I have been treated a 30 something year old female for disseminated Lyme and neuroborreliosis for over a year. Most symptoms cleared up with oral meds. The cognitive issues stubbornly refused to budge. This patient interestingly also developed a tremor with features of Parkinson's disease. The Rocephin took a while, but after 8 weeks started showing some very positive effects. Memory, brain fog, word retrieval, cognitive processing speed and tremor all improved. Antibiotic therapy was interrupted because of an unrelated medical problem. She did OK for two weeks; during week 3 off Rocephin she experienced a precipitous decline. All the target symptoms mentioned above rapidly returned. She even developed joint pain which had been absent for months. What happened? I am sure this patient is tired of me thinking out loud every time I see her. Where there is no science, I have to logically figure out the process and make therapy decisions based on working hypotheses.
Obviously we restarted the Rocephin right away- but what else, and why?
I had tried Zithro with the Rocephin earlier in the course but after 6 days it was stopped because of side effects (nausea and vomiting- I think).
Why does the disease reactivate so quickly and so aggressively. It is like I whacked a hornet's nest with a baseball bat. As long as I was batting away the hornets stayed in their nest. As soon as I stopped whacking, they came out madder than Hell.
It can't be a Herx reaction. The meds were removed. A reverse Herx? Of course not.
The spriochetes couldn't have grown and spread that quickly. They are very slow replicators- it takes a long time for them to reproduce and invade new tissues.
Is it due to an inflammatory or autoimmune response? Maybe. It is known that Rocephin has some anti-inflammatory neuroprotective effects. Could removing it quickly cause rebound inflammation and/or autoimmunity? Interesting- doesn't pass the sniff test.
Let me put this phenomenon together with something I recently read. Intracellular bacteria cause minimal pathological effects. That's interesting. Perhaps when the Lyme bacteria convert into L-forms and disappear into the cellular cytoplasm they cause less overt disease/symptoms. This is the opposite of what many Lyme experts have claimed, but maybe they are wrong. Many antibiotics like Biaxin and Zithromax can kill Lyme in both the L-forms and the spirochete forms. One thing we know about Rocephin is that it only kills spirochetes forms, leaving L-forms (intracellular) unscathed.
A picture appeared in my mind. I could imagine Rocephin molecules zipping down the blood stream like speeding cars on the Autobahn. Any Lyme (spirochetes) in the way would be wiped off the road instantly. The Lyme germs would have to respond quickly if they were to survive. Quickly they converted into cysts and L-forms and slipped into cells. The Rocephin would clear the blood stream and its surrounding watershed of cell wall possessing spirochete forms. Lyme in its other forms was safe.
Where does this leave us? Autoimmunity? Rocephin doesn't destroy auto-antibodies. Could there be increased inflammation with cytokines and cellular destruction? This could only occur if Rocephin has a very potent immune suppressing effect like a steroid or immunomodulator like an anti TNF drug. There is nothing in the literature to suggest that Rocephin has such properties. If it had a potent immunomodulating effect then benefits after treatment should occur quickly. Usually, the benefits of Rocephin are not seen for several weeks.
Maybe the signs and symptoms associated with Lyme neroborreliosis are mediated almost entirely by intact- motile spirochetes. Rocephin is strictly clearing these forms from body fluids and tissues.
When you take away the Rocephin what happens? The L-forms and cyst forms (metaphorically) duck there heads out from their hiding places. They put a toe in the water to check the temperature. All clear. Party time for spirochetes. It is the rapid release of spirochetes into tissues and fluids which causes the immune response and clinical disease. That is my best hypothesis. Hopefully you followed the logical chain which got me there.
Wasn't there a study showing that Amoxicillin alone controlled symptoms in chronic Lyme? Yes. Perhaps it has always been about the spirochetes after all. The cysts and L-forms were just put there to make it impossible to kill the bastards (pardon my French).
Getting back to the patient. Not having the luxury of time as I put my thought together in this piece I made an executive decision: I started Rocephin and IV Flagyl. The Flagyl should help one mechanism of escape. Before I take her off Rocephin I will have to close the other door as well. If she couldn't take Zithromax, another anti-L-form therapy will be needed. The possibilites include Biaxin, Doxycyline, Minocycline and Cipro.
Monday, December 15, 2008
Friday, December 12, 2008
Inside the Box
Physicians who treat Lyme disease have been accused of ignoring the proved science and working outside the box. I am at a medical conference for a week. I decided to buy a textbook. This behemoth 1500 page book called: Clinical Immunology- Principals and Practice was published this year- 2008. It appears to be the preeminent text on the subject. It was written for specialists in the field. Leafing through the pages of this tome is enough to give one vertigo. It is full of incredible information written in a language all its own, which is certainly intimidating to a non scientist like myself. Despite this, I have tried to make some sense of its relevance to the disease which is the perpetual obsession of this Blog- Lyme disease, of course.
