The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 41

50. How does mast cell disease affect hearing?

For readers who don’t know, I lost the majority of my hearing in 2009. I am profoundly deaf in my left ear and have moderate to severe hearing loss in my right. This happened years before I was diagnosed with systemic mastocytosis or Ehlers Danlos Syndrome.

Mast cell disease affects hearing in multiple ways. Some related diagnoses also affect hearing.

Mast cells are involved in sensorineural hearing loss. The exact role of mast cells is still being researched but hearing loss is not an unusual complaint for mast cell patients. Mast cell disease can also cause auditory processing disorder. This condition makes it difficult to understand speech. Ringing in the ears (tinnitus) is also a symptom of mast cell disease.

Many mast cell patients also have Ehlers Danlos Syndrome (EDS), a disease in which the body makes defective connective tissue. EDS patients are vulnerable to both sensorineural hearing loss, in which the nerves don’t correctly transmit sound from the ear to the brain, and conductive hearing loss, in which the ear is not able to carry the sound waves correctly to the inner ear. Having both types of hearing loss, sensorineural and conductive, is called mixed hearing loss.

Many mast cell patients are deconditioned. This means that their body has undergone lots of changes as the result of not being active. Sensory processing is affected in deconditioned patients. In particular, sounds must be louder to be heard correctly. POTS patients sometimes experience something similar.

Having certain autoimmune disorders can increase the risk of autoimmune inner ear disease, resulting in hearing loss. Many mast cell patients also have autoimmune disease.

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 32

39. How are mast cell disease, Ehlers Danlos Syndrome and POTS connected? (Continued)

I’m answering this question in two parts because there is a lot of information to relay and it’s important that it is done clearly. This is the second part.

Mast cells are found throughout the body. There is no record of a person living without mast cells. They perform many essential functions. This is the reason why killing off all of a person’s mast cells is not a viable treatment for mast cell disease. While mast cells cause so many symptoms and problems for patients with mast cell disease, life is unsustainable without mast cells.

Let’s specifically consider just a few of the mast cell’s essential functions here and how they relate to POTS and EDS.

Mast cells help the body to regulate blood pressure and heart rate. Many of the mast cell’s chemicals do this so it happens in many different ways all stemming from mast cells. This means that when mast cells are not behaving appropriately, there are many ways in which this dysfunction can lead to not regulating blood pressure and heart rate correctly.

  • Histamine can affect blood pressure and heart rate differently depending upon how it acts on the body. If it uses the H1 receptors, it can cause low blood pressure. If it uses the H2 receptors, it elevates blood pressure. If it uses the H3 receptor, it can cause low blood pressure. When it does this at the H3 receptor, it’s because it tells the body not to release norepinephrine. Not releasing as much norepinephrine lowers heart rate and making the heart beat more weakly.
  • Prostaglandin D2 lowers blood pressure and causes fast heart beat. However, the molecule made by breaking down PGD2, called 9a,11b-PGF2 increases blood pressure.
  • Vasoactive intestinal peptide lowers blood pressure.
  • Heparin, chymase and tryptase can decrease blood pressure. They do this by helping to make a molecule called bradykinin. When this happens, a lot of fluid falls out of the blood stream and gets stuck in the tissues, causing swelling.
  • Thromboxane A2 increases blood pressure.
  • Many mast cell molecules affect the amount of angiotensin II. This molecule strongly drives the body toward high blood pressure. Some mast cell molecules that affect blood pressure this way include chymase and renin.

Another very essential function of mast cells is to make connective tissue. Mast cells help the body to shape itself correctly and to make tissue to heal wounds. When mast cells are not behaving appropriately, their dysfunction can interfere with making connective tissue and wound healing. It can cause wounds to heal very slowly or for there to be too much scar tissue. It can also cause the connective tissue to be too weak or too strong.

