Fungus Allergy and Hypersensitivity
Notes from the Biotoxin Conference
by Alan B. McDaniel, MD
Introduction:
Some molds release toxins, as certain snakes are poisonous. These mold toxins activate our innate immune system and provoke disabling chronic inflammation and many hormonal disturbances. This is quite distinct from the hay fever-allergic reaction molds can provoke. There is a third way fungi (mold, yeast, etc) can make us sick. This is generally neglected because of scientific orthodoxy and institutional dogma.
Fungus hypersensitivity can create inflammation that mimics infection
Case 1: Doc’s oldest son AP got fungal ringworm. Doc prescribed Lotrimin cream, applied four-times daily by AP’s Mom, a nurse. It was no better after ten days and the boy was taken to a Dermatologist, Dr. Bob Weiss. When Weiss prescribed Lotrizone cream, Doc protested: This was the same antifungal that already had failed and it had steroids, which promote fungus growth. Weiss winked and said: “Try it!”
In three days, the ringworm was gone. Allergy tests confirmed AP reacted to Trichophyton not immediately but quite strongly 24 and 48 hours after the test was placed. The Trichophyton causing AP’s ringworm had been killed by the antifungal in Lotrimin but the dead fungal remains in his skin provoked immune inflammation – until that was quenched by the steroid in Lotrizone.
Inflammation from fungal hypersensitivity responds to immunotherapy
Case 2: Both of MB’s ear canals had been itching, then painful and swollen for years. A sensible ENT surgeon had performed a right mastoidectomy but found no disease. On Doc’s examination, both ears were red and chronically thickened with “peau d’orange” and neither canal could admit even a newborn speculum. She had skin tests for allergy and days later had big reactions to Aspergillus, Candida and Staph phage lysate.
Desensitization shots were started and she was put on a “Candida program.” Doc operated on her worst ear, removed a solid mass of scar tissue from the ear canal and placed skin grafts. After six months, the operation planned for her other ear was unnecessary – both ears were perfectly normal.
To understand what happened to these people, we must examine the immune system.
The immune system has one great task: It protects us from dangerous invaders. These micro-terrorists include parasites; bacteria; viruses; toxins (such as tetanus and Stachybotrys) and cancer cells.
To master this task, the immune system must first discriminate between the many, many things that make up our own body (properly called “self”) and the vast amount of everything else that is not our body (right, called “non-self”). Certainly, the immune system should not attack “self!”
Secondly, it must sort through that vast array of “non-self” and differentiate between the harmless and the dangerous. It must leave “harmless” things alone and save its killing energy to attack and destroy the “dangerous” foreign matter. When you think about it, that is an awesome task. To achieve this, the immune system has two main divisions.
Immunity 101: The innate immune system
First, some immune protection is programmed right into our DNA. Virtually all living things, even plants and quite primitive creatures are genetically – innately – directed to defend themselves by attacking a variety of biochemical molecules.
In humans, this Innate Immune System has developed several “operational arms.” First, white blood cells (WBCs) called macrophages – translated “big eaters” – using primitive amoebic action engulf annoying foreign material and “process” it chemically. What they do with this is important, as we’ll soon see.
Secondly, these white cells also release a variety of chemicals, by which the innate immune system recruits more WBCs (think “pus”) and promotes inflammation, which should be a protective defense.
Finally, a sequence of proteins collectively called the Complement Cascade is considered part of the innate immune system. When triggered by various immune responses – and by toxins, these proteins activate each other in a chain-reaction that amplifies the power of the immune response (
http://en.wikipedia.org/wiki/Innate_immune_system
).
Immunity 102: The acquired immune system
We higher vertebrates are also equipped with more versatile defenses, the Acquired Immune System. It fields a fields a team of “programmable” WBCs, including T and B-lymphocytes. These cells are at first called “naïve” and indeed they are harmless as puppies – but they won’t stay that way. Here’s how immune cells learn What to Attack:
These naïve cells become educated by hooking-up with “big eaters” of the innate system. From them, they receive their load of ingested foreign material. Macrophages’ processing has unmistakably labeled this as “bad.” The T- and B-cells are galvanized to attack the foreign material – and thus the immune response is acquired. It is also enduring: These educated immune cells alter their DNA, passing sensitization to all their descendants – creating clones of protective cells.
