In the ever-evolving drug overdose crisis in the United States, there is increasing public awareness that street drugs are frequently being adulterated or “laced” with the ultrapotent opioid fentanyl, often with deadly results among unsuspecting and intentional users alike. Now, fentanyl is increasingly being laced with a drug intended for use in veterinary medicine as a sedative and analgesic.1 The nonopioid drug xylazine — or “tranq” — has steadily made its way into the illicit drug supply, with an especially high presence reported in Pennsylvania, Maryland, and Connecticut.2
Some individuals are inadvertently exposed to the drug while using fentanyl or other substances, while others use xylazine intentionally. In any case, xylazine consumption is associated with high rates of fatal overdose, and since it is not an opioid, the overdose antidote naloxone is likely ineffective in these instances.1 In the 10-year period ending in 2019, the presence of xylazine detected in cases of fatal opioid overdose increased from less than 2% to 31%, according to recent findings published in Injury Prevention.3 In Connecticut, the number of reported opioid overdose deaths involving xylazine increased by 4-fold between 2019 and 2022.4
In addition, many people who use xylazine or drug mixtures containing xylazine have developed extensive, catastrophic skin ulcers and wounds.5 The necrotic skin ulcerations resulting from xylazine injection are “distinctly different from other soft-tissue infections (eg, cellulitis, abscesses) often associated with injection drug use,” according to an advisory released in November 2022 by the US Food and Drug Administration.1 “These ulcerations may develop in areas of the body away from the site of injection,” it was noted. The treatment of these conditions is further complicated by the circumstances associated with drug dependence and substantial gaps in health care services and treatment for substance use disorder.6,7
To learn more about this escalating public health problem as well as treatment implications for clinicians, we interviewed the following experts: hospital medicine specialist Varun Malayala, MD, MPH, FACP, FHM, system medical director of Crozer-Keystone Health System and facility medical director at Taylor Hospital, both in the Philadelphia area, and author of a 2022 case report5 on the topic; and Edward C. Traver, MD, assistant professor of medicine in the division of clinical care and research at the Institute of Human Virology at the University of Maryland School of Medicine in Baltimore.
What types of skin conditions are physicians seeing in people who inject xylazine, and where are these patients primarily seeking treatment?
Dr Malayala: Patients are developing necrotic ulcers and wounds because xylazine is a vasoconstrictor. Sometimes they have infections and sometimes they do not. However, people who inject drugs (PWID) have a very high risk of infections from organisms like Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Streptococcus, Pseudomonas, and even anaerobic infections, as these patients have very poor blood supply. Sometimes the infections can extend into the muscle and even into the bone. There are patients who have had leg amputations as well because the bone infections were life threatening.
Most of the patients are not receiving any treatment because of the phobia of bias when they go to the hospital, as they are often labeled as drug users. Also, they are afraid they might not receive adequate opiate replacement therapy because they tend to use a lot of fentanyl and heroin on the streets, and it is sometimes difficult to give equivalent doses while they are admitted to the hospital.
There are some patients who are going to the emergency room and getting treated with further hospitalization. Some patients come to the office and see their addiction medicine doctors but refuse to go to the hospital.
Dr Traver: Skin ulcers are well-recognized sequelae of injection drug use (IDU), even prior to the introduction of xylazine into the drug supply.8 The pathogenesis of these ulcers is unclear but is probably driven by a combination of venous and lymphatic insufficiency, thrombophlebitis, skin and soft tissue infections (SSTIs), and caustic and vasoactive effects of the drugs or adulterants. Injection of cocaine, for example, is thought to contribute to tissue necrosis through local vasospasm. Xylazine, a clonidine analogue, may also cause ulcers through vasoconstriction and necrosis.
Skin ulcers related to IDU may be superficially infected and may be associated with SSTIs, osteomyelitis, bacteremia, or endocarditis. SSTIs in people who inject drugs (PWID) are usually caused by the same bacteria as in people who do not inject drugs, namely Staphylococcus and Streptococcus species.
Since the emergence of xylazine as a drug adulterant in Puerto Rico in the early 2000s, there have been reports that xylazine causes more severe or frequent skin ulcers [than other drugs].2 As xylazine has spread to the drug supply in Philadelphia and now much of the country, there are continued reports of severe ulcers and even limb necrosis in PWIDs. The role of xylazine or other drug adulterants is difficult to determine, but many PWIDs and healthcare providers have noted this association. Currently, there is limited data about the prevalence of xylazine and its connection to ulcers.
PWID may seek care for skin ulcers or infections in emergency departments and hospitals, primary care offices, and in harm reduction facilities. Due to stigma and criminalization around drug use, PWID may not be able to readily access health care.
