Thursday, September 13, 2018

Vancomycin: the cure?


A study released from Northeastern University looked at the use of Vancomycin for Lyme. 

The drug which can only be administered intravenously and is more toxic than most commonly used alternatives.   IM therapy may be used but is perhaps very painful.  Oral vancomycin does not leave the GI tract and is only for C. diff. 
Studies are not in agreement.  Zhang found the drug to be relatively ineffective in vitro, as have others. 
The new study found that both Rocephin and vancomycin are effective against stationary phase cells – round forms and biofilms. Vancomycin was combined with a quinolone to sterilize a culture. In an immune deficient mouse doxycycline did not clear disseminated but both ceftriaxone (Rocephin) and Vancomycin were effective.  
Vancomycin may be slightly better than Rocephin but this far from clear.  Both inhibit peptidoglycan synthesis, the basis for cell walls.
In 2017, the Biophysical Journal published a study about the impact of Vancomycin on Lyme spirochete motility, significantly impaired.  The Peptidoglycan – cell wall material (under an outer membrane) was weakened with low concentrations, subtherapeutic, of vancomycin which also inhibited the formation of round forms or blebs.  Wounded spirochetes, unable to swim very far may do little harm. 
The drug may prove very useful, especially with subtherapeutic dosing, within a cocktail approach.
Vancomycin has been used for decades in the treatment of MRSA, a feared superbug.
The drug is very nephrotoxic and can cause irreversible kidney failure: serum concentrations and renal functions must be watched carefully. 
Although vancomycin is not hoarded over by ID docs like daptomycin, ID doctors will be concerned about sudden wild use of the drug.
Going back further, 1996 – A G Barbour, an IDSA stalwart, found the following. Vancomycin eliminated Lyme in immunodeficient mice only when given within 3 days of infection. When given at 7 days post infection the germs persisted; viable spirochetes were found in the mouse brains. 
In 1993 Barbour demonstrated that in vitro vancomycin was an effective anti-Lyme therapy.
It has been long known that vancomycin has anti-Lyme activity. 
We need to know a lot more. 
Treating Lyme falls within the large purview of “the art of medicine.” In “the system” so called evidence-based guidelines dictate medical practice. The guidelines dictate what the disease looks like and how it is to be treated. 
The existence of chronic Lyme as we know it is soundly rejected. Nothing has changed. 
Doctors who believe in chronic Lyme agree on a several things:  Lyme is a tragic, underappreciated epidemic; Lyme is very difficult to treat; Lyme has many faces, the “great imitator;” coinfections are an unappreciated huge factor and I am sure a few other things. 
Doctors collectively known as LLMDs are a heterogenous group.  They don’t agree on how best to treat the illness(es).  Doctors who treat the disease(s) realize we still know very little as we try to improve our approaches as times moves on. 
It is important not to jump on every new therapy as “the answer” and be mindful of toxicity and First do no harm
I ask readers to refrain from jumping from preliminary preclinical small, limited basic science trial data and making quantum leaps to a new people therapy. 
Vancomycin, unfortunately, is not the cure. 

Monday, September 10, 2018

Babesia cocktail therapy

A 56 year old male has suffered with Lyme off and on for the better part of 10 years.  Symptoms come and go but have fairly easy to control.

He suffers with a mood disorder.  Bipolar 2.  He has a history of mild manic episodes alternating with depression and the disorder is chemically controlled.

He has complained of recurrent low grade fevers and night sweats recently. He came in to my office stating his Babesia was relapsing.

He was right. The patient's blood smear confirmed the self diagnosis.

Some Lyme-literate people are quick to blame tickborne illness for everything - including all mental illness. It is easy to go overboard. Bipolar illness exists apart from tickborne disease in this case.

Babesia and other central nervous system infections may exacerbate preexisting mood disorders.

Lyme and associated infections have been associated with every neuropsychiatric syndrome reported.  Clues that infection is not the primary cause include: strong family history and mood disorder predates Lyme infection. 

Babesia is frequently associated with depression, especially increased tearfulness.

Babesiosis, the clinical syndrome associated with Babesia infection is frequently persistent, resistant to therapy and prone to relapse or recurrence. (Relapse same infection, recurrence new infection).

I have found multiple, simultaneous agents are needed.  Antimalaria agents are added sequentially creating a "cocktail" in much the same manner Lyme is treated

A new study was released last week ( UCLA) which amazingly discussed a new paradigm.  In the case of E. coli:  perhaps it best to hit highly resistant superbugs with 3-4 antibiotics, which all work by different mechanisms rather than a single drug which works only by one.

Some agents include: Mepron, Malarone, artemisinin, artemisia (bioavailability), Coartem - more bioavailable, cryptolepis,  "Buhner herbs" including sida acuta, Daraprim, Zithromax, Clindamycin, Quinine and low dose heparin.

For example, when Mepron doesn't do the job adequately it is not discontinued, rather something else is added. Patients may be on 3-4 agents simultaneously to get the job done.

We think human Babesia develop rapid resistance to various agents.

We don't know.There is no human data. Animal data supports the thesis.

The disease is underappreciated.  I suspect if suffers with guilt by association (Lyme).

