Discussion: Preliminary Results Supporting the Bacterial Hypothesis in Red Breast Syndrome following Postmastectomy Acellular Dermal Matrix- and Implant-Based Reconstructions.

Abstract

www.PRSJournal.com 993e D et al. seek to study a potential role of bacterial biofilms in the development of red breast syndrome.1 As the authors note, red breast syndrome is essentially a diagnosis of exclusion, where erythema of the skin overlying acellular dermal matrix develops days to weeks after implant reconstruction with no systemic signs of infection.2 As the authors themselves point out, the cause, incidence, time to onset, exact clinical definition, and appropriate treatment of red breast syndrome are either unknown, variable, or unclear. I commend the authors for their willingness to study red breast syndrome. In my view, fundamental methodologic flaws limit the value of this study. The authors describe prospective recruitment of study patients; however, an internal review board statement is lacking. This study has no control group against which samples from patients with red breast syndrome can be compared. The breast parenchyma and skin are known reservoirs of bacteria with substantial diversity that includes Gram-positive and Gram-negative organisms.3–6 The authors refer to a historical control of acellular dermal matrices from asymptomatic patients where bacteria were imaged on some, but not all, acellular dermal matrices.7 Experimental conditions, however, vary substantively between the studies. For one, the majority of patients presented with red breast syndrome within 3 to 4 weeks of implantation,1 whereas specimens were procured 4 to 16 months after implantation in the authors’ former work.7 Recovery time alone could have impacted the inflammatory and host immune response between cohorts. Sampling bias is another major issue with this work. Understandably, the authors limited their acellular dermal matrix biopsy specimens to a lateral 1-cm2 piece for culture and another for scanning electron microscopy to avoid aesthetic deformity. To put this in context, though, these two specimens represent only 1.5 percent of the surface area of a 128-cm2 sheet of acellular dermal matrix. Leaders in the field of biofilm research recommend a multiprong approach that speciates bacteria and then visually confirms their presence through imaging.8–16 The authors do perform cultures and scanning electron microscopy; however, as presented, we have no idea whether imaged and cultured bacteria correlated with one another. In fact, although I presume that the presented micrographs are from specific study patients, the authors do not actually confirm this. As the authors point out, characterizing bacterial biofilms can be challenging, but the authors should have leveraged other modalities to improve the relevance of their work.9,13,16 Immunohistochemistry with bacteria-specific antibodies could confirm the presence of (and inform the distribution of) cultured bacteria on acellular dermal matrix specimens. Background noise can limit the effectiveness of this approach on occasion. 16S rRNA sequencing of specific ribosomal hypervariable regions accompanied by alphaand beta-diversity analyses would characterize the relative composition of the microbiome on procured specimens even in the presence of biofilms embedded in a dense extracellular polymeric substance. This technology has its own set of limitations, however, and may not be broadly available.17 Another approach that the authors should consider as they continue to study red breast syndrome is metabolomics. In this approach, low-molecularweight molecules including intracellular metabolites and secreted extracellular molecular weight molecules can function as indicators of a disease process within a biological system.18 Metabolomics interrogates the host-pathogen interface, so that recovery of a difficult-to-identify biofilm is not required, thereby providing a workaround