What treatment approaches are required for these infections, and what are other important aspects of care for these patients – for example, referral to harm reduction services and treatment for substance use disorder?
Dr Malayala: People who develop extensive wounds need aggressive and early management as soon as possible. The ideal solution is to encourage them to go to the emergency room right away and get admitted to the hospital, as they require IV antibiotics and wound care. At the same time, they should be receiving medication-assisted treatment for their underlying opiate use.
Harm reduction is very important in these cases as well, especially when they refuse to go to the emergency room to get timely treatment. They should be advised not to inject drugs into these wounds, and they should be advised about clean needles and the need to avoid sharing needles.
Dr Traver: Skin ulcers and infections in PWID, including xylazine, require a multidisciplinary approach to care. In a hospital setting, this may include addiction, infectious disease, surgical, and wound care specialists. Antibiotics may be needed for associated infections but may not be required for ulcers that are only superficially infected. Wound care is of paramount importance. Sharp debridement of ulcers and infections may be needed.
To address the root cause of the ulcers, treatment of substance use disorders — including medication such as buprenorphine or methadone — should be offered if indicated. Patients should be counseled on harm reduction techniques to reduce the chance of recurrent ulcers, such as sterile and safe injection technique. Patients should also be connected to outpatient services including wound care, addiction treatment, and syringe service programs. There are more and more resources available for people to test their drugs for xylazine and fentanyl, which may be useful to inform people about what they are using.
What are additional recommendations for clinicians regarding this issue?
Dr Malayala: Clinicians, especially when they are not trained in addiction medicine, tend to focus on management of the wounds and the infections but are not adequately trained to manage the opiate dependence and misuse. With opiate misuse growing into a national emergency, clinicians should have better training and understanding about its management.
What are the top needs in this area in terms of resources, education, and research?
Dr Malayala: Law enforcement has a major role to play, as the effects of xylazine are unknown throughout most of the country. There is also not enough literature and data about xylazine use and its effects on the human body.
More research is required to develop management guidelines about xylazine use. The traditional urine toxicology screen also does not detect xylazine, and it might be worthwhile exploring a urine toxicology screen to identify its presence.
Dr Traver: There is a lack of scientific data on the causes of skin ulcers in PWID and if and how xylazine causes more severe ulcers. Research on the link between xylazine and other drug adulterants and skin ulcers is urgently needed. Clinicians, harm reduction practitioners, and PWIDs should be aware of the possibility of severe harm from injecting drugs that may be adulterated and nonsterile.
There is much that the government can do to address skin ulcers and other harms from IDU. Regulation of the drug supply would enable people to control what they use and better avoid overdose, infection, and other serious harms. The creation of safe places for people to use drugs — often called supervised injection facilities or safe consumption sites — allows people the time and space to inject in a sterile fashion and seek care if they need it.6
Healthcare providers and the public should strive to combat the stigma that contributes to illness and death among people who use drugs. All healthcare providers should educate themselves on substance use disorders and obtain the DEA waiver to prescribe buprenorphine for opioid use disorder.9 Even dermatologists can do it!
- US Food and Drug Administration. FDA warns about the risk of xylazine exposure in humans. Published November 8, 2022. Accessed December 28, 2022.
- Friedman J, Montero F, Bourgois P, et al. Xylazine spreads across the US: a growing component of the increasingly synthetic and polysubstance overdose crisis. Drug Alcohol Depend. 2022;233:109380. doi:10.1016/j.drugalcdep.2022.109380
- Johnson J, Pizzicato L, Johnson C, Viner K. Increasing presence of xylazine in heroin and/or fentanyl deaths, Philadelphia, Pennsylvania, 2010-2019. Inj Prev. 2021;27(4):395-398. doi:10.1136/injuryprev-2020-043968
- Altimari D. CT sees rise in deadly overdoses involving animal tranquilizer. CT Mirror. Published December 22, 2022. Accessed December 28, 2022.
- Malayala SV, Papudesi BN, Bobb R, Wimbush A. Xylazine-induced skin ulcers in a person who injects drugs in Philadelphia, Pennsylvania, USA. Cureus. 2022;14(8):e28160. doi:10.7759/cureus.28160
- Tanenbaum M. With ‘tranq dope’ afflicting more drug users, Philly steps up overdose response training and wound care. PhillyVoice. Published December 5, 2022. Accessed December 28, 2022.
- Joseph A. ‘Tranq’ is leaving drug users with horrific wounds. It’s spreading. STAT. Published December 2, 2022. Accessed December 28, 2022.
- Rodriguez T. Skin infections in people who inject drugs. Dermatology Advisor. Published August 6, 2021. Accessed December 28, 2022.
- Become a buprenorphine waivered practitioner. Published April 21, 2022. Accessed December 28, 2022.