Mixing Fillers-The Reversal Problem

Facial fi llers have become increasingly popular for masking true age by hiding facial lines, creases and wrinkles but can also be used in none cosmetic procedures for correcting disabling volumetric soft tissue loss in HIV associated facial lipoatrophy, Romberg disease and post-surgical and traumatic facial disfi guration [1,2]. When dermal fi llers are performed by experienced, well-trained practitioners, adverse events occur in less than 1% of patients and most of these are transient [3].


Introduction
Facial fi llers have become increasingly popular for masking true age by hiding facial lines, creases and wrinkles but can also be used in none cosmetic procedures for correcting disabling volumetric soft tissue loss in HIV associated facial lipoatrophy, Romberg disease and post-surgical and traumatic facial disfi guration [1,2]. When dermal fi llers are performed by experienced, well-trained practitioners, adverse events occur in less than 1% of patients and most of these are transient [3].
There are a number of studies discussing the ideal characteristics of soft-tissue fi lling material and the consensus on this is that the fi ller must have an acceptable longevity, biocompatibility, non-migratory, low adverse event profi le, and a reasonable cost-benefi t ratio.
Fillers can be classifi ed chemically as being biological or synthetic. Biological include bovine collagen, animal hyaluronic acid, and autologous fat. Synthetic fi llers include non-animal hyaluronic acid, Polymethyl Methacrylate (PMMA) microspheres, and hydroxyapatite micro-particles.
As well as classing these materials chemically they are also classed in terms of their longevity, short acting, long lasting or permanent [4].
In order to get both the ideal fi ller compatibility fi llers are being increasingly used in combination to achieve the ideal outcomes as in the following case where hyaluronic acid was used with calcium hydroxyapatite. Hyaluronic Acid (HA) has become one of the most popular facial aesthetic augmentation fi ller agents [5]. HA is a long unbranched polysaccharide found naturally in all tissues and body fl uids of vertebrates, HA has features that make it an attractive substance for dermal fi ller use, such as its ability to bind to large amounts of water, its natural presence in the skin, and its low potential for adverse reactions. There are many different types of HA based on its crosslinked capabilities which can change its longevity, fi rmness and biocompatibility [6]. Calcium Hydoxyapatite (CaHA) received food and drug administration approval for aesthetic use in 2006 for the correction of moderate to severe facial wrinkles and folds. It provides immediate correction with a 1:1 ratio of CaHA to tissue volume [7], and since its approval it has received a good safety record [8]. However, with ever Abstract Background: Injection of dermal fi llers has become one of the most frequent cosmetic procedures. Serious complications as a result are rare but can result in devastating results for both patient and clinician. Skin necrosis is one of the most severe complications and considering this, there is only very minimal incidence of such events reported in the literature along with diagnosing and treating this adverse event. Reversal agents can often resolve such complications; however, this article looks at the challenges when such agents are unavailable.

Methods:
We present a case of a 32-year-old gentleman who suffered from skin necrosis as a consequence of a mixed hyaluronic acid and calcium hydroxyapatite cosmetic injectable fi ller and discuss the diagnosis and possible treatment plan accompanied by avoidance of such adverse side effects.
Conclusion: Skin necrosis associated with dermal fi llers is a rare event but is an important risk factor to discuss when consenting individuals for the procedure. The increasing use of Calcium Hydroxyapatite as an additive to hyaluronic acid means that fi llers cannot be reversed as straight forwardly leading to a higher risk of irreversible or partially reversible facial skin necrosis. increasing demand for facial aesthetic treatments there is higher incidence of adverse events.

Case report
A 32-year-old male presented to the A and E department in Bath, England, complaining of worsening facial swelling to his left cheek following non-surgical injection of facial fi llers to augment his cheek profi le. Upon discussion, this was the 8 th time he had received this treatment and explained it was carried out every 9-12months. Since treatment 2days ago he suffered from pain and a throbbing sensation to the area plus changes in the color of his skin. He described the area as feeling different and hard and painful to touch. 5. Outline periphery of lesion with skin marker to assess for improvement or deterioration.
Following 24 hours of inpatient hospital care the patient was discharged following marked reduction in symptoms and reduced swelling, erythema and reduction in the dusky appearance noted upon presentation (Figure 2). The patient was subsequently followed up at 3day intervals for 2weeks to ensure full resolution.

Figure 2:
Following 24 hours of inpatient hospital care the patient was discharged following marked reduction in symptoms and reduced swelling, erythema and reduction in the dusky appearance noted upon presentation.

Discussion
Every aesthetic procedure has its potential risks, and each individual case is uniquely different. Specifi c regions of the face are at a higher risk for complications due to critical structures and the vascular system that supplies each area, the glabella and nasolabial fold being higher risk sites [10]. It's important that clinicians have an understanding of potential structures that could cause complications prior to surgery, knowing the specifi c techniques to administer each dermal fi ller and volume enhancer, knowing which specifi c high-risk areas to avoid, and knowing what to do if complications occur form the basis to ensure safe and optimal clinical outcomes with augmentation procedure. There is an argument to include this as standard in the undergraduate dental program to standardize training, improve patient protection and to regulate the industry [11].
The recommendation that fi llers should be distributed via small boluses of 0.1 mL or less should be balanced by the risk of injecting a larger number of sites, along with the diffi culty of getting reliable fl ashback into the syringe through fi ne needles fi lled with thick gels [12]. Deep tissue scars may stabilize and fi x arteries in place, making them easier to penetrate with small sharp needles as in the above case, previous injections to the same site is likely to increase the risk of intra-arterial injection.
Although injecting high volumes into an individual site may cause external vascular compression, attempting to recreate this mechanism has failed [13]. The more likely mechanism of skin necrosis following fi llers is intra-arterial injection.
The human face has a rich vascular network, and given the numerous collaterals and anastomoses present between vascular areas, it presents a target-rich situation. However, the presence of collateral pathways is also protective obstruction of any particular pathway often opens alternatives to provide satisfactory blood supply [13].
The clinician treating the above patient had combined fi lling materials using both HA and Calcium Hydroxyapatite meaning that only the HA aspect could be reversed using the hyaluronidase reversal agent [14]. Although evidence is emerging of possible CaHA reversal agents in the form of sodium thiosulfate, not enough in vivo testing has been carried out to make this at present a viable solution. Therefore, there is a higher risk that the blood supply to this tissue will be occluded for a greater amount of time, increasing complication risks following inter-arterial injection.

Conclusion
The use of dermal fi llers for facial aesthetics is increasing rapidly, due in large part to enhanced public interest in these products, and a larger range of effective options available for a number of cosmetic enhancements. A thorough understanding of facial anatomy is required by the clinician including a consideration into product selection and placement. Should early side effects be noted such as blanching of the skin, these should be treated early to avoid more serious complications as in this case. Although serious complications are rare, clinicians require suitable training in order to manage them early and correctly. More research is required into reversal agents for CaHA and this should be considered by clinicians when deciding whether it should be used in conjunction with hyaluronic acid.

Consent
Full written consent was achieved from the patient to publish the case fi ndings.