Identifying illicit drug reactions

By Emily Margosian, Assistant Editor, May 1, 2024

It was a medical mystery. A long-term patient with a persistent skin finding and no known cause.

“I had an individual who came to see me for this issue for the longest time. He had what looked like livedo reticularis,” said Rebecca Vasquez, MD, FAAD, associate professor of dermatology at UT Southwestern Medical Center. “It’s a lacy red pattern we usually see when there is a problem with the blood vessels. You want to rule out serious underlying conditions. We did biopsy after biopsy and couldn’t figure out what was going on. After carefully studying the patient’s chart, it turns out, he was taking methamphetamines and was seeing a psychiatrist for this. Patients don’t necessarily want to share that information.”

Across the United States, illicit drug use has never been higher. In 2018, the National Institute on Drug Abuse (NIDA) reported that almost half of Americans (49.2%) have used illicit drugs at least once in their lifetime. Amid growing usage, the U.S. overdose and opioid crisis continues. Accidental drug use is a leading cause of death among persons under the age of 45, and in 2017, 68% of drug overdose cases were opioid-related.

Amid an ongoing drug crisis, dermatologists are increasingly likely to encounter a patient who is struggling with addiction, and due to the unregulated nature of illicit drugs, new cutaneous manifestations continue to emerge alongside new substances and added adulterants.

“It’s tough approaching these conversations,” said Karl Saardi, MD, FAAD, director of inpatient dermatology service at George Washington University Hospital. “It’s important for us to stay up to date as new substances and use patterns emerge by keeping an eye on the literature and even the lay press.”

This month, experts discuss emerging substances of note, common cutaneous signs of drug abuse, and how dermatologists can assist with the coordination of often much-needed multidisciplinary care.

Emerging drugs and associated skin conditions

Xylazine (“Tranq”)

Xylazine, known colloquially as “Tranq,” is a non-narcotic drug used as a sedative, analgesic, and muscle relaxant in animals. Outside of veterinary medicine, it is increasingly used illegally as an adulterant in combination with other drugs to prolong a high.

First recognized in 2006 as an adulterant of fentanyl, xylazine is now prevalent in many fatal heroin and/or fentanyl overdose cases in the northeastern United States, particularly Philadelphia. Xylazine is now found in over 90% of illegal drug samples in Philadelphia according to the CDC.

“Xylazine-tainted fentanyl is definitely something we’re struggling with right now,” said Misha Rosenbach, MD, FAAD, Paul R. Gross Professor of Dermatology at the University of Pennsylvania. “Philadelphia is currently viewed as sort of the epicenter of the xylazine crisis, and physicians here are very familiar with how it looks and presents.”

Xylazine use can manifest on the skin in several ways. It often results in severe skin ulcers, soft tissue infections (abscesses, cellulitis), and eventually necrosis. “What we see in our patients is a couple of different skin findings. One is these large ulcers and the entire limb is very firm and hard. It’s not like a pitting edema that’s soft and squishy. That’s maybe because there’s so much foreign material that gets into either the veins or regional lymphatic that causes some sclerosis and thickening and scarring,” said Dr. Rosenbach. “Within that, you have ulcers that range in shape but are very large and deep, often with exposed tendon and muscle, that are incredibly complicated to manage.”

“Philadelphia is currently viewed as sort of the epicenter of the xylazine crisis, and physicians here are very familiar with how it looks and presents.”

Other features unique to xylazine-induced ulcers include islands of “normal” skin within the affected area. “For other dermatologists, this is something you should be aware of because the first time you see it, you may not recognize it,” said Dr. Rosenbach. “It looks like a large, bizarre ulcer with islands of skin within it, and this firm tissue around it. At this point, if you’re a physician in a major city, I’m sure there’s xylazine there.”

Lesions typically present on the arms and legs, although they have also been reported to develop across the body irrespective of claimed injection site. “The truth is we have patients who come in with polysubstance abuse or exposure to multiple adulterants (including overlap cases with cocaine-levamisole), and sometimes it’s challenging to get a clear history from people who maybe don’t want to either admit what they’re taking, or come in when some substances have left their system and we can’t necessarily detect them anymore on a urine drug screen,” said Dr. Rosenbach.

Managing patients with xylazine exposure is often a multidisciplinary effort complicated by the nature of long-term addiction. “This has been so much of a problem in our area that the emergency room has resorted to managing most cases. They consult us for the bad ones, but they don’t call us for all of them,” said Dr. Rosenbach. “Patients come in with these horrific wounds, and it’s so hard to help them break the cycle of addiction. Many patients will leave against medical advice and are unhoused individuals who don’t have access to clean water or a place where they can store their medical supplies. Wound care and outpatient care becomes very, very difficult.”

Kratom

Another emerging substance with increasingly documented dermatologic consequences is kratom. A tropical evergreen tree native to Southeast Asia, products derived from its leaves are frequently marketed as herbal supplements that can produce opioid- and stimulant-like effects.

