AUTOIMMUNE DISEASES CAUSED BY AN INFECTION?

[DougEE]

https://www.youtube.com/watch?v=h_j60JBZlnY

The posted comments under the video are interesting and it seems that others find his presentation as off-putting.

 

[Konstantin]

I'm eating beets my whole life. Last year I noticed that I started to urinate red. It never happened to me before. People here believe that beets juice is cure for many blood condition's. My mother used to make beets juice with some carrots and lemon juice. It was very tasty and probably very helpful. I'll try some more beets.

 

[Gaby]

Last day on allopurinol The adjusted dose was okay. It made me very tired and sometimes nauseated, but no vomit nor diarrhea.

Found this update from last year by Richard Horowitz. It summarizes the research he shares on his videos/talks:

Antibiotics found effective in schizophrenia

http://www.sott.net/article/300497-Antibiotics-found-effective-in-schizophrenia

Tetracyclines help treat psychosis as well as tick-borne disorders.

A controlled clinical trial was just published in the psychiatric literature, showing that minocycline is effective in treating negative symptoms in early phase schizophrenia. A prior pilot study, published in 2010 in the Journal of Clinical Psychiatry, also showed that minocycline was effective in schizophrenia, helping executive functioning such as working memory. The authors postulate that the mechanism of action of minocycline would include affecting glutamate pathways in the central nervous system, blocking nitric oxide-induced neurotoxicity, or inhibiting microglial activation in the brain, causing inflammation. All of these are reasonable potential mechanisms of action. Neither author discusses the obvious fact however that minocycline is a tetracycline antibiotic and that it may be treating an occult infection. Have infections ever been reported to cause schizophrenia?

Lyme disease causes a wide range of psychiatric manifestations. Published research has shown a higher prevalence of antibodies to Borrelia burgdorferi in psychiatric patients than in healthy subjects. There is also a known geographic correlation of schizophrenia with ticks and tick-borne encephalitis, with peer reviewed literature showing an association of Lyme disease with schizophrenia. Other tick-borne infections, such as Bartonella (cat scratch disease) have also been reported to cause neurological and neurocognitive dysfunction, as well as causing agitation, panic disorder and treatment resistant depression. Minocycline, as well as other tetracycline antibiotics like doxycycline, are well known treatments for neurological manifestations of Lyme disease and associated co-infections like Bartonella. It is therefore plausible that a certain number of cases of severe psychiatric presentations are due to underlying infections, especially since Lyme disease is the number one spreading vector borne infection in the world.

I have seen several patients who came to my medical clinic with a diagnosis of schizophrenia, on anti-psychotic medications like Risperdal. Upon further testing, their Western Blots returned positive for exposure to Borrelia burgdorferi, the agent of Lyme disease. They were given doxycycline (a similar tetracycline antibiotic), and their psychotic symptoms and cognition improved significantly. Working with their psychiatrist, we were able to reduce, and in some cases eliminate, all of their antipsychotic medication. They remained clinically stable as long as they remained on antibiotics. Their psychiatric symptoms returned once they were no longer being treated for Lyme and associated tick-borne disorders, as these organisms have been shown to be able to establish a persistent infection in the body.

When should we suspect Lyme disease as a potential etiological co-factor in psychiatric symptoms? Lyme disease is a multisystemic illness. If a patient presents with a symptom complex that comes and goes with good and bad days, with associated fevers, sweats and chills, fatigue, migratory joint and muscle pain, migratory neuralgias with tingling, numbness and burning sensations, a stiff neck and headache, memory and concentration problems, a sleep disorder and associated psychiatric symptoms (that may or may not be of recent onset), then we should suspect Lyme disease and associated co-infections. Have these patients fill out a Lyme screening questionnaire (link is external) that we developed in my medical office. Among 100 patients who filled out this form, a score above 46 was associated with a high probability of a tick-borne disorder. In that case, blood testing should be performed through a reliable laboratory to look for Lyme and co-infections, including Babesia and Bartonella, which can also significantly increase underlying symptomatology.

