Advice to Non-Medical Newcomers

Why are you here?  The reason is the same for all of us.  Either you or someone you care for is sick, so you're looking for something, anything to help.  Maybe it's MSi, CFSi, ME, FM, Lupus, Alzheimer's, unrelenting fatigue, pain and inflammationi, or something else.  You might  be desperate because you're up against a wall built of words like incurable, untreatable, and of unknown origin.  Perhaps a cutting-edge medication has been tried and failed.  With the media full of news about medical breakthroughs, you're frustrated that a meaningful treatment has not been found for your illness.  You're thinking that surely the answer lies somewhere out there in the vast body of knowledge that makes up modern medicine...someone just hasn't connected the dots yet.  You surf the internet and find websites offering support and education on the illness. You read articles about research and new treatments.  Much of it is written in medical-ese, and you may feel overwhelmed, even handicapped in your ability to milk the meaning out of the information you find.

I am a caregiver and care advocate for my husband who has a degenerative illness.  I have no medical background and I'm cyber-challenged.  If, like me, you're stubborn enough to keep struggling with all those research and treatment articles, and if you can make any sense out of them, a bigger picture emerges.  When you step back to assess the various bits of information collectively, you will find a gaping hole.  Something huge is missing.  The problem is that most of the current research and emerging treatments focus on "tinkering" with the disease process, not on addressing the root cause of the disease.  Why is that?

Things they forgot:  Entertain some what ifs with me.  What if research into the disease had been underway for several decades?  What if, in those early days, research efforts were concentrated on finding a microbe as the villain?  After all, the immunei systems of the people afflicted with the disease seemed to be attacking something that shouldn't have been there.  What if, after no infectious agent was found, the research community embraced the theory that the body sometimes goes nuts and attacks itself via a defective immune system?  What if this interesting autoimmune concept led researchers into some limited success in developing drugs that "tinker" with the immune system to some benefit for some of the afflicted some of the time?  Limited success is better than no success.  What if herd-mentality caused a stampede of researchers in one direction?  What if, in the meantime, there had been advances in microscopy and lab techniques that might have enabled those early researchers to find what they had been looking for?  What if the majority of the research/medical community had somehow lost track that the model of autoimmunityi was an unproven theory, and they had comfortably incorporated it into their thinking and efforts as though it were a given fact?  What if new technology applied to old ideas could result in the hope of treating the disease at its core rather than just "tinkering" with the disease process?

My husband's illness has been rubber-stamped as autoimmune.  Like you, I was searching, and like you, I am a relative newcomer to this website.  Most of the material on cpnhelp.org is very understandable, but you will eventually run into unfamiliar medical terms and processes.  Advice from other users, resource tips gleaned from their blogs, and my own experience have helped me develop a system for digesting the cpnhelp.org material and for understanding the medical-ese I encounter elsewhere on the internet as I investigate my husband's illness.  I'm offering you a shortcut.  Please let me help you in your quest to get the most out of this website, lits linked websites, other websites you are already visiting, and those you will visit in the future (especially those research articles).

THE SYSTEM:

Once over lightly - Follow the advice on the Homepage by reading Cpn Simple and The Basics Page in the Cpn Handbook...go back to the Handbook and skim through the sections concerning treatment just to know what's there.  Be sure to read the disclaimer and privacy statement.

Prepare to go deeper - Very simple, free, not much time, and so worth the effort.

• If you think you might want to try my system, print it and keep it handy.
• Build a small foundation of knowledge and understanding.  I can't emphasize enough how helpful this is.  After you do it, you'll want to revisit those research articles that were so befuddling.
• Click on this:  http://health.howstuffworks.com/immune-system.htm.  Read each short section.  Print it and keep it handy.  You will use it over and over again.
• Click:  http://en.wikipedia.org/wiki/Inflammation#Characteristics.  Read the entire page with particular thought given to the dysfunction aspect of inflammation.  Under the Outcomes heading, see if you don't recognize "collateral damage"  as it's called by the military.  Print it and keep it handy.

Read the entire Homepage again.

Read the Handbook.

• Read it all the way through or click on the topics in the Table of Contents found on the left side of the screen to read specific information.
• Use the glossary on the left side of the screen (you may need to use the up/down slide bar to locate it).
• Some terms in the Handbook will be marked with a highlighted " ⁱ  " at the end.  Click on the " ⁱ " for a definition or a comment about that term.
• For terms not found in the glossary, minimize the active cpnhelp.org page by clicking its identifying tab in the bar at the bottom of the screen.  Then go to medterms.com, wikipedia, or even howstuffworks.com (it's good, but has its limits).  You will discover other resources to use for the same purpose.
• After reading the definition(s) on the other websites, minimize the resource page(s).  Keep these resources at the ready in the bottom bar to pop up for future use.  Then click the appropriate bottom bar tab to restore the cpnhelp.org page.
• You may want to print the entire Handbook for portable reading.  Follow the printing instructions on the introduction page, especially the part about The Table of Contents.  A printed copy of the glossary is a good take-along aid as well.

