LETTERS AND COMMUNICATIONS A Cautionary Tale: A Vascular Event With Deoxycholic Acid Injection Vascular occlusive events with deoxycholic acid, ATX101 (Kybella), have not been previously described in the literature. We report a case of what appears to be a vascular occlusive event after deoxycholic acid injection. Deoxycholic acid is a cytolytic compound approved for the treatment of submental fat, which destroys the cell membrane and causes cell lysis after injection.1 Four Phase III trials have shown reduction in submental fat by visual appearance and magnetic resonance imaging.2 Adverse effects, after Phase III clinical trials, were said to be only mild to moderate, transient, localized to the injection site, and not preventative of further treatment.3 Adverse reactions noted include the following: injection site reactions such as edema, hematoma, erythema, pruritus, pain, induration, paresthesia, nodules, skin tightness, site warmth, and nerve injury as well as some minor systemic side effects.1 To the best of our knowledge, there have been no described vascular occlusive events using deoxycholic acid published in the literature, unlike hyaluronic acid filler, which has shown vascular occlusive events causing adverse effects such as skin necrosis and visual disturbance.4,5 Our patient, presented here, appeared to have a vascular occlusive event after deoxycholic acid injection.
removable pencil was used to mark out the treatment area, and a tattoo grid was placed. It was decided to inject 2 vials within the marked area of the submental fat zone. The tissue was pinched outward, and a 30gauge needle was inserted half way down into the subcutaneous tissue with each injection. Then, near the end of the treatment, an injection caused the patient to wince in pain. About one-eighth of the 0.2 mL of deoxycholic acid was injected when a white linear blanch was noted immediately running lateral and upward from the injection site (Figure 1). The needle was immediately removed, and the blanched area was massaged. Within minutes, a 2-cm erythematous patch was noted lateral and inferior to the
A 37-year-old woman presented with moderate submental fullness. The patient is a healthy Caucasian female, not on any medications, who denies any previous surgeries or procedures of the neck. She was first treated with deoxycholic acid submental injections with 2 vials in March of 2017 without complications other than the expected swelling, bruising, and mild numbness. Three months later, she returned for follow-up and desired repeat treatment. For 30 minutes before the deoxycholic acid injection, the patient applied ice to the submental area. A white
Figure 1. Initial white linear blanch after deoxycholic acid injection. Injection site (black arrow) and white linear blanch (red arrow).
© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2017;0:1–3
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© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
LETTERS AND COMMUNICATIONS
injection site. The patient was comfortable at this point without significant discomfort. After 10 minutes, the white linear blanch persisted, and thus 2% nitroglycerin paste was applied. The patient lives 3 hours away, and thus the plan was to correspond closely with photographs and telephone calls. The following morning, pictures sent from the patient revealed a flat erythematous patch in the distribution of the previous white blanched area and medial injection site ecchymosis (Figure 2). She described minimal tenderness of the area. There was slight paresthesia of the submental chin, but this did not extend laterally to the erythematous patch. The sequence of events appeared to resemble a vascular occlusive event, and, as such, aspirin was started along with warm compresses and oral corticosteroids. On Day 5, the patch was slightly more erythematous and a papular eruption had appeared (Figure 3). No obvious blisters were appreciated, and the patient was
Figure 3. Postinjection Day 5. Appearance of a new papular eruption within the erythematous patch.
pain free. Because of the concern of evolving blisters and necrosis, the patient was started on a 10-day course of cephalexin.
Figure 2. Twenty-four hours after injection. Flat erythematous patch and medial injection site ecchymosis.
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Figure 4. Complete resolution of the erythema (4 weeks postinjection).
DERMATOLOGIC SURGERY
© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
LETTERS AND COMMUNICATIONS
A telephone follow-up at 4 weeks revealed complete resolution of her erythema (Figure 4). The patient reported that the papular eruption had gradually improved after a few days on the antibiotics. The persistent erythema took a number of weeks to improve, however, but laser treatment was not needed. Fortunately, this did not evolve into a necrotic epidermal process, perhaps because of the small amount of deoxycholic acid injected, or perhaps from the immediate interventional medications given. To the authors’ knowledge, this is the first reported case of what appears to be a vascular occlusive event after subcutaneous injection of deoxycholic acid for the treatment of submental fat. It is possible that intravascular injection of deoxycholic acid would induce significant irritation and/or spasm of the vessel or endothelial wall swelling to the point of occlusion. Although the exact mechanism of this vascular event remains unclear, this is a significant risk that injectors should note. If vascular occlusive events are a possible peril of deoxycholic acid injections, perhaps further research into the mechanism of occlusion, as well as evaluation of injection technique with a potential of pulling back on the syringe before injections should be explored. As with any new therapy, postmarketing surveillance allows for a more thorough understanding and description of adverse effects associated with deoxycholic acid injection.
References 1. Kythera Biopharmaceuticals Inc. Kybella (deoxycholic acid) injection [prescribing information]. Available from: https://www.mykybella.com/ /media/Unique%20Sites/MyKybella/Documents/KYBELLACombined-FINAL-Labeling.pdf. Accessed June 27, 2017. 2. Georgesen C, Lipner SR. The development, evidence, and current use of ATX-101 for the treatment of submental fat. J Cosmet Dermatol 2017; 16:174–9. 3. Humphrey S, Sykes J, Kantor J, Bertucci V, et al. ATX-101 for reduction of submental fat: a phase III randomized controlled trial. J Am Acad Dermatol 2016;75:788–97.e7. 4. Hirsch RJ, Lupo M, Cohen JL, Duffy D. Delayed presentation of impending necrosis following soft tissue augmentation with hyaluronic acid and successful management with hyaluronidase. J Drugs Dermatol 2007;6:325–8. 5. Hu XZ, Hu JY, Wu PS, Yu SB, et al. Posterior ciliary artery occlusion caused by hyaluronic acid injections into the forehead: a case report. Medicine (Baltimore) 2016;95:e3124.
