Lyme aortitis and aneurysm

Patient with chronic Lyme disease typically present to me with a broad collections of symptoms. For simplification, I like to group Lyme symptoms into 5 general categories: 1) constitution – symptoms like fatigue, low grade fevers and night sweats; 2) musculoskeletal – symptoms like joint pain, swelling etc. 4) neurological symptoms including weakness, numbness, tingling etc.; 4) psychiatric symptoms such as anxiety and depression and 5)  other – “everything and anything else.”

Complaints from the 4 “core” categories seen with the vast majority of chronic Lyme patients. In fact, when such complaints are lacking I look extra hard for a non-Lyme explanation of the problem(s).

Then there is everything else.

A longstanding patient was seen in my office today. He suffers primarily with a profound motor/sensory neuropathy. (His insurance has refused to cover IVIG). He has had cognitive issues and joint issues which have largely resolved. He denies any cardiac symptoms. A recent abdominal ultrasound, performed to rule out gallbladder disease, serendipitously discovered a small thoracic aortic aneurysm. There were no typical risk factors for this. No hypertension, atherosclerosis, family history, Marfan’s syndrome or Ehler’s Danlos syndrome.

He went to a cardiologist who performed an echocardiogram and a significant, aortic root aneurysm, 4 cm was found. The patient asked me if this might be due to Lyme disease. After all, Lyme is like syphilis and syphilis is famously known to cause “luetic aneurysms” of the ascending aorta. I thought not.  I do not think Lyme and syphilis have all that much in common. They come from differing phylogenetic heritage. In general, Lyme is much worse.

Lyme patients tend to have a lot of cardiac symptoms like palpitations and irregular beats including PVCs. They frequently have POTS, but this is a neurological disease, not a primary cardiac one. Lyme patients famously have Lyme carditis causing heart block, an electrical rhythm disturbance frequently requiring a pace maker. Lyme can also directly affect the heart muscle (very rarely) causing a dilated cardiomyopathy and congestive heart failure. Lyme can cause inflammation of the pericardium, the sack around the heart and cause pericarditis. One of my patients who had already been intensively treated for Lyme disease) developed constriction around the heart from pericarditis, called tamponade, requiring emergency surgery to relieve the pressure.

I did not think that Lyme, like syphilis, caused aortic root aneurysms: I was wrong.

In “Pathology, 2014” 300 cases, sections of ascending aortic aneurysms were reviewed. There were 21 cases of aortitis or inflammation of the aorta with 19 aneurysms. Associated causes included: temporal arteritis, ankylosing spondylitis and undifferentiated autoimmune disease; IgA nephropathy, fibromyalgia and Lyme. Fibromyalgia is of course suspect for undiagnosed Lyme.

My patient’s proximal aortic aneurysm is 4 cm and may expand over time – with surgery recommended at 6 cm.

Do I think Lyme patients should be screened for heart disease? An EKG is a good idea since it screens for heart block and occasionally detects other conditions. I do not think screening echocardiograms are warranted. But what doctors call “the index of suspicion” should be low for ordering the test

Lyme, POTS, Mast cell activation syndrome: a constellation.

This 23 year old female is like many other, very sick and hard to fix patients. She was in extremely good health until age 17. She was an excellent student and a serious athlete: a happy, well-adjusted young adult on her way to college and other great things. Then the train derailed and broke into pieces. She developed a complex, multisystem disabling disease and had already seen a lot of specialists before coming to see me. When I met her she had been disabled for more than 5 years. Some of her primary complaints included: pain, fatigue and cognitive dysfunction, but there was much more. She had incapacitating, mysterious abdominal pain. She had new onset intractable daily headaches. She had severe, 9/10, diffuse joint pains. She spent most of her time in bed. Sleep was not restful or restorative. She had crushing post exertional exacerbations of all her symptoms. Conversation became difficult. Her focus and working memory were so poor that she was unable to watch TV – let alone read.

Born and raised in Northern Virginia, in a family with highly educated and successful parents, she grew up uninformed about the dangers of tickborne disease. She always had an active outdoor lifestyle. She was active in the Girl Scouts, hiking and riding her bike along trails. On a single day, age 12, after a bike ride she recalls 7 tick bites. She had numerous tick bites on a regular basis for years, seemingly without consequences. Like so many others she was told only to worry if there was a bull’s eye rash and this never appeared.

It is then not surprising that she suffered with chronic Lyme disease and the various attendant coinfections.

A lot bad things happened to her normal physiology. Sometimes it seems that good health is more precarious than we think. A final, unseen straw can break the camel’s back and the dominoes begin to topple.

She suffers with a constellation of Lyme, POTS and mast cell activation disorder. Clinically she suffers with a chronic pain syndrome, chronic fatigue syndrome and intractable-daily migraine syndrome.

