As a first-year podiatric surgery resident, the first consult I evaluated was a patient with opioid use disorder who had been injecting drugs into their lower extremities.  The wounds were deep and foul-smelling, with extensive necrosis of the subcutaneous tissues. My attending related that the wounds had a different appearance than the wounds we had seen in our previous opioid disorder patients who injected themselves with substances such as Heroin or Fentanyl.  Podiatrists who have not commonly encountered this type of pathology may not understand how the substances being injected may change the appearance of the wound and the treatment plan.  

To provide some background knowledge, prescription opioids were the leading cause of drug overdose deaths from 2007-2013, which eventually progressed to heroin from 2014-2015. From 2016 to the present day, Fentanyl is the leading cause of drug overdose deaths [1]. Xylazine (primarily used as a horse anesthetic) is found to be a common adulterant in the fentanyl supply due to its low cost, availability, and effects. Philadelphia is believed to be the forefront location of the Xylazine drug supply crisis. According to a most recent study by the Philadelphia Department of Health, 90% of street opioid samples had Xylazine detected within the sample [3]. The patient population in Philadelphia commonly refers to Xylazine as “tranq.”

Xylazine is an alpha-2 adrenergic agonist that decreases sympathetic nervous system activity, thus leading to a sedative effect. It has a synergic with other drugs, such as Fentanyl or Heroin, and is theorized to extend the duration of the sedative effects [2,4]. In addition to the psychological impact of Xylazine, dermatologic manifestations leave patients with debilitating pain and sizeable soft tissue deficits. The exact mechanism by which Xylazine causes dermatologic manifestations is not proven. However, many hypotheses exist, and more specific investigation is needed. Xylazine is deemed cytotoxic, which can cause dermal necrosis. Xylazine has vasoconstrictive effects on peripheral vessels, ultimately leading to hypoxia and subsequent tissue damage/death. Fentanyl, being commonly adulterated by Xylazine, has a short-lived manifestation, thus requiring a shorter period between injections to maintain psychoactive effects and leading to a higher concentration of xylazine within the soft tissues. [4]

Xylazine wounds commonly manifest on the extensor surfaces of the lower extremity. The wounds start as blisters with intact skin that develop at or around the injection sites. The blisters often harden into dry eschar (the most identifiable feature) or can develop into ulcers, which can be extensive and lead to exposed tendons, muscles, and bones [5]. Based on the experience of the two authors, these wounds are very extensive in terms of depth and exposed structures; however, most often, the wounds are not infected. 

Caring for these wounds in the at-risk population provides an extremely difficult task. In the proper setting, local wound care will suffice for treatment. Dressings such as xeroform, collagenase, or hypochlorous acid wound solution have been used for local care [6]. Xeroform, followed by gauze, is often used for local care upon initial consultation. The ability to perform local wound care following hospital discharge proves difficult for this patient population, given unstable housing scenarios and limited access to adequate wound care supplies. Secondly, the patient’s ability to refrain from further injecting is often the most significant barrier. Relapse with opioid use disorder is not uncommon, thus starting the cycle over again. Another complicating factor is that drug treatment (detox) centers may reject patients who need medical management, such as local wound care, and skilled nursing facilities may reject patients with opioid use disorders [5]. 

Most of these patients at our institution are seen by the wound care service. Given the large volume of patients seen with this pathology daily, the surgical services (orthopedics, podiatry, general surgery) are only consulted when clinical evidence of infection is present, such as cellulitis, abscess, or radiographic evidence of infection. The Burn Surgery team is our institution's leading service in performing operative debridement. Initially, our tentative treatment plan is to perform a surgical debridement. Surgical debridement may be ill-advised, given the uncertainty of adherence to postoperative recommendations. Recent publications regarding managing these wounds suggest that debridement may also impair wound healing by exposing deeper underlying structures such as tendons and bones. Therefore, aggressive local wound care should be the initial mainstay treatment for this pathology.  Surgical debridement should ultimately be saved when the patients are active and stable in substance use treatment [4] unless operative debridement is needed for infection eradication.

In conclusion, with a large amount of street drugs containing Xylazine, there is a noted increased prevalence of extensive lower extremity wounds associated with injection drug use. Treating providers should resist the urge to perform debridement and continue with local wound care. Ultimately, surgical intervention is reserved for patients who have demonstrated continued ability to participate in substance use treatment and are most likely to follow up with postoperative care. When social circumstances are not optimal, local wound care is the treatment choice for xylazine wounds in the absence of infection. 

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. 2022 Aug 19;14(8):e28160. doi: 10.7759/cureus.28160. PMID: 36148197; PMCID: PMC9482722.

[2] D'Orazio J, Nelson L, Perrone J, Wightman R, Haroz R. Xylazine Adulteration of the Heroin-Fentanyl Drug Supply: A Narrative Review. Ann Intern Med. 2023 Oct;176(10):1370-1376. doi: 10.7326/M23-2001. Epub 2023 Oct 10. PMID: 37812779.

[3] Philadelphia Department of Public Health Substance Use Prevention and Harm Reduction. Health Update: Xylazine (tranq) exposure among people who use substances in Philadelphia. 8 December 2022.

[4] Perrone J, Haroz R, D'Orazio J, Gianotti G, Love J, Salzman M, Lowenstein M, Thakrar A, Klipp S, Rae L, Reed MK, Sisco E, Wightman R, Nelson LS. National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings. Ann Emerg Med. 2024 Mar 15: S0196-0644(24)00080-5. doi: 10.1016/j.annemergmed.2024.01.041. Epub ahead of print. PMID: 38493376.

[5] McFadden R, Wallace-Keeshen S, Petrillo Straub K, Hosey RA, Neuschatz R, McNulty K, Thakrar AP. Xylazine-associated Wounds: Clinical Experience from a Low-barrier Wound Care Clinic in Philadelphia. J Addict Med. 2024 Jan-Feb 01;18(1):9-12. doi: 10.1097/ADM.0000000000001245. Epub 2023 Nov 29. PMID: 38019592; PMCID: PMC10967264.

[6] Carroll JJ. Xylazine-Associated Wounds and Related Health Concerns Among People Who Use Drugs: Reports from Front-Line Health Workers in 7 US States. Subst Use Addctn J. 2024 Apr;45(2):222-231. doi: 10.1177/29767342231214472. Epub 2024 Jan 2. PMID: 38258791.