I intend this thread to be a discussion for the people that research and are knowledgable about KD. It is long, as I have much to say along with a great deal of research. This post is not really a good starting point for people that have arrived here because their loved-ones have been recently diagnosed (I am sorry you have had to find your way here) and your time would probably be better spent reading the huge amount of fantastic feedback and support throughout the rest of this site.
Basically you catch a bug and get sick from it. This is the model of illness we are all familiar with. It is what the field of medicine diagnoses and treats to great success. It is how we catch the cold and flu, but is this the only model of infection? â€œIt is estimated that 500 to 1000 species of bacteria live in the human gut and a roughly similar number on the skin. The average human body, consisting of about 1013 (10,000,000,000,000 or about ten trillion) cells, has about ten times that number of microorganisms in the gut http://en.wikipedia.org/wiki/Human_flora.â€ Note that this number does not include fungi and archaea which are also a part of the human â€˜floraâ€™. There are also many pathogens that infect us and stay with us for life such as Epstein-Barr virus or herpes viruses. What happens when one of these many organisms is allowed to grow to a great abundance due to genetics, favorable conditions, an illness that allows them to proliferate, etc? It seems logical beyond refute that if there are organisms allowed to live in our body then there will be conditions that allow one of them to thrive. The treatment of too much of one type of organism in the body is a part of alternative medicine, with the professional designation being a Naturopathic Doctor. Naturopathy aims to strengthen the body through proper diet, exercise and supplements to control and eliminate these infections beforehand while boosting the immune system and therefore is more of a preventative medicine. In other cultures, it is the first line of defense before seeing a physician. In North American culture, we are conditioned to think of alternative medicine as a bit â€˜out thereâ€™ even though much of what they propose makes very good sense and nobody can really argue that you should eat good food, get all the right vitamins and exercise.
State of Alternative Medicine
Many practitioners of alternative medicine believe that pathogens naturally found in the body allowed to grow to huge numbers are the reason for many of the illnesses/diseases that we know little about. â€œThe Arthritis Trust of America/Rheumatoid Disease Foundation considers the nearly 100 rheumatoid diseases - including Rheumatoid Arthritis - systemic diseases. Since the disease can affect any organ or system in the body, manifestation of symptoms produced give rise to the various name classifications often misconstrued as totally separate diseases. Breaking physician health specialties into different practices according to parts of the body affected lends even more credence to the illusion that separate and distinct diseases are presented.â€ Another example is the Hoxsey Clinic â€“ an alternative medicine clinic that has been treating cancer as an infection since 1963. It has been driven out of the states but has a presence in Mexico http://www.cancure.org/hoxsey_clinic.htm.
These are both somewhat fringe, but I mention them because there does seem to be relationships as many have seen here â€“ you get KD and then have allergies, asthma, sinusitis, arthritis, eczema, etc. even though aneurysms is the only recognized long-term side effect. Most practitioners of Naturopathy present themselves in a much more subdued and non-sensational way. Many believe that Candida infection (a yeast/fungi naturally found in the human body) is at epidemic levels within the population due to high carb/sugar (pasta, bread, flour, alcohol) lifestyles as well as overuse of antibiotics and that this pathogen alone causes a great many illnesses. They believe that bad organisms naturally found in the body feed upon sugars (and what your body converts to sugar) and that Candida, benefits immensely from antibiotics by having all of its natural competition wiped out. They offer many treatments based around diet (eliminating food for bad organisms), supplements and lifestyle changes with a primary goal of strengthening the body and immune system to allow it to fight off infection.
Interestingly, many of the animal models of vasculitis and arteritis (i.e. inflammation) used to study KD are based upon Candida â€“ the yeast/fungi responsible for thrush, diaper rash and female yeast infections. It is recognized in medicine that it will grow to great abundance in immune-compromised people as evidenced in cancer and AIDS but anything more than this lacks experimental proof. Searching for case studies where Candida has been found results in almost every illness imaginable â€“ it is very opportunistic.
