Matthew S. Nole
Baldwin-Wallace College
November 23, 1998

Abstract

Klippel-Trenaunay Syndrome was first described by two French doctors, Klippel and Trenaunay in 1900. This congenital vascular disorder is described by three main symptoms, known as the "triad," affecting one or more limbs. The triad consists of cutaneous hemangioma, varicose veins, and bone and soft tissue hypertrophy. Typically, the cutaneous hemangioma is a substantial port-wine stain, or nevus. Varicose veins are easy to identify and often very numerous. The bone and soft tissue hypertrophy is variable and the affected limb may be either larger or smaller than the opposite, unaffected limb. Many treatments for this disorder have been attempted. Although surgical and non-surgical proc edures have been developed, most tend to have negative results. Research on this topic has shown that surgery with this disorder is very risky and often unnecessary. In severe cases requiring surgery, amputation was most often the final outcome. Many studies have successfully experimented with the effects of sclerotherapy on varicose veins. New research on non-surgical wraps and supports has been developed to decrease the effects of the symptoms of this disorder on the patients.

Introduction

Klippel-Trenaunay Syndrome is a rare, congenital, vascular disorder affecting one or more limbs. Klippel-Trenaunay Syndrome was first noted in a 1900 publication of Archives Generales de Medecine. In the article, Du Naevis Variquex, Osteo-Hypertrophique, French physicians Klippel and Trenaunay described a clinical syndrome with three major symptoms (Gloviczki, 1982). These main symptoms are often referred to as the "triad." The triad consists of hemangiomas, bone and soft tissue hypertrophy, and vein varicosities. Hemangiomas are often apparent at birth, or by two weeks of age (Samuel, 1995). The hemangioma, or nevus, is usually confined to a part of the limb. In other cases, the entire limb is affected by the hemangioma (Samuel, 1995). Capillary hemangiomas are the most common type and are called port wine stains due to the red and purple color (Letts, 1977). Bone and soft tissue hypertrophy is a result of increased growth around an organ. In many cases, limb length is affected and t he length of the limb is different than the normal limb. The soft tissue hypertrophy is symmetrical around the affected extremity. In most cases, the girth of the limb is larger, although atrophy is common in some patients. Varicose veins are often v ery noticeable in Klippel-Trenaunay Syndrome patients. Varicose veins result from damaged or defective valves in a vein. A vein becomes damaged when the smooth muscle in the wall of veins weakens and the valves cannot support the weight of blood. T he pressure on the valve causes it to collapse and it no longer functions properly. Klippel-Trenaunay Syndrome patients are affected by other symptoms as well (See Table 1). These symptoms are variably expressed and may not have identical effects on other patients. Each case of Klippel-Trenaunay Syndrome is unique. In 1907, Parkes and Weber described a disorder with the same symptoms involved in Klippel-Trenaunay Syndrome with the addition of arteriovenous fistula. This derivative of Klippel-Trenaunay Syndrome was called Klippel-Trenaunay-Weber Syndrome.

Although the cause of Klippel-Trenaunay Syndrome is still unknown, there are two theories that have been argued by the medical community. The first argument is that Klippel-Trenaunay Syndrome is a mesodermal abnormality during fetal development (Baskerville, 1985). The mesodermal abnormalities cause vascular and soft tissue malformations in the effected limb. The other argument states that Klippel-Trenaunay Syndrome is caused by gene mutation. Although heredity does not appear to be the cause of Klippel-Trenaunay Syndrome, it is a possible option (Nielson, 1987). If heredity were the cause, the mutation would be autosomal recessive due to fact that both sexes are equally affected and the involvement of this disorder is extremely sporadic.

Attempts to treat the symptoms to this disorder have included surgery, sclerotherapy, and compression therapy. Different types of surgical intervention include vein ligation, vein stripping, vein resection, and amputation. Vein ligation is a procedure which clamps or \ldblquote ties off\rdblquote a section of veins. The clamp prevents blood flow through the damaged section of veins and promotes blood flow through undamaged veins. Vein stripping uses a metal wire to remove varicosities from within the damaged vein. Vein resection, or excision, is a procedure that removes a section of veins from the body. Amputation is a procedure that removes a portion of a limb. Digits and extremities are commonly amputated. The use of Sclerotherapy denies blood flow through defective veins by introducing chemicals into a specific vein. The chemical, a sclerosing agent, causes inflammation in the inner lining of the defective veins. As the inner wall of the vein becomes inflamed, blood is not permitted to flow through the vein. The vein later collapses and is broken down and absorbed by the body. Some of the chemicals used in sclerotherapy include sotradecol, ethanolamine, and absolute ethyl alcohol. Various forms compression garments have been developed to control the effects of varicose veins and hypertrophy caused by edema. These garments have been effective in reducing the effects of Klippel-Trenaunay Syndrome. Compression socks, elastic wraps, neoprene wraps and other more complex devices are used in compression therapy.

