Late-Onset Inflammatory Adverse Reactions Related to Soft Tissue Filler Injections

Abstract

An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies; management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein.

Complications caused by injection of dermal filler in Danish patients

“…However, our study, in line with other studies [2][3][4][5], has shown that dermal filler treatments can have severe side effects and cause complications such as noduli, fistulation, granuloma, and infection. Some studies postulate that late onset of granulomatous reactions and noduli are more frequent after treatment with permanent filler [6,7]. This study has not been able to confirm the above since we have no information on the total number of treatments and the distribution among the different substances.…”

Late-Onset Adverse Reactions Related to Hyaluronic Acid Dermal Filler for Aesthetic Soft Tissue Augmentation

“…Although HA fillers are described as nontoxic and nonimmunogenic, some authors have reported hypersensitivity and granulomatous foreign body reactions after the treatment. 3,4,9,11 Adverse reactions to HA fillers may vary and emerge from minor problems related to procedures such as needle marks or pinpoint bleeding, erythema or redness, swelling and edema, pain, tenderness, as well as ecchymosis. 9 These early and immediate adverse reactions are uncommon and occur in only 0.05% to 2% of the cases.…”

“…7 Delayed reactions occurred in few cases demonstrating hypersensitivity and foreign body reactions, that is, within 6 to 24 months after the injection. 2,4,[9][10][11][12][13][14][15][16][17][18] Authors reported delayed reactions in 0.6% of the cases. 9,19 In this article, we report 2 cases of delayed adverse reactions related to the use of HA filler (Restylane) with oral manifestation.…”

“…Unfortunately, this kind of material has not yet been discovered and almost all agents may induce some degree of adverse reactions. 3,4 Hyaluronic acid has been the most frequent class of injectable product for soft tissue augmentation, accounting for 85% of such procedures in 2010. 2 It is one of the components of the normal extracellular matrix of the dermis and provides support for other tissues.…”

Massive Hemi-facial Edema After Permanent Filler Removal in an HIV-Positive Patient. Precautions and Patient Information

“…This massive edema was probably initiated by the same pathway as proposed for the inflammatory reaction in case of injection near an old Bio-alcamid injection. The acute inflammatory reaction might be based on a bacterial biofilm or structured colonies of microorganisms encapsulated in an extracellular matrix that surrounds a foreign body and leads to a low-grade chronic infection and injury-mediated reactivation [7]. The hypothesis of role of a biofilm has been suggested, but evidence for the role of a biofilm in late reactions in polyacrylamide is far from settled compared to the evidence for a biofilm in shelled silicone implants.…”