I have chosen to discuss this pathogen as a base infection of self because it has the most experimental data available, I have spent over a year researching it, it is used heavily in creating the models of vasculitis/arteritis studied in KD, it can cause aneurysms, it is superantigenic, it is in everyone to some extent, etc. Candida infection experimentally exhibits many of the medical markers of KD such as TNF alpha, V beta, SED rates, response to immunoglobulin and any other aspect I have researched (links to some of my research on this are here: viewtopic.php?f=7&t=1829 ). It has some very interesting properties, which I believe most are unaware of and which I suspect are very important.
Candida is normally found within the digestive system. It is both yeast and fungi depending upon whether it has colonized (called dimorphic). In yeast form it is basically harmless, but in a colonized form it can release up to 79 different toxins. The release of toxins by organisms is one of the research paths of KD as illustrated in this quote from Kawasaki Disease: A Brief History by Jane C. Burns, MD, Howard I. Kushner, PhD, John F. Bastian, MD, et al., â€œâ€¦the idea that bacterial toxins acting as superantigens could trigger the cascade of events that lead to KD has been widely debated. This controversial hypothesis has been supported by some studies and refuted by others http://pediatrics.aappublications.org/c ... /2/e27.â€ Note that it says â€œbacterialâ€ â€“ fungi are always overlooked but in some respects they are even more potent than other pathogens.
This is a decent write-up on what alternative medicine believes about Candida infections: http://www.cfs-recovery.org/docdarren2.html. Read it with a grain of salt if you are medically grounded. Medicine is based on experimental results while alternative medicine is based on observation of improvement with or without experimental proof where many treatments are based on hundreds of years of observations in various cultures. Some things linked to Candida through observation in alternative medicine include allergy, ear infections, sinus infections, eczema, fatigue, headaches, extreme sensitivity to mould and chemicals, etc.
Important Properties of Candida (and likely other pathogens)
Aside from the fact that Candida may exist as yeast or fungi and that a live fungal form in experimentation is essential in understanding it, there are several properties that are extremely important to understand:
1. The Herxheimer Reaction (http://en.wikipedia.org/wiki/Herxheimer_reaction). When massive quantities of an organism within the body die, the host experiences a Herxheimer or die-off reaction due to the release of a massive quantity of toxins. Basically, a large amount of inflammation is caused and the host experiences flu-like symptoms (fever, nausea, etc). This reaction is medically proven and first noted in the treatment of syphilis. In alternative medicine, it is well noted that patients being treated for Candida experience this and there are numerous cases/evidence. If you search for the Herxheimer Reaction and TNF alpha or sepsis, you will see quite a few cases where the medical markers (TNF alpha, IL6, IL8, etc.) match those in KD.
2. Quorum Sensing (http://en.wikipedia.org/wiki/Quorum_sensing). Candida can communicate and coordinate activities between fungal colonies by emitting and receiving molecules. It is disturbing that something within us can coordinate its own rate of infection, colonization and in all probability, response. This opens the possibility that there are various signals it could receive to make it behave in an unexpected way (i.e. chemicals, enzymes, our immune signals, etc.).
3. Killer-Sensitivity - the most important property. Candida is very sensitive to numerous â€˜killerâ€™ toxins. Certain toxins emitted by other organisms may decimate Candida and it cannot prevent its own demise from a small amount of toxin from another pathogen (http://www.pubmedcentral.nih.gov/articl ... tid=283789 and http://www.pubmedcentral.nih.gov/articl ... tid=272739). This is a bit different than â€˜Programmed Cell Deathâ€™ â€“ the situation where a huge amount of cells/organisms die (like a mass suicide); however, I have read some articles insinuating that programmed cell death could be triggered by something (http://stke.sciencemag.org/cgi/content/ ... ;170/3/391 ).
Until this point, everything written is a decent representation of medicine and alternative medicine to the best of my knowledge. I apologize if I have misrepresented or offended anybody with respect to my understanding.
