Xylazine (“Tranq”): The potential for loss of life and limb

By Warren R. Heymann, MD, FAAD
Dec. 7, 2022
Vol. 4, No. 48

The U.S. overdose crisis continues its exponential growth, although the landscape of responsible substances has changed over the past two decades — cocaine (2000-2006) to prescription opioids (2007-2013), heroin (2014-2015), and illicitly-manufactured fentanyl (2016-present). (1)

Xylazine (street name “Tranq”) is a non-narcotic drug synthesized in 1962 by Bayer that is used as a sedative, analgesic, and muscle relaxant in animals. It is approved for use in dogs, cats, horses, and other animals. Xylazine’s chemical structure closely resembles the phenothiazines, tricyclic antidepressants, and clonidine. According to Ruiz-Colón, “Illicit drugs, such as cocaine and heroin, are often adulterated with other agents to increase bulk and enhance or mimic the illicit drug’s effects… Literature shows some similar pharmacologic effects between xylazine and heroin in humans. Both drugs cause bradycardia, hypotension, central nervous system depression and respiratory depression. Because of these similar pharmacologic effects, synergistic effects may occur in humans when xylazine is use as an adulterant of heroin. Therefore, fatalities among drug users may increase due to the use of xylazine as an adulterant, especially due to the potentiation of the respiratory depressant effects of heroin.” (2) Despite the risk, people may use the combination because it provides a prolonged high. (3)

In Philadelphia, since the mid-2010s fentanyl replaced most of the city’s heroin. By 2020, xylazine-contaminated fentanyl (tranq) has become prevalent. (4) Xylazine was first recognized as an adulterant of fentanyl in 2006. (5) In 2012, Reyes et al surveyed 89 drug users in Puerto Rico to document the use of “anestecia de caballo” (literally translated as “horse anesthesia”). More than 65% reported “speedball” (a mixture of heroin and cocaine) as the principal drug of use; the prevalence of xylazine use was 80.7%. (6) In Philadelphia, xylazine went from being detected in less than 2% of cases of fatal heroin and/or fentanyl overdose between 2010 and 2015 to 31% of 858 fatal heroin and/or fentanyl overdose cases in 2019. (7) Xylazine use is now present throughout the United States; although foremost in Philadelphia, Maryland and Connecticut now follow close behind. (1)

Dermatologists must be cognizant of the severe skin ulcers that may complicate xylazine administration. A characteristic case was reported by Malayala et al: “The patient is a 37-year-old female who was injecting about eight to ten ‘bags’ of ‘dope’ (fentanyl, which is typically mixed with xylazine in Philadelphia) every day. She typically injected into her veins on the hands and sometimes into the legs. She presented with ulcers on her lower extremities extending from the knees to ankles, associated with copious purulent drainage and a foul smell. There was extensive necrosis of the subcutaneous tissues, abscesses, and tibial osteomyelitis. This led to multiple hospitalizations with bacteremia from Strep pyogenes, methicillin-resistant Staphylococcus aureus, methicillin-sensitive S. aureus, Enterococcus faecalis, Escherichia coli, and Proteus requiring intravenous antibiotics. She required debridement of the wounds and topical care to treat them.” (8)

Chronic injections of xylazine have been associated with skin ulcers and abscesses. (7) Lesions may develop over various body parts irrespective of the intravenous injection sites reported. The presumed mechanism is thought to be the direct vasoconstricting effect on local blood vessels and resultant decreased skin perfusion. Additionally, hypotension, bradycardia, and respiratory depression, may lead to lower tissue cutaneous oxygenation. Complications include severe soft tissue infections (abscesses, cellulitis), skin ulceration, and impaired wound healing. (8) Unfortunately, these complications may be perpetuated by continued injection of the painful ulcers because of the anesthetic effect of xylazine. (7)

Managing these patients mandates multidisciplinary care involving addiction medicine, infectious diseases, wound care, plastic surgery, and dermatology. If there is any question of other causes of ulceration (vasculitis, pyoderma gangrenosum, malignancies, panniculitis, etc.) a skin biopsy could be performed, although, in the clear-cut context, it is not mandatory. Appropriate wound cultures should be performed. To date, there are no rapid or simple tests for xylazine, although it may be detected by thin layer chromatography or gas chromatography mass spectrometry. (2) Clinical suspicion is paramount.

