Juvenile Spondyloarthritis: Classification and Treatment Considerations

Sleeping girl with inflammatory arthritis
Sleeping girl with inflammatory arthritis
Juvenile spondyloarthritis is a distinct form of childhood arthritis because of the male predominance, later age of onset, and involvement of the entheses and axial skeleton.

Juvenile spondyloarthritis (SpA) is a distinct form of childhood arthritis that is closely associated with the presence of human leucocyte antigen (HLA)-B27.1 In certain parts of the world, SpA represents up to one-third of juvenile idiopathic arthritis (JIA) cases. In North America, cohort studies of people with JIA suggest a prevalence of 10% to 11% for enthesitis-related arthritis, 6% to 11% for psoriatic arthritis (PsA), and 1% to 2% for undifferentiated JIA.1 Unlike other forms of JIA, juvenile SpA predominantly affects male patients. Onset may occur in children as young as 5 years, but typically, juvenile SpA presents in early adolescence.

Although age of onset influences certain clinical features and outcomes, the classification system2 for JIA developed by the International League of Associations for Rheumatology has several limitations pertaining to SpA, according to a review article published in August 2018 in Pediatric Clinics of North America.1 For example, SpA is not recognized as a distinct entity, and most childhood SpA is classified as enthesitis-related arthritis, and other cases are classified as PsA and undifferentiated arthritis. The authors further noted that the criteria do not specifically recognize axial disease or conditions such as inflammatory bowel disease (IBD)-related arthritis, reactive arthritis, and juvenile ankylosing spondylitis (AS).

Differences and common symptoms

Compared with adults with SpA, those with juvenile SpA typically do not have axial involvement in the early course of the disease, and peripheral disease is more prevalent. Additionally, cardiovascular disease affects these patients less frequently compared with those who have adult-onset AS.3

Although the presentation of juvenile SpA is variable, some of the more common symptoms include dactylitis, swollen ankle, enthesitis, and morning stiffness in the lower back or affected joints.1 Extraarticular manifestations may include bowel inflammation, skin and mucocutaneous manifestations, and anterior uveitis. The authors of the current paper note that juvenile SpA should be considered in adolescents with lower extremity arthritis and enthesitis or inflammatory back pain, particularly in boys.

To discuss treatment considerations and research needs pertaining to juvenile SpA, Rheumatology Advisor interviewed Pamela F. Weiss, MD, MSCE, attending rheumatologist at the Children’s Hospital of Philadelphia and associate professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, as well as coauthor of the review mentioned above and numerous other articles4-8 on the topic; and Sangeeta D. Sule, MD, PhD, associate professor of pediatric rheumatology at Johns Hopkins University.

Rheumatology Advisor: What are specific treatment considerations for this form of childhood arthritis? How is treatment modified for this group compared with those with other forms of childhood arthritis?

Dr Weiss: The peripheral arthritis is treated the same as for other forms of childhood arthritis. The mainstay of therapy is glucocorticoid joint injections if there are a small number of joints, and methotrexate if there are many joints. When there is arthritis of the lower back, which is primarily seen in this form of arthritis and not others, methotrexate is not effective and tumor necrosis factor inhibitors should be considered. Other comorbidities that can occur with SpA that influence treatment decisions include IBD and symptomatic eye inflammation.

Dr Sule: The treatment of SpA in children depends on which clinical manifestation is present. If the child has associated symptoms, such as psoriasis or IBD, treating these underlying disorders can help bring the arthritis under control. This is different from other types of juvenile arthritis where the treatment is focused on the joint disease. That is not to say that [we don’t aim to] reduce pain, inflammation, and swelling in the joints in children with SpA as well.

Rheumatology Advisor: What is the suspected role of the microbial environment in SpA pathogenesis?

Dr Weiss: The role of the microbiome in pathogenesis is an area of active research. We know that many patients with SpA have inflammatory gut lesions that may or may not meet criteria for IBD. We know that patients with SpA have altered microbiota compared with healthy controls and that patients with SpA can also have a pathologic response to normal microbiota.

