Is May-Thurner Syndrome linked to Ehlers-Danlos Syndrome and POTS?

What is May-Thurner Syndrome (MTS)?

May-Thurner Syndrome (MTS), also known as iliac vein compression syndrome, is a vascular compression condition where the right common iliac artery compresses the left common iliac vein against the lumbar spine. This compression leads to impaired venous outflow from the left leg, resulting in a range of symptoms, most notably deep vein thrombosis (DVT). While MTS itself is relatively uncommon, it often goes underdiagnosed due to its subtle presentation and symptom overlap with other vascular disorders. The condition is particularly significant in patients with connective tissue disorders, such as Ehlers-Danlos Syndrome (EDS), and those with autonomic dysfunction disorders like Postural Orthostatic Tachycardia Syndrome (POTS).

Signs and Symptoms

The hallmark of MTS is the development of deep vein thrombosis in the left leg. Common symptoms include:

• Leg Swelling and Pain: Patients typically experience swelling, pain, and a feeling of heaviness in the left leg. The pain may worsen with prolonged standing or sitting.
• Venous Ulcers: In severe cases, poor blood flow can lead to the development of venous ulcers, which are difficult to heal and can cause significant discomfort.
• Varicose Veins: Some patients may develop varicose veins in the left leg as a result of the increased venous pressure.
• Skin Discoloration: Chronic venous insufficiency can lead to changes in skin color, particularly around the ankle and lower leg.

Causes and Risk Factors

May-Thurner Syndrome is caused by the physical compression of the left common iliac vein by the right common iliac artery. This anatomical anomaly is often exacerbated by certain risk factors, including:

• Female Gender: MTS is more common in women, particularly those who have been pregnant, due to the additional pressure on the pelvic veins during pregnancy.
• Prolonged Immobility: Extended periods of immobility, such as long flights or bed rest, can increase the risk of DVT in patients with MTS.
• Connective Tissue Disorders: Conditions like Ehlers-Danlos Syndrome, which affect the integrity of connective tissues, can make veins more susceptible to compression and related complications.

The Link Between MTS, Ehlers-Danlos Syndrome, and POTS

Ehlers-Danlos Syndrome (EDS) is a group of genetic connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Patients with EDS, particularly the vascular subtype (vEDS), are more prone to vascular complications due to the weakened structure of their blood vessels. This fragility increases the risk of venous compression syndromes, including May-Thurner Syndrome.

In individuals with EDS, the abnormal collagen synthesis and altered connective tissue properties can lead to structural vulnerabilities in blood vessels. These abnormalities can predispose them to the development of MTS, as their veins may be more susceptible to compression from adjacent arteries. Additionally, the hypermobility seen in EDS can result in anatomical variations that exacerbate the risk of vascular compression.
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Postural Orthostatic Tachycardia Syndrome (POTS) is a condition characterized by an abnormal increase in heart rate upon standing, often accompanied by symptoms such as dizziness, lightheadedness, and fainting. The connection between MTS and POTS lies in the shared impact on blood flow and autonomic function. Patients with POTS often experience dysregulation of blood circulation, leading to issues like venous pooling in the lower extremities.

Research suggests that the venous compression seen in MTS can exacerbate the symptoms of POTS by further impairing venous return from the legs to the heart. This exacerbation can lead to increased pooling of blood in the lower body, reducing the amount of blood available for circulation when standing. As a result, patients with both MTS and POTS may experience more severe symptoms of orthostatic intolerance, including dizziness, fatigue, and palpitations.

In some cases, treating the venous compression caused by MTS, such as through stenting, has been shown to alleviate POTS symptoms, highlighting the importance of considering MTS as a potential underlying factor in POTS patients who present with symptoms of venous insufficiency.

Diagnosis of May-Thurner Syndrome

Diagnosing May-Thurner Syndrome can be challenging, particularly because its symptoms overlap with other conditions. A combination of clinical evaluation and imaging studies is typically used:

• Doppler Ultrasound: Often the first step in diagnosis, this non-invasive imaging technique assesses blood flow and can detect venous compression.
• CT or MRI Venography: These imaging modalities provide a detailed view of the pelvic vasculature, allowing for the visualization of the iliac veins and the extent of compression.
• Intravascular Ultrasound (IVUS): In some cases, IVUS is used during venography to provide a more detailed assessment of the vein from within, helping to confirm the diagnosis.

Treatment Options for May-Thurner Syndrome

The treatment of May-Thurner Syndrome focuses on relieving symptoms, preventing complications like DVT, and addressing the underlying venous compression. Treatment options include:

• Anticoagulation Therapy: The first line of treatment for MTS-associated DVT is the use of blood thinners to prevent further clot formation and reduce the risk of pulmonary embolism.
• Endovascular Interventions: For patients with significant symptoms or recurrent DVT, minimally invasive procedures such as balloon angioplasty and stent placement are often employed. These procedures help to relieve the venous obstruction and restore normal blood flow.
• Surgical Options: In severe cases where endovascular treatments are ineffective, more invasive surgeries like vein bypass or vein transposition may be considered. However, these procedures are less common due to their higher risk and complexity.

Conclusion

May-Thurner Syndrome, though often underdiagnosed, can lead to significant complications, particularly in individuals with underlying conditions like Ehlers-Danlos Syndrome and Postural Orthostatic Tachycardia Syndrome. The link between MTS, EDS, and POTS highlights the importance of a comprehensive approach to diagnosis and treatment, particularly in patients with connective tissue disorders and autonomic dysfunction. With advancements in imaging and minimally invasive therapies, there is hope for improved management and outcomes for patients with this complex condition.

References

• Mohammed, A., Zinabu, S.W., & Michael, M.B. (2024). Navigating Complexities: A Case of Multiple Abdominopelvic Vascular Compression Syndromes in Ehlers-Danlos Syndrome. Cureus, 16(7): e63848. doi:10.7759/cureus.63848.
• Pruitt, P.C., & Mossé, K.N. A Cellular and Genetic Approach to Ehlers-Danlos Syndrome. Journal of Vascular Surgery.
• Ormiston, Cameron K., et al. “May-Thurner syndrome in patients with postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome: a case series.” European Heart Journal Case Reports, vol. 6,4 (2022): ytac161. doi:10.1093/ehjcr/ytac161.

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