The interaction between POTS and mast cell disease

In POTS, the body is already predisposed toward not regulating blood pressure and heart rate correctly. When a person with POTS stands up, their body quickly causes the heart to beat very fast. When your body does this, it takes steps that cause mast cells to become activated. In turn, the mast cells release chemicals to try and regulate the heart rate. However, if you have mast cell disease, the mast cell may release the wrong chemicals, or too many chemicals, failing to regulate the heart rate. This in turn results in a situation where the body becomes very stressed. Stress activates mast cells, which results in more release of chemicals. Patients can very easily become trapped in a cycle where POTS and mast cell disease irritate each other.

POTS can be exacerbated by the use of medications that affect blood vessels. Medications that are vasodilators (that make the blood vessels bigger) are taken by many people, including mast cell patients. In some people, using medications that blocks the action of histamine or prostaglandins can help to improve symptoms of both POTS and mast cell disease. Conversely, some of the medications used to manage POTS, like beta blockers, can trigger mast cell reactions and raise the risk of anaphylaxis. However, some POTS treatments can also help alleviate mast cell symptoms, specifically the use of IV fluids.

A paper published in 2005 found that hyperadrenergic POTS was sometimes found in patients with mast cell activation disorders.

The interaction between EDS and POTS

POTS is a form of dysautonomia. Dysautonomia means dysfunction of the autonomic nervous system. This is the part of your nervous system that helps to control automatic functions like heart rate, blood pressure and digestion.

In EDS patients, the body does not make collagen correctly. Collagen is the most common connective tissue protein in the body. This can cause vascular laxity. Blood vessels change size depending upon how much blood they need to move through them. If they get larger, it is called vasodilation. When they get smaller, it is called vasoconstriction. When a person has vascular laxity, their vessels can get larger than they should and they can stay that way longer.

POTS is the most common form of orthostatic intolerance in HEDS. Orthostatic intolerance is when a patient has symptoms specifically as the result of standing up. All EDS patients have more autonomic symptoms than healthy people. Among patients with EDS, autonomic symptoms are more common and more severe in HEDS. 94% of HEDS patients have orthostatic symptoms, including lightheadedness, dizziness, palpitations, nausea, blurred vision, and anxiety. Dysautonomia is much worse in HEDS compared to CEDS and VEDS patients.

Patients with HEDS were found overall to have overactive sympathetic nervous systems. However, when their body needed to activate in response to regulate heart rate and blood pressure in response to changing position, their responses were not strong enough.

In EDS patients, the connective tissue does not support blood vessels enough. This makes the harder for the blood vessels to get the blood back to the right places when you stand up, exacerbating POTS.

The interaction between EDS and mast cell disease

Mast cells are involved in making and repairing connective tissue, which involves collagen. For this reason, there are many mast cells living in connective tissues. Mast cells are stimulated when the body is making or trying to make collagen. Because EDS causes the body to make collagen incorrectly, mast cells can become activated to try and make collagen and other connective tissue correctly. When mast cells in one place are activated a lot over a long time, they can activate other mast cells elsewhere, resulting in systemic symptoms.

The interactions among mast cell disease, POTS and EDS

It is undeniable that there is an association among mast cell disease, EDS and POTS. However, there is not much data published on this topic. There was a poster presented in 2015 that found some combination of EDS, POTS and MCAS in a group of 15 patients. This is a very small population and we need larger studies to understand incidence. There is ongoing work to tie this group of conditions to specific genetic markers. However, this also requires further investigation and more patients. In the absence of hard data, we are forced to use some early data and understanding of similar conditions to try and figure out exactly what happens. As more data comes out, this understanding may change.

This is very much a chicken and egg situation where it’s not clear exactly what begets what. EDS is a genetic disorder and considered primary. However, that does not necessarily mean POTS or mast cell disease is secondary in this scenario.

Regardless of which is the initiating condition, the relationship seems to be something like the following:

1. A patient has EDS. They make defective connective tissue. These defective tissues do not support the bodily organs and vessels properly.

2. A patient stands up. Blood quickly moves from the torso into the legs.

3. The blood vessels in the legs try become more narrow and more able to keep fluid in the bloodstream. However, in an EDS patient, the blood vessels are stretched out and not held in the right place because the connective tissue is too weak.

