The Role of Endotoxin in Sterile Inflammation After Implanted Acellular Dermal Matrix: Red Breast Syndrome Explained?

Background Red breast syndrome (RBS) is a non-infectious erythema associated with acellular dermal matrix (ADM). The underlying cause remains unknown despite multiple suggested etiologies. No similar presentations to RBS have been reported in other anatomic regions. Objective To describe and identify a common etiology for ADM-associated sterile inflammation in the breast and upper extremity. Methods A retrospective review of medical complaints reported to MTF Biologics (Edison, NJ) from July 1, 2017 to January 3, 2018 was performed. Inventory samples were tested for endotoxin content in endotoxin units (eu) via the Limulus Amebocyte Lysate (LAL) method to determine a common etiology for sterile inflammation. Results Cases of RBS and upper extremity sterile inflammation, “red hand syndrome” (RHS), are presented. Two patients developed RBS following implantation of ADM from the same donor; associated grafts in inventory had endotoxin levels of 167 eu and 320 eu per graft, respectively. Two patients developed RHS after joint arthroplasty with ADM from another donor; associated graft in inventory showed endotoxin level of 1,282 eu. Cultures were negative in 3 of the 4 cases obtained. Since endotoxin screening of ADM donor lots began in January 2018 at MTF Biologics, no cases of sterile inflammation have been reported from screened units through December 31, 2018 (RBS rate, 39/15,529 [0.25%] vs. 0/18,275 [0%], p<0.0001). Conclusion The sterile inflammatory response in RBS and newly reported red hand syndrome may be attributable to the presence of endotoxin in implanted ADM. Endotoxin screening has been adopted by MTF Biologics with significant decrease in reported reactions.