Printer Friendly

Fungus allergy and hypersensitivity in mold-related illness.

Introduction

Some molds release toxins, as certain snakes are poisonous. These mold toxins are diverse (1,2): They can activate or Impair our innate immune system, may provoke disabling chronic inflammation, cause many hormonal disturbances, and more-even promote cancer. (3-8) This is quite distinct from the hay fever-allergic reaction that molds can produce. (9-11) There is a third way that 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 got fungal ringworm (tinea corporis). (12) Doc prescribed Lotrimin cream (clotrimazole 1%), applied 4 times daily by the boy's mother, a nurse. It was no better after 10 days and the boy was taken to a dermatologist, Dr. W. When he prescribed Lotrisone cream (clotrimazole and betamethasone dipropionate, 1%/0.05%), Doc protested: This was the same antifungal that already had failed and it had steroids, which promote fungus growth. Dr. W winked and said: "Try It!"

In three days, the ringworm was gone. Allergy skin tests confirmed that No.1 Son reacted to Trichophyton, not immediately but quite strongly 24 and 48 hours after the test was placed. The Trichophyton causing No.1's ringworm had been arrested by the antifungal in Lotrimin, but the fungal remains in his skin provoked immune inflammation until that was quenched by the steroid in Lotrisone.

Inflammation from Fungal Hypersensitivity Responds to Immunotherapy

Case 2: Both of M. B.'s ear canals started itching and progressed to became 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 normal flora of the external canals. (13-15)

Desensitization shots were started and she was put on a "candida program." (16,17) Several months later, Doc operated on her worst ear, removing a mass of scar tissue that obstructed the ear canal and placing "pinch" skin grafts. Six months later, the operation planned for her other ear was unnecessary: Both ears had returned to normal appearance and function.

To understand what happened to these people, we must examine the immune system.

The Role of the Immune System

The immune system has one great task: It protects us from dangerous invaders. These microterrorists include parasites, bacteria, viruses, toxins (such as tetanus and Stachybotrys), and cancer cells. (18)

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 (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. All things considered, that Is an awesome task. To achieve It, the Immune system has two main divisions.

Immunity 101: The Innate ('Nonspecific') 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. (19)

In humans, this innate immune system has developed several "operational arms." First, white blood cells (WBCs) called macrophages literally big eaters--using primitive amoebic action engulf annoying foreign material and "process" it chemically. This material is importantly used to direct acquired Immunity.

Second, 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 defensive and "direct" wound healing, if not in excess or prolonged. (20)

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. (21)

Immunity 102: The Acquired (Adaptive) Immune System

We higher vertebrates are also equipped with more versatile defenses, the acquired immune system (also called adaptive). It fields a team of "programmable" WBCs, including T and B lymphocytes. These cells are at first called "naive," and indeed they are harmless as puppies--but they won't stay that way. Here's how immune cells learn "what to attack":

These naive cells become educated by hooking up with "big eaters" of the innate system. (22) From them, they receive their load of ingested foreign material. Having been processed by the macrophages, this is now unmistakably labeled as "bad." The T and B cells are thus galvanized to attack the foreign material--and so the immune response is acquired. It is also enduring. (23) These educated immune cells alter their DNA, passing sensitization to all their descendants--creating clones of protective cells. (24)

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 naive. (25)

B lymphocytes, having received the same information and similarly primed, begin to make protein antibodies called immunoglobulins (especially IgG, -M and -E). (26) These molecular equivalents of Predator drones are released into the blood and specifically target the foreign material presented by the macrophages. Some reactions provoke little incident, but others produce very much inflammation indeed.

Both T- and B-cell activity lead to the release of chemicals that promote inflammation and recruit many other cells to the sites of conflict. (27,28) Both these effects amplify the innate system and trigger the complement cascade. Please note that ultimately, the innate and acquired immune systems both stimulate the same final consequences. This is a key point.

Immunity 201: Immune Protection

Many of a pregnant woman's immunoglobulins-G cross the placenta to her child. Thus, babies at birth are endowed with a good measure of immune protection, received "passively" from mother. (29) This is temporary, lasting 12 months or more (hence, babies of HIV-positive women are tested for antibodies only after age 18 months). (30) So, the baby's acquired immune system quickly gets busy learning its "craft," a lifelong process.