“Most people use it in low doses as a stimulant. The patients I’ve seen who have used kratom often have some history of opiate use, so they take it at higher doses either to wean themselves off opiates, or maybe see it as a healthier alternative,” said Ted Ryser, MD, FAAD, co-author of a recent JAAD Case Report on kratom as a novel cause of photo-distributed hyperpigmentation. “You can buy it in powder form, but I believe you can also buy the leaves. Now I know it’s even sold with vape cartridges as well. It’s easy to get, obviously addicting, and is being sold at vape shops or other dispensaries.”

Kratom is technically not illegal — yet. Although kratom is not recognized by the DEA as a controlled substance, it is listed by the agency as a “drug of concern.” Currently, it is also illegal in six states and several U.S. cities. “Kratom is being used a lot more, and it can have some very striking side effects. Before we published our case report, I hadn’t seen much in the literature about kratom. It was mostly just people on Reddit and other online forums discussing it. I have a feeling the FDA is eventually going to step in, because it’s not a safe alternative to narcotics,” said Dr. Ryser.

Studies have observed kratom use to be associated with hyperpigmentation, photosensitive patches, and itch after extended use at high doses. “I saw two patients in the same month, which was coincidental. However, both had been using it for quite a while, and from what I understand, that’s really what leads to this photo-distributed hyperpigmentation that we see. I’m not aware of any short-term cutaneous side effects,” said Dr. Ryser.

The mechanism of action by which kratom produces hyperpigmentation is unknown, as well as whether its effects on the skin will fade with time. “This is all theoretical, but we think that the kratom is most likely stimulating an overproduction of melanin. Some have hypothesized that the drug is binding to melanin, and then depositing in the skin. Whereas our thought is that it induces melanin because the sun seems to be a major factor. The hyperpigmentation does not appear in areas where people don’t get sun, even when they’re on high doses,” said Dr. Ryser. “I believe it should fade with time if they stop using kratom and practice better sun protection. However, I haven’t been able to keep in touch with patients who have experienced this, so we really don’t know.”

According to Dr. Ryser, dermatologists should consider inquiring about kratom use when seeing patients with otherwise unexplained hyperpigmentation. “Generally, when we see someone with hyperpigmented skin, depending on the pattern, distribution, and other risk factors, there are often other things to consider. However, if someone is presenting with blue-gray discoloration, especially in sun-exposed areas, I think kratom is something to ask about. It can help us to uncover that history we wouldn’t have otherwise.”

Signs of injection drug use on the skin

Addiction can often be unseen. However, long-term injection drug use can leave visible clues on the skin.

While injection marks, or “track marks,” are commonly associated with injection drug use, this indicator has become less frequent with the advent of clean needle exchanges, according to Dr. Saardi. “They’re often one of the first things that pop into people’s minds when they think about injection drug use. These linear tattoos or ‘track marks’ develop when people sterilize used needles under a lighter. The flame oxidizes any kind of oil or dirt. When people inject tar that’s accumulated on the needle, it causes the marks. However, nowadays people are using mostly clean needles, so there’s less need to try and clean them with a flame.”

When present, track marks often appear on a patient’s non-dominant arm. However, individuals may also inject in unseen places, like behind the knee, on the dorsal veins of the feet, and in the inguinal veins (pelvic area) to avoid stigma from the marks. “The most common site would be the inner part of the elbow, usually on the non-dominant arm. If they’ve exhausted all the veins in there, other areas they might try to inject are the veins in the neck, maybe behind the knees, in the groin. Males will sometimes look to inject the penis, which can be devastating if they get infected,” said Dr. Vasquez.

“One thing dermatologists can do that’s very easy and can save lives is to check if Narcan is available over the counter in your state or jurisdiction and let patients know. I was recently in Walgreens here in Virginia and saw it on the shelves for maybe $30. We can encourage people to at least get that as a first step to keep themselves and those around them safe.”

Injection drug users whose veins are sclerosed from previous use may resort to “skin popping,” in which a substance is injected under the skin instead of into a vein. “A lot of times when people are using injection drugs and no longer have viable veins, they’ll start to inject directly into the skin. The medical term is intradermal injection, but it’s referred to colloquially as ‘skin popping,’” explained Dr. Saardi.

“Some may skip that altogether and go into the muscle,” added Dr. Vasquez. “Over time, those areas may get infected depending on how clean the needles are, or they may develop abscesses.” Over time, skin popping can leave irregular, leukodermic, atrophic, punched-out scars caused by irreversible tissue injury. Hypertrophic scars or keloids can also develop over these areas. “If you see those types of skin findings, consider asking about where they developed those lesions or how they happened,” advised Dr. Vasquez.

