Inflammatory Nodules Following Soft Tissue Filler Use: A Review of Causative Agents, Pathology and Treatment Options

Abstract

Nodule development is a common complication following the use of fillers for soft tissue augmentation and is commonly categorized as inflammatory or non-inflammatory in nature. Inflammatory nodules may appear anywhere from days to years after treatment, whereas non-inflammatory nodules are typically seen immediately following implantation and are usually secondary to improper placement of the filler. Although inflammatory nodules are more common with permanent fillers such as silicone, inflammatory nodule development following administration of temporary fillers such as hyaluronic acid and collagen has also been reported. Treated many times with corticosteroids due to their anti-inflammatory properties, inflammatory nodules may be secondary to infection or biofilm formation, warranting the use of alternative agents. Appropriate and prompt diagnosis is important in avoiding delay of treatment or long-term complications for the patient. This paper addresses the etiology, development, and studied treatment options available for inflammatory nodules secondary to each of the major classes of fillers. With this knowledge, practitioners may expeditiously recognize and manage this common side effect and thus maximize functional and aesthetic benefit.

Consensus Recommendations for Optimal Augmentation of the Asian Face with Hyaluronic Acid and Calcium Hydroxylapatite Fillers

“…7,49 More severe reactions are fortunately rare but do occur, and may be divided into those that occur early after implantation and those that can appear weeks to years after treatment. 50 Treatment recommendations for these complications focus on both prevention and management (Table 16).…”

Polymethylmethacrylate-induced nodules of the lips: Clinical presentation and management by intralesional neodymium:YAG laser therapy

“…Nodules may also be due to biofilm formation or infection (da Costa Miguel, Nonaka, dos Santos, Germano, & de Souza, 2009;Ledon et al, 2013). Nodules may also be due to biofilm formation or infection (da Costa Miguel, Nonaka, dos Santos, Germano, & de Souza, 2009;Ledon et al, 2013).…”

“…In general, PMMA-induced adverse events include (a) nodular masses, (b) inflammation, (c) allergic reactions, and (d) discoloration (Park, Seo, Kim, & Chang, 2012 Ledon et al, 2013). Cutaneous sarcoidal granulomas have been observed after PMMA filler injection in a patient with previously unknown systemic sarcoidosis (Sidwell, McL Johnson, Francis, & Bunker, 2006).…”

Delayed sclerosing granulomatous reaction to dermal filler injection of poly‐hydroxyethyl‐methacrylate suspended in hyaluronic acid: Histochemical and confocal laser scanning microscopical analysis

“…Authors report on the histologic (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. HA is a constituent of several normal tissues and, as such, does not lead to adverse reactions; therefore, when FBGs develop, 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 .…”

“…Also, it was postulated that macrophages would incorporate foreign particles, thus keeping the foreign particles in a latent stage. Subsequently, additional priming events (eg, supervening infections) would be needed to re‐activate macrophages, lead to multinucleated giant cell accumulation, and, finally, to fully developed granulomatous reaction . Such pathogenetic mechanism may explain the prolonged course of the disease, with only late development of clinically detectable nodular lesions.…”