As with Lyme, most experts believe in acute Babesia, not chronic babesiosis.

The Babesia lifecycle is presented below.  In mice the lifecycle is more interesting -- sexual reproduction. This allows for the transfer of genes from one organism to another. This is an evolutionary advantage RE the development of resistance.

In the human host the cells reproduce via an asexual process. The slides can look quite different at times. Most commonly small, dark staining round bodies are seen with Giemsa staining.

Resistance develops because random mutations -- mistakes made copying DNA -- occur with great regularity.

Sporozoites are released from an infected red blood cell.  The small forms attach to the cells and gain entry morphing into the larger merozoites. The merozoites divide in cells, rarely 2 at a time (Maltese Cross). The red cells rupture and the cycle repeats.

Additional information: sporozoites morph into an intermediary ring form, trophozoite before becoming a merozoite.  Ring form are readily observed.  Mature merozoites can rupture creating vermicules, small infective particles. These are harder to pick out. Intermediary morphological forms can present in many ways.





Friday, September 7, 2018

Are you a tick magnet?


Do mosquitoes make a beeline for you and ignore your companion?

You are not crazy.  Ticks do like you. 
A recent European study showed a species of Ixodes ticks preferentially seek out certain blood types.  From the ABO Rh subgroups ticks prefer type O blood and type B blood is relatively protective. Ticks find type A blood only slightly less appealing. Ticks, mosquitoes and other blood sucking insects are primarily attracted by CO2 but there are other important factors. The insects can detect hundreds of volatile organic compounds which emit signature scents from our skin. Sweat plays a role. Skin flora play a role. Other genetic factors may be in play. 
I am lucky and have type B blood – 9% of the US population.  You are probably not so lucky. 
It is true:  some of us smell sweeter to ticks and mosquitoes than others of us. 
Certain chemicals make us less attractive.  DEET and Picardin are well known insect repellents and are moderately effective. Other natural substances may be effective, such as: lemongrass, citronella, cedar, peppermint, lavender and geranium. 
I have no specific recommendation here.  There is a lot of discussion on the internet.  A patient recently told me he combines several of these substances and has good results. 
The most important preventative is permethrin. Permethrin is applied to clothes and allowed to dry overnight.  Clothes pretreated with permethrin are commercially available.  Permethrin persists in/on fabric for a month or more – even if clothes are washed. 

Wednesday, August 15, 2018

Lyme and the rule of 3s.


I had this conversation today. 
“Are Babesia symptoms better?”
“Which are those?”
“You have had Lyme for 10 years. Let me try to make it simple.”
Here is -- I hope -- an easy way to remember Babesia symptoms and others.

Rule of 3s.

3 pathogens.
Each pathogen has 3 prototypic, characteristic symptoms.
A patient yesterday what to know if she was different because she has Rocky Mountain Spotted Fever. 
First off, she does not have and never did have Rocky Mountain Spotted Fever.  The positive test shows cross reactivity to other related species of Rickettsia.  
As a rule, it doesn’t matter what else you tested positive for, outside of the big 3.  They get better. Almost always. 
The big 3 pathogens may not get better.  They are tenacious and hang on despite best efforts. 
Lyme is variably pathogenic.  The other two are opportunistic conspirators.  They hit you when Lyme has knocked you down and jump into the fray. 
We start with an alliteration. 
Borrelia (Lyme), Babesia and Bartonella. 
These are stereotypic symptoms. You may have a few or none of the above. But here it goes:
Lyme:  Fatigue.  Pain (tends to come and go) and brain fog (cognitive dysfunction).
Babesia:  Night sweats (at times fevers).  Air hunger.  Depression, especially random tearfulness. 
Bartonella: Pain, not joint (shin, heel, neck, headache), craziness (irritability, anger, rage, psychosis and others) and rashes.
After I presented my rules of 3s, the patient said:  Yes. Nigh sweats and air hunger are improving.  Mood is better.  Babesia symptoms. 
You might want to know why these pathogens are different from all others. Why won’t they just leave?
Narrative of persistence. 
We explain persistence of pathogenic microbes with a science based, biologically plausible explanation. 
Lyme:  Context is always important.  A few points.  Doctors have argued about the existence of chronic or persistent Lyme symptoms for decades.  First: no such thing.  Then: Post-Lyme syndrome, autoimmune residua. Now: Post treatment Lyme disease syndrome.  The new term is a concession to science. Science informs it has thus far been impossible to eliminate Lyme from mice, dogs and monkeys. Further, some studies prove persistence in humans after treatment. Lastly, Lyme is about impossible to eliminate in a test tube. The experts who propose no chronic Lyme have been wrong on the first two account are sure that got it right this time.  Even if organisms persist, additional treatment hurts patients and doesn’t help them.  Patients have chronic persisting infection.  Long-term antibiotics make symptoms go away, frequently only temporarily. The other side has been wrong 2/2 times. Shall we go for 3?
Babesia:  If I failed to mention it. I did. Lyme is pantropic, meaning it goes everywhere, infects virtually every tissue and organ.  Babesia is organ specific – blood system.  It’s minions exclusively inhabit red blood cells.  Clinically we know it doesn’t go away because it keeps coming back.  We side it hides or sequesters in small blood vessels (capillaries), the spleen and bone marrow.  The mechanism is not fully understood. In general, the immune system functions poorly within cells. 
Bartonella: Lives in cells lining blood vessels.  Hides inside cells or sequestered in the intracellular milieu. This is a safe harbor against the immune system.  Clinically the thing is difficult to kill. 
We have effective treatments for the all the above. Some new things are working. If you would like to learn more call our office for a consultation.