On receiving this molecular mug-shot, T-lymphocytes are programmed to fasten onto and destroy anything carrying that particular foreign “label.” They become killer cells – certainly no longer naïve.
B-lymphocytes, having received the same information and thusly primed, begin to make protein antibodies called immunoglobulins (especially IgE and IgG). These molecular equivalents of Predator drones are released into the blood and very specifically target the foreign material processed by the Big Eaters. Some reactions provoke little incident but others produce very much inflammation, indeed.
Both T- and B-cell activity leads to the release of chemicals that promote inflammation and recruit many other cells to the sites of conflict. Both these effects amplify the innate system and trigger the complement cascade. Please note that ultimately, the innate and acquired immune systems stimulate the same final consequences. This is a “key” point for today.
Immunity 201: Immune protection
Many of a pregnant woman’s immune globulins cross the placenta to her child. Thus, babies at birth have a good measure of immune protection received “passively” from our mother. This is temporary, lasting some 3 months. So, the baby’s acquired immune system gets busy learning its “craft,” a lifelong process.
History, 1796: Smallpox killed one of five people who contracted it but survivors never got it again; their acquired immune system had become educated to kill the virus on sight and prevent a recurrence. When Dr. Edward Jenner noted the mild infection called Cowpox made milkmaids immune to Smallpox, he inoculated his patients with Cowpox. By this, they were protected from Smallpox. Many have credited Jenner with saving more lives than anyone else in the history of the world (
http://en.wikipedia.org/wiki/Edward_Jenner
).
Vaccinations educate our immune system. They present harmless proteins that will stimulate an immune response protecting us from dangerous ones. When the immune system attacks dangerous “invaders,” it keeps us well. This is healthy immunity.
Immunity 202: Unwanted immunity
History, 1819: Tom was an agricultural worker. Every year, he’d get sick when bringing in the harvest: Watery eyes, running nose, sneezing and fullness and itching in his throat. He thought it was a cold, caught from other workers who had it too – but it happened every year. He saw Dr. John Bostock, who diagnosed “hay fever” (
http://www.allergyclinic.co.nz/guides/39.html
).
When the immune system is confused between harmless and dangerous, it attacks harmless substances. This unnecessary immunological “warfare” makes us sick. We call this illness “allergy.”
Case 3: Big Al was a surgeon with five kids and a stressed wife. He was really tired and needed to drink two pots of coffee daily to keep going. He repeatedly asked his GP test his thyroid gland. Every time it was checked, thyroid-stimulating hormone was normal but the level got worse and worse. The gland was failing. Fine-needle aspiration biopsy showed Big Al had Autoimmune Thyroiditis (AIT), which was slowly destroying his thyroid gland.
When the immune system cannot recognize “self” is harmless, trouble follows. It may attack some part of its own body and destroys it, as though it were rejecting a mismatched transplanted organ. Our thyroid gland is the most common target: 15% of Americans have AIT, including 24% of allergic women. We call this auto-immune disease.
Graduate Immunology: Application to patient care
Medical science has several occupations. In outline form, we endeavor to:
- observe what is happening
- understand what we have observed
- apply this knowledge to cure people or relieve their suffering
- improve our results by observing what is happening, etc
There are many types of immune reactions – as you might expect from having learned there are two types of immune system, many types of white blood cells and very many chemicals produced by their activities. Doctors have observed these reactions for generations. Unfortunately, they still argue about what they mean.
Case 4: When Percival’s cat scratched him, his skin swelled all along the scratch. The first deliberate skin test for allergy was done in 1869 by Charles Blakely, who had hay fever. He nicked his skin, put some pollen onto the cut and within 20 minutes saw his skin swell up all around the cut. (
http://www.allergyclinic.co.nz/guides/39.html
)
Do skin tests actually identify trouble-making pollens? Yes; when pollens identified by positive skin tests are spritzed into the person’s eyes, nose and airways, they provoke the person’s “hay fever” symptoms.
Nineteenth Century Immunology
Case 5: Dr. Wright made a night-call on a household with diphtheria. Arriving home, he stabled his horse and to prevent contagion, changed his clothes in the barn. Before going to bed, he paused look through the doorway at his only son, baby George. The baby sickened and died of diphtheria the following week.