Lyme disease is a major cause of psychiatric symptoms. Psychiatric case reports, as reported by psychiatrist Dr Brian Fallon, have linked Lyme disease to paranoia, thought disorders, delusions with psychosis, schizophrenia, with or without visual, auditory or olfactory hallucinations, depression, panic attacks and anxiety, obsessive compulsive disorder, anorexia, mood lability with violent outbursts, mania, personality changes, catatonia and dementia. Other psychiatric disorders in adults due to Lyme disease include atypical bipolar disorder, depersonalization/derealization, conversion disorders, somatization disorders, atypical psychoses, schizoaffective disorder and intermittent explosive disorders. In children and adolescents, Lyme disease can also mimic Specific or Pervasive Developmental Delays, Attention-Deficit Disorder (Inattentive subtype), oppositional defiant disorder and mood disorders, obsessive compulsive disorder (OCD), anorexia, Tourette's syndrome, and pseudo-psychotic disorders. The take home message: Lyme is the "great imitator". Don't exclude Lyme disease and associated infections as a possible underlying cause of psychiatric symptoms, and don't assume that a positive response to an antibiotic like minocycline is not treating an underlying infection.

 

[Voyageur]

Thanks for the synopsis of the Horowitz video, Gaby, and the additional info - glad you are at the end of the allopurinol part. Thanks Jeep, Herondancer, SeekinTruth, Hesper (Google docs update) and others for the breakdown on the Von Sarbacher's video (I'll have a look, too). The beet thing is interesting, and it happens to be in good supply around here, and also my partner has always enjoyed canning them. Now their preparation was mentioned as being critical, so not sure if the canning process degrades them.

 

[SeekinTruth]

I've been thinking about the beets, etc. and how to best cook them too. I'm wondering if steaming them is the best as opposed to boiling them in water? There should be less mineral loss, for example, as when boiled (I'd think minerals would remain in the water and therefore be much less in the beets).

 

[Konstantin]

I've been thinking about the beets, etc. and how to best cook them too. I'm wondering if steaming them is the best as opposed to boiling them in water? There should be less mineral loss, for example, as when boiled (I'd think minerals would remain in the water and therefore be much less in the beets).

I prefer them raw, but my family makes them boiled. Raw they are very hard to eat. Boiled they become soft enough to be eaten. I don't know how they will be steamed. I don't know how much nutrients they lose when its termicly processed. Maybe then they are much easier for digestion.

 

[Kasia]

I've been thinking about the beets, etc. and how to best cook them too. I'm wondering if steaming them is the best as opposed to boiling them in water? There should be less mineral loss, for example, as when boiled (I'd think minerals would remain in the water and therefore be much less in the beets).

I prefer them raw, but my family makes them boiled. Raw they are very hard to eat. Boiled they become soft enough to be eaten. I don't know how they will be steamed. I don't know how much nutrients they lose when its termicly processed. Maybe then they are much easier for digestion.

IMO the best option is drinking self-made raw beet juice with some smashed garlic, and for lazy ones - raw (unpasteurized) bought at the grocery store.

 

[goyacobol]

Video explaining how autism, cancer, .... Have been introduced in altering the auto immune system.

Link: _https://youtu.be/cALgIHETMDU

It is a long list to really know how parasites enable stress, curtailment of mental and physical energy toward chronic/deadly diseases. Perhaps even how they interact with electromagnetism and spiritual attachments.
All this seems like a major focus of an existential war, that few are aware. The destruction of the parasites in us has to be connected with be vigilant to not get infected again, which maybe will allow to be prepared for a future great invasion of cometary parasites.

l apprenti de forgeron and wattsup,

I have not even finished this whole thread but could not help notice the implications of the link above about GcMAF. I know there are many other factors in the pollution we are dealing with but this really seems important to me because of all the promotion for everyone to be vaccinated for practically everything.

Although it is disgusting to think about it makes perfect sense in a way that if you want to control the population for what ever reason you just use the "problem, reaction, solution method". Weaken by vaccination, wait for the panic and offer the drug solutions. I am thankful that this information may be very important if we can use it.

