Adverse reactions to the injection of face and neck aesthetic filling materials: a systematic review.

BACKGROUND: Adverse reactions, caused during the inflammation and healing process, or even later, can be induced by the injection of dermal filler and can present a variety of clinical and histological characteristics. In this study we aimed to review the adverse reactions associated with the injection of aesthetic filling materials in the face and neck. MATERIAL AND METHODS: The review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies published that mentioned adverse reactions in patients with aesthetic filling materials in the face or neck were included. Risk of bias was assessed using the Joanna Briggs Institute appraisal tool. After a 2-step selection process, 74 studies were included: 51 case reports, 18 serial cases, and five cohorts. RESULTS: A total of 303 patients from 20 countries were assessed. Lesions were more prevalent in the lip (18%), nasolabial folds (13%), cheeks (13%), chin (10%), submental (8%), glabella (7%), and forehead (6%). Histopathological analysis revealed a foreign body granuloma in 87.1% of the patients, 3% inflammatory granuloma, 3% lipogranuloma, 2.3% xanthelasma-like reaction, 1% fibrotic reaction, 0.7% amorphous tissues, 0.7% xanthelasma, 0.3% sclerosing lipogranuloma, 0.3% siliconoma, and 0.3% foreign body granuloma with scleromyxedema. In addition, two patients displayed keratoacanthoma and two others displayed sarcoidosis after cutaneous filling. The most commonly used materials were silicone fillers (19.7%), hyaluronic acid (15.5%), and hydroxyethyl methacrylate/ethyl methacrylate suspended in hyaluronic acid acrylic hydrogel (5.6%). All patients were treated, and only 12 had prolonged complications. CONCLUSIONS: There is evidence that adverse reaction can be caused by different fillers in specific sites on the face. Although foreign body granuloma was the most common, other adverse lesions were diagnosed, exacerbating systemic diseases. In this way, we reinforce the importance of previous systemic evaluations and histopathological analyses for the correct diagnosis of lesions.

Submucosal lifting agent ORISE gel causes extensive foreign body granuloma post endoscopic resection.

BACKGROUND: Submucosal injection of lifting solution is often performed to facilitate endoscopic mucosal resection or endoscopic submucosal dissection. ORISETM gel is a synthetic solution recently approved by the US Food and Drug Administration (FDA) in 2018 for use as submucosal lifting solution for endoscopic resection procedures and has gained popularity for its convenient pre-filled syringe. However, here the present two cases show that ORISETM gel induces marked foreign body giant cell granulomatous reaction in the submucosa and muscularis propria following endoscopic resection. METHODS AND RESULTS: A 73-year-old female underwent laparoscopic right colectomy after her initial endoscopic polypectomy of a hyperplastic polyp, and a 78-year-old male had partial gastrectomy following endoscopic mucosal resection of an invasive adenocarcinoma. Both patients had submucosal injection of ORISETM gel during endoscopic procedures, and the surgical resection specimens showed ORISETM gel deposition and extensive foreign body giant cell granulomatous reaction in the submucosa and muscularis propria. CONCLUSION: These cases raise the awareness that ORISETM gel stimulates extensive foreign body reaction at the injection site, and the further consequence is still unclear.

Vulvar Silicone Granuloma.

We report a case of vulvar silicone granulomas following injection of liquid silicone into the labia. The patient is a 51-yr-old female who presented with vulvar pain and enlarged, indurated labia majora. In the past, she had undergone bilateral labial cosmetic augmentation with a silicone-based filler injected directly into the labia and into the gluteal regions. This had been performed in a nonmedical setting. At surgery, oblong firm soft tissue masses were removed from both labia. Microscopically, the lesions demonstrated replacement of the subcutaneous adipose tissue by fibrous tissue containing innumerable round empty spaces of different sizes, either within or surrounded by macrophages and occasional foreign-body giant histiocytes. The clear vacuoles corresponded to silicone fluid which had been dissolved during tissue processing. There are only rare case reports of vulvar silicone granuloma in the literature, and these were due to migration of silicone to the vulva from distant sites. Our report details a case of vulvar silicone granuloma secondary to direct injection of liquid silicone material into the labia.

