Spondyloarthritis in children

INTRODUCTION — In children, the spondyloarthropathies are a group of rheumatic diseases characterized by enthesitis and arthritis, most frequently involving the lower extremities initially and, in a variable proportion of cases, the sacroiliac and spinal joints later in the disease course [1].

The clinical aspects of childhood spondyloarthritis, particularly enthesitis related arthritis (ERA) and juvenile ankylosing spondylitis (JAS), are discussed here. Other categories of juvenile idiopathic arthritis (JIA) are discussed separately. (See "Classification of juvenile idiopathic arthritis" and "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis" and "Systemic juvenile idiopathic arthritis: Course, prognosis, and complications" and "Systemic juvenile idiopathic arthritis: Treatment" and "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications" and "Polyarticular juvenile idiopathic arthritis: Treatment" and "Oligoarticular juvenile idiopathic arthritis" and "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis" and "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)

Detailed discussions of the corresponding disorders in the adult, including psoriatic arthritis, reactive arthritis, and ankylosing spondylitis (AS), are presented separately. Arthritis associated with inflammatory bowel disease (IBD) and other gastrointestinal diseases is also discussed in detail separately. (See "Overview of the clinical manifestations and classification of spondyloarthritis" and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults" and "Clinical manifestations and diagnosis of psoriatic arthritis" and "Reactive arthritis" and "Clinical manifestations 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".)

TERMINOLOGY AND CLASSIFICATION — The terms "spondyloarthropathy" and "spondyloarthritis" are used to refer to a group of related seronegative (ie, rheumatoid factor-negative) inflammatory diseases generally characterized by involvement of the spine (sacroiliitis and spondylitis), large joints (most frequently lower limb asymmetric oligoarthritis), and entheses (enthesitis or enthesopathy; inflammation of the sites where tendons, ligaments, or joint capsule insert into the bone). Spondyloarthritides are strongly associated with the presence of human leukocyte antigen (HLA) B27. The term "spondyloarthritis" primarily includes children meeting criteria for the juvenile idiopathic arthritis (JIA) categories of enthesitis related arthritis (ERA) and psoriatic arthritis [2] but also encompasses children with:

●Juvenile ankylosing spondylitis (JAS)

●Reactive arthritis (see "Reactive arthritis")

●Inflammatory bowel disease (IBD)-associated arthritis (see "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases")

ERA and JAS identify similar groups of patients, with the criteria for JAS requiring radiologic evidence of bilateral sacroiliitis. The classification of JIA is reviewed in greater detail separately. (See "Classification of juvenile idiopathic arthritis".)

EPIDEMIOLOGY — Enthesitis related arthritis (ERA) accounts for approximately 10 to 19 percent of children classified with juvenile idiopathic arthritis (JIA) [3-6]. The mean age at diagnosis for children with ERA is approximately 12 years [6]. ERA is more common in males, who make up approximately 60 to 80 percent of cases [6,7]. It is estimated that approximately 8 to 11 percent of adults with ankylosing spondylitis (AS) had onset of their disease in childhood [8]. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults" and "Reactive arthritis".)

The epidemiology of all forms of JIA and specifically psoriatic JIA, reactive arthritis, and inflammatory bowel disease (IBD) associated arthritis are reviewed separately. (See "Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis" and "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Epidemiology' 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'.)

PATHOGENESIS — The underlying etiology of spondyloarthritis is unknown. There is a strong association with human leukocyte antigen (HLA) B27, and an infectious etiology has been suggested but not proven. In addition, alterations in gut microbiota may be a contributing factor [9]. Various animal models, including an HLA-B27 transgenic rat that may develop psoriasis, axial and peripheral arthritis, and colitis, are helping to shed light on this disorder [10]. The pathogenesis of spondyloarthritis, particularly ankylosing spondylitis (AS) in adults, is discussed separately. (See "Pathogenesis of spondyloarthritis".)

