Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections

Greg J Goodman; Cara B McDonald; Adrian Lim; Catherine E Porter; Anand K Deva; Mark Magnusson; Anita Patel; Sarah Hart; Peter Callan; Alice Rudd; Stefania Roberts; Katy Wallace; Philip Bekhor; Michael Clague; Linda Williams; Niamh Corduff; Nina Wines; Firas Al-Niaimi; Sabrina G Fabi; Howard M Studniberg; Saxon Smith; Angelo Tsirbas; Sean Arendse; Antoinette Ciconte; Terence Poon

doi:10.1093/asj/sjad028

Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections

Aesthet Surg J. 2023 May 15;43(6):NP438-NP448. doi: 10.1093/asj/sjad028.

Authors

Greg J Goodman¹, Cara B McDonald², Adrian Lim³, Catherine E Porter⁴, Anand K Deva⁵, Mark Magnusson⁶, Anita Patel⁷, Sarah Hart⁸, Peter Callan⁹, Alice Rudd¹⁰, Stefania Roberts¹¹, Katy Wallace¹², Philip Bekhor¹³, Michael Clague¹⁴, Linda Williams¹⁵, Niamh Corduff¹⁶, Nina Wines¹⁷, Firas Al-Niaimi¹⁸, Sabrina G Fabi¹⁹, Howard M Studniberg²⁰, Saxon Smith²¹, Angelo Tsirbas²², Sean Arendse²³, Antoinette Ciconte²⁴, Terence Poon²⁰

Affiliations

¹ Honorary professor at the University College of London, London, United Kingdom.
² Dermatologist, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
³ Practicing dermatologist, Department of Dermatology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
⁴ Cosmetic physician in private practice in Sydney, New South Wales, Australia.
⁵ Professor, Department of Plastic and Reconstructive Surgery, Macquarie University, Sydney, Australia.
⁶ Associate professor, Department of Plastic and Reconstructive Surgery, Griffiths University Southport, Queensland, Australia.
⁷ Dermatologist in Private practice in Bondi Junction, New South Wales, Australia.
⁸ Aesthetic physician in private practice in Auckland, the North Island, New Zealand.
⁹ Specialist plastic surgeon in private practice in Geelong, Victoria, Australia.
¹⁰ Dermatologist, Department of Dermatology, Alfred Hospital Prahran Victoria, Victoria, Australia.
¹¹ Aesthetic physician in private practice in Melbourne, Victoria, Australia.
¹² Nurse practitioner at a private dermatology practice in South Yarra, Victoria, Australia.
¹³ Dermatologist, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
¹⁴ Cosmetic nurse in private practice in South Yarra, Victoria, Australia.
¹⁵ Cosmetic physician in private practice in East Brisbane, Queensland, Australia.
¹⁶ Plastic surgeon in private practice in Geelong, Victoria, Australia.
¹⁷ Principal dermatologist in private practice in Sydney, New South Wales, Australia.
¹⁸ Dermatologist, Department of Dermatology, Aalborg University, Aalborg, Denmark.
¹⁹ Dermatologist, Department of Dermatology, University of California San Diego, La Jolla, CA, USA.
²⁰ Dermatologist in private practice in Sydney, New South Wales, Australia.
²¹ Dermatologist at the Sydney Clinical School, ANU Medical School, College of Health and Medicine, Australian National University, Canberra, ACT, Australia.
²² Oculoplastic surgeon in Sydney, New South Wales, Australia.
²³ Cosmetic physician in private practice in Melbourne, Victoria, Australia.
²⁴ Dermatologist at Eastern Health Hospital, Box Hill and Canterbury, Victoria, Australia.

Abstract

Background: The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain.

Objectives: To formulate a rational theory for DTN development and their avoidance and treatment.

Methods: A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement.

Results: Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide.

Conclusions: The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors-filler, inflammation, and infection-separately.

MeSH terms

Cosmetic Techniques* / adverse effects
Dermal Fillers* / adverse effects
Humans
Hyaluronic Acid / adverse effects
Inflammation / etiology
Injections

Substances

Hyaluronic Acid
Dermal Fillers