I will attempt to transfer some relevant information to the reader. I have found that some of my prior comments were erroneous. I hope this will correct the record.
For the most part however, I have found validation of the concepts previously presented to a greater extent than I would have anticipated.
The immune system is magical. The book is broken down into chapters. I suspect that it is impossible to take in the breadth of knowledge presented here in a single glance. The immune system is highly complex, evolved and robust system. Nonetheless: "The vertebrate immune system is a product of eons of evolutionary struggle and their much less rapidly reproducing, and hence less adaptable, hosts." (Rich page 3).
Immune cells have pattern recognition receptors (PPRs). Everything in immunology has annoying acronyms which I sometimes think were put there to keep nosy neophytes, like me out of mix. These receptors on immune cells called T cells are necessary so that the immune system can distinguish things that belong (and not attack them), like your own cells, from things that do not belong like bacterial invaders. I have long suspected that some patients seem to have a natural immunity from developing Lyme disease after infection. Chapter 3, page 48 indicates that certain genes which regulate certain TLRs- Toll like receptors- a type of PPR, confer either susceptibility or resistance to Lyme disease. The incidence of these genetic variations is not mentioned.
The literature about Borrelia burdorgferi, the Lyme germ clearly indicates that it has both intracellular and extracellular forms. Chapter 25 deals with the immunology of intracellular bacteria. On pages 390-391 the authors make it very clear that with rare exception- intracellular bacteria cannot be eradicated from the host. The authors state that the intracellular environment provides a protective niche. Such bacteria are of low toxicity. The extent of disease frequently relates to damage caused by the immune response rather than the infection itself. The primary mode of attack involves the innate immune system rather than the acquired immune system.
One immune cell which "eats" foreign bacteria is called the neutrophil. This is a major actor in the immune system. Page 397, the neutrophils are inactive against intracellular germs, because they are inside cells. Nonetheless, the bacteria may enter the short lived neutrophils and use them as a "Trogan horse." The dying neutrophils containing our buddy (Lyme),as an intracellular germ, is "eaten" by a macrophage, which in a resting state has a long life, low antimicrobial activity and provides a good home for such germs. Many such bacteria live in a phagosome, a structure which would ordinary assist in their elimination, but intracellular bacteria may have the ability to escape into the cytoplasm, the main body of the cell, and enjoy a safe nutrient rich environment. These bacteria have also figured a way to transfer directly from cell to cell without venturing into the dangerous waters of the circulating blood stream. (Page 400). While much is understood about the production of protective antibodies against extracellular bacteria, little is known about (T cell) immunity required to protect against intracellular germs. B cells which produce the protective antibodies for extracellular germs have a minor role here due to the bacteria's "lifestyle." Page 403.
Chapter 26 actually deals with the immune response to spirochetes. So I had to buy the book. It does contain significant factual errors but is still a treasure trove of great information.
The Ixodes tick actively participates in the transmission of Lyme to the host. This is one reason why it is unlikely that other vectors, like mosquitoes transmit the infection. The tick secretes a protein (Salp 15) which inactivates host T cells, helper CD4 cells. Bb latches onto the beneficial protein via the Lyme OspC protein (associated with 23 band on WB), as part of an immune avoidance strategy. (Page 418). Lyme- Bb is a very smart germ. It comes with a daunting array of immune defeating weapons. It has 21 plasmids. These are extra pieces of DNA, not integrated into the nucleus of the organism. It's genomic structure (DNA) is able to recombine with the extra pieces of DNA and change it's structure to thwart the immune resposnes. One surface protein, Ops A is present when the spirochete is living in the tick's gut. It apparently is useful for bacterial attachment in this environment. A tick receptor protein TROSPA is involved. This acronym is frequently encountered. It simply stands for tick receptor outer surface protein A. As soon as mammalian blood, like ours is encountered it reduces OspA by ninety fold and produces OspC- the immune system avoiding protein. A neat trick! (Page 411).
