1 Introduction 1 引言

Dermal fillers such as hyaluronic acid (HA) have been widely employed in cosmetic procedures for decades. More recently, patients have increasingly opted for biostimulators over HA fillers, driven by a preference for the natural stimulation of collagen rather than the filling effect provided by HA products [1-6]. Injectable poly-lactic acid is recognized as a collagen-stimulating filler. There are two variants: injectable poly-L-lactic acid (PLLA) and injectable poly-D,L-lactic acid (PDLLA), which are specifically used in this case report [5, 7-11]. Injectable PDLLA (Juvelook; VAIM Inc., Seoul, Korea) includes PDLLA and sodium hyaluronate as a carrier gel. It is supplied in vials as a lyophilized powder, necessitating reconstitution with a diluent before injection.
幾十年來，透明質酸 （HA） 等真皮填充劑已廣泛用於整容手術。最近，患者越來越多地選擇生物刺激劑而不是HA填充劑，這是由於更喜歡自然刺激膠原蛋白而不是HA產品提供的填充效果[1-6]。可注射的聚乳酸被認為是一種刺激膠原蛋白的填充劑。有兩種變體：注射用聚-L-乳酸 （PLLA） 和注射用 poly-D，L-乳酸 （PDLLA），在本病例報告中專門使用 [5， 7-11]。可注射 PDLLA （Juvelook;VAIM Inc.，韓國首爾）包括 PDLLA 和透明質酸鈉作為載體凝膠。它以凍乾粉的形式以小瓶形式提供，需要在注射前用稀釋劑重新配製。

Tear trough deformity is characterized by a deepening of the crease beneath the lower eyelid, leading to a darkened and sunken appearance. There is a growing desire to address the cosmetic effects of aging, particularly in the eye area, resulting in an increase in the diagnosis and treatment of tear trough deformity [12-14], Treating the tear trough area is challenging because of the thin skin and racial variability of the region.
淚溝畸形的特徵是下眼瞼下方的摺痕加深，導致外觀變暗和凹陷。人們越來越希望解決衰老對美容的影響，尤其是在眼部區域，導致淚溝畸形的診斷和治療增加 [12-14]，由於皮膚薄和該區域的種族差異，治療淚溝區域具有挑戰性。

PDLLA induces collagen synthesis by stimulating fibroblasts and causing a subclinical inflammatory reaction. Although PDLLA is absorbable, biocompatible within human tissue, and has a relatively strong safety profile, complications such as nodules, papules, and granulomas have been documented in the literature [15-19].
PDLLA 通過刺激成纖維細胞並引起亞臨床炎症反應來誘導膠原蛋白合成。儘管PDLLA在人體組織內具有可吸收性和生物相容性，並且具有相對較強的安全性，但文獻中已記錄了結節、丘疹和肉芽腫等併發症[15-19]。

There are reports of nodule formation as an adverse effect of using poly-lactic acids, and there have not been established treatment plans for these side effects [16, 18-20]. Previously, these nodules were treated with excisions [20]. This case study presents a case of an unusual nodular reaction following a PDLLA injection for the management of tear trough deformity and its subsequent treatment.
有報導稱，使用聚乳酸會導致結節形成，但尚未針對這些副作用制定治療計劃[16,18-20]。以前，這些結節通過切除治療 [20]。本案例研究介紹了一個 PDLLA 注射后異常結節反應的病例，用於治療淚溝畸形及其後續治療。

2 Clinical Case 2 臨床案例

A 42-year-old immunocompetent woman presented with tear trough hollows secondary to aging and received PDLLA injections bilaterally in the tear trough region (Figure 1). Prior to this treatment, she had received three PDLLA injections to her forehead and temples over a year ago but had no previous aesthetic treatments to the tear trough region. Concurrently with the PDLLA injections for her tear troughs, she also received botulinum neurotoxin type A injections for the glabellar region and lateral canthal rhytids. Her medical history was unremarkable, with no known allergies.
一名 42 歲的免疫功能正常女性出現繼發於衰老的淚溝凹陷，並在淚溝區域接受雙側 PDLLA 注射（圖 1）。在接受這種治療之前，她的前額和太陽穴已經接受了三次 PDLLA 注射，但之前沒有對淚溝區域進行過美容治療。在為她的淚溝注射 PDLLA 的同時，她還接受了針對眉間區域和外眦皺紋的 A 型肉毒桿菌神經毒素注射。她的病史無明顯異常，無已知的過敏史。

