cyclic fever Archives - Hormones Matter

Autoinflammatory Syndromes Induced by Adjuvants: A Case for PFAPA

Published on July 5, 2017

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If there was one lesson I learned from my painful struggle with FQ toxicity, it was to be vigilant and informed about what goes into my body. I learned a great deal about the abundance of chemicals and genetically modified organisms (GMOs) in our food supply. I became an advocate for organic food, natural products and a life with as few medications as possible. One thing I still failed to question, however, was the safety and efficacy of vaccines.

Vaccine Side Effects: Learning the Hard Way

I’m a health psychologist, a teacher and researcher by trade. I have read about and believed in the public health benefits of vaccines since I became pregnant. After all, no matter your stance on the vaccine issue, no mother wants to see their child get severely ill from a preventable illness like measles. Having suffered tremendously in the early years of my child’s life with my own health issues, I wanted to make sure she was as healthy as possible, and I believed that vaccines were the best way to protect her health and her life, for that matter.

My daughter had her first fever of unknown origin at just 16 months old, shortly after a round of vaccinations. The fever reached 104 degrees and did not respond to Tylenol or Ibuprofen. She had no appetite and vomited when the fever would spike. I took her to our pediatrician and was told it was likely a virus. However, the doctor was perplexed as to why the fever was not coming down with fever reducing medication. We put her in tepid baths and held her for three days until the fever finally broke. My daughter seemed to bounce back quickly and we believed the pediatrician’s diagnosis that she had somehow caught a virus that caused her high fever. When the same fever returned four weeks later, I took her back to the pediatrician for answers. This time, she presented with a red throat, but the rapid strep test was negative. We were sent home with a diagnosis of another virus. My daughter again recovered after 72 hours, but I was uncomfortable with the diagnosis. Something just did not seem right. We were told that kids that young often get viruses and we should expect up to 7-12 illnesses a year. However, my daughter was not in daycare, and I was notorious for washing hands. Where was she picking up these viruses? To my knowledge, she had not been exposed to anyone who had been sick.

Cyclic Fevers

Four weeks later my daughter spiked another high fever in the middle of the night, and would vomit when the fever would reach it’s highest, generally around 24 hours after it first began. Tylenol and Ibuprofen only took the fever down one or two degrees, but this time I knew what to expect. I took her to our pediatrician, and once again, my daughter presented with a red throat and a negative strep test. We were sent home yet again with a diagnosis of a virus, but I knew in my heart something more complicated was going on. The month before, I had become even more vigilant about hand washing, and would use hand sanitizing wipes whenever we went out. I kept her home and out of the public as much as possible, because I had a feeling that we might be dealing with an immune system issue.

Mystery Diagnosis: Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA)

Given my training as a scientific researcher in the health field, the first place I went was the scientific literature. I typed “cyclical fever” into the Pubmed search engine. I came across this article and was introduced to a periodic fever syndrome called PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis). With PFAPA, children spike a high temperature every 2-8 weeks, usually with eerie periodicity, and often present with pharyngitis, swollen glands, and mouth sores. Fever reducers are usually ineffective. My daughter certainly had the high fever and the sore throat that seemed to come almost exactly four weeks apart. I continued with my research, and read that PFAPA can present with a variety of combinations of the above named symptoms (and other possible symptoms such as joint pain and headaches), but the hallmark is the regularly occurring high fever. PFAPA is generally not harmful to a child’s growth or development, and children eventually grow out of it before their teen years. Regardless, it is still extremely difficult to watch your child suffer month after month for days at time. PFAPA children often miss up to 30 or more days of school a year; vacations and childhood activities are often interrupted by illness, and children can suffer distress over being chronically ill. Many PFAPA children also experience febrile seizures from temperatures consistently reaching 105 degrees or higher.

I called my pediatrician, who had heard of PFAPA but assured me that it was rare and not a cause for concern at the moment. He suggested taking a watchful waiting approach. I agreed, as I did not want to subject my daughter to unnecessary testing. But when the fever occurred again three and a half weeks later, I became more forceful in my request for additional testing. Periodic fevers can also be caused by serious syndromes including cyclic neutropenia and juvenile rheumatoid arthritis (JRA), and I wanted to know what we were dealing with so I could get her treatment as soon as possible. We were referred to an infectious disease specialist at our local Children’s hospital who was able to rule out those alternate diagnoses.