Sunday, June 24, 2018

C. Diff and doxycycline magic


C diff is a dread complication of antibiotic therapy. Clostridia difficile, an anaerobic bacterium may reside in gut as an innocent bystander, causing no trouble unless something happens.  We call this germ an opportunistic pathogen.  It causes disease only when favorable circumstances present.  The degree of illness varies.  It may present as diarrhea which resolves when antibiotics are stopped or a life threatening disease. 
Risk factors  for C diff are well known.  Antibiotics are at the top of the lists. Other risk factors include age (greater than 65), chronic medical illness, hospitalization and admission to long-term care facilities, including nursing homes. 
C diff patients may have diarrhea:  frequent, watery stools. There may be associated mucous and/or blood and stools may be fowl swelling.  Symptoms and signs of more serious infection include:  fever, elevated white blood cell count, abdominal pain, abdominal swelling and shock. 
In the past Flagyl and Vancomycin were effective therapy. A new drug, Dificid is approved for C. diff.  Drug resistance strains have started appearing, of great concern. 
Sometimes infection is like a runaway wildfire and very hard to stop.  Surgery may be required. Fecal transplants are sometimes used.  Fatal cases occur. 
We like to think probiotics ward off the disease, but this is far from certain.  Traditional probiotics may have some benefits, but limited.  Florastor or Saccharomyces boulardii may be slightly beneficial.
There is something else to consider before we discard long-term antibiotics. 
The choice of antibiotic makes an enormous difference. 
When first described, C diff was tied to clindamycin. Later it was learned that other or most antibiotics can cause C diff colitis. Sometimes it is writ that “any antibiotic” can cause C diff.  Maybe not.
There is a hierarchy of which antibiotics and classes of antibiotics are most likely to cause C diff.
Clindamycin is at the top. Quinolones including Cipro and Levaquin are a close second. Cephalosporins, including Ceftin are next. Penicillins like amoxicillin are on the next rung. These drugs are all considered high-risk.  The next group, medium-risk, includes Macrolides such as Biaxin and Zithromax and Sulfa drugs such as Bactrim. Low-risk drugs include tetracyclines, doxycycline and minocycline, rifamycin including rifampin and certain antiparasitic drugs including Flagyl. 
And this brings us to my next topic. Doxycycline: the magical drug. 
It turns out that studies show not only that doxycycline is a C diff low-risk drug, but doxycycline seems to reduce the incidence of acquiring C diff when compared to a control group taking no antibiotics.  In other words, doxycycline may protect against getting C diff. 
This is huge.
No wonder dermatologists prescribe doxycycline to armies of 15-year-olds with impunity. 
Rifampin may have a similar benefit, lowering the risk of C diff. 
 Although there is not data regarding Flagyl, claims to the contrary, it is likely the risk of Flagyl is very low since this is one of the traditional drugs used to treat C diff. 
The prejudice against doxycycline percolating up through internet sources is unfounded.
It stems from the fact that doxycycline is ineffective against Lyme persister forms, round forms and biofilm communities. Take another look.
Doxycycline is the most active drug against spirochete forms.  No one drug does a great job killing persister forms, except daptomycin which is not a realistic option.  Cocktail therapy always works best. There is one drug which shows up in every cocktail group proposed through Zang’s research, with on exception, that is doxycycline. In the other group minocycline was used instead. 
Doxycycline appears to have unique, broad synergy when combined with a host of other antibiotics from other classes. 
Lyme killing cocktails rely on synergy between or amongst chosen antimicrobial agents. The above data show possible advantages of cocktail combining doxycycline, rifampin and Flagyl (Tindamax) and/or artemisinin, in some form (in theory).  Informational purposes. I am not recommending any specific therapy.  