Proteins are not the only structures to which antibodies can be formed. Lipids and carbohydrates can also be immunogenic, cause antibody production. Other spirochetes express lippopolysacharides on their surface. Borrelia is the only member of the spirochete family which does not do this. It does not engage Toll like receptor 4. It is not clear how this effects the overall immune response. It's variable responses to TLRs 2 and 4 is mentioned and this seems to have an effect on limiting immunological responses to Bb. (Page 415)
Lyme has mechanisms to evade the complement system which is a main effector mechanism for the destruction of bacteria. (Page 416)
I seem to have gotten the Th1 and Th2 issue somewhat confused. While the Th1 mechanisms is essential in the control of intracellular infection, The Th2 mechanism is essential for the antibody response of B cells and immunoglobulin switching. The shift towards a Th1 response seen with Lyme infection actually results in more inflammation and less antibody production. (Page 417) Is this because the immune system is confused since it is dealing with both an intracellular and an extracellular infection- my own conjecture.
My last comments relates to statements on page 418. Antibodies against OspB (Band 34) can be thwarted by a mutation of this protein which removes a lysine amino acid.
Lyme can attach to intracellular matrix proteins such as decorin to avoid detection by the immune system. Lyme can acquire host antigens- from our cell, to avoid the immune system. And Lyme can constantly change it's surface proteins giving the immune system a run for its money. Finally, one example is given of how Lyme can recombine genomic DNA and plasmid DNA to alter a specific surface protein antigen.
Believe it or not, this blog has omitted 95% of the arcane details of the immunological mechanisms. I have here tried to offer some simplified information.
This information is right off the pages of the most current text in immunology. Ostensibly it is information with which IDSA members should be intimately familiar with.
Inside the box data would seem to provide biological support for the notion that 14 days of antibiotics would frequently be ineffective against Lyme disease. This contradicts "facts" presented in the 2006 IDSA guidelines.
I will attempt to transfer some relevant information to the reader. I have found that some of my prior comments were erroneous. I hope this will correct the record.
For the most part however, I have found validation of the concepts previously presented to a greater extent than I would have anticipated.
The immune system is magical. The book is broken down into chapters. I suspect that it is impossible to take in the breadth of knowledge presented here in a single glance. The immune system is highly complex, evolved and robust system. Nonetheless: "The vertebrate immune system is a product of eons of evolutionary struggle and their much less rapidly reproducing, and hence less adaptable, hosts." (Rich page 3).
Immune cells have pattern recognition receptors (PPRs). Everything in immunology has annoying acronyms which I sometimes think were put there to keep nosy neophytes, like me out of mix. These receptors on immune cells called T cells are necessary so that the immune system can distinguish things that belong (and not attack them), like your own cells, from things that do not belong like bacterial invaders. I have long suspected that some patients seem to have a natural immunity from developing Lyme disease after infection. Chapter 3, page 48 indicates that certain genes which regulate certain TLRs- Toll like receptors- a type of PPR, confer either susceptibility or resistance to Lyme disease. The incidence of these genetic variations is not mentioned.
The literature about Borrelia burdorgferi, the Lyme germ clearly indicates that it has both intracellular and extracellular forms. Chapter 25 deals with the immunology of intracellular bacteria. On pages 390-391 the authors make it very clear that with rare exception- intracellular bacteria cannot be eradicated from the host. The authors state that the intracellular environment provides a protective niche. Such bacteria are of low toxicity. The extent of disease frequently relates to damage caused by the immune response rather than the infection itself. The primary mode of attack involves the innate immune system rather than the acquired immune system.
One immune cell which "eats" foreign bacteria is called the neutrophil. This is a major actor in the immune system. Page 397, the neutrophils are inactive against intracellular germs, because they are inside cells. Nonetheless, the bacteria may enter the short lived neutrophils and use them as a "Trogan horse." The dying neutrophils containing our buddy (Lyme),as an intracellular germ, is "eaten" by a macrophage, which in a resting state has a long life, low antimicrobial activity and provides a good home for such germs. Many such bacteria live in a phagosome, a structure which would ordinary assist in their elimination, but intracellular bacteria may have the ability to escape into the cytoplasm, the main body of the cell, and enjoy a safe nutrient rich environment. These bacteria have also figured a way to transfer directly from cell to cell without venturing into the dangerous waters of the circulating blood stream. (Page 400). While much is understood about the production of protective antibodies against extracellular bacteria, little is known about (T cell) immunity required to protect against intracellular germs. B cells which produce the protective antibodies for extracellular germs have a minor role here due to the bacteria's "lifestyle." Page 403.
Chapter 26 actually deals with the immune response to spirochetes. So I had to buy the book. It does contain significant factual errors but is still a treasure trove of great information.