The purpose of this study was to compare the final results from surgical intervention, chemical intervention (sclerotherapy), and compression therapy in patients with Klippel-Trenaunay Syndrome. Since compression therapy does not seem to cause further harm to the body, the focus on my study will look at whether or not compression therapy is more effective than surgical intervention and chemical intervention at reducing the effects of Klippel-Trenaunay Syndrome.

Methods

This study was a collaboration of research p ublished by medical professionals. A list of published articles pertaining to Klippel-Trenaunay Syndrome was obtained from the director of the Klippel-Trenaunay Syndrome support group. Various articles from this list were col lected from several libraries: Pickerington Public Library, Prior Library at the Ohio State University, the Health Science Library at Case Western Reserve University, and the National Organization of Rare Disorders web page. The articles found from these sources were carefully reviewed. On November 6, 1998, I presented my findings to the Biology department at Baldwin-Wallace College in the form of a Microsoft Power Point presentation. The topics of the presentation were placed into this paper.

Results

The three predominate studies that were found included a review of 18 surgical cases, a review of 5 cases that underwent sclerotherapy, and finally a review of compression therapy on 16 patients with Klippel-Trenaunay Syndrome affecting their lower extremities.

The first study, by Lindenauer, reviewed 18 cases of surgical intervention on patients with Klippel-Trenaunay Syndrome (see Tables 2 and 3). The most common procedures used in this study were vein ligation and vein excision. One patient was treated with sclerotherapy. The effect of Klippel-Trenaunay Syndrome on the patients in this study is written on table 2. In the cases that did not receive treatment, 40 percent had negative outcomes. In contrast, 92 percent of the patients who underwent a surgical procedure had negative results.

The second study, by de Lorimier, treated 5 patients who had severe cases of Klippel-Trenaunay Syndrome with sclerotherapy. These patients required between 1 and 30 treatments of sclerotherapy to treat their malformations. Although quantitative analysis was not conducted in this study, the recurrence of varicose veins and hypertrophy was minimal. The patients in this study were very pleased with the results of sclerotherapy.

The final study, by Stringel and Dastous, concentrated on the effects of compression therapy in dealing with the symptoms of Klippel-Trenaunay Syndrome (see Table 4). Of the 16 patients, 81 percent involved in this study showed improvement in their symptoms of Klippel-Trenaunay Syndrome. None of the patients showed any signs of negative results.

Discussion

A negative result in these studies was a result of the recurrence of varicose veins, increased soft tissue hypertrophy or increased bone tissue hypertrophy. In the study by Lindenauer, the 2 control cases that were noted as worse almost passed as "no change." The tendency of these studies seems to be that surgical intervention has negative results. This is because vein ligation, vein stripping, and vein resection, or excision, can be potentially harmful to surrounding tissues. Due to the scaring from these procedures, damage to surrounding tissues could lead to further complications after surgery. Although sclerotherapy creates a wound and the injection site, many believe that it is effective because it is more localized. The injury site is very small, which decreases the chance of further damage to the surrounding tissues. Compression therapy has been very effective in controlling the symptoms of Klippel-Trenaunay Syndrome. Many studies reviewed have given positive outlooks to patients using compression therapy. The study by Stringel reflects these positive views.

In a study by Servelle (1985), the symptoms of Klippel-Trenaunay Syndrome were artificially duplicated in seven dogs. At one month of age, the veins in either the groin or popliteal region were ligated in each of the seven dogs. Hypertrophy of the limb was evident 12 to 18 months later. This clinical synthesis of Klippel-Trenaunay Syndrome could be useful in finding better treatments for the symptoms of Klippel-Trenaunay Syndrome. Compression therapy and chemical therapy could be compared to surgical intervention in a laboratory setting. More quantitative analysis needs to be conducted between surgical intervention, chemical intervention, and compression therapy. What effect does intervention have on the performance of the patient after the therapy. Years after the therapy, what is the extent of the patients Klippel-Trenaunay Syndrome symptoms. These are a few of the questions that should be looked into when searching for future research ideas.

Research

Baskerville, P.A. J.S. Ackroyd, and N.L. Browse. 1985. The Etiology of the Klippel-Trenaunay syndrome. Annals of Surgery. 202(5):624-7

De Lorimier, A.A. 1995. Sclerotherapy For Venous Malformations. Journal of Pediatric Surgery. 30(2):188-94

Gloviczki, P., L.H. Hollier, R.L. Telander, B. Kaufman, A.J. Bianco, and G.B. Stickler. 1983. Surgical Implications of Klippel-Trenaunay Syndrome. Annals of Surgery. 197(3):353-360

Letts, R.M. 1977.Orthopaedic Treatment of Hemangiomatous Hypertrophy of the Lower Extremity. Journal of Bone and Joint Surgery. 59(6):777-783.