4. The blood vessels in the legs are not able to pump blood back to the heart quickly enough. The body interprets this as having low blood pressure.

5. The nervous system sends signals to increase heart rate to compensate for the “low” blood pressure.

6. The signals sent to increase heart rate activate mast cells.

7. Mast cells activate release mediators to try and regulate blood pressure and heart rate.

8. Mast cell mediators activate other mast cells, eventually affecting other parts of the body.

9. The molecules released by mast cells make blood vessels bigger and more leaky.

10. As fluid leaves the bloodstream and gets stuck in places where it can’t work (third spacing), blood pressure decreases and heart rate increases. This exacerbates POTS symptoms. The cycle repeats.

For more detailed reading, please visit these posts:

Cardiovascular manifestations of mast cell disease: Part 1 of 5

Cardiovascular manifestations of mast cell disease: Part 2 of 5

Cardiovascular manifestations of mast cell disease: Part 3 of 5

Cardiovascular manifestations of mast cell disease: Part 4 of 5

Cardiovascular manifestations of mast cell disease: Part 5 of 5

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 1)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 2)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 3)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 4)

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part 5)

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 4

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 5

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 7

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 31

39. How are mast cell disease, Ehlers Danlos Syndrome and POTS connected?

I’m answering this question in two parts because there is a lot of information to relay and it’s important that it is done clearly.

Let’s talk about what EDS and POTS are first.

Ehlers Danlos Syndrome (EDS) is a connective tissue disease. It can be, and often is, inherited. About 1 in 5000 people have some form of EDS.

There are several subtypes of EDS. The ones you hear about most are called classical, vascular, and hypermobility. The different forms of EDS used to be distinguished by numbers (like Type I, Type II, etc) but now they use descriptive terms instead. Types I and II EDS are now called classical EDS (cEDS); type IV EDS is now called vascular EDS (vEDS); and type III EDS is now called hypermobility type (hEDS or htEDS). There are also other rare variants of EDS.

Each of these subtypes has distinguishing features that make them unique from the other forms of EDS. All forms of EDS cause major systemic dysfunction of connective tissue, the pieces of you that hold your body together and keep everything in the right place. Generally, in EDS patients, their connective tissues tear easily and heal slowly. They usually (but do not always) show hypermobility in their joints (being double jointed or overly flexibility). Skin that is very stretchy or that heals very poorly is common.

Because you have connective tissues holding your whole body together, EDS can affect your entire body. All patients are at risk for symptoms that specifically impact their joints, muscles and bones. VEDS can significantly affect life span because it increases the risk of an aneurysm or a blood vessel bursting. HEDS patients often have cardiovascular, GI, and neurologic symptoms. CEDS patients often display the trademark skin stretchiness and many have extraordinary difficulties in healing incisions and wounds. Of course, many EDS patients have other symptoms, and there is a lot of symptom overlap among these forms. I am just generalizing here.

There is no cure and treatment is largely about managing symptoms and complications. EDS is usually diagnosed by a geneticist. There are genetic markers for most forms of EDS that can be found with genetic testing. However, the most common form of EDS, hypermobility type EDS (hEDS), does not have a known genetic marker. For this reason, geneticists often assess how hypermobile a patient is and then uses that to support the diagnosis of hEDS.

Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance, which means symptoms and problems caused specifically by standing up. POTS patients have a big jump in heart rate when they stand up (increase of 30 beats per minute or heart rate over 120 beats/minute in adults) that is not due to a drop in blood pressure. POTS is a form of dysautonomia, an umbrella term that covers several conditions in which the body is not able to control some of the body’s automatic functions like heart rate and blood pressure. (For those wondering, automatic is not a typo, and I did not mean to write autonomic, which is related here.)

There are multiple types of POTS. I’m just going to cover neuropathic POTS and hyperadrenergic POTS as they are the most applicable here. POTS can be a primary or secondary condition. It can cause very severely disabling symptoms and effects. It can cause a huge array of symptoms, including dizziness; fainting; exhaustion; inability to exercise; nausea; vomiting; major GI disturbances (both diarrhea and constipation); inappropriate sweating; chest pain; coldness, numbness, pain and weakness of extremities; and anxiety. Some patients are unable to stand up at all.

