Overview of the clinical manifestations and classification of spondyloarthritis

INTRODUCTION — The term spondyloarthritis (SpA) is used for a family of disorders, including ankylosing spondylitis (AS, radiographic axial spondyloarthritis [r-axSpA]), nonradiographic axial spondyloarthritis (nr-axSpA), forms of arthritis associated with psoriasis and with inflammatory bowel diseases, and other conditions. The different forms of SpA share a group of clinical features; the most distinguishing features are inflammation of axial joints (especially the sacroiliac [SI] joints), asymmetric oligoarthritis (especially of the lower extremities), dactylitis (sausage digits), and enthesitis (inflammation at sites of ligamentous or tendon attachment to bone). Compared with the general population, patients with SpA have higher frequencies of the human leukocyte antigen (HLA) B27, and of sacroiliitis by radiography or magnetic resonance imaging (MRI) [1]. (See 'Major musculoskeletal features' below and 'Laboratory findings' below and 'Imaging' below.)

Additional features include skin and genital lesions, eye and bowel inflammation, an association with preceding or ongoing infectious disorders, positive family history, and elevated acute phase reactants [2-5]. Other terms that have been used for this family of arthritis are spondyloarthritides, spondyloarthropathy, and spondyloarthropathies.

An overview of the clinical manifestations and the classification of SpA in adults will be presented here. The clinical manifestations and diagnosis of AS and nr-axSpA, psoriatic arthritis, reactive arthritis (formerly called Reiter's syndrome), and SpA in children are discussed separately, as is an overview of peripheral SpA. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Clinical manifestations and diagnosis of psoriatic arthritis" and "Spondyloarthritis in children" and "Reactive arthritis" and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults".)

FORMS OF SPONDYLOARTHRITIS — The spondyloarthritis (SpA) family consists of the following members, which can be classified further according to the distribution of joint involvement as being predominantly axial (axial SpA) or peripheral (peripheral SpA):

●Ankylosing spondylitis (AS, radiographic axial SpA [r-axSpA]) (see "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults")

●Nonradiographic axial SpA (nr-axSpA) (see "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Nomenclature and classification')

●Peripheral SpA (see "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults")

●SpA associated with psoriasis or psoriatic arthritis (see "Clinical manifestations and diagnosis of psoriatic arthritis")

●SpA associated with Crohn disease and ulcerative colitis (see "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases")

●Reactive arthritis (see "Reactive arthritis")

●Juvenile-onset SpA (see "Spondyloarthritis in children")

The reasons for the classification of SpA into these categories are both historical and practical, but each category does not necessarily represent a discrete entity, and the clinical, laboratory, and imaging findings can overlap [3]. The diagnosis and management approaches for patients suspected of having any type of SpA are also generally similar [6,7].

Axial SpA patients with definite radiographic sacroiliitis are conventionally diagnosed with AS, while patients with axial SpA who do not show radiographic changes of sacroiliitis or have only very mild changes are classified as having nr-axSpA [8]. Patients with nr-axSpA were formerly included in a category termed "undifferentiated SpA" (USpA), but are generally considered clinically, diagnostically, and for management purposes together with patients with AS [9].

The smaller number of patients with predominantly peripheral manifestations of SpA (eg, arthritis, enthesitis, and dactylitis, rather than predominantly back and spine pain) who do not meet established classification criteria for AS, reactive arthritis, psoriatic arthritis, or SpA related to inflammatory bowel disorders can be considered as having peripheral SpA, but often evolve to develop a specific diagnosis [5,10]. By contrast, on follow-up, patients with axial SpA seldom switch to become peripheral SpA [1]. (See "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults".)

Historically, the term "Reiter's syndrome" was often used to refer either to reactive arthritis or patients with a subset of features seen in some patients with reactive arthritis, including the triad of arthritis, conjunctivitis, and urethritis; the term "reactive arthritis" is preferred for practical and historical reasons and encompasses these patients as well [11]. (See "Reactive arthritis".)

