Tuesday, March 31, 2009
Prior to our experience, I understood the importance of listening to my gut. Now I know it can be critical for survival. I encourage mothers of sick children to rely on your "gut feeling" as you search for answers. At the height of our illnessses I found it difficult to believe I had any intuition whatsoever. I was desperate and vulnerable. I was inundated with advice. I questioned myself as a mother and as a decision-maker. It was invariably my husband who would listen and knowingly ask, "What does your gut say?"
When we came to Arizona in December we encountered one obstacle after the other. Not molehills. Mountains. Kilimanjaro mountains. Numerous voices saying, "Turn around. Go back."
It was so loud inside of me that something good is here. Don't turn back. Hang in there. Again, my husband reminded me, "Just because it's hard doesn't mean we should leave." Only now am I seeing the truth. We are finding help. Things are happening that wouldn't have if we would have left. I'm grateful for the extra brain cells.
Saturday, March 28, 2009
Until our mold exposure I dismissed symptoms. I was quick to assume psychological issues when I heard of a chronic condition. My 11-year-old daughter Kaitlyn asked me a perceptive question after she watched the trailer. It hit me like Nathan's conversation with David in 2 Samuel.
"Mom, if it were someone else with mold would you have thought they were crazy?"
I thought of all the times I heard the words "stress" and "enabling." The doctors who told me my child needed a psychologist. The unbearable helplessness and isolation. I took a deep breath and answered, "I don't know honey. I honestly don't know."
The truth is I probably would have thought they were crazy. And I hate that.
I hope I come away from this experience a different person. Bigger inside. Softer. More willing to walk in another's shoes. Less apt to judge. Less critical.
Maybe I'll start today.
Thursday, March 26, 2009
In the questionnaire you are asked to rate the severity of your symptoms on a 0 to 10 scale.
a. Problems with your head, such as headaches, or a feeling of pressure or fullness in your face or head?
b. Problems with your ability to think, such as difficulty concentrating or remembering things, feeling spacey, or having trouble making decisions?
c. Problems with your mood, such as feeling tense or nervous, irritable, depressed, having spells of crying or rage, or loss of motivation to do things that used to interest you?
d. Problems with your balance or coordination, with numbness or tingling in your extremities, or with focusing your eyes?
e. Problems with your muscles or joints such as pain, aching, cramping, stiffness or weakness?
f. Problems with your skin such as a rash, hives, or dry skin?
g. Problems with your urinary tract such as pelvic pain or frequent or urgent urination?
h. Problems with your stomach or digestive tract, such as abdominal pain or cramping, abdominal swelling or bloating, nausea, diarrhea, or constipation?
i. Problems with your heart or chest, such as a fast or irregular heart rate, skipped beats, your heart pounding, or chest discomfort?
j. Problems with burning or irritation of your eyes or problems with your airway or breathing, such as feeling short of breath, coughing, or having a lot of mucus, postnasal drainage, or respiratory infections?
Again, these are research questions only and, frankly, the tip of the iceberg when it comes to biotoxin exposure.
Tuesday, March 24, 2009
Cathy also brought notes of encouragement from our church family, neighbors, school friends, even a friend from Illinois. I cried as I was, again, reminded we aren't alone on this journey. So many verses and quotes. I share this quote knowing that one of you is traveling a difficult road filled with obstacles, heartache, and darkness.
"A new life requires a death of some kind; otherwise it is nothing new, but rather a shuffling of the same deck. What we die to is an outworn way of being in the world. We experience ourselves differently. We are no longer who we thought we were. But I do not suggest for one moment that it is easy... No wonder, then, that a journey of this kind can seem fraught with danger, at least from the perspective of common sense. Danger and darkness are in the nature of any pilgrimage, whatever the destination."
Monday, March 23, 2009
Friday, March 20, 2009
When I brought the younger kids to Arizona in December she dropped everything to come. She knew she needed help. She began the protocol in earnest and began showing signs of a "die-off". Her rashes became extreme. Her mental state deteriorated. She was truly getting worse. It wasn't until I corresponded with a mom in Virginia that I considered something other than the mold exposure was involved. Her son appears to have a serious case of bartonella/lyme's disease. Thus began our quest to determine if Megan's parasite history is playing a part in her healing process. I have talked with two doctors who specialize in lyme's/bartonella. We are awaiting blood test results. In the meantime Megan is essentially housebound. We have backed off on the sequestering component of the treatment. It's too much for her system. Today we begin an herbal regimen recommended by one of the top doctors in this field. Ironically one of the herbs is from Peru. It makes sense to me that the de-tox caused whatever was hiding to surface. It also makes sense that the mold exposure contributed to her vulnerabilty and would have been reason enough to keep her from traveling to a third world country. But everything is always clear in hindsight.