After meeting with my pediatrician, PFAPA literature in hand, I requested a referral to a pediatric ear, nose throat specialist (ENT). In my research I discovered the only known cure for PFAPA (besides the natural progression of “growing out of it”) was a tonsillectomy, which fully ceases attacks in about 80% of cases. Although there is still much unknown about the etiology of the disorder, scientists have found that during PFAPA flares, IL-1–related, and IFN-induced genes are overexpressed, and when the child is healthy, gene profiles look normal. To put it simplistically, as an attack develops the body creates an inflammatory response to a phantom infectious agent by retaining T-cells in the tonsil tissue. By removing the tonsils, there becomes no place for these cells to congregate and episodes abort. I was granted the referral to the best pediatric ENT in our region of the country. He was familiar with PFAPA and agreed to perform the tonsillectomy on my daughter at the tender age of just 27 months. At the time of her surgery, ten months after her first fever, she had experienced twelve PFAPA episodes. Since her surgery, I’m happy to report that my daughter has been PFAPA-free for one year.

Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA)

Although I’m beyond grateful for her recovery, the story does not end there. I was still plagued with the “what caused this?” question. From my detailed and lengthy research, its seems doctors are still uncertain. What they do know is that unlike other periodic fever syndromes, there has not yet been a definitive gene identified for PFAPA, leaving much speculation to environmental causes. PFAPA is classified as an autoinflammatory disorder with the involvement of both innate and adaptive immunity. What could have caused her immune system to become so erratic?

My research revealed some possibilities. The first and most likely, in my opinion, was vaccinations. It was once believed that adjuvants in vaccines, such as aluminum, were not harmful and caused no independent threat, but more recently, scientists have concluded that adjuvants can induce autoimmune and autoinflammatory disorders in both human and animal models. In fact, adjuvants like aluminum are designed to create an inflammatory response in order to better facilitate the body’s production of antibodies to the antigen in the vaccine.

Only in the last few years has the scientific community began to formally recognize the role of adjuvants in inducing autoimmunity/inflammation. To date, a handful of syndromes have been identified as being associated with exposure to an adjuvant: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF), and a less specific cluster of symptoms referred to as “post-vaccination phenomena”. PFAPA children show many of the clinical manifestations of ASIA post-vaccination phenomena, including fever, arthralgias, increased erythrocyte sedimentation rate, skin rashes, and sleep and gastrointestinal disturbances. Furthermore, PFAPA children would meet many of both the major and minor criteria for diagnosis of ASIA.

I am not arguing that PFAPA is likely induced by vaccines alone. I recognize that my daughter likely holds an unidentified genetic susceptibility to this syndrome. In fact, although not conclusive, new research is beginning to identify candidate genes for the syndrome. I do believe, however, that vaccines were the environmental trigger that likely caused the gene(s) expression to be altered. I am also not arguing that all cases of PFAPA are induced by vaccinations. Other environmental triggers in combination with genetic susceptibility such as illness, stress, trauma, allergies or other toxins may play a role.

Vaccine Safety and Advocacy: Incompatible Arguments

As mentioned before, I had always supported vaccination programs and acknowledged them as a pillar of public health efforts. Since my daughter’s diagnosis, I feel discouraged and confused regarding vaccinations. I’m discouraged because it seems parents have no other options for immunization other than vaccinations that contain harmful adjuvants like aluminum. Although I recognize that my daughter may have had a genetic susceptibility for PFAPA, I have put together an evidence-based argument that her syndrome was triggered by her vaccinations. I have done so through careful research, collaboration with her physicians, and through the process of elimination of other causal factors. My research has also convinced me that many children who suffer from autoimmune or autoinflammatory syndromes may have had healthy childhoods had they not been exposed to routine vaccinations. Unfortunately, medical science has not yet reached the point of being able to easily identify susceptible children and prevent this phenomenon from occurring.

With that being said, I still do not want to see my daughter suffer from something worse than PFAPA, including deadly diseases like meningitis. How can one argue for vaccine safety while still acknowledging the benefits of being protected by immunizations? In my experience: you can’t. They are incompatible arguments that create cognitive dissonance. You simply cannot say, “Vaccinations are a good thing, except they are not safe.” The minute you begin fighting for vaccine safety is the minute that you begin to be ousted by the medical community and anyone else that vaccinates their children, for that matter. You are immediately put into the category of “anti-vaxxer”, and people stop listening before your argument even begins. The backlash against those who question vaccine safety is quite biased, largely unwarranted and, in my opinion, offensive.

