Thursday, April 19, 2018

Lyme and the mixing of world views

EPCDS and Lyme:  an evolving paradigm
I have been tossing the idea around in my head.  A Different spin, a new way of thinking, a new acronym. People like acronyms. Exhaustion, Pain, Cognitive Dysfunction Syndrome. These symptoms are the common threads, the bare bones of chronic illness known by different names, depending on your perspective.  I am writing this to introduce the topic, not discuss it in detail. 
What’s in a name?  A universe of thought. Some thinker, group of thinkers, doctors and scientists etc. have looked at a bunch of symptoms and arrived at a name. Many of the names and acronyms are familiar to us all. FMS for fibromyalgia syndrome. CFS for chronic fatigue syndrome. CLD for chronic Lyme disease or PTLDS post treatment Lyme disease. POTS for postural orthostatic tachycardia syndrome. Newer acronyms have popped up like MCAS for mast cell activation disorder. 
What these diagnoses and others (without acronym) have in common is that they swirl around EPCDS.  Exhaustion, pain and cognitive dysfunction or brain fog.  
They are all described in medical literature and associated with contemporary notions of evidence-based or science-based medicine.  In each case it looks like advocates of a particular approach think are onto a theory of everything (TOE). Like the unifying field theory that Einstein and others have failed to find in physics. 
Specialists all have blinders on. And – specialists tend to know a lot about their field of interest and read their journals but not the literature from other specialties which are reinventing the same wheel with a different twist. 
Exhaustion. Let’s start here. Fatigue isn’t adequate. In fact, I don’t know a word in the English language which is adequate.  Patients can’t get of bed. Moving a finger, lifting an arm can be a challenge.  Taking a shower an impossibility.  Nobody really understands this, the “pathophysiology.”
A rheumatologist sees fibromyalgia. They see it as a functional illness (whatever that means).  A CFS specialists, perhaps a neurologist sees SEID, systemic exertion intolerance syndrome, something likely post-viral. A sleep specialist may see idiopathic hypersomnia, a sleep disorder similar to narcolepsy. Idiopathic is a big doctor word that means unknown cause (or the doctor’s an idiot and the patient is pathological). A cardiologist, endocrinologist or other POTS specialists may see an impaired autonomic nervous system or dysautonomia.  Perhaps HPA dysfunction (adrenal fatigue) will be stressed. A pain specialist may hone in on central sensitization, alteration in pain-brain pathways as the cause. Those so inclined may always diagnose MCAS, mast cell activation. A Lyme specialist may be convinced that germs are the cause. Others doctors may focus on: genetic issues, poor DNA methylation; toxins; oxidative stress/mitochondrial dysfunction; disruption of the microbiome; autoimmune disease; systemic inflammation; nutritional issues including gluten sensitivity; chemical imbalances within the brain and others. 
Doctors are mostly hammers in search of nails, patients with EPCDS, for example. 
We could repeat the discussion for pain and cognitive dysfunction. The discussions would be very involved, but the same names would likely come up.  This is an introduction to the topic- a preview. 
So far, nothing new. Its not about new; it’s about thinking differently.
Sleep. Let’s back up a step. Disordered sleep is a common denominator. Patients have trouble falling asleep, can’t stay asleep, sleep is fragmented and sleep is unrefreshing.  Time and again I am astonished that such patients have seen scores of specialists and never had a sleep study.  Let’s turn our attention to the sleep specialists. Patients may have narcolepsy. Patients may have abnormal “sleep architecture.”  Most commonly there is a deficit of deep sleep.  Patients may have unexpected sleep apnea – perhaps central sleep apnea.  It is not enough to know Lyme and coinfections. A good Lyme doctor should understand a polysomnogram and MSLT.  Sleep is something we can address.  Therapies for fibromyalgia, dysautonomia, Lyme disease, coinfections and others may completely overlook this.  The notion that the sleep will improve when we fix the Lyme disease is --- well, wrong. Improve function and other things, like a dysregulated immune system or HPA axis may start to heal. Perhaps Lyme was the blow that knocked down the dominoes. While treating Lyme you also try to pick up as many dominoes as possible along the way. We might be able to address fatigue with drugs like Nuvigil or Adderall, at least a start. 
That’s it.
The idea is that a doctor should be a “holistic” Western practitioner at the least. Fuse things together. Read the literature: yes it takes a lot of time. Know a lot about the various specialties and how they think and try to make connections and draw things together.  We should not automatically cut out a specialty because they “don’t believe in Lyme.” That is their problem. Let’s not make it ours. They all have something to offer. Some more than others. 
There is another big plus. The approach gives us a bridge. A common language. When we talk about a dysregulated microbiome, hypersomnia, autonomic neuropathy etc. we are using words that make sense to many colleagues. When we talk to the same highly intelligent colleagues about: Borrelia burgdorferi sensu-stricto, pleomorphic round forms, biofilms, Babesia duncani, anaplasmosis, tickborne bartonellosis and rickettsiosis and Herxheimer reactions we are speaking Greek – gobbled gook.  But this is an aside.
The approach works and has helped many of my patients. 
As a stated. I am introducing the topic. A full discussion would take many pages, if not a book.
What do you think?

