Page 760 - Clinical Immunology_ Principles and Practice ( PDFDrive )

732 Part six Systemic Immune Diseases

the current recommendation is to increase the intensity of their management of children who attain prolonged inactive disease
treatment accordingly. 24 status will be an important future focus. 32
Treatment of Systemic Features of Systemic Arthritis TRANSLATIONAL RESEARCH
For decades, the mainstay of therapy for sJIA has been systemic
glucocorticoids and NSAIDs. Nearly all children with sJIA will
respond favorably to systemic glucocorticoids, if given in sufficient ON tHE HOriZON
doses. However, often children become “steroid dependent,” and
efforts to decrease the glucocorticoid burden to minimize adverse • Novel criteria for identifying macrophage activation syndrome (MAS)
effects have been unsuccessful. Presumably because of its different among children with systemic juvenile idiopathic arthritis (sJIA) have
been generated using real patient data that are diagnostically highly
pathogenesis, sJIA has not been shown to respond to TNF sensitive and specific.
inhibitors as favorably as the other categories of JIA. Instead, • Genetic screening for mutations in cytolytic pathway genes will help
IL-1 and IL-6 appear to be key cytokines in the disease process. identify those individuals at risk for developing MAS.
Accordingly, IL-1 (anakinra, canakinumab) and IL-6 (tocilizumab) • Murine models are paving the way for a better understanding of MAS
inhibitors are recommended as the first-line nonglucocorticoid immunopathology and potential pathways for clinical intervention.
treatments for sJIA. 25 • Clinical trials involving treatment of MAS with inhibitors of proinflam-
matory cytokines are just underway.
The appearance of clinically significant MAS generally requires
directed therapy. The typical treatment approach involves increased
systemic glucocorticoids. The calcineurin inhibitor cyclosporine The explosion in advances in immunology and genetics are
1,7
is frequently added, and some authors advocate IL-1 and IL-6 leading to major breakthroughs in therapy for rheumatic diseases,
1,7
inhibitors for treatment of MAS. In severe refractory cases, including JIA. Challenges remain, however, in diagnosing and
cytotoxic chemotherapeutic agents, such as cyclophosphamide treating MAS complicating sJIA. To distinguish a sJIA disease
or etoposide, may be warranted. flare-up from MAS, expert opinion and Delphi techniques are
currently being used to explore novel criteria for diagnosing
Treatment of Arthritis of Systemic Arthritis MAS in children with sJIA. Data collection regarding clinical,
Some children with sJIA will develop a chronic course of poly- laboratory, and pathological features of children with sJIA, with
arthritis with a relative absence of concurrent systemic features. and without MAS, have been used to develop new classification
33
In general, it is recommended that these children be treated as criteria. Furthermore, genetic mutations and polymorphisms
those with polyarthritis who did not have systemic features at in genes linked to the defective cytolytic pathway in lymphocytes
24
onset. Based on clinical trial results, the IL-6 inhibitor tocili- from patients with MAS are being explored to identify patients
18
zumab may be the most effective treatment for these patients. with sJIA with a propensity to develop MAS. Mouse models
of MAS are helping to better understand MAS immunopathology
Treatment of Uveitis and the role of pro-inflammatory cytokines in the process.
34
JIA-associated anterior uveitis frequently requires directed therapy. Early recognition of MAS and a better understanding of the role
Topical glucocorticoid eye drops, such as prednisolone acetate of various cytokines in the pathogenesis of MAS will allow for
1%, are frequently initiated at the time of diagnosis by the treating improved targeted therapy for this often fatal condition.
14
ophthalmologist. Although effective in decreasing the inflam-
mation of uveitis, glucocorticoid eye drops cannot be tolerated Please check your eBook at https://expertconsult.inkling.com/
in high doses for extended periods because of the risk of cataracts for self-assessment questions. See inside cover for registration
14
and glaucoma. For this reason, systemic medications are fre- details.
quently employed in the treatment of JIA-associated uveitis.
Methotrexate has been shown to be effective for uveitis and is REFERENCES
1,14
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