Tetanus and diphtheria were dreaded killers in pre-antibiotic times. By the 1890s, Physicians had learned how to protect people after they’d been exposed – by giving passive immunity, the kind a baby gets from its mother. Horses were injected with the deadly toxins and those that survived became immune – with lots of protective immune globulins circulating in their blood. This immune horse serum was injected and it protected the recipient (
http://en.wikipedia.org/wiki/Passive_immunity
). A century later, we have better methods but we must honor the innovative scientists of the Gaslight Era!
They also knew injections should not be contaminated with bacteria. To prove the horse serum sterile, they injected rabbits with some of each batch – and watched to see if an abscess would develop. These frugal scientists found they couldn’t use the same rabbits repeatedly: Previously-injected rabbits often died immediately after the shot. Dr. Arthus noted the surviving rabbits developed slow-healing lumps or nasty ulcers at the test site over a few days (
http://en.wikipedia.org/wiki/Arthus_reaction
). Humans had similar problems after repeated injections of horse serum – not with the first but on repeated injections.
Twentieth Century Immunology
The fledgling science of Immunology couldn’t explain all this but they tried. In 1921, Otto Prausnitz and Heinz Küstner demonstrated quite clearly that the immediate hypersensitivity of hay-fever and fatal horse serum injections was caused by a reactive substance in the serum; they called it “reagin” but we now know it as immunoglobulin E (IgE) (
http://en.wikipedia.org/wiki/Prausnitz-K%C3%BCstner_test
and
http://en.wikipedia.org/wiki/Reaginic_antibody
). Oh, how the Allergists of the world rejoiced at the demonstration of the “P-K reaction!” No longer were hay fever treatment and allergy shots a disreputable pseudo-science belittled by their more august colleagues.
What of the rabbits’ ulcers, the astute critic might ask? Because they weren’t fatal, they were largely ignored. Scientists later showed these lesions were caused by rabbit immunoglobulin binding to horse proteins, causing inflammation of blood vessels – “vasculitis.”
Immunology becomes politicized
Leading immunologists met first in Europe and then in the US, agreeing from thence forward they would define “Allergy” solely as the P-K reaction. Dr. Coca, who developed the solution still used to make allergy extracts, protested against this decision. He stated many types of immune reactions did not fit the P-K model but he and his supporters were voted down.
The argument was not solved though; it got worse. As the allergy academy embraced the creed and catechism of IgE, groups of members rebelled and left to form their own, less-dogmatic societies. First to go were the Ear, Nose and Throat docs in 1941, then General Practitioners in 1956 and finally dissenting Internists and Pediatricians in 1965.
The dispute over defining “allergy” became so acrimonious that there could be no reconciliation even after 1963, when Gell and Coombs showed there are at least 4 major types of acquired immune responses (
http://en.wikipedia.org/wiki/Hypersensitivity
). Their four “classical” pathways are:
- Type 1 reactions, caused by IgE (hay fever); they occur within minutes and give us protection against parasites
- Type 2 reactions, caused when immunoglobulin types G (IgG) or M (IgM) attach themselves to a foreign protein and provoke the complement cascade; these develop over hours to a day and protect against bacteria and viruses
- Type 3 reactions (Arthus reactions), occurring when IgG binds to a dissolved foreign substance and precipitates as an irritating, inflammatory complex; they occur in hours to a day and offer protection against toxins
- Type 4 reactions, caused by sensitized T-cells; these reactions peak at 48-72 hours (think Tb skin tests) and protect against bacteria
Please note this important fact: Hay fever allergy, the type 1 pathway does not activate the complement cascade. Are Allergists correct, who believe mold can stimulate the immune system only through type 1, IgE-mediated reactions? If so, Dr. Shoemaker’s observations that mold activates complement must be explained only as a direct effect of mold toxins, without acquired immunity.
But reaction types 2-4 trigger the complement cascade (
http://en.wikipedia.org/wiki/Hypersensitivity
). What if the dissenting Allergists are right; what if molds do indeed stimulate these late and delayed immune reactions? That would mean non-toxic molds can trigger complement – and that we are dealing with a broader problem than mold toxins alone. Treatments for these two conditions are very different.
