From the Department of Dermatology, Mount Sinai St. Luke’s-Roosevelt and Beth Israel Medical Centers of the Icahn School of Medicine at Mount Sinai, New York, New York.
Dr. Silverberg has participated in a roundtable discussion for LEO Pharma.
Correspondence: Nanette B. Silverberg, MD, Department of Dermatology, 1090 Amsterdam Ave, Ste 11D, New York, NY 10025 (nsilverb@chpnet.org).
Recent reviews of pediatric and adolescent psoriasis highlight the paucity of therapeutic information for these patient populations. Investigators typically focus on topical therapies as the basis of treatment,20 as well as the addition of phototherapy in mild to moderate plaque or guttate psoriasis and biologic or systemic agents in moderate to severe flares of plaque, erythrodermic, or pustular psoriasis.21 Further studies are needed to identify evidence-based therapeutic paradigms for pediatric psoriasis and to pinpoint therapies associated with the best quality of life in patients and their caregivers.
Tumor Necrosis Factor α Inhibitors
Safety and efficacy of etanercept for juvenile idiopathic arthritis including oligoarthritis, enthesitis-related arthritis, and psoriatic arthritis recently was reviewed by Windschall et al22 using data from the German pediatric Biologika in der Kinderrheumatologie registry. Juvenile Arthritis Disease Activity Score 10 improved from baseline for 127 pediatric patients with psoriatic arthritis in 3 to 24 months (mean [standard deviation], 14.7 [6.4], 5.0 [4.6], 5.3 [6.4] at baseline, 3 months, and 24 months, respectively). Overall side effects were relatively higher in the psoriatic arthritis group; the rate of serious (relative risk, 1.39 [0.95-2.03; P=.08]) and nonserious (relative risk, 1.18 [1.02-1.35; P=.03]) adverse events also was elevated. Uveitis risk was greatest in the psoriatic arthritis group and the number of associated cases of inflammatory bowel disease outnumbered those seen in other forms of arthritis. The investigators concluded that monitoring for extra-articular immunopathies should be conducted in pediatric patients with psoriatic arthritis who are undergoing etanercept therapy.22
Tumor necrosis factor α (TNF-α) inhibitors have been associated with triggering psoriasiform dermatitis in pediatric patients treated for inflammatory bowel disease. A Finnish study of infliximab side effects in pediatric patients with inflammatory bowel disease (n=84; Crohn disease: n=64) demonstrated that almost half (47.6% [40/84]) of the participants presented with chronic skin reactions, 23% of which were severe in nature.23 Psoriasiform lesions of the scalp and ears were most common, followed by the periorificial area, genitals, trunk, and extremities. Rare association with HLA-Cw*0602 genotype was noted. Skin manifestations did not correlate with gut inflammation (as determined by fecal calprotectin levels). Discontinuation of therapy rarely was required.23 Other studies also have highlighted this side effect, suggesting an incidence of 2.7% in adults with colitis treated with TNF-α inhibitors24 and 10.5% in pediatric patients with Crohn disease.25 In a study by Sherlock et al,25 pediatric patients with Crohn disease developing psoriasis following infliximab therapy were more likely to be homozygous for specific polymorphisms in the IL-23R gene (rs10489628, rs10789229, and rs1343151).
Methotrexate
For pediatric patients who are being treated with methotrexate, the polyglutamate assay recently has been reported to be helpful in identifying patients needing a dose escalation.26 Higher numbers on the polyglutamate assay are associated with superior response to methotrexate therapy. Doses can be increased after 12 weeks in patients with low assays.26
IL-23
The safety of IL-23 blockade in pediatric psoriasis patients has not yet been established, but data from adult cases have implicated the IL-17 and IL-23 pathways in psoriasis/psoriatic arthritis, including an association with IL-23R polymorphisms27 and increases in soluble IL-20 and IL-22 associated with disease severity and an association of IL-17 levels with activity on the psoriasis area and severity index scores.28 The data are more limited for pediatric cases. Pediatric patients with inflammatory bowel disease who have an IL-23R polymorphism appear to be susceptible to psoriatic flares while on TNF-α inhibitor therapy,25 which suggests that the IL-23 blockade may be of benefit for some pediatric patients with psoriasis or psoriatic arthritis.
Conclusion
Pediatric psoriasis and psoriatic arthritis have now been identified as being part of the autoimmune spectrum and are associated with metabolic syndrome, including obesity and excess central adiposity, similar to their adult variants. An overview of potential unmet needs in pediatric psoriasis is included in Table 2. These unmet needs include further delineation of diet and weight modification in the care and prevention of psoriasis; expansion of therapeutic trials and US Food and Drug Administration–approved medications for children with psoriasis, especially severe variants such as extensive plaque and pustular disease; and development of guidelines for ongoing monitoring of children with psoriasis. The role of therapeutic interventions and weight management on long-term disease course remains to be shown in extended clinical trials. Despite the great advancements in psoriatic care, knowledge gaps remain in pediatric psoriasis that will need to be addressed in the future.
