Novel management of granuloma formation secondary to dermal filler: A multi‐modality approach

Dermal fillers for soft tissue augmentation have become increasingly popular among patients of all ages and ethnicities. With more widespread use, there has been an increased incidence of adverse reactions, one of which is the granulomatous foreign body reaction (GFBR).

as disfigurement or pain and dysfunction, respectively. 1 Granuloma formation is a non-allergic inflammatory reaction and may occur in response to dermal filler use due to factors such as the volume of filler injected, impurities in the filler, and the physical properties of the filler. 2 Furthermore, GFBR is difficult to treat and there has yet to be a consensus on an efficacious treatment regimen.

| MATERIAL S & ME THODS
Our treatment regimen for granuloma formation secondary to dermal filler is multileveled. The first modality involves intralesional in- however, this can be successfully treated with pulsed dye laser, as previously reported. 3

| RE SULTS
In this case series, three separate patients are presented who received hyaluronic filler (Figures 1-4), biopolymer-based filler F I G U R E 1 Lateral view of the chin of patient 1 demonstrates erythematous pink to red plaques with overlying telangiectasias prior to treatment with the multi-leveled approach.
F I G U R E 2 Frontal view of the chin of patient 1 demonstrates erythematous pink to red plaques with overlying telangiectasias prior to treatment with the multi-leveled approach.

F I G U R E 3
Lateral view of the chin of patient 1 approximately 12 months after treatment demonstrates resolution of both the erythema and telangiectasias resulting in an overall improved aesthetic outcome.

F I G U R E 4
Frontal view of the chin of patient 1 approximately 12 months after treatment demonstrates resolution of both the erythema and telangiectasias resulting in an overall improved aesthetic outcome.

| DISCUSS ION
Granulomatous foreign body reaction secondary to dermal filler injections is relatively rare, however, it is becoming increasingly common secondary to increased popularity of fillers and counterfeit filler products being sold online direct to patients. 4 A 2017 study reported the incidence of GFRB to be 0.02-2.8% of patients, however, the explosion of injectable fillers in the last 5 years makes this number an underestimate of the true incidence. Most previous reactions were reported secondary to non-degradable filler material, such as fillers containing polymethyl methacrylate. GFRB may occur months to years following initial injection, and may present as subcutaneous nodules, abscesses, cellulitic changes, and/or edema. Diagnosis of GFRB can be made definitively from a skin biopsy demonstrating granulomatous inflammation in the dermis or subcutis with foreign body giant cells (Figures 9 and 10). Filler materials can also sometimes be seen on skin biopsies. However, in patients who defer skin biopsy, the diagnosis of GFRB can be made clinically based on history of prior injection and typical clinical symptoms. 4

F I G U R E 5
Photo of patient 2 demonstrating erythematous pink to red linear plaques involving the nasolabial folds, and an ill-defined pink plaque involving the glabella and philtrum prior to treatment with the multi-leveled approach.

F I G U R E 6
Photo of patient 2 approximately 5 months post-treatmen with a dramatic reduction of erythema and granulomatous response in the nasolabial folds, philtrum, and glabella.

F I G U R E 7
Photo of patient 3 prior to treatment with the multileveled approach. Ill-defined brown to pink plaques involving the bilateral dorsal hands can be appreciated. There has yet to be a consensus on the proper treatment regimen for GFBR secondary to dermal filler. Upon literature review, there have been documented cases of granuloma improvement with intralesional 5-FU, intralesional steroids, methotrexate, and long-term colchicine. In the literature, low dose methotrexate has been promising for patients with granulomas secondary to non-biodegradable fillers. However, methotrexate comes with its own risks to the patient and is not widely used in this setting. 1 Presented here is a multilayered regimen with sustained success in the treatment of GFBR in the treatment of the presented patients. This regimen demonstrated clinical success in the treatment of hyaluronic filler-induced GFBR (Figures 1-4) as well as biopolymer-based filler GFBR (Figures 5 and   6) and GFBR due to filler of unknown origin (Figures 7 and 8). The second aspect of the granuloma treatment regimen involves giving the patient colchicine 1.2 mg loading dose followed by 0.6 mg twice daily for 5 days. Colchicine, a microtubule assembly inhibitor, is a medication most used for gout but has been used for the treatment of various neutrophilic dermatoses such as leukocytoclastic vasculitis and Behcet's disease. Colchicine's precise mode of action in the treatment of foreign body granulomas is not well understood.
However, it is known that it downregulates cytokine production and secretion of downstream TNF-a receptors and decreases phagocytosis and neutrophil chemotaxis. 8 Colchicine has been used in previous cases of granulomas, but the exact length of treatment and dosage has yet to be determined. It is the authors' opinion that a short and potent dose of colchicine is the most efficacious treatment course in granuloma patients.
The third and final phase of treatment is oral naproxen 500 mg daily for 5 days. Naproxen is a nonsteroidal anti-inflammatory agent that works by inhibiting cyclo-oxygenase and thus decreases prostaglandin concentration in fluids and tissue. In this setting, naproxen F I G U R E 9 (A) An H&E dermatopathology image of the foreign body reaction taken from a punch biopsy of the hand of patient 3. Representative histologic analysis reveals multiple Swiss-cheese like cavities of varying sizes filling the dermis and subcutis.
F I G U R E 1 0 (B) An H&E dermatopathology image of the foreign body reaction taken from a punch biopsy of the hand of patient 3. At higher magnification, there is a granulomatous inflammation and multinucleated giant cells surrounding the clear pseudocysts. These features are classic for a foreign body granuloma secondary to silicone injection. aids in decreasing the inflammation in the area surrounding the granuloma. 9 In some GFBR cases, the granulomas may self-resolve, but postinflammatory erythema (PIE) tends to remain. In addition to the granuloma itself, studies have shown intralesional corticosteroids to induce release of nitric oxide from endothelial cells leading to development of telangiectasias and may be a contributing factor to the remaining erythema at the site of injection. 10  This is thought to target granulomas themselves by causing either the quiescence or resolution of multinucleated giant cells. 14 The increasing frequency of granulomatous reactions to both real and imitation dermal fillers necessitate an efficacious, safe, and feasible treatment for this condition. GFBR provides both a medical and aesthetic issue for these patients including mental distress, pain, and dysfunction, therefore having an effective treatment for GFBR will affect medical management of these patients, improving patient outcomes and satisfaction. Our proposed regimen for GFBR has been shown to be highly efficacious and safe for these patients, providing a significant improvement in both function and cosmesis of the area.

CO N FLI C T O F I NTE R E S T
No conflicts of interest.

E TH I C A L A PPROVA L
Authors declare human ethics approval was not needed for this study.

PATI ENTS CO N S ENT
Proper written informed consent was obtained from each patient.

DATA AVA I L A B I L I T Y S TAT E M E N T
The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials.