Tuesday, December 16, 2008

Plaquenil alone?

A 70 year old male patient was diagnosed with Lyme disease 6 or 7 months ago. He reported a history of tick bite and rash in 2002. He received a short course of antibiotics at that time. When I saw him initially he complained of knee pain and swelling, fatigue, generalized arthralgia (joint pain), numbness and tingling and an irregular heart beat. He was seropositive by Western Blot. He was treated with Amoxil, Biaxin and Plaquenil. After two weeks he reported that the antibiotics were causing nightmares and insomnia. He attributed this to Biaxin. The regimen was changed to Amoxil and Minocin. The knee pain and other symptoms rapidly improved over the next two weeks. Then one week later he complained of confusion and unsteadiness. I diagnosed a "brain Herx." I added Plaquenil back, as well as Welchol, presumptively to remove "neurotoxins." I also reduced the dose of Amoxicillin and Minocin. He continued to improve rapidly once more with a cessation of neurocognitive symptoms. However three weeks later he had a bout of gastroenteritis and the antibiotics were held for a few days. Like many of my patients, he was "lost to follow up" for a couple of months. The patient stopped the Amoxil and Plaquenil and took only Minocin, on his own which he increased back to the full dose, without consulting with me. He returned to my office after a total of 4 months of treatment stating that he was 85% better. I scolding him for non-compliance: it didn't do any good. I added Flagyl only 250mg twice daily. When he returned a month later he told me that the Flagyl had made him "spacey" so he stopped it after a few days. He was feeling close to normal. Call me! I tried him on Zithromax and Plaquenil about 6 weeks ago. I made the change because he was also complaining of sinusitis. It seemed that there may have been problems with Amoxil, Biaxin and other antibiotics. He came back to see me today. He felt perfectly fine: back to normal for the past four weeks. And by the way, he had only taken the Zithromax for a few days because it upset his stomach. Everything was fine he was taking only Plaquenil. To review: Brain symptoms, joint pain, neuropathy symptoms, palpitations and fatigue were gone. He Had been treated for a little more than 6 months. This was the best he had felt in years. So far the symptoms were not returning.

This is not my typical patient. Most actually do what I say; they take medicines as prescribed and return for follow up as instructed. In his defense, his wife had major surgery during this time frame; personal mitigating circumstances interfered with our process.

When patients go into remission it is unlikely that the Lyme bacteria have been eliminated. Let me insert an additional piece of information. This patient had a fairly strong IgG response on the standard Western Blot: 4/10 bands were reactive.

Patients with IgG responses may have some blocking immunity for intact spirochetes.
Per the immunology text book: symptoms related to intracellular infection relate mostly to the immunologic response to the infection- not the presence of the germs in and of themselves.

One could postulate that 1) The patient had a blocking IgG response to keep the spirochetes in check and 2) The immunomodulating effects of Plaquenil were keeping the lid on a potentially toxic T cell response to the intracellular component. The fact that he responded so favorably with primarily Minocin supports the hypothesis that the main issue in his case related to intracellular disease.

It was clear that cystic forms of the bacteria were still present. However, if they converted to spirochetes or L-forms the above two mechanisms would be in place to keep the disease quiescent.

I decided to leave him on just Plaquenil for the time being to see if this would foster a long term clinical remission. Sure, it doesn't follow any standard paradigm. But I can't argue with success.

19 comments:

dogdoc said...

Interesting case- they really are all different. Did the minocin knock back the Lyme and the plaq knock back the remaining immune rection to the dead stuff in the tissues maybe?

Lyme report: Montgomery County, MD said...

No. The live stuff.
Intracellular germs don't make you sick unless you immune system mucks with them: Cell mediated responses, NKTs, inflammatory cytokines.
It is a case of "let sleeping dogs lay" (or is it lie?)

dogdoc said...

Didn't think we were entirely intracellular. New cystic data showed extracellular persistance in tissues. Certainly intracellular data as well. Extracellular cystic forms would be reactive- yes? Intracellular forms not so.

gale said...
This comment has been removed by the author.
Lyme report: Montgomery County, MD said...

The cyst issue is not clear cut.

Some patients have resolution of all symptoms without Flagyl.

Some have persistent cognitive issues and even joint pains which resolve with Flagyl.

Some patients are doing great until you add Flagyl at which time they Herx and have increased symptoms, including cognitive ones.

Cystic Lyme does not induce effector immune responses to the extent that sprirochetes and L-forms do. Whether they are problematic is probably determined by individual immune responses.

The theory is that you can't cure anyone without Flagyl or Tindamax to disrupt cysts. Unfortunately due to intracellular persistence I don't think host "sterilization" is doable. Remission is the goal.
The balance between germ and host defenses must be balanced. There are clearly different ways of getting there.

5withLyme-PA said...

"Let sleeping dogs lie" -- am interested in your thoughts on treating more benign cases. Our whole family was very sick with Lyme- me being the sickest. DX: Lyme, Babs, Bart, Ehrli, Myco, Chlamy Pneu, HHV-6, EBV, supported by lab results in almost all of us. Husband wasn't as sick but had been experiencing a slow progression continuing after I started treatment. Fatigue, sleep issues, episodic depression and fogginess, new on-set erectile dysfunction (at the time he was 39), periodic headaches, etc., but never debilitating. He started trtment - and herxed immediately, and continued to on certain protocols. However, many things started to get much worse - his thyroid got out of whack, and increasing psych symptoms, so much so that as he looks back he sees a trend of deterioration rather than improvment "from the abx". He has tried to go off abx, only to find symptoms come back (coinfections, Babesia first). What are the possibilities here? Am interested in your thoughts on the less symptomatic patient and explanations for deterioration after abx initiation/ongoing trtmt? like- progression of immunosuppression allowing coinfections to become an issue, lysing cysts and allowing dissemination of the disease, etc. I know he feels that he might have been better off to have never started abx treatment. I am sure there are others out there with similiar situations, and docs must struggle with this all the time... help! thx - Family of 5 with Lyme (the other 4 of us are 85-95% better).

dogdoc said...

Lymemd- I agree with sterilization being impossible. We can't do that in any disease with any drug- we just knock stuff down enough for host immune system to get it back under control. Also if you look at the in-vitro concentrations required for cyst disruption at body temp (the lone study we have) and compare to the average acheivable serum peak concentration in metronidazole, we are not acheiving that most likely. Also there is much evidence that a balance of host immune response is required- limit Th1 and the spirochetes overwhelm, limit Th2 and the erosive, destructive responses overwhelm. I think you are very right about a balance being required. I have not seen much evidence relating the host reaction or signs to the form- cyst, l, extracellular, ect Here I think is a matter of conjecture as to what is doing what. Even what we assume kills different forms is really conjecture- we really do not have the in-vivo proof of what is going on yet.

Staris said...

Journal of Neuroinflammation (may have already seen):
http://www.jneuroinflammation.com/content/5/1/40

Valcyte Study:
http://www.vicd.info/clinicaltrial.html

Lyme Induced Parkinsonism:
http://arpa.allenpress.com/arpaonline/?request=get-document&doi=10.1043%2F1543-2165(2003)127%3C1204:LPANCS%3E2.0.CO%3B2

Staris said...

Meant to lead in to my previous comment - as discussed at appt today.

Lyme report: Montgomery County, MD said...

Patients who get worse with treatment, and then become dependent on treatment because cessation causes increased symptoms is an issue worth discussing.

Treatment may be causing excess activation of the immune responses. Related issues may include autoimmunity, excessive innate immune responses with complement activation, elevated cytokines in a self perpetuating cycle. It is interesting that innate immune responses can trigger autoimmune processes. This a feature which is shared with acquired immune responses.

If what you are doing isn't working you must try other approaches: rule of holes- when in a hole, the first thing you stop is digging.

If IV antibiotics have not been used they should be considered. Long courses of Rocephin can be very helpful.

Steroids, when used concomitantly with antibiotics, may dampen the immune response without harm, when used judiciously. Other immune modulators should be considered. Certainly Plaquenil is the most benign. If feasible, IgIV would theoretically be helpful by "cleaing up" autoantibodies. Your physician may need to consider more powerful immune modulating drugs such as methotrexate- if all else fails. This should be done in concert with a Lyme literate rheumatologist.

In this case the thyroid problem is powerful evidence promoting the autoimmune hypothesis.

These are the tough cases which require a great deal of thought and creativity. If one physician is unable to help you may consider other opinions.

There may be differing opinions and approaches related to the plethora of co-infections which you have been told are part of the process.

Karen said...

In our support group in Arizona, we had a few people who were going to Colorado for treatment. Prior attempts at treatment made these already frail people worse. While using the low dose method by the physician there, they not only tolerated treatment but improved for the first time. For one person it took two years, but she is now having more good days than bad.

Did lowering the dose, decrease the immune response?

Lyme report: Montgomery County, MD said...

Yes.

Approach A: Gradually ramp up- don't over-activate immune responses.
Problem: very slow. I don't have the patience and neither do most of my patients. Waiting 2 years to feel better would be excruciatingly difficult.

Approach B: Bite the bullet. Get worse for a while. If needed damp down immune responses- Plaquenil, vitamin D, Steroids or immune modulators. The improvements will generally be seen in less than a month.

Also: change antibiotic regimens. It can be surprising how patients will respond.

Today I saw a non-responder to even Rocephin. Posivitve Lyme serology. No bacteria on smear. PCR negative Babesia and Bartonell.

I tried: Levaquin, Minocin and Rifampin. This is the first time he has seen real improvement in a year. The response was dramatic. All the standard fare had failed.
Go figure. ? resistant strain of Bb.

Per recent posts by my readers I have the following thought: Massive vit D will lower inflammation by tilting towards a Th2 response. Ultimately Th1 responses don't really eliminate the intracellular forms. This might be a reasonable strategy for antibiotic hyper-stimulation of immunity.

dogdoc said...

Resistant strain perhaps. Also 3 best CNS penetration abs (with other than pure spirochete effect) used together. Sounds like a good call. I love the when in a hole, first of all stop digging. A truism with this stuff for sure.

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