History, 1796: Smallpox killed 1 of 5 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 that the mild infection called cowpox rendered milkmaids immune to smallpox, he inoculated his patients with cowpox. They were then protected from smallpox. (31) From this concept, he is popularly credited with saving more lives than anyone else in the history of the world. (32)

Vaccinations educate our immune systems. 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 healthy. This is beneficial immunity.

Immunity 103: Unwanted Immunity

History, 1819: Tom was a gentleman farmer. Every year, he'd get sick when the harvest was brought in: Watery eyes, running nose, sneezing, and fullness and itching in his throat. He thought it was a cold, noting that the farm workers had it too--but it happened every year. In London, he saw Dr. John Bostock, who diagnosed "hay fever." (33)

When the immune system is confused between harmless and dangerous, it attacks harmless nonself 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 to test his thyroid gland. Every time it was checked, thyroid-stimulating hormone was normal, though the level got worse and worse. The gland was failing. Fine-needle aspiration biopsy showed that Big Al had autoimmune thyroiditis (AIT), which was slowly destroying his thyroid gland.

When the immune system cannot recognize that "self" is harmless, trouble follows. It may attack some part of its own body and can destroy it, as though it were rejecting a mismatched transplanted-organ. Our thyroid gland is the most common target: 12.5% of Americans test positively for antithyroid autoantibodies, including 24% of allergic women. (34,35) We call this autoimmune disease. (36)

Graduate Immunology: Application to Patient Care

Medical science has several occupations. In the simplest 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 that 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 Henry's cat scratched him, his skin swelled all along the scratch. (37) The first deliberate skin test for allergy was done in 1869 by Charles Harrison Blakely, who himself had hay fever. He nicked his skin (having been unsuccessful in recruiting other volunteers), put some pollen onto the abrasion, and within 20 minutes saw his skin swell up and itch intensely around the application. (38)

Do skin tests actually identify trouble-making pollens? Yes: When pollens or other allergens identified by positive skin tests are spritzed into the person's eyes, nose, or airways, they provoke the person's "hay fever" symptoms and more. (39,40)

19th-Century Immunology

Case 5: Dr. Wright made a night call to 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 to 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 preantibiotic times. By the 1890s, physicians had learned how to protect people after they'd been exposed--by giving passive immunity, the kind that 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. (41,42) A century later, we have better methods, but we must honor the innovative scientists of the Gaslight Era! (43)

They also knew that 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. (44) Nicolas Arthus noted that the surviving rabbits developed slow-healing lumps or nasty ulcers at the test site over a few days. (45) Humans had similar problems after repeated injections of horse serum--not with the first but on repeated injections. (46)

20th-Century Immunology

The fledgling science of immunology couldn't explain all this, but it tried. In 1921, Otto Prausnitz and Heinz Kustner demonstrated quite clearly that the immediate hypersensitivity of severe food allergy--and of hay-fever and fatal horse serum injections--is caused by a reactive substance in the serum. (47) They called it reagin, but we now know it as immunoglobulin E (IgE). (48,49) The allergists of the world reportedly took heart at the demonstration of reagin in the "P-K reaction": Now their skin tests and allergy shots had a solid experimental basis, affording their treatments greater validity, if not gravitas.

What of the rabbits' ulcers, the astute critic might ask? Because they weren't fatal, they were largely ignored. Scientists later showed that these lesions were caused by rabbit immunoglobulin binding to horse proteins, causing inflammation of blood vessels--"vasculitis." (50)

Immunology Becomes Politicized

Following Prausnitz and Kustner's epochal report, leading immunologists --first in Europe and then in the US agreed from thence forward that they would define allergy solely in conformity with the P-K reaction. Arthur Coca, who coined the term atopy and developed the solution still used to make allergy extracts, protested this decision. (51,52) He stated that many types of food reactions did not fit the P-K model (being "nonreagenic/nonatopic"), but he and his supporters were voted down. (53)

The argument was not resolved, though; it got worse. As the world's allergists embraced the creed and catechism of reagin (IgE), groups of members found (as did Coca) that it did not encompass their clinical experience. They left to form their own, less-dogmatic societies. First to go were the ear, nose, and throat specialists in 1941, then general practitioners in 1956, and finally dissenting internists and pediatricians in 1965. (54-56)

The dispute over defining allergy became so acrimonious that there could be no reconciliation even after 1963, when Gell and Coombs showed that there are at least 4 major types of acquired immune responses. (57) 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 (e.g., Tb skin-tests) and protect against bacteria.

