Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults

INTRODUCTION — Peripheral spondyloarthritis (SpA) is the term used to describe patients with features of SpA whose symptoms and findings are predominantly or entirely peripheral rather than axial; these features include arthritis, enthesitis, and dactylitis. Patients included in this category, who have these findings in common, include those with psoriatic arthritis (PsA), reactive arthritis, SpA related to inflammatory bowel disease (IBD), and the subset of patients with such manifestations who do not meet established definitions for these three forms of SpA. Patients with radiographic axial SpA (or ankylosing spondylitis) and non-radiographic axial SpA are not included within the peripheral SpA category, even if peripheral manifestations of musculoskeletal involvement are also present. Even though the Assessment of SpondyloArthritis International Society (ASAS) classifies SpA into axial and peripheral groups [1,2], this binary division seldom exists in practice because there is considerable overlap between axial and peripheral SpA [3].

Within the peripheral SpA subset, a clear distinction between the clinically defined subsets is often lacking. As examples, in a considerable number of patients, skin manifestations of psoriasis do not occur until after the manifestation of rheumatic symptoms; preceding infections may be clinically asymptomatic (eg, with Chlamydia); and IBD can also be asymptomatic when patients present with musculoskeletal symptoms [4,5].

An overview of the clinical manifestations, diagnosis, and differential diagnosis of peripheral SpA in adults will be presented here, which is focused upon those adult patients with peripheral SpA who do not have psoriasis, IBD, or reactive arthritis. The treatment of peripheral SpA; the classification of SpA; and the clinical manifestations, diagnosis, and treatment axial SpA, PsA, reactive arthritis, arthritis associated with IBD, and SpA in children are discussed in more detail separately. (See "Treatment of peripheral spondyloarthritis" and "Overview of the clinical manifestations and classification of spondyloarthritis" and "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Clinical manifestations and diagnosis of psoriatic arthritis" and "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Spondyloarthritis in children" and "Reactive arthritis" and "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases".)

EPIDEMIOLOGY — The global prevalence of spondyloarthritis (SpA), including axial and peripheral SpA, has been estimated at approximately 0.6 percent [6]. In a 2019 cross-sectional study of 2423 SpA patients without associated psoriasis from a wide range of countries, only 6 percent of these SpA patients showed a peripheral arthritis predominant distribution [7]. Study results vary widely between different populations and ethnic groups, which can at least partly be explained by differences in the prevalence of human leukocyte antigen B27 (HLA-B27). Other important contributors to these differences are heterogeneity in the populations analyzed, variation in the criteria used for case definition, and the number of participants approached and included in each study.

The main manifestation of peripheral SpA is arthritis (96 to 98 percent), followed by enthesitis (41 to 48 percent) and dactylitis (40 to 49 percent) [3]. Peripheral SpA has an equal sex distribution [8].

CLINICAL MANIFESTATIONS — The clinical manifestations of peripheral spondyloarthritis (SpA) include most of the features common to other forms of SpA; only some of these may be present in a given patient. Those of greatest importance, as reflected by the classification criteria for peripheral SpA, include the three peripheral musculoskeletal manifestations, which are arthritis (predominantly of the lower extremities and/or asymmetric), enthesitis, and dactylitis [1]. Of similar importance are other features, including uveitis and the presence of psoriasis or inflammatory bowel disease (IBD; Crohn's disease/ulcerative colitis) or a history of an infection that may trigger reactive arthritis. Other features that may be present, but which are of lesser importance in the classification scheme, are a history of inflammatory back pain (IBP) in the past and a family history of SpA, which is defined as the presence in a first- or second-degree relative of SpA, uveitis, reactive arthritis, psoriasis, or IBD. (See 'Musculoskeletal features' below and 'Inflammatory eye disease' below and 'Inflammation of the bowel mucosa' below and 'Psoriasis' below.)

