Delayed inflammatory reactions to soft tissue fillers are uncommon and usually self-limited, with frequent spontaneous resolution. However, considering the ongoing pandemic and the worldwide demand for vaccines against COVID-19, we as aesthetic providers should be conscious of the risks posed by the interaction of such vaccines in patients who previously had or are seeking dermal filler injections.
In this case, we present a delayed reaction to polycaprolactone (PCL) soft tissue filler treatment of the cheek area following vaccination against SARS-Cov-2. The 55-year-old female who previously had her cheeks treated developed symptoms 48 hours after receiving her second AstraZeneca COVID-19 vaccine.
Filler complications and COVID-19
A wide range of dermal fillers are now available for use in facial aesthetics.1 All are potentially capable of causing complications,2,3 but fortunately, serious occurrences are rare. Careful attention to patient selection, education, and injection technique can minimise the incidence of complications, and an understanding of the early signs of complications and their proactive management can decrease their impact.4
Reactions caused by vaccinations to SARS-CoV-2 in patients with pre-existing filler is now a cause of concern.
There are currently few published cases that demonstrate a delayed inflammatory reaction (DIR) following either the COVID-19 vaccination or COVID-19 infection.5 Specifically, with regard to the Moderna mRNA-1273 trial, there were a total of three reactions possibly related to dermal fillers out of 15,184 vaccine recipients. It is unknown how many subjects in the trial had previous treatment with dermal fillers.6 Over the past six months, River Aesthetics has had one case involving hyaluronic acid and one involving PCL.
It is known that reactions can occur weeks, months or even years after receiving a soft tissue filler treatment when the immune system is challenged.1,2,3,7 Similarly, acute infection with COVID-19 can also profoundly stimulate the immune system and create a delayed inflammatory reaction in a patient who has previously undergone a filler treatment, as detailed below.
Post-filler injection complications vary and can be categorised based on their timing in relation to the filler injection as early events (occurring up to several days post-treatment) or delayed events (occurring weeks to years post-treatment).1,3,8,9
Delayed hypersensitivity reactions are characterised by induration, erythema, and oedema and are mediated by T lymphocytes rather than antibodies.2 They typically occur 48-72 hours after injection but may be seen as late as several weeks post-injection and can persist for months.3
Vaccines
The AstraZeneca vaccine works by delivering the genetic code of the SARS-CoV-2 spike protein to the body’s cells. Once inside the body, the spike protein is produced, causing the immune system to recognise it and initiate an immune response. This means that if the body later encounters the spike protein of the coronavirus, the immune system will recognise it and destroy it before causing infection.10,11
Vaccines safely deliver an immunogen (antigen able to elicit an immune response) to the immune system in order to train it to recognise the pathogen when it is encountered naturally by activating CD4+ helper T cells. This in turn stimulates B-cells to produce neutralising antibodies specific to the virus CD8+ cytotoxic T cells to recognise and kill cells infected by the virus.10 A type IV delayed hypersensitivity reaction occurs following a challenge, namely a vaccination in a sensitised individual. This is the only type of hypersensitivity reaction which is not mediated by antibodies and is instead dependent on the generation of T cells, specifically the TD cells, which contribute to the inflammation and the accompanying tissue damage by the generation and release of a variety of cytokines.12,13
It is known that the spike protein of SARS-CoV-2 enters cells by binding and blockading the angiotensin 2 receptors (ACE2), thus creating a pro-inflammatory response and a proliferation of T cells. A study by Li et al. (2020) demonstrated that the skin has moderately high levels of ACE2 proteins in the basal layer of the epidermis and also lining the vasculature, which may provide the mechanism to why soft tissue fillers may react in an adverse manner.13,14
From studies on other vaccinations, it is known that the immune response from administration to developing an antibody response that the first three weeks are pivotal, and this is when the immune system is most stimulated.15 Data from a study in Israel with a population of 500,000 has provided further evidence. Following the Pfizer vaccine, immunity within the first two weeks of administration remained almost at zero but then rose to about 90% at three weeks and then did not rise any further.15 Considering the above, current guidance from the Aesthetic Complications Expert (ACE) Group World inducates that practitioners should not be performing soft tissue filler treatments either two weeks before or three weeks after COVID-19 vaccination.5
Polycalprolactone properties
The non-hyaluronic acid bioresorbable PCL-based filler has a proven safety profile, but rare potential complications such as nodules and granuloma can occur.16,17 Furthermore, PCL-based fillers cannot be immediately removed by injection of hyaluronidase as it is a polymer but is broken down into H2O and CO2 by cleavage of the ester bonds shortening the polymer over time. These potential drawbacks have yet to be described in the literature.
The PCL-based filler is a collagen stimulator composed of PCL microspheres (30%) suspended in an aqueous carboxymethyl cellulose (CMC) gel carrier (70%),17 which provides an immediate but temporary filling effect. The PCL microspheres contribute to long-term volume by stimulating new collagen production.16 As the CMC gel is absorbed in the first six to eight weeks, the loss in volume from the carrier gel is gradually replaced by the newly formed collagen because of the PCL-induced neocollagenesis.16 In our clinical practice it is used in 60% of our patients due to its compatibility with threads (which we do a lot of) and its natural rejuvenating effects.
