Background & Objectives
Typical patterns of inflammation occur in the joints of patients with inflammatory arthritis, but in each individual, arthritis affects only a subset of all possible sites. Beyond the broad disease patterns characterizing distinct forms of arthritis, each patient exhibits an individual pattern of joints that are involved or spared, both with respect to the type of joint (e.g., wrist, knee) and to laterality.
In previous studies of patients with rheumatoid arthritis (RA), joints affected in the first year of disease comprised most of the joints that are ever involved, including all joints needing subsequent joint replacement. Another study showed that joints swollen at baseline were at higher risk of subsequent swelling, with wrists, metacarpophalangeal (MCP) joints and metatarsophalangeal (MTP) joints reaching recurrence rates of 60%. These observations suggest that, in addition to systemic autoimmunity, factors local to individual joints render them susceptible to subsequent inflammation.
The purpose of this study was to identify patient-specific patterns of joint flare to distinguish local from systemic drivers of chronic disease in patients with juvenile idiopathic arthritis (JIA).
Methods
Patients with JIA were followed without interruption from disease onset into adulthood at two large academic centers. Medical records were reviewed to determine the joints that were inflamed at each visit. Flare was defined as physician-confirmed joint inflammation occurring subsequent to documented inactive disease.
Results
Among 222 adult candidates, 95 had complete serial joint examinations since the time of disease onset in childhood. Mean follow-up was 12.5 years (interquartile range 7.9–16.7 years). Inactive disease at some point during follow-up was achieved in the joints of 90 (95%) of 95 patients, after which 81% (73 patients) experienced at least one flare.
Intraarticular steroid injection did not evidently alter joint-specific memory. In the 13 patients with oligoarticular JIA, 11 of 12 distinct knee joints that were injected with intraarticular steroids flared again at least once. Several of the joints were injected multiple times, but this did not prevent future flares from recurring in the same joint.
Among 940 joints identified as being affected with a flare (total of 253 flares), 74% had shown previous involvement in a flare. In flares affecting easily observed large joint pairs in which only one side had been involved before (n=53), the original joint was affected in 83% and the contralateral joint in 17% (P<0.0001 vs. random laterality). However, disease extended to at least one new joint in ~40% of flares, a risk that remained stable even decades after onset of JIA.
Chang et al. found that 23% of arthritis flares occurred while patients were not receiving medications and that 77% occurred in patients receiving NSAIDs, oral steroids and/or conventional or biologic disease-modifying anti-rheumatic drugs (DMARDs). Previously unaffected joints were involved in 32 (54%) of 59 flares that occurred while patients were not receiving medications, and previously unaffected joints were involved in only 70 (36%) of 194 flares that occurred while patients were receiving medications (for involvement of new joints if the patient was not receiving medication at the time of flare, odds ratio 2.09 [95% confidence interval 1.16–3.80], P=0.015 by two-tailed Fisher’s exact test), suggesting that recurrent arthritis flares in the absence of a protective agent pose a particularly high risk of disease extension to new sites.
Conclusion
Arthritis flares preferentially affect previously inflamed joints, but carry an ongoing risk of disease extension. These findings confirm joint-specific memory and suggest that prevention of accumulation of new inflammatory features in the joint should be an important target for arthritis therapy.
For full study details, including source material, refer to the full article.
Excerpted and adapted from:
Chang MH, Bocharnikov AV, Case SM, et al. Patterns of arthritis flare revealing joint-specific memory together with sustained risk of new joint inflammation. Arthritis Rheumatol. 2022 Oct;74(10).