Although the clinical picture is often very similar, patients with psoriasis, IBD, and reactive arthritis each do have some features specific for their diseases which are described in detail separately [9-11]. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Clinical manifestations' and "Reactive arthritis", section on 'Clinical manifestations' and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Clinical manifestations'.)

Musculoskeletal features — The three peripheral musculoskeletal manifestations characteristic of peripheral SpA are peripheral arthritis, enthesitis, and dactylitis. The other musculoskeletal manifestation that may be present is back pain, including IBP, current or in the past. The back pain, however, is not a dominant feature compared with the peripheral symptoms and findings [12].

●Peripheral arthritis – Peripheral arthritis is present in most patients with peripheral SpA. The peripheral arthritis in SpA is often chronic but can be self-limiting and predominantly involves the lower extremities, especially the knees and ankles [1,3]. However, any joint can be involved. Arthritis is asymmetric in approximately 70 percent of patients and often affects only one to three joints [1]. A small percentage of patients have involvement of four or more joints.

●Enthesitis (enthesopathy) – Enthesitis is a hallmark clinical feature of SpA (and also of psoriatic arthritis) [13]. Enthesitis (or enthesopathy) refers to inflammation around the enthesis, which is the site of insertion of ligaments, tendons, joint capsule, or fascia to the surface of the bone, and is relatively specific to SpA [14]. Although enthesitis is less common than peripheral arthritis, it is still present in approximately 57 percent of patients [15].

The most noticeable clinical manifestation of enthesitis is swelling at the heels, either at the insertion of the Achilles tendon (figure 1 and picture 1) or at the insertion of the plantar fascia ligament into the calcaneus. It is usually associated with severe pain and tenderness.

During physical examination, the patient often has difficulty walking on the heels when barefoot. Swelling at the side of the Achilles tendon may be appreciated when the patient is observed in the standing position from behind. 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 that do not become visibly swollen, but which can be tender, include those at the iliac crests, greater trochanters, epicondyles at the elbows, quadriceps insertion into superior border of patella, patellar ligament insertion into the inferior pole of the patella or into the tibial tuberosity, costochondral junctions at the sternum, humeral tuberosities, manubrial-sternal joints, occiput, and spinous processes [16].

The presence of enthesitis detected by tenderness alone might require imaging for confirmation [12].

●Dactylitis (sausage digits) – Dactylitis, also known as sausage toe or sausage finger (picture 2), is present in approximately 23 percent of patients with peripheral SpA without psoriasis [15]. Because it is more often found in association with psoriasis, presence of dactylitis heightens the suspicion of psoriatic arthritis (PsA). 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. Although dactylitis is a characteristic manifestation of SpA, it may also be seen in other conditions, including tuberculosis, syphilis, sarcoidosis, sickle cell disease, and tophaceous gout [17].

●Inflammatory back pain – A pattern of back discomfort referred to as IBP is characteristic of axial SpA, but by definition is not the predominant feature of peripheral SpA, although up to 21 percent of patients with predominantly peripheral symptoms have a history of back pain in the past that is consistent with IBP [18]. However, IBP is considered present in patients with at least four of the following five features: an insidious onset of back pain, onset before the age of 40 years, improvement with exercise, a lack of improvement with rest, and pain at night [19]. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Low back pain and neck pain'.)

Subclinical spinal disease is also frequently present in patients with peripheral SpA. In a clinical trial, including patients with early SpA, 35 percent had sacroiliitis on magnetic resonance imaging (MRI), while only 12 percent reported having back pain [20].

Inflammatory eye disease — Ocular inflammatory diseases, including conjunctivitis and anterior uveitis, may occur. Conjunctivitis is typically transient with symptoms subsiding within a few weeks. A more serious problem is anterior uveitis (iritis), which is mostly associated with human leukocyte antigen B27 (HLA-B27) positivity and may occur in 17 percent of the patients with peripheral SpA [15]. The initial attack of uveitis is usually acute and unilateral and may be the presenting problem. Patients typically note redness, pain, and photophobia. Although ocular inflammation often responds to topical therapy, permanent impairment of vision is possible if treatment is unsuccessful. (See "Uveitis: Treatment".)