Lindenauer, S.M. 1965. The Klippel-Trenaunay Syndrome: Varicosity, Hypertrophy, and Hemangioma with No Arteriovenous Fistula. Annals of Surgery. 162(2):303-314.

Nielson, J.R. and E.H. Tschen. 1987. Klippel-Trenaunay-Weber Syndrome. Cutis. 40(1):51-53

Samuel, M. and L. Spitz. 1995. Klippel-Trenaunay Syndrome: Clinical Features, Complications, and Management in Children. British Journal of Surgery. 82:757-761.

Servelle, M. 1985. Klippel and Trenaunay's Syndrome, 768 Operated Cases. Annals of Surgery. 201(3): 365-373.

Stringel, G. and J Dastous, 1987. Klippel-Trenaunay Syndrome and Other Cases of Lower Limb Hypertrophy: Pediatric Surgical Implications. Journal of Pediatric Surgery. 22(9): 645-650.

Table 1 - Secondary symptoms of KTS

Arteriovenous fistulae	an abnormal communication between an artery and a vein, bypassing the capillary bed
Cellulitis	Infection of the skin or connective tissues
Edema	abnormal swelling of some part of the body due to retention of fluid in body tissues
Lymphangioma	Mass of lymphatic vessels or channels that vary in size
Pelvic Asymmetry
Pelvic Nonfusion
Phlebitis	Inflammation of a vein
Thrombophlebitis	Clotting within an inflamed vein
Thrombosis	Clotting within a vein
Tumors	An abnormal swelling or mass

Table 2 - The symptoms of KTS displayed by the 18 surgical cases in study #1.

Lower Limb	94%
Symptoms at birth	100%
Hemangioma	83%
Limb - Length Difference	83%
Soft Tissue Hypertrophy	88%
Varicosities	100%
Average age	25.7 years

Table 3 - Procedures and results of 18 surgical cases involved in study #1.

#	Extremity	Onset	Hemangioma	Length	Girth	Varicosities	Venogram	Treatment	Result
1	Left Lower	Birth	Extensive	Greater	Greater	Marked	Absent Deep Calf Veins	Ligation and Stripping	Worse
2	Right Lower	Birth	Extensive	Greater	Greater	Marked	Absent Deep Veins	None	Worse
3	Right Lower	Birth	Moderate	Greater	Less	Very Marked	No Deep Veins	None	No Change
4	Left Lower	Birth	Extensive	Shorter	Less	Marked	Absent Deep Veins	Ligation and Injection	Worse
5	Right Upper	Birth	Extensive	Greater	Greater	Moderate	Absent Deep Veins	None	Worse
6	Left Lower	Birth	Extensive	Equal	Greater	Marked	Absent Deep Veins	Ligation and Stripping	No Change
7	Right Lower	Birth	Extensive	Greater	Greater	Marked	*	Ligation and Stripping	Worse
8	Left Lower	Birth	None	Greater	Greater	Marked	No Superficial Femoral Vein	Ligation	Worse
9	Right Lower	Birth	None	Greater	Greater	Marked	*	Excision	Worse
10	Left Lower	Birth	Present	Greater	Greater	Marked	*	Ligation and Stripping	Worse
11	Right Lower	Birth	Extensive	Greater	Greater	Marked	*	None	Worse
12	Left Lower	Birth	Extensive	Equal	Equal	Marked	*	Ligation and Stripping	No Change
13	Right Lower	Birth	Extensive	Greater	Greater	Marked	*	Ligation and Stripping	Worse
14	Right Lower	Birth	Present	Equal	Equal	Moderate	*	Ligation and Stripping	Worse
15	Left Lower	Birth	None	Greater	Greater	Marked	No Superficial Femoral Vein	Exploration, No Superficial Femoral Vein	Worse
16	Left Lower	Birth	Extensive	Greater	Greater	Marked	*	Ligation and Stripping	Worse
17	Right Lower	Birth	Extensive	Greater	Greater	Moderate	Absent Deep Veins	None	No Change
18	Right Lower	Birth	Extensive	Greater	Greater	Marked	No Deep Veins	Ligation and Stripping	Worse

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Red = denotes no treatment Blue = denotes surgical intervention

Table 4 - Procedures and results of 16 cases involved in study #3.

Case	Limb Affected	Treatment	Result
1	Right lower	None	Same
2	Left lower	Shoe Lift	Improvement
3	Right lower	Compression Garment	Improvement
4	Right lower	Compression Garment	Improvement
5	Left lower	Supportive Wrap	Same
6	Left lower	Compression Garment	Improvement
7	Right lower	Compression Garment	Improvement
8	Left lower	Compression Garment	Improvement
9	Right lower	None	Same
10	Right lower	Compression Garment	Improvement
11	Right lower	Compression Garment	Improvement
12	Left lower	Digit Amputation	Good
13	Left lower	Compression Garment	Improvement
14	Left lower	Compression Garment	Improvement
15	Right lower	Compression Garment	Improvement
16	Both Legs	Digit Amputation	Good