EPIDEMIOLOGY — There is considerable variation in the prevalence of spondyloarthritis (SpA) reported worldwide, depending upon the genetic background in the country or region under study, and to a certain extent upon the criteria used by the surveyors. The prevalences of ankylosing spondylitis (AS) have been reported in Europe as between 0.12 and 1.0 percent, dependent also on the human leukocyte antigen (HLA) B27 background prevalence, and as 0.17 percent in Asia, 0.1 percent in Latin America, and 0.07 percent in Africa. The prevalence for the whole group of axial SpA has been estimated to be two to three times higher than that of AS alone [12,13]. The low prevalence of AS in Latin America and Africa is partly because those are the regions with lowest prevalence of HLA-B27 [14,15]. AS and nonradiographic axial SpA (nr-axSpA) are the most frequent types of SpA. In the United States, they each have a prevalence of approximately 0.35 percent [16].

The male to female ratio is 2:1 in AS and 1:1 in nr-axSpA [2], but there is a frequent delay in diagnosis in females [4]. In contrast to axSpA, the sex distribution in peripheral SpA is equal between males and females [5].

The prevalence rate for SpA is approximately 0.9 to 1.7 percent, peripheral SpA accounting for approximately 25 percent of the total [5]. Reactive arthritis is the least common form of SpA. The epidemiologic characteristics of the individual forms of SpA are described in detail separately. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Epidemiology' and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults", section on 'Epidemiology' and "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Epidemiology and relation of arthritis to skin disease' and "Reactive arthritis", section on 'Epidemiology' and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Prevalence'.)

CLINICAL MANIFESTATIONS — The major clinical features which differentiate spondyloarthritis (SpA) from other forms of arthritis are the distribution and type of musculoskeletal manifestations and certain extraarticular features. Patients with axial SpA characteristically have chronic low back pain. Patients with peripheral SpA can exhibit peripheral musculoskeletal features, which include dactylitis (sausage digits), enthesitis (heel pain and/or swelling), and peripheral arthritis. Patients with peripheral SpA may experience one or more of these peripheral manifestations concurrently or in the past. Patients can also have both axial and peripheral manifestations.

Certain extra-musculoskeletal manifestations can be associated with the musculoskeletal features seen in SpA, including uveitis, psoriasis, features of inflammatory bowel diseases, and others. Reactive arthritis is sometimes associated with genital lesions.

Major musculoskeletal features

●Low back pain/inflammatory back pain – Back pain that is chronic and almost constant is one of the cornerstones of axial SpA. Patients with axial SpA typically have chronic low back pain of more than three months' duration; in most axial SpA patients, the onset of low back pain is before age 45. However, chronic low back pain of all causes, especially mechanical or nonspecific back pain, is common, with a prevalence estimated at about 20 percent of the general population [17]; only a small minority of these individuals has axial SpA. (See 'Epidemiology' above.)

A combination of low back pain features designated as "inflammatory back pain" is present in 70 to 80 percent of patients with axial SpA. These features include an insidious onset, most often before the age of 40 years; improvement with exercise but not with rest; and pain at night. However, inflammatory low back pain is also observed in 20 to 25 percent of back pain from other causes [18]. In addition, in a review of 10 years of records of 124 patients with new-onset inflammatory back pain, the probability of having SpA was only 30 percent [19]. Thus, despite its prevalence among patients with AS, only a minority of individuals with symptoms characteristic of inflammatory back pain will have SpA, and the lack of typical features of inflammatory back pain does not exclude axial SpA in a chronic back pain patient [20]. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Low back pain and neck pain'.)

An additional feature of low back pain in some patients with axial SpA is a good response to treatment with a nonsteroidal antiinflammatory drug (NSAID). Patients with back pain of many causes may improve somewhat when treated with an NSAID, but marked improvement in pain within 24 to 48 hours is more typical of SpA [21].

●Peripheral arthritis – Peripheral arthritis occurs at some point in approximately 37 percent of patients with axial SpA and 79 percent of patients with peripheral SpA [22]. The peripheral arthritis in SpA often predominantly involves the lower extremities, especially the knees and ankles, and is associated with swelling [23]. Arthritis is frequently asymmetrical and often affects only one to three joints [24]. The severity ranges from mild to disabling [25]. When compared with other rheumatic diseases, the sensitivity and specificity of asymmetric oligoarthritis for SpA are 41 and 87 percent, respectively [23]. Thus, the presence of asymmetrical oligoarthritis is very suggestive of SpA, but its absence would not be helpful in excluding this possibility.