Tuesday, March 17, 2009
We re-located to Tucson and I had less time than ever to even think about my hair. When we moved into our current home there was no hot water, and I need hot water to wash my hair! A plumber fixed the water issue, but I soon found I didn't have time to even brush my hair. Just look at the slideshow from a few days ago and you'll see reality.
Last week when I found myself in a deep valley I knew something had to change. I talked with our biofeedback, neurobehaviorist, psychologist who has been helping our kids with the brain injury component of the mold exposure. He has seen hundreds of mold patients and says this is the most traumatized group of individuals he has ever seen. He helped me sort through the overwhelming task of helping each child recover from their own brain injury/trauma. And then we talked about grieving. The reality that life will never be the same.
When we first left the house I honestly thought, "We'll get better and soon be back to normal." I think the denial that goes with trauma is really a gift. I couldn't have handled anything more at that point. As our health continued to suffer and we re-located, I thought, "We'll be here for a couple of months and then get back to normal." Now, as we continue to face medical, financial, and emotional challenges, it's time to face reality.
When I left his office that day, I went straight to Great Clips. My daughter, Shannon, met me and with her encouragement I told the stylist to cut off all of the color. It was time. I can't say I like my hair. It's quite short with lots of grey. But I feel much freer. No more covering up the roots. No more trying to look younger than I am. No more hiding the fact that life has changed. With every loss comes opportunity. A chance for something new. I think I'm ready.
Monday, March 16, 2009
In 2003, the American College of Occupational and
Environmental Medicine (ACOEM) published its evidence-
based statement, “Adverse Human Health Effects
Associated with Molds in the Indoor Environment,” in
its Journal of Occupational and Environmental Medicine
(JOEM). ACOEM’s author selection, development, peer
review, and publication of its mold position paper
involved a series of seemingly biased and ethically dubious
decisions and ad hoc methods. The resulting position
paper resembled a litigation “defense report”
which omitted or inadequately acknowledged research
validating the association between mold and buildingrelated
symptoms. ACOEM nonetheless released the
paper as an “evidence-based” statement and then published
it in JOEM without any further changes or conflict
disclosure. The Mold Statement has been relied
upon by attorneys and expert witnesses representing
defendants in mold litigation to disclaim and invalidate
individuals’, families’, and workers’ claims of buildingrelated
health effects from indoor mold exposure. Key
words: ACOEM; conflicts of interest; evidence-based
statement; indoor air quality; JOEM; mold.
In other words, the government has supported the belief that mold is not a risk to human health.
According to Dr. Craner, the government needs to reconsider. For those with a keen interest in this subject the entire article can be read at the link below.
Saturday, March 14, 2009
This family of mycotoxins
causes multiorgan effects including emesis and diarrhea,
weight loss, nervous disorders, cardiovascular
alterations, immunodepression, hemostatic
derangements, skin toxicity, decreased reproductive
capacity, and bone marrow damage.4,6
In this chapter, we will concentrate on T-2 mycotoxin,
a highly toxic trichothecene that, together
with some closely related compounds, has been the
causative agent of a number of illnesses in humans
and domestic animals.1,2,4 During the 1970s and
1980s, the trichothecene mycotoxins gained some
notoriety as putative biological warfare agents in Southeast Asia.
The report is quite detailed but here's the summary:
... trichothecene mycotoxins are proven lethal agents in warfare.
Symptoms include vomiting, pain, weakness, dizziness,
ataxia, anorexia, diarrhea, bleeding, skin
redness, blistering, and gangrene, as well as shock
and rapid death. Sensitive immunoassays and
chemical procedures are available for the identification
of trichothecene mycotoxins in biological
samples, but no detection kits have been fielded.
Prevention of exposure is the only current defense,
with a protective mask and clothing worn
when under attack. Previous successful lethal attacks
have always occurred against unprotected civilians
and soldiers. Skin decontamination with
water and soap can be used effectively up to 6 hours
after exposure. Experimental treatments for systemic
toxicity are being investigated, but no therapy
is available for humans..