I am available for consultations in my Rockville Maryland office.
301 528 7111

Tuesday, April 10, 2018

Lyme, Babesia, MCAS, FMS, CFS, disordered sleep and PTSD.

A 39-year-old female sought my attention some years ago.  She has a history of PTSD.  She was sexually abused as a small child by numerous close family relatives.  She came to see me for the treatment of Lyme disease.
Many don’t understand PTSD.  It is a specific syndrome with characteristic features:  flashbacks and nightmares.  Time is different for those with PTSD.  Another patient, a former special ops soldier watched a buddy shot gruesomely a few feet away.  With flashbacks it happened 10 minutes ago, not 20 years ago. The flashbacks and nightmares are surreally vivid.  The colors, sounds, smells, adrenalin, fear, sweat and blood are real and now.  PTSD survivors do not trust.  They feel disconnected and depersonalized.  Forming bonds and establishing relationships is difficult at best.

The patient I am discussing ( her PTSD) improved a lot with 14 years of intense therapy.  She is still treated with EMDR and other therapies.

She has always lived in Frederick County Maryland, a Lyme hot spot.  She recalls a lot of tick bites over many years. She never had an EM (bull’s eye) rash and has no recollection of acute symptoms associated with a particular tick bite.  Her chief complaints included FATIGUE, COGNITIVE DYSFUNCTION/BRAIN FOG, POOR SLEEP, ANXIETY and PAIN.  Her pain was diffuse involving small, medium and large joints, upper and lower extremities.

She felt like she was always walking through fog.  She was distractible and confused.  Simple tasks were onerous.  She was in bed for 12-14 hours but slept only 5.  Sleep was not refreshing. She experienced regular night sweats and bouts of air hunger.  She experienced irritability and mood swings with episodes of random tearfulness. She experienced weird dizziness, difficult to explain – but she felt like her head was disconnected from the rest of her. She experienced numbness and tingling and bouts of weakness. She had a boatload of other symptoms, circling most symptoms on my symptom inventory form.
She previously worked as a special ed teacher but had been on leave for several years.  A previous doctor had diagnosed Lyme 3 years before and treated her with supplements, IV Myer’s cocktails and low doses of pulsed antibiotics:  such and such MWF, something else TuTh and something else one weekends with off weeks over the course of a month. This treatment went on for over a year.  She never got better and was referred to me.

Something key in her history proved very helpful.  She admitted to frequent episodes of flushing and itching. She had dermatographia: when you scratch her skin the color changes from white to red and stays red.  She also suffered with orthostatic intolerance.  When she stood up she felt like she had to sit down again after a few minutes.

Physical exam remarkable for paired tender spots associated with fibromyalgia, decreased sensation lower extremities peripheral neuropathy pattern and facial flushing and dermatographia (writing on her back legible 40 min later). Lyme Western Blot from Stony Brook:  IgM 18,41,64,93. A sleep study showed absent stage 3-4 sleep with alpha wave intrusion. A brain SPECT showed decreased perfusion diffusely.
The main diagnoses were:  Lyme, Babesia, MCAS, FMS, CFS, disordered sleep and PTSD.

One of the turning points of therapy was treating mast cell activation. Different drugs were best for different people. Yesterday a patient responded miraculously to Claritin. For this patient ketotifen has been key.  Klonopin, a benzodiazepine has been very effective.  Mast cells have benzodiazepine (BZD) receptors and BZDs and similar like Ambien may be very helpful.  As with other patients she has not responded well to typical antidepressants like Cymbalta. (SSRI/SNRI antidepressants are prescribed without thought and patients are usually not informed that getting off these drugs is frequently fraught with severe withdrawal symptoms).
We went to IV antibiotics for quickly and she responded very well to several months of Rocephin and others.   Babesia was treated with high doses of several agents and improved after many months.