●Enthesitis (enthesopathy) – Enthesitis (or enthesopathy) refers to inflammation around the enthesis, which is the site of insertion of ligaments, tendons, joint capsule, or fascia to bone, and is relatively specific to SpA [26]. The enthesis is composed of dense collagen, fibrocartilage, adjacent bursae, and synovial folds [26]. Enthesitis occurs at some point in the disease course in approximately 32 percent of patients with axial SpA and 63 percent of patients with peripheral SpA [4,22]. The most common observable clinical manifestation of enthesitis is swelling at the heels, at the insertion of the Achilles tendon (figure 1), or at the insertion of the plantar fascia ligament into the calcaneus [23]. It is usually associated with severe pain and tenderness. During physical examination, the patient with plantar fasciitis may have difficulty walking on the heels when barefoot. Swelling at the site of the Achilles tendon can be appreciated when the patient is observed in the standing position from behind; however, visible changes are not always present. On palpation, there is tenderness at the sites of insertion of the Achilles tendon and/or of the plantar fascia on the calcaneus.

Other sites of enthesitis which are often not swollen but which can be painful and/or tender include those at the patellae, iliac crests, greater trochanters, epicondyles at the elbows, tibial plateaus, costochondral junctions at the sternum, humeral tuberosities, manubrial-sternal joints, occiput, and spinous processes [27].

●Dactylitis (sausage digits) – A characteristic feature of SpA, especially psoriatic arthritis and occasionally reactive arthritis, is dactylitis, also known as sausage toe or sausage finger (picture 1). Unlike synovitis, in which swelling is confined to the joints, with dactylitis, the entire digit is swollen. Joints do not show the discrete palpable fusiform swelling of synovitis, and there may be surprisingly little pain or tenderness. The diffuse swelling arises from flexor tendon, sheath, and marked adjacent soft tissue involvement, but may also involve the bone and joints. Dactylitis occurs in only 5 percent of patients with axial SpA and 17 percent of patients with peripheral SpA [22]. Dactylitis is not specific for SpA and may also be seen when the digits are involved with tuberculosis, syphilis, sarcoidosis, sickle cell disease, and tophaceous gout [28].

●Other musculoskeletal features – Approximately 35 to 50 percent of axial SpA patients experience anterior chest wall pain from involvement of the manubriosternal, sternoclavicular, and costosternal joints [29]. Additional musculoskeletal features sometimes but not always seen in patients with SpA include pain in the neck, dorsal kyphosis, head-forward posture, and limitation in ranges of motion of lumbar and cervical spines and chest expansion. These are relatively nonspecific and either absent or also seen in other diseases. Limitation of ranges of motion of the spine, for example, depend on the duration of disease, disease activity, extent of structural damage, and age [30-32]. Pain that alternates between the left and the right gluteal regions is more specific to axial SpA.

Major extra-musculoskeletal features — The major extra-musculoskeletal features are uveitis, associated inflammatory bowel diseases, and psoriasis:

●Inflammatory eye disease – Several forms of ocular inflammatory disease can be associated with SpA, including conjunctivitis and anterior uveitis [33,34]. Conjunctivitis is typically non-purulent and transient, with symptoms subsiding within a few weeks. A more serious problem is anterior uveitis (iritis) [34]. Uveitis, which is usually anterior uveitis, occurs in up to 30 percent of patients with SpA, and becomes recurrent in approximately 50 percent of affected patients [35]. The initial attack is usually acute and unilateral and may be the presenting problem. Patients complain of redness, pain, and photophobia. Uveitis may be the first problem to require medical evaluation and should alert clinicians to the possibility of SpA. About 20 to 50 percent of patients with acute recurrent unilateral anterior uveitis have a form of SpA that might have been previously undiagnosed until the appearance of uveitis. Many patients with initial attacks of uveitis are not aware of the possibility of SpA [36,37]. Although ocular inflammation usually responds to topical therapy, 10 percent can become chronic and threaten permanent impairment of vision [38,39]. (See "Uveitis: Treatment".)

An accurate diagnosis of uveitis requires slit-lamp examination by an ophthalmologist or other expert in uveitis. Episodes of uveitis do not necessarily parallel the course of the musculoskeletal manifestations such as back pain, peripheral arthritis, or enthesitis. (See "Uveitis: Etiology, clinical manifestations, and diagnosis".)

