Abstract
Background/Objectives: This systematic review analyzed the epidemiologic and macro/microscopic features of manifestations of hypersensitivity reactions with oral and extra-oral involvement in orthodontic patients with fixed (FAs) or removable (RAs) appliances or clear aligners (CAs), and evaluated them based on patient and treatment characteristics to provide clinical recommendations. Methods: The study protocol followed the PRISMA guidelines and was registered on PROSPERO (CRD42024517942). Results: Thirty-one studies were qualitatively assessed and synthetized, involving 858 subjects (114 males and 714 females, 9-49 years old), of whom there were 86 with a history of allergy, and 743 wearing recorded appliances (FAs = 656, FAs and RAs = 81, intra- and extra-oral RAs = 3, CAs = 3), with a mean treatment duration of 21.5 months (6 weeks-40 months). Among 75 reports, 29 (38.67%), describing burning, gingival hyperplasia, erythema, and vesicles, had oral involvement, while 46 (61.33%) had skin, eye, and systemic involvement, with erythema, papules, conjunctival hyperemia, and vertigo. Positive allergy tests concomitant with the manifestations identified nickel 451 times, cobalt 6 times, titanium 5 times, and chromium 4 times. Management included antihistamines or corticosteroids and removing the offending materials, with treatment discontinuation/appliance substitution. Conclusions: Pre-treatment evaluations, including patient histories and allergy testing, are essential to identify potential allergens and select hypoallergenic materials like titanium or ceramic brackets; regular monitoring and early intervention during treatment are crucial to prevent severe outcomes.