Hypersensitivity reactions to Hyaluronic acid fillers are very uncommon with the incidence quoted as being between 0.3 and 4.25%. A literature review would place the 4.25% figure as an outlier with a more accurate average incidence being between 0.3 and 0.9%.
Nevertheless, this condition is an important one, about which all injectors need to be aware, and which appears to go under-recognised. The Delayed Type IV Hypersensitivity reaction is mediated by T-lymphocytes rather than antibodies. It may not appear for weeks or even months after the injection event and because of the T lymphocyte involvement the trigger may be another immunological event such as a viral infection. Macrophages can retain an immunological memory. Unpredictability of foreign body granuloma may be explained by infection or a drug interaction acting as such a trigger. This may also explain why such reactions may occur even many years after the biodegradation of the HA implant.
The details of such a possible aetiology of delayed hypersensitivity in relation to HA fillers is not completely understood.
HA, is not considered as an antigen itself, but given it is a glycosaminoglycans molecule and present in large qualities through our skin it can be implicated in a variety of dermatological responses. But it is not just the HA to consider. In all formulations of HA injectable products there are adjuvants such as cross-linking chemicals and a variety of preservative products as well as their degradation products. Such degradation products include low molecular weight HA fragments which can act as pro-inflammatory agents.
From a treatment perspective, a critical element is an awareness of the possibility of the Delayed Type IV Hypersensitivity reaction and a recognition of the salient features, swelling, induration, possible pain and tenderness and sometimes the presence of nodules. Timing of onset is also a signal feature often occurring some weeks or even months after the injection episode.
Treatment will include Hyalase and very possibly antibiotics to cater for the possibility of infection, albeit perhaps subclinical, and associated with biofilm. Early referral to an appropriately experienced practitioner should be considered if the injector is unsure of either the diagnosis or its management. Surgical drainage should only be used as a last resort not the first response, as most of these reactions can be managed conservatively.
Below is a short bibliography of interesting articles which are readily found on a web search. I would encourage you to access some of these and form your own opinions.
Mohammed G Turkmani,1 Koenraad De Boulle,2 and Wolfgang G Philipp-Dormston3. Delayed hypersensitivity reaction to hyaluronic acid dermal filler following influenza-like illness. Clin Cosmet Investig Dermatol. 2019; 12: 277–283.
Beleznay K, Carruthers JD, Carruthers A, Mummert ME, Humphrey S. Delayed-onset nodules secondary to a smooth cohesive 20 mg/mL hyaluronic acid filler: cause and management. Dermatol Surg. 2015;41:929–939.
Arron ST, Neuhaus IM. Persistent delayed-type hypersensitivity reaction to injectable non-animal-stabilized hyaluronic acid. J Cosmet Dermatol. 2007;6:167–171.
Lee JM, Kim YJ. Foreign body granulomas after the use of dermal fillers: pathophysiology, clinical appearance, histologic features, and treatment. Arch Plast Surg. 2015;42:232–239.
De Boulle K, Heydenrych I. Patient factors influencing dermal filler complications: prevention, assessment, and treatment. Clin Cosmet Investig Dermatol. 2015;15(8):205–214.
Tahera Bhojani-Lynch, MRCOphth, CertLRS, MBCAM, DipCS. Late-Onset Inflammatory Response to Hyaluronic Acid Dermal Fillers. Plast Reconstr Surg Glob Open. 2017 Dec; 5(12)