An accurate diagnosis and optimal management of uveitis requires slit lamp examination by an ophthalmologist or other expert in uveitis. Episodes of uveitis can last several months but usually do not run a chronic course or necessarily parallel the course of arthritis. (See "Uveitis: Etiology, clinical manifestations, and diagnosis".)

Inflammation of the bowel mucosa — Bowel mucosal inflammation associated with peripheral SpA can be symptomatic, as in patients with IBD, or can be asymptomatic. Approximately 10 percent of patients with IBD present with signs or symptoms of SpA [10,21]. In patients with IBD, the peripheral arthritis can be associated with skin, oral mucosal, and ocular manifestations of IBD (See "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases" and "Pathogenesis of spondyloarthritis".)

Up to two-thirds of patients with SpA have inflammatory lesions of the bowel mucosa, but these are frequently clinically silent [22]. The prevalence of gut inflammation in patients with peripheral arthritis is approximately 4 percent and similar to those with axial involvement [15]

Psoriasis — Psoriasis is found in 12 percent of patients with peripheral SpA [15]. However, it is mainly considered as psoriatic arthritis. Arthritis associated with psoriasis is described in detail separately. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Diagnosis'.)

Reactive arthritis – Reactive arthritis is characterized by a history or evidence of an episode of a triggering infection that precedes the onset of musculoskeletal symptoms. Reactive arthritis is discussed in detail separately. (See "Reactive arthritis".)

LABORATORY FINDINGS — There are no laboratory findings that are pathognomonic for peripheral spondyloarthritis (SpA) or SpA in general, although individuals with human leukocyte antigen B27 (HLA-B27) are at increased risk for SpA, and, in some patients, acute phase reactants may be elevated. Occasionally, laboratory tests can identify microbial infections which can trigger reactive arthritis.

●HLA-B27 – HLA-B27 is present in 62 percent of the patients with peripheral SpA without other associated disease, but is present in a lower frequency in patient with psoriatic arthritis (PsA) and arthritis associated with inflammatory bowel disease (IBD) [15]. A positive HLA-B27 by itself is supportive but not diagnostic of SpA, since a significant proportion of subjects in the general population are also positive. All features of SpA can also occur in HLAB27-negative patients, although acute anterior uveitis is rare in this population [23-25].

●Infection – Specific infectious diseases are best established as a trigger of SpA for reactive arthritis. (See "Reactive arthritis", section on 'Definition' and "Reactive arthritis", section on 'Preceding infection' and "Reactive arthritis", section on 'Acute inflammatory changes' and "Pathogenesis of spondyloarthritis".)

●Acute phase reactants – Acute phase reactants, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are often increased, although normal ESR and CRP levels do not exclude the presence of SpA. Increased levels of CRP are present in approximately 48 percent of peripheral SpA patients who do not have psoriasis [15].

IMAGING — Sacroiliitis on imaging, detected by either plain radiography or MRI, can be present in patients with peripheral spondyloarthritis (SpA), even if patients do not complain about typical back pain [15,20]. The other imaging findings depend upon the form of peripheral SpA that is present. Radiographs of peripheral joints, including those with inflammatory bowel diseases (IBD), are often normal [26]; a particular exception is patients with more advanced psoriatic arthritis (PsA). (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Imaging findings' and "Reactive arthritis", section on 'Imaging abnormalities' and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Radiographic findings' and "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Musculoskeletal imaging'.)

●Peripheral joints – Plain radiographs of peripheral joints are often unremarkable in peripheral SpA. By contrast, in patients with PsA, both osteo-proliferative and osteo-destructive lesions may be seen not only in the same patient, but also in the same joint. Other typical radiologic changes in PsA 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. The distal interphalangeal joints are frequently the first to be affected, followed by the proximal interphalangeal joints, the metacarpal phalangeal joints, and the wrists. (See "Clinical manifestations and diagnosis of psoriatic arthritis".)