Alternate Ideas of Pathogenesis
Given the experimentally proven properties of Candida, the fact that Candida is commonly used to create the animal models of inflammation studied in KD, and the fact that Candida portrays many of the medical markers of KD, I have to wonder:
â€¢ If a person had a large amount of Candida (for example) in their body and they were exposed to another pathogen that it was sensitive to (Killer-Sensitivity), could this cause a massive die-off of the base Candida infection and result in a huge Herxheimer reaction (which would be acute KD)?
â€¢ Could there be a relationship between virulence/infestation, quorum sensing and human genetic polymorphisms (i.e. the genetic deviations already found in KD)?
â€¢ Could a massive toxic response be generated by exploiting the quorum sensing abilities of this organism? If (as in first bullet) a secondary pathogen were introduced with a killer toxin, could quorum sensing illicit a huge toxic response against a threat?
The question of how to figure out the pathogenesis of KD would then be a matter of pairing base infections to other pathogens or chemicals that they are sensitive to or which triggers a response and there is no shortage of pathogens found in KD. This would mean that acute KD is not one infection, but two â€“ called â€˜concomitant infectionâ€™ in medical terminology. I have spent countless hours researching this aspect of KD and as far as I can tell, no experiment has ever been performed where a KD animal model is exposed to another pathogen (my top pick is exposing a Candida animal model to active Epstein - Barr virus or pseudomonas). Epstein-Barr virus is heavily implicated in KD with no conclusive findings, it is superantigenic, it is very common in the population and ultimately it has been found to be involved in several types of cancer and other terrible illnesses.
Some Research Paths
Given the â€˜important properties of Candidaâ€™ and â€˜alternate ideas of pathogenesisâ€™ above, the belief in alternative medicine that high amounts of sugar allow proliferation of bad organisms and several other details mentioned throughout this write-up, I hope to offer some research to provoke your thoughts. The animal models of inflammation used to study KD lack a trigger for acute KD. They seem to be more of a model of long-term infection of one type of organism.
Acquiring a base infection:
â€¢For Candida, is there relationship between inositol 1,4,5-triphosphate (ITKPC) as a signal to proliferate and colonize (http://mic.sgmjournals.org/cgi/reprint/143/2/437.pdf) to the already found KD genetic relationship to ITKPC (viewtopic.php?f=7&t=1801). â€œIn Japan, experience of treating IVIG resistant KD cases successfully with Cyclosporin A (CsA) is accumulating (unpublished observations). CsA is an immunosuppressant targeting calcineurin that dephosphorylate and lead nuclear translocation of NFAT http://journals.lww.com/pedresearch/Ful ... ase.8.aspx .â€ What does this mean when compared to, â€œCalcineurin Is Essential for Virulence in Candida albicans http://iai.asm.org/cgi/content/abstract/71/9/5344.â€ I cannot fully understand all of this but generally these articles seem to state that there are genetic deviations in an area that codes enzymes/CA+/NFAT signaling in KD and that Candida may use these somehow. If the genetically deviant signal is to proliferate and colonize, then this could be a method to grow a large fungal infection.
â€¢In alternative medicine it is believed that bad organisms thrive on sugar (and what your body converts to sugar).
- o â€œKawasaki Disease in Young Adult with Concomitant new Onset of Type 1 Diabetes and Autoimmunethryoiditis.â€ http://www.endocrine-abstracts.org/ea/0 ... 010P23.htm
o â€œInsulin-Dependent Diabetes Mellitus in 2 Male African American Children After Kawasaki Diseaseâ€ http://pediatrics.aappublications.org/c ... /110/2/e27
o Do these people truly have a new case of diabetes, or does diabetes cause a large amount of sugar, proliferation of a base infection consuming it, death of a huge amount of the base infection from exposure to something else and subsequent recognition of KD followed by recognition of diabetes?
â€¢â€œKawasaki Disease Onset During Concomitant Infections with Varicella Zoster and Epstein-Barr Virus.â€ http://www.pubmedcentral.nih.gov/articl ... =pmcentrez. Two herpes viruses.
