Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations (

vascular malformation A vascular malformation is a blood vessel or lymph vessel abnormality. Vascular malformations are one of the classifications of vascular anomalies, the other grouping is vascular tumors. They may cause aesthetic problems as they have a growth cyc ...

s) and also malformations of the

lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoi ...

. A medicine is injected into the vessels, which makes them shrink. It is used for children and young adults with vascular or lymphatic malformations. In adults, sclerotherapy is often used to treat spider veins, smaller

varicose veins Varicose veins, also known as varicoses, are a medical condition in which superficial veins become enlarged and twisted. These veins typically develop in the legs, just under the skin. Varicose veins usually cause few symptoms. However, some indiv ...

hemorrhoid Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term '' ...

s,William R. Finkelmeier, Sclerotherapy, Ch. 12, ACS Surgery: Principles & Practice, 2004, WebMD (hardcover book) and hydroceles.Darren T Beiko, Aspiration and Sclerotherapy versus hydrocelectomy for treatment of hydroceles, Urology Vol 61, Issue 4 (Apr 2003) Sclerotherapy is one method (along with surgery,

radiofrequency Radio frequency (RF) is the oscillation rate of an alternating electric current or voltage or of a magnetic, electric or electromagnetic field or mechanical system in the frequency range from around to around . This is roughly between the upper ...

, and

laser ablation Laser ablation or photoablation (also called laser blasting) is the process of removing material from a solid (or occasionally liquid) surface by irradiating it with a laser beam. At low laser flux, the material is heated by the absorbed laser ...

) for the treatment of spider veins, occasionally varicose veins, and venous malformations. In

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

-guided sclerotherapy,

is used to visualize the underlying

vein Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenate ...

so the physician can deliver and monitor the injection. Sclerotherapy often takes place under ultrasound guidance after venous abnormalities have been diagnosed with duplex ultrasound. Sclerotherapy under ultrasound guidance and using microfoam sclerosants has been shown to be effective in controlling reflux from the sapheno-femoral and sapheno-popliteal junctions. Padbury A, Benveniste G L, Foam echosclerotherapy of the small saphenous vein, Australian and New Zealand Journal of Phlebology Vol 8, Number 1 (Dec 2004) However, some authors believe that sclerotherapy is not suitable for veins with reflux from the greater or lesser saphenous junction, or for veins with axial reflux. This is due to the emergence of more effective technologies, including laser ablation and radiofrequency, which have demonstrated superior efficacy to sclerotherapy for treatment of these veins.

Historical aspects

Sclerotherapy has been used in the treatment of spider veins and occasionally varicose veins for over 150 years. Like varicose vein surgery, sclerotherapy techniques have evolved during that time. Modern techniques including ultrasonographic guidance and foam sclerotherapy are the latest developments in this evolution. The first reported attempt at sclerotherapy was by D Zollikofer in Switzerland, 1682 who injected an acid into a vein to induce

thrombus A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...

formation. Goldman, M., Sclerotherapy Treatment of varicose and telangiectatic leg vein, Hardcover Text, 2nd Ed, 1995 Both Debout and Cassaignaic reported success in treating varicose veins by injecting perchlorate of iron in 1853.Sharmi S, Cheatle T. Fegan's Compression Sclerotherapy of Varicose Veins, Hardcover Text, 2003. Desgranges in 1854 cured 16 cases of varicose veins by injecting iodine and tannin into the veins. This was approximately 12 years after the probable advent of

great saphenous vein The great saphenous vein (GSV, alternately "long saphenous vein"; ) is a large, subcutaneous, superficial vein of the leg. It is the longest vein in the body, running along the length of the lower limb, returning blood from the foot, leg and thi ...

stripping in 1844 by Madelung. However, due to high rates of side-effects with the drugs used at the time, sclerotherapy had been practically abandoned by 1894.Coppleson VM, The Treatment of Varicose Veins by Injection, Hardcover text, 2nd Ed. 1929. With the improvements in surgical techniques and

anaesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into ...