And I thank you for noticing and sharing it.

 

[SeekinTruth]

I've been thinking about the beets, etc. and how to best cook them too. I'm wondering if steaming them is the best as opposed to boiling them in water? There should be less mineral loss, for example, as when boiled (I'd think minerals would remain in the water and therefore be much less in the beets).

I prefer them raw, but my family makes them boiled. Raw they are very hard to eat. Boiled they become soft enough to be eaten. I don't know how they will be steamed. I don't know how much nutrients they lose when its termicly processed. Maybe then they are much easier for digestion.

IMO the best option is drinking self-made raw beet juice with some smashed garlic, and for lazy ones - raw (unpasteurized) bought at the grocery store.

I've been cooking it in boiling water (actually haven't had any for about a month) along with carrots. Then, after cooling, put some olive oil and apple cider vinegar, oregano, salt and pepper on it. Goes great with a big slab of butter. I'm going to try steaming it and see how it comes out.

 

[Kasia]

I've been thinking about the beets, etc. and how to best cook them too. I'm wondering if steaming them is the best as opposed to boiling them in water? There should be less mineral loss, for example, as when boiled (I'd think minerals would remain in the water and therefore be much less in the beets).

I prefer them raw, but my family makes them boiled. Raw they are very hard to eat. Boiled they become soft enough to be eaten. I don't know how they will be steamed. I don't know how much nutrients they lose when its termicly processed. Maybe then they are much easier for digestion.

IMO the best option is drinking self-made raw beet juice with some smashed garlic, and for lazy ones - raw (unpasteurized) bought at the grocery store.

I've been cooking it in boiling water (actually haven't had any for about a month) along with carrots. Then, after cooling, put some olive oil and apple cider vinegar, oregano, salt and pepper on it. Goes great with a big slab of butter. I'm going to try steaming it and see how it comes out.

Beet soup is also a good idea - in Polish called czerwony barszcz. Just boil many choped beets and some carrots, onion, garlic, leek, celery (+ some bones/meat if you will)... When ready take the veggies (and bones/meat) out and to the liquid add some salt, pepper, herbs, olive oil... Voila!

 

[Gaby]

Beet soup is also a good idea - in Polish called czerwony barszcz. Just boil many choped beets and some carrots, onion, garlic, leek, celery (+ some bones/meat if you will)... When ready take the veggies (and bones/meat) out and to the liquid add some salt, pepper, herbs, olive oil... Voila!

Borsch soup, without the potatoes and tomatoes. Butter instead of sour cream :)

Borsch – The Russian Beetroot Soup
_http://masterrussian.com/russianrecipes/borsch.htm

Borsch is the famous soup in many Russian families, as well as many Eastern and Central European countries. The recipes of borsch vary, but vegetables (mainly beet) and sour cream are always the main ingredients. The beetroot used in cooking borsch gives the soup its trademark deep reddish-purple color.

 

[SeekinTruth]

Yeah, great reminder. Haven't made borsch in ages. It often also has cabbage.

 

[Kasia]

Yeah, great reminder. Haven't made borsch in ages. It often also has cabbage.

With cabbage, potatoes and sour cream is an Ukrainian version of borsch. Here other veggies also stay inside.

Polish version of borsch is without cabbage. Other veggies have to be taken out to let the pure liquid remain.

 

[aragorn]

This was quite interesting. For those of us who suffer from fatigue (form me it kind'a comes and goes, often without any logic), this could - just perhaps - be one of the reasons:

_http://simmaronresearch.com/2014/03/1591/

EBV I: A Deficient Immune Response, Increased Levels of Epstein-Barr Virus Opens Up EBV Question in Chronic Fatigue Syndrome Again

EBV [Epstein Barr Virus) infection was proposed as the cause of chronic fatigue syndrome not long after the disorder became prominent in the 1980s, but inconsistent study results in the 1980s and 1990s followed by Straus’s 2000 paper (which suggested the search for herpesvirus infections in ME/CFS was over) put a damper on EBV research efforts.

