Thursday, February 13, 2020

CFS, SEID, (a little POTS?)

If you treat Lyme you see boatloads of patients with chronic fatigue syndrome and many with POTS. CFS, myalgia and encephalitis has been renamed SEID, systemic exertional intolerance disorder. Many patients with SEID have orthostatic intolerance.  When they stand up for any period of time they feel the need to sit down or lie down. Is there a connection we are missing?

POTS, postural orthostatic tachycardia syndrome is a manifestation of dysautonomia, a broken autonomic nervous system. This important part of the nervous system does many things. With POTS with focus on a cardiac manifestation.

A lot of disorders are diagnosed based on cutoffs. The numbers are somewhat arbitrary. For example, POTS is diagnosed when supine pulse goes up 30 points with standing.  Perhaps a lying down heart rate goes from 60 to 90 when a patient stands, and stays there and may increase.

A patient may need to stand for 15-20 minutes before the change occurs.  Some patients are tortured with a tilt table test (not originally designed to diagnosed POTS).

Today I saw a 54 year old male I have been following for a number of years.  His main problem has been crippling fatigue.  Maybe he has Lyme, not clear.  Antibiotics were a little helpful (or placebo effect). With high viral titers, EBV and HHV6 the antiviral Valcyte helped, for a while. Maybe. Always looking for the next thing he asked me to prescribe rituximab (kills EBV?). NO WAY. He is always looking for a new cure. He tends to overdo exercise when he feels better and relapses.. Treatment for mast cell activation disorder has been somewhat helpful. 

Today he is feeling the best he has felt in 10 years -- normal.  How did we get there?

When he changed position lying to standing his pulse only increased about 12 points. No POTS by standard criteria.

I wondered what would happen if I treated him for POTS.

I didn't make many changes.  He has high blood pressure.  I changed his BP med, an ARB, Cozaar, a standard go to BP med to Coreg.  Coreg is an alpha/beta blocker and has been shown to help POTS. Normal B blockers should not be used.  I started him on salt (only started  one gm NaCl) and he added more to food. ( crazy in a patient with HTN, right?)

The change in pulse corrected.  His blood pressure did not go up.  Only a small subset of blood pressure patients are salt sensitive, especially blacks and the elderly.

Will it work for others? I don't know. I don't  know if it will continue to work for him.

The experience of one patient may be a fluke and mean nothing.

Both POTS and CFS are poorly understood.  They share certain features.

Mast cell activation syndrome may overlap as well in many cases. The diagnosis is usually clinical.

This therapy must be done slowly with careful patient monitoring.

A  little dysautonomia, a little POTS, a spectrum, continuum? Maybe. Medicine is frequently gray. Black and white cut off points should be looked at critically.

A thought.

Tuesday, February 4, 2020

Lyme update 2020: Key points



Eradication

We go back to the three legged monster I described so many years ago. The tickborne monster has legs of Lyme, Babesia and Bartonella.

For the first time Lyme has been eradicated in an animal model (murine/mice).  Dr. Zang of Hopkins was successful with a daptomycin based 3 drug cocktail: daptomycin, ceftriaxone and doxycycline. These 3 FDA approved drugs are well known and well used. Short of human studies, considered repurposing of vetted drugs may be considered. 

IV therapy is preferred and/or the standard of care in specific cases: sometimes indications are gray.  The risks of IV therapy include infection and venous access line and possible sepsis, thrombosis/blood clots and pulmonary embolism.  The use of intravenous antibiotic does not decrease the likelihood of C. difficile infection. The mainstay of intravenous antibiotic therapy has been Rocephin for many years.  Other antibiotics frequently employed include Flagyl, azithromycin and doxycycline.  Treatment incorporating daptomycin is new and has been well tolerated.  The drug itself is actually quite old.  It has been reserved for serious, resistant infections in many institutions and infectious disease experts have cautioned against first line therapy or other inappropriate use.

The primary indications for intravenous therapy include: Acute/subacute neurological disease ranging from encephalitis, meningitis to peripheral neuropathies including Bell’s palsy and others; acute inflammatory arthritis nonresponsive to oral therapy; Lyme carditis.  Patients with chronic Lyme encephalitis, /neuroborreliosis with cognitive problems are frequent candidates.  Patients who fail aggressive oral therapy, suffering with a multisystem disorder and poor quality of life are candidates.  The choices available for oral therapy are evolving.  As a general rule, IV antibiotics and oral antibiotics should be started and added one ag a time. The anticipated duration of therapy is always completely unknown. Every case is different.

Antabuse

Antabuse/disulfiram may be a game changer. In Vitro studies (Stanford University) demonstrated efficacy against Lyme spirochetes, round forms and biofilm forms. Antabuse has been used for more than a century as an antiparasitic, a commercial agent used for rubber manufacturing and for treating alcoholism.  Antabuse inhibits degradation of acetaldehyde, a toxic intermediary of alcohol metabolism.  Alcohol with disulfiram is a miserable experience one will never forget.  There are better ways to treat alcohol abuse. Antabuse has new life as a Lyme killer.  Antabuse has been effective against resistant forms of bacteria, including Staphylococcus (including biofilms) in-vitro. It seems to have a narrow spectrum against gram positive bacteria and should be easier on the gut. 