Test tube data are really important, especially at this stage of our understanding,. This data cannot be and should not be translated directly into clinical recommendations. Please. 
There are other factors the Zhang data cannot take into account.  Antibiotics in a test tube are judged based on concentration in a culture broth, a surrogate for serum concentration. It turns out that the ability of drugs to concentrate in tissue is extremely variable.  Tissue concentration of an antibiotic, for example doxycycline, are frequently many fold higher than serum level.
This might seem irrelevant because after all, doxycycline has no impact on non-spirochete forms. Right? 
Maybe not.  In the 2017 study round forms of Borrelia burgdorferi, Lyme bacteria were cultivated the effects of many agents tested.  A goal of the study was to test the effects of sulfa drugs. Sulfa drugs performed poorly.  Drugs were tested at three different concentrations: low, medium and high. Concentrations are reported in molar values and I have no idea how this compares to real life serum values. The data show that as serum concentration increase the ability of the drugs to kill the round, persister form increases. At higher concentration doxycycline starts to diverge from the control and show benefits comparable to other drugs and drug combinations (still poor), having an impact on round forms. 
 Other factors are: bioavailability, tolerability and toxicity, clinical factors outside the sphere of test tube studies. Clinically, these are all very important.
Doxycycline has unique bioavailability, nearly 100% when taken orally. It is not metabolized by either the liver or kidneys. It has very low toxicity and is often well tolerated. These factors are clinically very important. 
Then there is the other thing, when it comes to treating and/or preventing tickborne infections.
Only one drug can kill germs associated with:  ehrlichiosis, anaplasmosis, STARI associated Borrelia species, Rickettsia (including Rocky Mountain Spotted Fever), Mycoplasma, Chlamydia pneumonia, tularemia, brucellosis and prevent early bartonellosis and babesiosis. 
You guessed it:  Doxycycline. 
Sure, a lot of people don’t tolerate it well in the summer and a lot of people experience GI upset.
Minocycline may be second choice, although I can’t say it has all the same benefits.
Keep this is mind when amoxicillin is offered as the second choice drug after a tick bite.

Tuesday, June 19, 2018

A 24 year old male with brain fog and more

Dear readers:

Thank you for reading my Blog which is now in its 10th year.

I am trying something different:  talking rather than writing. I am more experienced with the latter.

For those who live nearby:

I will be giving a presentation in the conference room in the basement of my office building in Rockville, MD

15245 Shady Grove Road (North entrance) on June 26, 2018 -- one week from today, 6PM.
The talk will not be recorded.

I am planning on doing a series of talks over the ensuing months.

Last month I discussed an approach to patients suffering with fatigue, pain and cognitive symptoms.

This talk is something different.

I present the case of a 24 year old male complaining of brain fog.  Symptoms are added one at a time leading us in different directions as the case unfolds.

I am adding a brief talk (I just put together) called Lyme the Big Picture to precede the other.

I will be taking Q&A at the end.

We do have limited space.  If possible call my office and gives us a heads up.  Reservations not required.  There is no charge.

I will continue to write the blog as well.


Dr. Jaller




Monday, June 11, 2018

Choosing the right antibiotic


I want to discuss several factors to be considered when choosing antibiotics in the management of Lyme disease. 
There is a lot of confusion about the basic biology of the Lyme spirochete, Borrelia burgdorferi. A lot has been worked out but there is some confusion and misinformation on the internet. 
Lyme is primarily an extracellular bacterium and resides in spaces between the cells, extracellular matrix. Without question Lyme spirochetes are occasionally intracellular but this is not the pathogen’s primary modus operandi. Not primarily intracellular.
Lyme is pleomorphic – takes on various forms and has modes of persisting. It forms round forms sometimes called cysts and congregates within biofilms.  Does not form L-forms. Discussed elsewhere.
There are many classes of antibiotics. Antibiotics within a class share features, typically chemical structure and mode of action. I will mention a few examples. 
The macrolide story is interesting.  Zithromax and Biaxin are the two clinical agents of this class most used. On the face they sound similar. Both work by an intracellular mechanism inhibiting protein synthesis.  But clinically there are differences.  Biaxin is more effective against Lyme and Zithromax is more effective against other organisms, for example Babesia. 
Zithromax has a unique and well-known ability to concentrate inside cells many times the concentration in serum.  Because Lyme is primarily extracellular this quality is not a critical factor. Otherwise Zithromax would be much more effective than Biaxin. 
When evaluating the effectiveness of an antibiotic against a particular bacterium, test tube, in-vitro data is cited.  Numbers include:  MIC (minimal inhibitor concentration), MBC (minimal bactericidal concentration).  The time during which the antibiotic concentration exceeds the minimum kill level is called AUC, area under curve. These numbers estimate what may happen in humans taking the drugs. The numbers have limitations and can mislead.
Doxycycline is a favorite drug. It is extremely bioavailable and easily reaches a steady state in the blood stream. For this reason, many experts claim there is no reason to ever give the drug IV. Not true. There is evidence that tissue levels are much higher when the drug is given IV. Our target is tissues where the germ resides – not the blood. 
Antibiotics may be: bactericidal, kill the bacteria or bacteriostatic stop their growth.  In clinical practice there is no difference.
Antibiotics may interact with bacteria in diverse ways. In most cases a sustained blood level is preferred, example, B lactam drugs, amoxicillin and Ceftin.  In other cases, drugs are more effective when there is a distinct peak serum level, as in the case with gentamicin, used for Bartonella.
Lyme has persister forms and is difficult to eradicate at best. Strategies to eliminate persister forms have including antibiotic cocktails and pulsing. Doctors have various theories and preferences.

Questions to consider when choosing an antibiotic:

1)     What germ(s) are we targeting? What is the pathobiology of the germ? Big word. How does the pathogen make us sick? Where does the target germ reside? 

2)     Does the antibiotic reach the target(s)?

3)     Is the antibiotic bioavailable (get into blood stream)?

