COVID-19 infection-associated hypersensitivity reaction to dermal filler-A case report and review of the histologic features.

To the Editor,

Dermal fillers using hyaluronic acid (HA) have become a popular therapy for patients who desire minimally invasive treatment with relatively low risk. While uncommon, hypersensitivity reactions to HA have been documented. Delayed‐type hypersensitivity reaction (DTHR) to HA is rare, occurring anytime between 24 h to weeks or months after injection. It typically presents as a tender firm erythematous swelling. SARS‐Cov‐2 is a respiratory virus causing widespread community transmission of COVID‐19 disease in the general population. Several case reports have been published in the Journal of Cosmetic Dermatology describing the new onset of reaction to HA following COVID‐19 infection among patients who never had any reaction before. , DTHR to HA triggered by COVID‐19 infection seems to be the most credible explanation for the late‐onset event described in such reports. Histopathologic examination is vital in confirming the clinical impression. However, patients have previously refused biopsy. Therefore, no definitive histologic diagnosis could be made.

We present a case with histologic examination. The case involves a 58‐year‐old female patient who had undergone facial rejuvenation with injection of HA dermal fillers in the past several years at a different office. Her last HA injection (Restylane) at the labiomental folds was in 2016. She had never reported any adverse reaction in the past. In January 2021, she tested positive for COVID‐19 (she was unvaccinated) after having presented to the emergency department with respiratory and abdominal complaints. She required a 6‐day hospitalization. A month later in February 2021, the patient suffered left‐sided Bell's Palsy thought to be a possible sequela of her recent COVID‐19 infection. Promptly thereafter, she developed a subcutaneous nodule in right perioral area. The mass was initially small but then progressively enlarged. She presented to our office 9 months later in November. Our working diagnosis for the nodule included sebaceous cyst or foreign body reaction to HA. Due to its persistent and continued enlargement, the patient elected to have the nodule excised and submitted for pathologic examination as opposed to hyaluronidase treatment. Patient had tried massage and warm compresses previously, without improvement.

The microscopic examination reveals a diffuse infiltrate of granulomatous inflammation in the dermis (Figure 1). There are numerous non‐necrotizing granulomas with various size and shape. The granulomas are predominantly composed of multi‐nucleated giant cells and histiocytes. Numerous round empty vacuoles are identified within giant cells, representing HA particles (Figure 2). The pathology findings are consistent with foreign body granulomatous reaction to HA.

FIGURE 1

Skin excision shows a dermal infiltrate of a diffuse granulomatous process (arrow)

FIGURE 2

Dermis is replaced by numerous non‐necrotizing granulomas with various size and shape. Within each granuloma, multinucleated giant cells (arrow) engulf round empty vacuoles (asterisk), which represent HA dermal fillers

Hypersensitivity reactions are classified into four types based on the onset of the reaction. The fourth type is considered a DTHR because it occurs more than 12 h after exposure to the allergen. , Granulomatous reaction, one of three subtypes of DTHR, can occur in response to infectious pathogens and foreign body. Macrophages engulf antigens but are unable to destroy them. More macrophages are recruited to the site. A collection of macrophages filled with intracellular antigens is termed granuloma. , Due to its native presence in mammalian tissue, HA is considered biologically inert by nature. However, due to its short half‐life, artificial cross‐linking has been added to stabilize the molecules for cosmetic use by manufacturers. It has been postulated that these cross‐linking agents may precipitate an immune response. In our study, this patient appeared to be immunotolerant with HA for many years. The new onset of reaction is most likely triggered by the systemic inflammation caused by COVID‐19 infection. Although the exact mechanism remains to be elucidated, the histologic finding of foreign body granulomatous reaction validates the clinical impression of DTHR. This may assist in the future management of the reported cases.

CONFLICT OF INTEREST

The authors have no conflict of interest.

ETHICAL APPROVAL

Authors declare human ethics approval was not needed for this study.