Cyanoacrylate glue reactions: A systematic review, cases, and proposed mechanisms.

OBJECTIVE: Cyanoacrylate glue closure was first used in humans 10 years ago to treat venous reflux of the axial veins. Studies have since shown its clinical efficacy in vein closure. However, great need exists to elucidate further the types of specific adverse reactions that cyanoacrylate glue can cause for better patient selection and to minimize these events. In the present study, we systematically reviewed the literature to identify the types of reported reactions. In addition, we explored the pathophysiology contributing to these reactions and proposed the mechanistic pathway with inclusion of actual cases. METHODS: We searched the literature for reports of reactions following cyanoacrylate glue use in patients with venous diseases between 2012 and 2022. The search was performed using MeSH (medical subject headings) terms. The terms included cyanoacrylate, venous insufficiency, chronic venous disorder, varicose veins, vein varicosities, venous ulcer, venous wound, CEAP (clinical, etiologic, anatomic, pathophysiologic), vein, adverse events, phlebitis, hypersensitivity, foreign body granuloma, giant cell, endovenous glue-induced thrombosis, and allergy. The search was limited to the literature reported in English. These studies were evaluated for the type of product used and the reactions noted. A systematic review, in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) method, was performed. Covidence software (Melbourne, VC, Australia) was used for full-text screening and data extraction. Two reviewers reviewed the data, and the content expert served as the tiebreaker. RESULTS: We identified 102, of which, 37 reported on cyanoacrylate use other than in the context of chronic venous diseases and were excluded. Fifty-five reports were determined appropriate for data extraction. The adverse reactions to cyanoacrylate glue were phlebitis, hypersensitivity, foreign body granuloma, and endovenous glue-induced thrombosis. CONCLUSIONS: Although cyanoacrylate glue closure for venous reflux is generally a safe and clinically effective treatment choice for patients with symptomatic chronic venous disease and axial reflux, some adverse events could be specific to the properties of the cyanoacrylate product. We propose mechanisms for how such reactions can occur based on histologic changes, published reports, and case examples; however, further exploration is necessary to confirm these theories.

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.

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

BACKGROUND: 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). MATERIALS & METHODS: We present a three patient case series in which GFBR secondary to dermal filler was successfully treated with a multi-leveled approach. The first modality involves intralesional injection of a mixture containing 1 cc of 5-fluorouracil (5-FU), 0.5 cc of dexamethasone sodium phosphate, and 0.1 cc of triamcinolone 10. The lesion is injected intradermally in small aliquots, similar to scar treatment. The patient then takes colchicine 1.2 mg loading dose on day 1, then 0.6 mg twice per day for 4 days concurrently with naproxen 500 mg orally once daily for 5-7 days. This process may be repeated in 6 weeks if the lesions have not resolved and PDL laser may be employed for residual post-inflammatory erythema. RESULTS: All three patients presented in this case series had significant aesthetic improvement in their dermal filler-derived foreign body granulomatous reactions. CONCLUSION: 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.

Delayed complication of botulinum toxin and hyaluronic acid filler injections: A case report.

BACKGROUND: Botulinum toxin and hyaluronic acid (HA) filler injections are popular minimally invasive cosmetic procedures owing to their convenience, efficiency, and durability; however, adverse reactions often occur. MATERIALS AND METHODS: We describe the delayed hypersensitivity reaction that occurred after sequential injections of botulinum toxin and HA filler. RESULTS: The histopathologic and dermatoscopic findings suggested a delayed hypersensitivity reaction with the formation of a dermal foreign body granuloma. The rash resolved 2 months following treatment with antihistamines and topical steroids cream. CONCLUSION: We assume that local trauma during the blepharoplasty stimulated an immune response, which was the basis for this complication.

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.

Dermal Filler Presenting as Parotid Mass: A Case Report.

Dermal filler injections are common cosmetic procedures and are growing in popularity. While frequently performed, dermal filler injections carry a risk of adverse events including vascular compromise and foreign body granulomas. Here, we discuss an unusual case of a patient with a history of dermal filler injections presenting with a parotid mass and an eyebrow mass requiring surgical resection. This case demonstrates the risk of delayed granuloma formation many years after dermal filler injection and highlights the importance of awareness and management of these potential long-term complications.

Delayed Acute Granulomatous Anterior Uveitis after Inadvertent Intraocular Injection of Tattoo Ink from a Scleral Tattoo Procedure.

Purpose: To improve awareness of delayed onset uveitis in patients with a history of intraocular tattoo ink injection.Results: A 47-year-old man underwent a scleral tattoo procedure during which there was inadvertent intraocular injection of tattoo ink into his right eye. He subsequently developed endophthalmitis, retinal detachment, and retinal necrosis. He was treated with intravitreal and oral antibiotics and underwent vitreoretinal surgical intervention. A vitreous specimen was obtained and demonstrated significantly elevated levels of several heavy metals. One month later, he developed an acute granulomatous anterior uveitis in the same eye that was managed with a combination of topical and perioperative intravitreal, intravenous, and oral corticosteroids.Conclusion: This case highlights the importance of monitoring patients with a history of intraocular tattoo ink injection for delayed onset uveitis in addition to retinal toxicity.

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.

Polytetrafluoroethylene granuloma-associated facial palsy following microvascular decompression.

OBJECTIVE: Microvascular decompression (MVD) may be employed in the management of hemifacial spasm (HFS), wherein a pledget of polytetrafluoroethylene (i.e., Teflon, Chemours, Wilmington DE) is sometimes introduced to separate an offending vessel from the cisternal segment of facial nerve. Rarely, Teflon may cause a granulomatous reaction resulting in nerve palsy. We here present the first case series of facial palsy thought to be secondary to Teflon granuloma following MVD for HFS. METHODS: A data repository of 1,312 patients with facial palsy was reviewed to identify individuals who had previously undergone MVD for HFS. Data collected include age at time of MVD, age at onset of facial weakness and at presentation, House-Brackmann scores, clinician-graded facial function using the Electronic Facial Paralysis Assessment scale, imaging findings, and therapeutic interventions and outcomes. RESULTS: Six patients meeting criteria were identified. Average time between MVD with Teflon placement and onset of facial weakness was 16.1 (±4.9) years (range 9.3-23.3 years). Initial House-Brackmann scores were as follows: four patients with V/VI and one each with III/VI and IV/VI. Interventions included eyelid weight placement (n = 3), chemodenervation (n = 2), static suspension with tensor fascia latae (n = 2), dynamic reanimation with cranial nerves V to VII transfer (n = 1), and temporalis muscle transfer (n = 1). CONCLUSION: Teflon granuloma should be considered in the differential diagnosis for patients presenting with new onset facial weakness with a previous history of MVD for HFS. It remains unknown whether early granuloma extirpation is effective. Prompt diagnosis allows consideration of time-sensitive nerve transfer procedures to reanimate facial function. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1422-1427, 2020.

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.