I am still unsure of how to proceed regarding my daughter’s remaining vaccinations. I have spoken with her physician about formulating a plan on what is best for her health at this time. By discontinuing her vaccinations, I run the (probably small) risk of exposing her to potentially dangerous diseases. If I choose to continue vaccinating her, I run the (probably large) risk of negating the effects of the surgery, which to date is the only known cure for PFAPA. I have heard several stories from parents of PFAPA children whose child’s fevers returned post-surgery after a round of booster immunizations. Apparently, in these cases, the body chooses another route for the inflammatory response after the tonsils are removed. Alas, the vaccine argument is not as black and white as many propose, and it is unfair and inaccurate to treat it as such.

Vaccine and Medication Side Effects: Neither Rare nor Insignificant

The vaccine manufacturers and even some scientists maintain that adjuvant-induced syndromes are rare. In contradiction, however, the literature also states that (like with fluoroquinolones) the manifestation of these syndromes can be delayed for weeks or even years after exposure to the adjuvant. Therefore, it is unlikely that we have any sort of accurate estimate of how many individuals have developed autoimmune or autoinflammatory syndromes caused by vaccinations. As one scientist states,

“…this global view of ASIA probably represents only the tip of the iceberg. Encouraging physicians and patients to report adjuvant-related conditions will enable a better estimation of the true prevalence as well as the width of ASIA spectrum. It seems that the role of adjuvants in the pathogenesis of immune-mediated diseases can no longer be ignored, and the medical community must look towards producing safer adjuvants…”

Indeed, with the rise of complicated idiopathic illnesses occurring alongside the rise in prescription drug use and lengthened vaccination protocols in America, scientists and medical practitioners should be increasing their focus on pharmaceutical safety. Although this correlation does not imply causation (one could argue that the rise in prescription drug use is due to the rise in illness caused by other factors), causal relationships between adjuvants and these types of illnesses have already been demonstrated, warranting further investigation. Many people, including children, are suffering tremendously with complex and painful syndromes while their causes continue to be ignored by the medical community despite overwhelming scientific evidence for their existence. Their suffering is viewed as rare, therefore insignificant. I’m left wondering, how can a child’s suffering ever be insignificant?

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This story was published originally on Hormones Matter in May 2014.

Recurrent Fever With Swollen Glands: Febrile Lymphadenopathy and Thiamine

by Derrick Lonsdale MD, FACN, CNS

Published on April 19, 2016

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fever swollen glands - Febrile Lymphadenopathy.

Every profession has its jargon and the medical profession is no exception. Perhaps it is even more addicted to jargon than other professions. The title used here refers to an extremely common disease, particularly in children. Febrile is the word used to describe fever. Lymphadenopathy simply means that lymph glands are swollen. The mechanism is as follows: the throat becomes infected, often with streptococcus and may affect the tonsils or adenoids. A message is sent from the throat to the brain that reacts to cause the body temperature to be raised. We will see why later. The lymph glands in the neck are stimulated to get bigger as part of the immune response. The child feels sick and accepts bed rest and these essentially defensive reactions are referred to as the “illness”. Often a treatment such as aspirin is given to the child to bring the temperature down under the mistaken concept that this is the dangerous part of the illness. A previous post on this website described a case of Reye’s syndrome, a deadly disease known to occur as a result of giving aspirin to bring the fever down. It is of course true that a very high temperature such as 106°F is considered to be dangerous. But this is because the brain mechanism that initiates this temperature is itself in an abnormal state and may be the actual source of the danger.

Understanding Fever as an Immune Response

If we look at this situation in the cold light of day, we can come to false conclusions. Yes, this is the expected situation with an infected throat and it is invariably treated with antibiotics. But let us see what is really happening in all cases of this common affliction. The brain has received a message from the throat that an attack by a microorganism is occurring. The brain sets up a defense mechanism and I refer to the microorganism as a “stressor” (the enemy). The brain is programmed to recognize the attack as dangerous to the organism. The physical aspects of the infection and the brain mechanisms that receive the message and activate the defense are in constant communication. The body temperature is raised by the brain as part of this defense.

Microorganisms, the stressors, are programmed by Mother Nature to operate at maximum efficiency at 37°C, the normal temperature of the human body. By raising the body temperature, the environment for the microorganisms is detrimental to its action and decreases its virulence. No rise in body temperature indicates that the brain is sick!

Inflammation Is an Immune Response: Resting Boosts Immune Function

The inflammation of the throat makes it harder for the microorganism to gain entrance and is also part of the defense. Strangely enough, we now know that inflammation is controlled and governed by the brain. A message to the lymph glands in the neck increases their size to cope with the expected passage and trapping of bacteria from the infected area and is part of the immune response.

The bed rest or fatigue that occurs with illness is yet another part of the immune mechanism. Bed rest conserves the cellular energy needed to activate the defense mechanisms.