●Inflammation of the bowel mucosa – SpA is associated with the presence of the inflammatory bowel diseases Crohn disease and ulcerative colitis. In a systematic review. the pooled prevalence of inflammatory bowel disease among patients with ankylosing spondylitis (AS) was 6.8 percent [40]. Conversely, SpA musculoskeletal symptoms are the most common extraintestinal symptoms in patients with inflammatory bowel disease [35,41]. (See "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases".)

●Psoriasis – Psoriasis is associated with all forms of SpA. Some experts have suggested that all forms of arthritis associated with psoriasis should be classified as part of the SpA family, but this remains a matter of debate [3,42]. Psoriasis is present in up to approximately 10 percent of patients with AS [40,43]. In patients with AS, it was found that peripheral joint involvement and dactylitis are more frequently seen with concomitant psoriasis, and the disease course may be more severe than in patients without psoriasis [44].

Family history — Among patients with chronic back pain suspected of axial SpA, fulfillment of Assessment of SpondyloArthritis International Society (ASAS) criteria for axial SpA was more common in those with a positive family history of either ankylosing spondylitis or acute anterior uveitis in a first- or second-degree relative [35,45].

LABORATORY FINDINGS — Although not absolutely specific for spondyloarthritis (SpA), human leukocyte antigen (HLA) B27 is a very important laboratory test in assessing SpA. Also helpful, but to a lesser extent, are acute phase reactants.

●HLA-B27 – In most ethnic groups, 85 to 95 percent of patients with ankylosing spondylitis (AS) and 75 to 85 percent of patients with other forms of SpA are positive for HLA-B27 [35]. In that way, it is a cornerstone of the diagnosis of SpA. HLA-B27 testing is frequently obtained in patients suspected of SpA; however, a positive HLA-B27 by itself is not diagnostic of SpA, since a significant proportion of subjects in the general population are also positive [10,21,46]. Conversely, a negative HLA-B27 does not exclude a diagnosis of SpA. However, a diagnosis of axial SpA should be doubted if both HLA-B27 and imaging (including MRI) for sacroiliitis are negative. The diagnosis of SpA is discussed in detail separately. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Epidemiology' and "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Laboratory testing' and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults", section on 'Laboratory findings'.)

●Acute phase response – Acute phase responses, including the erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP), are increased in between 35 and 50 percent of patients with axial SpA [47,48] (see 'Axial SpA' below). Elevated levels of CRP are also a predictor of radiographic progression [49] and for a good response to tumor necrosis factor (TNF)-blocker therapy [50].

IMAGING — Imaging is a cornerstone in the diagnosis of axial spondyloarthritis (SpA). There are several characteristic imaging findings that may be seen in patients with axial SpA. Sacroiliitis, especially on plain radiography, is relatively specific for axial SpA. Typical syndesmophytes and other changes of spondylitis in the spine are also relatively specific for axial SpA, but are usually seen in more longstanding disease and are not often present early in the disease course. Other findings may include changes of enthesitis and erosive joint disease, but are not specific to axial SpA. In some patients with peripheral SpA, evidence for sacroiliitis can also be found, even if these patients do not complain of back pain [51]. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Musculoskeletal imaging' and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults", section on 'Imaging' and "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Imaging findings' and "Reactive arthritis", section on 'Imaging abnormalities'.)

Plain radiographs — Many patients with axial involvement have normal plain radiographs in early disease, although the presence of radiographic findings consistent with definite sacroiliitis strongly suggests a diagnosis of axial SpA. Plain radiographs of the spine, involved peripheral joints, and entheses may demonstrate abnormalities in longstanding axial SpA [52]. (See "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults", section on 'Imaging' and "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Imaging findings' and "Reactive arthritis", section on 'Imaging abnormalities' and "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Radiography'.)

Axial radiographs — The only plain radiographic findings that are specific for axial SpA are those of sacroiliitis. However, it may take several years from the onset of disease before radiographic sacroiliitis becomes apparent. Only in less than 5 percent of ankylosing spondylitis (AS) patients, AS-typical syndesmophytes, ossification originating from the intervertebral ligaments that may bridge the vertebral bodies, may be found in the spine in the absence of radiographic sacroiliitis. At least 50 percent of patients with AS develop syndesmophytes of the spine in the course of their disease. These syndesmophytes have a typical appearance and are easily differentiated from degenerative spinal osteophytes. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Spine'.)

