Monday, January 13, 2020

Lyme and biliary disease

Most readers have some familiarity with the liver and gallbladder.  The biliary (bile duct) system includes the gallbladder and a collection of ducts coming from the liver which join to enter the first part of the small intestines, the duodenum, the first part of the small intestines (bowel) just below the stomach. 

The liver is best known as our body’s detoxification organ (along with kidneys). The liver “metabolizes,” alters and excretes medicines and other substances. 

The liver makes bile, a yellow viscous fluid stored in the gallbladder, located directed under the liver. The gallbladder contracts with meals. Bile made of bile acids, from cholesterol, aid in the digestion of fat (an emulsifier) but has many other functions.  

The liver detoxifies medications and toxins through a system of enzymes with names like cytokine P450. Toxins and medications may end up in bile. 

Adsorption of medications may be dependent on something called the enterohepatic recirculation of bile.

Most bile is recycled from the gut which is considered 95% efficient. A particular bile acid molecule may be used 20 times before it is replaced. This is not necessarily a bad thing. The process of repeated cycling may enhance the function of therapeutic drugs and delay their excretion. For liver toxins this works the other way.  Proper functioning of the enterohepatic system depends in part on a healthy gut flora and specific bacterial enzymes.  Higher doses of antibiotics may be required because disruption of normal flora and necessary enzymes caused by the antibiotic(s). 

The use of bile acid sequestrants to remove unknown toxins like cholestyramine is not supported by scientific evidence. 

Some antibiotics promote the production of biliary cholesterol sludge and gall stones, primarily Rocephin, the popular intravenous drug used to treat Lyme disease.  Cholecystitis (gall bladder attacks) with or without the presence of gall stones is a common occurrence. 

Lyme anecdotally can attack the biliary system. Cases of positive Lyme PCR/DNA from gallbladder tissues are known to me but there are no published reports to date. 

Published reports have established Lyme liver disease in the form of granulomatous hepatitis. 
Tests like sonogram, HIDA/CCK scan and others may be used diagnostically for problems with gallbladder and bile ducts.  Negative test results do not rule out gallbladder/biliary disease. 

I am treating a patient with primary biliary cholangitis (PBC). Generally, the disorder is considered autoimmune, “idiopathic,” which of course means the patient is pathological and the doctor is an idiot. Some European literature (this patient is European) connects Lyme with this enigmatic illness. The patient has a clear history of Lyme. No such connection is made in the U.S. PBC is now a treatable disease. 

Bile via an array of ducts ultimately empties into the common bile duct. Bile the empties into the duodenum into a structure called the Ampulla of Vater. The flow of bile is regulated by a muscle called the sphincter of Oddi. 

After cholecystectomy, (surgical removal of the gallbladder), prior gallbladder pain may seem to recur. The bile ducts may become dilated. When a medical workup excludes a left-over stone stuck in bile duct, liver disease, pancreatic disease and other rare diseases, the diagnosis may be post-cholecystectomy syndrome or sphincter of Oddi dysfunction.

These syndromes are more common in Lyme patients, many of whom suffer with gallbladder disease and biliary tract disease and have had their gallbladders removed. 

The diagnosis is commonly missed or not taken seriously. The disorder can be disabling. Effective medical therapy, in my recent experience, is available but overlooked.

Monday, December 2, 2019

PANDAS: diagnosed 15 years after the fact

A young adult is struggling with PANDAS/PANS and much more.   He is 33 years old, I diagnosed him at age 29. I treated him briefly. We arranged a single dose of IVIG. The plan was long term therapy. He was directed to another physician who treated him with a single dose of IV rituximab. He got better – for a while but quickly regressed. 

He had a normal childhood – until he didn’t, excelling academically and in sports. But that changed overnight. One day normal the next the beginning of a nightmare that has never ended. Mom and dad wanted to know what happened to their son. He had become a different person, for no good reason, out of the blue. He became withdrawn, irritable and rageful. He developed tics, anxiety and OCD. Mom took him to his pediatrician who referred him to a psychiatrist. 

He was dosed with psychotropic meds which never made a difference. He refused to go to school.

Finding no alternative, his parents sent him off to boarding school for 2 years. He returned sullen, paranoid and angry.  He dropped out of school and worked odd jobs, never for more a few months. He wandered around, from on place to the next, from one relationship to the next. 