You can readily see that all of these reactions that we call sickness are scripted and controlled completely by the brain. It may come as a surprise to many readers, but fever, inflammation and energy conservations are necessary immune reactions. Diminishing or overriding those reactions, usually by trying to reduce fever with a drug or failing to rest rather than assisting the body’s defense systems, may only prolong the illness and perhaps even create new ones.

The modern method of treatment is, of course, to kill the organism. Little thought is given to whether the supply of energy in the brain is sufficient to run the complex organization of defense. It also assumes that the genes that oversee the immune response are intact and functionally healthy.

Nutrient Interactions With Immune Response

Now I must tell you about two children, both of whom had suffered from repeated episodes of febrile lymphadenopathy (Lonsdale D. Recurrent febrile lymphadenopathy treated with large doses of vitamin B1: report of two cases). Each child had been treated by antibiotic therapy with their recurrent episodes over a two or three-year period on the assumption that they were caused by bacterial infection. Both were medical puzzles because evidence of bacterial infection was lacking and it was assumed that the recurrent episodes were viral in nature. I had the opportunity to study one of them in detail.

The child had been admitted to a prestigious hospital and a swollen gland in the neck had been biopsied under the impression that it might explain the disease. The pathologist had reported an enlarged but otherwise perfectly normal gland structure. The mother told me that at this hospital he had also had the concentrations of vitamin B12 and folic acid measured in the blood, presumably because they were looking for evidence of deficiency. She volunteered that “the doctors told me that I was giving him too many vitamins”, apparently because the two vitamins had been found to be in an unusually high concentration. She also volunteered that this was very strange to her “because I had not been giving him any vitamins at all. The doctors didn’t believe me”. This naturally intrigued me.

Without going into the technical details, I found that he had evidence of abnormal thiamine metabolism. The folic acid and B12 concentrations were indeed extremely high. When I gave him the big daily doses of thiamine, these two vitamins each fell into its range of normal blood concentration. I discharged him from the hospital where these studies had been carried out, continuing the high dose treatment with thiamine. Two or three months later, the mother called me to say that her child had not had any episodes of fever and was extremely well. I responded to her by asking if she was interested in stopping the thiamine in the interests of science. She did stop it and three weeks later he had an episode of sleep walking, spontaneous urination as he went down the stairs and another episode of febrile lymphadenopathy.

You may well ask how the sleep disturbance could possibly be associated with the throat problem, so continue reading. I readmitted him to the hospital and clinical examination revealed the sore throat and a very large lymph gland in the neck. The folic acid and B12 concentrations were once more elevated. I restarted the thiamine and the two vitamin concentrations again fell into the normal range. The enlarged lymph gland disappeared and I discharged him from the hospital with instructions to continue the high dose thiamine. About a year later she reported that the episodes had begun again. I told her to add a multivitamin to the thiamine and again the episodes ceased. The other child also had evidence of abnormal thiamine metabolism that was resolved by the administration of large doses of thiamine, but unfortunately, I was not able to study him further. Please note that both children had been indulged with ad lib candy and soft drinks.

Nutrient Deficiency in the Face of High Sugar Intake: Altered Immune Responses

The explanation is construed from a rational approach to the genius of Mother Nature. I have already described the normal mechanism of defense to infection organized by the brain. Think of the body as being like an old-fashioned fortress. When an approaching enemy is spotted by soldiers on the Eastern battlements, a message is sent to the commander. The commander is then able to plan the defense and off duty soldiers are deployed to the scene of impending attack. Imagine that the commander is drunk and he sends the reserve soldiers to the Western battlements. Or perhaps the commander imagines falsely that he has received a message and deploys his defensive soldiers throughout the fortress unnecessarily, a “May Day” without reason. Obviously the commander would be to blame.

This is an analogy for the brain/body response to infection. Messages throughout the body are automatically relayed through the autonomic (automatic) nervous system and by the hormones released from the endocrine glands. Hormones, carried in the blood stream, are messengers. White blood cells are “the defending soldiers”. Both the autonomic and endocrine systems are under the control of the more primitive lower part of the brain, the commander in the analogy and the part of the brain that is known to be peculiarly sensitive to thiamine deficiency. There is good scientific evidence that thiamine deficiency will make the “commander” much more sensitive to incoming signals from the “battlements”. Like the “drunk commander”, it organizes a complete defensive reaction without there being any need.