Granulomatous Reaction to Cosmetic Soft Tissue Filler with Late-onset Inflammatory Response.

is missing (Short communication).

[Eruptive granuloma after injection of Ellansé® successfully treated using methotrexate]. / Granulomes après injection d'Ellansé®, résolutifs sous méthotrexate.

BACKGROUND: Collagen stimulators such as Ellansé® are soft tissue fillers able to induce nucleogenesis. We describe a case of eruptive foreign body granulomas following injection of Ellansé® that were successfully treated using methotrexate. CASE REPORT: A 47-year-old woman received injections of Ellansé® for the wrinkled aspect of her cheeks. She had previously undergone injections of hyaluronic acid on the nasolabial folds. Nine months after the Ellansé® injections, the patient consulted for the recent appearance of multiple nodules on her face. Histological analysis of one of these nodules confirmed the presence of foreign-body granulomas developed in contact with spherical gaps of a size substantially identical to the Ellansé® vacuoles. Methotrexate 10mg per week for 3 months followed by 20mg per week for 9 months resulted in complete regression of the nodules. DISCUSSION: Ellansé® is composed of two biocompatible and bioabsorbable polymers: carboxymethylcellulose, responsible for immediate volume creation, and polycaprolactone, which promotes collagen synthesis. However, any injected product can cause varying degrees of granulomatous reaction. Hyaluronic acid was previously injected at several other sites on the patient's face. These lesions were not the result of poor injection technique. CONCLUSION: Although collagen stimulators are biocompatible and bioabsorbable substances, the development of foreign-body granulomas, while rare, is still possible. Methotrexate resulted in significant regression of nodules as of the third month of treatment.

Foreign-Body Granulomata Caused by Injected Permanent Filler Masquerading as Cutaneous Sarcoidosis.

Foreign-body granuloma formation following filler injections is most commonly seen with permanent fillers; these reactions can occur years following the injections and often require either an intralesional steroid injection or surgical excision. The authors present a case of a 75-year-old woman with a history of systemic sarcoidosis previously treated with numerous immunosuppressive medications who was examined for bilateral infraorbital nodules and swelling that were unresponsive to treatment. She underwent a bilateral anterior orbitotomy through a transconjunctival approach with mass excision. The histologic analysis was consistent with foreign-body granulomata juxtaposed to implantable material, specifically ArteFill, which was injected many years prior. There were no separate noncaseating granulomas to suggest sarcoidosis as the underlying etiology. It is important to consider prior filler injections in patients with sarcoidosis who present with subcutaneous nodules as this changes management and may prevent the need for more aggressive immunosuppressive treatment.

Clinical value of high-resolution (5-17 MHz) echo-color Doppler (ECD) for identifying filling materials and assessment of damage or complications in aesthetic medicine/surgery.

PURPOSE: The purpose of this retrospective study is to evaluate the role of echo-color-Doppler (ECD) imaging in identifying a series of characteristics pursuant to aesthetic filling material such as their degree of absorbability and their potential complications which include their propensity to stimulate the formation of encapsulated foreign-body granulomas. In the latter case, ECD can be of aid by giving indication for surgical therapy. MATERIALS AND METHODS: Over a 4-year period, we studied 180 patients (60 ♂) who underwent an aesthetic medical/surgical treatment. We used ECD to evaluate the implant material, its thickness, the injection site, the integrity of dermal layers and the presence of any associated complications. RESULTS: In 97% (174/180) of our patients, we were able to identify the type of material used; furthermore, 57% of patients had a hyaluronic acid implant, 14% a lipofilling and 29% a non-absorbable filler (with 10% of silicone). In 6/180 (3%), we could not recognize the material used; 89% (161/180) of our patients presented post-injection complications; moreover, 67% showed peri-implant dermal-hypodermal thickening areas with adjacent lymphostasis, 6% displayed an abnormal implant site, and 17% showed inflammation with encapsulated foreign-body granulomas that required subsequent surgical excision. Biopsy samples were obtained from 37/180 patients (21%); among these, 31 patients had an ECD evidence of granuloma and on 6 patients we were not able to define the injected material. Histopathological examination identified 29 granulomas, 5 sterile abscesses and 3 chronic inflammations in the absence of granuloma. ECD showed an overall 78% diagnostic accuracy, with 90% sensitivity and 37% specificity in detecting filler granulomas. CONCLUSION: ECD is a low-cost technique that allows to identify filling materials and to assess the complications of an esthetic medical/surgical treatment.

