Granuloma Reaction: a Complication of Dermal Filler: A Review from an Immunological Perspective

Abstract

Background: Granuloma is one of the most common complications that appear very late after injection of filler material. Due to the multiplicity of filler materials and the increase in the rate of  cosmetic procedures with filler injections, we have witnessed an increase in the rate of occurrence  of granuloma. Objectives: This review was conducted to shed light on the causes of these complications and why they appear in some products and procedures but not others, with the specific aim of identifying the safest materials and those least likely to cause granulomas. Methodology: A narrative review of the literature was conducted using Google Scholar, ResearchGate, PubMed, and  the US National Institutes of Health. Search terms included "dermal fillers," "granuloma," and "complications." Twelve studies were selected based on their direct relevance to the topic. Results:  Granuloma formation is influenced by particle size, surface shape, and injection duration. Particles  smaller than 20 μm are more easily ingested, which may delay granuloma formation. Irregular or  coarse particles elicit stronger inflammatory responses than smooth, spherical particles. Among the  materials reviewed, polymethyl methacrylate (PMMA) showed the highest rate of immune cell infiltration, while hyaluronic acid (HA) showed the lowest. Calcium carboxymethyl cellulose hydroxylapatite (CaHA-CMC) had the lowest reported rate of granuloma formation. Permanent fillers  carry a higher long-term risk of granuloma formation compared to temporary fillers. Conclusion:  The risk of granuloma formation depends primarily on particle size, surface regularity, and duration of tissue retention. Fillers composed of medium- to large-sized, fine, well-purified particles  with a limited duration of tissue retention appear to be the safest. Clinically, the selection of appropriate fillers should be guided by these findings.