Clinical and Health Affairs
Juvenile Spondyloarthropathies
Inflammation in Disguise
By Evren Akin, M.D.
Abstract
Spondyloarthropathies are inflammatory conditions of the spine, joints, and entheses that present in a variety of ways. They can take years to develop and there are no pathognomonic laboratory tests that confirm a diagnosis. Because of this, they can be difficult to diagnose, particularly in children. This article reviews the clinical characteristics of these inflammatory conditions and diagnostic and treatment approaches that are used in children.
The spondyloarthropathies are a group of inflammatory conditions that involve the spine (sacroiliitis and spondylitis), joints (asymmetric peripheral arthropathy), and entheses (enthesopathy). The clinical subsets of spondyloarthropathies constitute a wide spectrum, including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease-associated arthritis, and undifferentiated sacroiliitis.1 Depending on the subtype, extra-articular manifestations might involve the eyes, skin, lungs, gastrointestinal tract, and heart. The most commonly accepted classification criteria for the spondyloarthropathies come from the European Spondyloarthropathy Study Group (ESSG) (Table 1).2
The juvenile spondyloarthropathies might be defined as any spondyloarthropathy subtype that is diagnosed before age 17. It should be noted, however, that adult and juvenile spondyloarthropathies exist on a continuum. In other words, many children diagnosed with a type of juvenile spondyloarthropathy will eventually fulfill criteria for adult spondyloarthropathy.
The prevalence of spondyloarthropathy is unknown because many people who are in the early stages or have a limited form may go for years without being diagnosed.
Initial diagnosis and classification of juvenile spondyloarthropathies is difficult. One of the reasons for the complexity in diagnosis is that inflammatory back pain and radiographic changes, which are noted as classic spondyloarthropathy symptoms, are rare in childhood, especially before age 9. Conversely, monoarticular or asymmetric arthritis associated with enthesitis is a common presentation (seronegative enthesopathy and arthropathy syndrome).3
Because psoriasis, bowel involvement, and other symptoms of spondyloarthropathy may take years to develop, children might be diagnosed initially with juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis.
To further complicate matters, up to 30 percent of children with psoriatic arthritis might have a positive antinuclear antibody (ANA) and no psoriasis upon presentation; up to 20 percent might have silent uveitis, which is indistinguishable from the uveitis associated with JRA.
It is unknown whether early treatment changes the long-term course of the disease. However, disability can be diminished with appropriate therapy.
Classification
Classifying juvenile spondyloarthropathies is an ongoing effort. Several classification systems have been proposed, each with its own caveat. The ESSG criteria have been validated in children, but the emphasis on inflammatory spinal pain is problematic because the symptom is uncommon in children.
The International League of Associations for Rheumatology (ILAR) classification (Table 2) of idiopathic arthritides of childhood includes a category of enthesitis-related arthritis that is more common than back pain in children with juvenile spondyloarthropathy. Inflammatory bowel disease-associated arthritis, however, is not included. Also problematic is that the ILAR classification includes in its criteria psoriasis but excludes a family history of psoriasis.4
What does spondyloarthropathy look like in a child?
Case. A 12-year-old boy is active in sports. When his right toe starts to hurt, an overuse injury is thought to be the cause. When his right toe eventually swells up, he is referred to a rheumatologist to be evaluated for gout. During the next few weeks, his right knee begins hurting as well. At the rheumatologist’s office, arthritis of the right second toe and the right knee is noted. Family history is remarkable for back stiffness in the father, which is attributed to sports participation.
The boy’s antinuclear antibody (ANA) and rheumatoid factor are negative; his HLA-B27 is positive. Although the boy is on naproxen, within several months of onset of symptoms, his right ankle also swells up. He is soon started on sulfasalazine. Again, the response is less than desirable, and his provider starts him on methotrexate.
The boy’s knee and ankle seem to be getting better, but he has an acute episode of redness and pain in his right eye about a year and a half into the illness. He is diagnosed with uveitis and treated with topical steroids. He then has a flare-up of arthritis in his right knee, and infliximab is added to the methotrexate and sulfasalazine regimen. He has a dramatic response to infliximab and is taken off sulfasalazine; his methotrexate dose is reduced to a minimum. The boy’s arthritis quickly goes into remission.
Six years later, at the age of 18, the patient is on minimal doses of infliximab and methotrexate, but each time the medications are discontinued, he develops morning stiffness in his lower back and joint pain in his right ankle. He has not had active arthritis for three years. He continues to play competitive sports in college and is otherwise healthy.
Discussion. This case showcases the most common presentation of juvenile spondyloarthropathy—enthesopathy followed by arthritis. The patient presented with vague joint pain in his lower extremities, which was initially attributed to his playing sports. Elusive joint pain with subtle exam findings are typical of enthesopathy. The most common sites are at the insertion of the patellar tendon, in the Achilles tendon, and at the attachment sites of the plantar fascia around the heel and the metatarsal heads.
The patient presented with two swollen lower-extremity joints, which easily could have been mistaken for juvenile rheumatoid arthritis (JRA). It took several years for associated symptoms typical of spondyloarthropathy to reveal themselves. Uveitis is commonly acute and painful in patients with spondyloarthropathy as opposed to asymptomatic silent inflammation in idiopathic JRA. The negative antinuclear antibody would not allow one to exclude JRA initially, but the disease course, the positive HLA-B27, and the acute uveitis eventually left little doubt.
