ABSTRACT Background No validated tools exist to evaluate chronic urticaria (CU) control in children. While the Urticaria Control Test (UCT) exhibits favourable clinometric properties in adult CU, it is not yet validated in children. Therefore, we sought to evaluate the validity of the UCT for the assessment of pediatric CU. Methods Children presenting with CU were consecutively recruited. Participants completed both the UCT and the Children’s Dermatology Life Quality Index (CDLQI). We assessed the internal consistency, convergent and known-groups validity, and screening accuracy of the UCT at study entry and at follow-up. Results A total of 52 children with CU were recruited. The UCT exhibited respectable internal consistency in the evaluation of CU (Cronbach’s α=0.73 [95%CI: 0.62, 0.85]). UCT and CDLQI scores strongly correlated (r=-0.74, P<0.01). The UCT distinguished between different strata of disease severities established by the CDLQI (P<0.01). Screening accuracy of the UCT was excellent in the discrimination of poorly controlled CU (area under the curve=0.82). An optimal cut-off of ≤10 was determined for defining poorly controlled CU (sensitivity=95.5%, specificity=63.3%). Data at follow-up were consistent with data at study entry. Conclusion The UCT is a valid tool for the assessment of pediatric CU and CSU, as evidenced by acceptable internal consistency, convergent and known-groups validity, and screening accuracy at multiple time points.

Increased prevalence of Autoimmune Diseases in Children with Chronic Spontaneous UrticariaMichelle Le, MD1, Lydia Zhang MD2, Sofianne Gabrielli MSc2, Connor Prosty BSc, MD(c)1, Laura May Miles LLM, MD(c)2, Elena Netchiporouk, MD, MSc1, Sharon Baum, MD3, Shoshana Greenberger, MD3, Luis F. Ensina, MD, MSc, PhD4, Fatemeh Jafarian, MD1, Xun Zhang, PhD5, Moshe Ben-Shoshan, MD, MSc21Division of Dermatology, McGill University, Montreal, QC, Canada2Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada3Department of Dermatology, Chaim Sheba Medical Center, Tel-Aviv University, Sackler School of Medicine, Tel Hashomer, Israel4Department of Pediatrics, Federal University of São Paolo, Brazil5Centre for Outcome Research and Evaluation, Research Institute of McGill University Health Centre, Montreal, QC, CanadaCorrespondence: Michelle Le, M.D., 1001 Decarie Blvd, Montréal, Québec, H4A 3J1 email: [email protected] type: LetterManuscript word count: 981References : 10Tables : 1Figures: NoneFunding sources : NoneConflicts of interest: None declaredIRB Approval Status : Reviewed and approved by McGill University Health Centre; approval 12-255GEN

Background The MAPK pathway, is a signal transduction pathway involved in the oncogenesis of a variety of pediatric tumors. The clinical use of BRAF inhibitors and MEK inhibitors is increasingly used in oncology practice. The toxicity profile of these drugs in the pediatric population, particularly in relation to development, growth and sexual maturation remains insufficiently studied. Procedure This study includes 22 pediatric patients with molecularly confirmed MAPK pathway driven tumors treated with MEK or BRAF between August 2014 and March 2020. Throughout treatment they underwent regular laboratory, endocrine, cardiac, ophthalmic and dermatologic evaluation. Toxicity was recorded and evaluated according to CTCA v4. Results Overall an adverse event frequency of 86% was encountered. Dermatological disorders accounted for 68% of the adverse events. Overall 8 patients suffered from severe adverse events including Erythema Nodosum, PLEVA-like rash, osteoporosis, Sarcoid-like massive lymphadenopathy, retinal toxicity and elevated liver enzymes & CPK. Four patients discontinued treatment as a result of adverse events. In this cohort we did not encounter any treatment-related abnormalities of sexual maturation or gonadal function nor statistically significant growth retardation, however a slower than expected growth rate was observed in one patient. In addition dose-dependent, non-symptomatic and within normal range for age decreased cardiac SF% was noted in two patients treated with MEK inhibitor. Conclusion Treatment with BRAF and MEK inhibitors was shown to be generally safe, we report drug tolerability of 82%. However, further prospective studies should be preformed to are characterize the full scope of side effects in the pediatric population.