MCAS treatment was as described in other posts. She also did well with cannabis. She obtained CBD which helped pain and anxiety tremendously.  (Cannabinoids are MCAS stabilizers). THC also helped with pain and sleep.  
Sleep is key for most patients.  Many need multiple agents. (Doxepin, Ambien, Neurontin, others).
She certainly has chronic fatigue syndrome.  Antibiotics quashed cognitive dysfunction and helped to significantly reduce pain.  She was able to get 9 hours of decent sleep.  She was still tired. The sleep study showed typical problems of disordered sleep “architecture.”  Without deep sleep, and this has been studied in college students, everyone develops chronic fatigue (syndrome).  A sleep specialist might use the term hypersomnolence or narcolepsy-like. It’s the same thing.  Drugs like Nuvigil and Adderall were/are indispensable for improving quality of life. 
She has the criteria for fibromyalgia. She has the tender spots. Pain doctors now call this central sensitization.  What you call it depends on your perspective bias.
CFS vs Fibromyalgia vs MCAS vs central sensitization vs hypersomnolence vs chronic Lyme disease etc. Perhaps it is important to listen to each camp since they may have something to offer.  The syndrome names are used above descriptively. FMS is used when discussing tender spots and pain and CFS is used when discussing fatigue. 

Luckily her pain level went from 9 to 3 with antibiotics and MCAS therapy.   Neuropathy also improved. 
Here are a few key points:  NSAIDS don’t usually work; antidepressants may help or make things worse – norepinephrine effect is needed, low doses of older TCA and antidepressants like Elavil may be effective without awful side effects; anticonvulsants, especially Neurontin may or may not work; cannabinoids, mostly CBD with some THC can be very effective.
PTSD is a very serious disorder and specialized care – not run of the mill mental health care is required. 
After more than a year with me:
She works full time -- sleeps OK, has no brain fog, fatigue is managed, MCAS is controlled and pain is managed.  She has a good quality of life and smiles a lot.

Wednesday, April 4, 2018

Deconstructing the Herxheimer (and Lyme toxins)

It is common knowledge that many patients feel much worse for a time when they start treating Lyme disease.  This temporary worsening of symptoms is known as Herxheimer reaction or simply Herx.  Commonly the reaction is attributed to “toxins” and it is commonly held that treatment which removes toxins – detox, alleviates symptoms. 

Critics of this reasoning say it is a lot of hogwash. What toxins? There are no toxins. Bacterial endotoxins occur with gram negative bacteria not spirochetes. And detoxing? Complete mumbo-jumbo. 