4)     Does the antibiotic offer the right “killing kinetics?”  This asks if there is a steady state versus a sharp peak and trough levels, as desired, based on the pharmacology of the antibiotic.

5)     Oral or intravenous therapy?

6)     Continuous or pulse therapy?

7) Single therapy or combination therapy and how to proceed?

There are many other factors and considerations. For example, when used in combination antibiotics may exhibit synergy, mechanism unknown.  Drug combinations may be toxic or cancel out the efficacy of the other.  For example, rifampin reduces the effective dose of Mepron by 50%.  

Figuring out how best to treat infections is complicated.  Standard therapies may be poorly explained and not be effective.  We may have to go a step or 10 further. But there should be a method to the madness.


Friday, June 8, 2018

Lyme on a dime


Treating Lyme disease can be expensive, incredibly so. 
I hear all the time about patients suffering with the disease who don’t seek help because they can’t afford it.   
Patients sometimes treat themselves with dubious advice from “the internet.”
Doctors sometimes distance themselves from patient costs.
We can do better than that.

You can get good care for your Lyme disease and keep the farm as well.
Rule one:  Be your own advocate
Rule two:  Know what you are getting into: is the practice allopathic, integrative, functional, naturopathic etc.
My practice is allopathic which is a little confusing.  Allopathic doctors follow Western Medicine.  My beliefs and practices run counter to mainstream medical practice which follows a sort or orthodoxy. In that sense I am an alternative practitioner. In the sense that I primarily rely on Western Medicine tools I am an allopath. 
I base my diagnosis and treatment on evidence and science.
Make sure you know what you are committing yourself too so you don't prematurely spend your entire Lyme budget. 
Supplements
Supplements can cost a fortune. Do you really need them?
I am not inherently opposed to supplements or nutraceuticals but think their use should be well conceived and limited. I don’t sell supplements because I see it as a conflict of interest. Whenever I research a supplement I become half convinced than that it is a life saver that I must take. The other half says: wait a minute. It is important to distinguish between hype and science. (I do take several supplements daily) I assume the reader has a limited healthcare budget.  Beware of the supplement trap. Vitamins, herbs and various nutritional supplements can quickly drain limited resources. A poor investment of Lyme dollars.
Labs
Do not order your own tests. 
Labs can cost an unnecessary fortune.
I my early days patients were diagnosed using this on formula describing sources of data used to make a diagnosis: patient history 85%, physical exam 10% and lab 5%. Today there is an overreliance on technology. The new formula reverses the numbers, diagnosis 85% lab.  When it comes to diagnosing Lyme and tickborne disease the old paradigm (history 85%) should be applied; one of our problems is that the new paradigm (85% lab) is leading to misdiagnosis.  Patients should have a comprehensive general examination by a qualified physician. Most patients have seen many.  Physicians frequently order expensive and experimental tests.  Many such tests will not be covered by commercial insurance.  As a rule, if results of a test will not change treatment, don’t have it done.   Some excellent labs participate with insurance plans and have reasonable fee schedules.  Testing for Lyme and coinfections is a necessity.  The Lyme Western Blot, a standard test, should be done at a specialty lab because there is a lot of room for human error with this complex test. And -- because the standard test is inadequate. I like MDL; they do an excellent job with a good test for a reasonable price and a lower rate charged to patients without insurance. Many automated tests can be adequately performed at commercial laboratories.  I order only antibody tests, not DNA/PCR tests. The latter are costly and miss most cases.  I limit initial testing. Here is what I typically order:  MDL: Lyme Western Blot, Anaplasma and Bartonella henselae antibody panels. LabCorp or Quest:  Babesia microti, Babesia duncani called WA1, Ehrlichia, Rickettsia antibody panels. If Babesia is suspected an in-office Giemsa stain may be ordered.

Don't waste limited Lyme dollars on dubious and/or unhelpful lab work.  A little homework might save a lot of money. 
Treatment 
In most cases generic options exist.
Coupons from sources such as GoodRx.com can save tons of money.  Lyme and coinfections are treated with antimicrobial “cocktails.”  There are many alternative options. 
For example, Babesia treatment with Mepron is notoriously expensive.  Much cheaper, alternative options which include herbs e.g. (artemisinin derived from artemisia, worm wood) exist.
There are many ways to treat Lyme and associated infections. There is no clear right way.  There is a best way: the way you can afford.

Even IV antibiotics can be inexpensive.
Generic Rocephin, the most commonly used IV antibiotic is surprisingly inexpensive through generic sources. 

I have discussed primarily saving money on supplements and testing.  The biggest budget buster is treatment.  I will not discuss treatment specifics here. This is where I save my patients the most money. 