s over that time, stripping became the treatment of choice. Work continued on alternative sclerosants in the early 20th century. During that time carbolic acid and perchlorate of mercury were tried and whilst these showed some effect in obliterating varicose veins, side-effects also caused them to be abandoned. Prof. Sicard and other French doctors developed the use of sodium carbonate and then sodium salicylate during and after the First World War. Quinine was also used with some effect during the early 20th century. At the time of Coppleson's book in 1929, he was advocating the use of sodium salicylate or quinine as the best choices of sclerosant. Further work on improving the technique and development of safer more effective sclerosants continued through the 1940s and 1950s. Of particular importance was the development of sodium tetradecyl sulfate (STS) in 1946, a product still widely used to this day. George Fegan in the 1960s reported treating over 13,000 patients with sclerotherapy, significantly advancing the technique by focussing on fibrosis of the vein rather than thrombosis, concentrating on controlling significant points of reflux and emphasizing the importance of compression of the treated leg. The procedure became medically accepted in mainland Europe during that time. However, it was poorly understood or accepted in England or the United States, a situation that continues to this day amongst some sections of the medical community. The next major development in the evolution of sclerotherapy was the advent of

duplex ultrasonography Doppler ultrasonography is medical ultrasonography that employs the Doppler effect to perform imaging of the movement of tissues and body fluids (usually blood), and their relative velocity to the probe. By calculating the frequency shift of ...

in the 1980s and its incorporation into the practise of sclerotherapy later that decade. Knight was an early advocate of this new procedure and presented it at several conferences in Europe and the United States. Thibault's article was the first on this topic to be published in a peer-reviewed journal. The work of Cabrera and Monfreaux in utilising foam sclerotherapy along with Tessari's "3-way tap method" of foam production further revolutionised the treatment of larger varicose veins with sclerotherapy. This has now been further modified by Whiteley and Patel to use 3 non-silicone syringes for more long lasting foam.

Methods

Injecting the unwanted veins with a sclerosing solution causes the target vein to immediately shrink, and then dissolve over a period of weeks as the body naturally absorbs the treated vein. Sclerotherapy is a non-invasive procedure taking only about 10 minutes to perform. The downtime is minimal, in comparison to an invasive varicose vein surgery. Sclerotherapy is the "gold standard" and is preferred over laser for eliminating large spider veins ''(telangiectasiae) elangiectasia is a condition in which broken or widened small blood vessels that sit near the surface of the skin or mucous membranes create visible' and smaller varicose leg veins. Unlike a laser, the sclerosing solution additionally closes the "feeder veins" under the skin that are causing the spider veins to form, thereby making a recurrence of the spider veins in the treated area less likely. Multiple injections of dilute sclerosant are injected into the abnormal surface veins of the involved leg. The patient's leg is then compressed with either stockings or bandages that they wear usually for one week after treatment. Patients are also encouraged to walk regularly during that time. It is common practice for the patient to require at least two treatment sessions separated by several weeks to significantly improve the appearance of their leg veins. Sclerotherapy can also be performed using microfoam sclerosants under ultrasound guidance to treat larger varicose veins, including the great and small saphenous veins. After a map of the patient's varicose veins is created using ultrasound, these veins are injected whilst real-time monitoring of the injections is undertaken, also using ultrasound. The sclerosant can be observed entering the vein, and further injections performed so that all the abnormal veins are treated. Follow-up ultrasound scans are used to confirm closure of the treated veins and any residual varicose veins can be identified and treated.

Foam sclerotherapy

Foam sclerotherapy is a technique that involves injecting "foamed sclerosant drugs" within a blood vessel using a pair of syringes – one with sclerosant in it and one with gas (originally air). The original Tessari method has now been modified by the Whiteley-Patel modification which uses 3 syringes, all of which are silicone-free. The sclerosant drugs ( sodium tetradecyl sulfate, bleomycin or polidocanol) are mixed with air or a physiological gas (

carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is t ...

) in a syringe or by using mechanical pumps. This increases the

surface area The surface area of a solid object is a measure of the total area that the surface of the object occupies. The mathematical definition of surface area in the presence of curved surfaces is considerably more involved than the definition of ...

of the

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

. The foam sclerosant drug is more efficacious than the liquid one in causing sclerosis (thickening of the vessel wall and sealing off the blood flow), for it does not mix with the blood in the vessel and in fact displaces it, thus avoiding dilution of the drug and causing maximal sclerosant action. It is therefore useful for longer and larger veins. Experts in foam sclerotherapy have created “tooth paste” like thick foam for their injections, which has revolutionized the non-surgical treatment of

and venous malformations, including Klippel–Trénaunay syndrome.