Neuropathic POTS, the most frequently described, is thought to be the result of the veins in the legs not being able to pump blood effectively. When you stand up from a sitting position or laying down, a lot of blood that was in your torso quickly moves into your legs. This happens to everyone. In most people, the veins in your legs are able to tighten and squeeze effectively to pump that blood out of the legs and get it back to your heart. In neuropathic POTS, your veins don’t seem to be able to do this as well so the blood gets stuck in your legs. Your body interprets this as having low blood pressure even though you have enough blood and it’s just not where your body expects it. In response to the “low blood pressure”, your heart starts beating very fast to try and get enough oxygenated blood to every place in your body that needs it.

Hyperadrenergic POTS is less common but relatively more common in mast cell patients. In this form, the body makes too much adrenaline (and often other similar molecules like noradrenaline). These molecules work together to cause the nervous system to tell the heart to beat way too fast in response to standing up and that blood moving into your legs. In patients with hyperadrenergic POTS, blood pressure is often increased while the heart rate is also increased instead of being normal or low as in neuropathic POTS.

The second part of this question (question 39) will be up in a day or two. Sorry for the length but I don’t think there’s a way to answer this question both clearly and with brevity.

The Sex Series – Part Six: Male pelvic dysfunction and mast cells

Chronic pelvic pain syndrome (CPPS) affects about 15% of male patients and 90% of patients with chronic prostatitis. Patients with these conditions experience pain in the pelvis, abdomen and genitalia, as well as urinary tract symptoms without evidence of infection. Pain can be intermittent or constant, and can interfere with daily activities including sitting, standing, urination and defecation.

CPPS also causes sexual symptoms. Painful ejaculation, erectile dysfunction, and other types of ejaculation dysfunction are all common in this patient group.  In one study, 40% of patients with CPPS were found to have erectile dysfunction.  In another, 72% of patients reported either erectile dysfunction or difficulty with ejaculation.

Pelvic floor dysfunction is a component of CPPS. Many of these patients have abnormally tense pelvic floor muscles, which can cause muscle spasm and obstruct bloodflow. CPPS patients are more likely than healthy controls to have vascular dysfunction associated with nitric oxide level. In a group of 146 patients with CPPS and verified pelvic floor spasm, 56% experienced painful ejaculation.  Visceral and myofascial pain and spasm of the muscles in the pelvic floor contribute to CPPS.  While pelvic floor dysfunction has been well researched for female patients, there are far fewer studies on pelvic floor dysfunction in men.  Biofeedback and pelvic floor physical therapy can resolve issues with erectile dysfunction and other sexual issues.

IL-17, expressed by special T cells called Th17 cells, is required to develop CPPS-like conditions in animal models. IL-17 triggers mast cell degranulation and secretion of many inflammatory molecules.  A number of mast cell mediators are elevated in patients with CPPS. IL-1b, TNF, IL-6 and IL-8 are higher in seminal fluid of these patients.  CCL2 and CCL3 expression is also increased. In the prostate of animals with a CPPS model, TNF, IL-17a, IFN-γ and IL-1b are all increased.

Tryptase has been found to induce pelvic pain. Levels of tryptase and carboxypeptidase A3 are higher in CPPS patients than in healthy controls.  Tryptase binds to a receptor called PAR2.  When tryptase binds to this PAR2 receptor, it is thought that it makes nerves oversensitive. If the PAR2 receptor is blocked, pelvic pain is mitigated.  In animal models where they cannot make tryptase-like products, pelvic pain does not develop in CPPS.

Nerve growth factor (NGF) is a mast cell mediator that has been implicated in CPPS. It is elevated in seminal plasma of CPPS patients and directly correlates with pain level. It is thought that NGF makes the peripheral nerves oversensitive and causes more nerve cells than usual to be present. NGF and tryptase were elevated in prostate secretions of most CPPS patients in a small patient group. Of note, NGF release occurs and increases weeks after initial symptoms.

