A 33 y.o. male with a hx of fentanyl use arrives with a lesion on his arm and shortness of breath.
Shown are images of his L arm and a cxr. What is a unifying diagnosis?
Our patient admitted to using xylazine. Xylazine is an alpha 2 adrenergic receptor similar to clonidine and dexmedetomidine. It is an alpha 2 agonist acting centrally to inhibit the release of NE. This leads to inhibited sympathetic activity centrally causing bradycardia, hypotension and sedation. Xylazine was originally developed as an antihypertensive agent but it was not approved for human use because it causes severe CNS depression so it was repurposed for verterinary uses as a sedative. But because it prolongs the duration of opiod activity , producing a high which can last six hours, it began to be used in Puerto Rico in the 2000s by opiod users. Unfortunately one of its side effects is that it causes disfiguring skin ulcers from direct constriction of alpha 2b receptors in the vascular smooth muscles, leading to decreased skin perfusion.
Xylazine use spread from Puerto Rico to the the US where it first appeared in Philadelphia. A study done at Cook County shows the rise in deaths in which xylazine was detected. A group at Hennepin County discussed the clinical effects of xylazine; including skin ulcers. They noted in all their cases with individuals presenting with severe skin ulcers they all signed out AMA. They postulated rebound withdrawal from xylazine might be a factor. Withdrawal from xylazine can result in rapid increases in catecholamines resulting in hypertension; rebound similar to clonidine. The cases of Takotsubo after xylazine use may have a similar mechanism.
Recent developments include the development of xylazine test strips and approval of nausublingual dexmedetomidine. The FDA receently approved a dexmedetomidine sublingual film for the treament of agitation in schizophrenia and bipolar disorder.
QUESTION FOR THE FUTURE
Does xylazine withdrawal contribute to the failure of this population to quit drug use and should a taper of dexmedetomidine be offered? Or a clonidine taper? Spoiler alert: it is never this simple; most drug users have no idea what is in the drugs they use and complex mixtures may complicate treatment.
Our patient saw plastics and they recommended he have an amputation of the L arm. He underwent bronchoscopy for his LUL infiltrate and grew MSSA. He had pulmonary emboli but had a normal TEE with no vegetations. He refused suboxone and signed out AMA after he was found obtunded with drug paraphernalia in his room.
Giovannitti JA, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015 Spring;62(1):31-9.
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;14(8):e28160.
Chhabra N, Mir M, Hua MJ, et al. Notes From the Field: Xylazine-Related Deaths — Cook County, Illinois, 2017–2021. MMWR Morb Mortal Wkly Rep 2022;71:503–504