Visit other cpnhelp.org resources by clicking the tabs found at the top of the screen.  The Patient Stories are sure to be a favorite resource.

Find out what the website users are blogging about by clicking recent posts on the left side of the screen.  If you spot a blogger that may be of interest because you suspect you have an illness in common, click on that user's highlighted name.  This will take you to a window where you can track other comments made by that user.

Navigate your way to the older posts; they are still new to you.

Search for a specific topic in the Search slots located in the upper right and lower left sides of the screen.

Check out what's happening on the right side of the screen.  Click around here and there and you'll soon become an expert navigator.  You will eventually want to participate, or perhaps you will want to go where only a user can go.  Welcome aboard, it's time to REGISTER!

 

 

 

 

Cpn Simple

 

Cpni Simple- The shortest explanation we could think of!

Cpn has been clearly proven to have persistencei in the body despite “standard” antibiotic treatment (two weeks of a single antibiotic).

Cpn has been implicated in a wide variety of diseasesi (see bottom of this page).

Blood tests and cultures are not reliable indicators of whether Cpn is part of your disease.

If you have any of the diseases in which Cpn has been implicated, it may be worth trying an “empirical” (based on symptoms alone) combination antibiotic protocol (Link).

Most doctors are not familiar with this, and you will have to present a rational and evidence based case to them for prescription of the appropriate antibioticsi through information such as on this site.

Is this right for you? 

Four indicators can be used to help you determine if an empirical test of the full combination antibiotic protocol is useful for you. You should be on it for for a minimum of 6 months to a year. The first three suggest that you have Cpn and you should continue this treatment.

1. You experience distinct reactions to the antibiotics indicative of Cpn die-off (see Reactions to Treatment link).

2. You have improvement of disease symptoms.

3. You have noticeable halting of symptom progression.

4. Nothing at all and decide this isn’t for you.

Diagram from David Wheldoni (http://www.davidwheldon.co.uk/killing.jpg) used by permission. 

Phases of the Cpn bacteria and what agents effect those phases:

EB’s- Elementary Body What are they? EB’s are spore-like forms which are infectious and metabolize minimally (aren’t using nutrients, replicating, exchanging with the environment, etc.). They are tough, tiny and reside in the intercellular tissues (outside of actual body cells). What do they do? EB’s attach to your body’s cells and invade them. Since there can be more EB’s than can get into cells, EB’s build up in local tissues causing inflammationi and immunei response.

What kills them? They are killed by amoxicillini, which is transformed to penicilamine in your own body, and destroys the bonds which hold the EB cell wall together. An amino acid NACi (N-acetyl cysteine) also is used for this purpose. What happens? When you kill them, they release toxin into the tissues in which they have built up, and you get inflammation and pain there, which can last for days or weeks afterwards before you feel relief of symptoms. Most people taking NAC report a period of flu-like feeling of malaise, achyness, nunning nose, perhaps coughling.

RB's- Reticulate Body What are they? Once an EB enters a host cell it transforms into a form which can replicate new EB'si which is called a Reticulate Body or RB. The RB has no energy source of it's own for this, so it must steal energy (ATP) from the host cell, leaving the host cell weakened and less functional. The RB also inhibits the natural cell deathi of the host cell so that it can survive while it replicates. After the production of many new EB's the host cell bursts and dies, spreading the infectious new EB's into the surrounding tissue.RB's are inhibited in replicating by various antibiotics such as doxycycline, azithromycin, roxythromycin and others, and subject to this will convert into the Cryptic (and nonreplicating) form where they can be killed by metronidazolei. RB's are prevented from forming by rifamcini.

Cryptic formi What are they? When RB’s face an environment which threatens their survival inside a cell (lack of food, antibiotic attack, etc) they can transform into a “Cryptic” form which stays inside the cell, but is in hibernation, so to speak. What do they do? In this form it is not vulnerable to regular antibiotics and can reside there until conditions change, then become an RB again and start to replicate and reinfect with EB’s. What kills them? Flagyl (metronidazole) or Tinactini (tinidazole) are used to kill the cryptic forms of Cpn. Nitrofurantoin, an old urinary tract infection drug, also has antichalmydial effect in this phase. These drugs can be hard to tolerate for various reasons, and so are commonly “pulsed” by taking a course for 5 days every 3-4 weeks, rather than taken continuously. Some protocolsi may eventually have one of these drugs taken continuously for some period as the patient can tolerate. Patients may experience fatigue, nausea, bowel upset, deep joint achyness and muscle pain as the cryptic orgnanisms are killed and the immune system engages in clean up.

Much of the discomfort from treating Cpn is a combination of the organism's endotxin itself, and the inflammation caused by your own immune system (cytokinei) reactions to that.

SUMMARY

Amoxicillan and NAC kills the infectious spore-like EB forms which build up in the tissues.

Rifamcin kills EB’s transforming to RB’s in a vulnerable enzyme transformation phase.

Doxycycline and either Rozithromycin or Azithromycin, are used in combination to interfere with the RB’s ability to replicate. Two are used which work on different proteins to minimize creating resistance.