●Entheses – Fluffy erosions can sometimes be seen using plain radiography in areas of enthesitis, such as the heels, although these findings are not specific for SpA [14]. Studies using B-mode ultrasound with power Doppler capability (PDUS) can demonstrate abnormal vascularization at the entheses in patients with SpA in the hands of experienced operators [14]. (See "Musculoskeletal ultrasonography: Clinical applications", section on 'Entheses'.)

●Dactylitis – Plain radiographs of dactylitis in patients with SpA do not show changes affecting the bone itself, which distinguishes SpA-related dactylitis from the swollen digits of dactylitis that may be seen in tuberculosis, sarcoid, sickle cell disease, and syphilis [27] (see 'Differential diagnosis' below). The MRI and ultrasound change common to the dactylitis of SpA is flexor tenosynovitis [27].

●Axial skeleton – Findings of sacroiliitis by plain radiography or MRI may be present in up to 50 percent of patients with peripheral SpA, even in those with only several weeks of disease [1,15,28]. Axial findings in patients with PsA and the arthritis of IBD may be more asymmetric, especially in those who are human leukocyte antigen B27 (HLA-B27)-negative, than is typically seen in axial spondyloarthritis. The radiographic findings of axial SpA are described in detail separately. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Musculoskeletal imaging' and "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Imaging findings' and "Reactive arthritis", section on 'Imaging abnormalities' and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Radiographic findings'.)

DIAGNOSIS AND CLASSIFICATION

Diagnostic strategy — The diagnosis of peripheral spondyloarthritis (SpA) is entirely clinical, which may be challenging. There are no established diagnostic algorithms or criteria for peripheral SpA and presenting signs and symptoms may overlap other entities. There are four principle elements that should be weighed collectively to establish the diagnosis:

●Identification of characteristic clinical findings, such as asymmetric and/or oligoarticular large-joint arthritis, enthesitis, or dactylitis, and other associated features that may be present (eg, anterior uveitis, family history of SpA-related disease). (See 'Clinical manifestations' above and 'Laboratory findings' above and 'Imaging' above and 'Use of classification criteria' below.)

●Identification of features of one of the subgroups of peripheral SpA (eg, psoriasis, Crohn disease/ulcerative colitis, or reactive arthritis). (See 'Peripheral SpA subgroups' below.)

●Exclusion of conditions that may mimic peripheral SpA (see 'Differential diagnosis' below). This is a very important step in the diagnostic strategy.

●Ongoing monitoring of patients during follow-up for additional features of peripheral SpA or of conditions in the differential diagnosis of peripheral SpA to allow for a more definitive diagnosis.

Patients suspected of having a peripheral SpA based upon the presence of one or more features of the disease should undergo a thorough medical history and physical examination with particular attention to manifestations that are common to the various subgroups of peripheral SpA (see 'Clinical manifestations' above), which distinguish patients in one from another subgroup (see 'Peripheral SpA subgroups' below), and those that would help to identify patients with one of the disorders important in the differential diagnosis. (See 'Differential diagnosis' below.)

It is important to always include assessments of objective signs of inflammation in order to confirm the inflammatory nature of peripheral involvement [3,12]. Clinical examination includes a full joint count, assessment of dactylitis, palpation of entheses, and inspection of the skin and nails for psoriasis. In particular, in the case of entheseal pain, ultrasound or MRI might be necessary to distinguish enthesitis due to peripheral SpA from tender points in fibromyalgia.

Testing for human leukocyte antigen B27 (HLA-B27) may be useful in some patients, depending upon the extent to which additional findings are present. Its presence alone is not diagnostic, and its absence does not exclude the diagnosis. Other laboratory testing, including C-reactive protein (CRP; or alternatively an erythrocyte sedimentation rate [ESR]) should be obtained in patients suspected of peripheral SpA, but both tests are normal in half of the patients, which does not exclude the diagnosis.