Side effects and tolerability described in older literature regarding aplicability for alcoholism does not to apply to our experience with Lyme patients.  For example, rare neuropathy described in alcoholics is not rare for Lyme patients. Herxheimer reactions are common and frequently severe; lower doses of the drug is required.

One option is to cut a 250 mg tabs into quarters enabling initial treatment with 62.5 mg. Compounding allows for more flexibility. Disulfiram can be compounded to any dose you like, for example, 10 mg or 25 mg. A target dose of 250 mg is frequently effective. Some patients claim that the 500 mg dose is more effective. I still combine disulfiram with traditional antibiotics for an optimal response. 

In my experience disulfiram does not eradicate Babesia. In many cases Lyme and Babesia are mysteriously linked. When Lyme clears and remits Babesia too may recede into remission. This may give the appearance the drug kills Babesia. 

Babesia

The malaria like red blood cell parasite is very problematic.   B. duncani and other unidentified organisms are very troublesome. Full eradication should be the goal.  Recurrences can be very difficult since the parasite often returns resistant to an arsenal of anti-Babesia drugs. Most “virgin” Babesia cases respond to Mepron. It is important to start with 10 cc or 2 tsp twice daily with fat. The 5 cc dose frequently recommend is inadequate. Mepron must be used with Zithromax.  Zithromax has the unique ability to concentrate inside cells at an incredibly high level. Other drugs like Biaxin, doxycycline, Bactrim and clindamycin are not effective.   I recommend more than one anti-Babesia drug even when Mepron appears effective. Bellwether symptoms:  night sweats, air hunger, random tearfulness are important but Babesia may cause many other symptoms as well. Coartem is my next favorite agent. It includes a much more bioavailable and effective artemisinin derived component, artemether. 

My third preferred agent is tafenoquine (well tolerated excluding G6PD deficiency). It comes in 2 forms.  Krintafel comes in 150 mg tabs and is used as a single dose for Malaria, repeated at intervals, e.g. weekly and  Arakoda, approved for malaria prevention.  The 100 mg tab is approved for daily use for malaria prevention. 

How long is Babesia treated? We say until symptoms are gone.  I have seen many cases of hoped for cure relapsee. I currently treat for 4 months beyond the point of complete remission if possible.  . 

Bartonella

This small bacteria lives in the cells that cover the inside of blood vessels. The bacteria may occupy red blood cells after infection until they "Uber" into blood vessel lining cells (endothelial cells).  Bartonella persistern forms have been observed.  Complex antibiotic cocktails with multiple bacteriostatic antibiotic, including tetracyclines, macrolides, rifamycins and sulfa drugs do not eliminate the bacteria. Bactericidal drugs, including gentamicin and daptomycin have proved effective. (only by injection, IV or IM). Quinolones should be avoided for safety reasons. 





Monday, January 27, 2020

Chronic nocardiosis, Morgellons?


My lab is certified by CLIA and the College of American Pathologists for blood parasitology.  I examine blood for bloodborne parasites: Plasmodium (malaria), Babesia, Trypanosomes – flagellates, microfilaria. Today I became aware of a bacterium which may appear in the blood but is not bloodborne. Nocardia. I have a patient with this infection. I have been treating her for a long time.  We think Nocardia infection it is chronic along with tickborne pathogens. The bacterium is found in soil and water and is ubiquitous, there are numerous species, some not yet speciated/characterized. We (the patient and me) have thought she suffers with chronic nocardiosis.  She has a clear, documented history of Nocardia: positive pulmonary infiltrate and positive blood culture. This is a slow growing organism. Texts say this rarely seen organism cultures slowly, 3-5 days. Her culture was positive only after 28 days. Nocardia infections is thought to primarily occur in patients with impaired immunity. She lacked clear evidence of immune dysfunction. The bacteria forms lesions in the skin, lungs and brain. Generally, IV antibiotics are recommended initially followed by oral therapy. Standard sources say skin infection is always curable, lung infection is usually curable and brain infection is curable half the time. Texts don’t address chronic nocardiosis, but I haven’t done a literature search.

This bacterium takes on an unusual appearance.  We are accustomed to rods, cocci and spirochetes.  Microscopically these appear as fungal-like filamentous structures.  The filaments vary in length.  Over the years I seen similar things I thought they were contaminants or artifacts and most likely were (not using the same stain).  Perhaps I missed something.  Of course, this was not on my radar.  Images are startling. Images of clumped filamentous structures, looking not like bacteria at all but rather the dense threads seen with Morgellons appear. The images, if correct (I have not validated them) can be found on google images. I know for a fact that some images on google images are incorrect.

Then there are patient images of skin lesions of the cutaneous form of the disease. Some look horrible.  Some clearly resemble lesions seen with Morgellons.

The chest X rays and brain MRIs are distinct from those seen with tickborne disease.

Again, this organism is found on skin and in the lungs and brains. In severe cases it may also appear in blood, gram stains. I don’t know if it also appears in Giemsa stains I perform.

I wonder if some cases of Morgellons are misdiagnosed nocardiosis. I wonder if Lyme immunosuppression plays a role in the pathogenesis of the disease.  Antibiotics recommended are some of the same ones used for Lyme but not exactly the same ones. The initial early treatment recommended is IV Bactrim.

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.