In animal models, injecting cetirizine (H1 antihistamine) into the peritoneal cavity decreased pain by about 13.8%; ranitidine (H2 antihistamine), 6.1%; cromolyn, 31.4%. A combination of all three decreased pain by 69.3%. When cromolyn and cetirizine were used together, larger pain relief was achieved than when used individually, but this was not seen when using ranitidine and cromolyn together.  These data suggest that H2 signaling is not a major contributor in chronic pelvic pain in male patients.

Pelvic floor dysfunction is also common in heritable connective tissue diseases and is often present in hypermobile patients.

References:

Done JD, et al. Role of mast cells in male chronic pelvic pain. Journal of Urology 2012: 187, 1473-1482.

Roman K, et al. Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome. Pain 2014: 155 (7), 1328-1338.

Cohen D, et al. The role of pelvic floor muscles in male sexual dysfunction and pelvic pain. Sex Med Rev 2016; 4, 53-62.

Murphy SF, et al. IL17 mediates pelvic pain in experimental autoimmune prostatitis (EAP). PLoS ONE 2015, 10(5) : e0125623.

 

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part Five)

HEDS patients showed overactivity of sympathetic nervous system (part of autonomic nervous system) at risk.  Conversely, when presented with a trigger that should activate the sympathetic nervous system, they show a lower response than they should.  In response to Valsalva maneuvers, their blood pressure dropped more than it should. In tilt table testing, the diastolic blood pressure increases less than it should.  Hypermobility was associated with worsened dysautonomic symptoms.  POTS is the most common subtype of dysautonomia found in HEDS patients.

Dysfunction of sympathetic nervous system is common in HEDS.  Laxity of connective tissue and use of medications that affect blood vessels aggrevate dysautonomia. Autonomic dysfunction in HEDS patients is associated with poor disease prognosis, decreased quality of life, unstable blood pressure, increased risk of cardiac disease and death as a result of it, particularly under anesthesia.

Deconditioning has a complicated relationship to orthostatic intolerance and dysautonomia.  Deconditioning lowers blood volume and alters response to adrenalin, contributing to orthostatic symptoms.

However, a study on the relationship between HEDS and dysautonomia found that decreased physical activity was not linked to worsened orthostatic symptoms.  As a result, it is thought that deconditioning in this group is probably not the primary cause of orthostatic intolerance, but a secondary contributor.

References:

de Wandele I, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Seminars in Arthritis and Rheumatism 2014, 44: 93-100.

de Wandele I, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and healthy controls. Seminars in Arthritis and Rheumatism 2014, 44: 353-361.

Wallman D, et al. Ehlers-Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study. Journal of Neurological Sciences 2014, 340: 99-102.

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part Four)

The relationship between Ehlers Danlos Syndrome and dysautonomia, the dysfunction of autonomic nervous system, is currently being elucidated.  There is a correlation between hypermobility and autonomic symptoms. One study found that in patients with autonomic dysfunction, 18% had EDS, compared to the control group, in which only 4% had EDS.

Ehlers Danlos Syndrome alters collagen structure throughout the body. In HEDS, this usually affects the skin less than in other types of EDS.  In the cardiovascular system, this contributes to vascular laxity, which allows excessive dilation of the blood vessels, causing orthostatic intolerance. Importantly, you do not see the spontaneous rupture of blood vessels seen in VEDS.

In HEDS, connective tissue defects in the GI tract lead to dysfunctional peristalsis (contraction of GI tract to move food through it), excessive stretching or swelling, dysregulation of intestinal permeability and damage to the epithelial cells of the GI tract. Without proper connective tissue support, the bladder can become distended or impinge on other structures, as in cystocele.  HEDS frequently causes weakness in the pelvic floor and can lead to prolapse of pelvic organs.