In the opening paragraph, it was stated: "There is a third way fungi (mold, yeast, etc.) can make us sick. This is generally neglected because of scientific orthodoxy and institutional dogma." The important fact that hay fever allergy, the IgE-mediated, type 1 pathway called "allergy" does not activate the complement cascade. (58)

Are the majority of allergists correct, those who believe that mold can stimulate the immune system only through type 1, IgE-mediated reactions? If so, Shoemaker's observations that mold activates complement must be explained only as a direct effect of mold toxins, without acquired immunity. (59)

But antigen-antibody complexes (types 2 and 3 reactions) trigger the complement cascade (and type 4 may also be involved with complement). (60) What if the dissenting allergists are right; what if molds do indeed sbmulate these late and delayed immune reactions? That would mean that nontoxic 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, for most, orthodoxy requires them to believe that 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. An academy expert describes these as "a delayed, IgE dependent reaction, without sufficient IgE to result in an immediate reaction" (does this sound strained?). (61) In a personal communication, a past-president of an allergy academy said his opinion was that such mold test results are "meaningless Arthus reactions" and the patient's symptoms were called "nonallergic."

Delayed type hypersensitivity to fungi was identified and described long ago. (62) However, in keeping with the IgE-orthodoxy, delayed type reactions on skin tests were attributed to "pathogenic fungi" and the immediate type (IgE)-sensitivity was associated with nonpathogenic, or allergenic, fungi. In this author's experience of recording late and delayed reactions after intradermal tests, the distinction is questionable. (63,64) It is plausible that Arthus reactions are not "meaningless"--and that the type of sensitivity is what renders the fungus pathogenic, rather than the implied converse.

How would allergists learn any differently? Commonly, protocols for provocation challenges require first, determining which allergens should be tested by positive skin tests. (65) While sensible and efficient if IgE were indeed required to precede all significant hypersensitivity reactions, this protocol clearly excludes all of what Coca (in 1943) called "nonreagenic" reactions.

Fortunately, some researchers have used a different approach, challenging common allergens regardless of their skin test responses. This is far from inefficient: they've found that a significant number of allergens provoking airway reactions were negative on skin tests--up to 45% (and only 14% IgE-RAST-positive!). (66,67) Indeed, antigens can provoke late or delayed reactions with no preceding immediate response--the "isolated late type" in 35% and "isolated delayed type" in 10%. (68) This is "key" information: Antigens that do not provoke immediate hypersensitivity ("non-lgE") can cause clinically significant immunological reactions.

Human-Fungus Interfaces and Hypersensitivity

Before science described the fungus kingdom, humanity had given its members common names: mold, mildew, yeast, rusts, smuts, and blights --they are all fungi and are rather similar. (69) Fungi are always present in the human environment. They live in our homes and the great outdoors and we breathe them. They populate our food, often intentionally: With fungus, bread is raised and wine fermented. (70) Blue cheese is made with Penicillium and soy sauce uses Aspergillus (black mold!). (71,72)

Fungus also lives on and inside humans: Aspergillus and Candida normally live in the external ear canal. (73) Fungus can (and does) live in anyone's gut--the frequency and dominant species are related to diet; knowledge about these populations is advancing with new analytic methods. (74) The healthy human has up to 10,000 fungi per gram of stool; Candida species are most common. (75,76) Informal polling at medical meetings indicates that Geotrichum (Camembert cheese), Rhodotorula, and other fungi are also seen (less frequently) on stool cultures. (77)

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 (Thl 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-lgE 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-lgE 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-sensitivlty 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

(1.) Hussein HS, Brasel JM. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology. 2001 Oct 15;167(2):101-134. PMID: 11567776.

(2.) Bennett JW, Klich M. Mycotoxins. Clin Microbiol Rev. 2003 Jul;16(3):497-516. doi:10.1128/CMR.16.3497-516.2003. PMID: 12857779.

(3.) Lee HJ, Ryu D. Advances in Mycotoxin research: public health perspectives. J Food Sci. Epub 2015 Nov 13. doi:10.1111/1750-3841.13156. PMID: 26565730

(4.) Kankkunen P, Valimaki E, Rintahaka J, et al. Trichothecene mycotoxins activate NLRP3 inflammasome through a P2X7 receptor and Src tyrosine kinase dependent pathway. Hum Immunol. 2014 Feb;75(2):134-140. doi:10.1016/j. humimm.2013.11.010. PMID: 24269698.