Other laboratory testing (complete blood count, renal and liver chemistries) may be useful in the evaluation for the presence of potential comorbidities, especially when further treatment is planned, but are often not required for establishing the diagnosis.

Patients with axial SpA are not included within the diagnostic category of peripheral SpA, even if peripheral manifestations of musculoskeletal involvement are also present [1,2]. However, imaging of the sacroiliac joints may be useful in the diagnosis of peripheral SpA to determine if asymptomatic disease is present that may support the diagnosis of a SpA.

An initial estimate of the likelihood of disease also depends upon whether features suggesting an alternative diagnosis are present, and additional testing may also be obtained depending upon the differential diagnosis generated from the presenting features and other abnormalities that may be identified.

Use of classification criteria — There are two sets of classification criteria for SpA that have been developed by ASAS, one for those presenting with axial involvement and the other for those presenting with predominantly peripheral involvement [1,29]. The classification criteria were developed for use in epidemiologic and clinical research. They are not meant for diagnosis as they lack sufficient sensitivity and specificity to be used as the only diagnostic tool in clinical practice [30]. (See 'Diagnostic strategy' above and "Overview of the clinical manifestations and classification of spondyloarthritis", section on 'Axial SpA'.)

The ASAS criteria emphasize the role of presenting symptoms in the identification of patients with peripheral SpA and the distinction between patients with axial SpA and peripheral SpA. 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 diagnosed by a clinician:

●Arthritis (compatible with SpA, typically asymmetric and/or predominantly of the lower extremities)

●Enthesitis (at any site)

●Dactylitis

In addition to the entry criteria, patients need to have elements from one of two groups of features, termed Group A and Group B. The features in Group A and B do not necessarily have to be present at the time the patient is being seen. A criterion used to satisfy the entry step may not be counted twice. If the patient satisfies the entry criteria, the patient should show at least one of the features of SpA in Group A (below) or at least two other of the features of SpA in Group B (below):

●Group A SpA features:

•Anterior uveitis (present or past, documented by an ophthalmologist)

•Psoriasis (present or past, documented by a clinician)

•Crohn disease or ulcerative colitis (present or past, documented by a clinician)

•Preceding infection (urethritis/cervicitis or diarrhea within one month before onset of arthritis/enthesitis/dactylitis)

•HLA-B27

•Sacroiliitis on imaging (bilateral grade 2 to 4 or unilateral grade 3 to 4 on plain radiography or active sacroiliitis on MRI) (see "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Imaging studies')

●Group B SpA features:

•Arthritis (present or past, documented by a clinician)

•Enthesitis (present or past, documented by a clinician)

•Dactylitis (present or past, documented by a clinician)

•Inflammatory back pain (IBP) in the past (classify using axial SpA criteria if present at the time of evaluation)

•Family history of SpA (first- or second-degree relative with ankylosing spondylitis, psoriasis, acute uveitis, reactive arthritis, or inflammatory bowel disease [IBD])

The ASAS criteria are inclusive of disorders such as psoriatic arthritis (PsA), IBD-related arthritis, and reactive arthritis. (See 'Peripheral SpA subgroups' below.)

Peripheral SpA subgroups — A diagnosis of peripheral SpA can be made in patients with other defined medical conditions characterized in part by peripheral arthritis, dactylitis, and enthesitis; another subgroup of peripheral SpA is composed of patients without an associated illness (see 'Diagnosis and classification' above and 'Use of classification criteria' above). Subgroups of patients with peripheral SpA include:

●Psoriatic arthritis – A subset of patients with PsA can have features characteristic of peripheral SpA (arthritis predominantly of the lower limbs and/or asymmetric arthritis; enthesitis; or dactylitis), although many other PsA patients present with an arthritis not typical for peripheral SpA (eg, polyarthritis predominantly of the hands or axial SpA). The diagnosis of PsA is described in detail separately. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Diagnosis'.)

●Reactive arthritis – Most patients with reactive arthritis have findings consistent with peripheral SpA following a gastrointestinal or urogenital infection. The diagnosis of reactive arthritis is described in detail separately. (See "Reactive arthritis", section on 'Diagnosis'.)

