Foreign-body granuloma formation in the lower eyelid after injection of poly-D,L-lactic acid as a collagen stimulator: a case report
Article information
Abstract
Poly-D,L-lactic acid (PDLLA) is widely used in facial rejuvenation as a collagen stimulator, with a lower risk of granuloma formation compared to poly-L-lactic acid (PLLA). However, granulomas may still occur. In this case, a 58-year-old woman developed firm, non-tender, bilateral infraorbital granulomas 2 months after her third PDLLA injection for infraorbital hollowing. The lesions were unresponsive to intralesional trichloroacetic acid (TCA) and intense pulsed light therapy, necessitating surgical removal. Histopathological analysis confirmed foreign-body granulomas caused by the PDLLA filler. This case highlights the need for caution when injecting PDLLA into thin-skinned areas like the infraorbital region, where granulomas can be more visible due to limited tissue volume. Although PDLLA fillers are generally safe, granuloma formation remains a potential complication. Early diagnosis and treatment with non-surgical methods, such as intralesional TCA, should be prioritized. If these methods fail, surgical excision, aimed at preserving as much normal tissue as possible, may be necessary for optimal outcomes.
INTRODUCTION
In recent years, the aesthetic market has witnessed a surge in interest in minimally invasive procedures, especially those that involve collagen stimulators [1]. This trend is attributed to the ability of collagen stimulators to deliver more natural and enduring results by promoting the body’s own collagen production [2]. The increasing popularity of these treatments is also evident in their higher patient satisfaction rates, more favorable safety profiles, and increased effectiveness [3].
Poly-L-lactic acid (PLLA) filler, marketed under the name Sculptra, was designed to boost collagen production and achieve sustained restoration of facial volume. The microparticles of PLLA induce a subclinical inflammatory response that, in turn, promotes collagen synthesis. However, concerns have been raised regarding the irregular shape and larger size of PLLA particles compared to those of poly-D,L-lactic acid (PDLLA), which could potentially increase the risk of granuloma formation [4,5].
To address these issues, a PDLLA filler known as Juvelook was developed, featuring a more uniform and smaller particle size to minimize these risks. However, despite these advancements, granuloma formation can still occur with the use of PDLLA, similar to other dermal fillers [2].
In this paper, we present a case of granuloma that developed 2 months following the third injection of PDLLA into the periorbital region, where it was used as a collagen stimulator.
CASE REPORT
A 58-year-old woman presented with edema and protruding lesions in both lower eyelid areas, which had been present for 2 months. The lesions were movable but firm, and there was no erythema, tenderness, or ulceration. The patient was afebrile, and a review of systems revealed no other remarkable findings. Her medical history was significant only for hyperlipidemia, with no other known underlying conditions. Twenty years prior, she had experienced a traumatic accident involving her right cheek, during which a glass fragment became embedded. This fragment had remained asymptomatic.
The patient received a series of three monthly PDLLA injections in both lower eyelid areas to address age-related infraorbital hollowing. No abnormalities were noted following the first and second injections. However, after the third injection, significant lesions suddenly appeared in the lower eyelid regions (Fig. 1). Subsequent treatments, including an intralesional trichloroacetic acid (TCA) injection and intense pulsed light (IPL) therapy, proved ineffective. Therefore, surgical removal of the lesions was deemed necessary.
Bilateral infraorbital granulomatous lesions in a 58-year-old woman who presented 2 months after the second poly-D,L-lactic acid (PDLLA) injection. The lesions are firm, non-tender, and movable, located under both eyes.
Under local anesthesia, a subciliary skin incision was made parallel to the lid margin. Adhering to recent guidelines for safe incision placement, the muscle incision was carefully planned and executed to minimize the risk of nerve damage [6]. The surgery revealed granulomatous lesions protruding through the orbicularis oculi muscle (OOM) and fat pads. These lesions were excised, after which the OOM was meticulously sutured to complete the procedure. Additionally, a glass fragment from a prior injury to her right cheek was removed during the same surgery (Fig. 2).
(A) Intraoperative view of surgical removal under local anesthesia. (B) During the same procedure, a glass fragment from a previous right cheek injury was also removed.
The lesion on the right side was larger than the one on the left. The characteristics of the excised lesions, along with histopathologic analysis, suggest that the granulomas were indicative of a foreign-body reaction involving PDLLA (Fig. 3). The patient was followed up for 3 months without any notable complications, although small residual nodules remained on both medial sides of the lower eyelids (Fig. 4). Triamcinolone injections were administered to these areas. After the surgery, the patient was diagnosed with Hashimoto’s thyroiditis, and appropriate medication was initiated.
Histopathological analysis of the granulomatous lesion. A histological image showing a central area of mixed inflammatory infiltrate, including lymphocytes, plasma cells, and multinucleated giant cells, indicative of a foreign-body granuloma, marked with a circle. Adjacent to this area is the orbicularis oculi muscle fibers, demonstrating the lesion’s extension into the muscle layer, marked with asterisks (hematoxylin and eosin stain, ×40).
Three-month postoperative follow-up of a patient treated for infraorbital granulomatous lesions. No protruding lesions were observed, though a small residual nodule remained on both medial sides.
DISCUSSION
PLLA is a synthetic polymer composed exclusively of L-lactic acid isomers. Its primary mechanism of action is to gradually induce collagen production through a foreign-body reaction following injection into the skin. Designed to stimulate fibroblasts, PLLA particles encourage the synthesis of new collagen fibers over time. However, due to their solid and non-porous nature, PLLA particles initially produce only a minimal immediate volume effect. This effect is mainly attributable to the filler material, which, as it degrades, is replaced by newly formed collagen.