(5.) Mehrzad J, Devriendt B, Baert K, Cox E. Aflatoxin B1 interferes with the antigen-presenting capacity of porcine dendritic cells. Toxicol In Vitro. 2014 Jun;28(4):531-537. doi:10.1016/j. tiv.2013.11.015. PMID: 24389110.

(6.) Li SJ, Pasmans F, Croubels S, et al. T-2 toxin impairs antifungal activities of chicken macrophages against Aspergillus fumigatus conidia but promotes the pro-inflammatory responses. Avian Pathol. 2013;42(5):457-463. doi:10.1080/0 3079457.2013.822958. PMID: 23930935.

(7.) Mehrzad J, Devriendt B, Baert K, Cox E. Aflatoxins of type B and G affect porcine dendritic cell maturation in vitro. J Immunotoxicol. 2015 Apr-Jun;12(2):174-180. doi:10.3109/1 547691X.2014.916366. PMID: 24870031.

(8.) De Ruyck K, De Boevre M, Huybrechts I, De Saeger S. Dietary mycotoxins, co-exposure, and carcinogenesis in humans: Short review. Mutat Res Rev Mutat Res. 2015 Oct-Dec;766:32-41. doi:10.1016/j.mrrev.2015.07.003. PMID: 26596546.

(9.) Pestka JJ, Yike I, Dearborn DG et al. Stachybotrys chartarum, trichothecene mycotoxins, and damp building-related illness: new insights into a public health enigma. Toxicol Sci. 2008 Jul;104(l):4-26. PMID: 18007011.

(10.) Wheatley LM, Togias A. Clinical practice. Allergic rhinitis. N Engl J Med. 2015 Jan 29;372(5):456-463. doi:10.1056/ NEJMcp1412282. PMID: 25629743

(11.) Hadley, JA. Immunology of allergic upper respiratory disorders. Krouse JH, Chadwick SJ, Gordon BR, Derebery MJ. Allergy and Immunology: an Otolaryngic Approach. Philadelphia: Lippincott Williams & Wilkins; 2002:19-34.

(12.) Antifungal agents for common paediatric infections. Can J Infect Dis Med Microbiol. 2008 Jan;19(l):15-8. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC2610275. Accessed Dec. 22, 2015.

(13.) Amigot SL, Gomez CR, Luque AG, Ebner G. Microbiological study of external otitis in Rosario City, Argentina. Mycoses. 2003 Sep;46(8):312-5. PMID: 12950900.

(14.) Anwar K, Gohar MS. Otomycosis; clinical features, predisposing factors and treatment implications. Pak J Med Sci. 2014 May;30(3):564-567. doi:10.12669/pjms.303.4106. PMID: 24948980 http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4048507. Accessed Dec. 22, 2015.

(15.) Park C, Yoo YS, Park HJ, Park YS. An analysis of the bacterial flora found in the external auditory canals of microtia patients: results and clinical applications. Ann PlastSurg. 2010 Aug;65(2): 197-200. doi:10.1097/SAP.0b013e3181clfeff. PMID: 20585234.

(16.) McDaniel AB: Food allergy and the candida complex [paper and panel discussion]. AAOA Annual Meeting; September 1992;Washington, DC.

(17.) Kroker GF. Chronic candidiasis and allergy. In: Brostoff J, Challacombe SJ. Food Allergy and Intolerance. London: Bailliere Tindall/W.B. Saunders. 1987:850-872.

(18.) Institute for Quality and Efficiency in Health Care. How does the immune system work? Pub Med Health. 2013 Oct 30. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072548. Accessed Dec. 18, 2015.

(19.) Janeway CA Jr., Travers P, Walport M, Shlomchik MJ. Immunobiology: The Immune System in Health and Disease. 5th ed. New York: Garland Science; 2001. http://www.ncbi. nlm.nih.gov/books/NBK27138. Accessed Dec. 16, 2015.

(20.) Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007 Mar;127(3):514-525. doi:10.1038/sj.jid.5700701. PMID: 17299434.

(21.) Janeway CA Jr. et al. 2001. Op. cit.

(22.) Ibid.

