Latent Granulomatous Foreign Body Reaction to Dermal Fillers: A Case Report

Abstract

Introduction: Cosmetic dermal fillers are increasingly being used to smooth out and correct facial contour deficiencies. They can categorically be classified on the basis of the biodegrading properties of the injectable material. A known but rare complication of dermal fillers is the formation of foreign body granulomas. Case Presentation: An 85-year-old woman with a remote history of cosmetic dermal filler injections presented with a left hemi-facial swelling. Histological examination revealed granulomas formed due to an inflammatory reaction to the injected silicone material. She was treated with intralesional and systemic corticosteroids and responded well to treatment. Discussion: Cosmetic dermal fillers can be associated with early and late-onset complications. Filler migration and granulomatous foreign body reaction are notable complications that may occur years after the procedure. The use of a non-biodegradable agent or a semi-permanent agent increases the risk for complications. A biopsy is required to confirm the diagnosis. There are multiple treatment options including intralesional injections, systemic therapy, and surgical excision.

Introduction

The use of dermal fillers for cosmesis is rapidly increasing and has become one of the most utilized cosmetic procedure in North America. Dermal fillers, also known as soft tissue fillers, are injectable implants, usually inserted at the nasolabial folds, infra-orbital region, lips, cheeks, and chin to smoothen and correct facial contour defects in cases of acne scars and wrinkles. They can also be used to create more volume in the facial region in cases of lipoatrophy. ¹ Dermal fillers are classified into 2 categories, biodegradable versus non-biodegradable and can be temporary, semi-permanent, and permanent.^2,3 Absorbable fillers are temporary or semi-permanent fillers that eventually degrade and are resorbed by the body. A common example would be hyaluronic acid filler where their effects last around 6 to 18 months and they have a hydrating smoothening effect on the skin.^1-3 Non-absorbable fillers have a permanent effect and may cause a foreign body reaction resulting in the stimulation of collagen that can cause long-lasting complications.^1,3 Common examples of non-biodegradable fillers include polymethylmethacrylate, polyalkylimide, and silicone.

A known yet uncommon late complication of non-biodegradable fillers is the formation of inflammatory nodules and foreign body granulomas. ³ Furthermore, the “migration” of fillers is another uncommon complication that may be explained by high-volume and high-pressure injection, or it may be caused by muscle movement or gravity. Filler migration may result in the occurrence of nodules in unusual areas within the vestibule, or deep to the cutaneous sites where the original injection had occurred. ⁴ In this case report we will discuss a case of an 85-year-old patient who presented with a foreign body reaction and dermal filler migration to fillers that were injected 30 years prior.

We used the CARE checklist when writing our report. ⁵

Clinical Presentation

An 85-years-old female, a non-smoker, with a past medical history of type 2 diabetes mellitus, dyslipidemia, hypothyroidism, and osteoporosis, presented to the emergency department with a 1-month history of a left-sided slowly progressive, painless hemi-facial swelling. She was referred to our outpatient department for further investigation. The left-sided facial swelling extended posteriorly to the pre-auricular region, inferiorly down to the mandible and medially to the angle of the mouth (Figure 1A). A second smaller lesion was noted at the glabellar region measuring around 3 × 2 cm (Figure 1A). Examination of the oral cavity revealed extensive induration of the left buccal mucosa (Figure 1B). She did not have any cranial neuropathy, including facial nerve palsy. There was no cervical lymphadenopathy and fiberoptic nasopharyngolaryngoscopy was unremarkable.

Figure 1.

The images were taken after the punch biopsies were performed. (A) Left-sided hemi-facial swelling and glabellar swelling. (B) Induration of the left buccal mucosa.

Computed tomography imaging of the facial bone and sinuses was done next which showed a non-specific mass like swelling with associated fat stranding of the subcutaneous soft tissue of the left cheek measuring approximately 1.5 × 4.5 × 4.0 cm with adjacent skin thickening. There was no collection or abscess formation, and the underlying osseous structures were unremarkable.

Magnetic resonance imaging showed a subcutaneous infiltrative process involving the left infra-orbital, left upper lip and left mandibular regions (Figure 2). Similar changes were noted in the central forehead subcutaneous tissues which did not appear to communicate with the left facial changes. There was no evidence of bone, muscle, or nerve involvement. The differential diagnosis at this time was broad: infective versus inflammatory versus neoplastic process.

Figure 2.

Axial magnetic resonance imaging T1-post gadolinium scan revealing significant inflammatory soft tissue of the left hemiface.

Punch biopsies of all 3 sites were taken under local anesthesia.

Histopathological analysis revealed benign skin and mu-cosa with prominent granulomatous foreign body reaction. Microscopic examination of the specimen showed a prominent granulomatous foreign body reaction with abundant variably sized optically clear globules, morphologically consistent with silicone. The histological findings are in keeping with a granulomatous foreign body reaction to dermal cosmetic fillers, most likely silicone with intra-oral migration (Figure 3).

Figure 3.

Silicone granulomas in the skin of the forehead (A-C) and left buccal mucosa (D) with vacuolated and “bubbly” histiocytes and multinucleated giant cells containing variably sized and optically clear intracytoplasmic vacuoles (hematoxylin & eosin). The granulomas extend into the subcutaneous adipose tissue (C).

Further patient questioning revealed a remote history of cosmetic dermal filler injections performed around 30 years prior. The type of filler used was thought to be silicone.