Pain and fatigue are often attributed to dysautonomia in EDS patients, but it could also be caused by HEDS. Peripheral neuropathy is prevalent in HEDS and can drive pain in this population.  Many HEDS patients have sensory pain, such as tingling, pins and needles, numbness, radiating or burning pain. If the autonomic nervous system is responsible for the pain signals, it could provide a link between dysautonomia and pain. Chronic pain and inflammation can change the structure and behavior of the nervous system, making it easier to transmit pain signals.  Orthostatic intolerance can activate the sympathetic nervous system, part of the autonomic nervous system, contributing to these types of symptoms.

By contrast, many HEDS patients are known to frequently have anxiety, palpitations, dizziness, shortness of breath and high affective distress.  Rather than being from HEDS directly, these are likely from dysautonomia.

References:

de Wandele I, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Seminars in Arthritis and Rheumatism 2014, 44: 93-100.

de Wandele I, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and healthy controls. Seminars in Arthritis and Rheumatism 2014, 44: 353-361.

Wallman D, et al. Ehlers-Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study. Journal of Neurological Sciences 2014, 340: 99-102.

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part Three)

Autonomic dysfunction can present in many ways.  Patients complained of orthostatic symptoms like fatigue, difficulty concentrating, brain fog, chest pain, palpitations, headache, visual disturbances, shortness of breath and feeling “absent.” Common GI symptoms were early satiety, bloating, nausea and vomiting (particularly after a meal), colonic spasms, constipation and diarrhea.  Sweating too much or too little and dry eyes and mouth were reported.  Raynaud’s phenomenon and purple limbs upon standing affected many HEDS patients.  Sensitivity to light and difficulty focusing vision occurred due to dysregulation of pupils. Urine retention, failure to empty bladder while urinating, and incontinence of urine were also common.

Some symptoms were strongly associated with others.  Fatigue and difficulty in concentrating was most often seen in association with symptoms that affected blood vessels changing size, symptoms that affected secretion by glands, and GI or sleep symptoms.  An overall large burden of autonomic symptoms was also seen in patients with fatigue and difficulty concentration.  Greater concentration difficulties also correlated with worse orthostatic symptoms, bladder symptoms, gastroparesis, dysregulation of pupil motion and an overall large burden of autonomic symptoms.

Many autonomic symptoms (but not those affecting motion of blood vessels or fainting) were correlated to neuropathic pain.  Orthostatic, GI, bladder, pupil and gland secretion symptoms, sleep dysfunction, and overall high autonomic burden were linked to pain severity. Tachycardia when upright and dysautonomia generally were related to severity of pain.

Dysautonomia symptoms were often seen in HEDS, particularly orthostatic and GI symptoms.  Dysautonomia symptoms greatly impacted quality of life and were associated with more fatigue and pain. Dysautonomia was much worse in HEDS than in CEDS, VEDS or fibromyalgia. In particular, orthostatic intolerance dramatically affected quality f life.  The physical limitations observed in POTS patients, the most common form of orthostatic intolerance for HEDS patients, were comparable to those seen in people with congestive heart failure or COPD.  These symptoms contribute to the lower quality of life seen in HEDS patients when compared to other EDS patients.

References:

de Wandele I, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Seminars in Arthritis and Rheumatism 2014, 44: 93-100.

de Wandele I, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and healthy controls. Seminars in Arthritis and Rheumatism 2014, 44: 353-361.

Wallman D, et al. Ehlers-Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study. Journal of Neurological Sciences 2014, 340: 99-102.

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part Two)

The Autonomic Symptom Profile (ASP) is a questionnaire that assesses symptoms in functional areas controlled by the autonomic nervous system.  The autonomic nervous system regulates many involuntary functions, such as heart rate, blood pressure, urination and digestion.  Dysfunction of the autonomic nervous system can affect many organ systems.

One study evaluated Ehlers Danlos patients for autonomic symptoms using the ASP.  The patients in this study had classic Ehlers Danlos (cEDS), vascular Ehlers Danlos (vEDS) or hypermobility type Ehlers Danlos (HEDS).  Symptom burden was compared among these different presentations of EDS and to healthy controls.