This explains why avoidance for those exposed to stachybotrys is the first and foremost line of defense. The good news, of course, is that there are now therapies available.
If you would like to see the report it is available at this website.
Friday, March 13, 2009
Wednesday, March 11, 2009
Our 12 year-old son Reagan spent the day photographing us. From first thing in the morning to 9:00 at night. This is his 6 minute representation of our new life. From our breakfast supplements, to Chris' daily radio show (he uses our beds for sound protection), to our swim at a salt water pool 30 minutes away.
The pictures don't show the tears over the loss of our dogs, the longing for Colorado, and the discouraging news that our insurance carrier has refused coverage. But the beauty of the sunset somehow surpasses our "light and momentary affliction" and compels me to hope in something much bigger and brighter.
Tuesday, March 10, 2009
"Sometimes words get to you. For the first time you get a glimpse of the past,the present, and the future. You realize what has happened, what is happening, and what is going to happen. I've always been afraid of death, but for the first time I feel hope, forgiveness, and happiness because I have got family close to me no matter what. Life seems peaceful now, but at the same time it feels harder than ever. There are some things in life that are unforgettable. Loosing 3 loved and loving pets is one of those things. But we as a family should never give up what we have started. Like i'd like to say it we've come to a fork in the road but we haven't turned back. This message goes out to all the people out there who understand that life is a roller coaster. There is always a story behind your beloved ones. So we, as humans have to understand the great creations that are made around us. Those creations are what inspire anyone to do what they are doing now. Think about what you own. Sometimes I ask myself, why do I have all of this stuff? The answer is that the people surrounding you are caring for you every second of the day. When I would wake up in the morning I would have a glimpse of happiness. My bird was chirping, Frodo stuck his ears up at the sight of us, and Pippen whimpering around following Frodo. Those three creatures brought us happiness."
Sunday, March 8, 2009
Friday, March 6, 2009
The therapy of all hypersensitivity diseases must be based on avoidance. In the case of fungi, it is important to recognize that there are three sources of exposure: The airborne particles, mostly spores, which result from water intrusion at home, school and work; ingestion as in the enormous amounts, and types of fungal products used by the food industry; and colonization of skin, lung, sinuses and other mucosal surfaces.
A. Environmental molds
A moldy environment must be remediated or destroyed. All sources of water intrusion have to be discovered and sealed. All wetted surfaces must be completely dried (e.g. both sides of sheet rock) and any surfaces showing fungal proliferation must be replaced including walls, floors, carpets and pads, cabinets, furniture, etc. In many cases of fungal hypersensitivity, the affected individual may not be able to return to the remediated space because his sensitivity is too great for the level to which remediation may reduce fungal efflux. There is a simple canary-in-the-mine parallel. No amount of surveying the remediated site can assure that the patient will be able to tolerate the reduced fungal levels. More times than not, they cannot. Avoidance may require a move to different quarters.
High efficiency particulate air filters (HEPA) are useful in removing spores from the air. They remove a great majority of the particles greater than 0.3 microns in size, which includes all mold and bacterial spores. However, a heavily mold-infested indoor space may overwhelm the ability of a HEPA room air purifier to significantly reduce ambient spore levels.
A. Food molds
Fungi are prolific enzyme and toxin generators, which is the basis for much of their use in modern food technology. Bread will rise more quickly, require less baking time and lower baking temperatures if amylase is added to the dough. The amylase digests the cross linkages of the cellulose in the dough making it less tough. This results in considerable economic gain for the baking industry. Its downside is that it has produced substantial illness in bakers and it loads the bread with mold products that add to the burden of a mold sensitive individual. These additives are listed on the ingredient labels of breads as dough conditioners or malted grains (for malt, read mold). Fruit juice manufacturers discovered that if hemicellulases (of fungal origin) are added to the crushed fruit prior to squeezing out the juice, the yield can increase as much as 25%. The enzymes digest the cellulosic structure of the fruit and allow more juice to be obtained from the cells. This is a wonderful economic gain for juice makers, but adds fungal elements to the juice.