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Dr Sule: In studies by Stoll et al, children with SpA had altered stool microbiota compared with controls.9 These differences may be important in triggering the response against self seen in SpA. The pathogenesis is probably multifactorial, including genetic and environmental interactions.

Rheumatology Advisor: What is known about the prognosis of patients with this disease?

Dr Weiss: Longitudinal cohort studies of patients with SpA have reported that less than 20% achieve remission off medication within 5 years.1 It has also been shown that these children have more impaired function and higher pain intensity than children with other forms of childhood arthritis.10

Dr Sule: Children with SpA have more pain, stiffness, reduced function, and lower remission rates compared with other types of arthritis. There are certain factors associated with worse outcomes, including presence of HLA-B27, older age of onset, sacroilitis, tenosynovitis, and increased number of active joints in the first 3 years after disease onset.

Rheumatology Advisor: What are some of the gaps in treatment and remaining research needs in this area?

Dr Weiss: There a number of newer and exciting drugs that target the interleukin-17/interleukin23 pathway that have shown very promising results in adults.1 These drugs are not yet available for use in children because the necessary clinical trials have not been completed. There is also a lack of clinical trials to study axial disease in children, which is likely due to a number of challenges including a lack of classification criteria for axial disease in children — so we can identify who to enroll — and a lack of validated measures to follow over time to assess treatment efficacy and effectiveness.

Dr Sule: The link between the gut microbiota and disease inflammation is an area that needs continued exploration. Also, being able to identify which medication would be best for a particular child — akin to personalized medicine — is a topic that warrants further research.

Interview was lightly edited for style and clarity.

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  1. Weiss PF, Colbert RA. Juvenile spondyloarthritis: a distinct form of juvenile arthritis.Pediatr Clin North Am. 2018;65(4):675-690.
  2. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390-392.
  3. Huppertz H, Voigt I, Müller-Scholden J, Sandhage K. Cardiac manifestations in patients with HLA B27-associated juvenile arthritis.Pediatr Cardiol. 2000;21(2):141-–147.
  4. Weiss PF, Xiao R, Biko DM, Chauvin NA. Assessment of sacroiliitis at diagnosis of juvenile spondyloarthritis by radiography, magnetic resonance imaging, and clinical examination. Arthritis Care Res (Hoboken). 2016;68(2):187-194.
  5. Gmuca S, Xiao R, Brandon TG, et al. Multicenter inception cohort of enthesitis-related arthritis: variation in disease characteristics and treatment approaches. Arthritis Res Ther. 2017;19:84.Weiss PF, Xiao R, Brandon TG, et al. Comparative effectiveness of tumor necrosis factor agents and disease-modifying antirheumatic therapy in children with enthesitis-related arthritis: the first year after diagnosis. J Rheumatol. 2018;45(1):107-114.
  6. Weiss PF, Maksymowych W, Lambert RG, et al. Feasibility and reliability of the Spondyloarthritis Research Consortium of Canada Sacroiliac Joint Structural Score for Children with Spondyloarthritis [published online June 15, 2018]. J Rheumatol. doi:10.3899/jrheum.171329
  7. Weiss PF, Xiao R, Brandon T, et al. Radiographs in screening for sacroiliitis in children: what is the value? Arthritis Res Ther. 2018;20(1):141.
  8. Stoll ML, Kumar R, Morrow CD, et al. Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis.Arthritis Res Ther. 2014;16(6):486.
  9. Weiss PF, Beukelman T, Schanberg LE, Kimura Y, Colbert RA; CARRA Registry Investigators. Enthesitis-related arthritis is associated with higher pain intensity and poorer health status in comparison with other categories of juvenile idiopathic arthritis: the Childhood Arthritis and Rheumatology Research Allianc Registry. J Rheumatol. 2012;39(12):2341-2351.