Plain radiographs of the sacroiliac (SI) joints can be semiquantitatively graded based upon the presence of the characteristic radiographic findings [52] (see "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Plain radiography'):

●Grade 0: Normal (image 1).

●Grade 1: Suspicious changes (image 2).

●Grade 2: Minimal abnormality – Small localized areas with erosions or sclerosis, without alteration in the joint width (image 2). Erosions usually first appear on the iliac side.

●Grade 3: Unequivocal abnormality – Moderate or advanced sacroiliitis with erosions, evidence of sclerosis, widening, narrowing, or partial ankylosis (image 3A-B).

●Grade 4: Severe abnormality – Total ankylosis (image 4A-B).

According to these grading criteria, a patient is regarded as positive for evidence of radiographic sacroiliitis if the radiographic study is rated at grade 2 or higher bilaterally, or at grade 3 or higher unilaterally [52]. By convention among experts, nearly all patients considered to have nonradiographic axial SpA (nr-axSpA) do not have definite plain radiographic findings of sacroiliitis [53].

Radiographic sacroiliitis is considered the hallmark of AS, but whether it should continue to be used as a diagnostic criterion is a matter of debate. It is frequently absent in the first year of the disease, and a substantial proportion of the patients with axial SpA will never develop it [54]. Furthermore, disagreement among radiologists or rheumatologists reading the same film is frequent, resulting in false-positive or false-negative diagnoses of AS, and additional training does not improve recognition of sacroiliitis. The highest variability is observed in the evaluation of grades 1 and 2 [55,56]. Further investigation is needed to determine whether MRI-T1 sequences or low-dose computed tomography (CT) can substitute for radiographs for the detection of structural lesions in the SI joint, as was suggested in one study [57,58].

Radiographs of peripheral joints and entheses — There is some variation in the degree and type of radiographic change seen in different types of SpA. In patients with axial SpA, the most severe peripheral joint involvement observed on plain radiographs is in the hip joints, where extensive destructive changes may occur. By contrast, although the knees might show considerable swelling, sometimes persistent for years, radiographs of the knees in patients with SpA often show only mild osteoarthritic changes [59]. Similarly, radiographic changes in the shoulders are usually only minor in patients with AS [60]. Fluffy erosions can sometimes be seen in areas of enthesitis, such as the heels, although these findings are not specific for SpA [61]. (See "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Plain radiography'.)

Radiographic changes in peripheral joints are common in patients with psoriatic arthritis, even relatively early in the disease course [62,63]. Changes can develop in the course of psoriatic arthritis that exhibit a pattern usually not seen in other forms of inflammatory arthritis of coexisting erosive changes and new bone formation within the same joint or in different joints within the same digit. Other typical changes include lysis of the terminal phalanges; fluffy periostitis, as well as new bone formation, at the site of enthesitis; gross destruction of isolated joints; "pencil-in-cup" appearance; and the occurrence of both joint lysis and ankylosis in the same patient (image 5) [62,64]. Patients with psoriatic arthritis may exhibit more damage at the knees than patients with other forms of SpA. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Imaging findings'.)

In patients with arthritis associated with inflammatory bowel disease, plain film radiographs of the peripheral joints demonstrate soft-tissue swelling, juxtaarticular osteoporosis, mild periostitis, and effusions, usually without erosions or destruction. Radiographic abnormalities in the joints are common, even in asymptomatic patients. (See "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Radiographic findings'.)

Magnetic resonance imaging — MRI can reveal changes consistent with SpA, including sacroiliitis and spinal changes, but is usually not necessary for diagnostic purpose in patients with obvious abnormalities on plain radiography. MRI abnormalities of the SI joints in the face of normal plain radiographs are important in helping to establish the diagnosis of nr-axSpA. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Imaging findings' and "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Spine' and "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'MRI of sacroiliac joints'.)

MRI of sacroiliac joints — The most prominent SI joint findings on MRI that are characteristic of SpA are high-intensity bone marrow edema (BME) on short tau inversion recovery (STIR) or on T2 with fat absorption images. Typical locations are the subchondral or periarticular bone marrow (image 6) [58]. Specific definitions for active sacroiliitis have been formulated for use with some classification criteria. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'MRI of sacroiliac joints'.)