Patients with HEDS had the highest total burden of autonomic symptoms among EDS patients.  All EDS patients had more autonomic symptoms than healthy controls.  HEDS caused more orthostatic symptoms (symptoms that happen when standing up) than in other EDS forms.  94% of HEDS patients had orthostatic symptoms, including lightheadedness, dizziness, palpitations, nausea, blurred vision and anxiety.  Though many patients said they often “felt faint”, true fainting was not common.  These symptoms could be provoked or worsened with physical activity, heat, meals, or change in position.

Patients with HEDS also had the highest burden of GI symptoms compared to other types of EDS.  73% had gastroparesis, 66% had chronic constipation, and 64% had regular diarrhea.  Diarrhea was found to be the most impairing GI symptom.

HEDS patients had a larger impact of orthostatic symptoms and bladder dysfunction than either CEDS or VEDS.  Compared to just CEDS, HEDS showed more GI, secretomotor (release of fluid by glands) and pupillomotor (motion of pupil) symptoms.  Compared to just VEDS, HEDS patients had more vasomotor burden (symptoms related to the dilation of blood vessels).  HEDS autonomic burden was similar to those seen in fibromyalgia patients, with more bladder dysfunction and less sleep dysfunction.

Higher autonomic symptom burden was associated with more physical impairment, pain and decreased vitality.  More hypermobility was associated with higher burden of orthostatic symptoms, GI symptoms generally, gastroparesis, diarrhea, vasomotor symptoms and overall autonomic symptom burden.

References:

de Wandele I, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Seminars in Arthritis and Rheumatism 2014, 44: 93-100.

de Wandele I, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and healthy controls. Seminars in Arthritis and Rheumatism 2014, 44: 353-361.

Wallman D, et al. Ehlers-Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study. Journal of Neurological Sciences 2014, 340: 99-102.

Hypermobility Type Ehlers Danlos Syndrome and Autonomic Dysfunction (Part One)

Ehlers Danlos Syndrome (EDS) is a heritable connective tissue disease with six major subtypes. EDS occurs in approximately 1/5000 births.  Classical EDS (cEDS) and hypermobility type EDS (HEDS or ht-EDS) are the most common forms, with approximately 90% of patients having one of these types.  Vascular EDS (vEDS) affects about 5% of EDS patients.  The remaining types are rare. Generally, EDS patients demonstrate hypermobility of joints, excessive stretchiness of the skin (hyperextensibility) and fragility of soft tissues.

Ehlers Danlos is diagnosed by clinical evaluation and diagnostic testing.  Mutations affecting structure of collagen, a key component of connective tissue, have been identified for cEDS and vEDS.  For hypermobility type EDS, no consistent genetic anomality has been found.  As a result, diagnosis of this subtype relies upon patient history and clinical examination.

The Beighton scale is a nine point scale for evaluating hypermobility.  One point is granted for each: elbow hyperextended more than 10°, knee hyperextended more than 10°, thumb that can be touched to the forearm, and fifth finger that can be passively bent back more than 90°.  One further point is granted for being able to place the palms flat on the floor with knees fully extended.  A score of 5 points or more is suggestive of joint hypermobility, a major criterion for diagnosis of HEDS.

In addition to an appropriate Beighton score, soft skin with normal or slight hyperextensibility and absence of significant soft tissue abnormalities are also important for HEDS diagnosis.  Excessive skin hyperextensibility and serious fragility of connective tissue could be indicative of other forms of EDS.

Hypermobility type EDS was regarded for many years as a benign laxity of the joints.  In recent years, this position has been debunked, though this belief still persists for many medical providers. Hypermobility and musculoskeletal pain were previously recognized as the dominant manifestations, but we now know that HEDS can cause cardiovascular, gastrointestinal, genitourinary and neurologic symptoms, among others.  In fact, the aspects of this disease that aren’t musculoskeletal are the most disabling and are correlated with lower quality of life

Symptoms arising from dysfunction of the autonomic nervous system have serious impact on quality of life as demonstrated in a number of conditions, including chronic fatigue syndrome and fibromyalgia.  Autonomic dysfunction can be assessed with an Autonomic Symptom Profile (ASP), a questionnaire of 169 questions that evaluates symptoms in eight broad categories: orthostatic (upright posture), secretomotor (secretion of substances by glands), urinary, GI, pupillomotor (movement of the pupil), vasomotor (changing diameter of blood vessels), reflex syncope (dysfunction of blood pressure and heart rate) and sleep function. These functions are all controlled by the autonomic nervous system.