The Ixodes tick actively participates in the transmission of Lyme to the host. This is one reason why it is unlikely that other vectors, like mosquitoes transmit the infection. The tick secretes a protein (Salp 15) which inactivates host T cells, helper CD4 cells. Bb latches onto the beneficial protein via the Lyme OspC protein (associated with 23 band on WB), as part of an immune avoidance strategy. (Page 418). Lyme- Bb is a very smart germ. It comes with a daunting array of immune defeating weapons. It has 21 plasmids. These are extra pieces of DNA, not integrated into the nucleus of the organism. It's genomic structure (DNA) is able to recombine with the extra pieces of DNA and change it's structure to thwart the immune resposnes. One surface protein, Ops A is present when the spirochete is living in the tick's gut. It apparently is useful for bacterial attachment in this environment. A tick receptor protein TROSPA is involved. This acronym is frequently encountered. It simply stands for tick receptor outer surface protein A. As soon as mammalian blood, like ours is encountered it reduces OspA by ninety fold and produces OspC- the immune system avoiding protein. A neat trick! (Page 411).
Proteins are not the only structures to which antibodies can be formed. Lipids and carbohydrates can also be immunogenic, cause antibody production. Other spirochetes express lippopolysacharides on their surface. Borrelia is the only member of the spirochete family which does not do this. It does not engage Toll like receptor 4. It is not clear how this effects the overall immune response. It's variable responses to TLRs 2 and 4 is mentioned and this seems to have an effect on limiting immunological responses to Bb. (Page 415)
Lyme has mechanisms to evade the complement system which is a main effector mechanism for the destruction of bacteria. (Page 416)
I seem to have gotten the Th1 and Th2 issue somewhat confused. While the Th1 mechanisms is essential in the control of intracellular infection, The Th2 mechanism is essential for the antibody response of B cells and immunoglobulin switching. The shift towards a Th1 response seen with Lyme infection actually results in more inflammation and less antibody production. (Page 417) Is this because the immune system is confused since it is dealing with both an intracellular and an extracellular infection- my own conjecture.
My last comments relates to statements on page 418. Antibodies against OspB (Band 34) can be thwarted by a mutation of this protein which removes a lysine amino acid.
Lyme can attach to intracellular matrix proteins such as decorin to avoid detection by the immune system. Lyme can acquire host antigens- from our cell, to avoid the immune system. And Lyme can constantly change it's surface proteins giving the immune system a run for its money. Finally, one example is given of how Lyme can recombine genomic DNA and plasmid DNA to alter a specific surface protein antigen.
Believe it or not, this blog has omitted 95% of the arcane details of the immunological mechanisms. I have here tried to offer some simplified information.
This information is right off the pages of the most current text in immunology. Ostensibly it is information with which IDSA members should be intimately familiar with.
Inside the box data would seem to provide biological support for the notion that 14 days of antibiotics would frequently be ineffective against Lyme disease. This contradicts "facts" presented in the 2006 IDSA guidelines.
Monday, December 8, 2008
Lyme and a thrombotic Herxheimer reaction?
A new patient came to see me for chronic Lyme disease. The scenario was classic: history of tick bites, positive lab results and typical symptoms. He was in his late 50's. He had no history of thrombotic or cardiovascular disease. Shortly after starting antibiotic therapy he was admitted to a hospital for a myocardial infarction
(heart attack). During this hospital stay he also develop a blood clot in a leg which broke off and lodged in a lung (pulmonary embolism).
He was tested for medical causes of increased blood clotting- hypercoaguable state.
There are many genetic causes. There are also acquired causes. He tested positive for "lupus circulating anticoagulant"- this an acquired cause with genetic predisposition. His hematologist told him he may have lupus.
Lupus is a clinical disorder with a complex of symptoms and findings. He clearly does not have lupus. Circulating lupus anticoagulant is associated with autoimmune disease such as systemic lupus and other similar disorders. Infection is also a potential cause of this clotting disorder. Lyme is associated with increased autoimmunity as well as increased coagulation due to pro-inflammatory cytokine responses.
Generally antibiotics have anti-inflammatory effects. This is not always the case. For example, treatment recommendations for ulcerative colitis- an inflammatory bowel disorder includes the antibiotics Cipro and Flagyl. On the other hand, the use of antibiotics with the other inflammatory bowel disease- Crohn's disease may provoke a flare- (A pro-inflammatory effect?)
These pro-inflammatory and anti-inflammatory effects are hard to predict. There is the issue of timing and a variable impact on even similar autoimmune disorders. There are many influences which may tip the balance of the immune response.
Herxheimer responses are associated with a pro-inflammatory response. It is necessary to rev up the immune system before treatment can be successful.
It is well established that these effects can be quite negative in the short run. They generally cause no permanent impairments. It is the storm before the quiet.