Injection drug users without viable veins may also inject into open wounds as a point of entry. “Any time there’s a little sore or an opening in the skin, people who no longer have veins will inject directly into the edge of the ulcer. It’s very vascular, because it’s trying to heal, so there are a lot of new blood vessels being formed that people will try to take advantage of,” explained Dr. Saardi. “It’s a quicker high but will cause those ulcers to progressively expand as they continue to inject into the edges of it. That’s something that I’ve seen fairly frequently here in the D.C. area. It’s referred to colloquially as ‘shooter’s patch.’ It can be very hard to distinguish that from something like xylazine toxicity when you’re seeing these non-healing ulcers. Most patients are honest if you ask them if they’re injecting directly into an ulcer. It’s important to really discourage them from doing so because they’ll basically never heal.”

Common illicit drugs and associated skin disorders

Cocaine

Cocaine can result in a variety of skin complications, depending on the route of administration. Dermatologic signs of use can include burns and eyebrow/eyelash thinning (when smoked), vasculitis and retiform purpura, hemorrhagic blisters, and necrosis (https://doi.org/10.1016/j.jaad.2012.12.968).

Cocaine use can also result in “snorter warts” — nasal verrucae that have been reported in cocaine users caused by the transmission of human papillomavirus on dollar bills.

“There are different ways that you can take cocaine. You can snort it. You can inhale it with a pipe. You can inject it. If you’re snorting it, especially if it’s with a party or a group of people, you may notice intranasal warts,” said Dr. Vasquez. “If you see warts on the nose, that’s a little bit suspicious. That’s of course context-based — kids can potentially get warts on their nose — but something to consider given the history of the patient.”

Levamisole, a common adulterant found in cocaine, has also been linked to cutaneous complications. “Unfortunately, levamisole has been found to be the ideal adulterant. It’s inexpensive, and has the right look, taste, and melting point to really go unnoticed by people who use cocaine. For distributors, it’s an ideal way to save money and save product,” said Dr. Vasquez. “In 2009, the DEA estimated that nearly 70% of the cocaine entering the U.S. was contaminated with levamisole. The problem is you can’t easily test for this in a clinical setting. You have to guess that that’s what’s going on based on the clinical presentation. Usually, patients will develop hemorrhagic bullae or necrosis, which we tend to see on the cheeks, ears, and sometimes the nose.”

“Testing for levamisole is unfortunately not commercially available,” confirmed Dr. Saardi. “The only lab that I know of that does it is Mayo Clinic. Oftentimes in the hospital we’re able to get it, but if we’re seeing someone in the office then we’re not. You can rely on visual clues like acral purpura thrombosis. It almost looks like vasculitis or thrombotic vasculopathy. If you are able to test, levamisole is one of the few things that’s both p-ANCA and c-ANCA positive. So, if you get back an ANCA test that shows both p- and c-ANCA positivity, consider levamisole ingestion alongside ANCA-associated vasculitis.”

Heroin

Heroin can also result in a variety of skin conditions, depending on its route of administration. Dermatologic signs of use can include morbilliform rash, chronic itching, livedo reticularis, bacterial abscesses, and necrosis at injection site. “Hives can commonly occur with opioid use. They’re very itchy and can last for days,” said Dr. Vasquez.

“Puffy hand syndrome,” which refers to non-pitting edema of the back of the hands, has also been attributed to heroin use due to the presence of quinine, a common adulterant in heroin (https://doi.org/10.1016/j.jaad.2012.12.968).

Methamphetamine

Infamous for its effects on the skin, dermatologic signs of methamphetamine use can vary depending on route of administration. When injected, it can precipitate slowed wound healing and suppressed immune function, exacerbating susceptibility to Staphylococcus aureus.

Methamphetamine use also often causes formication syndrome, in which users hallucinate the feeling of insects crawling in, or under the skin, as well as delusions of parasitosis. These perceived effects can result in compulsive picking of the skin, causing wounds to appear across the body, also referred to as “meth sores” or “meth mites.”

“Commonly with amphetamines, patients will pick at their skin. You may hear patients report that they feel things crawling on their skin. So, if you have someone picking at their skin, and there’s no other explanation for it, you may want to inquire about ‘supplements’ or other things that they’re taking,” said Dr. Vasquez.

Dermatologists’ role in addiction medicine

While most dermatologists may not be at the forefront of addiction medicine, they are still an important link in the care chain for many patients. “There are a lot of things that show up in the skin and we may be many patients’ first contact with the health care system. Whether they have a known history of drug use or not, we may be the first people to identify them as such. Unfortunately, resources in a lot of places are really lacking to get them plugged into care,” said Dr. Saardi. “One thing dermatologists can do that’s very easy and can save lives is to check if Narcan is available over the counter in your state and let patients know. I was recently in Walgreens here in Virginia and saw it on the shelves for maybe $30. We can encourage people to at least get that as a first step to keep themselves and those around them safe.”

“Addiction is hard. Dealing with big wounds in combination with patients who don’t have good support systems is often challenging. Whether we are appropriately supporting hospitals and health care systems, and getting vulnerable patients access to dermatology are questions that our field should grapple with,” said Dr. Rosenbach.

“We are experts in wound care, and I think it’s important for us to make ourselves available,” agreed Dr. Vasquez. “Not just in treating some of the sequelae, but helping patients get the help they need.”

Additional DermWorld Resources