PDLLA incorporates both D- and L-lactic acid isomers, which give rise to a porous microsphere structure. This structure enables PDLLA to produce an immediate volumizing effect upon injection, as the porous particles are capable of retaining a larger volume of water or filler fluid. Moreover, the porosity of PDLLA provides a stronger scaffold for collagen growth, leading to a faster and more noticeable collagen-stimulating effect. The PDLLA particles form a framework that facilitates tissue integration and collagen deposition, thus reducing the likelihood of inflammatory responses and granuloma formation often associated with PLLA [4,5].
Granuloma formation can occur under various conditions, often as a result of the body’s immune response to foreign materials. Contributing factors to granuloma formation include the size and surface properties of the particles injected, the technique of injection, and the individual’s immune response. Moreover, particles that are larger or have irregular surfaces are more prone to triggering an inflammatory response. While PDLLA reduces the risk of granulomas compared to PLLA, it is not completely devoid of this potential complication and should be used cautiously as a dermal filler [2,7,8].
In this case, several factors may have contributed to the formation of granulomas and their subsequent detection. Firstly, injecting PDLLA into areas with thin skin, such as the lower eyelid, can make any resulting granulomas more noticeable due to the limited tissue volume and increased visibility in these regions. Consequently, special care is required when treating sensitive areas like the periorbital region, as well as the forehead, chin, and lips [7].
Second, the presence of an embedded glass fragment from a previous injury may have accelerated the foreign-body reaction, intensifying the inflammatory response. Research indicates that retained foreign bodies, such as glass fragments, can significantly amplify local inflammatory responses [9,10]. In this case, the lesion on the right side was larger than that on the left, indicating a more severe inflammatory response in that area.
Finally, patients with autoimmune diseases, such as Hashimoto’s thyroiditis, face an increased risk of exaggerated reactions to foreign bodies. Studies have shown that systemic immune conditions can alter the body’s response to foreign materials, leading to more severe inflammation and fibrosis [9,11,12]. The presence of adjuvants and other foreign substances can further exacerbate these reactions, potentially leading to conditions such as autoimmune/inflammatory syndrome induced by these materials. While the precise cause-and-effect relationship remains unclear, it is crucial to approach the treatment of patients with autoimmune diseases cautiously to avoid potential complications.
For PDLLA-induced granulomas, a variety of treatments are available. Intralesional TCA injections are commonly used as a first-line treatment because they chemically ablate the granulomatous tissue. TCA achieves this through controlled chemical cauterization, which leads to the necrosis of the granulomatous tissue, subsequently replaced by normal tissue. Additionally, systemic corticosteroids, antibiotics, and IPL therapy can be effective in reducing inflammation and the size of granulomas [13]. IPL functions by causing localized thermal damage that promotes collagen remodeling and diminishes the inflammatory response linked to granulomas. In this instance, a combination of intralesional TCA injections and IPL treatments was employed, but these proved ineffective, ultimately requiring surgical removal.
Complications from dermal filler injections can vary widely, encompassing vascular events, infections, and inflammatory responses. Among these, nodules and granulomas are significant complications that require differentiation. Nodules generally result from the accumulation of the product, manifesting as palpable lumps beneath the skin. Conversely, granulomas arise due to an excessive inflammatory response to the filler material, marked by a more intense immune reaction. Histological examination is crucial for accurate diagnosis and treatment planning, as the management strategies for nodules and granulomas differ significantly [8,14].
In this patient’s case, the granulomatous lesions that protruded into the OOM and fat pads posed a risk of muscle damage and impaired function. To achieve both cosmetic and functional outcomes, it is essential to preserve the anatomy of the skin and muscles as well as nerve function during lower eyelid surgery. Granulomas located in high-risk areas, where there is potential for nerve damage, were left intact to avoid complications such as pretarsal atrophy. Adhering to established guidelines for incision placement, which identify safe and danger zones around the lower eyelid, is crucial for reducing the risk of postoperative complications and ensuring a successful recovery [6]. Additionally, removing granulomas in the medial regions of the lower eyelid presents particular challenges due to the difficulty in isolating the affected tissue without affecting surrounding structures. Therefore, PDLLA injections should be avoided in these areas whenever possible. Should granulomas develop, initial management should focus on non-surgical treatments like TCA injections. Surgical removal should only be considered when non-surgical methods do not result in satisfactory outcomes, with an emphasis on preserving as much normal tissue as possible to minimize both functional and aesthetic complications.
In conclusion, granulomas resulting from dermal filler injections pose significant clinical challenges, especially in sensitive areas like the lower eyelid. Successful treatment hinges on accurate diagnosis, the judicious use of non-surgical interventions, and, when necessary, meticulous surgical excision to maintain both function and aesthetics. Particularly in the medial lower eyelid region, where surgical access and tissue preservation are challenging, it is advisable to avoid PDLLA injections when possible. In cases where granulomas do occur, the primary objective should be to maximize the preservation of normal tissue to reduce functional and aesthetic complications. Careful patient selection and tailored treatment approaches are crucial for minimizing complications and achieving patient satisfaction.
Notes
No potential conflict of interest relevant to this article was reported.
Ethical approval
The report was approved by the Institutional Review Board of Chosun University Hospital (IRB No. CHOSUN 2024-07-020).
Patient consent
The patient provided written informed consent for the publication and use of her images.