Supplementsi are recommended to help counter the impact of Cpn on the body, and of the inflammatory effect of the die off during treatment.

Treatment can take months to years to completely eradicate Cpn from the body.

What diseases has it been implicated in?

Slide Presentation on Cpn from Charles Stratton

 
 Click This Link for a powerpoint presentation by Charles Stratton on Cpn.
Although focused on respiratory disease, it provides and excellent summary of Cpn in general, and why combination antibiotic therapy is so important. 
Great pictures of the organism at different life phases, and links to other diseases.
Download a .pdf file of the slide show, thanks to Red (!) CLICK HERE 

The Basics Page

Hello and Welcome!

This site is focused on treatment of chronic disease like Multiple Sclerosis (MSi) Chronic Fatigue Syndromei (CFSi) and Fibromyalgia (FMSi) an many other diseasesi with antibioticsi. Recent research indicates that Chlamydia Pneumoniae (CPni) plays a role in these diseases.

Here are the basics that make it easier for people new to the site to get going (if your brain isn't ready for even this much right now-- we've all been there-- read Cpn Simple first):

Is this a sexually transmitted disease? No. this is chlamydia pneumoniae, a bacteria that can cause pneumonia. It may soon be called chlamydiophilia (meaning in the family of).

Is chlamydia pneumoniae (CPn) rare?

No it is a common cause of respiratory illness, but it has an interesting and abnormal way of existing because it can change forms and inhabit the very cells of your body. It can go into your monocytes (a blood cell), your macrophages (an immunei cell), microglia (a brain cell that causes immune reaction) endothelial cells (blood vessels) and others and actually take over.  We say then it has parasitized the cell. Your cell can't do the work it was meant to do now because it's busy supporting the CPn, all the energy of the cell going to make energy for the CPn and it using that energy to make new CPn cells.  For all intents and purposes, your cell is no longer a functional cell and cannot do what it was designed to do.

How does it spread?

From person to person when in the respiratory tract it is spread by droplets; in a cough for example. The form that goes from one to another is the elementary body (EB), a tough, little tiny bacteria. It may actually cause pneumonia in the respiratory tract. In some cases once inside, the EB will look for a home (cell) to parasitize so it can have an energy source. Once inside the cell the EB turns into a reticular body (RB) which can produce new infective cells (EB'si) that can find and parasitize other cells. Gradually the cells of your body lose the ability to do what they were meant to do. They are now supporting CPn lifecycle and not taking care of your lifecycle. If it's a monocyte that's infected for example, it is now a factory for EB's not a functional monocyte.  We say then the CPn has parasitized the cell.

Click here for a detailed explanation of of Cpn

Why doesn't my immune system kill it?

This is a complex question. It depends on where the infection is and how advanced it is and what cells have been infected. People who get CPn as a form of pneumonia and do have an active immune response to the bacteria in that instance, though as a form of pneumonia it is mild. Often it is referred to as "walking pneumonia" because people, while ill, are not prostrate with it. Since most people get CPn in their lifetime and get over it as evidenced by rising titers to the bacteria, we can assume that most of the time the immune response is effective enough to for all intents and purposes "get over it."

In some people however, perhaps because of their genetic makeup or some other factor, the bacteria is carried in blood or immune system cells In this case it "goes underground" and infects the tissues far from the origin of the lungs. Key to this discussion is that your immune system cells are some of the ones that now have these nasty little bacteria hiding in them, so where the immune system goes, the CPn goes too and over time may render the immune cells less effective.

Second, the germ is INSIDE the cells. Your immune system can't see them in there. Your immune system "sees" what is "you" and what is "foreign" by looking at the proteins on the outside of the cell wall. The outside of this cell is you. For all your system knows, it is a friendly cell, so your immune system is quiet and unexcited. Meanwhile the stealthy pathogen is hiding, slipping into the cells and taking over one cell at a time, and one cell at a time they are now CPn factories not whatever they were meant to be.

While in some cases CPn is a fairly "benign" germ under certain conditions such as when it is attacked by antibiotics or "starved" it becomes cryptic or shuts down so it can't be harmed or detected. When cryptic it is so quiet and hidden in the body, your body does not really notice it. It then becomes active at some later time causing a "new" infection, perhaps in new parts of the body.

Changing forms of Cpn

This bacteria diabolically can change from any form, EB, RB, Cryptic or persistent, to any other form based on the environment. It will choose the form least affected by whatever is threatening it! If you take an antibiotic, let's say for a bladder infection, the CPn will hide in a non replicating and non metabolizing form until the threat is over and your internal environment is less hostile. Virtually all people will have rising titers to CPn over their lifetime, meaning they have been exposed and make antibodies to it from the occasional experience with it as a respiratory pathogen, but also perhaps because they harbor this cryptic formi which later "wakes up" and then subsides or is treated. But as a cryptic pathogen we know little about it. It is just emerging as a known cause of disease. The Centers for Disease Control list it as an Emerging Pathogen in atherosclerosis. See the slides to see pictures of these germs in the cells.here

Why do steroids help MS then? This question was asked to Dr Wheldon and Dr A. The answer is found here

Why is it true that your doctor does not tell you about this?