There were numerous suicide attempts and hospitalizations. He was given every psychiatric diagnosis in the book, schizoaffective to borderline personality to bipolar. He was prescribed every psychotropic: atypical antipsychotics, SSRIs, SNRIs, mood stabilizers, anticonvulsants and lithium. The diagnoses were wrong, and the medications never worked. 

He lives on the other side of the country and I have not seen him in years. I care for a family member who referred him to me because he suffers with Lyme disease and thought the patient might have the same. 

Our patient is a little better than he was the day I met him, but he is not a functional human being.  

He is uncontrollably enraged constantly mourning the life he has lost. He is so angry at his parents. Unfairly he blames them for the delayed diagnosis of PANDAS (15 years), and there is so much other water under the bridge.

He in fact has Strep related PANDAS and also tickborne disease picked up later which stoked the fire. 

The medical literature offers nothing in this case and other like it stating PANDAS is a pediatric illness. An NIH paper admits some young adults may be afflicted but it stops there.

Unfortunately, I suspect there are a lot of patients who have a similar story. PANS was not diagnosed in childhood. In adulthood they are diagnosed. What is there to do about it. And I do have other similar patients in my practice. 

Do doctors imagine that undiagnosed pediatric PANDAS cures itself in adulthood?  The problem is doctors who write papers are academics and don't see a lot of patients. They only see cohorts of carefully culled patients who meet study criteria. And they usually don't see those patients for long term follow up.

Patients are frequently diagnosed with Strep, Lyme, Bartonella and others.

Treatment, the right treatment can be prohibitively expensive. Tonsillectomy is recommended and may help.  Antibiotics are part of the treatment.  There may be psychiatric Herxheimer reactions. Steroids are “the poor man’s IVIG.” A therapeutic response to steroids is predictive of a positive response to IVIG.  IVIG is dosed high, 1.5-2 gm/kg every 3 weeks may be effective. Rituximab is a third line treatment. Some patients are managed with a combination of IVIG, Rituximab, steroids and antibiotics. Whatever works. 

These patients need a lot of supportive services and therapies. 

All of this new, largely opinion driven, because there is little research or science. The waters are uncharted because PANDAS wasn’t recognized until the late 1990s and tickborne PANS much later. There may be countless young adults suffering in much the same way. 

Naturally I think my approach is the most logical and effective given what we currently know. 

Treatment: tonsillectomy, antibiotics, steroids, IVIG, rituximab. Rituximab is not a substitute for IVIG, it is third tier therapy.  

Intensive therapy and psychotropic meds are going to be part of the picture. Psych drugs are not bad. It fact, they are incredibly helpful. It must be understood these meds are adjunctive, supportive and do not target the underlying cause of the illness. 

Monday, November 18, 2019

Disulfiram resistant strains of Lyme!

No. I don't know if there are disulfiram resistant strains of Lyme. However, the emergence of such strains seems inevitable but may be preventable.

How does disulfiram kill bacteria?  Biochemistry.  Disulfides or thiols bind to critical metabolites in the bacteria. Medical literature claims it has a narrow spectrum of action killing specific gram-positive organisms, like Staph aureus and several others. The construction of the cell wall of susceptible bacteria determines the entre of the drug.  Spirochetes like Borrelia burgdorferi, are neither gram positive nor negative. The out surface of the spirochete is comprised of double membrane, one that is lipophilic (loves fat). The disulfiram molecule is also lipophilic (loves fat). This shared biochemistry dooms the Lyme spirochetes.  The disulfiram molecule carrying its poisonous chemicals is a trojan horse and quickly puts the spirochetes out of commission.

A narrow spectrum may be a good thing. This is the ideal scenario. The drug kills the target and only a few bystanders (collateral damage). Most antibiotics essentially nuke, or carpet bomb our bodies, carrying around their 2-8 pounds of normal flora – bacteria, indiscriminately killing huge numbers of good guys.

Disulfiram represents an entirely new class of antibiotic with a novel way of killing bacteria.

Traditional antibiotics work by inhibiting cell wall synthesis, inhibiting protein synthesis by disrupting ribosomes, interfering with DNA or RNA function – and that’s about it.