High-frequency ultrasound-based differentiation between nodular dermal filler deposits and foreign body granulomas.

BACKGROUND: The number of procedures involving dermal filler injection is still on the rise. Although their safety is improving, not all complications can be avoided. The late complications manifesting as nodules or granulomas pose a particular diagnostic and therapeutic challenge, due to the lack of uniform standards or guidelines. High-frequency, ultrasound imaging appears to be a useful method for distinguishing between granulomas and nodular dermal filler deposits. AIM: The aim of the paper was to evaluate the utility of high frequency ultrasound imaging for distinguishing between foreign body granulomas and nodular dermal filler deposits. MATERIAL AND METHODS: Eleven females aged 21-66 years (mean age of 43.6 years old) who had soft tissue fillers injected were enrolled. All patients had a high-frequency ultrasound scan of the involved skin area performed. The shape, margins, area, location and echogenicity of the lesions were assessed. Additionally, the lesions were evaluated histologically and photographs were taken. RESULTS: The analysis indicated differences between the ultrasound image of granulomas and dermal filler deposits. Characteristic ultrasound features of granulomas include oval shape and blurred, irregular outer edges. Small hyperechoic areas were seen inside the granulomas. The deposits were anechogenic, with sharp, regular borders. CONCLUSIONS: High-frequency ultrasound imaging enables distinguishing between granulomas and nodules-dermal filler deposits, which form after dermal filler injections.

Alopecia with foreign body granulomas induced by Radiesse injection: A case report.

Radiesse is a soft tissue filler which has been widely used for cosmetic enhancement. The safety of Radiesse has been thoroughly investigated via numerous studies. A late-onset complication of Radiesse injection consists of foreign body granulomas, with only three case reports in over 10 years of clinical use. Herein, we describe the case of a patient who experienced alopecia with foreign body granulomas at the injection region one month after receiving a Radiesse injection. To our knowledge, this is the first report in the English literature of alopecia as an adverse event associated with Radiesse injection. The present case reminded physicians to evaluate more cautiously the necessity of injecting filler into hair-bearing area for lifting purpose. This procedure may cause foreign body granulomatous reaction, which may result in hair loss at the injection region.

Granulomatous reaction to Belotero Balance: A case study.

OBJECTIVE: The most commonly used dermal fillers are hyaluronic acids (HAs), and in general, are well tolerated with mild to moderate risk of adverse events. The most frequently reported side effects are injection site erythema and bruising. We present the first case of a patient who developed a severe granulomatous foreign body reaction to the HA filler, Belotero Balance. In our review of the literature, a granulomatous reaction has never before been reported as a side effect of this particular HA filler (1). CASE: On exam, the patient had firm erythematous, granulomatous plaques on her bilateral cheeks, with a tender, fluctuant nodule on her right cheek. Complete resolution of this delayed reaction was achieved after several injections of intralesional Kenalog (IL-K) 2.5 mg/cc, and further fine-tuning was achieved through laser resurfacing. CONCLUSION: Granulomatous reactions can occur with any HAs, though such incidents are not commonly reported. These delayed reactions are generally localized immunological reactions, though biofilm infections should be excluded where appropriate. It is only with long-term (5-year) longitudinal studies that accurate numbers of such reactions will be known.

Cutaneous foreign body granulomas associated with lipolytic cocktail: Who is the enemy, mesotherapy or drugs injected?

Mesotherapy is widely used for its lipolytic effect as an alternative procedure to surgical methods. Although many benefits of lipolytic mesotherapy have been observed, numerous side effects have also been reported. Here, we report a case of cutaneous foreign body granulomas that occurred after lipolytic mesotherapy.