The procedure involved the use of PDLLA with a larger particle size, which led to adverse effects. This case occurred when the procedure was performed by a practitioner who was conducting it for the first time. In this case, the injectable PDLLA used was Juvelook Volume (Lenisna, VAIM Inc., Seoul, Korea). Each vial contains 200 mg of the product, comprising 170 mg of PDLLA and 30 mg of HA, with a particle size ranging from 40 to 60 μm. On the day of the procedure, one vial was reconstituted with 8 mL of normal saline and vortexed for 30 min before being used for tear trough rejuvenation. The patient received one session where 2 mL of PDLLA was injected into each tear trough. There was no immediate response to the injections posttreatment.
該程式涉及使用更大粒徑的 PDLLA，這導致了不良反應。本案發生在手術由首次執行手術的從業者執行時。在這種情況下，使用的注射劑 PDLLA 是 Juvelook Volume（Lenisna，VAIM Inc.，韓國首爾）。每個小瓶含有 200 毫克產品，包括 170 毫克 PDLLA 和 30 毫克透明質酸，粒徑範圍為 40 至 60 μm。在手術當天，將一個小瓶用 8 mL 生理鹽水復溶並渦旋 30 分鐘，然後用於淚溝回春。患者接受了一次治療，將 2 mL PDLLA 注射到每個淚溝中。治療后對注射沒有立即反應。

Three weeks after the treatment, the patient presented with visible, small, noninflammatory nodules in both tear trough regions (Figure 2). These nodules were firm and hardened but exhibited no signs of erythema, tenderness, fluctuance, or ulceration. The nodules were surrounded by minor soft tissue swelling. The patient had no fever, and a comprehensive systemic review revealed no other abnormalities. To date, the nodules have not recurred.
治療 3 周后，患者在兩個淚溝區域都出現了可見的小非炎症性結節（圖2）。這些結節堅硬而堅硬，但沒有紅斑、壓痛、波動或潰瘍的跡象。結節周圍有輕微的軟組織腫脹。患者無發熱，全面的系統評價未見其他異常。迄今為止，結節尚未復發。

The nodule occurred because the practitioner used the wrong product. Juvelook (VAIM Inc., Seoul, Korea), which has a particle size of 20 to 30 μm, typically does not cause nodules. However, the practitioner used Juvelook Volume, which has a larger particle size of 40–60 μm.
結節的發生是因為從業者使用了錯誤的產品。Juvelook（VAIM Inc.，韓國首爾）的粒徑為 20 至 30 μm，通常不會引起結節。然而，該醫生使用了 Juvelook Volume，它的粒徑更大，為 40-60 μm。

The monopolar radiofrequency device was used directly on the tear trough area with 150 shots administered using 4 cm² tips. The maximum energy level was set to 115 J or 28.75 J/cm². After one session, the nodules completely resolved within 24 h (Figure 3). Typically, patients begin treatment at the highest energy level of 5. If they experience discomfort due to the heat, the intensity is reduced to 95 J, 23.75 J/cm², and if necessary, further reduced to 75 J, 18.75 J/cm². Strong compression was applied following the use of a monopolar radiofrequency device.
單極射頻裝置直接用於淚溝區域，使用 150 cm 4 尖端注射² 次。最大能級設置為 115 J 或 28.75 J/cm²。一次治療后，結節在24小時內完全消退（圖 3）。通常，患者以最高能量水準 5 開始治療。如果他們因高溫而感到不適，強度會降低到 95 J，23.75 J/cm²，如有必要，進一步降低到 75 J，18.75 J/cm²。使用單極射頻設備後應用強力加壓。

3 Discussion 3 討論

In this study, we were the first to use energy-based devices for the thermal degradation of PLA-induced nodules. Specifically, we employed monopolar radiofrequency (1–2 MHz) treatment, using a thermometer to measure the surface temperature, which was maintained at 41–42°C [21]. The treatment involved either contact-type or rolling-type radiofrequency application. The mechanism for resolving the nodules is based on the concept of glass transition temperature (the temperature at which a material becomes malleable, like glass when heated). For PLLA, this temperature is around 60°C. However, for PDLLA, which is porous and hydrated, the glass transition can occur at 38–39°C, potentially explaining the treatment's effectiveness. The authors believe this approach is applicable specifically to PDLLA. Additionally, previous literature suggests that using multifrequency radiofrequency devices can induce M2 polarization, which may further support the effectiveness of this treatment method [22].
在這項研究中，我們是第一個使用基於能量的設備對 PLA 誘導的結節進行熱降解的人。具體來說，我們採用了單極射頻 （1-2 MHz） 治療，使用溫度計測量表面溫度，將其保持在 41-42°C [21]。治療涉及接觸式或滾動式射頻應用。分辨結核的機制基於玻璃化轉變溫度的概念（材料在加熱時變得具有延展性，如玻璃的溫度）。對於 PLLA，該溫度約為 60°C。 然而，對於多孔和水合的 PDLLA，玻璃化轉變可能發生在 38-39°C 時，這可能解釋了治療的有效性。作者認為這種方法特別適用於 PDLLA。此外，以前的文獻表明，使用多頻射頻設備可以誘導 M2 極化，這可能進一步支援這種治療方法的有效性[22]。