Family history is frequently overlooked, as inflammatory back pain tends to be attributed to past injury, sports participation, or sleeping on a worn-out mattress. Inflammatory back pain, unlike that associated with mechanical causes, tends to be worse at night, rather than during activity. Most parents won’t even mention plantar fasciitis (enthesopathy) or Achilles tendonitis, unless specifically asked. Also, psoriasis might be described as “eczema,” and mild cases of inflammatory bowel disease might be labeled as irritable bowel syndrome.
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Clinical Characteristics
It usually takes years to confirm a diagnosis of spondyloarthropathy because symptoms unfold over a long period of time. Nevertheless, the following should raise suspicion:
- Recurrent joint pain in patients with a family history of psoriasis, inflammatory bowel disease, or back pain and/or stiffness at rest;
- A history of recurrent tendonitis, apophysitis, or plantar fasciitis;
- A teenaged patient with monoarticular arthritis (especially of the hip) or asymmetric arthritis involving fewer than four joints (pauciarticular);
- Pauciarticular arthritis that is difficult to control with nonsteroidal anti-inflammatory drugs (NSAIDs) and methotrexate; and
- A history of frequent trips to a chiropractor for back adjustments.
Asymmetric arthritis of the lower extremities is typical but not the rule. Tenderness over insertion of the patellar tendon, in the Achilles tendon, and at the attachment sites of the plantar fascia around the heel and metatarsal heads would suggest enthesopathy. Tendonitis might be present. A modified Schober’s test might show limited spine flexion, although it is not common at presentation. Likewise, chest expansion is usually preserved early in the disease course.
The inflammatory back pain and radiographic changes of sacroiliitis—hallmarks of adult-onset ankylosing spondylitis—are uncommon in children. In rare instances, a teenager may present with “hip” pain that turns out to be sacroiliitis.
The pattern of psoriatic arthritis generally resembles JRA. The ANA might be positive. The arthritis of psoriasis might precede the rash by years. Uveitis might be present but asymptomatic; therefore, regular eye exams are necessary. A family history of psoriasis, presence of dactylitis, and other nail findings are helpful in differentiating this condition from JRA. Inflammatory bowel disease in children might start out with arthritis or arthralgias months or years before bowel inflammation becomes clinically evident. Isolated hip arthritis; longstanding, vague gastrointestinal complaints; growth failure; difficult-to-control arthritis; and anemia might all help in diagnosing a spondyloarthropathy. None of these signs and symptoms, however, are specific. Screening antibodies for inflammatory bowel disease have a high rate of false positivity in children, and pediatric gastroenterologists generally do not recommend these tests.
Laboratory Tests
There are no pathognomonic blood tests for spondyloarthropathies. Erythrocyte sedimentation rate might be elevated, although it is nonspecific. The negative ANA and rheumatoid factor (seronegativity), in combination with positive HLA-B27 in a child with asymmetric arthritis and enthesitis, are helpful. However, a small percentage of people who are HLA-B27–positive ever develop seronegative spondyloarthropathy, so diagnosis should not rely solely on this finding.1 As mentioned earlier, the ANA might be positive in patients with psoriatic arthritis.
Treatment
Medications and exercise programs are the mainstays of therapy for patients with spondyloarthropathy. NSAIDs may help to a degree, especially if the patient experiences inflammatory back pain. Sulfasalazine can work well for peripheral arthritis, but it is not as effective for axial disease. Methotrexate is a good option, although it might not induce remission on its own. Steroids are used sparingly, mostly as intra-articular injections. The combination of these conventional medications is often inadequate in controlling spondyloarthropathies.
The discovery and use of biological agents that inhibit the tumor-necrosis factor (TNF) alpha molecule, however, have advanced the treatment of spondyloarthropathies in recent years. Anti-TNF alpha agents also are approved for use in Crohn’s disease and psoriatic arthritis. These agents include etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira); they have been found to work in the majority of patients and have dramatically improved short-term outcomes in those with ankylosing spondylitis and psoriatic arthritis. Whether they change the long-term disease course and outcome is not yet known.
Regular exercises for stretching the spine are important to keep spinal mobility in patients with ankylosing spondylitis.
Prognosis
Patients are unlikely to “outgrow” spondyloarthropathies, but they might have long periods of remission. The majority of children who start out with enthesitis-related arthritis will eventually develop ankylosing spondylitis. It is difficult to accurately predict their prognoses because the spectrum of spondyloarthropathy is so wide. In one study, disease duration of longer than five years was found to be a negative prognostic factor, predicting more disability.5 MM
Evren Akin is a pediatric rheumatologist at Gillette Children’s Specialty Healthcare in St. Paul and an adjunct faculty member at the University of Minnesota.
This article first appeared in Gillette Children’s Specialty Healthcare’s A Pediatric Perspective (2008;17[2]:1-3). It is reprinted with permission.
References
1. Klippel JH (ed). Primer on the Rheumatic Diseases Edition 12. Arthritis Foundation. Atlanta, GA. 2001.
2. Tse SM, Laxer RM. Juvenile spondyloarthropathy. Curr Opin Rheumatol. 2003;15(4):374-9.
3. Malleson PN, Petty R. Clinical and therapeutic aspects of juvenile-onset spondyloarthropathies. Curr Opin Rheumatol. 1997;9(4):291-4.
4. Bukulmez H, Colbert RA. Juvenile spondyloarthropathies and related arthritis. Curr Opin Rheumatol. 2002;14(5):531-5.
5. Flato B, Aasland A, Vinje O, et al. Outcome and predictive factors in juvenile rheumatoid arthritis and juvenile spondyloarthropathy. J Rheumatol. 1998;25: 366-75.