Point to Remember: Xylazine (“Tranq”) is increasing and has been associated with severe ulcers and soft tissue infections. Dermatologists should recognize these lesions in the context of illicit drug use and assist in coordinating multidisciplinary care for these patients.

Our experts’ viewpoints

Jenny J. Wei, MD
Dermatology Resident PGY-3
University of Pennsylvania Perelman School of Medicine

Elizabeth Messenger, MD, FAAD
Assistant Professor of Clinical Dermatology
University of Pennsylvania Perelman School of Medicine

As highlighted by Dr. Heymann, xylazine is an emerging substance of abuse that is frequently used in conjunction with opioids to prolong the high and delay symptoms of withdrawal. First detected in 2006, xylazine is now found in over 90% of illegal drug samples in Philadelphia. This alarming rate of increase has led the CDC, FDA, and local public health agencies to issue warnings regarding the serious risks associated with xylazine exposure, including the development of severe skin ulcerations. Over the past year, through our inpatient dermatology consult service, we have experienced firsthand the significant cutaneous morbidity associated with xylazine use.

Many of our patients share a similar presentation. They typically report chronic multi-substance IV drug use including opioids, previously with limited cutaneous complications. Then, sometime in the past 2-3 years, they were exposed to xylazine, either as a primary substance of abuse or an adulterant and developed severe skin ulcerations shortly thereafter. The wounds most commonly involved the extremities and frequently had a cribriform appearance, with islands of eschars and normal skin within. Notably, the patients themselves were usually aware of this specific complication and able to point to xylazine as a possible culprit for their wounds. To quote one patient, “the people who use tranq… their arms and legs are just melting off.”

Despite the increasing prevalence and clinical relevance of xylazine, it remains an under-recognized entity and studies in the medical literature are limited. As its use continues to spread rapidly across the U.S., dermatologists in all practice settings will likely encounter affected patients. Xylazine exposure should be added to the differential diagnosis for patients presenting with severe skin ulcerations, and a thorough history is key to making this diagnosis.

1. Friedman J, Montero F, Bourgois P, Wahbi R, Dye D, Goodman-Meza D, Shover C. Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis. Drug Alcohol Depend. 2022 Apr 1;233:109380. doi: 10.1016/j.drugalcdep.2022.109380. Epub 2022 Feb 26. PMID: 35247724; PMCID: PMC9128597.

2. Ruiz-Colón K, Chavez-Arias C, Díaz-Alcalá JE, Martínez MA. Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: A comprehensive review of the literature. Forensic Sci Int. 2014 Jul;240:1-8. doi: 10.1016/j.forsciint.2014.03.015. Epub 2014 Mar 26. PMID: 24769343.

3. McNich JR, Maguire M, Wallace L. A case of skin necrosis caused by intravenous xylazine abuse. Abstract published at SHM Converge 2021. Abstract 559. Journal of Hospital Medicine. https:shmabstracts.org/abstract/a-case-of-skin-necrosis-caused-by-intravenous-xylazine-abuse/.November 23rd 2022.

4. Whelan A. A powerful sedative in Philly’s drug supply is causing severe wounds and agonizing withdrawals. It’s quickly becoming unavoidable. Philadelphia Inquirer. April 10, 2022. https://www.inquirer.com/health/opioid-addiction/xylazine-tranq-withdrawal-philadelphia-fentanyl-addiction-detox-20220410.html#loaded

5. Wong SC, Curtis JA, Wingert WE. Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner's Office. J Forensic Sci. 2008 Mar;53(2):495-8. doi: 10.1111/j.1556-4029.2007.00648.x. Epub 2008 Feb 14. PMID: 18284526.

6. Reyes JC, Negrón JL, Colón HM, Padilla AM, Millán MY, Matos TD, Robles RR. The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico. J Urban Health. 2012 Jun;89(3):519-26. doi: 10.1007/s11524-011-9662-6. PMID: 22391983; PMCID: PMC3368046.

7. 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 Aug;27(4):395-398. doi: 10.1136/injuryprev-2020-043968. Epub 2021 Feb 3. PMID: 33536231.

8. 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.

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