(23.) Shlomchik MJ, Weisel F. Germinal center selection and the development of memory B and plasma cells. Immunol Rev. 2012 May;247(1):52-63. doi:10.1111/j.1600 065X.2012.01124.X. PMID: 22500831.

(24.) Janeway CA Jr. et al. 2001. Op. cit.

(25.) Ibid.

(26.) Woof JM, Burton DR. Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol. 2004 Feb;4(2):89-99. PMID: 15040582.

(27.) Gutcher I, Becher B. APC-derived cytokines and T cell polarization in autoimmune inflammation. J Clin Invest. 2007 May;117(5):1119-1127. doi:10.1172/JCI31720. PMID: 17476341.

(28.) Crotty S. A brief history of T cell help to B cells. Nat Rev Immunol. 2015 Mar;15(3):185-189. doi:10.1038/nri3803. PMID: 25677493.

(29.) Niewiesk S. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol. 2014 Sep 16;5:446. doi:10.3389/fimmu.2014.00446. PMID: 2527894.

(30.) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Diagnosis of HIV infection in infants and children [online document]. Last updated March 5, 2015. http://aidsinfo.nih.gov/contentfiles/lvguidelines/ pediatricguidelines.pdf. Accessed Dec. 17, 2015.

(31.) Riedel S. Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent). 2005 Jan;18(1):2125. PMID: 16200144.

(32.) Edward Jenner [Web page]. Wikipedia. https://en.wikipedia. org/wiki/Edward_Jenner. Accessed Dec. 17, 2015.

(33.) Hadley JA. Immunology of allergic upper respiratory disorders. Op. cit.

(34.) Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-499. PMID: 11836274.

(35.) Hotze S. Unpublished data. Presented at: American Academy of Otolaryngic Allergy annual scientific meeting. New Orleans; September 1995.

(36.) Rose NR, Bona C. Defining criteria for autoimmune diseases (Witebsky's postulates revisited). Immunol Today. 1993 Sep;14(9):426-430. PMID: 8216719.

(37.) Lee, CH, Shepard EM, Scala LS. Allergy Neutralization: The Lee Method. St. Joseph, MO: Tri Sigma Press; 1987:10.

(38.) Blackley CH. Hay fever: Its Causes, Treatment and Effective Prevention: Experimental Researches. 2nd ed. London: Bailliere, Tindall & Cox; 1880:93-105. Available at https:// archive.org/stream/hayfeveritscaus00blacgoog#page/n7/ mode/2up. Accessed Dec. 18, 2015.

(39.) Klimek L, Hammerbacher AS, Hellings PW, et al. The influence of European legislation on the use of diagnostic test allergens for nasal allergen provocation in routine care of patients with allergic rhinitis. Rhinology. 2015 Sep;53(3):260-269. doi:10.4193/Rhin14.316. PMID: 26363167.

(40.) De Blay F, Doyen V, Lutz C, et al. A new, faster, and safe nasal provocation test method for diagnosing mite allergic rhinitis. Ann Allergy Asthma Immunol. 2015 Nov;115(5):385-390.el. doi:10.1016/j.anai.2015.07.014. PMID: 26265011.

(41.) Eastes T. Diphtheria cured by antitoxin. Br Med J. 1894 Jul 21;2(1751):125. PMID: 20754971. Available at http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC2404535/pdf/ brmedj08961-0013a.pdf. Accessed Dec. 18, 2015.

(42.) Dean HP. A case of recovery from tetanus in which antitoxin was injected BrMedJ. 1894 Sep 15;2(1759):579-581. PMCID: PMC2404879. Available at http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2404879/pdf/brmedj08969-0007.pdf. Accessed Dec. 18, 2015.

(43.) Principles of vaccination. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Washington D.C. Public Health Foundation; 2015. Available at http://www.cdc.gov/vaccines/ pubs/pinkbook/prinvac.html. Accessed Dec. 18, 2015.

(44.) Lewis PA. The induced susceptibility of the guinea-pig to the toxic action of the blood serum of the horse. J Exp Med. 1908 Jan 1;10(1):1-29. PMID: 19867119. Available at http://jem. rupress.org/content/10/l/l.long. Accessed Dec. 18, 2015.

(45.) Arthus M. Injections repetees de serum du cheval chez le lapin. C R Seances Soc Biol Fil. 1903;55: 817-820.

(46.) Jackson R. Serum sickness. J Cutan Med Surg. 2000 Oct;4(4):223-225. PMID: 11231202.

