• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report
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Enthesitis-Related Juvenile Idiopathic Arthritis

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Last updated: 4/5/2024
Years published: 2024


Acknowledgment

NORD gratefully acknowledges Shailee D. Parekh, MD Candidate, Creighton University School of Medicine and Daniel Reiff, MD, Pediatric Rheumatology, Boys Town National Research Hospital, for the preparation of this report.


Disease Overview

Summary

Enthesitis-related juvenile idiopathic arthritis is a subtype of juvenile idiopathic arthritis (JIA) that is characterized by both arthritis and inflammation of an enthesis site (the point at which a ligament, tendon or joint capsule attaches to the bone). Signs and symptoms generally develop in late childhood or early adolescence and include pain, stiffness and swelling in joints and at the enthesis. The most affected parts of the body are the knee and the back of the ankle (Achilles tendon). JIA is idiopathic, meaning that the underlying cause of the disease is unknown. It is very rare for more than one member of a family to have juvenile arthritis; however, research suggests that having a family member with juvenile arthritis or any autoimmune disease may increase the risk of having juvenile arthritis. Treatment usually involves different types of medications to help manage symptoms and/or physical therapy.

Enthesitis-related juvenile idiopathic arthritis (JIA) is a form of juvenile arthritis that involves joint pain and stiffness, as well as enthesitis (inflammation where a ligament or tendon attaches to bone). Pain and stiffness are common in the joints of the lower body, but it can sometimes also happen in the spine and sacroiliac joints. Some children may also have inflammation of the front portion of the eye (called acute anterior uveitis). Enthesitis-related JIA most commonly affects boys and is related to certain genetic risk factors and a family history of similar conditions. It can be diagnosed by a pediatric rheumatologist. Treatment is mostly through medications that reduce inflammation and help to manage pain and stiffness of joints.

 

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Synonyms

  • ERA
  • juvenile spondyloarthropathy
  • juvenile enthesitis-related arthritis
  • enthesitis related arthritis, juvenile
  • enthesitis-related arthritis
  • enthesitis-related JIA
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Signs & Symptoms

The symptoms of enthesitis-related juvenile idiopathic arthritis vary from person to person. Initial symptoms often include pain and stiffness in the joints of the lower body, especially knees, hips, ankles and feet. Joint pain, stiffness, and swelling are usually asymmetric (affecting each side of the body differently), and children can have trouble with walking as the joints of the lower body are commonly affected. While joint pain and stiffness may come and go initially, they can last for longer periods over time as the condition progresses. Pain and stiffness are often worse in the morning and can get better with movement. Enthesitis-related JIA is more likely to have pain and stiffness in the hips and midfoot area than other forms of JIA.

Enthesitis is another common symptom and is marked by pain or swelling at the sites where tendons or ligaments attach to bone. This usually happens at the knee where the patellar tendon attaches to the kneecap, at the bottom of the foot where the plantar fascia attaches to the bones of the feet and at sites on the top and bottom of the heel, although other sites can be affected as well.

Some children with enthesitis-related JIA develop acute uveitis, which is inflammation of the front part of the eye. Acute uveitis causes eye pain, redness and sensitivity to light, usually in one eye. Uveitis may occur multiple times and complications from recurrent uveitis include scarring of the iris (colored part of the eye), cataracts (clouding of the lens of the eye) and calcium deposition in the cornea (clear part of the anterior eye), although these are rare when flares are quickly treated.

Several years after the condition starts, some children may develop inflammation of the spine or sacroiliac joint (where the bottom of the spine (sacrum) meets the pelvis (ilium)). These children may have lower back pain, buttock pain and stiffness of the back which is worsened by long periods of inactivity. Back pain is seen in some children who progress to develop a condition called juvenile ankylosing spondylitis which is another kind of inflammatory arthritis that affects the spine. Therefore, identifying arthritis of the spine early on is important.

Children with enthesitis-related JIA may also experience symptoms such as rash (which may affect any part of the body), fever and fatigue. However, these symptoms, though common, are not specific to enthesitis-related JIA and may be seen in many other conditions.

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Causes

The exact cause of enthesitis-related juvenile idiopathic arthritis is not known, but it is thought that both genetic and environmental factors contribute. One gene that is strongly linked with the condition is called HLA-B27. HLA genes make proteins that help the immune system differentiate between its own cells and other harmful organisms. The precise way that HLA-B27 leads to symptoms of arthritis is still being studied, but it may be related to abnormal activation of the immune system towards its own cells. Children with enthesitis-related JIA have an increased number of immune cells in their blood and in the fluid within their joint spaces. These immune cells release more inflammatory proteins which likely contribute to developing the disease. Additionally, abnormal interactions between the immune system and bacteria found in the gut may also contribute to development of the disease.