We don’t know if antibiotic resistance will emerge against disulfiram. The best predictor of what might happen is history.

There currently exist bacteria resistant to antibiotics from each of the known classes.

It may be wise to listen to Alexander Fleming, the Nobel laureate who discovered Penicillin. Over the course of his career he watched susceptible strains of Staphylococcus become resistant to the the wonder drug, penicillin, in a few short years.

He cautioned that one must make sure the antibiotic is necessary, then make sure the dose is high enough and the drug is given long enough to prevent the emergence of resistant strains of bacteria.

Popular pulsing and prescription of low, subtherapeutic doses of antibiotics/disulfiram are practices which needed to be avoided lest we kill the goose who lays the golden eggs

The emergence of resistance is nearly universal.  It has happened with every bad infectious disease you can think of, ranging from malaria and tuberculosis to HIV. It is the rule, not the exception.

The Lyme buggers are very, very smart. Expect no less.

ID doctors and the IDSA frequently talk about stewardship of antibiotics. I think they are frequently wrong about the details, but the concept is sound.

The thousands of patients suddenly taking disulfiram are a Facebook ragtag army with no sense of the history of antibiotics and germs and the decades long battles, lost and won.

My suggestion is simple but probably hard to implement.

Hit Lyme hard and long (disulfiram, and as I think about, a cocktail of other antibiotics makes a lot of sense). Treat for months after the disappearance of symptoms.

Using disulfiram as monotherapy, the only drug, may accelerate the evolution of disulfiram resistant Lyme strains.

In the words of the immortal Bob Marley “you have to kill it before it grows.”

Friday, November 15, 2019

Disulfiram, disulfiram and Monurol?

Perhaps, when the  history of Lyme disease is told at some future date, it will be divided into the pre-and post-worlds of disulfiram.  Maybe since Antabuse is not classified as an antibiotic, the IDSA will back off, who knows.  

The drug seems to be amazingly effective for so many patients. Still, it’s not for everyone.  Some patients tolerate relatively high doses of the drug out of the gate; for the most part, is better start low and gradually increase the dose as many patients do not tolerate high doses.  The effective dose is unknown.  250 mg may be effective for  many patients (not 500 mg).

Patients have had a hard time finding the drug, scouring pharmacies across the continent.  A patient I saw today did incredibly well after 6 weeks of therapy.  Then, she could not find any more drug and symptoms returned with a vengeance.  She is now well stocked from an overseas pharmacy. With nearly 30 years of disease, the majority of her life, she suffers with POTS, EDS and MCAS – and chronic pain.  Antabuse is not going to fix everything.  I continue to enjoy excellent success managing pain without opioids. 

Antabuse for most patients may not be a quick fix.  But it’s effectiveness is undeniable and it is quickly changing the game.

Elevated liver function tests are common.  Frequently the drug can be stopped for several days until labs normalize and tolerated at a lower dose without budging liver numbers. Liver function tests in excess of 3 times the upper limit of normal (120ish) should be of immediate concern.  
Another novel therapy been very effective for 1 of my patients.  Fosfomycin, Monurol is a 3 g powder is typically used for urinary tract infections.  It also works very well against Lyme persister.  With a typical UTI the dose is a single 3 gm packet. The drug has a prolonged duration of effects, about 48 hours, despite a short half-life:  it continues to work because of its PAE (post antibiotic effect). A current patient is responding beautifully to twice weekly dosing along with doxycycline and Zithromax – Zithromax combined with Mepron for Babesiosis. 

There are more great and effective options than ever before, including IV daptomycin. 

I am accepting new patients with Lyme (and coinfections) and a host of other conditions: PANS, POTS, CVID, CIDP, EDS, MCAS, CFS, FMS, neuropathic and central pain syndromes, headaches and chronic, mysterious difficult to diagnose ailments. 

I offer blood Giemsa staining screening for active Babesia infection:  Lab CLIA approved and certified by College of American Pathologists.

Blogging about Lyme and related topics since 2008.

Tuesday, October 29, 2019


Its true: Antabuse/disulfiram is the most exciting new therapy for Lyme since daptomycin.