B Cell Lymphoma Underlying Paraffinoma of Glabella.

Soft tissue reactions to paraffin include inflammation, fibrosis, disfigurement, and granulomatous inflammation with foreign body giant cell reaction. The authors report the case of a 77-year-old woman with cutaneous marginal zone B cell lymphoma located on glabella, arising in association with underlying paraffinoma. While it is unclear whether the implant directly contributed to the development of lymphoma, this association has not been previously documented, prompting this report.

Perigraft vascularization and incorporation of implanted Dacron prostheses are affected by rifampicin coating.

BACKGROUND: Prosthetic vascular grafts are increasingly implanted to replace damaged arteries. However, their microbial contamination is highly problematic and often results in devastating clinical complications. To reduce the risk of infection, Dacron grafts may be coated with rifampicin. In this experimental study we analyzed whether this coating affects the early tissue incorporation of the grafts. METHODS: Saline- and rifampicin-coated Dacron (Dacron-Rifamp) grafts were implanted into dorsal skinfold chambers of C57BL/6 mice (n = 8 per group) to study vascularization, inflammation, cell proliferation, and apoptosis at the implantation site using repetitive intravital fluorescence microscopy and immunohistochemistry over an observation period of 14 days. RESULTS: Implanted Dacron-Rifamp grafts exhibited a impaired vascularization, indicated by a significantly lower functional capillary density (85 ± 1 cm/cm2) compared with controls (113 ± 1 cm/cm2; P < .05). This was associated with a reduced number of Ki-67-positive proliferating cells (9.4% ± 1.1% vs 13.5 ± 0.4%; P < .05) and an increased number of cleaved caspase-3-positive apoptotic cells (2.7% ± 0.3% vs 1.3% ± 0.3%; P < .05) in the newly developing granulation tissue surrounding the implants. In addition, the neutrophilic (652 ± 84 mm2 vs 934 ± 117 mm2; P = .06), lymphatic (26 ± 6 mm2 vs 39 ± 9 mm2; P = .24) and macrophage response (177 ± 42 mm2 vs 233 ± 86 mm2; P = .57) was decreased by trend in the group with Dacron-Rifamp grafts. CONCLUSIONS: Our novel findings show that early perigraft vascularization and incorporation of implanted Dacron prostheses are affected by the rifampicin coating. Because rapid graft vascularization and incorporation are thought to reduce the risk of infection, the use of Dacron-Rifamp Dacron grafts for antibacterial prophylaxis should be reconsidered particularly in cases of elective arterial reconstruction in a noninfected environment.

Minocycline for the treatment of cutaneous silicone granulomas: A case report.

Silicone oil injections are often used for soft tissue augmentation and local and general adverse effects occurring from a few months to 15 years after injection have been reported. Here, we present a case of delayed granuloma formation due to liquid injectable silicone with large extent of involvement, which precluded surgical removal. Our patient was successfully treated with minocycline, considering its anti-inflammatory, immunomodulating and antigranulomatous properties. This case presents minocycline monotherapy as a useful treatment option for the management of severe granuloma induced by silicone use when surgical excision is not possible.

Delayed granulomatous reactions to facial cosmetic injections of polymethylmethacrylate microspheres and liquid injectable silicone: A case series.

Polymethylmethacrylate microsphere (PMMA) and liquid injectable silicone (LIS) fillers are non-biodegradable, synthetic polymers utilized for long-term soft-tissue augmentation. Delayed granulomatous reactions to permanent fillers are a rare yet significant event that can occur months to years post procedure and are often refractory to treatment and associated with significant cosmetic morbidity. We report a case series of 4 patients who developed granulomatous reactions to PMMA or LIS, 15 months to 5 years post injection. The etiology of granulomatous reactions to permanent fillers is still poorly understood, with foreign-body reactions and/or biofilms purported to play a role. Real-time biochemical analysis with polymerase chain reaction should be performed when the index of suspicion for the presence of a biofilm is high.