â€¢Imagine a person has a high level of Candida and is given the BCG vaccination. Candida is a fungus and BCG (vaccination for tuberculosis) seems to have anti-fungal macrophages (http://www.pubmedcentral.nih.gov/articl ... tid=348022). This does not seem to be a â€˜Killer-Sensitiveâ€™ reaction or a trigger, though I suspect if you had the vaccine in your stomach (where most Candida live), it would be. Oddly enough, giving a BCG vaccine to the stomach is the therapy for several cancers of the digestive system.
- o â€œAn ulcerated lesion at the BCG vaccination site during the course of Kawasaki Disease.â€ (http://cat.inist.fr/?aModele=afficheN&cpsidt=2801408)
o â€œInflammation at a previous inoculation site: an unusual presentation of Kawasaki disease.â€ (http://www.cmaj.ca/cgi/content/full/174/4/459)
o â€œTuberculin skin test reactivity in Kawasaki disease.â€ (http://cat.inist.fr/?aModele=afficheN&cpsidt=2675483)
o â€œUsefulness of BCG reactivation in Incomplete Kawasaki Disease: A Case Series.â€ (http://www.ispub.com/ostia/index.php?xm ... wasaki.xml)
o â€œVasculitis induced by immunization with Bacillus Calmette-GuÃ©rin followed by atypical mycobacterium antigen: a new mouse model for Kawasaki diseaseâ€ http://www3.interscience.wiley.com/jour ... 7/abstract .
o BCG vaccine and then Candida: â€œThe Role of BCG/PPD-Activated Macrophages in Resistance against Systemic Candidiasis in Mice.â€ http://www3.interscience.wiley.com/jour ... 4/abstract. The opposite of what I would like to see in an experiment â€“ they are using BCG as a vaccine to prevent Candida.
â€¢â€œHemophagocytosis complicating Kawasaki disease.â€ http://cat.inist.fr/?aModele=afficheN&cpsidt=1414420 . Please search for Hemophagocytosis Syndrome â€“ you will find KD and a few other autoimmune disorders.
â€¢â€œHemophagocytic Syndromes and Infection.â€ http://www.medscape.com/viewarticle/414792.
â€¢ â€œEvidence that Amphotericin B Mediates Reactivation of Latent Epstein-Barr Virus in Hodgkin's Lymphoma Allowing Cytotoxicity by Acyclovir.â€ http://www.pubmedcentral.nih.gov/articl ... id=2687644 â€œ. They suspect that this person had an EBV infection that went dormant but and was reactivated with amphotericin B (a fungicide given to rid this patient of Candida). This allowed the EBV infection to be destroyed and thereby kill the cancer it caused. This person went into remission within a day because treatment was halted due to a septic (Herxheimer reaction?) condition after initial treatment.
â€¢â€œPseudomonas-Candida Interactions: An Ecological Role for Virulence Factors.â€ http://www.sciencemag.org/cgi/content/a ... /5576/2229
- o â€œCan pseudomonas infection in experimental animals mimic Kawasaki's disease?â€ http://www.ncbi.nlm.nih.gov/pubmed/6542120
o â€œMUCOCUTANEOUS LYMPH NODE SYNDROME (KAWASAKI DISEASE) IN ISRAEL.â€ http://www3.interscience.wiley.com/jour ... 1&SRETRY=0
â€¢Ortho Phenylphenol is a relatively common microbiocide (anti-fungal and anti-bacterial) found in carpet cleaners and many other items. What happens if a little person inhales this? Can it induce a reaction if they have large base infection of self?
