Tuesday, November 4, 2008

Pieces of the puzzle

Tough case I have been treated forever. Every symptom in the book. She went to a "famous" LLMD and now she is getting better! He diagnosed Bartonella (clinically): She has already been treated for this in spades. This time she is getting better. RX: Minocin, Zithromax and Rifampin. Is there something special about this combo? It involves two separate protein synthesis inhibitors and an RNA inhibitor. I had used the same stuff and more, not all at the same time. Now she is also using the gluten free diet I recommended (He agreed). What's working?

Does Lyme cause gluten sensitivity or does it just make an underlying gluten issue more problematic? I don't know. The patients don't have celiac disease. But- the tTG IgA level is greater than zero. The antigliadin antibody is greater than zero. The stool antigliadin antibody level is elevated as tested by Enterolab in TX.

The diet frequently makes a surprising difference. It is a difficult diet; it must be strictly adhered to; improvement won't occur for at least 8 weeks.

But I really want to talk about B12 and especially folic acid. The levels can be quite low, especially in sicker patients. The patients do not have pernicious anemia or any obvious GI dysfunction. What are the causes of folate deficiency? Medical texts claim: poor diet, alcoholism, GI maladsorption, drugs like sulfonamides and INH which compete with folate metabolites and "chronic illness." None of these apply. Besides, folic acid levels can remain very low in the face of massive supplementation. Hemolysis is also listed. This is what makes sense to me. Red blood cells may be infected with bacteria like Ehlichia and Bartonella. This in turn leads to an increased turn over of RBCs. Nutrients required in the manufacture of red cells such as B12 and folic acid become "lost?" in the process. The process occurs rather slowly. Overt hemolysis is not observed. If significant hemolysis were to occur then urine dip would show blood (myoglobin) with no RBCs. The serum LDH level, related to lysed RBCs would be elevated. The patient would be anemic. Haptoglobin levels would be increased. The reticulocyte count would be elevated.
I don't see these things (I also don't test for them).
Lots of RBCs with bacteria can be seen on blood smears. Something must be happening to infected RBCs. Babesia should do the same. But Babesia are hard to find on a blood smear. There doesn't seem to be enough organisms to cause the same effect. Perhaps the organisms are infecting progenitor cells in the bone marrow where such effects occur unseen. The idea of bacteria like Borrelia competing for use of these nutrients doesn't make sense. vitamins are trace nutrients needed to complete enzymatic functions. B12 and folate are used for red blood cell synthesis and nervous tissues. Spriochetes and other bacteria do not have these needs. Why would they compete for these nutrients? Lyme- Tick Borne Disease patients frequently have a mix of hematological abnormalities that have not been explained or cataloged: Unexplained anemias, low white cell counts, low neutrophil counts, increased lymphocyte counts, low platelet counts and other abnormalities which seem to vary from patient to patient. If I were to write a book about tick borne disease a whole chapter could be dedicated to hematological abnormalities- if I ever figure them out.

I am rambling a bit, but these is about pieces of the puzzle- see title.
Perhaps things like Bartonella do cause mild flu like symptoms and chills (min-hemolysis?) No. why would cells rupture with synchrony. It should be a slow trickling process. Wait. The same should be true about Babesia. Why then do patients experience drenching sweats and shaking chills. It really isn't like malaria where large numbers of blood parasites can be observed in red cells causing obvious hemolysis. Perhaps it is toxin medicated with a central hypothalamic effect.I have more questions than answers.

I am convinced that B12 and folic acid are key puzzle pieces. Where do they fit?

And where does Bartonella fit and what are the best treatments? Finally, do these two pieces of the puzzle dovetail?


Sarah said...

I was just beginning to look into a gluten, sugar and dairy free diet. Is there a specific gluten free diet you recommend or just google gluten free diet?

Jenny said...

I just found your blog. I live in Indiana and I have been unable to get treatment here despite a positive Western Blot for Lyme. I contracted this in 2000. Do you have any recommendations for LLMDs in Indiana? A good recommendation for a doctor in the Philly area, or Long Beach Island, NJ would work too (my husband has family there). Please e-mail me at sdevenney1@indy.rr.com. I would travel to see you, if that is possible?

dogdoc said...

Food for thought- let me look into it more and mull it around.

dogdoc said...

On folic acid deficiency, I found two quick references on this process with chronic subclinical malaria and chronic babesiosis. Evidently, the slow, chronic hemolysis leads to the deficiency via consumption with RBC replacement. The folic acid deficiency is secondary and not severe enogh to cause macrocytic anemia. The hemolysis is chronic over an extended period of time and may not be apparent (ie no hemoglobinuria or serum parameter changes). Reticulocytosis may not be present due to secondary iron deficiency along with folic acid/
B12. Or that is what the mayo clinic proceedings on human babesiosis describes. A similar discussion was given in context to chronic low grade malaria in endemic countries creating low birth weight babies due to folic acid deficiency.

dogdoc said...

