Transparietal diffusion of polidocanol: Potential complication of sclerotherapy?

Dear Editor,

The occurrence of necrosis after sclerotherapy is a troublesome, potentially major complication, regardless of whether injections are administered for medical or cosmetic purposes. In this journal, an excellent two-part review by Kang et al. summarizes the causes and prevention of necrosis after sclerotherapy.^1–2

Blistering and round shaped necrosis by extravasation occur mainly after the injection of osmotic or irritating agents. The risk of necrosis is low when detergent sclerosing agents, mainly polidocanol (POL), are injected, even paravascularly.

According to Kang et al., necrosis due to arterial obliteration or spasm has a “stellate aspect, caused by intra-arterial injections, intravenous injections triggering the veno-arteriolar reflex vasospasm response, and intravenous injections near persistently open arterio-venous anastomoses or defective boundary valves.” ¹ However, this logical physiopathological classification does not explain all cases of necrosis, including pattern of stellate necrosis, after detergent sclerosant injection. Indeed, the electron microscopy studies of Staubesand and colleagues from 1982 to 1995 have been overlooked and are difficult to find. These authors demonstrated that transparietal diffusion of subfascial paravasal injected POL in rats thigh led to alteration of the media and intima in both arteries and veins. ³ Diffusion was also observed in nerves, which could explain the occurrence of exceptional algias after sclerotherapy.^3–5

Could this form of transparietal diffusion not explain certain exceptional and “incomprehensible” complications or, more positively, the favorable results obtained during voluntary paravasal sclerotherapy with POL of very fine scarlet telangiectasias ⁶ or of hemorrhoids? ⁷

The transparietal diffusion observed by Staubesand is undoubtedly objective, but of limited consequence in clinical practice, and the tissue damage may be reversible. To our knowledge, such electron microscopy work has not been repeated by others.

More recent publications have placed this damage into perspective. Although Hansen ⁷ described necrosis, with significant obliteration of the veins and arteries of the paw, after injection of large amounts of POL into the ankle of rats, subcutaneous injection of POL into the abdomen did not lead to any severe complications, apart from panniculitis at the injection site. ⁸

In humans, Schibler et al. reported a histopathologically confirmed spontaneously resolving panniculitis after accidental subcutaneous injection of 5 mL of POL 0.5% fluid into the forearm. ⁹ Some cases of Nicolau livedoid dermatitis have occurred immediately after sclerotherapy in the lower extremities, after intra-arterial injection or arterial spasm. However, at least three reports have described the late onset (2–4 days) of Nicolau’s dermatitis.^10–12 Tran and Parsi described the appearance of Nicolau’s dermatitis 2 days after sclerotherapy of a very dilated small saphenous vein (10 mm) with sodium tetradecyl sulphate (STS) and suggested this reaction occurred due to a reflex vasospasm of the small saphenous artery subsequent to abrupt dilatation of the small saphenous vein. ¹⁰ The delay between injection and symptoms is however surprising. One case of very painful Nicolau livedoid dermatitis occurred abruptly 4 days after injection, partially paravasal, of 4 mL of 2% POL foam (4:1) in an intrafascial portion of the great saphenous vein on the medial aspect of the knee. ¹¹ In a third case, livedoid dermatitis occurred 2 days after sclerosing injection of POL into the popliteal fossa. ¹² How can these late reactions, which are quite different from the immediate appearance after injection of severe pain and livedoid dermatitis, be explained?

Should we incriminate symptoms of extraluminal irritation with late vasospasm? Or might the slow transparietal diffusion described by Staubesand et al. ³ after injection of POL in rats, be followed by vasospasm, which could explain a very delayed reaction, and whose evolution may be favorable.^4,10–12 Might such an arterial transparietal diffusion and inflammation extending to the intima induce arterial occlusion and cause typical stellate necrosis?

According to our experience of several decades and to that of general opinion, POL is a remarkable product for sclerotherapy, with an exceptional tolerance, which has been improved further since the introduction of the sclerosing foam formulation.

In exceptional cases of necrosis, neuralgia, and “inexplicable” subcutaneous damage, the transparietal diffusion described by Staubesand et al. is an alternative hypothesis that must be considered, both in cases of sclerotherapy of telangiectasias and of truncal varicose veins.