I must entertain the possibility that this patent's heart attack and pulmonary embolism were directly related to an unexpected Herx. An autoimmune process was triggered which increased blood clotting leading to these two events. Thankfully the patient is no worse for the wear.
I would rather chalk it up to a coincidence. Unfortunately (for me), I don't believe in coincidences.
(heart attack). During this hospital stay he also develop a blood clot in a leg which broke off and lodged in a lung (pulmonary embolism).
He was tested for medical causes of increased blood clotting- hypercoaguable state.
There are many genetic causes. There are also acquired causes. He tested positive for "lupus circulating anticoagulant"- this an acquired cause with genetic predisposition. His hematologist told him he may have lupus.
Lupus is a clinical disorder with a complex of symptoms and findings. He clearly does not have lupus. Circulating lupus anticoagulant is associated with autoimmune disease such as systemic lupus and other similar disorders. Infection is also a potential cause of this clotting disorder. Lyme is associated with increased autoimmunity as well as increased coagulation due to pro-inflammatory cytokine responses.
Generally antibiotics have anti-inflammatory effects. This is not always the case. For example, treatment recommendations for ulcerative colitis- an inflammatory bowel disorder includes the antibiotics Cipro and Flagyl. On the other hand, the use of antibiotics with the other inflammatory bowel disease- Crohn's disease may provoke a flare- (A pro-inflammatory effect?)
These pro-inflammatory and anti-inflammatory effects are hard to predict. There is the issue of timing and a variable impact on even similar autoimmune disorders. There are many influences which may tip the balance of the immune response.
Herxheimer responses are associated with a pro-inflammatory response. It is necessary to rev up the immune system before treatment can be successful.
It is well established that these effects can be quite negative in the short run. They generally cause no permanent impairments. It is the storm before the quiet.
I must entertain the possibility that this patent's heart attack and pulmonary embolism were directly related to an unexpected Herx. An autoimmune process was triggered which increased blood clotting leading to these two events. Thankfully the patient is no worse for the wear.
I would rather chalk it up to a coincidence. Unfortunately (for me), I don't believe in coincidences.
Thursday, December 4, 2008
Novel combinations of Lyme medications
It is hard to predict how patients will respond to antibiotic combinations. As I review records of patients that I have treated over several years, I have noted that Doxycyline in combination with Plaquenil had been very effective. I was using this before I became more "Lyme literate" and discovered that Burrascano and Donta claimed that Plaquenil was only effective with macrolides. I saw a patient yesterday who has had chronic Lyme disease. She presented mostly with fatigue, brain fog and muscle/joint pain. She was in the past diagnosed by a rheumatologist with a mixed connective tissue disorder. She had borderline auto-antibody immune indicators-low level RF and ANA. She was treated with prednisone and methotrexate with a poor response. Her condition devolved into what was called fibromyalgia before I began treating her. I have found that quinolones, particularly Cipro can be very effective for fibromyalgia symptoms. In this case I used Cipro in combination with Amoxicillin. She had a good response. She became 60% better. I then added Flagyl. She "loved" Flagyl. She felt much better. She was perhaps 80% better. This process transpired over about 18 months. She would try off antibiotics and relapses would occur.(Other antibiotics were used but this combo was the most effective consistently) Two months ago the Flagyl wasn't working as well. She was back down to the 60% better level. I tried something different: Amoxil- Cipro(250mg twice daily) and Plaquenil. The Flagyl was stopped. She returned for follow up. Plaquenil was magic. For the first time in decades- she was 100% better. Perhaps this relates to her tendency for autoimmune responses. Nonetheless, this is an example of how experimentation with atypical combinations of Lyme agents can pay off.
Chronic Lyme and poor IgG response
Chronic Lyme patients frequenly have a poor antibody response as seen on a Western Blot. Frequently there is a predominance of IgM bands. IgG responses may be sparse or absent. Patients who test positive according to the national CDC surveillance criteria usually do so by meeting the IgM criteria. This is still seen in patients who have had Lyme disease for many years. IgM antibodies are the "quick and dirty" response of B lyphocyte antibody production. These are churned out early after antigen (Lyme protein) presenation to helper T cells. IgM antibodies are not particularly effective. They are larger and do not bind all that well to target antigen proteins. These antibodies may show less specificity and be more like to induce autoimmune reactions due to molecular mimicry. The same B cells or plasma cells that produce IgM antibodies (immunoglobulins) also produce IgG antibodies. A molecular switch is pulled after the initial period of infection. IgM production is shut down. The B cells or plasma cells now kick into gear manufacturing IgG antibodies. These smaller, more precise antibodies bind better to the target proteins. It takes time for the "antibody factory" to gear up and make these preferred antibodies. This is why the Immune system provides this two punch approach to dealing with germs. These (IgG) antibodies are typically associated with immunity to a particular disease. This is for example the response one would expect to see after an effective vaccine.
