DELAYED SCLEROSING GRANULOMATOUS REACTION TO HYALURONIC ACID REINFORCED WITH POLY-HYDROXY-ETHYL-METHACRYLATE INJECTION

Abstract

Objective On the basis of manufacturers’ and some authors’ claims, all commonly used injection materials for aesthetic correction and different formulations of hyaluronic acid (HA), with or without adjunctive substances, result in no immunogenic reactions or other complications; nevertheless, unexpected, late or early adverse reactions have been reported. Overall, HA reinforced with hydroxyethyl-methacrylate (HEMA) can promote the formation of late foreign body granulomas (FBGs). The authors report on the histological (conventional and confocal laser scanning microscopy) features of a case occurred 10 years after the injection of HA+HEMA in the lower lip of a female patient. Findings The nodular lesion was mainly composed by several almost empty and polygonal spaces, surrounded by fibrous collagen and sparse multinucleated giant cells, pointing at long-standing FBG. The polygonal spaces were 20–120m in size and partly filled with translucent particles, with a broken-glass appearance. Conclusions HA is a constituent of several normal tissues and, as such, does not lead to adverse reactions. When FBG is present, one should argue that additional components were bound to HA. HEMA has been used as a stabilizer of HA-based fillers but it is known to induce transient macrophagic reaction, fibroblast proliferation with scarce collagen deposition and multinucleated giant cells. The morphological features of the present case are consistent with previous injection of HA+HEMA and the prolonged time interval from injection to clinical manifestations indicates the adverse reaction is slowly progressive. Also, it was postulated that macrophages would incorporate foreign particles, thus keeping the foreign particles in a latent stage. Subsequently, additional priming events (e.g., supervening infections) would be needed to re-activate macrophages, lead to multinucleated giant cell accumulation and finally to wide granulomatous reaction. Such pathogenetic mechanism may explain the prolonged course of the disease, with only late development of clinically detectable nodular lesions.