From 2000 to the present only Dr. Lerner with his stream of positive studies (but sometimes challenging study designs) and Dr. Glaser published fairly consistently on EBV in ME/CFS. Recently Dr. Lipkin stated (unpublished) he found no evidence of active EBV infection using high throughput sequencing in the plasma of hundreds of ME/CFS patients. Despite study inconsistencies, EBV has remained a pathogen of interest in ME/CFS. Both Lerner and Glaser have produced evidence suggesting that a defective form of the EBV virus may be causing the symptoms in some people with ME/CFS. Recent studies suggesting that EBV triggers autoimmune disorders are intriguing given the successful ME/CFS Rituximab treatment trials. EBV’s ability to reactivate during stress and in hypoxic conditions may have implications for its possible role in ME/CFS as well. A recent laboratory study suggesting that high rates of oxidative stress can reactivate EBV and that antioxidants (including NAC, catalase, and L-glutathione) might be helpful in reducing EBV reactivation is intriguing given the high rates of oxidative stress found in ME/CFS.

Now, in a surprising turn, German researchers have not only put the spotlight back on EBV, but have dug deeper into EBV, ME/CFS, and the associated immune response than any group has before. {ME = myalgic encephalomyelitis}

Paper: Deficient EBV-specific B- and T-cell response in patients with chronic fatigue syndrome.
Loebel M, Strohschein K, Giannini C, Koelsch U, Bauer S, Doebis C, Thomas S, Unterwalder N, von Baehr V, Reinke P, Knops M, Hanitsch LG, Meisel C, Volk HD, Scheibenbogen C. PLoS One. 2014 Jan 15;9(1):e85387. doi: 10.1371/journal.pone.0085387. eCollection 2014.
Link: _http://www.ncbi.nlm.nih.gov/pubmed/24454857

The Study

“Taken together, our study provides clear evidence that deficiency of EBV-specific immune response is present in CFS” –The authors

The adaptive part of the immune system, the one that takes time to kick in, comes in the form of B-cell produced antibodies that lock onto proteins the virus produces and cytotoxic T-cells that attempt to the kill the virus. (B-cell’s attack the virus in the blood and cytotoxic T-cell attack virally infected cells.) Noting some unusual findings in their lab, these researchers looked at these antibodies and T-cells to see if people with chronic fatigue syndrome were mounting an effective immune response against EBV. They also looked for direct evidence of an active EBV infection. EBV replication occurs when the virus produces proteins in a sequence that allows it to build another virus. One theory, developed by Dr. Lerner and a group at The Ohio State University (that includes Drs. Ariza, Glaser, and Williams), proposes that EBV undergoes ‘abortive replication’ in some people with ME/CFS. In abortive replication, a defective form of EBV produces early proteins, but is unable to produce later ones. The Ohio State group believes continual production of these proteins is causing a chronic inflammatory state in some people with ME/CFS.

Results

First, the German researchers found evidence of primary EBV infection or reactivation (increased IgM antibodies to a late EBV protein in @15% of patients vs 3% of controls) in significantly more ME/CFS patients than controls. The fact that this could be a ‘primary infection’; i.e. it represents the first time these patients are exposed to the virus is intriguing. A primary infection of EBV early in life usually leads to nothing more than a cold; a primary infection later in life can have serious consequences including infectious mononucleosis. Having found evidence that an active EBV infection was more common in people with ME/CFS than controls, they looked to see if a reduced immune response was responsible for that. The first hint of a reduced immune response to EBV in ME/CFS came in the form of a lack of antibodies to EBV-produced proteins VCA and EBNA1.

[...]