This is new understanding and it's not well defined yet. For example why is it cryptic in some people? We are not certain at all. The CPn was first seen in 1965 and was identified as the cause of an outbreak of pneumonia in the early 80's. Before that time we had no research or concept about bacteria with lifecycles that included changing forms from one to another and hiding inside the cells of your body. Bacteria were seen as one form either a cocci, or a spirochete, or a rod and you were given one antibiotic and it would go away. Everyone who was trained in medicine was taught this and spent long hours studying these facts.

Now, research on CPn indicates it plays a role in several chronic diseases by using these peculiar and not well understood ways of being in the body. We have to go back to the books and learn a whole new kind of bacterial science where germs evade and hide from our treatments in ways that seem impossible or outlandish based on prior learning and understanding. New knowledge takes time to filter into the mainstream because physicians spend so many years studying biochemistry and microbiology that they feel like experts. This is so different that it sounds "wrong". Also some other research seems to find it is not a factor in chronic illness, which gives the individual physician a sense this is too new to act on yet.

For example, some research in CPn in multiple sclerosis (MS) does not find an increased incidence of CPn in the nervous system in people with MS while other research does find CPn DNA in the nervous system of people with MS. This creates doubt in the minds of physicians and a sense that we need to wait for more definitive research before acting. And finally, medicine is extremely slow to change paradigms.

We have a superb example of this in helicobacter pylori, a bacteria, in peptic ulcer disease. This bacteria was discovered in 1982 by Barry Marshall. He produced a large amount of good research on h. pylorii causing peptic ulcers that went largely ignored. Why? Because "everyone knew" that bacteria could not survive in the stomach (wrong) and he literally had to swallow the bacteria himself and prove that it then caused him an ulcer. When he healed it with antibiotics others to finally accepted his research. It's very difficult to get medicine in general to accept new science, even if it's absolutely correct.

I bet you're thinking that everyone gets antibiotics for ulcers these days, but you'd be wrong. Up to 9 out of 10 ulcers can be healed by treating with appropriate antibiotics for 2 weeks. Yet today, 23 years after the discovery that ulcers are caused by bacteria, not lifestyle or stress, over 50% of ulcers are STILL treated with proton pump inhibitors (medicines that decrease stomach acid)or other palliative measures that do not kill the bacteria, which also may play a role in gastric cancer. This link is to the American Centers for Disease Control detailing these facts HERE There is a serious "blind spot" in medicine about potential infectious causes of chronic disease. Clearly, even a proven fact can still be ignored by doctors.

Why does research say it's not a factor sometimes?

The fact of the matter is that CPn in cryptic form, that means in the cells in an unmetabolizing and non relicating form, is hard to detect. It's virtually impossible to detect without extremely complicated procedures and even in the infectious form it is hard to detect with sensitive DNA (PCRi, below) tests, let alone less sensitive antibody tests. You cannot just see if the person is making antibodies to the bacteria as you would in other infectionsi and as mentioned above, people have rising titers (rising numbers of antibodies) to CPn over their lifetimes as most all of us are exposed repeatedly.

Instead of checking for antibodies a newer advanced kind of technique must be done called polymerase chain reaction (PCR) to see if CPn is in the tissue. This technique uses small amounts of DNA to detect the presence of the bacteria, not the old method of just screening the blood to see if you have antibodies to CPn.

The trouble with this is that just like our understanding of CPn is growing so is our understanding about how to detect it. Labs are developing ways of finding and testing for the DNA fragments, however this is still early days. Some labs use one part of the DNA for detection; others use another. This accounts for discrepancy in results as it has not yet been agreed upon by everyone that one lab's approach is the clear winner for accuracy.

It appears at this time that the Vanderbilt University test is the best at detecting the DNA via PCR. They have doccumented that they have concordance with split samples. In other words, samples tested as positive are positive and negatives are negative in a second test done at another lab. VU finds CPn in the majority of MS cases.

Another reason we have confusion about whether CPn is in chronic disease or not is some research almost inexplicably seems to be set to NOT find it. For example, just testing the antibody titers of people with MS or CFS or FM and people who have no chronic disease is sure to result in no difference between the groups since this is a common bacteria we all will be exposed to over our lives. Yet we still see some "research" doing exactly this; saying that the titers were the same in both the chronic illness group and the normal group and reaching a conclusion that CPn plays no role in the disease. This is silly! The question is not have you been exposed to CPn and do you have a high titer, the question is whether it is an active infection and or whether it has gone cryptic in your particular case. There is no consensus yet as to how to determine that all important question. However evidence is emerging, and in some areas it's substantial (as it is in the area of atherosclerosis) that CPn is the cause of chronic illness. The CDC lists CPn as an emerging pathogen in the cause of atherosclerosis.

What is empirical treatment for Cpn?

