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Friday, February 9, 2018

POTS: nuts and bolts

Postural orthostatic hypotension syndrome is one of the most common medical issues encountered in my medical practice. I would like to review the basics to help cut through some of confusion that surrounds the syndrome.  I sometimes refer to POTS as a “disorder” rather than disease; I make this distinction because POTS is triggered by something and I want to find out what it is.  Patients are told that POTS is a chronic “disease” which may or may not get better over a period of years. Those who suffer know that POTS can be devastating and disabling.  POTS results from an imbalance of the nervous system.  The autonomic nervous system which I think of as “automatic nervous system” unexpectedly breaks down.  The autonomic nervous system regulates numerous functions we take for granted on any given day. When the system stops working properly the consequences can be horrible. A lot of POTS patients go from one doctor to the next never receiving the correct diagnosis. The chief complaint may not give the diagnosis away.  POTS is a mainstream disease but one of which doctors are ill informed. Most physicians fail to recognize the common symptoms of POTS.  Many mistakenly think it is a rare condition when it is in fact quite common. 
Patients are misdiagnosed because the symptoms sound like so many other things; the symptoms are considered “vague” or “no disease causes all of those symptoms”.  POTS patients may experience fatigue, exhaustion, inability to get out of bed, inability to tend to usual activities of daily living, brain fog, weakness, pain, trouble standing, trouble exercising, problems with sweating, bowel/bladder dysfunction, racing heart, palpitations, headaches and many others. Symptoms range from very mild to very severe.   Symptoms mimic those of other multisystem disorders, including Lyme, MCAS, fibromyalgia and CFS. Sometimes these syndromes coexist. POTS should be easy to diagnose: unlike other multisystem disorders, POTS has a clear calling card. If a patient tells a doctor:  when I stand up my heart rate goes crazy high and I feel dizzy, like I might pass out, and it only gets when I lie down, the doctor should have an Ah Ha moment. But not necessarily. At this late date, many primary care physicians, cardiologists and other specialist are unfamiliar with the syndrome. Doctors are more familiar with Potts – TB of the spine, something they will never see in clinical practice. 
Vital signs change when the patient changes position (orthostatic). Doctors may be focused on blood pressure, wrong metric. With POTS the blood pressure doesn’t change; it is the pulse or heart rate that changes. 
The diagnosis may be made in the office. The heart rate is measured supine, sitting and standing at intervals over several, up to 10 minutes. 
When a normal person goes from lying to standing the heart rate may go up 15 beats per minute or so but it rapidly returns to baseline and is within normal limits (60 – 100).
With POTS the heart rate climbs 30 points or more and stays there. The elevated heart rate, tachycardia may increase over time rather than normalizing. Other conditions that cause a rapid pulse, like atrial fibrillation need to be ruled out with an EGK.  The POTS patient may feel weak and have trouble standing beyond 2-10 minutes. If this occurs the patient must immediately sit down/lie down. For adults the positive POTS diagnosis cut off is defined as difference of 30 beats per minute or more or a sustained heart rate of greater than 120.  With kids there is more variability. Standards exist because – we need standards. A lot of POTS patients don’t meet the criteria.  A negative test does not exclude the diagnosis. Sometimes, where there is doubt, other tests, like a formal tilt table test may be ordered. Alternatively, the patient and/or family can track vital signs at home.  
So, what gives?
When we go from lying down to standing there is a rapid shift of fluids in our bodies. About 1/3 of circulating blood/fluids follows gravity and pools downward. This is a dramatic change in our physiology. Normally our bodies respond quickly: blood vessels, mostly the medium sized arterioles constrict and narrow - like pinching a garden hose and pressure is restored and blood flows to essential organs, especially the brain.  Without the blood, oxygen and glucose required by the brain we lose consciousness or experience syncope.  The appropriate physiological response described in controlled by the autonomic nervous system. 
The autonomic nerve fibers “fire”, cause the blood vessels to constrict – or to dilate, as appropriate. When the autonomic system fails to send the proper message the arterioles do not constrict and narrow, the blood vessels remain in the wide-open position; adequate perfusion (blood flow) to the brain and other organs does not occur.  The body tries to compensate by speeding the heart rate in an effort to increase blood flow to the target organs. The heart rate goes up but the organs are still without adequate blood flow (hypoperfused).  Given Einstein’s definition of insanity: doing the same thing over and over and expecting a different result, our bodies are insane. The pointless increase in heart rate occurs each time. 
The autonomic system is comprised of two parts. The sympathetic and the parasympathetic nervous systems. Dysfunction of the system is called dysautonomia with POTS the most obvious manifestation.  The nervous system is dived into 2 parts: the central nervous system (brain and spinal cord) and the peripheral nervous system (nerves that branch off from the spinal cord). The autonomic nervous system is part of the peripheral nervous system. The autonomic nervous system is partially controlled by the brain (central nervous system).   
Nerve transmission, communication of one nerve cell with another, involves chemicals (molecules) called neurotransmitters. For the sympathetic nervous system, the chemical is adrenalin (norepinephrine). The sympathetic nervous system is famously associated with the “fight or flight” response -- increased heart rate and blood pressure, pupillary dilatation, increased sweating, hyper-alertness and others.  The parasympathetic nervous system uses the neurotransmitter acetylcholine and is associated with a relaxed state – eating and digesting a meal, resting, bowel, bladder and sexual functions and others. Both systems must function for homeostasis, balance throughout the body to occur at any point in time. 
How do we treat POTS?
Patients may improve tremendously with treatment, but there is no specific treatment or cure.  Goals of therapy are:  correct abnormal physiology, treat symptoms and improve function and quality of life. (Treat underlying cause(s) if possible). 
The first step in therapy usually is to increase the volume of fluids in the body, specifically circulating volume of fluids. The principal is straightforward. More fluid equates with more pressure. The higher pressure drives more blood to brain and vital organs despite abnormal neuro-vascular dysfunction (autonomic dysfunction).
Patients are encouraged to increase fluid and sodium intake. Sports drinks and salt tablets may help. The drug fludrocortisone, Florinef may be prescribed.  The drug acts like the kidney hormone aldosterone causing our kidneys retain more salt and water. When available, IV normal saline solution dripped in overnight can be very useful.   