Immune Holes to Epstein-Barr Virus Found

Immune Hole #1 – reduced antibody response

Evidence of a impaired B-cell response to EBV first came in the form of missing IgG antibodies to VCA and EBNA in 13% of ME/CFS patients compared to 4% of controls. This indicated that 13% of their ME/CFS study population did not have some of the memory B-cells needed to detect an EBV infection. Increased IgM antibody responses in ME/CFS (17.5% in ME/CFS vs 4% in controls), on the other hand, suggested active and perhaps primary EBV infections were more commonly found in ME/CFS patients. All told, 30% of the ME/CFS patients either had reduced IgG (EBNA-IgG) or increased IgM (VCA) responses to EBV. That finding prompted a deeper look, and a much larger study that found no IgG response to a protein expressed during latency by EBV (called EBNA-1 protein) in 10% of IgG positive ME/CS patients. This indicated that the immune systems of approximately 10% of the ME/CFS group were unable to detect a very early stage of EBV latency.

Latency

For EBV to maintain itself in the body over time, it needs to be able to maintain itself in B-cells in a process called latency. EBNA-1 is a protein that helps maintain EBV’s viral genome in the earliest stages of latency. The authors noted that people with severe infectious mononucleosis and chronic active Epstein-Barr virus disease have similar findings (although it’s not clear why, given that EBNA-1 is not involved, so far as we know, in replication). That brings up the question of how many people with ME/CFS would have fit into the category of severe mononucleosis at the time they got ill. The Dubbo studies found that more severe infections greatly increase the risk of coming down with ME/CFS.

Immune Hole #2 – reduced frequencies of two B-cell antibody producing cells

Intrigued by the findings, the German researchers dug deeper into the immune response to EBV. They took blood (PBMCs) from ME/CFS patients and then stimulated it with CpG, SAC, and PWM for seven days, and found reduced frequencies of B-cells producing antibodies against VCA and EBNA-1, and for the first time they found evidence of immune deficiencies in most people with ME/CFS. No less than 59% of ME/CFS samples had a diminished response to a later stage EBV protein (VCA) produced during the late stage of lytic replication, and a whopping 76% of ME/CFS samples had a diminished response to the EBNA-1 protein. With the VCA finding we have evidence suggesting many people with ME/CFS may have trouble controlling EBV replication.
Calling the findings ‘remarkable’, the authors suggested that either the memory B-cells associated with these EBV antigens had been lost or had failed to develop into antibody-secreting cells.

Immune Hole #3 – Reduced T-cell response to EBNA-1

A similar deficiency in the T-cell response to EBNA-1 indicated that both arms of the adaptive immune response to Epstein-Barr Virus, the B-cells and the T-cells, had difficult recognizing and responding to this protein. Citing other disorders such as HIV, they suggested that persistent EBV reactivation in ME/CFS had driven the T-cell response in ME/CFS into ‘exhaustion’. (A similar suggestion has been made with regard to natural killer cells that attack pathogens early in an infection, which use killing methods similar to those employed by T-cells.) Further analysis suggested that T-cell suppressor cells which decrease B-cell responses were not responsible for the B-cell suppression found. Normal B-cell responses to herpes simplex and cytomegalovirus suggested that the deficient B-cell responses were associated with EBV and not other herpesviruses.

Immune Hole #4 – reduced T-cell response to EBNA-1, reduced T-cell responses to EBV

Next they explored T-cell induced cytokine production. The T-cells should produce an array of cytokines against EBV. About 20% fewer ME/CFS patients (70% of controls vs 50% of ME/CFS patients) were able to mount an IFN-y response against EBV. Looking specifically at the latency associated EBNA-I protein, they found the startling result that no ME/CFS patients mounted an IFN-y response against it. They also found that ME/CFS patients produced significantly lower amounts of the pro-inflammatory cytokine TNF-a in response to EBV. Finally, a lower percentage of patients produced IL-2 as well. The reduced cytokine production suggested cytotoxic T-cells, one of the big guns of the adaptive immune response, were not being strongly activated in response to EBV.

Immune Hole #5 – Reduced frequencies of EBNA-1 specific T-cells

The researchers dug deeper still. Next they stimulated the blood (PBMCs) of ME/CFS patients and healthy controls (n=40) with the EBNA-1 protein, expanded the cells in the presence of IL-2 and Il-7, and then checked the T-cell response to them. Specific types of T-cells should be produced to attack EBV, but reduced frequencies of EBV-specific T-cells occurred in about 50% of the ME/CFS samples. That again suggested the cytotoxic T-cell response to the EBNA-1 protein was substantially reduced in ME/CFS.

