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A Foot Ulceration Caused by Unintentional Xylazine Injection
Xylazine, also known as Tranq, is a nonopioid sedative increasingly found in the American illegal drug trade; a cheap, addictive additive to illegal substances, most notably, fentanyl and heroin.
Injecting xylazine into soft tissue can cause severe wounds, some of which are potentially life-threatening. The drug causes vasoconstriction and skin oxygenation deficiency, leading to skin necrosis and subsequent ulceration in and around the area of injection.1
Xylazine is an anesthetic used for specific types of veterinary surgeries, specifically meant for larger animals, such as horses. When humans use xylazine, it has opioid-enhancing effects and can lead to increased dependency by its users. Drug dealers use xylazine to increase the physical mass of the drug it is used with and therefore has street value in many different opiates.2
The drug acts as a nervous system agonist and therefore when combined with heroin or other opiates, xylazine enhances their effects by mimicking a neurotransmitter. More specifically, xylazine’s direct vasoconstrictive effect activates peripheral alpha-2b receptors in the vascular smooth muscles.3 This leads to decreased skin perfusion, which researchers believe to be the pathophysiology of skin ulcers that develop due to chronic use.3
A Closer Look at the Patient Presentation
A 47-year-old female with a history of illegal opioid abuse presented to the emergency room claiming that about 4 days prior, she injected heroin into her right anterior ankle/foot area. She had some amoxicillin/clavulanate at home from a friend and began using that, which initially improved the symptoms, but they subsequently got worse.
On her initial visit to the emergency department, the patient complained of pain, redness, warmth, and edema near the injection site to the extent that she was unable to ambulate (Figure 1). She was admitted to the hospital and an initial ultrasound showed a 3.3 cm2 heterogeneous lesion. She had no leukocytosis. The patient was started on IV vancomycin and piperacillin/tazobactam and after 1 day changed to cefazolin.
A computed tomography (CT) scan showed a 5 x 1.0 x 0.5 cm rim-enhancing collection. Physicians increased the cefazolin dose and her pain and symptoms improved. Magnetic resonance imaging (MRI) showed no abscess present but severe tibialis anterior tenosynovitis so infectious disease recommended discharge and starting the patient on oral cephalexin for 14 days.
Five days later the patient returned to the ER complaining of worsening pain to the same area (Figure 2). She presented with a foul-smelling, necrotic, draining 3 cm2 ulceration with erythema up to the mid-calf area. She stated she did not inject anything further. The hospital admitted her again and started her on IV vancomycin and cefazolin. Another CT scan showed no collection or abscess present and again no leukocytosis present on her bloodwork.
Infectious diseases started the patient on IV linezolid, cefepime, and metronidazole, and consulted podiatry. A day later doctors discontinued her linezolid and put her back on vancomycin. The patient then explained that when she went home after the initial hospital stay, she tested her heroin and cocaine, and it was positive for Tranq. Figure 3 shows the wound 2 days after the patient’s second admission.
We dressed the wound with a xeroform-based dressing initially and on day 4 (Figure 4) she underwent sharp debridement down to and including the muscular layer, exposing an intact tibialis anterior tendon and now mostly granular tissue with some intermixed fibrous tissue noted. Figure 5 shows the wound after debridement. The next day her symptoms began to improve. She spent another 48 hours on IV medications and then was discharged with a plan for oral amoxicillin/clavulanate and trimethoprim/sulfamethoxazole. We gave the patient follow-up appointments with infectious disease and wound care but unfortunately she did not attend any of the appointments and did not return phone calls.
In Conclusion
Xylazine-induced necrosis presents a significant challenge in clinical treatment, largely due to the poorly understood interactions of xylazine with heroin and other injectable opioids. Current management strategies primarily involve antibiotic therapy and surgical debridement, aimed at controlling infection and promoting wound healing.
However, this case highlights the critical need for more comprehensive research into xylazine-induced ulcers. This is necessary to improve patient outcomes and develop effective treatment and prevention strategies. Further studies are essential to elucidate the underlying mechanisms and optimize therapeutic approaches.
Eric Michael Kaplan, DPM, is a Diplomate of the American Board of Foot and Ankle Surgery and is certified in Foot Surgery. He is a partner in Family Footcare Group, LLP, in New York. He is also consulting staff at Garnet Health Medical Center Catskills, attending staff at Garnet Health Medical Center Middletown, surgeon at Hudson Valley Ambulatory Surgery Center, and attending staff at Garnet Wound Care Center Middletown.
Jacob Kaplan is a BS candidate in Ecology and Evolutionary Biology at Tulane University.
References
1. Malayala SV, Papudesi BN, Bobb R, Wimbush A. Xylazine-induced skin ulcers in a person who injects drugs in Philadelphia, Pennsylvania, USA. Cureus. August 19, 2022. Accessed May 1, 2024. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482722/.
2. Centers for Disease Control and Prevention. What you should know about xylazine. Published February 22, 2024. Accessed May 1, 2024.
3. Papudesi BN. Xylazine toxicity. StatPearls [Internet]. July 17, 2023. Accessed May 1, 2024.