BERLIN – Recent evidence strongly suggests that enthesis-related arthritis in adolescents has two distinct clinical phenotypes, according to Dr. John Ioannou of University College London.
"The traditional view of enthesis-related arthritis has been that peripheral joint involvement and entheseal disease are common at presentation and then sacroiliitis occurs after many years as a late feature. I think that’s a paradigm that has been borne out not to be true. We can confidently shred that up and throw it away," he declared at the annual European Congress of Rheumatology.
Dr. John Ioannou
The increasing use of MRI in the evaluation of patients who meet revised International League of Associations for Rheumatology diagnostic criteria for enthesis-related arthritis (ERA) has demonstrated that sacroiliitis appears early in the course of the disease in many of them. This early-onset sacroiliitis doesn’t show up on standard radiography, he explained.
ERA is an understudied subtype of juvenile idiopathic arthritis. The true incidence and prevalence of ERA aren’t known. Dr. Ioannou and his coworkers are conducting a long-term observational study at University College London. Analysis of the first 68 patients in the ERA cohort who have undergone MRI scanning indicated that 36, or 62%, had axial disease while the remainder did not.
The axial phenotype of ERA is characterized by a strong association with HLA-B27-positivity; more than 80% of patients with axial ERA were HLA-B27 positive, as was true for only a minority of those with the peripheral ERA phenotype. Extra-articular manifestations of ERA – inflammatory bowel disease and acute anterior uveitis – occurred only in HLA-B27-positive patients with axial disease.
Patients who were unaffected by axial disease had a strong proclivity for ankle arthritis, which was present in 80% of that group, compared with one-fourth of patients with axial ERA.
Fifty-eight of the 68 patients in the ERA cohort are male. Their median age at disease onset was 11 years and 1 month. The median time from disease onset to the appearance of inflammatory spinal symptoms was 2 years and 8 months.
The London experience matches that described by Italian investigators at the University of Florence, who are following a cohort of 59 patients with ERA. Twenty-one of the 59 reported symptoms of inflammatory back pain beginning a median of 1 year and 3 months after onset of ERA. MRI revealed the presence of sacroiliitis in 17 of the 21, all of whom had negative X-rays of the sacroiliac joints. As in the London series, the Italian patients with axial involvement were far more likely to be HLA-B27-positive, while those without axial disease had a greater frequency of ankle arthritis (J. Rheumatol. 2010;37:2395-401).
Twenty-nine of the 68 patients in the London cohort are on anti–tumor necrosis factor (anti-TNF) therapy plus methotrexate or another nonbiologic disease-modifying antirheumatic drug.
"Our anecdotal experience is that anti-TNF therapy tends to work pretty well in patients with ERA, but the remission rate is low. We’ve not been able to discontinue anti-TNF therapy in our patients," Dr. Ioannou noted.
This is consistent with the experience of a Dutch group. They reported that two-thirds of 22 ERA patients treated with an anti-TNF agent had inactive arthritis and enthesis after 15 months; however, none was able to discontinue biologic therapy without flaring of their disease (J. Rheumatol. 2011;38:2258-63).
The pathogenic mechanisms driving the two clinical patterns of ERA aren’t understood yet. Defining those mechanisms will provide a rationale for deciding on the best treatments for patients with one clinical phenotype or the other. At present, treatment is largely based upon extrapolation from data gathered in treating other forms of juvenile idiopathic arthritis or adult ankylosing spondylitis, the rheumatologist said.
Dr. Ioannou reported having no financial conflicts.