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Juvenile Psoriatic Arthritis: Bathwater Or Baby?

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Juvenile Psoriatic Arthritis: Bathwater Or Baby? Editorial Juvenile Psoriatic Arthritis: Bathwater or Baby? Arthritis in children represents a markedly heterogeneous these groups across a set of variables such as pattern of joint family of conditions. To get a handle on this complexity, involvement and clinical course. The authors found that pediatric rheumatologists have developed an evolving set of such differences were scant, which they conclude casts classification criteria. The most recent iteration of the juve- doubt upon the validity of JPsA as an independent diagnos- nile idiopathic arthritis (JIA) nomenclature recognizes 7 tic entity. subgroups defined on the basis of compelling features of the This study represents a thought-provoking contribution clinical phenotype, supported in some cases by laboratory to the ongoing debate about the classification of juvenile tests such as rheumatoid factor or HLA-B271. One of these arthritis. The results highlight the challenges of attempting subgroups is juvenile psoriatic arthritis (JPsA), which may to draw lines between diseases in the absence of biological be diagnosed in children with arthritis (1) in the presence of understanding. Yet before proceeding too far down the path psoriasis, or (2) in the absence of psoriasis, if 2 features sug- of skepticism, it is worth considering whether the current gestive of a psoriatic diathesis are present, including dactyli- study was designed optimally to discern the presence of tis, nail changes, or psoriasis in a first-degree relative, all in psoriasis-associated arthritis in children. Reasons for con- the absence of specified exclusions. cern arise in 3 areas: classification of study patients, Unfortunately, the differentiation of psoriatic from assumptions of homogeneity in the groups studied, and lim- non-psoriatic arthritis in children is challenging. In about itations imposed by demographic matching. half of children with JPsA, the classic rash presents after the Classification. The key initial step in any case-control study onset of arthritis, with a lag time that may be 10 years or is to determine who is a case and who is a control. This more2. Manifestations of psoriasis in the young child are turns out to be rather difficult in JPsA because many chil- often atypical or incompletely specific, such as erythema dren develop psoriasis years after arthritis, a problem that is and scale behind the ears, features taken into consideration especially acute among younger children. Did the current by an earlier (Vancouver) set of JPsA criteria but excluded study assign all patients correctly? Within the non-psoriatic under the JIA nomenclature3. Even in cases where evidence group, 4 patients (7.5%) had dactylitis while an additional 7 for psoriasis is unambiguous, it remains an open question (13%) exhibited nail pits, findings with a specificity of whether psoriasis is relevant to proper categorization of the 95–98% for adult psoriatic arthritis (PsA) and recognized in child with arthritis. Is JPsA sufficiently distinct from other children with arthritis and psoriasis well before the advent forms of JIA to merit its own category? of current JPsA criteria5-7. Further, 4 patients with oligo- In this issue of The Journal, Butbul and colleagues exam- articular-onset non-psoriatic JIA exhibited small joint ine this question from a practical vantage point4. They ask: inflammation at presentation, a pattern suggestive of JPsA8. Do patients meeting JIA criteria for JPsA exhibit a different These cases raise the possibility that there was admixture of phenotype and outcome from patients who do not? To JPsA into the non-JPsA category. Indeed, among patients answer this question, they identified about half the patients followed at Children’s Hospital Boston, strict application of with JPsA followed at the Hospital for Sick Children in JIA criteria was found to scatter more than half the patients Toronto and paired them with non-JPsA patients matched with Vancouver-defined JPsA into other JIA subgroups, for onset type (oligo- or polyarticular), gender, age of onset, despite the presence of nail pits, dactylitis, or other findings and date of diagnosis. Using a case-control design, they suggestive of a psoriatic diathesis9. While all classification examined whether differences could be identified between debate is hampered by a lack of gold standard, these results See, Comparison of patients with JPsA, non-JPsA, and nonpsoriatic JIA, page 2033 Personal non-commercial use only. The Journal of Rheumatology Copyright © 2009. All rights reserved. Nigrovic: Editorial 1861 Downloaded on September 26, 2021 from www.jrheum.org have gained support from a recent study by Flatø and col- JPsA differs from that of other