BME becomes especially important when associated with structural lesions, such as fat metaplasia, sclerosis, erosions, backfill (fat metaplasia in the joint space), or bony ankylosis [65,66].

Although BME in the SI joint is suggestive of axial SpA, it can also be seen in healthy subjects as well as in postpartum women, and individuals with other diseases such as infection, malignancy, and osteitis condensans ilii [3,66]. In addition, for the same MRI, there can be discrepancy among different readers. However, when MRI findings are interpreted together with clinical findings, the discrepancies do not affect the clinical decisions [67]. The use and importance of MRI of the SI joints in the diagnosis of axial SpA is discussed in detail separately [68]. (See "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'MRI of sacroiliac joints'.)

MRI of the spine — Typical spondylitis-related MRI lesions are triangular in shape and are located at one or more of the four corners of the vertebrae. They include BME observed with the STIR or the T2 with fat absorption sequences, as well as fatty deposits observed as high-intensity lesions in the T1-weighted sequences. Again, such findings are not specific for SpA [69]. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Spine'.)

Other imaging techniques — Other imaging techniques are less frequently used.

●Ultrasonography for enthesitis – The ultrasonographic features of enthesitis include inflammation (hypoechogenicity, increased thickness of the tendon insertion, and Doppler activity) and structural changes (intratendinous calcifications and enthesophytes) [70].Although ultrasound might detect the inflammatory changes of sacroiliitis, its use is presently limited to research and is not recommended in routine clinical practice [71]. The findings and use of ultrasonography in SpA and other conditions are described in detail elsewhere. (See "Musculoskeletal ultrasonography: Clinical applications", section on 'Entheses' and "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Imaging of enthesitis' and "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Nomenclature and classification'.)

●CT scanning – CT is more sensitive than plain radiography for the detection of structural changes in the sacroiliac joints [72]. However, CT scanning has several disadvantages compared with MRI. CT and MRI are comparable for the detection of bony changes such as erosions and sclerosis, but only MRI allows detection and analysis of inflammatory changes in subchondral bone and entheses (STIR sequence), as well as the detection of fatty change (T1 sequence) [73,74]. Moreover, radiation exposure from CT studies is a clear disadvantage compared with MRI. This might be overcome in the future with low-dose CT [57,58,75-77].

●Scintigraphy – Bone scintigraphy reveals high uptake in areas of inflammation. However, it is too nonspecific to be useful for diagnosis of SpA [78]. (See "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Imaging studies'.)

CLASSIFICATION OF SPONDYLOARTHRITIS — Classification criteria for spondyloarthritis (SpA) in general and ankylosing spondylitis (AS) specifically were developed for use in epidemiologic and clinical research such as clinical drug trials; similar to other rheumatic diseases [79], they do not have sufficient sensitivity and specificity for use as the only diagnostic tools in clinical practice and thus cannot be regarded in clinical practice as inviolable rules [54,80,81]. The classification criteria developed by the Assessment of SpondyloArthritis International Society (ASAS) are broadly inclusive, used widely by experts in SpA, and distinguish between axial and peripheral SpA (see 'ASAS classification criteria' below). Use of the ASAS criteria has largely replaced the use of older classification criteria, including the Modified New York criteria for AS, the European Spondyloarthritides Study Group (ESSG) criteria, and the Amor criteria, among SpA investigators [23,82,83]. (See 'Other SpA classification criteria' below.)

ASAS classification criteria — There are two sets of classification criteria for SpA that have been issued by the ASAS: one for those presenting with axial involvement (see 'Axial SpA' below), published in 2009, and the other for those presenting with peripheral involvement (see 'Peripheral SpA' below), published in 2011 [52]. The classification criteria were generated from a cross-sectional study of patients newly referred for possible SpA and of control arthritis patients. In the ASAS study population, in patients (largely) who were under age 45 and who presented with either undiagnosed back pain or peripheral arthritis (or enthesitis or dactylitis) at the time seen, the combined criteria had a sensitivity of 80 percent and a specificity of 83 percent [24]. These criteria compared favorably with other previously established criteria sets. (See 'Other SpA classification criteria' below.)