●Arthritis associated with inflammatory bowel disease – Some patients with arthritis associated with IBD have features consistent with peripheral SpA, but axial symptoms are also frequently reported. The diagnosis is described in detail separately. (See "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases" and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Diagnosis'.)

●Peripheral SpA without an associated illness – A subset of patients with peripheral SpA do not have features of one of the well-defined disease subgroups. Patients whose disease manifestations could not be classified as a specific disease entity were previously classified as having undifferentiated SpA (USpA). However, USpA is frequently mistakenly understood to be a mild and ill-defined or early stage of ankylosing spondylitis or PsA, whereas increasing evidence supports the concept that SpA is better seen, with respect to pathophysiology, clinical findings, and treatment, as a single disease with different phenotypes [23]. (See "Pathogenesis of spondyloarthritis".)

The term "undifferentiated SpA" has disappeared with the wider acceptance of the ASAS classification criteria and their underlying assumptions, as most patients with conditions historically described as USpA can now be classified as having either peripheral SpA or non-radiographic axial SpA, depending upon the predominant features of their disease.

DIFFERENTIAL DIAGNOSIS — Several conditions that may also cause peripheral arthritis or heel swelling and sausage-like digits are described here and should be considered in the differential diagnosis of peripheral spondyloarthritis (SpA) and excluded as part of the diagnostic evaluation. Most can be distinguished from peripheral SpA based upon the clinical history and examination, but occasionally additional laboratory testing or imaging are required, depending upon the presenting symptoms and findings. The broader differential diagnoses of polyarticular or monoarticular joint pains are reviewed in detail separately. (See "Evaluation of the adult with polyarticular pain" and "Monoarthritis in adults: Etiology and evaluation" and "Achilles tendinopathy and tendon rupture" and "Plantar fasciitis" and "Non-Achilles ankle tendinopathy".)

The major conditions that should be considered in the differential diagnosis of peripheral SpA include:

●Rheumatoid arthritis – Inflammatory arthritis in peripheral joints characterizes both rheumatoid arthritis (RA) and SpA. Patients with RA typically experience symmetric polyarthritis of the small joints as a major component of their joint involvement, while the arthritis in peripheral SpA is more frequently asymmetric and oligoarticular and often predominantly affects the lower extremities. Other features of peripheral SpA, such as dactylitis and enthesitis, are not seen of RA, and rheumatoid factor or anti-citrullinated peptide antibodies are uncommon in peripheral SpA compared with RA. (See "Clinical manifestations of rheumatoid arthritis" and "Diagnosis and differential diagnosis of rheumatoid arthritis" and "Clinical manifestations and diagnosis of psoriatic arthritis".)

●Osteoarthritis – Both peripheral SpA and osteoarthritis (OA) may be characterized by pain and swelling in the knees. However other features typical of SpA but not OA, such as inflammatory synovial fluid, enthesitis, dactylitis, evidence of sacroiliitis, and elevated C-reactive protein (CRP) levels; or of OA but not SpA, such as joint space narrowing without erosions, help to distinguish these conditions from each other. (See "Clinical manifestations and diagnosis of osteoarthritis".)

●Gout – Both SpA and gout can present as an acute monoarthritis or oligoarthritis predominantly of the lower limbs or with sausage-like digits [31]. The diagnosis of gout can be confirmed by finding monosodium urate crystals on examination of the synovial fluid and the characteristic pattern of acute then remitting crystal arthritis seen in patients with gout. However, SpA and gout can coexist, and SpA associated with psoriasis (psoriatic arthritis [PsA]) can be associated with hyperuricemia. The identification of other features of SpA is important in establishing the diagnosis of SpA in such patients. (See "Clinical manifestations and diagnosis of gout".)