Citric acid is perhaps the greatest misnomer in the ingredients listing of any food. It is added to most processed foods including soft drinks, jams and jellies, frozen meals, etc. as a preservative. It conjures up visions of lemons, oranges and limes. It is none of these; it is a direct product of Aspergillus fermentation in commercial quantities. It is a highly impure “citric acid” contaminated by many other Aspergillus products including toxins, antibiotics, etc. One wonders if pure citric acid would confer the same excellent preservative properties as commercial “citric acid” on foods? Again, this is an excellent product for the food industry in extending the shelf life of foods, but it adds fungal elements to the food.
Some foods are obligate products of fermentation such as aged cheese (usually Penicillium), soy sauce (usually Aspergillus), chocolate (mixed molds), and black tea (Aspergillus). While wonderful on the educated palate, they must be eliminated in a mold-free diet. The patient trying to avoid mold in his food must be instructed in how to maintain a fresh food diet. This means shopping more frequently than weekly. Farmer’s markets are often excellent sources of fresh fruits and vegetables. This may be especially difficult in small towns where the supermarket is the only source of food.
Colonization of the human mucosa is a common phenomenon that seems to be poorly understood. The human body is colonized by bacteria in the nasopharynx, mouth, gastrointestinal tract, skin, etc. No one questions this and the concept of a balanced ecology in the gut is considered essential for proper gastrointestinal (G.I.) function and a stable supply of nutrients such as vitamins. Fungal colonization is also a widely accepted phenomenon, as for example, toenail fungus, athlete’s foot, vaginal candidiasis, chronic fungal sinusitis and seborrheic dermatitis. But the concept that fungi can become part of the normal mucosal flora, and that once established, fungal colonization can place a heavy burden on the body’s defenses is not always appreciated. Some fungi produce toxins and all fungi produce and secrete enzymes into their environment. The body has to protect itself against all foreign proteins, especially those that carry enzymatic activity. The immune response is that protection. Foreign enzymes are known to be among the most powerful stimulants of an immune response (Larson et al., 1996).
Patients who have become ill from living or working in a moldy space are often improved when they move, but their health does not always return to normal. This means either that the fungal exposure resulted in permanent damage, which is quite possible with tissue deposited immune complexes or certain mycotoxins, or there is continued exposure to the fungus because of colonization. Colonization is more likely to occur first where there has been previous tissue damage. The nasopharynx is the first filter for airborne fungi and would expect to be first to be colonized along with adjacent communicating structures like the sinuses or middle ear. Colonization is more likely to occur where there are residual scars from past disease or surgery. This is where the body’s first line of defense, mucous flow, ciliary action and IgA secretory antibody function is likely to be missing. The lungs are easy targets for colonization when there has been previous damage as in a past pneumonia. Children with cystic fibrosis are virtually 100% colonized in the lungs (Etzel et al., 1998) and patients with chronic asthma are said to be about 30% colonized. The esophagus is a common site for colonization because of its vulnerability to damage from hot foods, spicy foods and acid reflux.
When possible, colonization is best treated topically. The oral cavity and esophagus can be treated with liquid fluconazole (40 mgm/ml) or Itraconazole, (10 mgm/ml), 40 or 50 mgm four times daily. Neither of these is well absorbed in a non-acid media and they can be quite effective topically until they reach the stomach where they may be absorbed. Nystatin is a non-absorbed antifungal with an excellent safety record. It can be given as a powdered suspension in water at 500,000 units four times daily. It will continue to provide antifungal activity throughout the G.I. tract, as it courses its way from mouth to anus.
Fungal colonization of the nasopharynx, sinuses and middle ear is best treated with an antifungal nasal spray. A 2% ketoconazole suspension or a 0.01% amphotercin B solution applied generously four times daily to the nose is effective in many cases. It must be delivered deep into the nasal cavity and be felt passing into the pharynx. Neither will be significantly absorbed in the pH neutral mucosa of the nose. The benefits of therapy are likely to be noted within a few weeks but a cure, where therapy can be safely stopped without recrudescence of the illness, is months and sometimes years in the future. This is likely due to the resistance of the spore to killing with available antifungal drugs which means that therapy must be continued until all spores are eliminated or germinate and become susceptible to the action of the antifungal.
Colonization of the lungs and sometimes the sinuses requires a systemic antifungal such as Itraconazole, ketoconazole or voriconazole. Each are given at 200 to 400 mgm per day (Schubert, 2000) (Gallin et al., 2003). In some cases of lung disease a nebulized antifungal is helpful. Ketoconazole has been successfully used nebulizing 50 mgm per treatment, twice daily.
