A Case of Xylazine-Induced Necrotic Skin Ulcerations in an IV-Drug User in Florida

Abstract

Introduction

As illicit drug manufacturers find new ways to market their products and increase their profit margins, multiple contaminants have found their way into the illicit drug supply. The newest addition, xylazine, also known as “tranq,” has spread through the city of Philadelphia and has recently been gaining ground across the United States, including in the state of Florida.

Case Presentation

This case describes a 37-year-old male with a significant past psychiatric history of severe polysubstance intravenous (IV) use, including fentanyl and methamphetamine. He was comorbid with other mental and physical conditions and presented to the emergency department with acute psychosis and worsening multi-digit ulcerations. The patient reported that the ulcerations started and progressed since he began injecting fentanyl cut with tranq. The patient was hospitalized for over 30 days due to his complex psychiatric illness as well as complications related to his ulcerations. Over the course of the hospitalization, the ulcerations began to heal, which was likely due to stopping IV drug use and receiving IV antibiotics in a restricted setting.

Conclusion

Continued use of IV drugs that are contaminated with xylazine or other dangerous additives can lead to increased morbidity and mortality. Suspicion of xylazine contamination should be prompt in patients with a history of IV drug use, skin ulcerations, and suspected opiate overdose that is unresponsive to naloxone. Further research on and awareness of the presence of xylazine in illicit drug supplies across the country is crucial to the prevention and early detection of xylazine-related complications.

Introduction

Discovered in 1962, xylazine, also known as “tranq” and “zombie drug,” is FDA-approved as an anesthetic, sedative, and muscle relaxant only for veterinary purposes. Since the early 2000s, it has increasingly been purchased online by illicit drug suppliers in the United States for use as an adulterant in various illicit drugs, most commonly fentanyl. Although many users are unaware of the addition of xylazine, some users deliberately seek the altered products. Due to its psychoactive properties, its addition to illegal drugs such as fentanyl, heroin, or cocaine not only increases profit for drug traffickers, but also attracts consumers seeking a longer-lasting euphoria, similar to the high caused by the use of opioids.¹

Overdose and death have become rising outcomes for many users of xylazine-contaminated drugs, which has raised concern for more legal control of the substance.² Legislation to make xylazine a Schedule III drug under the Controlled Substances Act, 1 level below dangerous drugs such as opioids like fentanyl, has been proposed. However, the National Harm Reduction Coalition rejected this proposal and would rather approach controlling the crisis by implementing evidence-based harm reduction, such as overdose prevention and syringe access programs, to allow users to make healthier choices.²

Since xylazine is not approved for human use, information on its effects in humans is limited to reports from users. Xylazine is a potent alpha-2 agonist,³ similar to detomidine and medetomidine but at 100-fold less affinity for the alpha-2 receptor subtypes.⁴ Common side effects noted with xylazine use include drowsiness, dry mouth, changes in heart rate (including both brady- and tachycardia), changes in blood pressure (both hyper- and hypotension), respiratory depression, and coma. However, those who use the injection route for any variant of xylazine often also develop soft tissue lesions that can quickly become necrotic and require amputation.¹ Although the use of xylazine has been reported in Puerto Rico since the early 2000s, many of the early cases seen in the United States were in northern states such as Pennsylvania.⁵ With cases of xylazine-related health issues continuing to rise, we intend to describe a unique case seen in Northern Florida to increase awareness and consideration of xylazine-induced soft tissue injury when a patient with a drug use history presents with acute skin conditions.

Case Presentation

We present the case of a 37-year-old male with a past psychiatric history of schizoaffective disorder bipolar type, post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), attention deficit hyperactivity disorder (ADHD), and polysubstance use disorder who presented to the emergency department (ED) for auditory hallucinations and painful finger ulcerations. His symptoms began after a 4-day methamphetamine binge, during which he had a decreased need for sleep and increased cravings for fentanyl, which he had recently begun using.

Upon initial presentation, he described the auditory hallucinations as negative and derogatory but not commanding in nature. He also denied any suicidal or homicidal ideation, intent, or plan. In the ED, the patient was subsequently placed under involuntary hospitalization under the Baker Act, Florida’s mental health services act to provide temporary detention for evaluation and initiation of treatment for those impaired by their mental illnesses. He was admitted to the medical floor for evaluation of the ulcerations, and psychiatry was consulted for mental health evaluation and stabilization. He first noticed the ulcerations about 1 month prior as darkening of his fingertips, worse on his left hand than right, gradually worsening and becoming more painful (Figures 1–3).

Figure 1.

Necrotic ulcerations are shown on digit 1 of the right hand.

Figure 2.

Necrotic ulcerations are shown on digits 2 and 3 of the left hand.

Figure 3.

Necrotic ulcerations are shown on digit 2 of the left hand.