With this in mind, I have started paying attention to the balance sheet, as it were. I compare the IgM and IgG responses seen in various patients. Patients with a predominat IgG response fare much better in general. For example, I saw a patient yesterday who had presented with severe symptoms of longstanding disseminated Lyme disease about 18 months ago. He responded remarkably well to treatment, despite an advanced age of 76. Therapy was stopped after one year. He experienced a prompt therapeutic response followed by full remission. Six months later he reports
robust health. I glanced at his Western Blot. He had 7 IgG bands and zero IgM bands. His immune responses to Lyme were appropriate. Unfortunately this is the exception not the rule.
Patients with predominant IgM responses generally do not respond nearly as well to therapy. Therapy is required for a much longer period of time. These patients require more creative combination therapies and attention to co-infection.
It is not essentially a host response issue. Patients make normal IgG antibodies when exposed to other infectious diseases. There is something unique about Lyme disease. Somehow it short circuits the switching of IgM and IgG antibodies.
There is a subset of patients whose immune systems apparently go beserk when exposed to Lyme. Dr. Kilani reports Western Blot strips in which the entire strip, IgG and IgM turn black. He suspects these patients may have autoimmune hyper-reactivity. I have no experience to support or confirm this observation. I will keep a look out.
With this in mind, I have started paying attention to the balance sheet, as it were. I compare the IgM and IgG responses seen in various patients. Patients with a predominat IgG response fare much better in general. For example, I saw a patient yesterday who had presented with severe symptoms of longstanding disseminated Lyme disease about 18 months ago. He responded remarkably well to treatment, despite an advanced age of 76. Therapy was stopped after one year. He experienced a prompt therapeutic response followed by full remission. Six months later he reports
robust health. I glanced at his Western Blot. He had 7 IgG bands and zero IgM bands. His immune responses to Lyme were appropriate. Unfortunately this is the exception not the rule.
Patients with predominant IgM responses generally do not respond nearly as well to therapy. Therapy is required for a much longer period of time. These patients require more creative combination therapies and attention to co-infection.
It is not essentially a host response issue. Patients make normal IgG antibodies when exposed to other infectious diseases. There is something unique about Lyme disease. Somehow it short circuits the switching of IgM and IgG antibodies.
There is a subset of patients whose immune systems apparently go beserk when exposed to Lyme. Dr. Kilani reports Western Blot strips in which the entire strip, IgG and IgM turn black. He suspects these patients may have autoimmune hyper-reactivity. I have no experience to support or confirm this observation. I will keep a look out.
Tuesday, December 2, 2008
Babesia Herxheimer reactions?
I haven't seen anything written about this phenomenon. When I learned about the Jarish Herxheimer reaction the literature indicated that it was limited to an exclusive club of microbes. It was associated with syphilis, leptospirosis, relapsing fever, rate bite fever, Lyme disease, anthrax and very few other infections. The reaction was related to two things: 1) the infection was disseminated and 2) the germ antigens, released when the germ was killed, caused an exaggerated immunological response associated with an unusually exuberant cytokine response.
Now the term Herxheimer reaction seems to be associated with a whole host of other infections. My clinical experience confirms that when patients are placed on anti-Babesia therapy they experience massive Herxheimer reactions. The sweating increases. Pain and fatigue increase. Even cognitive dysfunction- brain fog and memory loss increases substantially. These reactions can be much more intense than those associated with initial anti-Borrelia (Lyme) therapies.
Let's take a look. We are told that Babesia is associated with specific symptoms. These include: recurrent chills and sweats- the sweats are frequently drenching, neck pain and air hunger. We are told that it is a clinical diagnosis and that lab tests are inaccurate and cannot be relied upon. Babesia is a malaria like parasite, and resides in red blood cells. Malaria is associated with a parasitic infection of the red blood cells associated with hemolysis, rupture of the red blood cells. The afflicted individuals experience sever chills, sweats and fevers and are frequently very ill. It is diagnosed when the parasites are observed in the red cells under the microscope. The blood smears for Babesia are generally negative. We are told it is because the parasites infest a very small percent of red blood cells.