  

Wednesday, June 6, 2018

Fibromyalgia, a perspective


Estimates of the number of cases of fibromyalgia – fibro (FMS) in the US are unclear.  Ten percent of the population suffers with chronic, generalized pain.  Half of the patients seen in pain clinics suffer with the FMS – fibromyalgia syndrome.   Estimates for the number of cases in the US range from 4- 6 million but the true number may be in the 10s of millions.  More than one million Americans suffer with CFS, chronic fatigue syndrome which may be indistinguishable from fibromyalgia. 
The annual incidence of Lyme disease is at least 300,000 (CDC figure). A significant percent of patients with acute Lyme develop chronic Lyme. 
The symptoms of fibromyalgia, CFS and Lyme and a few other syndromes are virtually identical.  
Patients with all these syndromes experience a disintegrating quality of life, becoming increasingly disabled, unable to work and to participate in normal life activities. 
Fibromyalgia, once considered controversial -- a “garbage can diagnosis” is now widely accepted as “real” and the medical community extends their apologies to those previously told it is all in your head.  
Lyme disease is where FMS was 1-2 decades ago, but more so. As you have likely learned, doctors are poorly informed about FMS and some of the old prejudice remains – doctors and lay people alike. I am sure you still hear it is not real.  The politics of Lyme keep its truths whirling and swirling and hidden, endlessly churning in the washing machine of Medicine, hidden (writ large).  
The standard line from most doctor is that Lyme doesn’t exist – at least in a form causing chronic fibro-like illness. 
These doctors are poorly informed.  The CDC accepts the notion that some patients, diagnosed with and treated for Lyme disease have persistent FMS-like symptoms. These authorities say this group of folks are suffering with Post Treatment Lyme Disease Syndrome (PTLDS). The premise is that – maybe germs persist, acknowledged grudgingly – scientific facts are stubborn things, but still, the authorities state unequivocally that additional antibiotics are not beneficial and may be harmful. 
The minority view, the one that treatment of persistent germs helps many patients is trampled on by the system. 

Lyme facts.
One half of the patients diagnosed with and treated for chronic Lyme disease have no recollection of a tick bite. 
The ticks that transmit Lyme are increasing in numbers annually as is the percent of ticks infected with tickborne pathogens.  A veritable menagerie of germs: Borrelia species, Babesia, Ehrlichia, Anaplasmosis, Rickettsia, Mycoplasma, Bartonella, viruses – sometimes deadly and others, along with new and emerging strains, substrains and species of tickborne germs have been identified which may cause acute and/or chronic disease. 
Most patient never had/have a bull’s eye rash. Symptoms may begin suddenly or come on gradually. A stress to the immune system, like a car accident, seemingly unrelated, as with FMS may trigger Lyme disease. 
Lyme patients usually have chronic pain – joint and muscle pain which changes locations and intensity over time in an unpredictable manner.  
Lyme patients have impaired sleep, profound fatigue, brain fog and cognitive dysfunction.
Lyme patients frequently experience low grade fevers, night sweats and other associated symptoms suggesting the presence of a troublesome co-infecting tickborne pathogen such as Babesia. 
If you have been diagnosed with fibro and you experience so many symptoms it makes your head spin and if your doctor, no longer listening to your symptoms insists “no disease causes all of those symptoms” and suggests you need to see a psychiatrist -- join the club.  This frustrating or maddening experience is common amongst many with Lyme. 
Community is an important word. The world of patients with fatigue/pain/brain fog is divided into camps and associated support groups. 

I am concerned about medical tribalism, a tendency to adhere to a community world view and to block out competing views and information. 
CFS.  Fibro.  POTS.  Mast cell activation disorders.  Chlamydia pneumonia. EBV. Chronic candidiasis etc.  Beware of a "theory of everything." No one has it all figured out. 
It is likely that a common threads runs through the groups.  I would never claim that Lyme is always the common denominator but it should be strongly considered in many cases. 
Some symptoms commonly seen in Lyme patients are: exhaustion, low grade fevers, feeling feverish without a fever, chills, night sweats, fragmented sleep, unable to stand, unable to exercise, change in vision, photosensitivity, ringing in the ears, sound sensitivity, (associated thyroid disorders), shortness of breath, “air hunger,” racing heart, chest pain, gastrointestinal dysfunction, altered menstruation, other hormone imbalance, urinary dysfunction, headache, migraines, depression, anxiety, mood disorders, irritability, anger, rage, social isolation, depersonalization, poor memory, confusion, ADD-like symptoms, numbness, tingling, weakness, neuropathy and others. 
Lyme patients suffer with depression and many other psychiatric symptoms.  Preexisting depression, anxiety and other psych symptoms may have been there already -- or not --but germs residing in the brain make psych symptoms or cause psych to occur symptoms de novo - never experienced before. 

More Lyme facts.
Patients may not recall a tick bite; tiny ticks, the  size of a poppy seed may be the stealthy culprits; the classical rash rarely appears; Lyme is increasing common in regions of the country where it was once rare; any outdoor activity, not only hiking, camping and gardening or picking berries but also sitting on a picnic blanket at the park place you at increased or high risk; blood tests are unreliable and doctors and clinics are generally ill informed about testing; only a doctor who is familiar with the disease and “believes” in the disease is likely to get the diagnosis right (my opinion and that of many others);  patients are frequently misdiagnosed with depression, CFS and fibromyalgia. 
The existence of fibromyalgia is unimpeachable. But it is a syndrome – a collection or constellation of symptoms reliably found in cohort of patients who share certain characteristics. 
Experts suggest the “pathophysiology,” that which is wrong with the nervous system and brain is understood.  The underlying cause of the syndrome is unknown.  A few FDA approved therapies are available. These meds may help, help a little, do nothing or make symptoms worse. 
If you have Lyme and associated infections specific and helpful therapies may be available. 
These are opinions of the author and should not be used to diagnose or treat any disease or syndrome.