JIA subtypes, then there are leagues10. As part of an inquiry into the longterm outcome grounds for maintaining the category. Indeed, the evidence of JPsA, these investigators compared patients with JIA- that psoriasis and arthritis are related is overwhelming. defined JPsA, patients fulfilling Vancouver but not JIA cri- Adults with psoriasis manifest inflammatory arthritis with a teria for JPsA, and patients with undifferentiated JIA. After frequency exceeding 20% in some studies, a dramatic a median followup of 15 years, the prevalence of overt psori- increase over the general population12. Arthritic changes asis was equivalent in both JPsA groups and much higher accompany a murine model of psoriasis13. Large adult than in non-psoriatic JIA. To the extent that development of cohorts show that PsA exhibits distinctive demographics, psoriasis is an unambiguous declaration of the psoriatic joint distribution, radiographic pattern, and associated diathesis, these data support the suggestion that current JIA extraarticular features, despite responsiveness to the same criteria for JPsA are drawn too narrowly. medications used in RA5,12,14. Psoriatic synovium differs In the present study4, potential misclassification of cases from rheumatoid synovium in vascular pattern and cellular and controls becomes particularly problematic because of infiltrates15,16. Synovial fluid from seropositive RA shows sample size. With 31 oligoarticular-onset and 21 poly- depletion of complement, while psoriatic fluid does not17. articular-onset JPsA patients, matched 1:1 to non-psoriatic Even more fundamentally, inflammation in adult PsA fre- JIA controls in parallel analyses, the study had limited quently involves, and may originate at, periarticular entheses power to detect differences of potential importance. For — a mechanism that offers a potential explanation for both example, the authors found that small joint disease was dactylitis and nail pits, features common in JPsA18-20. These more common in oligoarticular-onset JPsA (14/31 vs 9/31 in studies have yet to be replicated in children, and it may of JIA, odds ratio 2.0) but had to reject this result as non-sig- course be that children are entirely different. However, the nificant. By contrast, a larger study identified oligoarthritis initial presumption should be that shared phenotype reflects with small joint disease as a hallmark pattern within JPsA8. at least some degree of shared pathophysiology. A second limitation intrinsic to the study design arises There will undoubtedly be something uniquely pediatric out of heterogeneity within disease categories. Earlier series about JPsA, at least in the youngest children. The epi- suggested, and we have recently confirmed, that younger (< demiology of JPsA mirrors that of JIA as a whole, with an 5 yrs at onset) and older children with JPsA differ substan- early-onset incidence peak (before age 5 or 6 yrs) that par- tially in gender ratio, pattern of joint involvement, antinu- allels that of non-psoriatic JIA2. As highlighted by clear antibody (ANA) status, and clinical course2,11. Professor Alberto Martini, younger children with arthritis Age-dependent differences have also been noted within tend to be female, ANA positive, seronegative, and at risk non-psoriatic oligoarthritis. By grouping younger and older for subacute anterior uveitis — features that cut across not patients together, the current study pools apples and only the psoriatic/non-psoriatic boundary but also the tra- oranges, obscuring true differences (and similarities) while ditional oligoarticular/polyarticular divide21. Early-onset introducing variability that constrains statistical power. JPsA may well have more in common with early-onset JIA A final caveat to the current study arises out of the than with JPsA in older children. Yet uncertainty about case-control methodology. By matching on age and gender, these young patients should not translate into doubt about Butbul, et al gain the ability to control for these variables but older children with JPsA. These patients exhibit a near 1:1 lose the ability to assess the demographics of JPsA and JIA. male:female ratio, tend to have oligoarticular involvement, In adults, one of the most compelling arguments that PsA is often manifest enthesitis and occasionally sacroiliitis, and distinct from rheumatoid arthritis (RA) is a striking differ- therefore bear an unmistakable resemblamce to PsA in the ence in gender ratio between these entities5,12. A case-con- adult12. Much more work will be required before we can trol study of JPsA will necessarily be blind to such demo- accurately assess the true biological subdivisions within graphic clues. childhood-onset arthritis, including the role of the psoriat- These concerns notwithstanding, there is something intu- ic diathesis in modulating, or defining,
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