(47.) Otto Carl W. Prausnitz, Heinz Kustner. In: Cohen SG, Samter M, eds. Excerpts from Classics in Allergy. Carlsbad, CA. Symposia Foundation. 1992;90-91.

(48.) Johansson SG. Raised levels of a new immunoglobulin class (IgND) in asthma. Lancet. 1967 Nov 4;2(7523):951-953. PMID: 4167514.

(49.) Ishizaka K, Ishizaka T, Hornbrook MM. Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol. 1966 Jul;97(1):75-85. PMID: 4162440.

(50.) Broder KR, Cortese MM, Iskander JK, et al. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 Mar 24;55(RR-3):l-34. PMID: 16557217. http://www.cdc. gov/mmwr/preview/mmwrhtml/rr5503al.htm. Accessed Dec. 18, 2015.

(51.) Coca AF, Cooke RA. On the classification of the phenomena of hypersensitiveness. J Immunol. 1923;8:163-182. http://www. jimmunol.org/content/8/3.toc. Accessed Dec. 19, 2015.

(52.) Arthur Fernandez Coca. In: Cohen SG, Samter M, eds. Excerpts from Classics in Allergy. Carlsbad, CA. Symposia Foundation. 1992;94-95.

(53.) Coca AF. Familial Nonreaginic Food-Allergy. Springfield, IL: Charles C. Thomas; 1943.

(54.) King HC. A history of otolaryngic allergy. In: Krouse JH, Chadwick SJ, Gordon BR, Derebery MJ, eds. Allergy and Immunology: An Otolaryngic Approach. Philadelphia: Lippincott Williams & Wilkins; 2002:3-18.

(55.) About us--the history of the Pan American Allergy Society [Web page], http://wp.paas.org/us. Accessed Dec. 18, 2015.

(56.) Randolph TG. Environmental Medicine--Beginnings & Bibliographies of Clinical Ecology. Fort Collins, CO: Clinical Ecology Publications; 1987.

(57.) Gell PGH, Coombs RRA. Clinical Aspects of Immunology. Oxford: Blackwell Scientific Publications; 1963.

(58.) Hadley JA. Immunology of allergic upper respiratory disorders. Op. Cit.

(59.) Shoemaker RC, Schaller J, Schmidt P. Mold Warriors: Fighting America's Hidden Health Threat. Baltimore: Gateway Press; 2005.

(60.) Janeway CA Jr, Travers P, Walport M, et al. The complement system and innate immunity. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. http://www.ncbi.nlm.nih.gov/books/ NBK27100. Accessed Dec. 22; 2015.

(61.) Lieberman P, Ledford DK. Delayed reaction to hymenoptera testing [online article]. American Academy of Allergy, Asthma & Immunology. 2015 April 16. http://www.aaaai.org/askthe-expert/reaction-hymenoptera-test.aspx. Accessed Dec. 22.2015.

(62.) Pepys J. Allergic hypersensitivity to fungi. Postgrad Med J. 1959 Aug;35:436-440. PMID: 14431680 http://pmj.bmj.com/ content/35/406/436.full.pdf. Accessed Dec. 22, 2015.

(63.) McDaniel AB. Late and delayed reactions in testing common molds. AAOA Annual Scientific Meeting. New Orleans, LA; September 1995.

(64.) McDaniel AB. Dust mites cause late and delayed skin-test reactions. American Academy of Otolaryngic Allergy (AAOA) Annual Scientific Meeting. Washington, DC; September 2000.

(65.) Pelikan Z. Rhinitis, secretory otitis media and sinus disease caused by food allergy. In: Brostoff J, Challacombe SJ, eds. Food Allergy and Intolerance. 2nd ed. London: Saunders; 2002; 499-528.

(66.) Ibid., 502.

(67.) Ibid., 505.

(68.) Ibid., 510.

(69.) Ahmadjian V. Fungus. In Encyclopedia Britannica Online. 2015. http://www.britannica.com/science/fungus. Accessed Dec. 23, 2015.

(70.) Jeddi MZ, Yunesian M, Gorji ME, et al. Microbial evaluation of fresh, minimally-processed vegetables and bagged sprouts from chain supermarkets. J Health Popul Nutr. 2014 Sep;32(3):391-9. PMID: 25395902. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC4221445. Accessed Dec. 24, 2015.