To be a little more scientific, thiamine deficiency causes reactions in the lower brain that are exactly like a mild to moderate deprivation of oxygen. That is why thiamine deficiency is reported scientifically to cause pseudo-hypoxia (pseudo, false: hypoxia, deficiency of oxygen). These children had been indulged with ad lib. candy and soft drinks. Even if they had had the average intake of thiamine from the diet, essential to the processing of sugar, it was insufficient to metabolize the sugar. You might say that this was an increased sugar/thiamine ratio, equivalent to dietary thiamine deficiency with a normal healthy diet.

Microorganisms Attack: The Immune Response Defends

Each case of the usual form of febrile lymphadenopathy can be visualized as a hostile attack by a microorganism (a stressor) requiring a defense response. However, in the case of these two children, when the brain ”commander” was exposed to thiamine deficiency (pseudo-hypoxia), itself imposing brain stress, it became hypersensitive to virtually any form of incoming signal from the environment. It is therefore possible that a change such as ambient temperature was being perceived falsely as a dangerous threat to the organism (the patient). Hence, it is hypothesized that any proposed minor form of stress initiated the defensive response, mediated and organized by the lower brain that is programmed to perceive danger. It is possible that a virus in each case may or may not have been responsible for being the “stressor” but it is more likely that the “commander” was initiating an unnecessary defense based on a false perception of a non-existent attack such as ambient temperature change.

I have to turn to analogy once more. A car has an engine. Its essential function is to produce energy. The energy has to be transmitted to the wheels through individual mechanical parts that are connected together to form an energy consuming transmission. In the human body each cell has its own engines and they are called mitochondria. Their function is also to produce energy that has to be converted into mental and physical action. Thiamine is essential to energy production from the mitochondria and a series of enzymes are the equivalent of the mechanical parts of the transmission in a car and therefore can be thought of as an energy consuming biochemical device. Therefore, mitochondria produce energy; the transmission consumes it in mental and physical action. Folate (folic acid) and vitamin B12 are essential to this biochemical transmission. Because thiamine deficiency depletes cellular energy, the enzyme dependent (energy hungry) transmission developed problems. Folate and B12 accumulated in the blood simply because they were not being used. When thiamine was given to this boy, cellular energy improved and the two vitamins were consumed in their actions and their concentrations decreased in the blood.

Sleepwalking: An Example of Brain Dysfunction?

Sleepwalking has always been a puzzle. A sleepwalker is not consciously aware of what he or she is doing. I remember the case of a man who drove his car for 70 miles and had no recollection of doing it. I had found from my clinical experience that sleepwalking children would stop doing this with the administration of nutrients, particularly thiamine and magnesium. The fact that the subject of this discussion urinated as he descended the stairs indicated abnormal automatic autonomic nervous system activity. This was pretty good evidence that it was oxidative deficiency in the brain that was responsible for both physical and mental abnormal activity after therapeutic thiamine had been withdrawn.

The Use of a Multivitamin: Completing the Nutrient Team

As the story above indicated, the episodes of febrile lymphadenopathy began to return about one year after he had been discharged with instructions to take only thiamine. There is a particular relationship between thiamine and magnesium because both of them are cofactors together for the same enzymes. However, vitamins and minerals are non caloric nutrients that work as a complex team. There might still be nutrients in naturally occurring food that await discovery. Mother Nature knows how they all should be balanced. The further we move from our biologic origins by the introduction of artificial foods in our hedonistic pursuit of pleasure, the more illness can be expected. Our present medical model is concerned only with killing the attacking agent. Rather simple clinical research revealed an anomaly of this nature in the organization of defense, without knowing how common it is. It should surely focus our attention on the role of nutrition in providing the raw materials for this organization. An infection gives rise to a battle. There are only three possible outcomes: the enemy wins: the defense wins: there is stalemate. The stalemate possibility suggests that chronic long term infection can be tackled by the use of energy producing nutrients that improve the efficiency of a defensive program.

Unfortunately, there are problems with what appears to be a simple solution. Even natural food does not have the nutrient density that it used to have because of changes in farming practices. Also, whether we like it or not, evolution is going on all the time and in the modern world, the smartest brains have the greatest evolutional advantage. Those interested in following the numerous posts on this website will note that post Gardasil thiamine deficiency appears to affect the brightest and the best. I have suggested that relatively poor nutrition, coupled with a smart brain, creates a greater risk of succumbing to a risk from vaccination, mild infection or trauma.

I have seen several articles that state the uselessness of dietary supplements, claiming that the numerous vendors are cheating the public. My own library research reveals numerous papers on the subject of supplementary nutrients coming from many parts of the world other than America. Although they are not cheap, the expense is very much less than the drugs issued by pharmaceutical companies and their curative or preventive properties are huge. Humanitarian research in this area of relative ignorance is a modern necessity.

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