying antirheumatic drugs (DMARDs). But if peripheral arthritis is present, those with spondyloarthritis should get treatment with conventional DMARDs before TNF-blocker medication and after the failure of NSAID therapy.<ref name="New evidence">Template:Cite journal</ref>
According to a recent Cochrane systematic review of published work, supervised group physiotherapy 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.<ref name="Physiotherapy">Template:Cite journal</ref> Recreational exercise, whether performed in a group setting or alone, helps people with ankylosing 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.<ref name="Exercise">Template:Cite journal</ref><ref name="Physiotherapy"/>
NSAIDs continue to be the first line of treatment for spondylitis, 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 be tolmetin or indomethacin, although there is insufficient evidence to support this theory in rheumatologic practice. The majority of those with established peptic ulcer disease should take selective COX-2 antagonists.<ref name="pathogenesis and management" />
When peripheral arthritis coexists with axial illness, conventional DMARDs such methotrexate,<ref name="w959">Template:Cite journal</ref> sulfasalazine,<ref name="d200">Template:Cite journal</ref> or leflunomide may be useful in treating peripheral spondyloarthritis.<ref name="u424">Template:Cite journal</ref> These drugs are typically ineffective in treating axial symptoms of spondyloarthritis.<ref name="2010 update">Template:Cite journal</ref>
After 2000, a number of studies examining the effects of TNF blockers on people with ankylosing spondylitis were published. These studies demonstrated that TNF-blocker therapy improves clinical symptoms, CRP levels, and MRI-detectable inflammation in the spine or sacroiliac joints.<ref name="New evidence"/> These improvements were noted with certolizumab pegol,<ref name="a655">Template:Cite journal</ref> etanercept,<ref name="e666">Template:Cite journal</ref><ref name="x571">Template:Cite journal</ref> infliximab,<ref name="u991">Template:Cite journal</ref><ref name="d880">Template:Cite journal</ref> adalimumab,<ref name="r471">Template:Cite journal</ref> and golimumab.<ref name="g050">Template:Cite journal</ref>
Outlook
The lives of people with ankylosing spondylitis are profoundly affected.<ref name="Spondyloarthritis Elsevier" /> According to recent statistics, people with ankylosing 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 with ankylosing spondylitis were less likely to have had children.<ref name="j089"/> People with ankylosing 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 of rheumatoid arthritis.<ref name="s346">Template:Cite journal</ref> Furthermore, increasing evidence indicates that cardiovascular illness puts those with ankylosing spondylitis at risk for early death.<ref name="d794">Template:Cite journal</ref>
Early research on the course of reactive arthritis indicated a poor prognosis.<ref name="Spondyloarthritis Elsevier" /> But more recent research has shown that the prognosis for reactive arthritis is generally favourable.<ref name="Wendling">Template:Cite journal</ref> Within six months of onset, the majority of cases seem to resolve.<ref name="Spondyloarthritis Elsevier" />
The prognosis for psoriatic arthritis is worse than previously thought, according to recent research.<ref name="t219">Template:Cite journal</ref><ref name="i350">Template:Cite journal</ref> It has also been demonstrated that those with psoriatic arthritis have a higher mortality rate, which is linked to high erythrocyte sedimentation rate, high usage of medications, and early radiographic damage.<ref name="Spondyloarthritis Elsevier" />
While not well researched, the prognosis for juvenile spondyloarthritisis is unknown.<ref name="e330">Template:Cite journal</ref> 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.<ref name="Spondyloarthritis Elsevier" />
Epidemiology
The prevalence of ankylosing spondylitis and spondyloarthritis, in particular, varies across populations and is similar to that of HLA-B27.<ref name="Spondyloarthritis Elsevier" /> The incidence of spondyloarthritis as a disease entity was recorded in only four investigations, and ranged from 0.48/100,000 in Japan<ref name="Japan">Template:Cite journal</ref> to 62.5/100,000 in Spain.<ref name="Spain">Template:Cite journal</ref><ref name="Epidemiology">Template:Cite journal</ref> Data on the prevalence of spondyloarthritis were reported from 16 investigations; the results ranged from 0.01% in Japan<ref name="Japan"/> to 2.5% in Alaska.<ref name="s010">Template:Cite journal</ref><ref name="Epidemiology"/>
Those with European heritage have a 0.2% to 0.7% prevalence of ankylosing spondylitis.<ref name="Global Prevalence">Template:Cite journal</ref><ref name="IBD epidemiology">Template:Cite journal</ref><ref name="Prevalence psoriasis">Template:Cite journal</ref> 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.<ref name="Spondyloarthritis Elsevier" /> In the general community, 1–3% of people have psoriasis.<ref name="Prevalence psoriasis"/> It is less known how common psoriatic 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%.<ref name="Global Prevalence"/> Inflammatory bowel disease about 400 Caucasians per 100,000 people, with a male–to–female ratio of 1:1.<ref name="IBD epidemiology"/><ref name="Global Prevalence"/> People of Asian and African ancestry rarely experience it. Varying reports have varying risks for spondylitis and peripheral arthritis, which may be related to the observer's specialty. 15% to 20% of people with inflammatory bowel disease have spondylitis.<ref name="Spondyloarthritis Elsevier" /> Peripheral arthritis is generally less common in those with ulcerative colitis (up to 10%) than in those with Crohn's disease (up to 20%), but it is more common in cases where a rheumatologist served as the assessor.<ref name="IBD epidemiology"/><ref name="Global Prevalence"/>
History
Moll and associates first proposed the idea of a collection of similar conditions known as seronegative spondyloarthritides in 1974.<ref name="m505">Template:Cite journal</ref> Psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel disease, a subtype of juvenile idiopathic arthritis, and ankylosing spondylitis comprise the group of disorders currently referred to as spondyloarthritis.<ref name="Spondyloarthritis Lancet" />
See also
References
Further reading
External links
Template:Arthropathies and related conditions Template:Dorsopathies Template:Authority control