If you are tested as positive for Cpn either through antigen or PCR testing, then you clearly know you need to treat it. In that case, know that the standard two week course of a single antibiotic may be inadequate to kill the Cpn in some of it’s life-phases, and re-infection can occur unless a combination antibiotic protocol such as the Vanderbilt or Wheldon protocolsi, is followed. But if you have any of the diseases in which Cpn has been implicated (see list on Home page), it may be worth doing an “empirical” (based on symptoms) course of a combination antibiotic protocol even if your tests for Cpn are negative or uncertain. The antibiotics used are not considered harmful, even for long courses. If you have Cpn involved in your disorder and try this protocol you will likely experience the following: an inflammatory reaction or worsening of some of your symptoms (caused by the bacteria dying and releasing it’s toxin in larger amounts), followed by a gradual improvement in your disease symptoms. Reactions to treatment can range from mild, if your load of Cpn is not great, to very strong and uncomfortable. In the latter case, you have to go very slowly to get to full dose of the protocol. Similarly, improvements in your condition depend on how long you have been infected, and what your total load of Cpn is, and how much permanent damage it might have created to your body.

Why are there so many antibiotics?

CPn exists in your body in several different forms. The first is the elementary body. It is small hard and is not actively replicating or metabolizing. It is "looking" for a cell to adhere to and be absorbed by. At this stage amoxicillini can force the EB into the cells.

Once inside a cell, the EB goes through a transformation becoming metabolically active and replicating. To make this transformation, proteins are used and reassembled to cause the change. It grows huge compared to it's EB size and when the transformation is complete, it takes over the cell's energy system, robbing all the energy for it's own purposes. At this point the tetracycline antibiotics block one of the proteins used in the transformation process (that's how antibiotics work; by blocking proteins used to replicate) so the EB is stuck halfway transformed to an RB (replicating body).

Now, one of the problems we have with antibiotics in general is that bacteria are very crafty and they have "learned" to resist different antibiotics by replicating using different pathways than before so the blocked protein is no longer needed. This is what we mean by resistance. A certain bacteria is no longer stopped by a certain antibiotic from replicating. The concern about CPn resistence can be stopped in it's tracks by adding a macrolide antibiotic such as rifampin, azithromycin or roxithromycin in addition to tetracyclines because it blocks protein synthesis in a second part of it's pathway. It is effectively impossible for CPn to develop resistance with this double whammy.

Both the tetracyclines and the macrolides are considered bacteriostatic. They do not kill germs outright, but stop replication so your body can clean up and win the battle without a growing bacterial population to deal with. In the case of CPn however, the EB is stuck halfway converted. It is not able to take over the cell's energy system, so it's on it's own. It has some rudimentary ability to survive on it's own in this anaerobic (without oxygen) state, but not much. As a result a number of the CPn germs will die causing an endotoxini reaction (see below) even though at this stage you are only taking bacteriostatic drugs.

However a good number of the bacteria will survive even though many die under the stress of living stuck halfway between EB and RB, reducing the overall bacterial loadi by a good margin. This brings us to flagyl (metronidazolei). This antibiotic kills the CPn outright, causing for some people a big reaction to the endotoxin, depending on how extensive the bacterial load still is for them as they begin it's use. For this reason, many people wait a number of months after starting the bacteriostatics before taking their first dose of flagyl. Then, they may take flagyl for only one dose the first time they take it, then wait for the body to recover a bit before dosing again. Pulsing the flagyl kills off some germs,  then gives the body and tissues reacting to the released LPSi a rest.

The Wheldon regimen recommends using the flagyl for 5 days once every three weeks while continuing to take the other antibiotics. Effectively the CPn is stuck by the bacteriostatic agents waiting to be killed by your next flagyl pulse, though some die simply waiting. The VU protocol recommends flagyl without rest in between and amoxicillin to force the EB's into the cells where they can be killed by the flagyl. This can result in a fairly vigorous LPS reaction (below). Dr A stated in his interview he has no probelm with people pulsing flagyl if they wish to do so.

What is endotoxin and how is that related to "herxheimer"?  

Endotoxin is a lipopolysaccharidei (LPS), the protein that is on the outside of every gram negative bacteria.  A gram negative bacteria is one that does not take gram stain.  LPS is very immunogenic meaning it causes a brisk reaction by the immune system to it's presence.  When gram negtive bacteria die, either naturally or by antibiotic, the resulting load of LPS floating around is toxic to the person. "Toxic shock syndrome" is a reaction to LPS in a gram negative bacteria.  The kinds of reactions to LPS vary a bit depending on the bacteria in question, some being more toxic than others.  CPn LPS is not very toxic as far as LPS goes, though it does cause a noticable reaction, it's not threatening as other LPS can be. 

Syphilis as another gram negative bacteria.  When antibiotics were first applied to this dread disease, the patients got markedly worse as the LPS built up in thier systems.  This was named for the doctors that described it as "Jarisch Herxheimer Reactions".  It has been specualted that the phrase "you have to get worse before you get better" came from this phenomenon.  Today the term herxheimer or herx has been in common usage to mean any reaction to a gram negative bacteria.  I have even heard of people using the phrase in relation to the die off of candida after appropriate anti-yeast drugs have been taken.

