Geoff’s Translation
The GIST
This is part one of a series of blogs on the Mast Cell Masterminds Conference, which took place in September 2024 in Fort Hood, Oregon. Thanks to Dr. Kaufman and the conference organizers for making it possible for me to view the presentations.
Alexis Cutchins MD spoke on connective tissue and venous disease.
One thing to note is that a mast cell conference will never solely be about mast cells. Mast cell activation can affect the body in so many ways that any mast cell conference will include presentations on a wide range of disorders.
Take connective tissues. They’re loaded with mast cells! When mast cells go off, they can damage the connective tissues, and the connective tissues (skin, blood vessels, spinal cord, gut lining, ligaments) are everywhere.
Some of the 3 1/2-day Mast Cell Masterminds conference presentations addressed connective tissue issues, and this overview will focus on a specific type of connective tissue: the blood vessels.
This blog will cover the following presentations:
- Alexis Cutchins – Emory University – “It’s Not Just POTS: The Role of Connective Tissue Disorders, Venous Disease, and Mast Cells in Postural Orthostatic Tachycardia Syndrome“
- Meredith McDermott, MD (Minimally Invasive Procedure Specialists, South Denver) – “A Clinical Approach to the Diagnosis and Treatment of Pelvic Venous Disease“
Some information not in the presentations is included in the blog.
The GIST
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Connective Tissues and Postural Orthostatic Intolerance Syndrome (POTS)
Meredith McDermott MD spoke on diagnosing and treating pelvic venous syndromes.
In her POTS presentation, Dr. Cutchins noted that she doesn’t just look for the signature finding in POTS – an increased heart rate during standing – but for signs that the connective tissues have been damaged; i.e.. things like hypermobility, elastic skin, abnormal stretch marks, flushing, rash, dermatographism (raised marks after scratching/rubbing the skin), evidence of venous pooling, and edema (swelling, color changes in the feet).
As we’ll see, if the connective tissues on the outside show signs of damage, it’s possible that damage on the inside – in the pelvic veins, for instance – has occurred as well.
A Locus of Damage – the Veins
While connective tissue damage can occur in many areas of the body, the veins appear to be at special risk. The beefy, muscular arteries that send oxygenated blood flowing to the tissues are not so affected, but the weaker, more flaccid veins that return the used-up blood to the heart/lungs are.
They may be less robust, but because the venous system holds 70% of our blood volume and regulates blood flows to the heart, the venous system plays a major role in cardiac output. (David Systrom has found that preload failure – the failure to deliver normal amounts of blood to the heart and reduced cardiac output is common in ME/CFS and long COVID.)
Since the venous system relies on collagen and elastin, two components of connective tissue, to regulate blood flow, and because veins contain more collagen than arteries, connective tissue problems affecting collagen are more likely to occur in the veins.
Collagen damage leads to “stretchy veins” which don’t close properly, allowing blood to accumulate in the abdomen and lower body when we stand, and potentially causing problems like orthostatic intolerance, varicose veins, skull-based venous compression syndromes and pelvic vein compression.
Venous Insufficiency
Under high pressure, muscular arteries provide oxygenated blood to the tissues. The weaker veins bring blood back to the heart and contain 70% of our blood volume.
Venous Insufficiency refers to the inability of the veins to deliver normal amounts of blood, a seemingly serious but underdiagnosed problem. Most vascular surgeons, on the lookout for clots, often do not recognize the symptoms or signs of venous insufficiency. Only in the last five years or so has it become clear that venous insufficiency/venous compression can cause an array of ME/CFS-like symptoms.
This is one of those puzzlingly tricky diagnoses. Twenty to 40% of people have some compression of the veins in the pelvic area and are asymptomatic. One study found that almost 70% of POTS patients and 40% of healthy controls exhibited some compression of the left iliac vein.
The same thing is true with postural orthostatic tachycardia syndrome (POTS) and hypermobile Ehlers-Danlos Syndrome (hEDS). Most people who fit the heart rate criteria for POTS or who are hypermobile are completely healthy, and up to 90% of people who meet the hEDS criteria have no symptoms.
A number of factors can turn asymptomatic venous compression in the pelvic region pathological. A high degree of narrowing, the buildup of scar tissue, the development of collateral veins that impact the nerves, lesions that cause symptoms only when put under load such as when standing, the presence of other factors (Leiden V, antiphospholid antibodies, estrogen exposures, pregnancy, obesity, immobility) and probably other factors can turn an asymptomatic case of venous compression or insufficiency into a symptomatic problem.
Please note that ultrasounds are not sufficient for diagnosing these conditions. MRVs (magnetic resonance venographies) are needed to accurately assess blood flows and can also pick up other pelvic problems.
Beyond the Pelvis
Most people with hypermobility, who meet the heart rate criteria for POTS, or have some degree of venous compression are asymptomatic.
If pelvic venous syndromes were just about pelvic pain, this blog would not exist. The real surprise is that they’re also linked to and may be contributing to many ME/CFS/FM/long-COVID symptoms. Check out the list of symptoms they can cause: achy and heavy feeling legs, tingling sensations in the legs, pelvic pain, flank pain, cramping muscles in the legs – particularly at night, restless legs, swollen and discolored feet and ankles, pain that is worse when you stand and gets better when you lie down, dizziness, orthostatic intolerance, anxiety and fatigue.
Smith and Rowe showed there was more to pelvic venous symptoms than the usual pelvic and leg pain doctors look out for. Their 2022 survey showed that people with pelvic congestion – which is caused by a blockage of blood flows in the pelvic veins – often experienced symptoms not associated with the pelvis such as severe fatigue (72%), dizziness (63%), IBS symptoms (61%), brain fog (33%), migraines (49%), polyuria or dysuria (41%), excessive sweating (31%), TMJ pain (31%), and loose skin or lax joints (18%).
In a paper submitted for publication, Cutchins estimated 80% of POTS patients had signs of pelvic venous disease; 73% were diagnosed with MCAS or had suspected MCAS, 24% had hypermobile EDS, 26% polycystic ovary syndrome (pCOS), and 53% experienced symptom worsening or had their symptoms triggered by COVID-19.
The pelvis appears to be another place where connective tissue and circulatory problems can occur.
The high incidence of pelvic venous disease in POTS is likely due to blood pooling in the abdomen/pelvis/legs, which reduces blood flows to the heart, thus triggering the baroreceptors to increase the heart rate in an attempt to improve them.
While pelvic venous syndromes have not been studied in long COVID, an increased risk swelling, varicose veins, clot risk, impaired blood vessel functioning, and hypercoagulation suggests that pelvic vein problems may be present.
The takeaway: Pelvic venous diseases are part of the ME/CFS/FM/POTS/IBS/long-COVID suite of diseases. If you have symptoms associated with them and ME/CFS-like symptoms, these syndromes might be something to check out. The chief problem – obstructed blood flows – fits very nicely with the idea that problems with reduced blood flows – whether from the heart, through the veins, or in the microcirculation – play a key role in these diseases.
The connective tissue connection potentially fits with the spinal and blood vessel issues, Peter Rowe’s neuromuscular strain, the pathological hypermobility that is sometimes present, the pain hypersensitivity, and even the gut problems sometimes seen in these diseases. The pelvis appears to be simply another place where connective tissue damage/problems with blood flows can occur.
Collateral Damage
Collateral veins (left) disappear after a stent.
When a vein becomes compressed or blocked in the pelvis (or other areas), the body produces a tangle of small collateral veins in an attempt to maintain blood flow. While collateral veins can often help move blood and thereby relieve symptoms, they can also press on nerves or other structures, causing pain.
Pelvic Venous Syndromes
Note that most of these syndromes are considered by the medical profession to be “compression syndromes,” not connective tissue diseases. At some point, that may change, but for now, note that they are also associated with connective tissue problems that can weaken the veins, making them more susceptible to being compressed. Patients can have a variety of issues that may require both stenting and emobolization.
May-Thurner Syndrome
The primary issue McDermott sees is left iliac vein compression, also known as May-Thurner Syndrome. In May-Thurner Syndrome, a thick, muscular artery, sitting on top of the weaker, less robust left Iliac vein, compresses it, reducing blood flows from the legs to the upper body.
Stenting is a minimally invasive procedure commonly used in several pelvic venous syndromes.
Symptoms can include left leg swelling and heaviness that worsen late in the day or with prolonged standing/sitting, and which improves when the leg is elevated. There may also be feelings of pressure and pain during walking that eases when lying supine, as well as red or purplish-brown skin, or visible spider or varicose veins. Other ME/CFS symptoms may be present.
Treatment – Conservative options include leg elevation, compression stockings, and monitoring to determine if the problem resolves. The standard of care for relieving vein compression, however, is stenting. First, a balloon widens the narrowed vein, and then a stent is permanently placed to hold it open, restoring normal blood flow. This often dramatically reduces pain, swelling, and risk of further thrombosis or venous insufficiency. More severe cases may involve relocating the right iliac artery to prevent it from compressing the vein.
Nutcracker Syndrome
In Nutcracker Syndrome, the left renal vein gets trapped between the abdominal aorta and the mesenteric artery.
Symptoms can include blood in the urine (hematuria – can be microscopic and intermittent), orthostatic proteinuria (increased protein levels in urine when standing), left flank and/or abdominal pain, varicose veins in the pelvic area, feelings of pelvic congestion, dysmenorrhea (menstrual pain), fatigue, dizziness, orthostatic intolerance, gut bloating/pain, pain during or after intercourse (dysparenuria).
Treatment – Treatment is similar to May-Thurner. Anticoagulants may be tried. Putting in stents to decompress veins has proven to be “a safe, effective, and ‘minmally invasive’ treatment”. In more severe cases, vascular surgery can reposition the vein so that it is no longer compressed.
A short stent doesn’t work (middle image), but when a longer stent was put in (right image) and blood flow was restored and the collateral veins disappeared, the patient’s pain disappeared.