When fludrocortisone fails, another drugs that causes water retention may be helpful.  Desmopressin or DDAP.  It is an analogue of anti-diuretic hormone, secreted by the pituitary gland.  A diuretic causes urination and water loss.  Anti-diuretic hormone does the opposite: it causes the retention of water. The drug is used for other diseases and may be re-purposed for POTS. 
Lower body strengthening, with exercises like bicycling or rowing may help.  Increased muscle tone helps push fluid in the lower parts of the bodies upwards towards the heart. 
The arterioles responsible for vascular pressure can be directed stimulated to contract and narrow with the drug midodrine. Midodrine is perhaps the most commonly use pharmacotherapy for POTS.  Improved perfusion to the brain and other organs may occur with postural change despite dysautonomia (dysfunction of autonomic nervous system).   The drug can elevate blood pressure and needs monitoring. 
Beta blockers which lower heart rate are sometimes prescribed. These drugs can make things worse. Tachycardia is a compensatory response. I typically consider adding a beta blocker only when other pharmacotherapies are in place. 
Mestinon, pyridostigmine, prevents the degradation of the neurotransmitter acetylcholine and may help parasympathetic dysfunction. The drug may be more helpful in certain specific clinical scenarios. 
Clonidine, a blood pressure drug has central effects on the brains output of adrenalin and may be helpful in some cases. 
Antidepressant drugs, which variably effect the neurotransmitters serotonin, norepinephrine, dopamine may be beneficial.  
Stimulant drugs like Adderall with dopaminergic effects in the brain may help some patients. 
Many other agents may help in some cases. 
Who gets POTS?
POTS can occur with either sex and at any age, but more often than not, its victims are teenage girls and/or young women in their 20s. Older adults with chronic illness -- diabetes, Parkinson’s disease and others may get POTS-dysautonomia. The widely held theory is that most cases of POTS are triggered by a viral infection.  Most cases are said to be “idiopathic” – cause unknown, also translated: the patient is pathological and the doctor is an idiot. POTS can accompany other syndromes or constellation of syndromes, for example MCAS and EDS or hypermobile joint syndrome. 
In my practice, many POTS patients also suffer with Lyme disease and tickborne disease, the presumptive trigger for the illness. 
POTS is a multisystem disease with widely variable clinical manifestations. Misdiagnoses are common. Incorrect diagnoses may include: exercise intolerance syndrome, fibromyalgia, chronic fatigue syndrome, depression, psychosomatic disorders and others.  Diagnosis is generally not difficult. Or the diagnosis is impossible if the evaluating clinician has not heard of the disease.  Specialized tests including tilt table and QSART are rarely needed.  
Non-specific management of symptoms is important.  This includes: sleep, pain, brain fog, depression, lack of conditioning and others.
A good support network is key. 
The long-term prognosis is good.  Treating the underlying disease is essential.