Many physicians show great concern when talking of systemic antifungals because of the possibility of liver damage. This concern is grossly overstated. Most antifungals used in high doses are given to immunocompromised individuals with severe fungal infections including blood-borne dissemination. Elevated liver enzymes in such catastrophic illness is not rare and must be considered in the decision to use such therapy. However, in my ten-year experience with antifungals in immunologically normal individuals colonized by fungi, I have yet to see a single episode of elevated liver enzymes, which can be attributed to the use of the antifungal. Testing for liver function at two to four month intervals is recommended by the FDA. It has been reported that in those rare instances where liver enzymes have risen, cessation of therapy results in a rapid return to normal in all but a few rare instances. The antifungals are metabolized in the liver and place some burden on the detoxification enzymes of the liver, which are also used to metabolize certain drugs. The use of antifungals may influence the serum and tissue levels of such drugs generally causing a rise in concentration as the rate of metabolism of the drug is reduced. Such changes can be handled by careful assessment of tissue levels of drugs used simultaneously with the antifungals.
Fungal colonization of the G.I. tract is a relatively common phenomena encouraged by the over use of antibiotics in medicine and their use in the production of meat for human consumption. This usually manifests as abdominal discomfort, heartburn, increased gastric emptying time, bloating, crampy abdominal pain and increased transmucosal uptake of large food protein molecules (leaky gut). Treatment is best begun with a non-absorbed antifungal such as Nystatin or poorly absorbed antifungals such as miconazole or econazole. Nystatin is best given as a powdered suspension, two to three million units per day in divided doses (bid or tid). The miconazole and econazole are not generally available in pure powder form from regular pharmacies and must be formulated. This increases the cost somewhat but still leaves them far cheaper than the newer antifungals already mentioned. They are given in 250 mgm capsules twice daily.
1. Jarisch-Herxheimer Reactions
The treatment of fungal colonization in patients hypersensitive to fungi almost always produces a Jarisch Herxheimer (JH) reaction if given too aggressively. It is safest to begin with one quarter or less of the therapeutic target dose and advance every three to four days in doubling doses to those reach the desired dose. The JH reaction can occur at the initial dose or at any time the dose is increased. It manifests as a flu-like reaction in its broadest sense, i.e., headache, rash, low grade fever, myalgia, arthritis, night sweats, malaise, cough, diarrhea, etc. When it appears, treatment should be stopped until the symptoms disappear (usually one to two days) and then a lower amount should be introduced and held there for two weeks before any attempt to increase the dose. It is best to be guided by the patient who quickly learns if there is a limit to the dose he can tolerate, but he may subsequently have to be encouraged to try to take more medicine if past experience(s) has been severe enough to be alarming. The JH reaction can also occur when the patient who is seemingly stable (on full dose), suddenly experiences a larger fungal burden, such as in staying in a moldy hotel room on a trip or following a day of spreading compost in a vegetable garden.
Colonization of the skin in the form of abscesses on the skin or dry scaly rashes over the palms of the hands (dishydrotic eczema) can be treated with topical antifungal creams, sometimes coupled with systemic antifungals. The topical antifungal action on the skin can be enhanced by use of occlusive dressings. Patients are directed to apply the cream liberally at bedtime and then cover the lesion with a watertight membrane (e.g., plastic food wrap) which remains overnight.
All fungal therapy must be prolonged, often for a year or longer. This is likely due to the resistance of fungal spores to any medicine and the rapid reestablishment of colonization, should therapy be ended too soon. All the spores must have been shed or have germinated and been killed by the action of the antifungal and the body’s natural defense system before the colonization is truly ended.
The best treatment for health problems arising from exposure to high fungal levels is prevention. A key prerequisite to prevention is education. Information about the nature of fungi, their presence in foods, their rapid proliferation after water intrusion in homes, workplaces and schools, and their potential for health effects must be made easily available to the general public. The Internet has already provided such information to millions who use computers. Insurance companies are excluding mold damage from the coverage provided in homeowner policies and this may alert the homeowner to the danger and to his/her responsibility to move rapidlyto minimize the effects of water leaks. Reports in the media of litigation by celebrities experiencing fungal illness, also helps increase public awareness of the problem. Public health service organizations have to date been more concerned to quell the public’s concern about mold problems by suggesting that it is not an important issue. This is a disservice. It would be far better to acknowledge the potential health effects of mold exposure along with suggestions for controlling mold levels in homes, workplaces and schools.
