Juvenile Spondyloarthropathy

Key Points:

  • Juvenile spondyloarthropathy is an HLA-B27 associated pediatric rheumatic disease typically manifested by enthesitis, lower extremity arthritis, and eventual spine and SI joint involvement
  • Extra-articular involvement includes anterior uveitis and gastrointestinal inflammation
  • Anti-TNF alpha therapy can be an effective disease modifying treatment
  • Delay in diagnosis and treatment can lead to progressive loss of spinal motion

Description:

In a broad sense, juvenile spondyloarthropathy can be thought of as an HLA-B27 associated pediatric rheumatic disease typically manifested by enthesitis and lower extremity arthritis with, in most cases, eventual involvement of the spine and sacroiliac joints. As with juvenile idiopathic arthritis, symptom onset typically occurs before age 16 (Scofield, 2012). Most forms of juvenile spondyloarthropathy have an equivalent disease with adult onset. The one exception is ankylosing spondylitis in which the usual diagnostic criteria do not have a lower age limit (Ehrenfeld, 2012). 

The most common forms of juvenile spondyloarthropathy include enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Juvenile spondyloarthropathy can also be classified more broadly as a disease with primarily axial or appendicular skeleton involvement (Hofer, 2002).  While the presence of HLA-B27 is variable depending on the population studied, rheumatoid factor is absent in juvenile spondyloarthropathies. 

Epidemiology:

Due to the difficulty in identifying this disease process with certainty as well as differing diagnostic criteria amongst rheumatologic organizations, establishing disease prevalence is challenging. There are larger epidemiological studies that give an idea of the relative frequency of these diseases in the pediatric population. A study of nearly 1,800 patients with juvenile arthritis found the prevalence of enthesitis-related arthritis to be 7.4%, psoriatic arthritis to be 6.3%, and undifferentiated arthritis to be 19.7% (Scofield, 2012). And, in a study of 2,500 adults with ankylosing spondylitis, 11% had an onset of symptoms between ages 5 and 16 years (Scofield, 2012).

Clinical Findings:

Juvenile spondyloarthropathy is characterized by periods of mild to moderate inflammatory flares between times of disease quiescence. Peripheral or hip arthritis is the most common presenting features in children. In adults, inflammatory back pain is the most common presenting feature (Ehrenfeld, 2012). Lower extremity involvement is typically confined to the large joints and is asymmetric. Involvement of the hip has a high association with eventual total hip arthroplasty. Hip arthritis has also been shown to be an independent risk factor for the development of sacroiliitis (Stoll, 2010). In terms of sacroiliitis, the lack of inflammatory back pain at presentation does not preclude involvement of the sacroiliac joints. Up to 20% of children with juvenile spondyloarthropathy may have a “silent” sacroiliitis detectable only on advanced imaging studies (Stoll, 2010).  

The most common extra-articular manifestation of juvenile spondyloarthropathy is acute anterior uveitis. This unilateral ocular inflammation occurs most frequently in HLA-B27 positive individuals and presents with redness, pain, and photophobia (Ramanathan, 2013). Gastrointestinal inflammation may also be present in up to 60% of patients with juvenile spondyloarthropathy (Ramanathan, 2013).

As with juvenile idiopathic arthritis, strict diagnostic criteria established by the International League of Associations for Rheumatology (ILAR) exist for the subtypes of juvenile spondyloarthropathy. The enthesitis-related arthritis diagnostic criteria mandate:
  1.  the presence of enthesitis
  2. and/or arthritis prior to the age of 16 years.
Furthermore, two (or more) of the following must be present: 
  1. sacroiliac tenderness
  2. inflammatory back pain
  3. presence of HLA-B27
  4. history of anterior uveitis or acute uveitis
  5. or a family history of spondyloarthropathy
   (Petty, 2004).
   
Enthesitis is more likely to be a presenting symptom in a child than an adult with the insertions of the patellar and Achilles tendons as the most commonly symptomatic sites of disease (Ramanathan, 2013).

Psoriatic arthritis is defined by:
* the presence of arthritis prior to the age of 16
* as well as two (or more) of the following:
  1.  psoriasis in a first-degree relative
  2.  dactylitis
  3.  nail pitting
  4.  onycholysis (Petty, 2004). 

Children with psoriatic arthritis only rarely have skin findings and may not develop psoriatic skin changes until years after symptom onset (Ramanathan, 2013). 

Symptomatic children who do not fit into either of the two previously discussed categories or one of the remaining four categories defined by the ILAR are classified as having undifferentiated spondyloarthropathy. There is typically a 3:1 female to male preponderance of undifferentiated spondyloarthropathy. Extra-articular manifestations are less common in the undifferentiated form of the disease (Ramanathan, 2013). 

Imaging Studies:

Imaging studies can play an important role in the early diagnosis of a spondyloarthropathy. The initial imaging modality of choice is plain radiography of the pelvis to look for involvement of the sacroiliac joints. Early radiographic changes include loss of the cortical white line along the iliac aspect of the sacroiliac joint followed by erosions and pseudo-widening of the articular surface (Mattar, 2013). In an attempt to heal the joint erosions, new bone is deposited. This newly deposited bone can lead to sclerotic changes and eventual ankylosis of the sacroiliac joint (Stoll, 2010). 