GENETICS — There is frequently a familial pattern to the spondyloarthropathies and related disorders. Patients with positive human leukocyte antigen (HLA) B27 and no family history of ankylosing spondylitis (AS) have a 1 to 3 percent lifetime risk of AS, whereas AS is 10 to 20 times more common in relatives of patients with AS, and the frequency is even higher in siblings of patients with AS [8,11]. (See "Pathogenesis of spondyloarthritis", section on 'Genetic factors'.)

CLINICAL PRESENTATION — The disease onset is typically insidious, although it may become evident following a febrile illness or musculoskeletal trauma in some cases [12]. Examples of presenting features include a swollen ankle, a sausage digit, or what appears to be recurrent tendonitis. Morning stiffness is common, especially in the affected joint or lower back, and is responsive to heat (such as a long morning shower) or nonsteroidal antiinflammatory drugs (NSAIDs).

Children with spondyloarthropathies initially may be misdiagnosed with recurrent sprains or strains since the onset of symptoms is often early in the second decade and frequently coincides with a period of increased physical activity. In addition, children may lack axial and/or extraarticular manifestations on presentation, with some of the features associated with the spondyloarthropathies, including inflammatory bowel disease (IBD), psoriasis, and ankylosing spondylitis (AS), only becoming clinically evident after the original presentation with enthesitis related arthritis (ERA) [13]. Over time, these children may develop definite sacroiliitis [13,14]. (See "Pathogenesis of spondyloarthritis" and 'Laboratory testing' below and "Classification of juvenile idiopathic arthritis".)

Articular manifestations — At disease onset, the arthritis is usually oligoarticular (involving ≤5 joints), asymmetric, and primarily involves the joints of the lower extremities. Enthesitis (inflammation of the sites where tendons, ligaments, or joint capsule insert into the bone) is present in approximately 66 to 82 percent of children with ERA or juvenile spondyloarthritis at disease onset [7]. The enthesitis also most commonly occurs in the lower extremities, specifically at the inferior pole of the patella, the plantar fascia insertion at the calcaneus, and insertion of the Achilles tendon at the calcaneus.

Approximately 10 to 24 percent of children have axial involvement (spondylitis, sacroiliitis) at disease onset, which most frequently presents as spinal or sacroiliac joint pain and stiffness [7,8,15]. Inflammatory back pain typically is insidious in onset, mostly worse at night, improves with exercise, and does not improve with rest. Some patients with sacroiliitis are asymptomatic [16,17]. Others may present with hip or alternating buttock pain rather than back pain. Tarsitis (inflammation of the joints of the midfoot) presents as pain with movement of the foot, such as with walking or running. It is seen in approximately one-third of children with spondyloarthritis at disease onset and is more common in children with spondyloarthritis than other categories of juvenile idiopathic arthritis (JIA) [18].

Dactylitis is seen in some patients with reactive arthritis and psoriatic JIA. (See "Reactive arthritis", section on 'Musculoskeletal signs and symptoms' and "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Dactylitis' and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults", section on 'Musculoskeletal features'.)

Extraarticular manifestations — A variety of extraarticular manifestations are associated with the spondyloarthropathies and may occur prior to or following the onset of musculoskeletal symptoms. The most common extraarticular manifestations are:

●Anterior uveitis, particularly acute (symptomatic) anterior inflammation characterized by eye pain, photophobia, or conjunctival injection

●Diverse skin manifestations (eg, erythema nodosum, pyoderma gangrenosum, psoriasis)

●Recurrent gastrointestinal complaints (eg, abdominal pain, diarrhea)

These extraarticular manifestations may occur as part of an undifferentiated spondyloarthritis. However, in other patients, the spondyloarthritis may be associated with another systemic disease, such IBD, psoriasis, or infection, in the case of reactive arthritis. Signs and symptoms suggestive of these disorders include:

●Inflammatory bowel disease – Recurrent or persistent aphthous ulcers, uveitis, poor weight gain, decreased longitudinal growth, and persistent anemia. Studies in adults with undifferentiated spondyloarthritis or AS suggest that IBD may be the underlying cause in selected patients, and it has been shown that many children with spondyloarthritis also have subclinical gastrointestinal disease [19,20]. (See "Growth failure and pubertal delay in children with inflammatory bowel disease" and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Clinical manifestations'.)

