Therapeutically, if a fungal overgrowth is present (in which case we assume a stressed GI system, propensity to yeast or fungal overgrowth, not the likelihood of systemic infection), this can be supported by the die-off or kill-off reaction. It is open to debate whether this represents a medical Jarisch-Herxheimer (“Herxheimer reaction”) or a release of potential toxins (aldehydes) with lysis of the yeast/fungi. There is a period of more fatigue, more tiredness, usually more “spaciness”; then within usually ten to fourteen days the patient should be doing better clinically (sharper, brighter, healthier). If the die-off or kill-off lasts longer, one must suspect a problem or the possible need to change the antifungal. If there is a possible resistance, we must evaluate by medical decision whether improvement is occurring, the child needs some additional help or support, or it is better to proceed with changing the antifungal. Another issue of an ongoing negative reaction (usually different than straight die-off/kill-off) may be due to a medication formulation often not agreeing with that patient versus the straight medication itself. This is a potential issue with any medication used, particularly generics. These effects may be minimized by having pure compounds made, avoiding red dyes or liquids. (When using a liquid, try to stay grape or orange with the flavoring.)
While Candida albicans is arguably the single most important fungal pathogen, it is also a commensal organism, present in virtually all human beings from birth. It is ideally positioned to take immediate advantage of any weakness or debility in the host, and probably has few equals in the variety and severity of the infections for which it is responsible.1 While we will research and fight for many years re the role of candida in different disease states, many of those issues are clearer if thought of as an opportunistic overgrowth, not as the primary cause of many symptoms or disorders it is often associated with. Clinically, there is abundant inferential evidence that both mucocutaneous and systemic candidiasis are typically associated with defects or weaknesses in the cell-mediated immune response.2 They may reflect specific deficiencies in this context, such as in chronic vaginal candidiasis3, 4 or chronic mucocutaneous candidiasis.5 (One should note that while one might anticipate neurocognitive dysfunction in these states, it is not a primary focus of discussions. Significantly, these states do not account for or induce an “autistic” state of CNS dysfunction, seeming to help negate many metabolic theories that abnormal fungal metabolic products, seen in exceptionally high volume in these types of patients, induce “autism”—again support against yeast as the primary pathogen in many diseases with which it is supposedly associated!)
Epidemiological studies of C. albicans have been hampered by the lack of precise and reproducible methods for identifying isolates. Whatever the ultimate role and pathogenesis of candida, there seems to be no doubt that it can play a role in many pathologic conditions. As noted, yeast is certainly a potential pathogen in any immune dysfunction/dysregulated state. Yeast may be seen as a secondary phenomenon due to a generalized immune dysfunctional state (often documented by altered delayed hypersensitivity when tested). Clinically, it is not inconceivable that a yeast overgrowth in the GI tract can in theory interfere with nutrient absorption, altering amino acid and protein metabolism, thereby altering multiple body functions. I do believe that it is logical, if you are in an immune-dysregulatory state, you may be prone to an overgrowth in the GI tract. It is likely candida may play a role in what is referred to as the “leaky-gut” phenomena. Some physicians believe you have a toxin (an aldehyde derivative) released by the yeast and absorbed into the body, affecting the nervous system. Many physicians make the mistake of giving medication to control the yeast for only a few weeks or even a month and then stopping. If the patient was starting with a normal or healthy immune system this would be a very logical step. But working on the premise that a major part of the problem is the ongoing issue of the immune system dysfunction, trying to help it return to a healthy state, until it is there, and not offering some form of useful support is clinically foolish. In fact, one can argue that on-and-off therapy may be more inducive to resistance than some ongoing rotation of a maintenance therapy. (Again, with better true markers, we should be able to investigate this appropriately.) If, with treatment, a child becomes fully “normal,” and their immune system is healthy, it is possible to withdraw all treatment and the child should remain healthy. Ultimately, the key is the body’s own ability to keep appropriately in check an organism that it doesn’t want to have there to start with. We are supposed to do that when we’re healthy, but the body may have a problem when the immune system is stressed or compromised. At present, there is very little benefit to blood, stool, or urine testing for yeast or fungi. In a reputable lab, when any of these tests are positive, they are likely significant, but just because they are negative does not mean there is not a problem. (Note: Some of the children will have eosinophilia secondary to a parasite. One should not hesitate to send stool for O&P to a reputable lab if indicated.) All drug therapy is based on monitoring clinical and laboratory parameters with drug or dose modification as indicated.
Application
History of multiple ear and sinus infections with multiple antibiotics
Thrush or “suspicious” dermatitis along with markers of low NK cells raise significantly the likelihood of a fungal or yeast overgrowth in a child or adult
The idea of yeast or fungal overgrowth will be received skeptically until better markers facilitate accurate identification, but is interesting (particularly in children) how the symptoms seem to relate to yeast byproducts (i.e., fermentation, drunkenness). If one thinks of altered delayed hypersensitivity as a component of the stressed immune systems, low NK cell function, the rationale, the idea of yeast as a superinfection becomes logical, just like we now recognize its potential role in many other immune related disorders.