Seeking the Truth: “Think for yourself and question authority.” – Timothy Leary, PhD
Allergists in the US agree that type 2-4 immune reactions – call them “late and delayed” reactions (L/D) – can be clinically important, causing asthma and other stubborn problems. However, their orthodoxy requires them to believe type 1 reactions must trigger significant L/D hypersensitivity. So, when skin tests show no immediate reaction but only later develop large red bumps lasting days to weeks, these lesions are dismissed as “meaningless Arthus reactions” and patient’s symptoms are called “non-allergic.”
How would Allergists learn any differently? Americans studying late and delayed reactions after provocation-challenges choose only allergens positive on skin testing. Fortunately, European and Asian researchers use a different approach; they challenge common pollens regardless of the skin test responses. This is far from being futile: They’ve found that up to 30% of allergens provoking airway reactions do not produce an immediate skin response. This is “key” information: Antigens that do not provoke immediate hypersensitivity can cause clinically significant immunological reactions.
Fungi provoke the immune system differently than do pollens
Before Science described the Fungus Kingdom (
http://en.wikipedia.org/wiki/Fungi
), Mankind had given its members common names: Mold, mildew, yeast, rusts, smuts and blights – they are all fungi and are rather similar. Fungi are always present in the human environment. They live in our homes and in our food. With fungus, bread is raised and wine fermented. Bleu cheese is made with Penicillium and soy sauce uses Aspergillus (black mold!).
Fungus also lives on and inside of humans: Aspergillus and Candida normally live in the external ear canal. Fungus lives in everybody’s gut: The average healthy Englishman has >1,000 fungi per gram of stool; Candida, Geotrichum and Rhodotorula are most common.
Why do molds and yeast occupy center-stage today? Exposure leads to sensitization. To be sure, some make toxins but they also provoke late and delayed-type hypersensitivity much more often – and more severely – than do pollens. It appears this difference is due to the types and locations of exposures and even the kinds of proteins involved.
Type 1 reactions to pollens seem related to the relatively brief seasonal exposure of large quantities of allergens that remain on the surface of our mucous membranes, where macrophages and IgE-laden Mast cells “hang out.” In contrast, molds and yeast are ubiquitous and perennial. Living in and on the human body, they cross our mucosa and enter our fluid compartments, where IgG and IgM rule.
Fungal antigens are also biochemically different from those of pollen. All these characteristics lead molds to produce type 2-4 immune reactions. Fungi so commonly cause late and delayed reactions that Candida is among the antigens doctors used to test a patient’s immune competency.
Case 6: Doc’s left hand developed dyshidrotic eczema when he was an undergraduate. The Dermatology resident at Student Health said it was caused by a fungus but couldn’t say where the fungus was located. Other Dermatologists scoffed at the fungus theory and recommended many peculiar treatments. The problem gradually disappeared after about ten years.
That is, until six years later, when he heard Billy Crook lecture on the Yeast Connection and decided to find out what the non-absorbed antifungal nystatin would do …he did! After taking one-eighth teaspoon at dinner and another at bedtime, Doc woke with his biggest-ever jock rash. Then two days later, he had his worst-ever outbreak of dyshidrotic eczema – on both hands! The Derm resident had been right – and the fungus was in Doc’s gut. Nystatin killed it and dead yeast proteins flooded Doc’s bloodstream. Every part of his skin that had ever been sensitized to fungus reacted (it was bad, y’all!).
With near-preternatural timing, Doc’s allergy nurse then came to him with an issue: Marlene wanted to take Candida (“yeast”) off the testing menu. Every time a patient tested positive for Candida, they had treatment problems. They did not react to the shot right away but got big, red lumps after a day or two – which lasted a week or more. Obviously, Candida provoked type 2-4 reactions more strongly than it did the type 1. Doc had not known to check for L/D hypersensitivity before treating with fungus.
Diagnosing late and delayed-type hypersensitivity
When humans are tested, most doctors record only the type 1 IgE responses at ten minutes. They truly ignore reactions that develop over the next few days, calling them “meaningless Arthus reactions.” Yet foreign research shows many provocative allergens have no immediate hypersensitivity responses.