The author is grateful to his daughter, Tess Marinkovich for critical reading of this manuscript and to Mary Borch for her help in preparing the text.
· Anger, P.L., Gourdean, P., Miller, J.D. (1994). Clinical experience with patients suffering from a chronic fatigue-like syndrome and repeated upper respiratory infections in relation to airborne molds. Am. J. Ind., Med., 25:41-2.
· Banaszak, E.F., Thiede, W.H., Fink, J.N. (1970). Hypersensitivity pneumonitis due to contamination of an air conditioner. N.Eng. J. Med., 283:271.
· Burr, M.L. (2001). Health effects of indoor molds. Rev. Environ. Health, 16:97-103.
· Cakmak, S., Dales, R.E., Burnet, T., Judeck, S., Coates, F., Brook, J.R. (2002) Effects of airborne allergens on emergency visits by children for conjunctivitis and rhinitis. Lancet,359:947-48.
· Cochrane, C.G. and Vaffler, D. (1973) Immune Complex Diseases in Experimental Animals and Man. Adv. In Immunol., 16:185-264.
· Croft, W.A., Jarvis, B.B., Yatawara, C.S. (1986). Airborne outbreak of trichothecene toxicosis. Atmos. Environ., 20:549-52.
· Dales, R.E., Zwanenburg, H., Burnett, R., Franklin, C.A. (1991). Respiratory health effects of home dampness and molds among Canadian children. Am. J. Epidemial, 134:196-203.
· Dearborne, D.G., Smith, P.G., Dahms, B.B., Allan, T.M., Sorenson, W.G., Montana, E., Etzel, R.A., (2002). Clinical profile of 30 infants with acute pulmonary hemorrhage in Cleveland. Pediatrics, 110:627-637.
· Dearborn, D.G., Yike, I., Sorenson, W.G., Miller, M.J., Etzel, R.A. (1999). Overview of investigations into pulmonary hemorrhage among infants in Cleveland, Ohio. Environ Health Perspect., 107 (Suppl 3):495-9.
· Emanuel, D.A., Wenzel, F.J., Bowerman, I. Lawton, B.R. (1964). Farmers lung: Clinical pathologic and immunologic study of twenty-four patients. Am. J. Med,. 37:392.
· Etzel, R.A., Montana, E., Sorenson, W.G., Kullman, G.J., Allan, T.M., Dearborn, D.G., Olson, Dr., Jarvis, B.B., Miller, J.D. (1998). Acute pulmonary hemorrhage in infants associated with exposure to Stachybotyrs atra and other fungi. Arch. Pediatric Adolesc. Med., 152:757-762.
· Fink, J.N., (1984). Hypersensitivity pneumonitis. J.Allergy Clin. Immunol., 74:1-19.
· Fink, J.N., Banaszak, E.F., Thiede, N.H., Barboriak, J.J. (1971). Interstatial pneumonitis due to hypersensitivity to an organism contaminating a heating system. Ann. Intern. Med.; 74:80.
· his list goes on but I will leave it at this point.
Tuesday, March 3, 2009
The human immune response, part of the body’s system of adaptive immunity can be amazingly sensitive. A person allergic to cats can sense the presence of cat dander in a room months after the cat has departed. And rarely, one reads of a sudden death from anaphylaxis provoked by exposure to a tiny amount of antigen such as vespid venom from a single bee sting or the steam rising from a fish stew, or tiny particles of peanut contaminating a package of almonds processed on machinery previously used to process peanuts (Samson, 1992). The extreme sensitivity potential of the immune system is rarely seen but frightening when it occurs. When the number of individuals exposed to such spore levels is very high, as seems to be the case today in homes, schools and workplaces, a significant number of cases will occur. To deny this is akin to denying the existence of significant pollen or cat allergies because the great majority of people do not show such symptoms on exposure. Genetic polymorphism is the basis for a considerable number of differences within the human population and the immune response, based on the same mechanisms, shows the same wide variations in response among individuals.