PCR tests, antibody tests and a wide variety of special diagnostic assays searching out confirmation of Babesia are usually negative. There is no evidence of ruptured red blood cells. Occasionally antibodies for a Babesia strain may be present. This indicates exposure to the organism- not active infection. If IgM antibodies are present active infection is more likely. For the most part there is no confirmation whatsoever. The standard wisdom (mainstream medicine) is that Babesia is generally a self limited infection which is cleared by the immune system.
Let me play Devil's advocate. Lyme can cause sweats, flu symptoms, breathing problems and pains of all sorts. The same symptoms frequently clear when only Lyme therapy is given. Is Babesia really present at all? Or is a case of the emperor without any clothes. If we have invisible "Bartonella like organisms," perhaps we should have "Babesia like organisms." or Babesia syndrome associated with Lyme disease. Perhaps the anti-Babesia therapy is really killing a form of Lyme via some unsuspected mechanism. If the Babesia organisms are rare and hard to find then why does killing them cause a Herx reaction? Is there any precedent for the treatment of parasitic (piroplastic) infection associated with a described Herxheimer response?
I believe it is important to question all the assumptions of what has now become the new orthodoxy of Lyme literate dogma.
Let's put this argument aside. When I treat patients for Babesia they do have dramatic Herx reactions. The reactions can be disabling and cause serious setbacks.
Patients may Herx with a single dose of Artemesia or Malarone. Frequently Mepron cannot be tolerated due to excessive Herxing. The dose of anti-Babesia therapy must be gradually ramped up based on individual tolerances. One can start with Artemesia/Artemesin or Malarone/Mepron. When the second agent is added it must be done gradually. The clinical response is that the sweating and associated symptoms increase for a period of time and then gradually wane and disappear. It works.
For now I do believe in chronic, persistent Babesiosis, despite the lack of supporting evidence, as part of the Lyme disease complex; but my mind is open to other possibilities.
Now the term Herxheimer reaction seems to be associated with a whole host of other infections. My clinical experience confirms that when patients are placed on anti-Babesia therapy they experience massive Herxheimer reactions. The sweating increases. Pain and fatigue increase. Even cognitive dysfunction- brain fog and memory loss increases substantially. These reactions can be much more intense than those associated with initial anti-Borrelia (Lyme) therapies.
Let's take a look. We are told that Babesia is associated with specific symptoms. These include: recurrent chills and sweats- the sweats are frequently drenching, neck pain and air hunger. We are told that it is a clinical diagnosis and that lab tests are inaccurate and cannot be relied upon. Babesia is a malaria like parasite, and resides in red blood cells. Malaria is associated with a parasitic infection of the red blood cells associated with hemolysis, rupture of the red blood cells. The afflicted individuals experience sever chills, sweats and fevers and are frequently very ill. It is diagnosed when the parasites are observed in the red cells under the microscope. The blood smears for Babesia are generally negative. We are told it is because the parasites infest a very small percent of red blood cells.
PCR tests, antibody tests and a wide variety of special diagnostic assays searching out confirmation of Babesia are usually negative. There is no evidence of ruptured red blood cells. Occasionally antibodies for a Babesia strain may be present. This indicates exposure to the organism- not active infection. If IgM antibodies are present active infection is more likely. For the most part there is no confirmation whatsoever. The standard wisdom (mainstream medicine) is that Babesia is generally a self limited infection which is cleared by the immune system.
Let me play Devil's advocate. Lyme can cause sweats, flu symptoms, breathing problems and pains of all sorts. The same symptoms frequently clear when only Lyme therapy is given. Is Babesia really present at all? Or is a case of the emperor without any clothes. If we have invisible "Bartonella like organisms," perhaps we should have "Babesia like organisms." or Babesia syndrome associated with Lyme disease. Perhaps the anti-Babesia therapy is really killing a form of Lyme via some unsuspected mechanism. If the Babesia organisms are rare and hard to find then why does killing them cause a Herx reaction? Is there any precedent for the treatment of parasitic (piroplastic) infection associated with a described Herxheimer response?
I believe it is important to question all the assumptions of what has now become the new orthodoxy of Lyme literate dogma.
Let's put this argument aside. When I treat patients for Babesia they do have dramatic Herx reactions. The reactions can be disabling and cause serious setbacks.
Patients may Herx with a single dose of Artemesia or Malarone. Frequently Mepron cannot be tolerated due to excessive Herxing. The dose of anti-Babesia therapy must be gradually ramped up based on individual tolerances. One can start with Artemesia/Artemesin or Malarone/Mepron. When the second agent is added it must be done gradually. The clinical response is that the sweating and associated symptoms increase for a period of time and then gradually wane and disappear. It works.
