Risk Profiles of Different Injectable Fillers: Results From the Injectable Filler Safety Study (IFS Study)

By Hendrik Zielke, M.D., Linn Wölber, M.D., Luitgard Wiest, M.D., & Berthold Rzany, M.D., ScM
Published in Dermatol Surg 2008, 34;3:326–335

Introduction

Facial filler injections are one of the most popular esthetic treatments. Due to the newness of many of these substances, there has been limited information available regarding long-term adverse reactions from facial filler injections and the time of onset. The purpose of this study was to evaluate complication type and frequency resulting from facial filler treatments via case submission.

Materials and Methods

Dermatologists, plastic surgeons, and maxillofacial surgeons from Berlin were invited to participate in the Injectable Filler Safety Study (IFS) Study. The physicians were asked to report any adverse events related to facial filler injections that occurred from January 1999 to December 2003. Adverse events included pain, erythema for more than one week, nodule formation, discoloration, hyperpigmentation, ulceration, and abscess formation. Physicians faxed these cases to the authors who then interviewed the patient utilizing a formatted questionnaire. Data collected included:

• Personal data
• Risk factors
• Prior injectable filler treatments
• Reaction type, location, duration, and outcome
• Reaction intensity rate on a severity scale based on discoloration, nodularity, pain, swelling, and erythema

Results

Fifty-six patients with an average age of 48.5 years were assessed. Nine different filler substances were evaluated. Five forms of hyaluronic acid fillers were evaluated:
Restylane® (Medicis, Scottsdale AZ)
Perlane® (Medicis, Scottsdale, AZ)
Hylaform® (Allergan/Inamed, Irvine CA)
Matridur® (BioPolymer GmbH & Co., Montbaur, Germany)
Dermalive® (Dermatech, Paris France)

Other fillers evaluated included:
Sculptra™ (Sanofi-Aventis, Bridgewater NJ)
ArteFill® (Artes Medical, San Diego CA)
Aquamid® (Contura International, Soeborg, Denmark)
liquid injectable silicone

The average onset of complications involving biodegradable fillers occurred 4.9 + 5.8 months following treatment. The average onset of complications involving non-biodegradable fillers occurred 18.3 + 19.0 months following treatment. The most common complications included pain, swelling, nodules, pigmentation, abscess, and erythema.

Discussion

This study focused on the type and profile of facial filler complications as related to the type of filler substance used. The most common complications observed with hyaluronic acid fillers were swelling, erythema, and nodules. All of the patients experiencing complications following poly-L-lactic acid suffered from granulomas. Reactions resulting from PMMA included nodules and inflammation. PMMA treatment complications showed the longest time frame for complication onset at 37.1 + 25.4 months. Dermalive® injection treatments resulted in the most severe reactions for erythema and granulomas. PAG complications were pain, nodule formation, and hyperpigmentation.

Conclusion

The authors of the study concluded that adverse events are experienced with all dermal filler products. They suggested that development of complication profiles for the respective filler substances would result in better filler selection for patient treatment. Non-biodegradable facial fillers need to be more closely examined, due to the difficulty of complication management.

Reviewer’s Comment

Because the number of treatments each physician provided is unknown, it is difficult to gauge the incidence of adverse events. Filler complications and adverse events are product related, injection related, or technique related. The commentary in the study indicated that there is bias. The fact that 51% of the patients that experienced an adverse event did not return to the physician who treated them does not allow for proper evaluation. Without the ability to assess the number of treatments versus the number of adverse events, it is not possible to determine the frequency of either the complication or the contributing factors. It is the reviewer’s opinion that many of the events experienced by these patients were technique driven and the result of an untrained treatment provider.

Reprint requests: Berthold Rzany, M.D., ScM, Division of Evidence-Based Medicine, Department of Dermatology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.