Direct Evidence of Active EBV Infection

“Remarkably, in line with this finding we could provide evidence of enhanced viral load of EBV by detection of EBV DNA in a significantly higher proportion of patients compared to healthy controls.” –The authors

Using a real-time PCR test in the whole blood that looked for ‘low-copy’ numbers (<1,000-2930 copies/ml) they found evidence of increased EBV viral load in 7.2% of 290 ME/CFS patients. When they dug deeper and did the same test in PBMCs in a subset of patients, they found that a whopping 55% of patients (vs 13% of controls) tested positive for EBV. The viral loads were far below those found in other EBV associated illnesses such as infectious mononucleosis or post-transplant EBV infections, and there was no evidence of lytic replication (i.e., full replication of the virus), but something the authors called ‘latency-associated replication’ was common in people with ME/CFS, yet not in healthy controls.

The Lipkin Study
Using PCR the German researchers found much higher rates of EBV infection in PBMCs vs whole blood and no evidence of EBV infection in plasma. Neither the Lipkin CFI ME/CFS pathogen study nor the CFIDS Association of America BSR study found evidence of EBV infection in ME/CFS. According to Russell Fleming’s transcript of the Lipkin talk, the CFI study looked in the plasma of both the Montoya and the ME/CFS experts’ samples. Whole blood contains plasma, red blood cells, white blood cells, and platelets. Plasma makes up 55% of blood volume and contains water (90%), proteins, nutrients, waste products, clotting factors, hormones and carbon dioxide. It does not contain red or white blood cells or thrombocytes. EBV DNA has certainly been found successfully in plasma before and plasma has been used to track EBV activation. Serum/plasma EBV PCR kits are available for purchase. Researchers search and find EBV in plasma frequently.

Dr. Chia, however, reportedly stated he believes the use of plasma rather than blood was a serious mistake, and the Germans were able to find evidence of EBV activation in blood but not in plasma.EBV (and CMV and HHV-6) are ‘cell-associated viruses. The only times their DNA escapes the cells is when the cell dies (and the DNA goes into the plasma) or when the virus is replicating. Otherwise the virus sits in a latent or semi-latent state in the cells.

Medical dogma states if you can’t find EBV in the plasma, the infection is not active. EBV DNA can be found in the plasma when EBV replication rates are high, as sometimes occurs in transplant patients, but it’s not likely to be found in the smoldering infection believed present in ME/CFS. Many researchers do not accept the idea of a smoldering infection that pumps out proteins which trigger an inflammatory response. The German researchers are deepening their study of EBV and ME/CFS and currently evaluating antibody responses against a broader variety of EBV peptides derived from 8 different proteins. They are also quantifying the levels of memory B-cells targeting EBNA-1 and VCA.

Conclusion

“We think the altered pattern of the specific immune response to EBV may be suitable as a diagnostic marker for CFS.” –Authors

It was if these researchers kept pulling a string that got longer and longer. First their interest was piqued by some paradoxical antibody findings, then they found widespread deficiencies in some antibody responses and T-cell responses, and finally they saw evidence of an active EBV infection in the blood of 55% people with ME/CFS (vs 7% of controls). Much is still unclear. The EBNA-1 protein that the immune systems of ME/CFS patients had trouble responding to is associated with ‘early latency’, not EBV replication. The authors’ reference to ‘latency associated replication’ is unclear given that latency is not usually associated with replication. When asked what importance their findings have for EBV reactivation or EBV survival or more severe casesof infectious mononucleosis in ME/CFS, the authors stated they can’t answer those questions yet.