In an afflicted adolescent or young adult, radiographs of the spine can show syndesmophytes: ossifications of the deep fibers of the anterior longitudinal ligament connecting two vertebral bodies across a disc space (Mattar, 2013). In ankylosing spondylitis, syndesmophytes will begin in the lumbar spine and be symmetric and confluent producing the characteristic “bamboo spine.” In the remaining spondyloarthropathies, the syndesmophytes may be asymmetric and show a skip distribution (Gomez, 1997).  Involvement of the cervical facet joints, particularly in psoriatic arthritis, can predispose an individual to atlantoaxial instability due to erosion of the facets. 

Magnetic resonance imaging, in both adults and children, has demonstrated earlier detection than plain radiography of inflammatory changes, such as bone marrow edema within the sacroiliac joints (Mattar, 2013). More recent classification schemes now integrate the presence of MRI-detectable changes into the diagnostic criteria for juvenile spondyloarthropathy (Ramanathan, 2013). 

Finally, ultrasound can be used to aid in the diagnosis of enthesitis. Typical ultrasound findings of enthesitis include tendon thickening, calcification, or hypoechogenicity and bony erosions at the tendon insertion sites (Mattar, 2013).

Etiology:

The exact etiology and pathogenesis of juvenile spondyloarthropathy remains unclear. Strong evidence supports the development of the disease in genetically predisposed individuals exposed to environmental triggers (Ramanathan, 2013). Regardless of the etiology, the pathogenic result is the release of pro-inflammatory cytokines such as TNF-alpha. Recent research has indicated genetic mutations in the IL-23/IL-17 axis as pathogenic for juvenile spondyloarthropathy (Ramanathan, 2013). This axis may be a target of future drug therapy. Finally, the genetic heritability of juvenile spondyloarthropathy is not completely understood. HLA-B27 accounts for approximately 25% of the known heritability with newly discovered gene mutations accounting for 2.1% of inherited cases (Ramanathan, 2013).

Treatment:

As with juvenile idiopathic arthritis, effective treatment of juvenile spondyloarthropathy requires careful attention to the both the medical, physical, and psychosocial aspects of the disease process. Medical therapy should be combined with child and parent education and physical and occupational therapy. 

The first line therapy for juvenile spondyloarthropathy is with NSAIDs in both axial and peripheral disease. A positive response to the anti-inflammatory effects of these medications will lead many rheumatologists to pursue further treatment with disease-modifying antirheumatic drugs (DMARDs) (De La Mata, 2011). Traditional DMARD agents, such as methotrexate and sulfasalazine, have only limited applicability in disease affecting primarily the axial skeleton. The mainstay of current medical treatment is anti-TNF therapy with medications like etanercept, infliximab, and adalimumab (De La Mata, 2011). These medications have been shown to be both safe and efficacious in a pediatric population. Successful treatment with anti-TNF therapy has been shown to limit disease flares and, in some cases, induce disease remission. Importantly, children with early axial involvement have the greatest risk for progression to ankylosing spondylitis and are most likely to benefit from early intervention (Gomez, 1997; Ramanathan, 2013).

Complications:

The main difficulty in adequately treating juvenile spondyloarthropathy is a delay in accurate diagnosis. Untreated, the disease can lead to progressive involvement of the axial skeleton, thereby limiting spinal motion. Atlantoaxial instability can develop due to facet joint erosions in the cervical spine. Involvement of the hip joint at a young age greatly increases the risk for end stage hip arthritis and may necessitate total hip arthroplasty (Ramanathan, 2013).

The main complications associated with anti-TNF therapy are infectious. Infections with tuberculosis and histoplasmosis have been documented in endemic areas such as the central United States. Other complications associated with anti-TNF therapy include: autoimmune disease such as lupus or multiple sclerosis, inflammatory bowel disease and Whipple’s disease (De La Mata, 2011). 

References:

  1. De La Mata, J., et. al. Current evidence of the management of undifferentiated spondyloarthritis: a systematic literature review. Semin Arthritis Rheum. 2011;40:421-29.
  2. Ehrenfeld, M. Spondyloarthropathies. Best Prac Res Clin Rheumatol. 2012;26:135-45.
  3. Gomez, KS., et. al. Juvenile onset ankylosing spondylitis – more girls than we thought? J Rheumatol. 1997;24:735-7.
  4. Hofer, M. and Southwood, TR. Classification of childhood arthritis. Best Prac Res Clin Rheumatol. 2002;16:379-96.
  5. Mattar, M., Salonen, D., and Inman, RD. Imaging of spondyloarthropathies. Rheum Dis clin N Am. 2013;39:645-67.
  6. Petty, RE., et. al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision. J Rheumatol. 2004;31(2):390-92.
  7. Ramanathan, A., Srinivasalu, H., and Colbert, RA. Update on juvenile spondylarthritis. Rheum Dis Clin N Am. 2013;39:767-88.
  8. Scofield, RH., and Sestak, AL. Juvenile spondylarthropathies. Curr Rehumatol Rep. 2012;14:395-401.
  9. Stoll, ML., et. al. Spondyloarthritis in a pediatric population: risk factors for sacroiliitis. J Rhuematol. 2010;37:2402-8.

Top Contributors:

Brian E. Kaufman, MD
Karen Bovid, MD