While the symptoms seen in patients exposed to high ambient levels of fungal elements can vary a great deal among different individuals, a fairly consistent pattern of illness is seen in patients presenting with sufficient symptoms to warrant seeing a physician. Most patients describe a progression of symptoms beginning a few months to a few years after the onset of exposure (e.g., moving into a mold-infested house). Initially the complaints are nasopharyngeal (sore throats, hoarseness, stuffy nose, transient hearing loss), or pulmonary (cough, wheezing, shortness of breath). With time, symptoms progress to include headaches, fatigue, rashes, vertigo, muscle and joint pain, fever, recurrent sinus or ear infections, etc (Rylander, 1994). Many of these symptoms are the result of an overactive immune system trying desperately to overcome what it perceives to be an overwhelming infection. The immune system generates antibodies to the absorbed materials (or antigens). These antibodies react with the antigens to form immune complexes, which is all part of the body’s normal immune elimination function. These complexes are quickly taken up by scavenger cells, which remove the complexes from the circulation thus limiting their inflammatory effects. When complex formation continues over a long period of time, this clearing mechanism can become overloaded. The complexes then remain in the blood stream causing myriad symptoms, known to clinical immunologists as serum sickness or immune complex disease (Cochrane et al., 1973). To the patient, the symptoms appear to be a severe, unrelenting flu syndrome. When one looks up in the older literature the classical symptoms seen in serum sickness, they are exactly those symptoms the patients with fungal illness describe to their physician (Von Pirquet, 1951).
Since hypersensitivity states develop only after relatively long exposure times, normal children under ten years of age do not have significant antibody titers to fungi. However, when children experience very high exposure levels in the home or school, measurable antibody levels appear rather quickly, i.e., within a few months of exposure. Normal mature adults living in temperate or tropical climates commonly show antibody activity toward fungi and experience symptoms following unusual exposures. The onset of symptoms often follow exposures by one or two days, are not recognized for what they are, and are likely to be diagnosed as a virus infection.
Mycotoxins are the most respected of fungal products for their potential to cause serious illness through their direct biochemical action on key body functions (Johanning et al., 1996) (Croft et al., 1986) (Leino et al., 2003). The immune system is not involved. One of these, aflatoxin, is known to be among the most potent of carcinogens. Another group, trichothecenes, are toxins released by the fungus Stachybotris atra (also known as Chartarum) as well as others. There is controversy regarding the role of trichothecene mycotoxins in pulmonary hemosideroisis (Dearborn et al., 1999). Other toxins can affect various hormonal, neurological and other body functions to produce serious health effects (Sorensen, 1999). They are so effective in certain biological activities that they have been harnessed by the pharmaceutical and food industries for commercial use such as antibiotics, immune suppressants to control graft rejection, medicine for cholesterol control, and enzymes used in food processing and preservation. Mycotoxins are produced by fungi under specific growth conditions and their role in human illness is not well understood. Exposure to certain mycotoxins producing organisms such as Stachybotrys seem to cause neurological damage seen as short-term memory loss, cognitive dysfunction, inability to concentrate and “fuzzy thinking”. There are common complaints of patients with fungal illness. The changes seem to be reversible, at least in part, but they can take years to resolve. Hyperactive immune systems responding to the influx of fungal antigens following chronic exposures are much more likely to be a cause of symptoms in most individuals
VII. The role of IgE and non-IgE
Allergists have accepted the role that fungal spores can play in eliciting allergy symptoms in susceptible individuals. This is akin to the effects of other airborne organic particles such as pollen, animal dander and insect dust The illness affects only individuals programmed genetically to make large quantities of specific IgE antibodies on exposure to relatively small amounts of allergen. This is type I immunopathology as defined by Gell and Coomb (Gell et al., 1964) and involves the release of pre-formed histamine and other biologically active cytokines from sensitized mast cells and basophils. Symptoms include watery nasal discharge, sneezing paroxysms, itching of the naso-oro-pharyngeal mucosa and tearing eyes, and can be significantly disabling. Symptoms disappear quickly upon cessation of exposure, leaving little, or no, residual effects. It has been suggested that perhaps five percent of the population may be affected in this way by fungi, although those numbers will vary in different climates (e.g., more in Florida than New Mexico). The great majority of patients presenting with symptoms of fungal illness do not show IgE antibody to the fungus (Fink, 1984). This may be the result of isotype switching from IgE to IgG production as stimulation of the immune system increases. When this happens far more elaborate and damaging immune responses can be generated by the body following exposure to large amount of fungal particles, especially when the exposure is chronic. These illnesses were originally described in association with various occupational exposures in unprotected workers such as farmer’s lung, bagassosis in sugar cane workers, and many others. More recently such conditions have been identified and studied in office workers whose workplace is contaminated by fungi, especially in buildings with closed ventilation systems (Fink, 1984), in individuals exposed to swamp coolers (Marinkovich et al., 1975) or contaminated air conditioners in the home (Bavaszak et al., 1970), and in many other school, home and workplace exposures, generally as case reports involving a few patients per report (Cakmak et al., 2002) (Hodgeson et al., 1998) (Dales et al., 1991). These symptoms can occur in all individuals with normal immunity because they are ultimately manifestations of a robust immune response to a heavy unrelenting airborne fungal load with consequential overload of clearing mechanisms or macrophages, and the activation of inflammatory processes.