We are getting a lot more experience with disulfiram/Antabuse.  In some cases, it seems to be very effective.  I don’t think it is clear which microbes it is active against. It is an old drug repurposed as an antibiotic.  Its antimicrobial spectrum may remain unknown for the foreseeable future (there is no money researching it).  One thing worse than dreaded MRSA is VRSA – vancomycin resistant Staph aureus.  In vitro it was shown that the addition of disulfiram to vancomycin conferred the ability to kill this dreaded superbug. This should be catching some eyes, even outside the Lyme world.

Disulfiram clearly has potent antibiotic effects. It also has side effects. Twenty five percent of users have some rise in liver function tests –markers of liver inflammation. The rise is usually modest, and therapy can continue if AST/ALT numbers don’t exceed 2-3 twice the normal limit, with close monitoring. Three times makes me nervous. My comfort zone limits closer to 2.  Waiting for numbers to normalize and restarting with a lower dose may work. Severe liver disease may occur 1-2% of the time, not a trivial number.


You should never treat yourself. The man who has himself as his doctor has a fool for a patient.

Side effects may include, dizziness, brain fog, fatigue, GI intolerance and others – in my patients. Many patients have had to discontinue because of side effects. Monotherapy may be fine. It runs counter to my experience, so I tend to prescribe it with doxycycline.

A word for the wise. We don't really know how safe the drug is.  Sometimes problems only become known when an occasional drug becomes one in common use. We have seen it over and over, for example, fenfluramine off fen-fen fame caused unexpected heart and lung disease and Vioxx the great new anti-inflammatory caused heart disease. Drug companies who have studied drugs extensively and had FDA approval call this "post-marketing" side effects.

Yes, Antabuse is an old drug used by hundreds of recovering alcoholics. When this old drug, largely disregarded from decades, it is suddenly used by thousands of lyme sufferers it many ways acquires characteristics of a new drug. In this case one that has not been tested. Quality control of generics is increasingly becoming an issue, e.g. Zantac.

I am prescribing the drug, just not throwing caution to the wind.

There is the issue of dose.  For alcoholics the loading dose is 500 mg and maintenance dose is 125-250 mg. This suggests that lower doses have efficacy.

There is some confusion about Lyme Herxheimer reactions.  From experience, Lyme, Babesia and Bartonella have separate and distinct Herxheimer responses.  Herxheimer reactions occur when mass killing of chronic, entrenched infection leads to an over-reaching immune response, a cytokine storm. The average, non-Lyme doctor, is unaware of the phenomenon treating mostly acute infections. These same doctors no doubt encounter a fair number of Herxheimer reactions which are misdiagnosed, e.g. drug allergy. Some patients have an “allergy” to every antibiotic. No, they don’t. Other patients say, “every time I take an antibiotic it hits me hard.”

Babesia and Bartonella Herxheimer reactions are very vexing, chronic and sometimes difficult to manage. They are qualitatively different from Lyme Herx reactions.

Lyme “Herxes” tend to be easier and follow a specific pattern.  An antibiotic is introduced, with days severe symptoms ensue, like fatigue (inability to get out of bed fatigue) low grade fevers, brain fog, achiness etc. After a period of days, weeks, usually no more than 3 weeks, symptoms begin to improve and go away and the patient improves. The Herxheimer reaction (Lyme only) should not return in cycles. Such cycles, apparent recurring Herxes, may be the result of normal ups and downs of the disease or due to killing something else other than Lyme. If we add one or more drugs, which gain access to a previously off-limits group of bacteria (round forms, biofilms etc.) a Herx may return, maybe even a more difficult Herx.

Dr. Zhang has dichotomized Lyme bacteria for us: active forms (free spirochetes) and stationary/persister forms (round bodies, biofilms).

After a reasonable amount of treatment with antibiotics targeting both populations, e.g. doxycycline, rifampin and Flagyl we would like to think there are few Lyme bacteria left. We are incorrect.

Add in disulfiram and an intense Herxheimer reaction may ensue (in some cases, not all).  Patient tolerance to  varying doses of the drug is all over the map.  Some handle 500 mg out of the gate, others struggle with 125 every other day.

It makes sense to start with a low dose and gradually increase over time.  I am more aggressive apparently than many others.  Most patients can increase from 250 mg daily ramped to 500 mg over a week or two. For sensitive patients much lower doses and more gradual ramping is required.

