From the Archives
Added online October 2016
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Fungi Provoke the Immune System Differently than do Pollens
Why do molds and yeast occupy center stage today? Exposure leads to sensitization. To be sure, some fungi 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 may cross our mucosal barrier and enter our fluid compartments, where IgG and IgM rule.78
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 that 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 that 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 10 years.
That is, until 6 years later, when Doc heard Billy Crook lecture on the "yeast connection" and decided to find out what the nonabsorbed antifungal nystatin would do … and he did! After taking 1/8 teaspoon at dinner and another at bedtime, Doc woke with his biggest-ever jock rash. Then 2 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: Queen Bee 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 10 minutes. Years of interviewing patients has validated this statement: Most allergists truly ignore late and delayed reactions developing over the next few days, calling them "meaningless Arthus reactions." Yet, as we've seen, research shows that 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, to Sue's distress. Cappy's owner told Sue that 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 6 hours for 2 days. He had terrible late and delayed reactions to molds: Can we call it "sick-stall syndrome?" His stable was thoroughly cleaned, giving him astonishing relief.
Case 7: Dr. G.'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
Along with "usual" efforts to improve your patient's health with nutritional, endocrine, psychosocial, and other support, avoidance is the most obvious first step in dealing with immunological hypersensitivity to harmless substances. Common recommendations are to keep the cat out, don't drink milk if it makes mucus, and put allergen-proof covers on your mattress and pillows if you react to dust. But what about the ubiquitous fungi? Home remediation improves the parameters of environmental tests, but the hypersensitive patient finds that molds cannot long be avoided.79
Case 8: An ENT-allergist from New Mexico spoke with Doc at an allergy course. After their arrival in the Southwest, his wife continued to be ill with headaches and "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 delightedly reported that 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, switching the response from one dominated by IgE to IgG.80 If the allergic response calls out the Marines (Th2 regulatory T-cells), treatment with IT means that instead, social workers (Th1 cells) will answer the summons. Quantitative skin tests measuring immediate, late, and delayed-type reactions yield the best data to formulate effective immunotherapy.81
Immunotherapy, injected or sublingual, is seen to be effective treatment for hypersensitivity – both immediate and late/delayed. Environmental control works only as long as the environment is controlled – remember: sensitization is long enduring. Desensitization by shots or sublingually – and by standard or enzyme-potentiated desensitization (also called LDA and LDI) – can give lasting tolerance.82,83
Summary
Fungi (molds, yeasts, etc.) cause immunological inflammation three ways. They can stimulate IgE-mediated immediate hypersensitivity. They also provoke non-IgE late and delayed-type hypersensitivity. Some of them, such as Stachybotrys, will release toxins that directly activate the complement cascade.
Nearly every physician knows about the first of these, though tests usually show that IgE is rather insignificant. The latter is becoming more widely recognized and stimulates discussion of ingenious testing and treatment options. The second – non-IgE immune hypersensitivity – is the most commonly encountered but the least often recognized. Our challenge is learning how to distinguish between these problems.
Monitoring mold-sensitivity intradermal skin test responses at appropriately strong dilutions for 48 hours shows more late- and delayed-hypersensitivity responses than immediate.63 It is no surprise to the author (himself an allergic Tulane medical graduate) that a study of post-Katrina New Orleans children found no correlation between multiprick tests for immediate, IgE-sensitivity to mold and their asthma.84
There is an impressive proliferation of studies validating the correlation of mold exposure and illness: A search of PubMed for "asthma mold home" yields 240 references; many are new; most validate the relationship.85 An authoritative and objective review of medical literature shows that exposure to water-damaged buildings is harmful to health, with "sufficient evidence to convincingly associate": asthma, lower respiratory symptoms, and bronchitis; allergic rhinitis, upper respiratory symptoms and respiratory infections; and eczema.86 These three groups are typical not of IgE-mediated hay fever but of late and delayed hypersensitivity.
Of course, patients can have several, overlapping problems. Some fungi do provoke immediate as well as late/delayed reactions. Surely some people poisoned with mold toxin will already be allergic to molds. There is a great need to study "mold-patients" for these and other related problems associated with an overstimulated immune system and increased cytokine production – including fibromyalgia, insulin resistance, adrenal fatigue, and autoimmune thyroiditis and "nonthyroidal illness," to name a few.
There is reason to hope that this can be accomplished. As the science of immunology becomes increasingly sophisticated, doctrines and dogma laid down in the 1920s are reappraised and revised. Ultimately, we shall embrace a more inclusive paradigm of fungus-related environmental illness. This can encompass the reports of patients suffering from such conditions, rather than invalidating their complaints and the observations of their physicians. Most importantly, it will allow these physicians to cure the patients.
Notes .pdf
 Alan McDaniel, MD, is a 1977 Tulane medical graduate. He trained in general surgery and emergency medicine before becoming board certified in otolaryngology with subspecialties in neurotology and allergy. He practices privately since a two-year professorship at the University of Louisville. Dr. McDaniel has presented to various national meetings, including the American Neurotology Society and the American Academy of Otolaryngology – Head and Neck Surgery and to the World Congress of Otorhinolaryngology. He has been a faculty member for American Academy of Otolaryngic Allergy Basic and Advanced Courses. His two-day course, New Endocrinology, has been presented annually at the American Academy of Environmental Medicine since 2005, to physicians from five continents. Work with dizziness and allergy in the 1980s led him to seek solutions for chronic fatigue syndrome. In turn, these investigations extended to the endocrine aspects of this and related conditions. Since basic surgical training emphasizes the need to know several alternative approaches to an operation, it was logical for him to study integrative and controversial medical methods. He has endeavored to understand these in the light of new facts from research, perceiving that medical history shows innovation begins as a minority opinion. He is excited that applying new research to patient care offers solutions to many of the chronic and worsening problems that are epidemic in modern society.
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