I am available for consultation in my Rockville Maryland office.










Thursday, May 24, 2018

Lyme arthritis and reactive T cells


A friend told me that a new mouse study gave us the answer regarding Lyme arthritis. 
Not quite.  The study was done at the University of Utah (U of U) in mice.  Mice with Lyme arthritis had severe inflammation with thickened synovium. Low levels of spirochetes, referred to as residual bacteria were usually found in the joints. The pathology and immunology revealed the basis for the inflammation was abnormal T cells. This has been described in the past. 
The germ response immune system has two primary legs:  Killer T Cells vs antibodies (behaving badly).  Most autoimmune diseases -- based on current knowledge are due to antibody responses. 
The first leg, the T cell leg is referred to as the innate immune system.  The antibody side -- connected with B cells comprises the acquired immune responses.  
This is the simplest and easiest way to understand the dichotomy.
Patients may go to rheumatologists and report they have fully tested, they don’t have any autoimmune diseases. Rheumatologist only test for things like rheumatoid factor, CCP antibodies, ANA antibodies and a host of other antibodies. Antibodies which attack our healthy tissues. Not poorly acting T cells.  Commercially available tests only measure autoimmune antibodies. 
There likely exist numerous autoimmune disorders for which there is no available test. The rheumatologist should say that based on currently available tests there is no evidence of an autoimmune disease. 
Lyme arthritis is autoimmune without antibodies.  We know the immune system frequently struggles to make Lyme antibodies, explaining some negative tests in Lyme infected individuals.  
There is no test, especially one that would be agreed upon.
The autoimmune, inflammatory reactions were associated with a small number of residual Lyme bacteria.   Small numbers of spirochetes, stubborn and hard to eradicate may cause a lot of inflammation as we have long suspected. 
There are two belief systems here.
One can choose to believe that the T cell response is part of a self-perpetuating process irrespective of residual or germ. In this case, powerful immune suppressing drugs and/or surgical removing of the synovium, the joint lining is the way to go. Not my opinion.
I have found that long term antibiotics, including IV antibiotics work for most patients. 
This is the rub:  Lyme bacteria are the oxygen which feed the fire – the inflammatory T cell medicated response.  Take away the oxygen and the fire goes out -- the joints improve. 
Lyme is in Utah.
Of course, people (most people,) are not mice. You cannot necessarily generalize mice data to people.

Of course in the film “A hitchhiker’s guide to the galaxy” (spoiler) we ultimately learn that white mice run the world and we humans are the guinea pig test subjects. 
You never know.




Tuesday, May 8, 2018

Lyme: my new and improved approach to patient care.