●Psoriatic arthritis – Psoriatic rash and nail pits. (See "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

●Reactive arthritis – Genitourinary symptoms; sometimes oral ulcers or psoriatic rash. (See "Reactive arthritis", section on 'Clinical manifestations'.)

EVALUATION

Physical examination — Spondyloarthropathies may be difficult to identify early due to subtle signs and symptoms. Keys to proper recognition include a careful history and a complete physical examination, with a particular focus on the musculoskeletal examination, to detect one or more of the following exam findings:

●Oligoarthritis – Usually asymmetric and primarily involves the large joints of the lower extremities. Findings include swelling, tenderness, increased warmth, erythema, and limited range of motion.

●Enthesitis – Most commonly at the patella and calcaneus. The primary finding is tenderness with palpation of the tendon and ligament insertion points. Other examples are Achilles pain and swelling if there is a retrocalcaneal bursitis or pain with walking due to a plantar fasciitis.

●Tarsitis – Pain or tenderness with movement of the midfoot that may be associated with arthritis of the first metatarsophalangeal joint.

●Axial arthritis (spondylitis, sacroiliitis) – Inflammatory back pain may be accompanied by reduced anterior spinal flexion.

The modified Schober test may be used to evaluate for lumbosacral spine involvement, particularly in patients who do not yet have radiographic evidence of sacroiliitis (picture 1). To perform the Schober test, the patient stands erect, and the position of the fifth lumbar spinous process is marked by a pen. Another mark is made 10 cm above it in the midline, and a third mark is made 5 cm below. The patient then bends forward maximally without bending the knees. In normal individuals, the distance between the top and bottom points should increase by 6 cm or more.

The sacroiliac (SI) joints can be examined by direct palpation, compression of the pelvis, and/or Patrick’s maneuver (picture 2), although these tests and the modified Schober have variable sensitivity and specificity.

Laboratory testing — Laboratory work-up for a child with suspected spondyloarthritis is similar to that of children with juvenile idiopathic arthritis (JIA) in general and may include complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), human leukocyte antigen (HLA) B27, and antinuclear antibody (ANA). Additional labs may be indicated based upon other associated symptoms or clinical findings. Many children with a spondyloarthritis have normal laboratory findings even in the setting of active disease, although ESR and other laboratory markers of inflammation, including CRP and platelets, may be elevated in some cases. Anemia of chronic disease is sometimes present. More significant anemia and/or elevations in acute-phase reactants may be suggestive of associated inflammatory bowel disease (IBD). ANA positivity is more likely in psoriatic arthritis, particularly in patients who have a pattern more typical for an oligo- or polyarticular arthritis, but is uncommon other forms of spondyloarthritis. Rheumatoid factor is usually absent. (See "Classification of juvenile idiopathic arthritis".)

HLA-B27 is present in 60 percent of children with spondyloarthritis and 90 percent of children with juvenile ankylosing spondylitis (JAS) [10,12,21]. Although HLA-B27 occurs with an increased frequency in these children, the presence or absence of the allele cannot be relied upon to establish or refute the diagnosis. The rates of HLA-B27 vary by ethnicity. (See "Pathogenesis of spondyloarthritis".)

Imaging — Radiographic findings are frequently normal at baseline. As the disease progresses, radiographic changes may be seen in the in the SI joints, vertebrae, pelvis, and entheseal insertion sites. Early in the disease course, SI changes are more frequently seen at the iliac side of the joint and the inferior, synovial aspect of the joint. Radiographic changes in the peripheral joints are similar in appearance to those associated with other categories of JIA.

Magnetic resonance imaging (MRI) is significantly more sensitive in detecting early sacroiliitis than plain radiographs, and the earliest findings may include subchondral edema and periarticular bone marrow edema [22-26]. MRI without gadolinium may be sufficient to identify sacroiliitis in children [26]. Although the presence of bilateral inflammatory sacroiliitis on MRI strongly supports a diagnosis of a spondyloarthritis, approximately half of cases of inflammatory sacroiliitis are unilateral. Infectious and oncologic processes may also present in the SI joints, usually with unilateral involvement [27,28].

Whole-body MRI has been preliminarily assessed as a means of diagnosing enthesitis related arthritis (ERA) and monitoring disease activity [28]. However, additional data in children are required before this imaging study is incorporated into routine clinical care.

Ultrasound (US) with power Doppler may have a role in the diagnosis and monitoring of enthesitis in these patients. However, additional data regarding the US appearance of normal pediatric entheses and the development of a standard scoring system for enthesitis are needed to support the incorporation of entheseal US into routine practice [29].

DIAGNOSIS — Enthesitis related arthritis (ERA) is one of the categories of juvenile idiopathic arthritis (JIA) defined by the International League of Associations for Rheumatology (ILAR) [30-32].

ERA in children aged <16 years is defined as:

●Arthritis (persisting ≥6 weeks) and enthesitis (no specific duration required)

OR

●Arthritis or enthesitis, as above, with two of the following additional criteria present:

•Sacroiliac (SI) tenderness or inflammatory lumbosacral pain

•Positive human leukocyte antigen HLA-B27

•Onset of arthritis in a male >6 years of age

•Acute (symptomatic) anterior uveitis

•First-degree relative with ERA, sacroiliitis associated with inflammatory bowel disease (IBD), reactive arthritis, or acute anterior uveitis

Juvenile ankylosing spondylitis (JAS) is defined similarly, with one additional requirement of radiologic evidence of bilateral SI inflammation [8]. (See 'Imaging' above.)

The initial assessment also should include evaluation for systemic diseases that may manifest as spondyloarthritis. These diseases, which are discussed in detail separately, include:

●IBD (see "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases", section on 'Diagnosis')

●Psoriatic arthritis (see "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnosis')

●Reactive arthritis (see "Reactive arthritis", section on 'Diagnosis')

As noted above, the musculoskeletal manifestations of these disorders may precede other evidence of the underlying condition by months to years. (See 'Clinical presentation' above.)

DIFFERENTIAL DIAGNOSIS — Spondyloarthritis in general should be differentiated from musculoskeletal injuries or developmental abnormalities. Back pain and stiffness are rare in young children and uncommon in adolescents and usually require additional evaluation. Careful evaluation to eliminate orthopedic, neoplastic, and infectious etiologies is important. (See 'Clinical presentation' above and "Back pain in children and adolescents: Causes" and "Back pain in children and adolescents: Evaluation".)

Mechanical, developmental, and orthopedic disorders other than spondyloarthritis may cause hip pain in children. These include slipped capital femoral epiphysis, Legg-Calve-Perthes disease, and osteoid osteomas. Clinicians can typically distinguish these conditions from spondyloarthritis based upon the age of the patient and a complete history and physical examination. (See "Evaluation and management of slipped capital femoral epiphysis (SCFE)" and "Nonmalignant bone lesions in children and adolescents", section on 'Osteoid osteoma' and "Approach to hip pain in childhood", section on 'Common causes of hip pain in children'.)

Enthesitis may occur in isolation as a result of mechanical issues and overuse. Sever disease (calcaneal apophysitis), Osgood-Schlatter disease (apophysitis of the tibia tubercle), and Sindig-Larsen and Johansson syndrome (tendonitis involving the lower pole of the patella) may have similar physical exam findings to enthesitis at these sites and should also be considered in patients who have findings isolated to these sites. (See "Overview of the causes of limp in children" and "Evaluation of limp in children" and "Approach to hip pain in childhood" and "Forefoot and midfoot pain in the active child or skeletally immature adolescent: Overview of causes" and "Heel pain in the active child or skeletally immature adolescent: Overview of causes", section on 'Calcaneal apophysitis (Sever disease)' and "Osgood-Schlatter disease (tibial tuberosity avulsion)" and "Approach to chronic knee pain or injury in children or skeletally immature adolescents", section on 'Sinding-Larsen-Johansson disease (patellar apophysitis)'.)