Pelvic Congestion Syndrome
PCS occurs when the valves in the veins fail, resulting in engorged, dilated veins. It can produce all the symptoms of venous insufficiency plus pelvic pain, low back and/or hip pain, pain after intercourse, urinary tract symptoms, increased urinary frequency, pain with urination, irritable bladder symptoms, palpitations, varicose veins, and orthostatic intolerance. As with venous insufficiency, all of these symptoms get better when lying down.
Treatment – Embolization is a “minimally invasive” procedure that stops the abnormal blood flow, thereby relieving pressure. It involves implanting tiny metallic coils or a liquid agent to block the dilated and damaged veins. The veins then shrink over time, reducing swelling, pain, and congestion. Depending on how many veins are being treated, the procedure usually takes 30 minutes to a few hours, and the patient can go home on the same day. It reportedly has a high success rate.
Valve Trouble – Varicose Pelvic Veins
When the valves in the veins break down, the veins become engorged. Embolizing agents can close these veins down.
Varicose veins can occur in all these syndromes. They occur when malfunctioning valves in the veins allow the blood to pool and stretch the veins, resulting in bulging, twisted, and, at times, visible veins. One cause is weakened blood vessel walls – possibly due to mast cell attacks. While they often cause only cosmetic concerns in the legs, they can also lead to pain, heaviness, swelling, cramping, skin changes, and ulcers, particularly in the areas around the ankles.
Treatment – Compression stockings, leg elevation, weight management, and increased exercise may provide relief for people with mild cases. Using ultrasound to target the source of the varicose veins, and then closing them down with embolizing agents (coils, plugs, or liquid agents) can reduce pressure and help alleviate interstitial cystitis and vulvodynia, as well as pelvic pain. It appears to be quite effective. Sclerotherapy may work for some types of pelvic veins.
Variococeles
Variococeles are a pelvic venous issue that occur only in men. They are usually not a problem.
The pelvic venous syndromes occur more often in women, but varicoceles occur only in men. Varicoceles (enlarged veins in the scrotum) on the left side in men are caused by valve or anatomical problems.
Like the pelvic venous syndromes, connective tissue problems can increase the risk of having a varicocele. (Both my twin and I have several connective tissue issues (varicocele, pectus carinatum). I also have a hiatal hernia and plantar fasciitis. He does not have ME/CFS…)
The ME/CFS/POTS Connection
A clear overlap exists between pelvic venous syndromes and the POTS/ME/CFS suite of diseases.
While we need more studies, the evidence to date suggests that treating pelvic venous syndromes may help alleviate orthostatic intolerance, brain fog, and fatigue in some people. People with POTS who have not responded to POTS treatments and who experience pelvic/leg pain might particularly take note of the pelvic venous syndrome connection.
Smith and Rowe found that treatments for pelvic venous problems resulted in significant decreases in symptom scores assessing pelvic pain and dysautonomia.
Several case studies have featured POTS or EDS patients who presented with pelvic and/or lower extremity pain. A 16-year-old with POTS and EDS experienced palpitations, concentration difficulties, dizziness, left leg swelling, and pelvic pain. Propranolol (10 mg) twice daily had not helped, and she was taking 0.1 mg of fludrocortisone once a day.
Her pelvic venography showed “severe obstruction of the left common iliac vein with near-complete flow arrest” and the development of numerous collateral veins. Stenting resulted in a significant reduction of her orthostatic symptoms as well as her pain, leg swelling, etc.
Similar results were seen in a case series of three female patients with POTS, Ehlers-Danlos syndrome (EDS), and May-Thurner syndrome (MTS). One woman with hypermobile EDS and POTS experienced left leg swelling and pelvic pain, brain fog, dizziness, and difficulty staying upright. Neither propanolol nor fludrocortisone had helped her POTS symptoms.
A pelvic ultrasound was normal, but an MRV found “severe compression” of both the left iliac and left renal veins, indicating that she had both May-Thurner syndrome and Nutcracker syndrome. Stenting of her left iliac vein resulted in a complete resolution of her POTS and concentration symptoms.
Another woman with EDS and POTS had it all. She experienced chronic abdominal pain, weakness, severe concentration difficulties, lightheadedness, palpitations, pelvic pain, left leg swelling, and lower abdominal bloating that would worsen during menses. An MRV showed narrowing of the left iliac vein (May-Thurner), blockage in the left renal vein (Nutcracker), and retrograde (backwords) flow in the left ovarian vein (pelvic congestion syndrome). The authors wrote:
“These findings are consistent with severe venous insufficiency, which is a common feature of POTS.”
A stent in her left iliac vein resolved her left leg pain and swelling, but she continued to experience abdominal pain and bloating. An embolization of the left gonadal vein resulted in a significant improvement in POTS symptoms, decreased abdominal bloating and leg pain, and an improvement in her ability to remain upright. To address occasional episodes of dizziness, she continued to take 2.5 mg of midodrine 3× daily.
Conclusion
If you experience unresolved abdominal/pelvic/leg pain and the symptoms of ME/CFS/POTS/long COVID you might want to investigate pelvic venous syndromes. From what I can tell, you’ll need a venography (MRV) (hopefully with contrast?) to tell if the veins in your pelvic area are being compressed or congested. If they are, the treatment options mostly include “minimally invasive” procedures such as stenting and/or emobolization.
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