Overdiagnosis of complications related to hyaluronic acid-based fillers leading to inappropriate therapeutic management

Introduction

Hyaluronic acid (HA) is a commonly used soft tissue filler that is popular due to its properties, such as low immunogenicity, stability, biocompatibility, and stimulation of neocollagenesis [1]. There is a wide range of HA-based fillers, which differ in price, quality, composition, or appropriate medical certificates [2]. They are generally considered safe. However, some complications can occur [3]. Cross-linked HA may result in overcorrection, Tyndall effect, infections, granulomas, embolic complications, or soft tissue necrosis [4].
Hyaluronidase injection is the treatment of choice for complications of cross-linked HA injections [5]. Hyaluronidase formulations differ in their qualities, such as biological origin and concentration. Additionally, some hyaluronidase products are not registered as drugs. These factors and a small number of reported complications result in the lack of a universal protocol for the dose and modality of administration [6]. Unfamiliarity with the previously used HA-based medical device, which usually occurs during the procedures performed by non-physicians, poses another difficulty in the treatment of the complications. We presented a patient in whom overdiagnosis of HA-related complications resulted in unnecessary delay in treatment.

Objective

The aim of the study was to underline importance of detailed clinical examination in the era of rapid technological development.

Case report

A 27-year-old woman presented to our clinic due to an undesirable aesthetic effect after 5 lip augmentation sessions with a dermal (probably HA-based) filler of unknown origin. The procedure had been performed by a non-physician. As a result, the lips were asymmetrical and swollen, with visible areas of mucosal hardening (fig. 1). In addition, the patient reported sensory distortion, paraesthesia in the labial area, impaired orbicularis oris muscle function, and asymmetry. Extensive diagnostic examinations were introduced in the first medical centre that the patient visited after the initial procedures. Ultrasound showed diffuse fibrosis and the filling material of heterogeneous echostructure at a depth of 2 mm (up to 5 mm in thickness). The patient reported that she had been given several hyaluronidase injections. Core biopsy of the upper lip was performed. The biopsy samples were sent for examination to the Department of Toxicology in Wrocław, Poland. HA was not found in any of the 6 biopsy samples. From November 2021 to January 2022, 10 procedures using unipolar radiofrequency were performed to heat the deposits of the implant and reduce its volume. However, the series of treatment did not result in clinical improvement. Due to persistent symptoms, the patient was consulted with a plastic surgeon, who suggested surgical excision. The patient presented to our clinic in September 2022. Due to the extent of the planned surgical procedure and its potentially unfavourable aesthetic results, hyaluronidase was injected despite the biopsy results that excluded the presence of HA in the biopsy material. We performed the injection of 30 IU of hyaluronidase (Hylase Dessau, Esteve Pharmaceuticals GmbH) diluted in 1 ml of 0.9% saline. In addition, azithromycin 500 mg was administered daily for 3 days to prevent infection. After 14 days, a decrease in the volume of the lips was noted. Softening of the lips was also reported (fig. 2). Next, 50 IU hyaluronidase was injected into the vermilion, which resulted in satisfactory aesthetic and functional effect., Next, the patient presented with excess mucosa due to the oedema associated with the presence of the previous filler (fig. 3). Filling the vermilion with a good quality HA or using fat transfer to shape and volumise it can be considered. Surgical reduction of excess mucosa may also be taken into account where appropriate.

Discussion

Although the use of HA may cause some adverse effects, many complications can be managed by hyaluronidase injection. Even small doses of hyaluronidase (< 3 IU) are effective in the treatment of HA overcorrection in the areas such as lower eyelids. Despite the lack of a consensus on the dosage of hyaluronidase depending on the type of HA, various complications, and the areas of application, guidelines on its dosage can be found in the literature (15–30 IU – perioral and perinasal areas, 30 IU – orbital area, 10–15 IU – suborbital area, 1.5 IU – lower eyelid) [7]. Due to the recommendations of the Aesthetic Dermatology Section of the Polish Dermatological Society, in most cases the dosage of 5–150 IU/1ml of hyaluronidase is enough to eliminate nodules. Most authors recommend higher doses of hyaluronidase [8].
Of note, we observed several problematic aspects in our case. Firstly, the primary procedures had been performed by a non-physician using material of unknown origin and composition. However, there was a risk that the material was different than HA. Secondly, the patient had initially been overdiagnosed by another physician, and several non-effective hyaluronidase injections were given before the biopsy. The reason for this is unknown and may result from the poor quality of hyaluronidase, inadequate reconstitution, or technique. Ultrasonography allows the assessment of the density of the filler, the uniformity of its distribution in the tissues, or the echogenicity of the material in relation to the surrounding tissues [9]. Nevertheless, its quality and clinical value depend on clinical experience. The biopsy results discouraged the physician from further attempts to dissolve the deposited formulation using hyaluronidase, which would have been the treatment of choice. Such a watch-and-wait approach resulted from improper performance of the procedure, too low a dose of hyaluronidase, or inadequate quality of the drug, as opposed to our treatment based on effective hyaluronidase administration.
To determine the origin and composition of the filler, a biopsy was performed. However, the biopsy findings did not show the presence of HA, which could have been due to an incorrectly performed (missed) biopsy. As a result, additional examinations discouraged physicians from applying the proper treatment. The patient was offered surgical removal of the material, which, according to the literature, should be implemented as a treatment of last choice [10]. We decided to use hyaluronidase despite the biopsy results. The implemented treatment resulted in significant improvement.

Conclusions

This case shows that although additional tests can be useful in managing complications according to HA procedures, they should not determine management. Additional examinations play an increasingly important role in the diagnosis and treatment of complications related to aesthetic medicine procedures. However, they should be analysed with the clinical presentation. Overdiagnosis can lead to inadequate therapeutic decisions and prolonged and ineffective treatment.

Contribution

Piotr Drozdowski and Aleksander P. Jaworski contributed equally to the work.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

References