With a history of poor psychotropic medication compliance, our patient had multiple past involuntary admissions and psychiatric hospitalizations, with his most recent being 3 months prior for worsening derogatory command hallucinations, suicidal ideation, and paranoid ideas. At that time, he was stabilized in the inpatient psychiatry unit and discharged on a combination of lithium carbonate 300 mg and aripiprazole 15 mg by mouth at bedtime along with bupropion 300 mg and hydroxyzine pamoate 50 mg by mouth daily to manage his psychotic and mood symptoms. The patient had multiple past suicide attempts secondary to relationship difficulties but denied any active suicide attempts recently.

Further social history revealed that the patient had been using methamphetamine daily for the past 8 years and did not view his methamphetamine use as problematic. On the contrary, he believed that it helped relieve his auditory hallucinations as well as the associated emotional and physical symptoms of his trauma and schizoaffective disorder. He also reported chronic alcohol and marijuana use along with his newly-started fentanyl use, and he had a history of smoking tobacco for 10 years but reported no tobacco use since his last psychiatric admission. He also has comorbid medical conditions including human immunodeficiency virus (HIV), Hepatitis C, and seizures. His family psychiatric history is notable for bipolar disorder in his brother and sister, GAD in his sister and mother, and PTSD in his mother.

His initial vital signs upon presentation to the ED were a body temperature of 98.8 °F, heart rate of 113 beats per minute, respiratory rate of 20 breaths per minute, blood pressure of 158/92 mmHg, and oxygen saturation 95% on room air. He was given both 20 mg of olanzapine and 5 mg of lorazepam intramuscularly for agitation, causing him to be quite sedated upon examination by the medicine team the next morning. His initial physical examination by the medicine service showed no clubbing, cyanosis, or edema on any extremities, but dark ulcers were noted on the fingertips of the left third and fourth digits and the right fifth digit.

Significant laboratory results included a urine toxicology screen, positive for amphetamines, ecstasy, and cannabinoids, and negative for a quantitative blood alcohol level of less than 3.0 mg/dL. An arterial ultrasound of the bilateral upper extremities was ordered to evaluate for any underlying intravascular pathology.

The patient was also seen by the psychiatry consulting team the morning after admission. He repeatedly expressed that he was very hungry and appeared bizarre, disheveled, hyperactive, and restless during the interview, maintaining poor eye contact and eating constantly. The patient’s mood was labile at times during the interview. Additionally, his affect was constricted and his attitude was inhibited, both incongruent with his stated mood. He demonstrated hyperverbal, slurred speech, and rapid and tangential thought processes but denied suicidal ideation, homicidal ideation, delusions, or auditory or visual hallucinations. The patient was subsequently started on valproic acid 500 mg twice a day for mood stabilization, olanzapine 15 mg twice a day for his hallucinations and mania, and prazosin 3 mg at bedtime for nightmares. Intramuscular olanzapine 5 mg every six hours as needed was also added for episodes of acute agitation. Although he was conversational and cooperative at the time of the interview, he became combative toward ultrasound technicians later that afternoon. Therefore, a single dose of lorazepam 2 mg was given 45 minutes prior to arterial imaging, which revealed no significant arterial stenosis or occlusions.

Over the next few days, the patient’s mental status gradually improved on the above medication regimen, with his thought processes becoming more linear, allowing him to have a meaningful and reality-based conversation with medical staff. He remained somewhat restless and pressured in his speech but was agreeable to continue psychotropic treatment. Regarding his finger ulcerations, antinuclear antibodies (ANA), rheumatoid factors, complement levels, and levels of inflammatory markers (ESR/CRP) were ordered by the consulting medicine team to assess for any autoimmune etiology, and the results were all within normal limits. The hand surgery team was consulted after the negative ultrasound results, and conservative treatment of the ulcerated areas needing wound care was recommended to keep them clean and dry. The wound care team also recommended establishing an outpatient follow-up with dermatology, hand surgery, and infectious disease following his discharge.

He was then transferred to the inpatient psychiatry floor, where he continued to express concerns regarding finger pain and anxiety but admitted his auditory hallucinations and sleep had improved on his current medication regimen. He expressed a preference for his antipsychotic to be switched from olanzapine to aripiprazole since he had a history of good response to long-acting aripiprazole in the past. To accommodate his request, he was switched to aripiprazole 10 mg daily at bedtime with a plan to transition to a long-acting formulation upon discharge plan to transition to a long-acting formulation, valproic acid 500 mg twice a day, upon discharge. During the first 2 days on the psychiatric unit, he continued to complain of finger pain and increased fatigue, decreased energy, and a feeling of unease, including a constant urge to move. He was given a 1 mg dose of benztropine at that time and started on benztropine 0.5 mg twice a day for this newly developed akathisia, likely secondary to the aripiprazole use.

Four days into his stay on the psychiatry ward, the patient experienced worsening of his auditory hallucinations, reporting them becoming more derogatory and discouraging regarding his goal of methamphetamine and fentanyl cessation. His psychotropic medication regimen was modified to include lithium 600 mg titrated up to 3 times daily, with his valproic acid dosage decreased to 500 mg once daily at bedtime to provide for stronger mood stabilization. A few days later, his aripiprazole medication was discontinued due to a complaint of dry mouth and development of delirium with disorientation to time or place, aggression towards other patients and staff, hyperactivity, emotional lability, and worsened auditory hallucinations during the morning hours. The patient’s delirium slowly improved over the next 2 days. He was able to independently perform his own wound care of his ulcers, which had remained unchanged in appearance throughout his hospitalization, in preparation for his discharge to an addiction rehabilitation center for polysubstance cessation.