What diseases has it been implicated in?

Multiple sclerosis

Chronic fatigue

Asthma

Arthritis

Fibromyalgia

Chronic refractory sinusitis

Cardiac disease

Interstitial cystitis 

Prostatitis

Crohn's disease

Inflammatory bowel diseasei

Alzheimer's disease

Additionally: chronic obstructive pulmonary disease, uveitis, optic neuritis, radiculitis, nerve deafness, transverse myelitis, sarcoid, myocarditis, pericarditis, culture-negative endocarditis, atheromatous arterial disease, aneurysm, giant-cell (temporal) arteritis, polyarteritis nodosa, Wegener's granuloma, primary sclerosing cholangitis, reactive arthritis, Reiter's syndrome, Behcet's disease, cutaneous vasculitides including pyoderma gangrenosa. Wheldon adds: "Conditions which may suggest the possibility of flare-ups of chronic Chlamydia pneumoniae infection deserving serological investigation include the following — a multiplicity being more strongly suggestive: recurrent sinusitis, recurrent chest infections, chronic fatigue (especially if following a respiratory infection), focal neurological deficits, myalgia, muscle fasciculation's, recurrent episodes of bronchospasm, unexplained pleuritic pain, angina, recurrent arthralgia, unexplained recurrent abdominal pain, unexplained menorrhagia, recurrent fistula-in-ano, recurrent cutaneous vasculitides, achalasia, intestinal dysmotility."

How Chlamydia Pneumoniae Causes Such a Plethora of Diseases

The following is a condensation of a slightly longer post which can be found at this link.

Jim K

Chlamydia pneumoniae and Rosacea: A potential link?

 

While the exact pathology of rosacea is not completely understood or widely agreed upon, recent studies suggest that chronic inflammation likely plays a role in many of the symptoms associated with this disease.

 

Background

Rosaceai is a chronic disorder of still unknown cause that affects an estimated 14 million Americans.¹ Rosaceai often initially presents itself with transient flushing and redness of the cheeks, nose, forehead and chin, but it may also involve other areas of the body, including the ears, neck, and chest. With time the transient flushing becomes more frequent, the transient redness tends to become more persistent, and papules, pustules, and visible blood vessels called telangiectasias may also appear. Facial swelling, or edema, also often accompanies rosacea, as do burning or stinging sensations of the affected areas. In addition, many people with rosacea often also have the concomitant chronically irritated eye and eyelid symptoms of ocular rosacea and blepharitis.²

The exact pathology of rosacea is not completely understood or widely agreed upon, but recent studies suggest that chronic inflammation likely plays a role in many of the symptoms associated with this disease. And the chronic inflammation and blood vessel involvement in this disorder may well point to involvement of gram-negative bacteria, or more particularly their endotoxins, which have been shown to elicit similar response upon entry into the bloodstream.

While several gram-negative bacteria, including H. pylori and B. oleronius (found in Demodex folliculorum) have been associated with rosacea in the past, they have not been shown to enter the bloodstream, and thus they are unlikely to play anything more than a secondary role in the disease. Chlamydia pneumoniae, however, has been associated with rosacea in one small study, and studies in other inflammatory diseases in which it is being studied closely indicate that it is quite capable entering and persisting in the bloodstream, as well as producing the type of chronic inflammatory response that has been associated with rosacea. This evidence suggests the potential for C. pneumoniae's involvement in rosacea, at least secondarily.

 

Evidence

Although the exact pathology of rosacea is still unknown, recent studies suggest that chronic inflammation likely plays a role in many of the symptoms associated with the disease. Supporting the role for chronic inflammation is the host of elevated proinflammatory cytokines (TNF-a, IL-1B), matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), nitric oxide (NO), and reactive oxygen species (ROSi) that have been associated with rosacea in recent studies.³ Rosacea has been associated with elevated vascular endothelial growth factor (VEGF) in recent studies as well.⁴

It is important to note that the discovery of these elevated inflammatory mediators in rosacea may suggest important clues to an underlying disease etiology when comparing them as a whole to other known pathologies. And indeed, the elevated cytokines, MMPs, VEGF, NO and ROS associated with rosacea, match closely with the known pathology of early gram-negative sepsis, an infection of the bloodstream caused by toxin-producing bacteria.⁵

In fact, endotoxins, or rather lipopolysaccharides (LPSi), portions of the outer membrane of gram-negative bacteria, are widely known to induce a variety of inflammatory responses, ranging from mild to severe inflammation (and death), depending on the virulence of the bacteria endotoxins themselves.⁶ Recent studies suggest as well that vascular endothelial growth factor (VEGF) itself may actually be a key biomarker for sepsis.⁷

While gram-negative bacteria such as H. pylori and even B. oleronius (found in Demodex folliculorum) have been associated with rosacea in past studies, since these bacteria have not been shown to enter the bloodstream, one would not expect them to produce pathology similar to early sepsis.⁸ So looking at other inflammatory diseases for clues relating to associated gram-negative bacteria, one such pathogen, Chlamydia pneumoniae, stands out for its association with many inflammatory diseases, including Atherosclerosis, Multiple Sclerosisi, Asthmai, Alzheimer's and other inflammatory disorders.⁹