Bleomycin electrosclerotherapy

Bleomycin electrosclerotherapy consists of locally delivering the sclerosant bleomycin and applying short high voltage electrical pulses to the area to be treated, resulting in a local and temporary increased permeability of the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the ...

s, increasing the intracellular concentration of bleomycin by a factor of up to several thousand. Preclinical studies also indicated that electroporation in combination with bleomycin impaired the barrier function of the

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...

by interacting with the organization of the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is comp ...

and the integrity of the junctions. This can lead to extravasation, interstitial edema and a desired collapse of the vascular structures. The procedure has been researched as

electrochemotherapy Electrochemotherapy is a type of chemotherapy that allows delivery of non-permeant drugs to the cell interior. It is based on the local application of short and intense electric pulses that transiently permeabilize the cell membrane, thus allowing ...

of skin tumors since the early 1990s and was first used in 2017 for vascular malformations. Initial reports indicated that the use of bleomycin in combination with reversible electroporation can potentially enhance the sclerotherapy effect. A retrospective study of 17 patients with venous malformations who did not respond to previous invasive therapies showed an average decrease in lesion volume measured on MRI images of 86% with clinical improvement in all patients after an average of 3.7 months and 1.12 sessions per patient, with a reduced dose of bleomycin and a reduced number of sessions compared to standard bleomycin sclerotherapy

Clinical evaluations

A study by Kanter and Thibault in 1996 reported a 76% success rate at 24 months in treating saphenofemoral junction and great saphenous vein incompetence with STS 3% solution. Padbury and Benveniste found that ultrasound guided sclerotherapy was effective in controlling reflux in the small saphenous vein. Barrett et al. found that microfoam ultrasound guided sclerotherapy was "effective in treating all sizes of varicose veins with high patient satisfaction and improvement in quality of life". A

Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profes ...

review of the medical literature concluded that "the evidence supports the current place of sclerotherapy in modern clinical practice, which is usually limited to treatment of recurrent varicose veins following surgery and thread veins." A second

review comparing surgery to sclerotherapy concluded that sclerotherapy has greater benefits than surgery in the short term but surgery has greater benefits in the longer term. Sclerotherapy was better than surgery in terms of treatment success, complication rate and cost at one year, but surgery was better after five years. However, the evidence was not of very good quality and more research is needed. A Health Technology Assessment found that sclerotherapy provided less benefit than surgery, but is likely to provide a small benefit in varicose veins without reflux from the sapheno-femoral or sapheno-popliteal junctions. It did not study the relative benefits of surgery and sclerotherapy in varicose veins with junctional reflux. The European Consensus Meeting on Foam Sclerotherapy in 2003 concluded that "Foam sclerotherapy allows a skilled practitioner to treat larger veins including saphenous trunks". A second European Consensus Meeting on Foam Sclerotherapy in 2006 has now been published.

Complications

Complications, while rare, include

venous thromboembolism Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off ( embolizes) and flows to the lungs t ...

, visual disturbances,

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

, thrombophlebitis, skin necrosis, and hyperpigmentation or a red treatment area. If the sclerosant is injected properly into the vein, there is no damage to the surrounding skin, but if it is injected outside the vein, tissue necrosis and scarring can result. Skin necrosis, whilst rare, can be cosmetically "potentially devastating", and may take months to heal. It is very rare when small amounts of dilute (<0.25%) sodium tetradecyl sulfate (STS) is used, but has been seen when higher concentrations (3%) are used. Blanching of the skin often occurs when STS is injected into arterioles (small artery branches). Telangiectatic matting, or the development of tiny red vessels, is unpredictable and usually must be treated with repeat sclerotherapy or laser. Most complications occur due to an intense inflammatory reaction to the sclerotherapy agent in the area surrounding the injected vein. In addition, there are systemic complications that are now becoming increasingly understood. These occur when the sclerosant travels through the veins to the heart, lung and brain. A recent report attributed a stroke to foam treatment, although this involved the injection of an unusually large amount of foam. More recent reports have shown that bubbles from even a small amount of sclerosant foam injected into the veins quickly appear in the heart, lung and brain. The significance of this is not fully understood at this point and large studies show that foam sclerotherapy is safe. Sclerotherapy is fully FDA approved in the USA. Contraindications include: bed rest, severe systemic diseases, poor patient understanding, needle phobia, short life expectancy, late stage cancer, known allergy to the sclerosing agent, and treatment with

tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...

References

External links

Management of venous malformations in Klippel–Trenaunay syndrome with ultrasound-guided foam sclerotherapy

Information about Lymphatic Malformations and the use of sclerotherapy to treat them from Children's Hospital, Seattle

Ultrasound video of a sclerotherapy taking place

Video of Sclerotherapeutic procedure

The American Vein and Lymphatic Society
is an Association of venous disease providers who practice sclerotherapy and other venous modalities.
Bleomycin Electrosclerotherapy of Vascular Malformations #YiiRS2021 by Prof. Walter A. Wohlgemuth (Video)

Bleomycin ElectroScleroTherapy (BEST) - Compendium Vascular Anomalies
{{Vascular procedures Vascular surgery