●Achilles tendinopathy, non-Achilles ankle tendinopathy, plantar fasciitis, and sequelae of ankle sprain – All these conditions can cause pain and/or swelling around the ankle and heel, as can peripheral SpA with enthesitis. A history of acute trauma or repetitive mechanical overload or microtrauma is often present in these other conditions and other features of SpA are generally lacking [32]. However, in some patients a thorough evaluation for other features of peripheral SpA and monitoring of the response to therapies and of the clinical status over time are required to distinguish an underlying inflammatory peripheral SpA from injury or overuse as the primary cause of such symptoms and findings. (See "Achilles tendinopathy and tendon rupture" and "Plantar fasciitis" and "Non-Achilles ankle tendinopathy".)

●Dactylitis of sarcoidosis and sickle cell disease – The appearance of sausage digits in sarcoidosis, sickle cell disease, and tuberculosis of the digits can be indistinguishable from those of SpA [33]. However, these conditions can each generally be distinguished from peripheral SpA on history and examination, based upon the major clinical findings that characterize these respective disorders, and by plain radiography, as characteristic changes are often seen in the bone in these conditions, unlike SpA-related dactylitis [33]. (See 'Imaging' above and "Clinical manifestations and diagnosis of sarcoidosis" and "Overview of extrapulmonary manifestations of sarcoidosis" and "Sarcoid myopathy" and "Sarcoid arthropathy" and "Overview of the clinical manifestations of sickle cell disease" and "Acute and chronic bone complications of sickle cell disease".)

●Lyme arthritis – Both Lyme arthritis and SpA can present with oligoarthritis, often of the knee or other large joints, and patients often do not remember the preceding tick bite and/or the cutaneous eruption of erythema migrans. Arthritis presenting in a geographic location in which Lyme disease is endemic should raise suspicion for this diagnosis, which can generally be established based upon serologic studies for Lyme borreliosis. Additionally, other findings typical of peripheral SpA are usually absent in patients with Lyme disease. (See "Musculoskeletal manifestations of Lyme disease" and "Diagnosis of Lyme disease".)

●Fibromyalgia – The tender points of fibromyalgia might be mistaken for enthesitis. However, true inflammatory arthritis and other signs of SpA are generally absent in these patients unless overlapping diagnoses are present. (See "Clinical manifestations and diagnosis of fibromyalgia in adults", section on 'Physical findings'.)

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)" and "Patient education: Psoriatic arthritis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical manifestations – Peripheral spondyloarthritis (SpA) refers to a group of diseases that share certain clinical features; all patients with peripheral SpA have one or more of the following: peripheral arthritis, enthesitis, and/or dactylitis. In addition, patients with peripheral SpA may also have one or more of the following: psoriasis, inflammatory bowel disease (IBD), anterior uveitis, an association with prior or ongoing infection, sacroiliitis by imaging, a past history of axial pain, a family history of SpA, and/or the human leukocyte antigen B27 (HLA-B27). (See 'Clinical manifestations' above and 'Laboratory findings' above and 'Imaging' above.)

●Diagnosis – The diagnosis of peripheral SpA is made in a patient with one of the characteristic musculoskeletal findings (peripheral arthritis, enthesitis, or dactylitis), usually with one or more other characteristically associated findings listed above, and, very importantly, after exclusion of conditions that may strongly resemble peripheral SpA.

Patients should be monitored during follow-up for additional elements suggesting SpA or features of a condition in the differential diagnosis. The Assessment of SpondyloArthritis International Society (ASAS) classification criteria for SpA provide helpful guidance but should not be used as a diagnostic tool. Diagnosis cannot be made by a checklist of items. (See 'Diagnosis and classification' above.)

●Differential diagnosis – The differential diagnosis of peripheral SpA includes rheumatoid arthritis (RA), osteoarthritis (OA), gout, Achilles tendinopathy, non-Achilles ankle tendinopathy, plantar fasciitis, ankle sprain and its sequelae, dactylitis of sarcoidosis and sickle cell disease, Lyme disease, and fibromyalgia. (See 'Differential diagnosis' above.)

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