<p>Management Patterns of Delayed Inflammatory Reactions to Hyaluronic Acid Dermal Fillers: An Online Survey in Israel</p>

Abstract

Background: Over the past few decades, soft tissue augmentation is ever-increasing, specifically hyaluronic acid (HA)-based filler injections. As the number of these procedures have risen, so have the adverse reactions. Delayed-type inflammatory reactions (DIRs) secondary to tissue fillers are typically classified according to the time of appearance postprocedure and have various presentations including nodules, abscesses, edema, and discoloration. Currently, the treatment of these complications varies among physicians. Objective: The aim of this study was to assess the knowledge and experience of practitioners in Israel who inject HA-based tissue fillers with respect to the management of lateonset procedural complications. Materials and Methods: A survey regarding management and treatment of late-onset inflammatory reactions was sent to 1120 physicians and dentists in Israel who practice tissue filler injections. Results: Three hundred thirty-four out of the 1120 practitioners replied to the questionnaire. The majority of respondents were dentists (group A) comprising 31% of all respondents. Group B accounted for 31% of injectors and consisted of dermatologists (19%) and plastic surgeons (12%), and group C (38%) accounted for all other practitioners; 48.2% of all injectors indicated that they have not previously encountered a DIR, whereas 11.4% responded that they have encountered more than 5 DIRs. In order to assess treatment management, we presented the injectors with a simulatory case of a woman with a lateonset complication. Most injectors referred the patient to the emergency department. When asked to establish a treatment plan, the majority of practitioners prescribed short-term oral steroids, ie, prednisone (35.3%). A limited number of patients were treated with intralesional hyaluronidase (31.4%) injection as only 34% of injectors kept hyaluronidase at their clinic. Conclusion: The varied approach regarding the management of delayed type reactions to HA-based filler injections, reflected in our study, illustrates the existing ambivalence in the current literature regarding the management and therapy of late-onset complications.

The Immunogenicity of Hyaluronic Fillers and Its Consequences

“…12 Groups of experts attempted at defining reactions to hyaluronic acid according to the time of appearance postprocedure: "early" (<14 days), "late" (>14 days to 1 year) or "delayed" (>1 year). [47][48][49] Other authors classified the reactions as early (up to a week), intermediate (duration: from a week to a month) and late (over a month). 50 Currently, late and delayed reactions are considered as one entity named delayed inflammatory reactions (DIR), as their cause is usually not well defined and the treatment is independent from the etiology.…”

“…58 Another term was proposed in 2020: Delayed Inflammatory Reactions (DIR). 48 Chung et al emphasized that DIR included four types of reactions: 1) DTH reactions (correctly called: delayed type IV hypersensitivity); 2) foreign body granulomatous reactions; 3) biofilm; and 4) atypical infections. A DTH reaction is a delayed cellular immune inflammation, which developed in response to an allergen.…”

“…58 As regards antibiotics, it is recommended to use oral ciprofloxacin (500-750 mg twice daily) with tetracycline or macrolide for 3-6 weeks. 42,48 Other authors recommended treatment with broad-spectrum antibiotics (doxacillin or rifampicin for at least 3 weeks) combined with multiple hyaluronidase injections (30-100 units intralesionally). 49,63 However, the use of ciprofloxacin is seen as contributing to severe adverse events (an increased risk of tendinitis and tendon rupture at all ages).…”

“…It revealed that almost half of them had not diagnosed DIR, while 11.4% of them responded that they had observed such a reaction over 5 times. 48 Reactions triggered by products manufactured by Allergan were very well documented during registration trials conducted to assess the safety. A similar reaction was reported in about 1% of 103 patients monitored for 24 months after the administration of Juvederm Voluma ® .…”

<p>Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm</p>

“…A recent Israeli survey illustrated extensive variations in DIRs definition and management protocols. 1 The aim of the current study is to provide a clear, easy-to-follow, stepwise approach to the therapeutic management of DIRs.…”