(71.) Blue-veined cheeses [online article]. Earthly Delights. http://www.earthy.com/Blue-veined-Cheeses-W599.aspx. Accessed Dec. 24, 2015.

(72.) Soy sauce [online article]. How products are made, http:// www.madehow.com/Volume-3/Soy-Sauce.html. Accessed Dec. 24, 2015.

(73.) Singer D, Freeman E, Hoffert WR, et al. Otitis externa; bacteriological and mycological studies. Ann Otol Rhinol Laryngol. 1952 Jun;61(2):317-330. PMID: 14944130.

(74.) Hoffmann C, Dollive S, Grunberg S, et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS One. 2013 Jun 17;8(6):e66019. doi:10.1371/journal.pone.0066019. Print 2013. PMID: 23799070. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3684604. Accessed Dec. 23, 2015.

(75.) Bernhardt H, Knoke M. Mycological aspects of gastrointestinal microflora. Scand J Gastroenterol Suppl. 1997;222:102-6. PMID: 9145460.

(76.) Cohen R, Roth FJ, Delgado E, et al. Fungal flora of the normal human small and large intestine. N Engl J Med. 1969 Mar 20;280(12):638-641. PMID: 5764842. http://www.nejm.org/ doi/full/10.1056/NEJM196903202801204. Accessed Dec. 24.2015.

(77.) Lessard MH, Viel C, Boyle B, et al. Metatranscriptome analysis of fungal strains Penicillium camemberti and Geotrichum candidum reveal cheese matrix breakdown and potential development of sensory properties of ripened Camembert-type cheese. BMC Genomics. 2014 Mar 26;15:235. doi: 10.1186/1471-2164-15-235. PMID: 24670012. http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC3986886. Accessed Dec. 24, 2015.

(78.) Sanderson IR, Walker WA. Role of the mucosal barrier in antigen handling by the gut. In: Brostoff J, Challacombe SJ, eds. Food Allergy and Intolerance. 2nd ed. London: Saunders; 2002;219-230. ISBN: 0-7020-2038-9.

(79.) Sauni R, Verbeek JH, Uitti J, et al. Remediating buildings damaged by dampness and mould for preventing or reducing respiratory tract symptoms, infections and asthma. Cochrane Database Syst Rev. 2015 Feb 25;2:CD007897. doi:10.1002/14651858.CD007897.pub3. PMID: 25715323.

(80.) Allergy can be treated by inhibiting either IgE production or the effector pathways activated by cross-linking of cell-surface IgE. In: Janeway CA Jr, Travers P, Walport M, et al., eds. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Bookshelf ID: NBK27112. http://www.ncbi.nlm.nih.gov/books/NBK27112. Accessed Dec. 24, 2015.

(81.) Mabry RL. Skin Endpoint Titration. 2nd ed. AAOA Monograph series. New York: Thieme Medical Publishers Inc.; 1994.

(82.) McEwen LM. Enzyme-potentiated desensitization. In: Brostoff J, Challacombe SJ, eds. 2002 Op. cit., 941-949.

(83.) Haydon RC, Gordon BR. Aeroallergen immunotherapy. In: Krouse JH, Chadwick SJ, Gordon BR, Derebery MJ. Allergy and Immunology: an Otolaryngic Approach. Philadelphia: Lippincott Williams & Wilkins; 2002:151-182.

(84.) Grimsley LF, Wildfire J, Lichtveld M, et al. Few associations found between mold and other allergen concentrations in the home versus skin sensitivity from children with asthma after Hurricane Katrina in the head-off environmental asthma in Louisiana study. Int J Pediatr. 2012;2012:427358. doi:10.1155/2012/427358. PMID: 23304171. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3523147. Accessed Dec. 27, 2015.

(85.) PubMed [website], http://www.ncbi.nlm.nih.gov/pubmed. Accessed Dec. 27, 2015.

(86.) Mendell MJ, Mirer AG, Cheung K, et al. Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence. Environ Health Perspect. 2011 Jun;119(6):748-756. PMID: 21269928. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3114807. Accessed Dec. 27, 2015. ^

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.
COPYRIGHT 2016 The Townsend Letter Group
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2016 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:McDaniel, Alan B.
Publication:Townsend Letter
Article Type:Report
Date:Apr 1, 2016
Words:7045
Previous Article:Allergy and immunotherapy.
Next Article:Prenatal fluoride and autism.
Topics:

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters