Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm

Ofir Artzi,1,2 Joel L Cohen,3 Jeffrey S Dover,4– 6 Atchima Suwanchinda,7,8 Tatjana Pavicic,9 Marina Landau,10 Greg J Goodman,11 Sahar Ghannam,12 Firas Al Niaimi,13 Jani AJ van Loghem,14 Kate Goldie,15 Sonja Sattler,16 Daniel Cassuto,17 Ting Song Lim,18 Rungsima Wanitphakdeedecha,19 Ines Verner,20,21 Tanja C Fischer,22,23 Vivian Bucay,24 Eli Sprecher,1,2,25 Dana Shalmon1,2 1Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3AboutSkin Dermatology and AboutSkin Research, , Greenwood Village and Lone Tree, CO, USA; 4SkinCare Physicians, Chestnut Hill, MA, USA; 5Dermatology, Yale University School of Medicine, New Haven, CT, USA; 6Dermatology, Brown Medical School, Rhode Island, USA; 7Department of Dermatology, School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, Bangkok, Thailand; 8Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 9Private Practice for Dermatology and Aesthetics Dr. Tatjana Pavicic, Munich 80539, Germany; 10Dermatology, Private Practice, Herzliya, Israel; 11Monash University, Clayton, Victoria, Australia; 12Associate Prof. of Dermatology, Alexandria University, Alexandria, Egypt; 13 152, Harley street, London, UK; 14UMA Institute, Amsterdam 1017, TX, Netherlands; 15Medical Director European Medical Aesthetics Ltd, London W1G 8QN, UK; 16Rosenpark Klinik, Darmstadt, Germany; 17Private Practice, Milan, Italy; 18Clique Clinic, Kuala Lumpur, Malaysia; 19Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 20Verner Clinic, Tel Aviv, Israel; 21Department of Dermatology, University of Rome, Guglielmo Marconi, Italy; 22Skin and Laser Center, Potsdam, Germany; 23School of Medicine, University of Frankfurt, Germany; 24Bucay Center for Dermatology and Aesthetics, UTHSC, San Antonio, TX, USA; 25Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Ofir ArtziTel Aviv Sourasky Medical Center, Weizman 6, Tel Aviv, IsraelTel +972-54-5968961Fax +972-77-2001801Email ofira@tlvmc.gov.ilBackground and Objectives: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose.Materials and Methods: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists.Results: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3– 6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement.Conclusion: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.Keywords: cosmetic techniques, dermal fillers/adverse effects, hyaluronic acid/adverse effects