Kayla Riswold, BS University of South Dakota—Sanford School of Medicine Sioux Falls, South Dakota Valerie Flynn, MD Internal Medicine Department of Dermatology University of South Dakota—Sanford School of Medicine Avera Medical Group Dermatology Sioux Falls, South Dakota The authors have indicated no significant interest with commercial supporters.
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© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
removable pencil was used to mark out the treatment area, and a tattoo grid was placed. It was decided to inject 2 vials within the marked area of the submental fat zone. The tissue was pinched outward, and a 30gauge needle was inserted half way down into the subcutaneous tissue with each injection. Then, near the end of the treatment, an injection caused the patient to wince in pain. About one-eighth of the 0.2 mL of deoxycholic acid was injected when a white linear blanch was noted immediately running lateral and upward from the injection site (Figure 1). The needle was immediately removed, and the blanched area was massaged. Within minutes, a 2-cm erythematous patch was noted lateral and inferior to the
A 37-year-old woman presented with moderate submental fullness. The patient is a healthy Caucasian female, not on any medications, who denies any previous surgeries or procedures of the neck. She was first treated with deoxycholic acid submental injections with 2 vials in March of 2017 without complications other than the expected swelling, bruising, and mild numbness. Three months later, she returned for follow-up and desired repeat treatment. For 30 minutes before the deoxycholic acid injection, the patient applied ice to the submental area. A white
Figure 1. Initial white linear blanch after deoxycholic acid injection. Injection site (black arrow) and white linear blanch (red arrow).
© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2017;0:1–3
·
·
1
© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
LETTERS AND COMMUNICATIONS
injection site. The patient was comfortable at this point without significant discomfort. After 10 minutes, the white linear blanch persisted, and thus 2% nitroglycerin paste was applied. The patient lives 3 hours away, and thus the plan was to correspond closely with photographs and telephone calls. The following morning, pictures sent from the patient revealed a flat erythematous patch in the distribution of the previous white blanched area and medial injection site ecchymosis (Figure 2). She described minimal tenderness of the area. There was slight paresthesia of the submental chin, but this did not extend laterally to the erythematous patch. The sequence of events appeared to resemble a vascular occlusive event, and, as such, aspirin was started along with warm compresses and oral corticosteroids. On Day 5, the patch was slightly more erythematous and a papular eruption had appeared (Figure 3). No obvious blisters were appreciated, and the patient was
Figure 3. Postinjection Day 5. Appearance of a new papular eruption within the erythematous patch.
pain free. Because of the concern of evolving blisters and necrosis, the patient was started on a 10-day course of cephalexin.
Figure 2. Twenty-four hours after injection. Flat erythematous patch and medial injection site ecchymosis.
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Figure 4. Complete resolution of the erythema (4 weeks postinjection).
DERMATOLOGIC SURGERY
© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
LETTERS AND COMMUNICATIONS
A telephone follow-up at 4 weeks revealed complete resolution of her erythema (Figure 4). The patient reported that the papular eruption had gradually improved after a few days on the antibiotics. The persistent erythema took a number of weeks to improve, however, but laser treatment was not needed. Fortunately, this did not evolve into a necrotic epidermal process, perhaps because of the small amount of deoxycholic acid injected, or perhaps from the immediate interventional medications given. To the authors’ knowledge, this is the first reported case of what appears to be a vascular occlusive event after subcutaneous injection of deoxycholic acid for the treatment of submental fat. It is possible that intravascular injection of deoxycholic acid would induce significant irritation and/or spasm of the vessel or endothelial wall swelling to the point of occlusion. Although the exact mechanism of this vascular event remains unclear, this is a significant risk that injectors should note. If vascular occlusive events are a possible peril of deoxycholic acid injections, perhaps further research into the mechanism of occlusion, as well as evaluation of injection technique with a potential of pulling back on the syringe before injections should be explored. As with any new therapy, postmarketing surveillance allows for a more thorough understanding and description of adverse effects associated with deoxycholic acid injection.
References 1. Kythera Biopharmaceuticals Inc. Kybella (deoxycholic acid) injection [prescribing information]. Available from: https://www.mykybella.com/ /media/Unique%20Sites/MyKybella/Documents/KYBELLACombined-FINAL-Labeling.pdf. Accessed June 27, 2017. 2. Georgesen C, Lipner SR. The development, evidence, and current use of ATX-101 for the treatment of submental fat. J Cosmet Dermatol 2017; 16:174–9. 3. Humphrey S, Sykes J, Kantor J, Bertucci V, et al. ATX-101 for reduction of submental fat: a phase III randomized controlled trial. J Am Acad Dermatol 2016;75:788–97.e7. 4. Hirsch RJ, Lupo M, Cohen JL, Duffy D. Delayed presentation of impending necrosis following soft tissue augmentation with hyaluronic acid and successful management with hyaluronidase. J Drugs Dermatol 2007;6:325–8. 5. Hu XZ, Hu JY, Wu PS, Yu SB, et al. Posterior ciliary artery occlusion caused by hyaluronic acid injections into the forehead: a case report. Medicine (Baltimore) 2016;95:e3124.
Kayla Riswold, BS University of South Dakota—Sanford School of Medicine Sioux Falls, South Dakota Valerie Flynn, MD Internal Medicine Department of Dermatology University of South Dakota—Sanford School of Medicine Avera Medical Group Dermatology Sioux Falls, South Dakota The authors have indicated no significant interest with commercial supporters.
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© 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
