The Evolution of Prepubertal Localized Aggressive Periodontitis in Primary and Mixed Dentition—Clinical Evidence

Background/Objectives: Prepubertal localized aggressive periodontitis/LPP is an extremely rare but extremely fast-progressing form of periodontal disease involving systemically healthy children, starting in primary and mixed dentition. Our aim is to synthesize the data (January 2014–April 2026) on LPP progression description in systemically healthy children aged 2–13 years; clinical and biological responses to available treatment strategies, focusing on disease progression pattern, treatment efficacy and factors influencing treatment outcomes; and correlating findings with a report of a 24-month follow-up of a female prepubertal Caucasian patient during the primary and early stages of mixed dentition. Methods: A total of 489 studies were found after deduplication for the selected period. Due to the eligibility criteria, 9 studies plus another 10 contextual publications were included. Additionally, a 24-month follow-up of a previous LPP case was correlated. Results: LPP displayed rapid tissular destruction in primary dentition with risks to transfers to mixed and permanent dentition. The systemic antibiotic treatment reduced tissue loss, enabling fast periodontal regeneration. LPP is rare but severe, with a continuous biological trajectory, and with the window of opportunity remaining when the first symptoms appear. A few months (4–6 months) delay in diagnosis leads to irreversible tooth loss even in young patients with high biological healing potential. Conclusions: Systemic antibiotic treatment is mandatory in LPP/C-MIP cases from the primary dentition phase but does not reset host susceptibility. The Amoxicillin/Augmentin–Metronidazole association is recommended, with caution regarding dosage (adverse reactions). Periodontal gains are radiologically and clinically proven, but rebounding is possible.