Understanding the immune system, the concept of stress, opens the door to a rational discussion of the potential role of an antifungal in some of these children. With the high-level researchers I have worked with, if I said these children were the way they are because of yeast or candida, they would never have spoken to me again. I would have been foolish beyond that if I implied yeast or bacteria were loose in their bloodstream. If that was the case, adults or children like that would not only be in an intensive care unit, they would likely be dead. If instead I carefully came from the direction that we know from working with adults with this disorder that they frequently have what is called altered delayed hypersensitivity, then one can attempt to be rational, logical. We are taught as physicians that when delayed hypersensitivity is not working correctly, that is the part of our immune systems that is supposed to control and contain yeast and fungi—so when approached from that direction, there is justification to talk about applying an antifungal during a more controlled trial. It is critical to understand that if there is a likelihood of a yeast or fungal component in a child or adult with this disorder, it is because of the immune system being in a stressed state, not because it’s a primary infection. I’ll stress again, in light of the large amount of misinformation given to parents and adults, that if these children (or an adult) had evidence of yeast and fungi in their bloodstream, they would be critically ill in a hospital, not walking around with this mistaken label “autism.” As discussed above with antivirals, if there’s a real problem, real indication to use an antifungal, one must monitor its use (particularly the liver functions) and treat adequately. Consistent with infectious disease teaching, if one wants success, one must achieve a true remission, not go on and off antifungal choices at random, increasing the chance of making them ineffective, again creating more resistance. Once again, it is important to stress that when yeast or candida is present, it is a secondary, not a primary, pathogen, what we in medicine refer to as an opportunistic infection/pathogen. An antifungal if effective should cause what is called a “die-off,” which will last from ten to fourteen days. A child or adult should use Advil, Motrin, or Tylenol for symptoms. If the
child is improving, one may let the die-off go a little while longer. If it continues, it may be a chemical problem (with that agent) or resistance; either way you will have to switch to another medication. In theory, the healthier the child’s body becomes, the less the need for a strong antifungal. Rather than starting or stopping at different intervals, it is a better principle to rotate antifungals every six to twelve months as long as they are needed.
CBC and chemistry panel are mandatory every one to two months.
There is no perfect test for candida. History is as important as any current test in making judgments for antifungal use
A trial with an antifungal (for now, until we have new markers available) may remain the best test for efficacy.
It is important that the parents check in during die-off, to be sure what is occurring is indeed die-off and not a reaction to the medication. The die-off usually lasts about seven to fourteen days, and after that time the change in the child can be rather dramatic. If the die-off does not end within fourteen to seventeen days, it is generally a reason to change choice of antifungal. (It may be an issue of resistance to medication or just a chemical reaction to that medication, particularly if it’s a generic.)
If the treatment is being successful, usually eye contact improves. The children seem more tuned in and less “foggy.” Parents will report that the frequency of inappropriate noises, teeth grinding, biting, hitting, hyperness, and aggressive behavior decreases. The children no longer act almost drunk by being silly and laughing inappropriately.
Sample Antifungals treatments:
(Initiate at ½ dosing for six days, then full)
Nizoral
➢—4—5 mg/kg hs—max. 200 mg Generally change after six to eight months maximum.
May have additional “immune” effect via “mild effect adrenal-cortical axis”—recent literature seems to support some direct effect on “neuroimmune” axis.
or
Diflucan
➢—4—5 mg/kg hs—max 200 mg Can be used longer term (per studies in other indications) • Limit to 1 yr. (before rotating)
or
Lamisil
➢ 250 mg (preferred for change over for maintenance rather than initial) ~ 1/4 tablet 30—50 lb.
~ 1/3 tablet 50—70 lb.
~ 1/2 tablet 70—95 lb
~ 3/4 tablet 95—120 lb
Full tablet above 120 lb.
The Potential Role (Limited) for Antibiotics
With the recognition of autism as a disease, a stressed and compromised but not broken immune system, opens the door, as discussed, to ideas of opportunistic organisms such as candida, and perhaps secondary chronic bacterial issues such as part of what we now call pediatric PANDAs. This was the recognition that somehow in the body, the presence of a chronic strep infection could trigger OCD (obsessive-compulsive) behaviors.5, 6, 7, 8,
Rather than long-term penicillin (not likely to be healthy for the GI tract), I use erythromycins usually. While sometimes an issue with GI tracts—stomachs (particularly in pill form, particularly in adults), I learned many years ago that while no longer considered a primary agent of choice, they were not only still effective (decades ago almost no resistance, now there is some), but unlike stronger antibiotics they were called bacteriostatic (they essentially paralyzed an organism, the body had to finish killing it off) rather than bacteriocidal (kill the organism directly). Because the body does not rush to kill off the “good guys,” it was recognized many years ago (particularly with adults with CFS/CFIDS) that erythrocins and erythromycins (if tolerated) were least likely to disrupt the normal flora.