- o â€œIt was concluded that the mode of action of OPP is similar to the mechanism of action of some antibiotics.â€ http://www.biomedcentral.com/1471-2164/9/411
o A patent: â€œUSE OF ORTHO-PHENYLPHENOL AND/OR DERIVATIVES THEREOF FOR INHIBITING THE ASEXUAL REPRODUCTION OF FUNGI.â€ http://www.wipo.int/pctdb/en/wo.jsp?wo=2006015725
â€¢Candida research link: viewtopic.php?f=7&t=1829
As stated previously, I suspect that acute KD is a case of base infection X meets new infector Y. The list of â€˜thingsâ€™ I have found that should probably be paired (from models and case studies) include Candida, tuberculosis/bcg vaccine, Yersinia pseudotuberculosis, Epstein-Barr virus (EBV), dengue, bocavirus, coronavirus, pneumonia, diabetes, staphylococcus aureus, varicella zoster, streptococcal infection, Aspergillus fumigates, herpesvirus 6, anaplasma species, pseudonomonas and Lactobacillus casei (Sick Kids, TO animal model). I am certain there are many more and I have not spent much time on this list.
Benefits of this Model of Infection in KD
From everything I have read of KD, the model of single infector = KD would need to cover a whole lot of ground to explain adult cases, incomplete and atypical KD, even with the variability in genetics/immunity. I think it more likely that we need a paradigm shift in our thinking of infection and how it applies to rheumatology. Using a model where a person has a base infection exposed to something to induce acute KD could explain all of the variability. I suspect it can explain:
â€¢ The space/temporal findings, epicenter and mini-epidemics (i.e. a virus pops up and those with base infection X get acute KD)
â€¢ Observation of carpet cleanings (look at orthophenylphenol as an antimicrobial in some cleaners even though KD has been noted in steam-only cleaning which could also stir up a secondary pathogen. This chemical inhibits asexual reproduction of Candida)
â€¢ Swamps and vaccines (other pathogens)
â€¢ Season correlation (links to the mould/fungi life cycle, flu season, etc)
â€¢ Noted BCG vaccine effects
â€¢ Atypical cases such as gangrene, diabetes, etc.
â€¢ Incomplete cases including lack of fever (only growth of base infection? missing a secondary infection?)
â€¢ Acquiring other rheumatologic/autoimmune disorders pre and post
â€¢ What is being observed in IVIG and steroid therapy (does the KD patient provide a genetically altered signal that an infection proliferates within and does IVIG and steroid therapy affect signals and states by introducing a normal signal, different pathogens would then determine the differences in therapy observed such as resistance, etc.)
â€¢ The usefulness of the KD animal models which has been an ongoing discussion in KD
â€¢ The field of rheumatology and everything from allergy to Sjorenâ€™s, BehÃ§ets and Coeliacs and anything that causes vasculitis/arteritis
â€¢ Unifies alternative medicinal theory with rheumatology which are both at somewhat of a standstill.
â€¢ Why your kids crave sugar, get joint pains, get sick more than average and have odd reactions to certain things.
â€¢ â€œKawasaki disease may be a hyperimmune reaction of genetically susceptible children to variants of normal environmental flora.â€ http://www.ncbi.nlm.nih.gov/pubmed/17337130
I am not a doctor or naturopath but a professional and academic computer programmer who had KD 27 years ago without IVIG treatment. I never put much thought into KD until a year and a half ago when I found that treating myself for GERD/acid reflux affected the migraines I began having within 2 weeks post KD that have haunted me since. I hope that someday one of the animal models of inflammation with a Candida base infection is exposed to other pathogens and chemicals to see if it could cause acute-KD. I believe that the model of infection I have explained above is the next step in understanding rheumatology and autoimmunity. Ultimately, KD would have two forms. One would be the long and slow growth of a base infection of self causing slowly increasing vasculitis and the other would be an immediate, acute response from exposure to another pathogen causing instant vasculitis. While I am certain I have misunderstood and misrepresented some things in this write-up, I do not think I am incorrect about everything. I have over 350 links to abstracts, cases and experiments I have gathered and each one paints a little bit of the picture. I have searched for proof that this is impossible and came up with nothing. This area is a void in experimentation and taboo to talk about. I suspect that this needs researched by somebody trained with proper/full access to data as I do not think it has never been considered and ultimately, there needs to be controlled experimentation.