For now I do believe in chronic, persistent Babesiosis, despite the lack of supporting evidence, as part of the Lyme disease complex; but my mind is open to other possibilities.
Monday, December 1, 2008
Lyme: Zebra or Horse?
A new patient waited in exam room one. I fumbled into the room juggling the new chart and my requisite morning coffee. We introduced ourselves. Her serious demeanor dissolved into an ambivalent, nervous smile as I settled in my chair. She found me through a Lyme forum on the net. Several months of symptoms troubled her. Admittedly the symptoms were not severe, but they had persisted for several months. She had sought answers from her primary doctor, her ENT and a neurologist. No one had an answer. She googled her symptoms and did her cyber research. The same diagnoses kept popping up: Lyme and MS. The neurologist at her behest had ordered a second Lyme test- the definitive one- the Western blot. A phone call reassured her that it DEFINITELY was not Lyme- the test proved this. She wasn't convinced. She found me.
Now I was supposed to settle the matter. Always healthy in the past, this attractive young mother of 4 was now saddled with- dizzy spells, tingling in her fingers, tremors, a loss of balance and mild joint pains. She had no real fatigue or cognitive issues. Nonetheless the symptoms were bothersome. After much research and ambivalent contemplation she made a decision- she sat on the exam table across from me.
As always I asked questions, probing her history and related symptoms. I did my exam, the careful neurological exam which has become the cornerstone of my Lyme disease evaluation. I look for subtleties that would be called "WNL" in most exams. This means within normal limits- As interns we claimed it meant "We Never Look." As usual, I found various abnormalities. There was evidence of: cranial nerve dysfunction, upper motor neuron disease, peripheral neuropathy and a subtle tremor suggesting mild Parkinsonian features. I ordered the usually battery of tests to help confirm the diagnosis I suspected at this point.
She didn't know anything about Lyme she said. In reality she was already steeped in the world of Lyme land, with its own language and complex iconoclastic paradigms.
She asked THE question. "Do I always diagnose Lyme disease in patients like her. Do the labs always point me in that direction?"
She had already been to three doctors. I had spent over 20 years considering all the other diagnoses, the usual suspects, until I wandered down the rabbit hole into Lyme land. Here's the odd twist. As a physician I was taught that one must consider common disorders first when making a diagnosis. If a patient had a cough it was likely due to bronchitis, asthma or pneumonia. It probably wasn't Wegeners granulomatosis. Odd ball diagnosis were called Zebras. This came from the oft told metaphor: If you hear hoof beats in Central Park think Horses- not Zebras.
As far as the rest of the Medical world is concerned the diagnosis of Lyme disease as an explanation for her symptoms would clearly constitute a Zebra. And now, in the new reality I inhabit, any diagnosis other than Lyme (think common first) could only be categorized as a Zebra.
Now I was supposed to settle the matter. Always healthy in the past, this attractive young mother of 4 was now saddled with- dizzy spells, tingling in her fingers, tremors, a loss of balance and mild joint pains. She had no real fatigue or cognitive issues. Nonetheless the symptoms were bothersome. After much research and ambivalent contemplation she made a decision- she sat on the exam table across from me.
As always I asked questions, probing her history and related symptoms. I did my exam, the careful neurological exam which has become the cornerstone of my Lyme disease evaluation. I look for subtleties that would be called "WNL" in most exams. This means within normal limits- As interns we claimed it meant "We Never Look." As usual, I found various abnormalities. There was evidence of: cranial nerve dysfunction, upper motor neuron disease, peripheral neuropathy and a subtle tremor suggesting mild Parkinsonian features. I ordered the usually battery of tests to help confirm the diagnosis I suspected at this point.
She didn't know anything about Lyme she said. In reality she was already steeped in the world of Lyme land, with its own language and complex iconoclastic paradigms.
She asked THE question. "Do I always diagnose Lyme disease in patients like her. Do the labs always point me in that direction?"
She had already been to three doctors. I had spent over 20 years considering all the other diagnoses, the usual suspects, until I wandered down the rabbit hole into Lyme land. Here's the odd twist. As a physician I was taught that one must consider common disorders first when making a diagnosis. If a patient had a cough it was likely due to bronchitis, asthma or pneumonia. It probably wasn't Wegeners granulomatosis. Odd ball diagnosis were called Zebras. This came from the oft told metaphor: If you hear hoof beats in Central Park think Horses- not Zebras.
As far as the rest of the Medical world is concerned the diagnosis of Lyme disease as an explanation for her symptoms would clearly constitute a Zebra. And now, in the new reality I inhabit, any diagnosis other than Lyme (think common first) could only be categorized as a Zebra.
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