Let's take a look.
There is a lot of stuff we don’t know. A great thing about science is we are always learning new stuff. 
We know that Herxheimer reactions are modulated by cytokines – the traffic cops that direct a very busy immune system hither and thither.
Its true. Lyme spirochetes do not process traditional endotoxins. Classic bacterial endotoxins are comprised of lipopolysaccharides (LPS). I have read this critique many times.  Lyme bacteria have something else: membrane derived lipoproteins. These molecules are not endotoxins but may be equally problematic.  Killed spirochetes spill these molecules into the circulation. These molecules wildly overstimulate usual immune responses leading to unbridled production of inflammatory cytokines. This is called a cytokine storm. 
A Herxheimer reaction, a well described scientific phenomenon, is caused by a cytokine storm. Unregulated cytokines cause chaos within a usually well-ordered machine.  There is a yin-yang balance within immune responses to kill germs. Some inflammation is necessary but this must be balanced against greater forces that diminish inflammation.  In a cytokine storm inflammation is unchecked.  Effector mechanisms (ways the immune system kills germs), T cell responses, B cell responses and complement activation become poorly regulated.  Germs are being killed but tissues cannot tolerate the excess inflammation. 
Inflammation is in part modulated by such molecules as histamine, leukotrienes, prostaglandins, enzymes and others, in part due to excess mast cell activation. This is something that can be limited with medical management. Cellular debris accumulates in the face of destroyed tissues, blood vessels and immune cells. Oxidative stress and mitochondrial dysfunction lead to an accumulation of intracellular toxins. Tissue damage may be associated with a build up of lactic acid. Macro toxins in excess, those eliminated by kidneys and liver may tax the system.
Let’s get to “detoxing.”  Two things are commonly recommended:  Lemon water and Alka-Seltzer Gold.  A gazillion patients have told me it works.  The first question is: what do lemon juice and Alka-Seltzer Gold have in common?  Citric acid. Citric acid has established anti-inflammatory properties. A recent study reported citric acid decreased the production of inflammatory cytokines: tumor necrosis factor, interleukins and cyclooxygenase (promotes prostaglandins) in LPS stimulated macrophages. The next question is why only Alka-Seltzer Gold? The main difference is aspirin. Regular Alka-Seltzer contains  aspirin, sodium bicarbonate and citric acid. The “Gold” version substitutes aspirin with potassium bicarbonate.  What’s wrong with aspirin? Isn’t it an anti-inflammatory? The answer is not always. Aspirin has different properties from other NSAIDS.  Peer reviewed studies have shown that in the presence of bacterial antigens aspirin has proinflammatory effects.  Sodium bicarbonate is best known as baking soda. It is also an antacid. Studies show that athletes who consume sodium bicarb  prior to intense exercise have improved performance. Our cells function best in the buffered blood pH of 7.4, slightly alkaline.  As in the case of Herxheimer responses, the athlete's tissues run out of available oxygen and Lactic acid accumulates. The blood become slightly acidic and metabolic functions suffer. Baking soda partially restores pH (acid-base) balance. Cellular metabolic dysfunction improves. 
How about those Epsom salt baths?  I have read various explanations and none make sense. It’s supposed to be about the magnesium which has healing powers. Its been scientifically shown that magnesium from Epson salts can’t get through the dermal barrier – the skin and therefore into tissues.  That’s not it.  Maybe it’s just the bath?  Hot water. Heat. Heat dilates blood vessels. Heat is well known to have healing properties. That is how saunas work. The process facilitates egress of inflammatory wastes from injured tissues. So, it’s just the water. The magnesium is for show – or is it?  When you mix molecules, they interact.  Magnesium sulfate “Epsom salts” is a salt.  Salt crystals have a particular physical characteristic. They hold on to heat.  Epsom soaks have a higher average temperature and stay warmer for longer than tap water baths.   
There are other detox strategies many of which seem helpful.  There is always a mechanism, an explanation, even if we do not yet know it.

Glutathione is the master antioxidant and help mollify oxidative stress and cellular dysfunction.  The problem is that oral forms are ineffective. Patients with IVs do great with IV GTH.  Other available forms, sublingual sprays and nasal spray (may require prescription) can be helpful. 

In my experience, and largely unknown, mast cell approaches can be very helpful for managing Herx responses -- in some patients. 

Monday, April 2, 2018

Is Lyme sexually transmitted?

The CDC says absolutely not. Research shows it does not occur in animal models. It turns out humans, at least most of us, aren’t rodents. Admittedly I have not studied rat copulation but on its face the anatomy and physiology are different.  The amount of body fluid exchanged, the presence of a large mucous membrane, methods and time are different for starters. Observations have been made that Lyme spirochetes have been recovered from human female genital secretion and to a lesser extent male. This is not a surprise since male seminal fluid contains natural antibiotic substances.  The paper in 2014 states the same strains of Lyme were found in both sexual partners. The findings are interesting but not proof. Alternate explanations are feasible: husband and wife did the same activities and were exposed to the same ticks. Retrospective data may be unreliable. We don't know if spirochetes in genital secretions are alive, dead or viable. When passed from a tick spirochetes are wrapped in a protective protein and secreted below the outer epidermis; we don't know if such steps are necessary for transmission. On the other hand, it is clear that vertical transmission occurs: a pregnant mother can clearly transmit Lyme to her unborn child. 
The CDC claims that epidemiology does not support the notion of sexual transmission. I don’t think we have data to support that claim.  Most Lyme infected individuals are asymptomatic and most symptomatic Lyme patients are misdiagnosed. Lyme is slippery and not easy to track like STDs with known calling cards – like gonorrhea. We really don’t know how many Americans are infected with Lyme. There are other STDs that have been missed because of their subtly, like HPV. It took decades for doctors to realize that the majority of the sexually active population is infected since the only manifestation in most cases is cervical cancer. The epidemiology argument does not hold water for now. 
We are left with considerations of biological plausibility. The argument is made that Lyme is like syphilis.  Lyme is a vector borne zoonosis. It resides in host animals and is occasionally passed to humans by specific ticks; the humans become accidental hosts.  It is different from syphilis which is solely sexually transmitted. The two come from different family trees: one is from the genus Borrelia and the other Treponema. Biologically they are different. The two pathogens evolved along very different lines.  After all, syphilis is not transmitted by ticks but humans are the only host of syphilis; this argument is weak. We have to consider other biological specificity. Malaria is transmitted by only one species of mosquito and plague by a specific rate flea. Well – this applies to vector specificity. We know there is Lyme vector specificity. This doesn’t prove anything. The question is: Is it biologically plausible for a vector borne organism to be spread by some other means, such as physical or sexual contact? The answer is maybe. Pathogens adapt. For example, the bubonic plague transmitted only by rat fleas evolved. It became the pneumonic plague transmitted by a cough. 
There are Lyme cases that are difficult to explain without conjuring the hypothesis of sexual transmission. In my practice these seem rare. Two recent patients tested positive for Lyme, one male and one female. One is a city apartment dweller who never goes outside. Her husband is an outdoorsman. The other lives in Colorado, a Lyme free zone and never ventures into the great outdoors. He became ill after an encounter with a female partner who resides in the East Coast. Interestingly, the female was suffering with a flulike illness at the time of the encounter. It is tempting to latch on to data from the 2014 study. I am not there yet. 
I tell my patients not to panic. Sexual transmission if it does occur may be rare. I think.  We don’t really know: is Lyme like hepatitis B – sexually transmitted or hepatitis C – rarely sexually transmitted? 
I think it is irresponsible to categorically stake out a position on this issue. The first order of business is an intelligent proportional, science-based discussion. Perhaps this doesn’t help patients who want a clear yes or no. Perhaps other interested parties who will happily meet that need.  Not me. 
Patients ask: are you a Lyme literate doctor. I answer: that is not important. The question is, are you a Lyme literate patient?  It seems very few things Lyme are black or white. If you don't like dealing with murky shades of gray you picked the wrong disease. 
It is important for us to acknowledge that which we know and that which we do not.

