Case Series of Concomitant Klippel-Trenaunay Syndrome and May-Thurner Syndrome

Introduction

Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder where the development of blood vessels, bones, and soft tissues may be affected. The exact etiology is unknown, however it has been shown to involve mutations in the PIK3CA gene which codes the phosphatidylinositol 3-kinase enzyme leading to abnormal angiogenesis. ¹ Various abnormalities result relating to persistent embryonic veins, hypoplastic superficial or deep venous systems, and some develop venous aneurysms. ² Clinically, it presents as the triad of port wine stains, hypertrophy of bone and soft tissues leading to limb hypertrophy, and venous malformations. ³ Complications include superficial thrombophlebitis, deep venous thrombosis (DVT) and/or pulmonary embolism, chronic lymphedema, and cellulitis.^4,5 The exact incidence, prevalence and genetic predisposition is unknown, however, is estimated to be at least 1 in 100,000 people. ⁶

May-Thurner syndrome (MTS) is caused most commonly by compression of the left common iliac vein (CIV) by the overlying right common iliac artery (CIA). Rarely it can present in the right iliac system in the setting of a left sided inferior vena cava (IVC). ⁷ Iliac vein obstruction may cause symptoms related to venous hypertension and DVT. The exact incidence of MTS is unknown but ranges from 18% to 49%, and presents most commonly in females with symptomatic lower extremity venous disease.^8,9 Clinical presentation includes DVT, lower extremity swelling, varicosities and ulcers. The incidence of DVT in patients with MTS ranges from 2% to 3% and is the most common presenting symptom.^10,11

The incidence of MTS concomitant with KTS is unknown and to our knowledge there is only one other reported case in the literature. In that report, Lu and colleagues treated the MTS with 2 Wallstents (Boston Scientific, Malborough, MA, USA) and subsequently treated the varicosities with small saphenous vein stripping and high ligation of the stump. ¹² That patient did well post-operatively with symptomatic improvement. Patient consent was obtained for all 3 patients prior to this publication.

Case 1

The patient is a 55-year-old Caucasian female with a history of KTS and left lower extremity hemangioma, who presented in 2014 with painful, ulcerated left lower extremity varicose veins (VVs). She was previously managed for over 2 years with 40-50 mm Hg compression stockings, however, developed worsening symptoms. On physical exam she had palpable pedal pulses, and large, non-tender varices on the lateral thigh; there was also moderate lower extremity edema. Venous duplex ultrasonography (DUS) revealed an incompetent perforator vein at the lateral mid-thigh with a maximum diameter of 5.0 mm and 2.4 seconds reflux. This perforator also had incompetent tributaries, maximum diameter measured 6.0 mm. All other veins were negative for reflux or thrombosis. There was normal anatomy of the deep venous system. The patient had worsening upper and lower leg swelling and pain despite compliance with compression stockings daily. Pelvic magnetic resonance venography (MRV) was obtained to evaluate for central venous pathology.

MRV revealed severe narrowing of the left CIV at the crossing of the left CIA, consistent with MTS. Given the severity and progression of disease despite daily compression therapy left iliac venography was performed to assess and treat her MTS. Intravascular ultrasound (IVUS) showed the proximal CIV had a 50% stenosis; and the CIV and external iliac veins (EIV) had opacities on IVUS consistent with intravenous webbing. The IVC was normal in caliber. Venoplasty was performed with severe waisting of the balloon related to persistent webbing, therefore an 18 mm × 16 mm Wallstent was placed with an excellent angiographic result (Figure 1A, B). The patient subsequently reported improvement in the tightness, swelling, and pain of her left leg. There was some recurrent swelling at 34 months and repeat venogram and venoplasty were performed demonstrating narrowing of the proximal portion of the CIV stent (Figure 2A, B). Her symptoms improved and she was stable at 7 months after the second procedure and 41 months after the initial procedure. She subsequently underwent microphlebectomy of her lateral thigh varices with additional symptomatic improvement.

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Figure 1.

A (Left), Severe waisting during venoplasty of the left CIV. B (Right), Significant improvement after deployment of Wallstent.

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Figure 2.

A (Left), Recurrent stenosis seen during venoplasty at the proximal CIV stent. B (Right), Resolution of the stenosis after venoplasty.

