Red Breast Syndrome (RBS) is an uncommon inflammatory complication that may occur following implant-based breast reconstruction and can clinically mimic cellulitis or surgical-site infection. This qualitative systematic review, based on comprehensive PubMed and Scopus searches conducted through October 31, 2025, summarizes the existing literature on RBS, focusing on its etiology, clinical presentation, diagnostic characteristics, and therapeutic approaches following breast reconstruction using acellular dermal matrices (ADMs). A management protocol is proposed based on available data, and a single-center case series is presented from the University Hospital of Udine (Italy), including patients who developed RBS after direct-to-implant (DTI) reconstruction with ADM between January 2022-December 2024. Twenty-nine studies met the inclusion criteria, comprising case reports, case series, and retrospective or prospective cohort studies. The reported incidence of RBS ranged from 0%-29.6%. Proposed etiologies include endotoxin contamination, residual cellular debris, delayed hypersensitivity reactions, and lymphatic or vascular impairment of mastectomy flaps. Most reports described localized erythema confined to the area of the ADM, with normal inflammatory markers and negative imaging findings, while antibiotic therapy frequently failed to achieve improvement. Corticosteroids represented the most consistently effective treatment, although some cases required ADM removal or replacement. In our institutional case series (n = 8), symptom onset occurred between 4 weeks and 7 months post-surgery. Inflammatory markers remained within normal limits, imaging rarely demonstrated fluid collections, and symptoms resolved within days to weeks with corticosteroid therapy or conservative management. Study limitations include overall low methodological quality, heterogeneity of ADM types and reporting standards, and small sample sizes. This review consolidates current evidence, proposes a diagnostic-therapeutic algorithm to differentiate RBS from infection, and highlights the need for prospective investigations and manufacturer-level endotoxin testing to elucidate pathogenesis and optimize clinical management.
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