Friday, March 23, 2018

CFS, FM, Lyme and others

According to experts, chronic Lyme isn’t real. This is a Lyme Blog, but let’s look at the other side. Fibromyalgia, chronic fatigue syndrome and depression are the real problems I am told.  Is this correct?

Chronic fatigue syndrome has changed.  The CDC guidelines are out.  The IOM guidelines are in.  Terms like chronic fatigue and immune dysfunction syndrome and myalgia encephalitis are out. Systemic exercise intolerance disease (SEID) is in.  The definition narrowly (by design) focuses on a few key symptoms. The emphasis is on: POST EXERTIONAL MALAISE, DISORDERED SLEEP, COGNITIVE IMPAIRMENT AND ORTHOSTATIC SYMPTOMS.
A lot of SEID patients have abnormal tilt table results and are misclassified and should be reclassified as POTS.  This is important because we know how to treat POTS.

CFS and FM are claimed to be subjective. Not true. There may be many objective findings. Abnormal immune system findings with altered levels of immunoglobulins and natural killer T cells. Increased cytokine levels. Endocrine changes with alterations of ACTH and insulin like growth factor.  Alterations in serotonergic activity in the CNS.  Abnormal sleep studies. Abnormal SPECT scans.  Cervical lymph node biopsy showing reactive hyperplasia.  Others. These facts are reported in current mainstream medical literature discussed in UpToDate. The term “functional” illness has been bandied about disparagingly. The idea is that there is nothing physically wrong and therefore it is a “psychosomatic” disorder – there is nothing wrong. The term functional illness, still used after so many decades serves only to disparage and impugn suffering patients, encouraging the mean attitudes held by so many physicians and should have no place in medical literature.  Many patients have a history of tick bites, tick exposure and positive blood tests for Lyme and/or other tickborne pathogens.  No mention is made in mainstream medicine.
We are informed that 70% of fibromyalgia patients and 70% of CFS patients overlap one another. The diagnosis depends on the bias of the doctor making the diagnosis. 
Fibromyalgia criteria have evolved.  The most recent guidelines were described in 2010-11.  Widespread pain is the overarching feature.  It is widely believed that FM is a disorder of pain regulation within the brain.  Patients are reported, according to standard criteria to suffer with: fatigue, impaired cognition, psychological symptoms, headaches, numbness and tingling and “others.”  Palpitations, GU symptoms, IBS, night sweats and others.  It may be associated with other “functional somatic disorders” including CFS, IBS, migraine, TMJ, chronic bladder pain and pelvic pain syndromes.  Sounds suspiciously like Lyme disease. The affixture of "other functional illnesses" is egregious.  Some experts can't resist telling us the syndromes are more common in young-middle aged women.  The undercurrent of sexist stereotyping is tenacious. 
Other syndromes with similar features include:  Mast cell activation syndromes, POTS, hypermobile joint syndromes and Lyme disease. 
In my experience (goes without saying), many patients suffer with Lyme disease and/or other chronic infections. Culprits include: Babesia sp, Bartonella sp, Chlamydia pneumonia, Candida and others.  Treatment of Lyme and coinfections is discussed elsewhere. 
What is standard therapy?  Cymbalta, Lyrica or Neurontin and a prescription for exercise.  Maybe it works for some, if so I only see the patients who fail this approach miserably. 
Disordered sleep is a common denominator.  Patients have abnormal sleep studies. They have various sleep disorders and hypersomnolence, akin to narcolepsy. This issue is described in completely different ways in sleep medicine language vs CFS language. 
Patients - everyone require good sleep.  Many need agents like Ambien, Trazodone, doxepin, hydroxyzine, Klonopin and others.  Sleep makes a huge difference.
Fatigue can frequently be effectively treated with drugs like Nuvigil.

