Dear Editors,
A recent biopsy study of sickle cell leg ulcers found ‘fibrin deposits within the vessel wall associated with intimal hyperplasia and narrowing of the vascular lumen… the changes … (also)… observed in… skin not directly part of the ulcer…’ 1. The genesis of this vasculopathy is at least partially understood: sickle red cells adhere to endothelium; they promote the generation of adhesion molecules and provoke the ingression of monocytes and proliferation of fibroblasts and smooth muscle cells 2.
A recent survey found that a third of patients with sickle ulcers are given hydroxyurea 3. This might inhibit ongoing vascular damage by increasing the red cell's haemoglobin F, reducing sickling and adhesivity, but it would not impact the existing vasculopathy. Moreover, hydroxyurea in non‐sickle diseases sometimes appears to be responsible for generating leg ulcers; its net benefit is uncertain. The writer, coping with several intractable sickle leg ulcers, searched for other options.
Transdermally applied carbon dioxide penetrates intact skin and improves tissue perfusion by inducing vasodilatation 4. It has been found to increase tissue oxygenation and to promote healing of wounds. A controlled study in an animal model found that bathing an ischaemic limb in CO2‐enriched water increased collateral blood vessel formation and mobilised endothelial‐lineage progenitor cells 4. A controlled study in human subjects found that bathing a revascularised limb in CO2‐enriched water reduced the recurrence of ischaemic ulcers in diabetic patients 5. The deployment of transdermally applied CO2 may be particularly applicable to sickle ulcers because in a hypoxic milieu, which is prevalent in the microvascular circulation of sickle patients 6, CO2 also inhibits sickling 7.
Thus, the possibility that the cutaneous application of CO2 – an intervention without immediately obvious toxicity – would help heal a sickle ulcer invites study.
Simeon Pollack, MD1
1Department of Medicine
Albert Einstein College of Medicine
Bronx, NY, USA
simeonpollack@optonline.net
References
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