Some researchers believe, however, that reduced cytotoxic T-cell responses to EBV increase the risk for autoimmune disorders. (We’ll be covering that possibility in the next blog.) {you can find that next blog here: _http://simmaronresearch.com/2014/05/epstein-barr-virus-autoimmunity-hypothesis-fit-chronic-fatigue-syndrome/} These findings also suggest that the proposal by Lerner and the OSU group of Drs. Ariza, Glazer, and Williams that an abortive lytic process (smoldering EBV infection) is present in many people with ME/CFS may be correct. While it will take more work to determine what these findings mean for ME/CFS, the broad range of dysfunction found and the high rate of active EBV infection (in plasma) would appear to put this pathogen back into play in a meaningful way in ME/CFS.

I remember having mononucleosis (which I caught by kissing a girl!) at the age of 20, but I wouldn't say it was too serious. But who knows, maybe there are some latent EBV-critters still hanging around in my body.

 

[Gaby]

I'm attaching a paper that could be useful as a resource to give to doctors and other health care providers. It is from the International Lyme and Associated Diseases Society. The article is titled "Evidence-based guidelines for the management of Lyme disease" and it was published in Expert Review Anti-infective Therapy in 2004. It highlights the need of prolonged use of antibiotics in some cases.

Other highlights:

B. burgdorferi has been detected in virtually every organ in the body, and the spirochete has a strong predilection for the central nervous system.

The presentation of chronic Lyme disease can be identical to that of other multisystem disorders, including systemic lupus erythematosus, rheumatoid arthritis and fibromyalgia.

The increasing sucesss of repeated and prolonged antibiotic treatment in chronic Lyme disease are more consistent with a persistent infection mechanism.

Early Lyme disease classically presents with a single erythema migrans (EM or 'bullseye') rash. The EM rash may be absent in over 50% of Lyme disease cases, however. Patients should be made aware of the significance of a range of rashes beyond the classic EM, including multiple, flat, raised or blistering rashes. Central clearing was absent in over half of a series of EM rashes. Rashes can also mimic other common presentations including a spider bite, ringworm, or cellulitis. One series of eleven EM rashes was misdiagnosed and treated as cellulitis, with all eleven patients showing clinical evidence of Lyme disease progression.

Physicians should be aware that fewer than 50% of all Lyme disease patients recall a tickbite. Early Lyme disease should also be considered in an evaluation of 'off-season- onset when flu-like symptoms, fever and chills occur in the summer and fall.

Neurologic and rheumatologic symptoms are characteristic, and increase severity of symptoms on wakening is common.

Available data suggest that objective evidence alone is inadequate to make treatment decisions, because a significant number of chronic Lyme disease cases may occur in symptomatic patients without objective features on examination or confirmatory laboratory testing.

Differential diagnosis with thyroid disease, degenerative arthritis, metabolic disorders, heavy metal toxicity, vasculitis and primary psychiatric disorders. Infectious causes can mimic certain aspects of the typical multisystem illness seen in chronic Lyme disease. These include viral syndromes such as parvovirus B19 or West Nile virus infection, and bacterial mimics such as relapsing fever, syphilis, leptospirosis and mycoplasma.

The clinical features of chronic Lyme disease can be indistinguishable from fibromyalgia and chronic fatigue syndrome.

Oral antibiotic options: oral amoxicillin, azithromycin, cefuroxime, clarithromycin, doxycycline and tetracycline.

One study has suggested that oral doxycycline (100mg twice daily for 30 days) is as effective as intravenous ceftriaxone (2g daily for 30 days) in early disseminated Lyme disease.

There are no studies comparing oral with IV antibiotics for persistent, recurrent and refractory Lyme disease.

Dosage. Increasingly, clinicians recommend that certain drugs used for Lyme disease be given at higher daily doses (i.e. 300-400mg doxy). Close monitoring of complete blood counts and chemistries are also required with this approach.

Serious adverse effects of antibiotics, however, were less common than previous estimates. In a recent clinical trial of chronic Lyme disease, the overall serious adverse event rate was 3% after three months of antibiotics, including 1 month of intravenous antibiotics.

For chronic persistent infections, i.e. refractory Lyme disease, several months of therapy are often required to produce clear evidence of improvement.

The patient's clinical response should guide duration of therapy.