Monday, February 5, 2018

MCAS, mast cell activtion syndrome, nuts and bolts

Mast cell activation syndrome – MCAS – a stand-alone theory of everything.  The disorder is not accepted by mainstream medicine.  Hematologist deal with a set of serious disorders which may involve tumors but that’s is not what we are going to discuss--not to say mast cell activation syndrome is not a serious disorder. It can be deadly serious.  MCAS is a novel way of looking at disease and is used to explain many diseases, symptoms and syndromes. 
What is a mast cell? Mast cells are important actors within the immune system. Stained, under the microscope, they are plump purple cells. They are like other cells found in the blood (eosinophils, basophils) But these cells are located in tissues, various organs, outside the blood stream and around blood vessels. Mast cells have a role in allergies and killing certain parasitic worms. Not the topic of the day. We are interested in inappropriate action of the cells.  
The granules inside the cells contain various substances which cause inflammation. These granules contain things like:  enzymes, histamine, leukotrienes and prostaglandins. 
Activation:  These caustic immune cells release many inflammatory substances causing severe swelling, immune responses and local tissue injury.  Instead of killing parasitic worms or attacking an allergen mast cells are attacking us and damaging our tissues. Mast cells are omnipresent and symptoms vary depending on which tissues are attacked.   For example, if mast cells activate in the intestinal tract symptoms may include bloating, diarrhea, GERD and other dysfunction. Mast cell activation in muscles and joints causes joint pain and swelling. Mast cells activating in the brain may cause brain fog, headaches and neuropsychiatric symptoms.  Diffuse mast cell activation can cause a “multisystem” presentation: fatigue, brain fog, joint pain, muscle pain, bowel and bladder dysfunction, neurological dysfunction, change in mood, confusion and many others. 
Patients may experience one mysterious problem after the next.  Symptoms may come and go over many years. Doctors scratch their heads or diagnose a psychosomatic disorder. Doctors will not think: MCAS.  MCAS is a new paradigm on the edge of medical practice and medical science. Doctors don’t know about it – except for the few. 
MCAS can explain a lot. 
Mast cells don’t typically act on their own. They are triggered by something. Triggers vary widely from one person to the next. 
Certain clinical scenarios make us think MCAS. Patients with hypermobility joint syndrome and POTS invariably also have MCAS. Lyme spirochetes may be a trigger as well as other infections. 
We look for clues: Recurring hives, unexplained itching, dermatographia and facial flushing. Patients may report sensitivity to scents and smells and to variation in temperature – hot or cold. A patient I saw today is sensitive to certain fabrics.  Chemicals may be a trigger. Foods and medicines are common triggers. It may be the inert ingredients in pills that triggers the response and some patients have all their meds compounded.  All of the above may be absent. 
Herxheimer reactions may have a MCAS component and may respond to appropriate therapy. 
Are there lab tests? Iffy. Labs tend to positive only in severe forms of the disease, not the syndromes we are discussing.  Occasionally serum tryptase or histamine may be elevated.  24-hour urine tests are sometimes abnormal. The diagnosis is usually clinical. 
MCAS is treatable -- frequently with remarkable results and commonly used meds are extremely safe. 
Diet may help.  Certain foods are known to be high in histamine or trigger histamine release. Reducing intake of certain foods can help.  Well-known examples include tomatoes, strawberries, avocado, nuts and deli meats. You may only have to cut down on certain foods, not eliminate them completely. Food reactions vary a lot amongst individuals. 
MCAS is not an allergic reaction. For example, an allergy to peanuts is something different, mediated by different pathways in the immune system. Still – there is some overlap. 
Meds. In most cases patients respond to simple, safe meds. But may have to take a lot of them.  The treatment has 2 parts:  Blocking the effects of inflammatory substances released from mast cells and stabilizing mast cells so they don’t activate in the first place.  There are 2 kinds of histamine receptors called H1 and H2.  H1 blockers are the familiar antihistamines. MCAS requires higher doses, and multiple antihistamines. The H2 blocker are thought of as ulcer/heartburn drugs, they block the production of stomach acid. The H2 receptors have other functions and blocking the receptors helps. Blocking leukotrienes (Singulair) is helpful.  Prostaglandin blockers, anti-inflammatories like aspirin may help. Stabilization is more problematic.  Cromolyn would be great but has poor bioavailabity but may still be effective. Ketotifen is mast cell stabilizer with antihistaminic properties.  It is available through compounding pharmacies. Effective mast cell stabilizers may include benzodiazepines and cannabinoids. More difficult cases may be treated with the asthma/hives injectable Xolair and an array of immunosuppressive drugs.