I use the term Lyme in a generic sense, encompassing coinfections, typically Babesia and Bartonella.

The POTS was clearly proved with a tilt table test. This explained why she topples over when she tries to get out of bed. It also helped explained her gastrointestinal symptoms, in part, associated with dysfunction of the autonomic nervous system. The POTS piece has been the easiest to address, responding to: salt, Florinef, midodrine and other agents, discussed elsewhere.

Lyme has only responded to heavy bombardment from long term intravenous antibiotics.

Babesia, with increasing resistance had been very difficult to treat. Numerous agents are frequently needed, generally in combination. Malarone + Coartem + Cryptolepis (infuserve) + low dose quinine and even Artesunate (from Canada) in selected patients. This continues to be an issue for this patient.

Bartonella can be tough too. In my experience the best drug by far is Rifampin (always be aware of drug interactions). In most of my Lyme patients I go to a three drug cocktail early on which includes Rifampin.

An overarching, key part of her treatment has been hyperbaric oxygen therapy. A new patient today informed me she was told it never works. I have never seen HBOT fail to help, at least to some extent. The myth that HBOT cannot be used in the presence of Babesia is just that – a myth. If this were the case it would never be used since the majority of patients suffer with the effects of this insidious parasite.

Hyperbaric therapy (HBOT) must be used correctly – which is: low pressure over a very long period of time. Low pressure means pressure less than 2X atmospheric pressure. I use a soft chamber made by Newtowne; with aftermarket valves I am able to treat with a pressure of 1.6 atmospheric pressure (ATA). Otherwise standard FDA approved, home use devices allow only a pressure of 1.3 ATA. The effective therapy for this patient has been 1-2 hours in the chamber daily.

The mast cell piece has added a lot to her recovery. A number of specific agents, discussed elsewhere, and a low histamine diet have been very helpful.

It is important to pay close attention to gut and microbiome. Large doses of probiotics administered several times a day will help. 

Oxidative stress plays into the overall illness in a big way. An advantage of the PICC used for IV antibiotics is that glutathione, the best antioxidant, can be administered intravenously as well and IV is the only effective route of administration.

Mitochondrial dysfunction is a problem. The only treatment I know of is the use of supplements. PPQ may be the most effective of the group.

HBOT helps with so many things: inflammation, immune dysregulation, oxidative stress and improved metabolic function.

More benefits include:  production of natural antimicrobials, biofilm dispersal, improved neuroplasticity and safety. It only works if you keep using it religiously.

The therapy I would love to add is IVIG. To convince a third part to pay we have to prove specific immune and/or specific neurological dysfunction. It works beautifully when available.

I have been treating this patient for 15 months. Where is she now?

Incapacitating abdominal pain is gone; she has headache free days for the first time in 5 years; she is able to think much more clearly, the fog is lifting, she is able to converse, watch TV and read; she is able to get out of bed and walk a few steps, now more – she recently walked an entire block to a friend’s house. Joint pain is still problematic: this can be a very vexing symptom to break.

Post exertional malaise is slowly lifting. She is inching her way towards recovery. She is greatly helped by a positive attitude and a very loving and supportive family.

It started with Lyme: then the dominoes fell. From this patient’s history it is clear that education about the dangers of tick borne disease is criminally unavailable to the general public.  The pattern of disease I see in this patient is one I am seeing frequently: Lyme, POTS, MCAS (mast cell activation syndrome). In many cases I am also seeing hypermobile joints and possible forms of Ehler’s Danlos syndrome. Gut dysfunction likely plays a much bigger role than I have appreciated.