Discussion

This patient’s digital ulcerations in the context of his multiple interplaying risk factors, made the possible diagnosis of xylazine-induced skin necrosis one requiring extensive evaluation and research. His baseline immunosuppressed status, secondary to chronic HIV infection and recent lapse in bictegravir/emtricitabine/tenofovir alafenamide, paired with his intermittent homelessness, placed him at extremely high risk for an infectious etiology. During the hospitalization, the patient was transferred to the medical floor for evaluation of worsening lesions, which required a course of intravenous (IV) antibiotics for wound cultures positive for methicillin-resistant Staphylococcus aureus (MRSA).

Buerger’s disease (thromboangiitis obliterans), a small vessel inflammatory disease that could also lead to digit ulceration, was considered in the differential diagnosis given the patient’s history of tobacco smoking. Against that diagnosis was that the patient reported not having smoked cigarettes since his last admission 3 months prior and that he had never noted any skin ulcerations in the past while he had been smoking. Additionally, he showed no occlusive disease in the arterial system below the popliteal artery on the ultrasound, nor did he demonstrate migratory thrombophlebitis, a common accompanying finding in cases of Buerger’s disease. Migratory thrombophlebitis involves a venous blood clot with inflammation of nearby veins, presenting as pain, redness, and edema of the general area. While this patient was experiencing pain around his ulcerations, his presentation was more indicative of an arterial process denoted by the gray, darker coloration of his fingertips and subsequent ischemia and necrosis on his digits.⁴

Similarly, it was essential to evaluate for the potential diagnosis of a drug-induced vasculitis, given the patient’s extensive substance abuse history, including methamphetamine use, for several years. His negative arterial ultrasound results showing an absence of characteristic segmental constrictions, negative ESR and CRP levels, and his lack of neurological signs made amphetamine-induced vasculitis unlikely. Furthermore, autoimmune etiologies for his finger ulcerations were largely ruled out by his negative ANA, rheumatoid factor, and inflammatory markers. Ultimately, the recent onset of his skin ulcerations within the past month, negative arterial imaging, negative autoimmune panel, and lack of infectious signs or symptoms guided this patient’s assessment away from the aforementioned conditions and toward a phenomenon related to his 2-month-old fentanyl usage.

We have a strong suspicion that the fentanyl the patient was using was being “cut” or adulterated with xylazine, given that his finger ulcerations developed during the time of his use. As a partial alpha-2 adrenergic agonist, xylazine decreases heart rate and myocardial contractility while also causing peripheral arterial constriction. Xylazine’s most common central side effects in humans include hypotension, bradycardia, and respiratory depression, explaining why xylazine has been increasingly linked to opioid overdose deaths.³ Since aripiprazole can cause dry mouth due to anticholinergic properties, our patient’s experience with this symptom was attributed to aripiprazole, which was discontinued. Interestingly, xylazine can also cause disorientation and dry mouth and could have been contributing to our patient’s symptoms.

Most notable to this patient's case, xylazine’s vasoconstrictive effects at peripheral locations, regardless of the fentanyl injection site, have been linked to the increased prevalence of painful skin ulcerations and even abscesses in opioid users. In addition to the local vasoconstriction mediated by alpha-2 adrenergic agonism and causing decreased skin perfusion, the central alpha-2 agonism that produces hypotension further exacerbates the reduced tissue oxygenation. ⁵ The low perfusion can also contribute to impaired healing of these wounds, causing opioid users to present with chronic ulcerations that don’t improve or worsen in appearance over time. This was consistent with our patient’s reports that his ulcerations had gradually become more painful and darker-appearing over the last month.

While many illicit drugs including methamphetamines and cocaine also cause vasoconstriction, ulcerations typically occur over or near where the illicit drug was injected. This patient denied injecting any substances into his fingers or his hands, stating that he would mostly inject in his arms or neck. Furthermore, the wounds and ulcers that arise from localized vasoconstriction are usually much more insidious and chronic in presentation and thus exhibit notable granulation tissue, purulence, and often microbial infection, none of which were noted in this patient’s case.⁴

This case is unique; a fair amount of research has been done on xylazine use in animals and rats, but case reports of human use are limited. Furthermore, this case is unique given its location in Florida.

Conclusion

Due to the rapid and stealthy infiltration of xylazine into the drug supply as well as the increased risk associated with the deadly combination of opiates and xylazine, it is imperative that all clinicians and first responders have increased suspicion and awareness of this adulterant. Evidence-based harm reduction and legislation are imperative to take public health action against this new epidemic to prevent the spread of this new adulterant drug with dangerous and often deadly effects.

Funding Statement

This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity