LAUSR

Dear Editor, Calciphylaxis is a rare vasculopathy that mostly occurs in the chronic renal failure population. Most commonly referred to as Uremic Calciphylaxis (UC), it may also be dubbed Calcific Uremic Arteriolopathy. UC is a vexing, enigmatic, and often lethal complication afflicting patients with chronic renal failure. UC occurs in about 1% in individuals with chronic renal failure. Integumentary lesions caused by calciphylaxis are associated with significant tissue necrosis and thus predispose to deep space infection and sepsis. Integumentary wounds caused by calciphylaxis are among the most painful wound types and thus negatively impact on a patient's quality of life, functional capacities, and dignity. The 1-year mortality rate in patients with calciphylaxis associated with UC has been reported at an alarming 45% to 80%, with sepsis being the leading cause of death. There is no effective standard treatment for UC leg ulcers, and thus, healing rates are dismal. A recent systematic review in UC found no significant clinical benefit from the five most frequently used treatment modalities: sodium thiosulfate, parathyroidectomy, cinacalcet, hyperbaric oxygen, and bisphosphates. It is important to note that all the aforementioned treatments are systemic, invasive (intravenous and/or intralesional injections), and associated with significant side effect burden and high financial costs. The endocannabinoid system (ECS) is a chemical signaling system that holds a ubiquitous presence in all organ systems among mammalian species. Furthermore, the ECS is embodied throughout all levels, components, and appendages of the integumentary system, both cutaneous and mucous membranes. ECS signaling goes beyond the classic cannabinoid receptors, CB1 and CB2, by involving other extracellular receptors such as TRPV, GPR, and 5-HT, as well as acting on nuclear receptors such as PPAR. It has been theorized that dysregulated ECS signaling is central to the pathophysiology of integumentary and wound conditions. Our multi-cohort open label clinical trial (ISRCTN16488940) treated 33 patients with high levels of co-morbid illness afflicted with intractable non-healing wounds. Proprietary cannabis-based medicines applied topically to both wound beds and peri-wound tissues demonstrated promotion of wound closure in up to 90% of cases. The overall clinical trial contained only one patient with uremic calciphylaxis. We have published our results using Topical Cannabis-Based Medicines (Table 1), VS-12 to wound beds and VS-14 to peri-wound tissues, in a cohort of patients with non-uremic calciphylaxis leg ulcers. A 74-year-old woman with bilateral leg ulcers of more than 12-month duration was treated with Topical Cannabis-Based Medicines, VS-12 and VS-14. She was extremely frail, sarcopenic, and suffered from end-stage cardiac failure and peripheral vascular disease while undergoing hemodialysis for end-stage diabetic nephropathy; her palliative performance scale score was 50% (healthy persons score 100%) and M3 multimorbidity index was 4.79 (two thirds of persons from typical populations score zero). During her treatment course, her average hemoglobin was 91 g/L and her oxygen saturation was consistently <90%. She presented with large necrotic wounds involving both legs that were debrided; biopsies confirmed the diagnosis of UC. She had medical contraindications to other available experimental treatments. Our protocol involved daily application of TCBM, VS-12 to the wound beds, and VS-14 to a 4 to 6 cm radial cuff of peri-wound integument. Tissues were then covered with one layer each of Jelonet and Mesorb, followed by spiral bandaging of her lower limbs, sequentially, using gauze kling roll, Comprilan, and Easifix. Unfortunately, her tri-weekly dialysis sessions limited her to only 11 TCBM treatments over 21 days. Representative digital images were acquired on day 0, 7, and 21, before the patient passed away from her cardiac conditions. Retrospective review of photographs using planimetric image analysis