On tough case, many of our chronic bacterial diseases need multiple drugs in combo to respond- monotherapy just isn't effective. Mino/zith and doxy/biaxin have been shown to be synergistic in many different bacterial diseases. Thats why I liked doxy/biaxin followed by doxy/levaquin with different drugs like rifampin added in in cycles. Many other diseases we end up treating with a combo - doxy and rifampin or tms and rifampin will get it but not monotherapies. I think of things like brucellosis, chronic Q fever, mycobacterium avium related disease, tb, - just a few off the top of my head. There are lots of explanations- synergistic drug actions are one. I think supression of drug resistance when long term therapy is needed is probably a key factor- its just a lot harder to develope resistance to three different drugs with different mechanisms of action at one time. I see your point about not trying to treat everything at the same time and that it would be impossible to do that well. However, covering all different things was a sidebar in my thinking. I started with... examples of bacterial disease that need to be treated longterm and use antibiotic monotherapy are rare. I know we aren't thinking we are using monotherapy- but if most of Borrelia is tissue bound after the first cell wall hit, we really are. Also, we have a bunch of other chronic bacteria potentially in the mix with different resistance patterns- M. hominas and M. fermentans for example are resistant to macrolides and doxy resistance is showing up (40% in one study). So we might think we can get the mycoplasma with any macrolide, tetracycline, or floroquinolone... but depends on which one it is. You might just have Levaquin that works. Bartonellas show considerable variability in resistance as well- certainly resistance to bactrim, floroquinalones, biaxin and doxy have been described. Bartonella in the cns is a real issue sometimes- rifampin and minocycline have better cns penetration than most of our bart drugs.
Anyway, this case was exactly the concept I was trying to get you to think about and discuss. I don't have the experience or the answers. But I have a different perspective as an outsider to this, so I'm trying to lend that to the problem hoping it might help stimulate some thinking in new directions.

dogdoc said...

I'm doing these one at a time so I can keep track. I hope a gluten free diet never becomes necessary- with 4 kids and a picky hubby, I don't think I could make it happen. For the case, a gluten challenge could show you what is working. I'm not going to go look up celiac disease again tonight- but doesn't that have an autoimmune basis? Borrelia living in gut wall could trigger off a minor form. Do these patients need to stay glutn free forever, or does the gluten intolerance go away when you finally get the Lyme?

dogdoc said...

On Bartonellas and Babesias and sweats- they don't have the same complex lifecycles as malarias, so I agree I don't think we'd see peroidicity in fevers for the same reasons. Effects of Bartonellas well described in AIDS and independently for some of them. I'll have to examine pathophys of fever at some point, but a number of chronic bacterial diseases can have an undulent or cyclic fever cycle- brucellosis, psittacosis, q-fever, some bartonellas.. just off the top of my head. Low grade on and off fevers may be more nonspecific immune response oriented (ie cytokine) as the organisms come out of intracellular hiding spots and expose immune system to their LPS or whatever they have. I like you have tons of questions, a number of theories in progress, and few answers or absolute evidence. Thinking is good- you cannot figure out what you don't try to figure out. Someone had to discover everything we have- from a current treatment to the electric light bulb.
A complete aside, ever thought that some of the "Babesia" we treat empirically in patients with heavy cns signs might be toxoplasmosis? That would respond to atovaquone or bactrim. It would be something many would carry in cns that would reactivate with suppression of cell mediated immunity. There is a lot of interesting info on aids coinfections and signs and treatments thereof which might help us in Lyme land. Including babesia and bartonella. But once again, I need sleep. So it will have to wait for now.

dogdoc said...