Axial SpA — Classification criteria for axial SpA, including criteria for those without plain radiographic changes (nonradiographic axial SpA [nr-axSpA]) and with radiographic (radiographic axial SpA) changes of sacroiliitis, were based upon a large multicenter study [47]. In patients with a history of back pain of unknown origin, which was of at least three months' duration and which began before age 45, the classification criteria for axial SpA exhibited sensitivity of 83 percent and specificity of 84 percent [47]. This algorithm is as follows:

●The entry step is that the patient must have back pain of any type for at least three months, and the age of onset must be less than 45 years.

●The second step consists of two arms that are evaluated separately based upon the presence either of sacroiliitis on imaging or of human leukocyte antigen (HLA) B27:

•HLA-B27-positive patients – In patients who test positive for HLA-B27, at least two additional features of SpA from the list below are required for classifying a patient as having axial SpA (see 'SpA features' below)

•Sacroiliitis on imaging – In patients diagnosed with sacroiliitis based upon plain radiographs (structural changes) or MRI (subchondral bone marrow edema [BME]), at least one other feature of SpA from the list below should be present (see 'SpA features' below)

SpA features — The following are SpA features that contribute to the classification criteria for axial SpA (see 'Axial SpA' above):

●Inflammatory back pain – Several definitions for inflammatory back pain have been proposed. For classification purposes, inflammatory back pain can be defined as having at least four of the five following parameters [84]:

•Age of onset <40 years

•Insidious onset

•Improvement with exercise

•No improvement with rest

•Pain at night (with improvement upon arising)

●Other SpA features (each of equal weight) – Other SpA features include the presence of one or more of the non-spinal features noted below. The occurrence can be either before or at the time of evaluation for the following items listed: arthritis, heel enthesitis, uveitis, dactylitis, psoriasis, and inflammatory bowel disease. The features are:

•Arthritis – As diagnosed by a clinician

•Heel enthesitis – Spontaneous pain or tenderness at site of insertion of Achilles tendon or plantar fascia at the calcaneus diagnosed by a clinician

•Uveitis – Confirmed by an ophthalmologist

•Dactylitis – Diagnosed by a clinician

•Psoriasis – Diagnosed by a clinician

•Inflammatory bowel disease – Crohn disease or ulcerative colitis diagnosed by a clinician

•Good response to nonsteroidal antiinflammatory drugs (NSAIDs) – Within 24 to 48 hours

•Family history of SpA – Presence in first- or second-degree relatives of AS or acute anterior uveitis [45]

•Elevated C-reactive protein (CRP) – After exclusion of other causes for elevated CRP

Peripheral SpA — Classification criteria for peripheral SpA were based upon analyses of data from a cross-sectional international multicenter study [24]. In patients with undiagnosed peripheral arthritis, enthesitis, and/or dactylitis, the ASAS classification criteria for peripheral SpA had a sensitivity of 78 percent and a specificity of 83 percent [24]. In the study, 85 percent of the patients were under age 45. For classification as having peripheral SpA, the patient should NOT have concurrent chronic (inflammatory) back pain. In that case, the axial SpA criteria should be used. However, inflammatory back pain in the past is considered as a contributing SpA feature. There are two steps in the algorithm for classifying peripheral SpA:

The entry step is that the patient should have, at the time of being seen, at least one of the following three findings:

●Arthritis

●Enthesitis (spontaneous pain or tenderness at any enthesis)

●Dactylitis

If the patient satisfies the entry criteria, the patient should show (or have had in the past) at least one of the features of SpA in Group A (below) or at least two of the features of SpA in group B (below):

●Group A SpA features:

•Uveitis – Confirmed by an ophthalmologist

•Psoriasis – Diagnosed by a clinician

•Crohn disease or ulcerative colitis – Diagnosed by a clinician

•Preceding infection – Urethritis/cervicitis or diarrhea within one month prior to onset of arthritis/enthesitis/dactylitis

•HLA-B27

•Sacroiliitis on imaging

●Group B SpA features:

•Arthritis – Diagnosed by a clinician

•Enthesitis – Diagnosed by a clinician

•Dactylitis – Diagnosed by a clinician

•Inflammatory back pain in the past

•Family history of SpA – Presence in first- or second-degree relatives of AS and acute uveitis

