Cutaneous manifestations following SARS-CoV-2 vaccination.

Dear Editor,

Full understanding of clinical response to vaccination against Covid‐19 remains unknown. Current data from completed vaccine trials reported adverse effects, including cutaneous adverse events (AEs).

Blumenthal et al. described the range of after‐vaccine cutaneous reactions, at injection sites but also in distant locations. They confirmed hypersensitivity reactions explained as delayed‐type or T cell‐mediated hypersensitivity. It has not been explained why delayed inflammatory reaction (DIR) affects only some filler‐treated patients. Decates et al. revealed that human haplotype B*08 or DRB1*03 could be responsible for considerable increase in chances of immune‐mediated AEs. Previously DIR to fillers following infections (dental, active sinusitis, or viral illness) have been reported.

A 63‐year‐old female patient received two hyaluronic acid (HA) filler injections (2 ml) in 2019–1 ml injected into the nasolabial folds area, the following one, 6 weeks later in the marionette lines region. Four months after the last injection, the patient presented to the office with severe oedema in the perioral area and easily palpated nodules, especially from the inside of the oral cavity. The symptoms appeared at the time of mild throat infection, but as tenderness and oedema continued to increase, she returned to the clinic asking for treatment. She refused hyaluronidase injection and was prescribed Clarithromycin 500 mg bid for 10 days with a single injection of Dexaven (Dexamethasoni phosphas, 8 mg). The following day she informed that the oedema completely disappeared and the nodules were still palpated but much smaller. She did not present to the clinic for a check‐up until recently. In the course of 2 years no aesthetic treatment was done, the patient has not gotten any severe illness, she has no allergies. She received the first Pfizer vaccine in June 2021 without any side effects, and the second one in July. Twenty‐four hours later, she noted mild swelling in the nasolabial folds area, followed by swelling of the whole perioral area (after a few hours). She could palpate small nodules in this area. She started to take over the counter antihistamine drug but without effect. After 48 h from the onset of the symptoms she appeared at the clinic (Figure 1A). She refused oral corticosteroids, afraid they might suppress the response to the vaccine. At this time her antihistamine medication was substituted with Lisinopril 5 mg once daily. An improvement was noted within ~10 h of Lisinopril treatment. Over a period of 24 h, swelling diminished (Figure 1B). Lisinopril was stopped 2 days later.

FIGURE 1

(A) Forty‐eight hours from the onset of the symptoms. (B) Twenty‐four hours after initiating the treatment. (C) Cutaneous manifestation 48 h after second dose of vaccine. (D) Forty‐eight hours after initiating Prednisone 40 mg

Another patient—a healthy 56‐year‐old female who had midface correction with HA filler (2 ml) placed over 10 months ago at a different clinic. She reports no allergies, nor any inflammatory reaction following filler injection. She received the first Pfizer vaccine dose in July 2021 and reported mild arm pain after the injection. A second dose of vaccine was done 3 weeks later. After 48 h she noted swelling of the cheeks, redness, oedema, and rash (Figure 1C). Her physician prescribed her Prednisone 40 mg for 7 days and referred her to our clinic. She started the treatment immediately and by 48 h she noted improvement bilaterally (Figure 1D). Residual swelling resolved completely 72 h after starting the medication so no further action was needed.

An explanation for DIR to HA fillers in COVID‐19‐associated cases is unknown. It is likely the blocking of angiotensin‐2 converting enzyme receptors by the SARS‐CoV‐2 spike protein when the virus enters the cell. Li et al. showed that angiotensin‐converting enzyme receptors are present in the skin to a higher extent than in other organs. ACE2 is responsible for transforming the angiotensin II into its anti‐inflammatory metabolites. Angiotensin II is a strong proinflammatory agent responsible for increasing levels of TNF‐α, IL‐6, and IL‐8 and stimulating immune response.

In the cases presented here, inflammatory reactions occurred rapidly within 24–48 h after the second dose of COVID‐19 vaccination (Pfizer).

In the first case angiotensin‐converting enzyme inhibitor (Lisinopril 5 mg) was used to decrease the level of angiotensin II. Other authors have described similar cases where they used the same treatment. Lisinopril—the ACE‐I blocks the production of angiotensin II and decreases the level of the substrate for ACE2. It has a quick onset of action (effect within hours after administration). It also increases sodium levels and water outflow helping to cease swelling. This method of treating hypersensitivity to HA filler symptoms seems very effective and safe compared to immunosuppressive mode of action of oral corticosteroids, but needs further evaluation.

In the second case the reaction was suppressed with orally administered corticosteroids. The situation was resolved rapidly however we do not know the effects of corticosteroids use on effectivity of COVID‐19 vaccination.

Another group of patients with hypersensitivity to HA filler has to be mentioned—those in whom inflammatory processes develop in response to a native Covid‐19 infection (may be a trigger factor). These might be more difficult to manage and probably would take longer to heal.

Therapeutic management of filler‐associated DIR following Covid‐19 or vaccination against SARS‐CoV‐2 cases should be focused on suppressing the inflammatory response by corticosteroids or decreasing the level of proinflammatory angiotensin II by ACE‐I (seems to be a promising and effective way of treatment, needs further evaluation). Complex cases would need combined treatment (corticosteroids, antibiotic, and hyaluronidase; steroids injected into lesions alone or in combination with 5‐FU).

CONFLICT OF INTEREST

The author declares no conflict of interests.

CONSENT FORMS

The patients have signed the consent for the procedure and written informed consent for publication of their image in the journal.