Although the general immune response to a heavy fungal antigen exposure may consist of all the immunoglobulin isotopes (IgA, IgM, IgG, IgD and IgE) plus sensitized lymphocytes or T-cells, specific IgG is the most efficient single marker of generalized immune responses. Specific IgG antibody levels to fungi are not diagnostic when taken alone. However, antibody levels to fungi are directly proportional to levels of exposure in any individual, and generally high exposure levels result in high antibody titers. These antibody levels drop when the patient’s exposure to the offending fungi ends. When elevated, they are helpful in arriving at the presumptive diagnosis and repeat measurements at four to six month intervals help verify compliance with the fungal avoidance program and helps monitor the success of therapy.
A. Immune Complexes
The presence of antibody in the serum is not pathologic in itself. All the immunoglobulins normally present in the tissues, with possible rare exceptions, are antibodies and they contribute to the immune state. It is only when antigen(s) combines with antibody(ies) that immune complexes are formed and a potentially pathologic state is initiated. Immune complexes are not stable since the union is one of complimentary surface configurational attraction between two or more molecules produced by Van der Wall forces. The complexes can easily be disrupted as the conditions in solution change. Changes in temperative, relative numbers of reacting molecules, their nature, the epitope specificity of the reacting antibodies, etc., can all effect changes in the size, shape, surface charges, solubility, of the complex. These factors are the ones that determine the inflammatory potential of the complexes formed and whether the complexes will tend to be deposited in kidneys, joints, blood vessel walls, skin, lungs, etc. (Cochrane et al., 1973). Because of the inherent instability of immune complexes in tissue and serum, they are difficult to study. Interest in understanding immune complexes was very high in the 1950’s and 1960’s and quickly dissolved away when IgE was discovered (Ishizaka et al., 1966) and the attention of the immunological research teams was attracted to the newly defined antibody responsible for classical allergy symptoms, Type I of Gell and Coombs.
There are sound scientific reasons why specific IgG antibodies to fungi are not always diagnostic. Some individuals with high antibody levels to fungi remain symptom free during re-exposure. Such individuals may be less likely to produce the toxic immune complexes required to induce symptoms by virtue of the fungal antigen epitopes to which they respond. They may respond to minor epitopes that allow measurement of the antibody, but which do not engage in the formation of toxic immune complexes. Other individuals may have a vast scavenger system, which can rapidly take up and extinguish all immune complexes generated before symptoms can ensue. Other individuals may satisfy the high exposure and the appropriate symptom requirements and have relatively low total specific antibody levels to fungi. They may be poor antibody responders with an even lower capacity to deal with immune complexes. The observation that they can still experience flu-like symptoms following fungal exposure demonstrates that a relatively low antibody level can still produce significant, disabling symptoms.
Mold toxins can be powerful immune suppressors. It is sobering to remember there would be no organ transplant program without the availability of fungal toxins (e.g., cyclosporin). It is possible and even likely that the fungal exposure of some patients will include exposure to immune suppressive mycotoxins. Another cause for low antibody levels in a symptomatic patient could be iatrogenic. Many patients develop arthritic symptoms and present themselves to rheumatologists who may choose to use an immuno-suppressive drug such as methotrexate to treat the arthritis. Such a drug will certainly depress the immune response, relieve the severity of arthritic symptoms while masking what could be the real trigger for the arthritis.
(To be continued)
Sunday, March 1, 2009
At the same time an event such as this propels me forward in my determination to give them every opportunity to recover their life.