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Affected populations

Enthesitis-related juvenile idiopathic arthritis most commonly affects boys older than six years. It is also the most common type of JIA in children of Asian descent. Children who have relatives with enthesitis-related arthritis or other conditions associated with variants in the HLA-B27 gene, such as ankylosing spondylitis, reactive arthritis, inflammatory bowel disease or acute anterior uveitis, are also at increased risk.

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Diagnosis

Enthesitis-related juvenile idiopathic arthritis is often diagnosed via thorough history and physical exam by a pediatric rheumatologist. Common findings in the history include joint pain and/or stiffness persistent for weeks (often worse in the morning) and enthesitis (pain at the insertion points of tendons and ligaments on bone). Physicians may test for enthesitis by physically pressing on the tendon/ligament insertions and checking for tenderness. Imaging studies may also help in diagnosis. Ultrasound and whole-body magnetic resonance imaging (MRI) are occasionally used to identify enthesitis although they are not used commonly in children. For children who are thought to have inflammation of the spine and sacroiliac joint, physicians can test for mobility of the spine during a physical exam. These tests are normal early in the disease course, so imaging of the spine and sacroiliac joint with MRI may be more helpful in showing inflammation.

Some blood tests are helpful when diagnosing children with arthritis. Certain proteins and inflammatory markers like antinuclear antibodies (ANA) and rheumatoid factor are elevated in the blood in certain types of arthritis and autoimmune conditions. However, in enthesitis-related JIA, these antibodies are usually at normal levels. Measuring these levels might aid in differentiating enthesitis-related JIA from other kinds of arthritis. Testing for variants in the HLA-B27 gene, which is strongly associated with enthesitis-related JIA, may aid in diagnosis as well. Children with enthesitis-related JIA can also have high levels of fecal calprotectin, a protein that is tested in the stool, and this is a marker for gut inflammation.

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Standard Therapies

Treatment

The treatment for enthesitis-related juvenile arthritis is aimed at providing pain relief, maintaining movement of the joints and protecting the joints from further damage. One or a combination of medications are typically used. Along with medications, a team of health professionals can support people with enthesitis-related JIA through a variety of ways. These include family education and psychosocial support due to the impact that the condition can have on the child’s day to day life.

Physical therapy is helpful for children in maintaining good joint movement and function. Occupational therapy is also beneficial in supporting children to learn how to best move around during their activities of daily living. Children should also get regular eye exams due to eye inflammation that is seen in the condition.

The initial medication for enthesitis-related JIA is non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen and indomethacin. NSAIDs work by reducing inflammation and can treat both joint pain and stiffness. Steroid injections can also work for pain relief, especially in swollen, affected joints, but must be used cautiously. When NSAIDs are not effective at providing symptom relief, another group of medications called disease-modifying anti-rheumatic drugs (DMARDs) are the next step. Sulfasalazine and methotrexate are examples of DMARDs. Children should be monitored with blood tests regularly while taking these drugs. For children who do not respond to either NSAIDs or DMARDs, the next option is biologic agents like TNF-alpha blockers. TNF-alpha is a molecule that is part of the immune system which causes a strong inflammatory response in the body. TNF-alpha blockers are given by injection weekly to monthly and are usually very effective in managing symptoms. However, children on TNF-alpha blockers are also at increased risk for infection.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

 

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References

JOURNAL ARTICLES

Barkhodari A, Lee KE, Shen M, Shen B, Yao Q. Inflammatory bowel disease: focus on enteropathic arthritis and therapy. Rheumatol Immunol Res. 2022;3(2):69-76. Published 2022 Jul 6. doi:10.2478/rir-2022-0012

‌Martini A, Ravelli A, Avcin T, et al. Toward new classification criteria for juvenile idiopathic arthritis: first steps, pediatric rheumatology international trials organization international consensus. J Rheumatol. 2019;46(2):190-197. doi:10.3899/jrheum.180168

Hahn YS. Enthesitis-related arthritis. Journal of Rheumatic Diseases. 2018;25(4):221. doi:https://doi.org/10.4078/jrd.2018.25.4.221

Aggarwal A, Misra DP. Enthesitis-related arthritis. Clin Rheumatol. 2015;34(11):1839-1846. doi:10.1007/s10067-015-3029-4

Weiss PF. Evaluation and treatment of enthesitis-related arthritis. Curr Med Lit Rheumatol. 2013;32(2):33-41.

Weiss PF. Diagnosis and treatment of enthesitis-related arthritis. Adolesc Health Med Ther. 2012;2012(3):67-74. doi:10.2147/AHMT.S25872

Saurenmann RK, Rose JB, Tyrrell P, et al. Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor. Arthritis Rheum. 2007;56(6):1974-1984. doi:10.1002/art.22709

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(2):390-392.

INTERNET

Parameswaran P, Lucke M. HLA-B27 Syndromes. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551523/ Accessed March 20, 2024.

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