Histopathologic Findings

The patient was initially started on a tapering dose of oral prednisone starting with a dose of 50 mg for 1 week, followed by 30 mg for 3 days and she continued her maintenance dose of 15 mg for 30 days. The patient experienced uncontrolled, elevated blood glucose levels as an adverse effect of her systemic corticosteroid treatment. She initially showed significant improvement of her symptoms, unfortunately there was a recurrence of her facial swelling after the cessation of the systemic corticosteroid treatment. A trial of intralesional triamcinolone injection, 40 mg/mL 0.6 mL was injected throughout her face. There was a decrease in the facial swelling which was noted in her 1-month follow- up. At 4 months from injection, the patient showed interval stability of the facial swelling (Figure 4).

Figure 4.

Results post-treatment.

Discussion

There has been a rise in reports of associated complications of cosmetic dermal fillers as they are increasingly being used for soft tissue augmentation over the past few decades.^2,6 Complications can be classified based on the onset of events, either early or late events. ² Early-onset complications may occur up to days post-procedure, and they include injection site reactions, infection, type 1 hypersensitivity reactions, non-inflammatory nodules, hematoma formation, contour irregularities, skin discoloration, and vascular occlusion.^2-6 Late-onset complications may occur weeks to years’ post-procedure and may include malar edema, persistent discoloration, type IV hypersensitivity reactions, infection, migration of the filler material, and the formation of inflammatory and foreign body granulomas.^2-7

In the above case, multiple biopsies were performed to rule out alternative diagnoses including lymphoproliferative disorders (lymphoma), systemic infiltrative disorders (example amyloidosis), and chronic infection.

The ideal dermal filler should be biocompatible, non-antigenic and stable with minimal foreign body reaction and with no migration potential.^6,8 Filler migration is when the injectable substance is found at a site that is distant from the original site of injection. ² This may occur several years after treatment with semi-permanent or permanent fillers, and it is most notably seen with the use of silicone fillers. ² Several factors that may contribute to filler migration, including poor injection technique, injection of a large volume of the filler, lymphatic spread, gravity or may be as a result of ageing skin resulting in a change of the contour of the face.^2,4,9

Granulomatous foreign body reactions post-injection of dermal fillers is rare. ² The reported incidences of granulomatous foreign body reactions range from 0.02 to 2.8%.^10-12 The risk of a granulomatous reaction is greater with the use of non-biodegradable fillers. ³ Other factors that may contribute to an increased risk of the formation of a granuloma include injection of larger filler volume, repeated injections, incorrect depth of injection, large particle size of the injectable agent, and previous infection or trauma at injection sites.^4-13 The reaction is due to the resistance of the enzymatic breakdown or phagocytosis of the filler material. The sequestration of the engulfed material results in the secretion of inflammatory products, attracting more macrophages. Macrophages eventually fuse to form multinucleated foreign body giant cells, granulomas.^2,3,13

Although there has been reported incidences of granulomatous foreign body reaction with biodegradable fillers such as hyaluronic acid, poly-L-lactic acid and calcium hydroxyapatite, the incidence is more likely to occur with permanent, non-biodegradable fillers such as polymethacrylate and silicone.^2,4,13,14

Duker et al. ¹⁵ conducted a study that showed that patient’s quality of life can be moderately to severely impacted due to the adverse reactions that occurred secondary to dermal fillers and the impact is greater with patients who had a non-biodegradable agent injected compared to those who had a biodegradable agent injected. This may be due to the higher incidence of adverse reactions associated with non-absorbable dermal filler agents.

There have been various proposed treatment options for foreign body granulomas formed secondary to dermal filler injections: intralesional injections, systemic therapy, and surgical therapy.^16,17 Intralesional corticosteroid injections, high-dose triamcinolone mixed with lidocaine, of the foreign body granuloma has been reported to be successful in many cases.^17-20 The corticosteroid agent interferes with the activities of fibroblasts, macrophages, giant cells, and collagen synthesis. ²¹ This has been shown to be successful in the case that we encountered with improvement seen after just one dose. Other injectable agents that may be used are bleomycin and 5-flurouracil. ¹⁷

Systemic therapy can be used in patients with recurrent or resistant granulomas. ¹⁶ The dose of the systemic corticosteroids used should be higher than that used in local injections to prevent recurrence of granulomas. ²² Methotrexate has been successfully used in the treatment of foreign body granuloma’s; low doses of methotrexate offer a low-risk alternative to systemic corticosteroid therapy. In order to determine long-term success, further follow-up is re-quired.^23,24 Methotrexate increases the adenosine release at sites of inflammation, diminishing leukocyte accumulation and activation, and clonal deletion of activated peripheral T-cells.^25,26 Other systemic therapies that have been used previously include minocycline, tacrolimus, etanercept, and imiquimod due to their immunomodulatory properties.^27-32

Surgical excision is not the first-line therapy as complete removal of the granuloma is difficult as they are invasive, and the borders of the granuloma are not confined. Surgical excision can be associated with abscess and fistula formation.^16,31 If the foreign body is localized, excision may be performed with reconstruction. ¹⁶ In the above case, surgical excision would be morbid with little assurance of entire removal of foreign body material.

Strengths and Limitations

We had an evidence-based approach to the diagnosis and treatment of foreign body granuloma, but further follow-up is required to ensure resolution.

Conclusion

Foreign body granulomatous reaction is a potential late-onset complication of cosmetic dermal fillers. In cases with persistent facial swelling without obvious cause, a biopsy of the lesion can help confirm the diagnosis. There are multiple treatment options varying from intralesional injections, systemic therapy, and surgical excision.