The PCL microspheres degrade into non-toxic, bioresorbable products that are metabolised into CO2 and H2O and excreted through normal pathways. The total bioresorption time of the product depends on the length of the PCL-polymer chain; in this regard, three product versions of Ellansé are available: S, M, L and which have bioresorption times of at least one, two, three years, respectively.18
At the time of writing, there were no documented cases of delayed onset nodules (DON) or delayed onset reations (DOR) with the non-replicating adenovirus vaccination that is used for the Oxford/ AstraZeneca COVID-19 vaccination and we were aware of three cases globally regarding DIR with the use of Ellansé.
Reactions can occur weeks, months or even years after receiving a soft tissue filler treatment when the immune system is challenged
Case study
In the initial treatment, formal consents were signed and images were taken. Maintaining a sterile technique Ellansé M was diluted with 0.2ml of 2% Lidocaine for ease of injection and patient comfort. Skin was prepared with Clinisept+ and makeup and other potential skin contaminants removed before injection. The patient was marked out as per Figure 1. Local anaesthesia using 0.1ml of xylocaine and adrenaline were injected at the entry points. Using a retrograde fanning technique, 1ml of product was placed along the zygoma, in the subcutaneous plane, placing 0.05ml per pass using a 25 gauge cannula and 0.2ml was placed into the marionette line bilaterally.
Treatment was uneventful. Both two week and three month reviews were satisfactory with no concerns. The patient had their first COVID-19 vaccination on 22/01/21 with the AstraZeneca vaccine with no adverse effects.
She then received her second vaccination approximately three months later. Within 48 hours of her second dose, the patient developed a scratchy throat, progressive periorbital swelling and allergy symptoms. They took over-the-counter antihistamines and reported mild improvement. However, over the next 48 hours she developed hard masses in her face and worsening facial oedema. The patient contacted the clinic at this point and was advised to come in urgently for a face-to-face assessment (Figure 3).
Patient examination
When the patient presented to the clinic she was anxious and upset, but afebrile. Her blood pressure and pulse were normal, there were no signs of facial erythema or infection, but she had marked periorbital oedema. Solid, non-fluctuant, non-tender masses along zygoma were palpated in areas of product placement and in the marionettes.
The case was reported to the manufacturer Sinclair Pharma and the Medicines and Healthcare products Regulatory Agency (MHRA), and a management plan was discussed with the clinic team.
Once a hypersensitivity reaction was suspected, the time of onset was established and the patient’s medical history was re-reviewed and a full medical examination was undertaken. Blood tests for inflammatory markers CRP, ESR, FBC and autoimmune profile were also arranged.
The complication was thought to be immunological in nature, as all injected areas were affected
Management plan
The case was discussed with Sinclair Vigilance and ACE Group World guidance was considered.5 The complication was thought to be immunological in nature, as all injected areas were affected. In the event of infection, symptoms would be localised or restricted to a discrete area rather than global.19 Moreover, at presentation the patient was systemically well and had been asymptomatic in the injection area for eight months between the last treatment and reaction onset. The lumps reported were hard and non-fluctuant and atypical of infection.20,21 Therefore, there was no need for an empirical antibiotic treatment.
Consensus opinion was to prescribe prednisolone at a dose of 1mg per kg of body weight, 60mg of for five days (Figure 4). Following a review on day five, the patient showed clinical signs of improvement, remained afebrile and all vital markers were normal, with less periorbital swelling, nodules shrinking, no erythema, and no evidence of infection.
In view of improvement, the prednisolone course was extended for a further 10 days. The patient was reviewed on day 12 of 15 days of treatment, and the symptoms were seen to be resolving. The autoimmune profile and CRP reported normal, and the only anomaly on FBC was slight neutrophilia. In view of the high dose and duration of treatment, a gradual diminution of the dose was carried out. During this time there was open communication with her GP to ensure holistic care, and following cessation of her prednisolone, the GP started her on fexofenadine 180mg daily as she had mild recurrence of itchy throat symptoms, but no further recurrence of oedema or nodule formation.
Completion of care
The patient was seen again in the clinic four weeks following her presentation, where she had made a full recovery with complete resolution of her swelling and nodules. Following her experience, the patient has not been put off further filler treatment, but we will wait and see how she progresses over the next few months. She was relieved she had been seen by qualified medical professionals who were able to recognise and manage this complication.
This was both a stressful time for patient and practitioner. We have a duty of candour to our patients, which should be upheld at all times and throughout this process an open line of communication was kept with the patient. The patient was very anxious, so empathy and clear explanations were greatly appreciated. With regards to the potential for the need for booster COVID-19 vaccinations in the future, we have advised her to proceed with this, and to liaise with us immediately should there be any recurrence of symptoms.
Conclusion
Due to the current minimal evidence concerning COVID-19 vaccine and hypersensitivity, it is even more important that cases are reported. Delayed complications are particularly difficult to diagnose and treat due to the time lapse from the last procedure.19,22,23 As observed in the described cases, type IV hypersensitivity reactions are unresponsive to antihistamines and steroids are required to alleviate the inflammatory signs.24 The main limitation of this article is the absence of a histological analysis. Biopsies were not performed due to the patient’s desire to have minimally-invasive resolutions for their symptoms as quickly as possible.
Due to the relatively new nature of the COVID-19 vaccines, there is not enough research into how they will react with aesthetic products, and many questions remain unanswered. There are still many studies needed to determine why some people experience complications related to the vaccine and some don’t, the effects of booster vaccinations, and whether patients who experience complications will be able to receive fillers again.
It is essential that we are mindful of this risk, consent our patients appropriately, risk assess our patients, carefully time their treatments around their expected vaccination date and are knowledgeable on how and when to intervene if a complication does occur.
