The spectrum of wound formation in desomorphine (Krokodil) and fentanyl/xylazine use disorders

Introduction: The increasing use of manufactured street fentanyl and other new synthetic opioids has led to unique and poorly understood wound manifestations. These wounds differ from those associated with heroin injection, which tend to be site-specific and representative of superficial and soft tissue infections. Krokodil, the desomorphine derivative (fentanyl-like) manufactured from codeine, can cause gangrenous skin and crocodile-scale necrosis. More recently, the combination of fentanyl and xylazine, a large animal veterinary tranquilizer, has led to the development of deep skin ulceration and distal gangrene. The etiology of where and how wounds form with desomorphine derivatives and xylazine is poorly understood. Treatment methodologies may improve with better understanding of wound pathology. Methods: A retrospective chart review of a single plastic surgeons’ patients from April 1, 2021 – November 30, 2023, was performed.  Fifty-two patients were identified who were admitted to a hospital with complicated wounds and skin infections secondary to fentanyl-like/xylazine use. Results: Five patients were admitted with cellulitis only, nine with a sub-cutaneous abscess, thirty-eight with wounds/ulcers. 24 patients had surgical procedures ranging from debridement to limb salvage reconstruction.   Five amputations of the upper extremity were performed secondary to untreatable osteomyelitis.  Anatomic distribution of wounds includes face (n=3), upper extremity (n=37) and lower extremity (n=12).  Very few patients had any outpatient follow-up. Discussion: There is a paucity of medical literature about the spectrum of wound manifestations seen with desomorphine derivative and xylazine use. Wounds secondary to the use of desomorphine derivatives appear to be related to the site of injection and are most likely caused by the presence of toxic agents that cause chemical necrosis. Wounds secondary to the use of xylazine do not appear to be related to the site of injection, as evidenced by the presence of wounds in individuals who use xylazine via the inhalational route. Rather, mirror image wounds suggest a metabolic or autoimmune etiology. This study furthers the understanding of the etiology and pathology of wounds associated with desomorphine derivative and xylazine use. As this phenomenon is poised to become a nationwide issue, better understanding of etiology is essential for the improvement of treatment strategies. References:1. Alves E. A. (2020). DARK Classics in Chemical Neuroscience: Krokodil. ACS chemical neuroscience, 11(23), 3968–3978. https://doi.org/10.1021/acschemneuro.0c00495 2. Alves, E. A., Grund, J. P., Afonso, C. M., Netto, A. D., Carvalho, F., & Dinis-Oliveira, R. J. (2015). The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity. Forensic science international, 249, 207–213. https://doi.org/10.1016/j.forsciint.2015.02.001 3. D'Orazio, J., Nelson, L., Perrone, J., Wightman, R., & Haroz, R. (2023). Xylazine Adulteration of the Heroin-Fentanyl Drug Supply : A Narrative Review. Annals of internal medicine, 176(10), 1370–1376. https://doi.org/10.7326/M23-2001 4. Sue, K. L., & Hawk, K. (2024). Clinical considerations for the management of xylazine overdoses and xylazine-related wounds. Addiction (Abingdon, England), 119(4), 606–608. https://doi.org/10.1111/add.16388