COURSE AND PROGNOSIS — Enthesitis related arthritis (ERA) is a heterogeneous condition, and its course is difficult to predict. However, children with ERA have greater pain, stiffness, and reduced function [33,34]; more refractory disease; are less likely to achieve inactive disease within the first year after initiation of treatment [35]; and have lower rates of remission overall than other categories of juvenile idiopathic arthritis (JIA) [36]. Patients can develop joint damage. It is not yet known how earlier diagnosis and the early use of tumor necrosis factor (TNF) alpha inhibitors may effect these outcomes.

A number of variables are associated with poorer outcomes. The presence of human leukocyte antigen (HLA) B27 is associated with refractory disease, older age at disease onset, sacroiliitis, tenosynovitis, an increased number of active joints within the first three years after disease onset, involvement of small joints of the lower extremities in boys, and overall unfavorable outcome [37]. Additional predictors of refractory disease include older age at disease onset, hip arthritis, and tarsitis [10,16,36]. Other predictors of an unfavorable outcome include family history of related diseases, patient sex (female sex and poor long-term physical health status, male sex and reduced anterior flexion of the spine), a persistently elevated erythrocyte sedimentation rate (ESR), early hip or ankle arthritis, and high numbers of affected joints [33,38]. Specific risk factors for development of sacroiliitis, in addition to the presence of HLA-B27, include higher numbers of active joints and sites of enthesitis at disease onset, hip arthritis, and elevated ESR [33,39,40].

TREATMENT — The goals for the treatment of spondyloarthritis in children are similar to that of other categories of juvenile idiopathic arthritis (JIA) and include preventing joint damage, controlling symptoms, and preserving functional ability. The approach to treatment for enthesitis related arthritis (ERA) and juvenile ankylosing spondylitis (JAS) is discussed here. The approaches for other forms of spondyloarthritis are discussed separately. (See "Treatment of arthritis associated with inflammatory bowel disease", section on 'Treatment approach' and "Reactive arthritis", section on 'Treatment' and "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)

Pain relief — Nonsteroidal antiinflammatory drugs (NSAIDs) are used to treat pain, stiffness, and enthesitis in children with spondyloarthropathies [8,41]. Several NSAIDs have been approved for use in children with JIA, including naproxen, meloxicam, celecoxib, and ibuprofen. Typical regimens are:

●Ibuprofen 30 to 40 mg/kg/day in three to four divided oral doses (maximum dose 2400 mg/day)

●Naproxen 15 to 20 mg/kg/day orally in two divided doses (maximum 500 mg twice daily)

Many other NSAIDs are routinely used by pediatric rheumatologists but have not been specifically approved for use in children. These include piroxicam and indomethacin.

NSAIDs are continued until symptoms improve, and then they are tapered as tolerated.

Concerns regarding potential adverse effects exist for all NSAIDs and are discussed in detail separately. (See "Nonselective NSAIDs: Overview of adverse effects" and "NSAIDs: Adverse cardiovascular effects" and "Overview of COX-2 selective NSAIDs", section on 'Toxicities and possible toxicities'.)

Peripheral arthritis — For patients with peripheral joint disease who have failed NSAIDs or who are nonambulatory on presentation, intraarticular injection of glucocorticoids is the most frequently used therapy. They are a particularly good option when disease is oligoarticular (≤5 joints affected) [8,41]. Triamcinolone hexacetonide is the preferred formulation, but is not currently available due to lack of supply; an alternative is triamcinolone acetonide. Intraarticular glucocorticoids are discussed in greater detail separately. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Initial therapy' and "Joint aspiration or injection in children: Indications, technique, and complications" and "Intraarticular and soft tissue injections: What agent(s) to inject and how frequently?".)

For patients with more diffuse, polyarticular disease or oligoarticular disease refractory to NSAIDs and intraarticular glucocorticoids, options include oral glucocorticoids or disease-modifying antirheumatic drugs (DMARDs) [8,41]. Given the well-established short- and long-term toxicities associated with oral glucocorticoids, they are not considered appropriate as long-term monotherapy for these patients. Of the DMARDs, sulfasalazine has been shown to have some benefit for children with ERA who have primarily peripheral arthritis [8,42]. Methotrexate is commonly used as first-line therapy for children with other categories of JIA and has utility for peripheral arthritis in children with ERA. However, it has not been shown to be effective for children with axial disease [43,44]. A biologic DMARD, specifically a tumor necrosis factor (TNF) inhibitor, is usually added if a patient failed to improve after intraarticular therapies or a trial of a conventional nonbiologic DMARD therapy. These therapies are discussed in greater detail separately. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Escalation of therapy' and "Polyarticular juvenile idiopathic arthritis: Treatment", section on 'Initial management'.)

Axial arthritis — For patients with ERA and axial disease, first-line therapy is NSAIDs. For those who fail NSAIDs, TNF-alpha inhibitors, including etanercept, adalimumab, and infliximab, are recommended for arthritis (both peripheral and axial) and enthesitis in children with ERA [41,45-49] given the known poor response of axial disease to conventional DMARDs. Secukinumab (anti-interleukin [IL] 17A), was approved for active ERA in children ≥4 years of age based upon adult safety and efficacy data and pediatric safety data [50]. It is an option for patients who are resistant to TNF inhibitors, particularly in those with psoriasis and arthritis. Additional biologics, including ustekinumab (anti-IL-12/23), have shown promise in adult ankylosing spondylitis (AS) and are under evaluation in children. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults".)

Physical therapy — Physical therapy to improve mobility and decrease stiffness is important in this type of arthritis, particularly if the back is involved.

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" and "Society guideline links: Juvenile idiopathic arthritis".)

SUMMARY

●The terms "spondyloarthropathy" and "spondyloarthritis" are used to refer to a group of related seronegative (ie, rheumatoid factor-negative) inflammatory diseases characterized by involvement of the spine (sacroiliitis and spondylitis), large joints (asymmetric oligoarthritis, especially of the lower extremities), and entheses (enthesitis or enthesopathy, inflammation of the sites where tendons, ligaments, or joint capsule insert into the bone). Diseases that can fall under this category in children include undifferentiated spondyloarthritis, enthesitis related arthritis (ERA), ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, and inflammatory bowel disease (IBD)-associated arthritis. (See 'Terminology and classification' above.)

●ERA is a category of juvenile idiopathic arthritis (JIA) that includes children with arthritis and enthesis or arthritis and other features associated with spondyloarthritis. It excludes the reactive arthropathies, psoriatic JIA, and the arthropathy associated with IBD. (See 'Terminology and classification' above.)

●The onset of the disease is often gradual but may be first recognized following a febrile illness or musculoskeletal trauma. The arthritis is usually oligoarticular, asymmetric, and primarily involves the large joints of the lower extremities. The knee, ankle, and mid-foot are the joints most frequently involved at presentation. Common associated features include painful tendon or ligament insertions (enthesitis), inflammatory back or sacroiliac (SI) joint pain, morning stiffness, and limited spinal mobility. (See 'Articular manifestations' above.)

●Extraarticular findings include anterior uveitis, diverse skin manifestations, and recurrent gastrointestinal complaints. These may be associated with undifferentiated spondyloarthritis or suggest an alternative diagnosis, including a related systemic disease (IBD, psoriatic arthritis, or reactive arthritis), or mechanical, developmental, and orthopedic disorders other than spondyloarthritis. (See 'Extraarticular manifestations' above and 'Differential diagnosis' above.)

●Human leukocyte antigen (HLA) B27 is associated with ERA and is increased in frequency in all of the spondyloarthropathies. (See 'Laboratory testing' above and 'Course and prognosis' above.)

●The treatment of spondyloarthritis is aimed at reducing symptoms, controlling inflammation, and preventing disability. The appropriate treatment depends upon which manifestations are present, particularly whether there is axial disease and whether the spondyloarthritis is a manifestation of an associated systemic disease (ie, psoriatic JIA, reactive arthritis, IBD-associated arthritis). (See 'Treatment' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas JA Lehman, MD and Sarah Ringold, MD, MS, who contributed to earlier versions of this topic review.