Veterinary Case: Sue loved her friend’s horse Cappy. He was a big, gentle 12 year-old with impressive dressage skills and bad lungs. In fact, his asthma got so severe that his destruction was planned but Cappy’s owner told Sue she could have him if she could help him. Sue got a trailer and drove Cappy 100 miles to the University of Pennsylvania Vet School. They promptly tested Cappy for allergies with skin tests – and measured his reactions every six hours for two days. He had terrible late and delayed reactions to molds: He had “sick-stall syndrome.” His stable was thoroughly cleaned, giving him complete relief.
Case 7: Dr. Gordon’s patient had chronic sinus infections, asthma and occasional eczema. Her symptoms worsened in cool, wet weather; in musty places and just before a rainfall. He tested her for allergy to mold using blood tests measuring both IgE and IgG. All 14 of her IgE tests were negative; 12 of 14 IgG tests were positive – several exceeding the upper limit of reporting.
Integrated Approach to treatment
Avoidance is the most obvious first step in dealing with immunological hypersensitivity to harmless substances. Put the cat out; don’t drink milk and put allergen-proof covers on your mattress and pillows are well-known recommendations. But what about the ubiquitous fungi – they cannot long be avoided.
Case 8: An ENT-Allergist from New Mexico spoke with Doc at an allergy course. After moving there, his wife was still sick with headaches, “sinus,” respiratory and skin problems. Skin tests had shown no allergies at all and he was baffled. Doc told him to repeat the tests and measure her reactions at 24 and 48-hours. There were lots of these reactions and he used them to formulate allergy shots for her. At the next annual meeting, he was delighted to report his wife had improved dramatically.
Immunotherapy (IT) develops tolerance by inducing T-suppressor cells that “quench” reactions to the foreign substances to which they are directed. If the allergic response calls out the Marines, treatment with IT means that instead, Social Workers will answer the summons. Skin tests measuring immediate, late and delayed-type reactions give us the best data to successfully formulate immunotherapy.
IT works both for immediate and late/ delayed hypersensitivity. Environmental control works only as long as the environment is controlled – remember: Sensitization is long-enduring. Desensitization, either by shots or sublingually, offers us lasting tolerance.
Summary:
Fungi (molds, yeasts, etc) cause immunological inflammation. They mildly stimulate IgE-mediated immediate hypersensitivity. They also provoke non-IgE late and delayed-type hypersensitivity. Some of them, like Stachybotrys, can release toxins that directly activate the complement cascade.
Nearly every physician knows about the first of these, though it is rather insignificant. The latter is becoming recognized and today we’ve heard about ingenious treatment options. The second is the most commonly encountered but the least often recognized. Our challenge is learning how to distinguish between these problems.
Of course, patients can have several, overlapping problems. Some fungi provoke immediate as well as late/ delayed reactions. Surely some people poisoned with mold toxin will already be allergic to molds. It would be wonderful to study “mold-patients” for these and other related problems including insulin resistance; adrenal fatigue and autoimmune thyroiditis and “non-thyroidal illness”– to name a few.
Some day, a group of patients may be randomly divided into two groups:
- One group could be treated by Dr. Shoemaker’s protocol
- The other group by desensitization and Environmental Medicine principles
After sufficient time, perhaps two years, symptomatic patients would “cross-over” and try the other treatment. Their outcome data could help determine which patient is best suited for what treatment. Applying that knowledge is the ultimate goal for all serious physicians.
Alan McDaniel, MD is a Board-certified Ear, Nose & Throat specialist with two sub-specialties. His work with dizziness and allergy in the 1980s led him to seek solutions for Chronic Fatigue Syndrome. Since 2003, Dr. McDaniel has taught physicians practicing on five continents to effectively employ nutrition and hormones for this and other issues in his two-day course titled “The New Endocrinology.”
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Over nine hours of video, including a “Shoemaker for Dummies” section by Dr. Neil Nathan, plus an additional CD that contains the event Syllabus, all Power Point Presentations as PDF documents (including slides not seen during the event), and other extensive documentation to support Dr. Shoemaker’s work. Of special interest were question and answer panels with Dr. Shoemaker and the Gordon Medical physicians, providing a range of physician experience with the treatment protocols in different patient populations.