Interestingly, one small study has linked C. pneumoniae with rosacea directly, detecting serum antibodies of C. pneumoniae in 8 of 10 patients with rosacea and detecting C. pneumoniae specimens in 4 of 10 cheek biopsy.¹⁰ Other studies suggest that infection with C. pneumoniae can lead to pustular rashes (acute generalized exanthematous pustulosis) and increased VEGF production, as in the case with wet age-related macular degeneration.^11,12 These of course are most likely caused as by-products of the chronic inflammation associated with this pathogen, but I point them out since papule and pustule rashes and increased VEGF production are symptoms of rosacea.

Persistent C. pneumoniae infection of epithelial cells has been shown to produce chronic blood vessel inflammation, resulting in production of a host of cytokines and growth factors such as those found in rosacea as well as promoting a "foci of inflammatory responses in addition to promoting cellular proliferation, tissue remodeling and healing processes".¹³ And additional studies suggest that chlamydiae, while classified as gram-negative bacteria due to their outer LPS coating, are actually a distinct group of eubacteria, with a unique multi-form, intracellulari and extracellular development cycle, allowing them to change between forms and promote the persistent infection that may lead to chronic inflammatory disease.¹⁴

Another clue potentially linking rosacea with C. pneumoniae involves recent studies in the anti-microbial peptides, cathelicidins, and their activity in rosacea. These recent studies have identified unusually high levels of kallikrein activated cathelicidins in rosacea and suggest that these two substances may be in part responsible for producing the papules and pustules associated with rosacea as well as in promoting the angiogenesis associated with the disease.^15,16,17 Some additional studies have shown too that C. pneumoniae seems to invoke unusually high levels of cathelicidin activity and that endotoxins in general activate the kallikrein-kinin system.^18,19 Intriguingly, still other studies suggest that cathelicidins seem to be ineffective in clearing C. pneumoniae infection.²⁰ Potentially this is due to C. pneumoniae's ability to revert between forms, effectively evading the immune response. If this were correct then a C. pneumoniae infection, with the resulting ineffective yet elevated levels of activated cathelicidins, could indeed explain the unusual cathelicidin activity found in rosacea.

Dr. Charles Strattoni, MD, at Vanderbilt University, in a recent interview, ²¹ summarized his observations of some of the emerging research on C. pneumoniae. He noted how C. pneumoniae crosses from the lungs to the bloodstream via infected macrophages. The spore-like Elementary Bodies (EBi's) then circulate in the bloodstream to infect other organs throughout the body, including the liver, bone marrow, spleen, kidneys and skin.²¹ Potentially this might explain how C. pneumoniae, whose initial entry into the body is via the respiratory system, might arrive in the skin to cause rosacea. This may explain too the discovery of C. pneumoniae in cheek biopsy of rosacea as in the study discussed above.

 

Conclusion

In summary, Chlamydia pneumoniae may be involved at least secondarily in the etiology of rosacea. C. pneumoniae is a persistent, gram-negative bacteria known to enter and exist in the epithelial cells of the bloodstream, and it is known to produce the type of chronic inflammation that can be found in rosacea. Studies suggest C. pneumoniae may be involved with the etiology of many other inflammatory diseases, and intriguingly, a small study suggests a potential link with rosacea itself. Combined, this evidence would suggest more study related to C. pneumoniae's potential involvement in rosacea is necessary.

 

 

References

1. National Rosacea Society. Information for Patients: If You Have Rosacea, You're Not Alone. Rosacea.org.

2. National Rosacea Society. Information for Patients: All About Rosacea. Rosacea.org.

3. Bikowski, Joseph. Examining Inflammation as a Common Factor in Theories of Rosacea Pathophysiology. RosaceaToday.com.

4. Smith JR, Lanier VB, Braziel RM, Falkenhagen KM,White C, Rosenbaum JT. Expression of vascular endothelial growth factor and its receptors in rosacea. Br J Ophthalmol. 2007 Feb;91(2):226-9.

5. Institute for Inflammation Research, Rigshospitalet Univ Hosp, Copenhagen. Diagram: Early events in sepsis. Inet.uni2.dk.

6. Todar, Kenneth. Online Book of Bacteriology: Mechanisms of Bacterial Pathogenicity: Endotoxins. Textbookofbacteriology.net.

7. Prescott, Bonnie. New Study Finds Key Role For VEGF In Onset Of Sepsis. Medical News Today. 21 May 2006.

8. Rebora, A. The management of rosacea. Am J Clin Dermatol. 2002;3(7):489-96.

9. Stratton, Charles W. Association of Chlamydia pneumoniae with Chronic Human Diseases. Antimicrobics and Infectious Diseases Newsletter. 2000 July; 18(7).

