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The wounds that appear on the arms and legs of people who use fentanyl adulterated with xylazine don’t look like other drug-related injuries. They are deep, necrotic, slow-healing ulcers that can appear far from the injection site — sometimes on limbs that were never injected. They can progress to bone. And they do not respond to naloxone, because xylazine is not an opioid.

A paper published this month in Open Forum Infectious Diseases does something that’s been needed for two years: it codifies a multidisciplinary approach to these wounds into a clinical protocol that emergency departments, addiction medicine programs, and harm reduction organizations can actually use.

What the Study Found

The guidance, produced by a team working across addiction medicine, wound care, infectious disease, and surgery, characterizes xylazine-associated wounds with clinical precision. Xylazine is an alpha-2 adrenergic agonist — a veterinary sedative used for large animals — that entered illicit drug supplies as a fentanyl adulterant primarily in the Northeast United States beginning around 2019 and has since spread nationally. Unlike opioids, which produce their effects through mu-opioid receptor binding, xylazine acts on alpha-2 receptors in the peripheral nervous system, causing sustained vasoconstriction — the narrowing of blood vessels — in the extremities.

That vasoconstriction is what produces the wounds. Sustained reduction in blood flow to peripheral tissues creates ischemia: tissue that isn’t getting enough oxygen to survive. The result is necrotic lesions that can appear on the legs, arms, torso, and even areas of the body distant from injection sites — a distribution pattern that initially confused clinicians who expected drug-related wounds to be injection-site injuries. They aren’t. They are circulatory injuries, caused by the drug’s systemic vascular effect.

The protocol’s key insight: these wounds require the same framework as burn care, not standard wound management. The authors recommend autolytic debridement — allowing the body’s own enzymes to break down necrotic tissue under a moisture-retentive dressing — combined with silver sulfadiazine, the antimicrobial cream developed for burn treatment, to control infection. This is a fundamentally different approach from the dried-out, open-wound management that many emergency departments default to for non-healing ulcers.

Why the Multidisciplinary Framework Matters

No single specialty can treat these injuries effectively alone.

An emergency medicine physician who correctly identifies the wound as xylazine-associated still needs addiction medicine input to address the underlying opioid use disorder — because the most effective wound treatment in the world fails if the patient returns to use, re-exposes the wound to xylazine, and re-injures the healing tissue. An addiction medicine specialist who initiates buprenorphine appropriately still needs wound care expertise to manage the progression of existing injuries and prevent sepsis. An infectious disease physician managing wound infection still needs the surgical team available if the wound progresses to the point where debridement requires operative intervention.

The burn center model the protocol borrows from is instructive precisely because burns learned this lesson early: severe burns require coordinated care across surgery, nursing, infection control, and rehabilitation. Xylazine wounds are the burn analogy for the fentanyl era.

The Access Gap

The guidance is clinically sound. The problem is structural.

The facilities best positioned to implement this protocol — academic medical centers with co-located addiction medicine, infectious disease, and plastic or reconstructive surgery services — are not the facilities most likely to see xylazine wound presentations first. Emergency departments in rural and semi-rural areas, community health centers, harm reduction organizations with wound care components: these are where many patients with xylazine injuries show up, often late, often when the wound has already progressed significantly.

Harm reduction organizations — particularly syringe service programs that already do wound care as part of their service model — are often seeing these injuries earlier than any clinical setting, because people trust them and the threshold to access is lower. The protocol’s recommendations are genuinely exportable to that setting; the dressing changes and debridement guidance don’t require a hospital. But distributing this knowledge to non-clinical harm reduction settings requires deliberate translation, training, and supply logistics that the paper doesn’t address.

But distributing this knowledge to non-clinical harm reduction settings requires deliberate translation, training, and supply logistics that the paper doesn’t address.

That gap between codified clinical knowledge and distribution to the people who need to use it is the persistent failure mode of harm reduction infrastructure in the United States. It isn’t a scientific problem. The science is there. It’s an organizational and funding problem, and it predates xylazine by decades.

What the Open Forum Infectious Diseases guidance does is give clinicians a legitimate, peer-reviewed foundation to stand on when advocating for multidisciplinary protocols in their institutions. For harm reduction workers who have been managing these wounds with improvised approaches for years, it validates what they’ve already been doing. For both groups, it closes a literature gap that has made it harder than it should be to argue for the resources these wounds require.

The wounds xylazine leaves behind are visible in a way that addiction often isn’t. That visibility is an opportunity — a chance to make the case for the full continuum of care that people in active opioid use need, before and after they’re ready to enter treatment. Missing that opportunity is a choice.