Lyme and the microbiome

The effect of long-term antibiotics used for Lyme disease is an 800 pound gorilla in the living room that my blogs have left unaddressed. The microbiome is a virtual organ comprised of thousands of species of microbes, primarily bacteria with a few yeast, archaea and protozoans thrown into the mix. The microbiome interacts closely with the mucosa of the gut creating a virtual organ system. The gut-microbiome influences endocrine functions, include the HPA axis (hypothalamic pituitary) dysfunction of which leads to adrenal fatigue amongst many other issues. It is now known that the gut-microbiome plays a major role in regulating innate and acquired immune responses. The microbiome plays a key role in regulation of the autonomic nervous system. Elaborate microbiome connection to the overall immune system and the neuro-immune system are of critical importance. We know there is a gut-brain connection which plays a critical role in overall health. The human microbiome is an area of intensive, multidisciplinary research. Alterations in gut function have been closely connected with mood disorders including depression – and anxiety.  The news regarding antibiotics is not all bad. For example, minocycline has some antidepressant effects. One hypothesis relates to inhibition of glial cell activation and neuroprotection. An alternate hypothesis is that changes in the microbiome may be the predominant mode of action. It has been suggested that alterations in gut flora contribute to cognitive dysfunction. An altered microbiome may relate to small intestinal overgrowth syndrome, various forms of dysbiosis and leaky gut syndrome. The antibiotic rifaximin has been used to favorably alter the composition of the microbiome and has been demonstrated to have clinical efficacy. Doxycycline has long been known to be associated with a low risk of C. diff compared to other antibiotics. A study in a major hospital showed that the addition of doxycycline to Rocephin for the treatment of pneumonia significantly decrease rates of C. diff. The choice of antibiotics and the method of administration will lead to variable effects on the microbiome. Antibiotic use has been associated with increased expression of resistance genes amongst the gut flora. Interestingly, these genes have been around for thousands of years, long before the antibiotic era. Many gut bacteria produce natural antibiotic-like substances. We are told to worry that overuse of antibiotics leads to the creation of superbugs. This can only happen when pathogenic bacteria are exposed to antibiotics. The antibiotics we take primarily impact the good guy:  the creation of superbugs is not as common as one is led to believe. Dysfunction of the gut flora is associated with pro--inflammatory cytokines, a driving force in many disease states. In addition, the dysregulated microbiome leads to release of gram negative derived LPS, lipopolysaccharides, into the systemic blood stream, the likely source of toxins that many associate with Lyme disease. Lyme spirochetes lack these toxins altogether. Lyme leads to overall immune dysregulation which may indirectly drive the release of gut cytokines and toxins. I have long wondered why patients may relapse only days after antibiotics have been discontinued; perhaps the explanation is tied to gut cytokines and endotoxins rather than Lyme (in the short term). Lyme bacteria just don’t reproduce that fast. This may also explain the benefits of weaning off antibiotics rather than abruptly discontinuing them.

I have found research only on the effect of short courses of antibiotics on gut flora. Even after a short course of antibiotics shifts in the microbiome can lasts for months or up to a year. We can only imagine what the effects of long term antibiotics might be.  

Mast cell activation, my recent area of focus, has been shown to play an important role in gut inflammation. A mast cell stabilizer, disodium cromoglycate reversed visceral colonic hypersensitivity in an irritable syndrome model (in rats).

The gut produces tryptophan, a key precursor of serotonin, a key signally molecule in the gut brain axis. This process is dependent on the microbiome. Most of our serotonin is in the GI tract, not the brain.

The microbiome has been shown to directly detoxify drugs such as digitalis.

Areas of interest in microbiome dysfunction research include fecal transplantation and purposeful infection with parasites including whip worm and hook worm. Strange, but true.

It should be clear that probiotics are key and should always be incorporated alongside long term antibiotics. For a long time I and others have recommended Florastor or other brands of Sacchromyces boulardii (the good yeast). There is one study that suggested that Florastor may have reduce the incidence of C. diff in antibiotic treated patients. While C. diff is a horrific game changer there is an increasing spectrum of other considerations. A rationale for this agent is that it can be taken with the antibiotics and not be destroyed on the way down. But S. boulardii constitutes a trivial portion of the microbiome. Other studies have suggested that Bifidobacterium and acidophilus are very beneficial. Many other bacteria species and strains, too numerous to list, also have beneficial effects. Many of these beneficial bacteria survive the journey to the gut despite antibiotics. Perhaps enteric coated preparations have a better change.  How many bacteria is enough: five billion, fifty billion one hundred billion? The answer is the highest number you can find/afford. Billions are a drop in the bucket: there are an estimated 100 trillion bacteria living in our guts.

Diet likely plays an important role. Many patients worry about the wrong diet feeding their Lyme. This does not happen. But we want our diet to feed our microbiome. Low carb diets are not the way to go. The complex carbohydrates or sugars, like inulin, which our bodies do not use are adsorb are microbiome food. Prebiotics are supplements made of these polysaccharides and are frequently taken with or in addition to probiotics. Eating the right diet will have a greater impact.  

So we can’t ignore the 800 pound gorilla. When we takes lots of antibiotics the microbiomes shifts in ways we do not understand and many of our friendly residents become highly resistant to antibiotics. The microbiome and gut generally continue to function well.

Lyme is a devastating disease. As clinicians we always have to weigh the risk/benefit analysis of any treatment we propose. We need to appreciate the emerging importance of gut-microbiome organ system. As we know, Lyme is a multisystem disease and can negatively impact virtually every organ system in the body. We have previously shown that Lyme can live in the gut, likely disturbing the microbiome without any help from us.

As we learn more about treating Lyme, in the future we will likely consider positive and negative impacts on the microbiome with a greater awareness of its impact on: mood, the neuro-endocrine axis, the HPA axis, the immune system, antibody production, inflammation and pain, detoxification and toxin production and many more things not listed here and many others yet to be discovered