First working with CFS/CFIDS and missed ADHD in children and adolescents, many patients would present with what was being called a “red crescent” (inflammation of the oral—pharynx opening) and many had glands in the neck enlarged. Particularly when the anterior cervical glands (glands in the front of the neck) are enlarged, it raises suspicion of an infection. Since this infection is low grade, often chronic, one would not expect a routine throat culture to show much. Without a controlled university study, it was not appropriate to do “needle biopsies” for direct cultures (which would have to be extensive in searching for what might really be there) of what was there, leaving the option of ignoring these findings in an ill patient, or “compromise” and use a relatively nonoffensive, noncrucial agent (the erythrocins/erythromycins) to try to suppress or eradicate the infection. Not only was this very successful over the years (leaving open the ongoing issue that this, like so many other findings in these children, should be investigated, questioned, not just ignored or “written off”), but also it was my repeated observation (hard to call a child “placebo”) that on an erythromycin/ erythrocin medication the child or adolescent would go to school, function successful, but off the erythromycin/erythrocin (similar names, different forms of same basic medicine: an old-fashioned antibiotic) would be bedridden or severely fatigued again.
It has been my experience that many parents would never have turned to alternative answers if the pediatric profession took an active role in diagnosing and treating these illnesses rather than taking a wait-and-see approach. I hope it is time pediatricians returned to being the primary doctors for “special needs” children, not observers from the sideline.
It is worth noting that if I were to be challenged with the question of what I was treating, I could reply I was not sure, but it was helping, and I was not creating likely harm. If I had advocated using a medication like Vancomycin, for example, without hard infectious disease evidence, that would have been irresponsible. To risk creating resistance to one of last major antibiotics used in hospital in life-threatening situations would have been negligent medicine. I stress again, that while a medication like erythromycin could be questioned, I have never, will not use stronger options unless they are directly indicated. It turns out, that with the information that erythromycins affect the “neuroimmune” system, one comes back to the question as to whether the medication is treating a bacterial infection or is it merely helping the neuroimmune system; for now my response remains “I don’t care, as long as it is helping.” To leave a child’s brain and body fighting a disease they cannot win by themselves, to not support them with potentially safe agents, safe pharmaceutically clean agents, is not an option for me.
The place for SSRIs and limited other neurotropic agents
After diet elimination (always), antiviral use (usually), and antifungal use (frequently), then I will begin to consider the use of an SSRI. What is an SSRI? SSRI stands for serotonin selective reuptake inhibitor. What does that mean? When I was growing up, our parents often turned to prescription pills, then to medications like Librium and Valium as antidepressants. I can say from experience with NeuroSPECT, there would nothing beneficial about giving Librium or Valium to these children or their brains. While they have their place therapeutically, they are not going to make an adult or child’s brain healthier. They essentially work by sedating areas that are involved in emotions such as depression in the brain.
The goal is to maximize a child’s cognitive development. Therefore, the last goal to me as a pediatrician is to try to sedate or control a child. I would never choose to use SSRIs or recommend SSRIs as antidepressants. Unlike old-fashioned antidepressants that sedated the brain, essentially SSRIs do one job: they block the reuptake of serotonin being produced naturally and make it stay around longer. In this case, and fortuitously, the temporal lobes are primarily serotonin mediated. Since the key to this process is the neuroimmune-mediated shutdown of function, blood flow to critical areas of the temporal lobes, if I can take and block the reuptake of the serotonin being produced naturally (although they were not invented for this purpose), it’s as close as I can come to titrate that area of the brain to get what one should be looking for therapeutically: first, a child or adult that wakes up rested in the morning, as if they had a good night’s sleep and a healthy stage IV REM sleep cycle, and, second, a child (or adult) who looks bright, fe
els alert, as one would expect with any other healthy child.
In pediatrics we are taught to tell parents not to compare children, but in this case, it is true that your child should have a bright look to his or her face, as does any other healthy child. They may still be behind developomentally (takes time to catch up), but they must be there physically to succeed in the long run.
With the goal of long-term safety, I have stayed with what are called the simple SSRIs. Up to this point that means Prozac, Paxil, Zoloft, or Celexa. I avoid and do not believe in what are called complex SSRIs. It is very important to monitor a child for that sharpness, that alertness I have been writing about, and make sure that clinically you are not really inducing any negative side effects. While SSRIs can induce all sorts of reactions (which is the reason to introduce them carefully, slowly, with other variables controlled), they are physically very safe. Within negative side effects, one is looking for “zoniness,” irritability, hyperness, or any response that, after time to adjust, is not in a positive direction for a healthier, better functioning brain/child. You are not asking an SSRI to control a virus, to control diet, or to control the immune system; rather, it is being asked to do one very important job, and this is help improve function in an area that has been sadly underworking, underused for a few years to many years.
The Myth of Autism Page 11