Hybrid fillers, such as calcium hydroxyapatite (CaHA) combined with HA or poly-L-lactic acid (PLA) combined with HA, have recently gained popularity because of their various advantages [23-25]. In the tear trough region, aging often leads to the reduction in fat in the superficial layer of the orbicularis oculi muscle, making the area appear more pronounced [26, 27]. Injecting HA filler superficially in this region can easily cause the Tyndall effect. To prevent this, PLA can be injected superficially, whereas HA filler can be used in deeper layers [28]. However, injecting PLA superficially can lead to the formation of nodules. A solution to this issue is the use of energy-based devices for the thermal degradation of the nodules.
混合填充劑，如羥基磷灰石鈣（calcium hydroxyapatite， CaHA）聯合HA或聚左旋乳酸（poly-L-lactic acid， PLA）聯合HA，因其各種優點而最近受到歡迎[23-25]。在淚溝區域，衰老通常會導致眼輪匝肌淺層的脂肪減少，使該區域看起來更加明顯[26,27]。在該區域淺表注射 HA 填充劑很容易引起 Tyndall 效應。為了防止這種情況，PLA 可以淺表注射，而 HA 填充劑可用於更深層 [28]。然而，淺表注射 PLA 會導致結節的形成。解決這個問題的方法是使用基於能量的設備來對結核進行熱降解。

Although nodules and granulomas are uncommon adverse events following treatment with biostimulators, they can cause significant cosmetic and psychological concerns for patients [26, 29]. The literature indicates that persistent, intractable nodules can remain despite multiple treatments, such as hyaluronidase and systemic or intralesional steroids. Surgical excision, typically considered a last resort, poses risks of complications, including incomplete removal of the granuloma and scar formation [30, 31].
儘管結節和肉芽腫是生物刺激劑治療后不常見的不良事件，但它們會給患者帶來嚴重的美容和心理問題 [26， 29]。文獻表明，儘管進行了多種治療，例如透明質酸酶和全身性或病灶內類固醇，但持續性、頑固性結節仍可保留。手術切除通常被認為是最後的手段，但存在併發症風險，包括肉芽腫切除不完全和瘢痕形成[30,31]。

It is crucial to differentiate between granuloma and nodular reactions because of their distinct aetiologies and clinical manifestations. Granulomas primarily arise from an exaggerated inflammatory response of the host and are characterized by significant edema and a substantial, hard granulomatous reaction that is both palpable and visible at the injection sites. They typically manifest between 6 and 24 months postinjection and can attain considerable size. Treatment with intralesional steroids is recognized as effective for managing granulomas. The diagnosis of granuloma should be confirmed by histopathological evaluation [32-34].
區分肉芽腫和結節性反應至關重要，因為它們的病因和臨床表現不同。肉芽腫主要由宿主的誇大炎症反應引起，其特徵是明顯的水腫和在注射部位可觸及和可見的實質性硬肉芽腫反應。它們通常在注射后 6 到 24 個月之間出現，並且可以達到相當大的大小。病灶內類固醇治療被認為對治療肉芽腫有效。肉芽腫的診斷應通過組織病理學評估來確診[32-34]。

Conversely, nodules primarily result from improper product deposition or accumulation within dynamic facial musculature. Clinically, nodules present as discrete, palpable lesions that may vary in visibility depending on their anatomical location, such as the neck, hands, or forehead. They typically appear within 1–2 months following the procedure and are usually solitary, ranging in size from small peas to larger lentils. Although some nodules respond favorably to intralesional steroid therapy, surgical intervention may be warranted in severe cases [15, 17, 20, 35, 36]. In our case, the clinical presentation strongly suggests nodular reactions, and the patient had no prior medical history or identifiable event that could plausibly trigger such a reaction.
相反，結節主要是由於產品沉積不當或在動態面部肌肉組織內積累所致。臨床上，結節表現為離散的、可觸及的病變，根據其解剖位置（例如頸部、手或前額）的不同，可見度可能會有所不同。它們通常在手術后 1-2 個月內出現，通常是孤立的，大小從小豌豆到大扁豆不等。雖然一些結節對病灶內類固醇治療反應良好，但嚴重病例可能需要手術干預 [15， 17， 20， 35， 36]。在我們的案例中，臨床表現強烈提示結節反應，並且患者既往沒有可能合理觸發此類反應的病史或可識別事件。