References:

de Wandele I, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Seminars in Arthritis and Rheumatism 2014, 44: 93-100.

de Wandele I, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and healthy controls. Seminars in Arthritis and Rheumatism 2014, 44: 353-361.

Wallman D, et al. Ehlers-Danlos Syndrome and Postural Tachycardia Syndrome: A relationship study. Journal of Neurological Sciences 2014, 340: 99-102.

Privilege

My body is changing. I am tired but do not sleep for twenty hours at a time. Bones and angles emerge as my swelling wanes. I exercise. I eat real food. I sleep at night.

At the same time, I am carefully engineering to encourage these continued changes. I still take a ton of medication. I still need IV fluids every day. I still need IV meds. I still need to manage my pain. I still need to be careful. This nethervoid I currently inhabit might never be mistaken for healthy, but it is healthy for me. It is stable at least, predictable. It is good for me.

Last week was composed of the oppressive, sticky summer days that Boston is known for. Heat, humidity and sunlight form my own personal triad of doom. I got halfway through my short walk between stations and started reacting badly. I went into a Starbucks and promptly threw up while hives appeared on my neck. All of my exposed skin was bright red. I took some Benadryl and drank some cold water and waited for things to calm down. They did. I continued on my way to work.

It is hard for me to gauge how bad I look on any given day, as I was for many years in a persistent reactive state. My only indication is that initial surprise when people look at me, that flash of concern as their eyes widen, a brief moment before they recover. I knew as soon as I got to work that I must look terrible.

We have a cold room at work that is essentially an enormous refrigerator. “Girl, you need to go stand in there,” one of my coworkers said with a supportive nod. So I did. It helped. When I emerged, multiple people told me they were worried I would anaphylax and to please take a cab home. I am so fortunate to work with this group of caring, wonderful people that understand my disease and want me to be safe.

I did end up taking a cab home. I didn’t want to, but I did. It’s hard for me to articulate why I didn’t want to, when I knew it was safer and easier, in a way that doesn’t make me sound crazy. Getting in that cab made me sad in this nebulous but palpable way.

Taking the train to work is a privilege. Going to work, cleaning your house, paying your bills, food shopping, making dinner, eating solids, crunching lettuce as you watch television, being part of the world. These are privileges. These are the things you miss when you are hospitalized or so tired that your whole body feels heavy or riding that knife’s edge of anaphylaxis because your body is fighting you on something you need to do.

All of the days you spend fighting – this is what it is for. You fight for these privileges. You fight to be in the world. These are the things you will miss. All you can ever hope for is to wake each day to a world full of mundane privileges.

Some days I want to take the train even if there is a chance I will get sick. Because there is a chance that I won’t. Once that was impossible. Maybe it will be again. Maybe tomorrow it will be impossible, but not today.

I am still sick. I am still in pain. I still have a poorly functioning GI tract. I still carry two Epipens and a backpack full of meds everywhere I go. I am still nauseous. After all of the effort put forth in the last three months, I did not get cured. I got to walk to work sometimes. I got to eat salad. I got to feel the sunlight on my skin. That’s what I got. And it’s enough, and even more than it’s enough, it’s amazing. All of this is amazing. I am alive this summer and I am alive in the heat and I am alive when I’m too hot and I’m alive in the sun.

You cannot always decide what you do, but you can always decide who you are. I cannot always walk in the summer sun, but I am always a person who wants to.

I choose to live in the world and to enjoy it and be alive. I choose this even when it might hurt me. I choose this even when it might kill me. It is where I want to be.

It is a privilege to participate in this world. It is a privilege to be alive.