I have seen patients on the border of needing IV antibiotics  get better with Disulfiram.

It doesn’t always work. There is still no one drug that works for every patient.  And symptoms still relapse quickly with discontinuation after a few months.  Some patients are still going to need IV antibiotics, (Rocephin, daptomycin, doxycycline) if possible.

In my experience disulfiram doesn't appear to kill Babesia. My experience. Babesia is an opportunistic infection riding on Lyme’s coat tail.  Lyme has inherent immune suppressing properties. If Lyme is largely gone, Babesia symptoms may abate as well. In a normal host the body's immune system can eradicate Babesia, or reduce it to a mild parasite causing no symptoms. Just a thought.

So far, we only know that Antabuse kills Lyme spirochetes and Staphylococcus. Hopefully research will be funded so we can learn more about the drug. We really don't know what it does or doesn't kill.

Bottom line: Go for it! Monitor labs, watch for side effects (no alcohol including herbal tinctures): disulfiram –is  not an overnight miracle cure -- but it is quickly rising to the top of the list of  go-to Lyme drugs.  

Monday, October 14, 2019

Unecessary suffering and beating a dead horse

My new 40 year old patient is besides herself.  She has struggled with a tickborne illness for 5 years.  She has managed to keep her job, but barely. She cries uncontrollably.  She is very irritable and angry. She complains of anxiety and panic attacks.  Mostly, she is depressed. She admits to night sweats.  She denies air hunger.  Ongoing symptoms include exhaustion, chills, poor sleep, tinnitus, painful lymph nodes, abdominal pain and nausea, GERD, irregular menses, joint pain, headache, dizziness and vertigo and feeling off balance, dysesthesias and crawling sensations, panic attacks, suicidal ideation (no plan or intent), brain fog, trouble with with focus and concentration and thinking clearly. She has had a lot of unexplained abdominal pain over the years.

She has seen 2 "Lyme"  doctors off and on over the last 5 years. She has also seen many "regular" doctors.  The first Lyme doctor diagnosed Bartonella and treated her extensively with minocycline, azithromycin and rifampin.She didn't get better.   A second Lyme doctor confirmed the diagnosis of Bartonella.  Laboratory tests were negative but the physician was certain on clinical grounds the diagnosis was correct.   After all, what else causes severe GI symptoms and abdominal pain?  Anxiety and irritability are typical symptoms, almost diagnostic - she heard somewhere.

The "regular" doctors diagnosed depression, fibromyalgia, chronic fatigue syndrome and hypochondriasis.

One Lyme doctor treated her with ivermectin for one year.   She states she thinks she had a Herxheimer reaction but does not know why this drug was prescribed. The treatment did not help.

The same doctor prescribed Biaxin and rifampin.  The dose of rifampin was increased to 1200 mg daily.  After 9 months of this therapy she has gotten worse.  The doctor told her she has not been treated long enough. She decided she has waited long enough.  She thinks she had Herxheimer reactions but never got better.

She has never been treated for Babesia or even Lyme. A course of doxycycline with other Lyme drugs was never prescribed -- or anti-Babesia therapy.

A LymeWestern Blot was equivocal by MDL standards, IgG only.
Serologial tests demonstrated a low positier titer for Rickettsia species.
All other serological tests, inclusive of  Bartonella and Babesia were negative.
CRP was elevateed at 10.

I am able to offer another test in my CLIA certified blood parasitology lab.

Her an image taken from her Giemsa smear:

If a patient doesn't respond to a therapy the clinician is obligated to go back to the blackboard and take another look.

The slide shows marked infection with the malaria-like red blood cell parasite: Babesia. Few things are black and white in Lyme's orbit. This is an exception.

This CDC endorsed standard malaria/Babesia smear is a gold standard.    Many tests circulating in the Lyme-osphere are questionable.

Even without this piece of dramatic evidence, the patient should have been treated for Lyme, e.g. Doxycycline/Ceftin (Tindamax, Flagyl, disulfiram and others) and also treated for Babesia.

This poor long-suffering patient went  5 years, with night sweats and profuse tearfulness (depression) and Babesia was never considered or treated.