Juvelook (VAIM Inc., Seoul, Korea) is a hybrid filler that merges the immediate volumizing effects of HA with the long-term collagen-stimulating benefits of PDLLA. The PDLLA in Juvelook has a distinctive structure, featuring an outer spherical and foamy shape combined with an inner reticular and porous design. This patented structure allows for gradual decomposition from the inside, leading to a slow and slight change in acidity around the particles, which improves tissue compatibility (Figure 4).
Juvelook（VAIM Inc.，韓國首爾）是一種混合填充劑，它將HA的即時豐盈作用與 PDLLA 的長期膠原蛋白刺激益處相結合。Juvelook 中的 PDLLA 具有獨特的結構，其特點是外部球形和泡沫狀形狀與內部網狀和多孔設計相結合。這種專利結構允許從內部逐漸分解，導致顆粒周圍的酸度發生緩慢而輕微的變化，從而提高組織相容性（圖 4）。

Based on our understanding, the porous nature of Juvelook's PDLLA allows for more effective degradation when energy-based devices are applied. There have been reports of refractory nodules developing after filler treatments that have been successfully resolved using a radiofrequency device [31, 37]. The device used in this study, the VolNewMer (VNM; Classys, Seoul, Korea), employs monopolar radiofrequency technology with a continuous water-cooling system. This system maintains an appropriate epidermal temperature by ensuring that the chilled water-circulating tip end remains in contact with the skin surface.
根據我們的理解，Juvelook 的 PDLLA 的多孔特性允許在使用基於能量的設備時更有效地降解。有報導稱，使用射頻設備成功解決填充劑治療後會出現難治性結節 [31， 37]。本研究中使用的設備 VolNewMer （VNM;Classys，韓國首爾），採用單極射頻技術和連續水冷系統。該系統通過確保冷水迴圈尖端末端與皮膚表面保持接觸來保持適當的表皮溫度。

The VolNewMer device system features several unique attributes, including an ergonomic tip design with a curved bottom surface and a “hidden edge” for enhanced coverage and maneuverability. The tips can tilt to allow optimal contact with the skin's contours, while the cushion function ensures constant pressure on the skin, irrespective of the applied pressure strength. Additionally, the device incorporates a sensor that alerts the user and halts energy emission when skin contact is incomplete, distinguishing it from other high-frequency devices.
VolNewMer 設備系統具有幾個獨特的屬性，包括符合人體工程學的尖端設計、彎曲的底面和“隱藏邊緣”，以增強覆蓋範圍和可操作性。尖端可以傾斜，以便與皮膚輪廓最佳接觸，而緩衝功能可確保對皮膚施加恆定的壓力，無論施加的壓力強度如何。此外，該設備還包含一個感測器，當皮膚接觸不完全時，該感測器會提醒使用者並停止能量發射，從而與其他高頻設備區分開來。

In conclusion, our case highlights the successful management of nodular reactions following PDLLA injections for tear trough deformity in a healthy 42-year-old woman using a monopolar radiofrequency device.
總之，我們的案例強調了一名健康的 42 歲女性使用單極射頻設備成功治療淚溝畸形注射 PDLLA 后的結節反應。

Author Contributions 作者貢獻

Conceptualization and visualization: Suk Bae Seo and Jovian Wan. Writing – original draft preparation: Jovian Wan, Suk Bae Seo, and Kyu-Ho Yi. Writing – review and editing: Jovian Wan. Supervision: Kyu-Ho Yi. All authors have reviewed and approved the article for submission.
概念化和可視化：Suk Bae Seo 和 Jovian Wan。寫作 – 原始草稿準備：Jovian Wan、Suk Bae Seo 和 Kyu-Ho Yi。寫作 – 審查和編輯：Jovian Wan。監督： Kyu-Ho Yi.所有作者均已審閱並批准了該文章的提交。

Conflicts of Interest 利益衝突

I acknowledge that I have considered the conflict of interest statement included in the “Author Guidelines.” I hereby certify that to the best of my knowledge, no aspect of my current personal or professional situation might reasonably be expected to significantly affect my views on the subject I am presenting.
我承認我已考慮「作者指南」中包含的利益衝突聲明。我特此證明，據我所知，我目前的個人或職業狀況的任何方面都不會合理地顯著影響我對我所提出的主題的看法。