Mood issues can be addressed.  Mood stabilizers with neuroprotective properties like Lamictal may be preferred over typical antidepressants. We keep hearing that depression hurts. Really?

Cognitive impairment and dysfunction may be treated with Namenda and others. Namenda also may help migraine. 
Pain. Patients need help. Unfortunately, pain doctors, under the eye of the Medical Board, are shuttering their practices.  Medical cannabis may be helpful.  Some patients are on massive doses of Oxycontin and its not working well.  Patients have high tolerance. Opioid receptors have long been saturated. The risk – reward ratio increases dramatically as does are pushed higher with minimal additional pain relief.  Raising the dose at some point becomes like squeezing water from a stone. Savvy pain doctors (I do not prescribe opioids) are trying their patients on smarter opioids like Belbuca.  
IV ketamine or compounded nasal sprays may help.
Botox may help.  HBOT may help.  
There are a lot of things that can be tried. 
Mainstream medicine has no empathy for pain.  Cymbalta and Lyrica may have many side effects and do not work for serious pain. 
Patients may feel suicidal because of pain.  There is no time to wait for antibiotics to work.  Patients need relief.  The consequences of not controlling pain can be deadly.  
Lyme patients have:  CFS, FM, MCAS, POTS, hypermobile joint spectrum illness, chronic pain disorders with hyperalgesia, Migraines, CRPS and others.  Patients with EDS/hypermobile joint syndromes with abdominal pain likely have MALS. These illnesses require proper diagnosis. All of these illnesses have specific treatments.

Disease is determined by a complex interplay of genes and environment (including germs).  Some of these illnesses more commonly afflict women than men.  This should cause empathy not derision. Men have higher rates of cancer and heart disease: what a bunch of lightweights.

These factors do not change the fact that chronic Lyme patients more often than not require long-term antibiotics. This is discussed elsewhere. 

The treatment of Lyme, MCAS and POTS is discussed elsewhere.

Tuesday, March 6, 2018


I am asked how I treat tachycardia since I recommend the avoidance of beta blockers. The goal of treatment is to correct aberrant physiology to the extent it is possible.  Tachycardia is a compensatory response which is maladaptive.  In general, initial therapy should target circulating volume (fludrocortisone/Florinef) and try to increase constriction of the blood vessels to improve perfusion - blood flow to brain and vital organs.

Midodrine is the most commonly used drug. Another option is Northera, FDA approved for central dysautonomia. It is an analog of norepinephrine and should promote constriction of blood vessels.  The two drugs work by different mechanisms. If we apply these solutions tachycardia may abate. Sometimes we need a beta blocker. Beta blocker are generally not the first drug prescribed for POTS.  Instead of beta blockers a novel drug approved for CHF, Corlanor is said to decrease heart rate without lowering blood pressure. This may be a good idea if low blood pressure is a concern.

Patients with cardiac symptoms should be evaluated by a cardiologist. Not necessarily to diagnose POTS but to exclude other organic issues:  electrical conduction issues, dysrhythmia, valvular heart disease and others. A tilt table test is not a bad thing. It may be uncomfortable and simply not needed in many cases.

Lyme can cause carditis, heart block and other cardiac complications.

These comments are for general information purposes only. If you have symptoms of concern please visit your personal physician for an evaluation. 

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.