I am excited about my new approach to patient care. 
The EPCDS concept (exhaustion/fatigue, pain and cognitive dysfunction/brain fog has led to a change in philosophy and approach.  
A patient has criteria for CFS, fibromyalgia, POTS, MCAS, Lyme and coinfections. These issues have arisen in the treatment of several patients over the past 2 days. 
First, I address fatigue. (Treating symptoms is not applying a bandaid.  When symptoms improve function improves. When function improves the immune system and other systems work better, facilitating the healing process. These patients are beyond fatigue and exhaustion; getting out of bed is a struggle.  I first look at sleep. I review meds. Many meds contribute to sleep problems and may exacerbate POTS and MCAS.  BP meds can be a problem.  A patient I saw today is taking a BP med Cozaar. Without getting into pharmacology, in some cases Cozaar may contribute to fatigue and exacerbate POTS.  Inderal, a beta blocker taken to prevent migraines may be similarly problematic. Another patient seen today with POTS is taking Abilify for bipolar 2. This med can cause orthostatic hypotension/POTS.  Other options are preferred.  Meds are a problem frequently and must be carefully reviewed. 
Sleep is horrible for these patients. Sleep is fragmented and unrefreshing.  My last patient today falls asleep in front of the TV in the living room at 3 am; wakes up at 6 am to let the dog out; and, it is only then that she goes her bed/bedroom to sleep for another 3 hours. She is nonfunctional without stimulants. Not surprising.  We always have to go back to sleep hygiene and help patients make changes if possible. Changing behavior is not easy. CBT (cognitive behavioral therapy) may help.  Perhaps we fix sleep and the patient will still be exhausted. That’s OK we have still made an important inroad.  There are various medications which may help patient sleep.  I have found that patients with chronic insomnia may only respond to cocktails of meds.  Specific drugs might be considered in each patient.  For example, the sedating muscle relaxer Flexeril has been shown to help patients with tinnitus and may also help fibromyalgia pain. The med may not be tolerated because of a hangover the next day; adjustments can be made.  Patient may only sleep with: Restoril, doxepin, gabapentin and possibly others.  Restoril may help with anxiety. Doxepin may help with mast cell activation. Gabapentin may help with central pain and neuropathic pain.  
We can frequently kill 2 birds with one stone. Sleep, sleep per chance to dream.  When patient report dreams it tells me that REM sleep is present which in some cases is not apparent on sleep studies. Fatigue can certainly be treated with drugs of promote wakefulness like Nuvigil.  Stimulants like Adderall may help.  These drugs are also nootropics and may help improve cognitive dysfunction.  Sleep doctors do not understand the intricacies of such complex patients. 
Pain.  We need to figure out what kind of pain.  The pain may be nociceptive or neuropathic.  The pain may be central.  The pain may be poorly understood as is the case with migraines.  Various pain types are treated differently.  Treating pain and treating sleep may dovetail with each other.  Nociceptive pain, physical pain, is frequently associated with central sensitization – pain amplification.  Patients may have allodynia.  Mild touch causes pain.  These patients do not have a low threshold for pain.  Their pain threshold has been modulated by changes in the central nervous system. An understanding helps the patient and the doctor.   Namenda blocks glutamine and may be effective for fibromyalgia – amplified pain and migraine. Specific drugs target specific types of pain.  Pain drugs can exacerbate or act as a nootropic and relieve brain fog, for example Namenda.  Antidepressant such as amitriptyline and possibly Cymbalta along with anticonvulsants like Neurontin may be helpful.  Other agents such as low-dose naltrexone and medical marijuana are sometimes helpful.  Etc.  Pain is a huge topic and there is much we can do. Unfortunately, many “pain doctors” just hand out prescriptions of Oxys and do their patients a disservice. 
Brain fog I have already touched on.  Treating the underlying illness is important. Still, there are things we can do.  The nootropics, brain drugs mentioned above may be helpful.  Others, for example, magnesium thionate may improve cognition.  Cognitive dysfunction in a young person is something we have to jump on. If neuroborreliosis is the cause intravenous antibiotics may be necessary. In this case, treating the underlying cause takes precedent over managing symptoms. POTS and MCAS can be associated with brain fog and need immediate treatment. We can start MCAS therapy with dietary change and H1, H2 blockers. We may need to prioritize POTS which can be truly disabling. (If MCAS is causing anaphylaxis etc. priorities change). We can juggle many balls if needed. In most cases POTS can be managed well and the treatment is discussed elsewhere.  The treatment of MCAS is discussed elsewhere. Cognitive dysfunction must be carefully evaluated.  If a patient has prominent night sweats, air hunger, bouts of tearfulness and depression babesiosis becomes the first priority. Etc. 
Treatment of chronic infection is addressed from the outset.  However, priorities must be established.  For example, doxycycline alone may be prescribed while sleep and pain and POTS are addressed. Every case is different. 
There is something to be learned from (the best) doctors who treat:  chronic fatigue syndrome, POTS, chronic pain and others. 
What is different in my approach?  I focus on symptoms and function. Patients do much better.  Other specialists may be consulted to cover the bases but sleep specialist, pain specialists and neurologist may not be particularly interested in the care of such patients and label them with: depression – go to the psychiatrist, fibromyalgia – not much can be done or psychosomatic.  The post is intended to give the reader a flavor of the approach and only scratches the surface. These disorders are extremely complex. A lot of thinking and figuring things out is required.

Many disorders may be associated with EPCDS: thyroid disease, adrenal dysfunction, metabolic disorders, genetic disorders, other autoimmune syndromes, cancer, depression, pernicious anemia - B12 deficiency, celiac disease, renal disease, liver disease, heart disease, other chronic infection, sarcoidosis and others. I am sure there are many more. This list is from the top of my head.   The EPCDS syndrome is common. Let's not make assumptions and do our best not to miss anything. 

The information discussed here is evidence based and discussed in peer reviewed journals.

Appointments available. Paradigm Medicine, Rockville MD.

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Tuesday, May 1, 2018

What is POTS? Corecting the record.



What is really going on with POTS?  Is it a neurological disorder, a cardiac disorder?
Probably neither, the answer may lie within the purview of endocrinology?
There is a genetic component. This is clear. For example, patients with hypermobile joints are more likely to develop POTS.
Nobody knows what causes POTS.  Apparently 10 different theories have been proposed.  It is not due to direct dysfunction of sympathetic and parasympathetic nerves.  It is not due to nerve damage such as what you might find in diabetic autonomic neuropathy. 
Autonomic neuropathy should not be confused with dysautonomia.  The two are quite different. 
The prevailing explanation, according to a recent review, primarily relates POTS to dysfunction of the RAS.  This stands for renin angiotensin system.  Receptors for angiotensin may be off kilter. Angiotensin is messenger molecule or hormone known to be associated with the regulation of blood pressure, constriction of blood vessels and retention of salt and water.  This what I remember from physiology.  It turns out that Angiotensin and its associated receptors have wide reaches effects in a wide array of organs and organ systems– including the cardiovascular and nervous systems. 
So, POTS is an endocrine disorder which may or may not be associated with genetic factors.  It has overlap with other specialties including neurology and cardiology.  
Drugs currently prescribed, including Fludrocortisone, DDAVP and Midodrine directly counter aberrant physiology associated with the disorder as viewed through this lens.

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.