10. Fernandez-Obregon A and Patton DL. The Role of Chlamydia pneumoniae in the Etiology of Acne Rosacea: Response to Oral Use of Azithromycin. Cutis. 2007 Feb;79(2):163-7.

11. Manzano S, Guggisberg D, Hammann C, Laubscher B. Acute generalized exanthematous pustulosis: first case associated with a Chlamydia pneumoniae infection. Arch Pediatr. 2006 Sep;13(9):1230-2. Epub 2006 Aug 17.

12. Leach, Mary E. Chlamydia pneumoniae present in eyes with 'wet' age-related macular degeneration. Medical News Today. 13 Nov 2005.

13. Blasi F, Centanni S, Allegra L. Chlamydia pneumoniae: crossing the barriers? Eur Respir J 2004; 23:499-500.

14. Hogan Richard J, Mathews Sarah A, Mukhopadhyay Sanghamitra, Summersgill James T, Timms, Peter. Chlamydial Persistence: beyond the Biphasic Paradigm. Infection and Immunity, April 2004, p. 1843-1855, Vol. 72, No. 4.

15. National Rosacea Society. Is Rosacea Like an Allergy?, Rosacea.org. Aug 2006.

16. Koczulla Rembert, von Degenfeld Georges, Kupatt Christian, Krotz Florian, Zahler Stefan, Gloe Torsten, Issbr¸cker Katja, Unterberger Pia, Zaiou Mohamed, Lebherz Corinna, Karl Alexander, Raake Philip, Pfosser Achim, Boekstegers Peter, Welsch Ulrich, Hiemstra Pieter S, Vogelmeier Claus, Gallo Richard L, Clauss Matthias, Bals Robert. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003 June 1; 111(11): 1665–1672.

17. Nizet Victor, Gallo Richard L. Cathelicidins and Innate Defense Against Invasive Bacterial Infection. Scand J Infect Dis. 2003; 35: 670-676.

18. Edfeldt K, Agerberth B, Rottenberg ME, Gudmundsson GH, Wang XB, Mandal K, Xu Q, Yan ZQ. Involvement of the antimicrobial peptide LL-37 in human atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1551-7. Epub 2006 Apr 27.

19. DeLa Cadena Raul A, Suffredini Anthony F, Page Jimmy D, Pixley Robin A, Kaufman Nathan, Parrillo Joseph E, Colman Robert W. Activation of the Kallikrein-Kinin System after Endotoxin Administration to Normal Human Volunteers. J Amer Soc Hematology. 1993; 81(12), 3313-3317.

20. Donati Manuela, Di Leo Korinne, Benincasa Monica, Cavrini Francesca, Accardo Silvia, Moroni Allessandra, Gennaro Renato, Cevenini Roberto. Activity of Cathelicidin Peptides against Chlamydia spp. Antimicrobial Agents and Chemotherapy, March 2005, 49(3), 1201-1202.

21. Jim K. Recent Observations by Dr. Charles Stratton on Chlamydia Pneumoniae (Cpn) Infection. Cpnhelp.org. Aug 2006.

 

 

Chlamydia Pneumoniae in CFS/ME & Fibromyalgia

Chronic Fatigue Syndromei, Fibromyalgia & Chlamydia Pneumoniae[1]

Introduction

(Note: the original page for this became non-functional for some reason. This copy is identical except for some minor text layout details)

Chronic Fatigue Syndrome (CFS), also called Chronic Fatigue Immunodeficiency Disorder (CFIDSi), or called Myalgic Encephalomyelitisi (ME) in Great Britain. CFS affects 1 million Americans, with "tens of millions" more who have a fatigue condition that doesn't meet the strict criteria for Chronic Fatigue Syndrome.[2] According to the Center for Disease Control (CDC), which considers CFS an accepted medical condition,[3] there is no officially known cause or cure for CFS or for the related, and often co-occurring, condition of Fibromyalgia Syndrome (FMSi).[4]

Despite the CDC's affirmation, the syndrome and its diagnosis is still considered controversial even in this day and age. Some doctors continue to insist that Chronic Fatigue Syndrome is not a "real" disease entity. It may be rather a surprise to it's sufferers when, naively seeking medical assistance, they find that their doctor doesn't believe that their symptoms are from a "real disease" or merits medical treatment. That there is no known "test" for Chronic Fatigue Syndrome that can conclusively demonstrate its existence is one of the difficulties here.

Perhaps another difficulty is that medical practitioners are socialized to believe that feelings of their own helplessness are a sign of personal failure. A solution to this psychological conundrum is to blame the patient by "psychologizing" the problem i.e. "It's in your head." Fortunately, acceptance of the legitimacy of the disease has increased in recent years, even if conventional medical treatment for it continues to have little to offer of help.

As the causal factors of CFS are considered unknown, conventional medical treatment for it and for Fibromyalgia Syndrome are all palliative (symptomatic) in nature: antidepressants for mood and pain associated with it, medications for sleep, stimulants for the fatigue, behavioral strategies, and so on. These can help make life bearable but don't fundamentally change the condition. [5]
Disease Syndromes: more common than you think -

Chronic Fatigue Syndrome is often