Case 2

The patient is a 31-year-old Caucasian female with a history of KTS diagnosed at 3 years of age. She had a history of superficial vein thrombosis after a flight, left lower extremity DVT, and a left popliteal vein aneurysm (PVA). Prior to presentation at this institution she underwent multiple procedures including left great and small saphenous vein ablations with laser and foam, and injection sclerotherapy for telangiectasias. Since then she experienced lower extremity pain and swelling managed with 40-50 mm Hg compression stockings. She initially presented for evaluation of left leg pain, throbbing, and achiness. Physical exam was notable for palpable pedal pulses, VVs on the left calf and thigh, telangiectasias bilaterally, and left calf edema with hyperpigmentation. DUS revealed a 3.01 cm by 3.28 cm left PVA, and reflux time >0.5 seconds in the perforator tributaries of the calf. An MRV revealed compression of the left CIV at the crossing of the right CIA; the IVC was normal in caliber. These findings were consistent with MTS.

Given the presence of venous hypertension, history of DVT despite multiple prior interventions, and longstanding symptoms, the patient underwent venography to treat her MTS. IVUS and conventional venography revealed an 80% stenosis of the left CIV, consistent with prior imaging. An 18 mm × 90 mm CIV Wallstent was placed with the central portion extending into the IVC. On repeat venography there was persistent stenosis in the EIV treated with a second 18 mm × 90 mm Wallstent. Post-operatively the patient recovered well with resolution of left leg pain. Fifteen months post-intervention, she continued to do well and DUS revealed a decrease in the size of her PVA to 2.6 cm. She has persistent mild edema which is managed with compression stockings.

Case 3

The patient is a 28-year-old Caucasian male with a history of lower extremity edema for 6 years and was diagnosed with KTS. He also had an absent left popliteal vein on DUS. The patient previously underwent an orthopedic procedure at 14-years-old due to abnormal left leg growth. DUS demonstrated deep and superficial venous reflux >0.5 seconds and the patient was advised to wear 30-40 mm Hg compression stockings. He presented 7 years later with a physical exam notable for palpable pedal pulses and painful, bulging VVs in the left leg despite compliance with 30-40 mm Hg compression stockings. A computed tomography venogram (CTV) demonstrated proximal left CIV compression of 50%, the IVC was normal in caliber, consistent with possible MTS. Venography and IVUS demonstrated >70% stenosis of the left CIV (Figure 3A, B). This was treated with a 24 mm × 70 mm Wallstent. At 30 day follow-up the patient remained compliant with compression stockings and had improvement in his lower extremity symptoms. A DUS demonstrated some laminar thrombus in a patent iliac vein stent, which was treated with apixaban for 8 weeks. DUS done at 90 day follow-up demonstrated resolution of the laminar thrombus. His symptoms of severe aching and pain in the left leg resolved and remained improved from his baseline over the past 7 years. He continues to be compliant with compression stockings.

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Figure 3.

A (left), B (right). Stenosis of the left CIV at the crossing of the right common iliac artery on IVUS (left) and immediately peripheral to the stenosis (right).

Discussion

Congenital vascular disorders are extremely rare, and presenting concomitantly with a second structural abnormality is an even more unusual occurrence. KTS may effect either limb with a nearly equal incidence, 36% on the right and 33% on the left. ⁵ Once the diagnosis of KTS is made, recurrent and residual venous pathology in that extremity may lead to multiple interventions over many years. In contrast, MTS is a single anatomic obstructive pathology that can be treated in a single surgical intervention. The lesion more commonly effects the left lower extremity and is thought to cause of 49%-62% of left lower extremity venous disease. ¹¹ It is frequently treated with iliac vein stenting with a very high technical success rate, even in the setting of DVT. ¹³

These cases highlight the importance of identifying the etiology of proximal compression in patients with KTS, particularly when they are refractory to high-grade compression. Treating only peripheral disease will prove inadequate if more central pathology is not investigated. While DUS is considered the gold standard for diagnosing infrainguinal venous pathology, axial imaging and IVUS can provide additional information of the pelvic venous system. ¹⁴ It may be challenging to identify which patients require axial imaging (CTV/MRV) to assess for central venous pathology, and this must be balanced with increased cost of those modalities over DUS, as well as exposure to contrast, and radiation.

Indications for central imaging may be persistent unilateral symptomatology and venous hypertension despite daily use of tight compression and peripheral treatment. These cases highlight the importance of broadening the differential diagnosis to include more central pathology when multiple peripheral interventions have been performed or consistent compression therapy has be used without symptomatic relief.

Conclusion

KTS and MTS are independently rare clinical entities. However, they may occur concomitantly. Complete central and peripheral imaging in selected patients can diagnose these uncommon pathologies and allow successful treatment. Iliac venous stenting with or without adjunctive microphlebectomy can lead to symptomatic improvement in patients afflicted with these rare conditions. For the clinician, it is important to keep a broad differential diagnosis when assessing patients with KTS and persistent lower extremity symptoms after adhering to tight compression and multiple prior peripheral interventions.