Good morning- you throw out these things and I always have so much to say. I really enjoy the musing and questions and case examples. It is good food for thought.
Combination drug therapy note- many of the combos we use are merely drugs that all have some efficacy for the same organism. Where we don't have a single really great drug, we will use combos of drugs with some activity and acheive organism clearance and reduced reccurrance rates. Or at least do better than we would in monotherapy. Case in point- Babesia treatment. Clindamycin and quinine, mepron and zith. Magic combos? No. Clindamycin and mepron works according to big guy in our group. In Aids, deperate docs keep Babs at bay with clindamycin, biaxin, and doxy used longterm. After they failed the standard therapies.
An aside on Clindamycin- those that are using, what are they killing? That drug is one of the few with good efficacy against the Mycoplasma hominas/fermentans group consistantly. We have toxoplasmosis efficacy. Babesia efficacy. Does IV use create less c. diff? Drug is poorly absorbed so lots leftover directly in the gut- I find references to this.
Imaginine a small research grant from Turn the Corner or the like to lab study patients- you could get a very thorough PCR panel from Clongen looking for all of the things incl zebras and potential opportunists. Instead of guessing, we could get some real data. Conjecture is one thing, but if you test 200 recovered patients, 200 in treatment patients, and 200 treatment naive first presentation patients for example... we might find toxo positive PCR's in a prolonged treatment group indicating a coinfection we haven't addressed. We can treat it and see if they go negative along with clinical response. See that 75 times and we have data. We might see Bart PCR positives on treatment naives but not in in process or recovered groups- ok we have data, we are getting that one fine. Good quality ultrasensitive PCR's for things that like to be in the bloodstream should have decent yield. We can correlate with active titers, cultures, ect. Sigh- in other words, we need a clinical research setting and funding. We need data. The trenches are a hard place to gather data. Mostly due to funding. Would be easy to get patients to get free testing especially this group. Gotta run to my own trenches.

Starlings Preschool said...

An alternative medicine MD told me that a gluten free and juicing diet is alkalinizing, and that his experience has been that Lyme and the co-infections dislike an alkaline environment. Could this be why the symptoms become less pronounced?
However he also said that mycoplasmas and viruses seem to flourish in this environment, so a bit of a catch-22...?

Shawn said...

>I am convinced that B12 and folic acid are key puzzle pieces. Where do they fit?

If you haven't already you should look into methylation (http://www.drmyhill.co.uk/article.cfm?id=401)

B12 (methly) and Folate (5-L-Tetrahydrofolate or FolaPro) are being used to treat CFS and autism by improving damaged methylation which greatly improves patient detox ability.

(glutathione levels and phase II liver conjugation)

Lyme report: Montgomery County, MD said...

I couldn't get link. I am not into alternative medicine. I believe that the "lesion," the infecion, the disease needs to be treated. I believe that the body is smart enought to correct whatever imbalances remain.

Gluten is a different matter. One needs to look at the evolution of humans and other mammalian species.
Wheat was cultivated and never a part of the original hunt and gather diet of our ancestors. Gluten sensitivity is rampant. It is not an allergy. The body produces antibodies directed against the gluten protein. This causes autoimmune dysfunction and wide ranging symptoms. Similarly, we were not designed to drink milk. In addition to lactose intolerance, many of us are allergic to cassein which creates problems for us. Food sensitivity becomes more problematic when we are ill from other causes. It can be the proverbial straw that broke the camel's back. Foods don't detox us persay, but the wrong foods can harm our immune system and normal homeostasis.

The stuff about alkinalizing our bodies sounds like hooey to me. The issue is that some organisms, like Bb, have the adapted ability to exist in an acid environment which occurs in lysosomes in cells. This is a normal cellular mechanism for destruction an elimination of these germs. Some drugs like Biaxin work better when the intracellular environment is make alkaline. This is why Plaquenil is given. The acid base balance of the blood is not affected. Juicing is nonsense as far as I am concerned. There is much greater nutritional value when the fruit or vegetable is consumed whole.

I am skeptical of many things that alternative medical doctors say. So should you be. Caveat Emptor.

AW said...

Regarding post, I think:

(btw does post refer to Bartonella exclusively, or when seen as a co-infection with that patient?)

Minocin: much higher bioavailability than Doxy, so resistance less likely as it can more easily penetrate any thicker lipid layer occurring when resistance builds. (read it in a study on net)

Zithromax: doesn't penetrate brain, cns or eyes (at least not like Doxy/Mino) but will work within the eukaryotic cells unlike the other two that work extracellularly.

I think the Doxy may be less harsh on the liver than Mino (read it on Wikipedia), and Doxy clears Rocky Mountain spotted fever, unlike Mino.

Also, I think the success in your treatments is the high Doxy dosages: 400mg per day: might make it bacteriacidal. Generally, recommended dosages for this drug is 200mg/day, max 300mg/max.

AW said...

... also:

Minocin, Zithromax and Rifampin

is the golden combination for Bartonella (from my research). The key is reaching all the niches in the body. Rif + Mino means 2 drugs in the CNS, and 3 in the rest of the body (with the rest of the body having an intra and extracellur agent: zith + mino respectively)

Also, combination Rif and Doxy is formally recommended for Retinitis. Interesting, that Doxy alone won't get it, even though it reaches the aqueous humor: need something overtly bactericidal.

The eyes are the telltales for the rest of the body. (at least for me)