Hundreds of things can cause abdominal pain other than Bartonella, etc, etc. The symptoms of Lyme and common coinfections overlap. No one symptom should be attributed to  a particular tickborne pathogen.

Babesia treatment includes Zithromax and high doses of Mepron plus Coartem plus Krintafel. It is important to completely knock out Babesia when first encountered.  Otherwise, the parasites relapse and return mean and drug resistant.  *Please don't use Malarone because Mepron, the yellow paint is hard to stomach. Two malarone twice daily provides a daily Atovaquone dose of 1000 mg.  Two tsp of Mepron twice daily provides 3000 mgs of atovaquone, three times the dose. This dose falls within FDA approved, manufacturer guidelines. This high initial dose must be used to avoid drug resistance and years of misery. If its virgin Babesia you have one change to hit it hard and fast. Don't miss.

I am optimistic. We will get her better and sooner rather than later.

Tuesday, September 3, 2019

Lyme germ warfare?

Complex subjects, like the provenance of Lyme, are oversimplified into a soundbite and the truth is lost in the noise. The Washington Post does us a disservice.

Sam Telford, in the Washington Post told us that Lyme is not an escaped military bioweapon. The headline is  an implicit smirk at the alternative Lyme community said to be steeped in unfounded conspiracy theories. Ant-science. Fits right into the IDSA narrative.

Dr. Telford is a smart guy, a professor of Biowarfare at Tufts University, who has researched the topic for decades. Largely, he is telling the truth. Largely.

Let's listen to his truth. It speaks volumes.

Lyme is an old disease, even ancient.   Lyme was found in the 5300-year-old ice man dug up from the permafrost in the Alps – previously published in National Geographic.  Lyme infected ticks were found from 1945 and 1896 in the northeast US. Facts.

Ticks (Lyme carrying ticks) were studied during the cold war as a means of transmitting germ warfare.  Fact.

Deadly agents, including Tularemia and Q fever – transmitted by the same Ixodes ticks were studied (and continue to be an area of research -- other source).

The double helix of DNA was discovered in 1953.  Scientists during the cold war (1950s - 1980ish) lacked technology to modify germs and make them more deadly. Now it can be done.

Germ warfare research was done at Fort Dietrich and Plum Island. Modern Biocontainment procedures were unknown. (Animals and Ixodes ticks were allowed to roam free on the Island, with the belief they could not leave the island -- other sources). It was unknown that seabirds could ferry ticks to the mainland.

Lyme and the coming epidemic was something military researches could not have imagined.  The Lyme Bacteria was not discovered until 1981.

The Lyme epidemic cannot be entirely sourced to Plum Island since the epidemic broke out in the Midwest and West Coast at around the same time as Lyme Connecticut. The author does not say that Plum Island didn't contribute to the epidemic. 

Willie Burgdorfer participated in tickborne biowarfare research for the US Department of Defense.

Dr. Telford says a few dumb and obviously incorrect things: Willie was just joking with the interviewer about his role in germ warfare research.  Plum Island was repurposed for agriculture research in 1954 -- during the height of the cold war. (not a cover story).
And -- the US stopped bioweapon research in 1969 because Nixon said so. 

These are the clearly established facts.

In summary:  Our government was involved in germ warfare research for years. Some of the research involved ticks and tickborne disease (Q fever, Tularemia). Willie Burgdorfer, whose names is attached to the Lyme agent, B. burgdorferi worked for the government and  some of this research was with the same ticks that transmit Lyme disease. Biocontainment procedures were unknown and government scientist did not know the ticks and the unknown pathogen (Lyme) could easily jump across the Long Island Sound to Lyme Connecticut. 

It is easy to conjecture the Government unwittingly helped spread the epidemic of Lyme disease to New England as an unexpected consequence of secret germ warfare research. And, it is widely known the Government has a habit of not admitting wrong doing and covering its tracks. 

When we say Lyme was not an escaped bioweapon the statement is both true and false. There was no conspiracy to infect Americans with a horrible disease. But is seems likely that an unexpected consequence of tickborne disease bioweapon research on Plum Island was the spread of some Lyme infected ticks to the mainland. 

The law of unintended consequences applies and there is much we will never know.

Congress can investigate and it will be a waste of time.