Other SpA classification criteria — Research prior to the 2009 and 2011 publication of the ASAS criteria (see 'ASAS classification criteria' above) usually classified patients using either the ESSG criteria, the Amor criteria, or the modified New York Criteria for AS [23,82,83]. These criteria sets differ somewhat from each other and from the ASAS classification criteria (table 1). The ESSG and Amor criteria cover the whole spectrum of SpA and include a broader range of manifestations of SpA compared with the modified New York criteria. However, unlike the ASAS classification criteria, these criteria do not differentiate axial from peripheral disease, a distinction that may be important for providing optimal care and for testing treatment strategies, and MRI findings are not taken into consideration. Because certain medications have been approved by the US Food and Drug Administration (FDA) for AS alone, the Modified New York criteria for AS still play a role in decision making [81]. Patients fulfilling these criteria are largely overlapping with radiographic axial SpA (as part of axial SpA), with identical definitions for the radiographic changes in the SI-joints, but with some differences in the definition of the nonimaging parameters:

●1984 Modified New York Criteria – For most research carried out from the mid-1980s to 2009, patients were regarded as having AS only if they fulfilled the 1984 Modified New York Criteria for AS. However, these criteria do not recognize patients with nonradiographic axial SpA (nr-axSpA), because such patients lack radiographic sacroiliitis, one of the required criteria. The modified New York criteria consist of a subset of clinical parameters and a subset of radiological parameters, with a patient regarded as having definite AS if they fulfill at least one radiologic parameter plus at least one clinical parameter:

•Clinical parameters

-Low back pain and stiffness for more than three months that improves with exercise but that is not relieved by rest

-Limitation of motion of the lumbar spine in both the sagittal and frontal planes

-Limitation of chest expansion relative to normal values correlated for age and sex

•Radiological parameters using plain radiographs alone (see 'Axial radiographs' above):

-Sacroiliitis grade ≥2 bilaterally, or

-Sacroiliitis grade 3 to 4 unilaterally

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Spondyloarthritis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Reactive arthritis (Beyond the Basics)" and "Patient education: Axial spondyloarthritis, including ankylosing spondylitis (Beyond the Basics)")

SUMMARY

●Spondyloarthritis (SpA) refers to a group of diseases that share the combination of several major clinical features. The most important features are chronic low back pain, positivity with the blood test for the human leukocyte antigen (HLA) B27, and radiographic or MRI changes in the sacroiliac (SI) joints in patients with axial SpA; and (oligo)arthritis, heel enthesitis and dactylitis in patients with peripheral SpA. Additional characteristics include a good response to nonsteroidal antiinflammatory drugs (NSAIDs), a positive family history for SpA, uveitis, inflammatory bowel disease, psoriasis, and increased levels of acute phase reactants. (See 'Forms of spondyloarthritis' above and 'Clinical manifestations' above and 'Laboratory findings' above.)

●Disorders considered as forms of SpA include ankylosing spondylitis (AS), nonradiographic axial SpA (nr-axSpA), peripheral SpA, psoriatic arthritis, inflammatory bowel disease-related arthritis, reactive arthritis (formerly called Reiter's syndrome), and SpA in children. (See 'Forms of spondyloarthritis' above.)

●Characteristic imaging findings that may be seen in patients with axial SpA include sacroiliitis, which may result in structural lesions such as sclerosis, joint space widening, or erosion, and is relatively specific for axial SpA on plain radiography; and syndesmophytes and changes of spondylitis in the spine, which are most often detected in more longstanding disease. Evidence of active sacroiliitis (subchondral bone marrow edema [BME]) on MRI in patients with normal plain radiography is very frequently seen in patients with nr-axSpA. (See 'Imaging' above.)

●Sets of classification criteria for axial and peripheral SpA have been developed for epidemiologic and clinical research purposes. The Assessment of SpondyloArthritis International Society (ASAS) criteria broadly distinguish between axial SpA (AS and nr-axSpA) and peripheral SpA; the ASAS criteria are inclusive of disorders such as psoriatic arthritis or inflammatory bowel disease-related arthritis. AS, a subset of axial SpA, is defined by the Modified New York criteria for AS. (See 'Classification of spondyloarthritis' above and 'ASAS classification criteria' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David Yu, MD, who contributed to earlier versions of this topic review.