The diagnosis of fungal hypersensitivity syndrome rests on four criteria: Exposure to an identified heavily contaminated source, appropriate symptoms temporally related to exposure, high serum specific IgG levels to molds, and finally a positive response to therapy. IgE antibodies are usually not involved in hypersensitivity phenomena secondary to exposure to high dose antigen such as fungi, foods and occupational exposures to organic matter (Fink, 1984). Skin tests are, therefore of little, if any, value. The fourth criterion for diagnosis is an essential feature of all medical therapy, namely, the clinical improvement resulting from a fungal avoidance regimen. When this condition is not met, the diagnosis must be revisited. Either avoidance is inadequate, therapy is insufficient or the diagnosis is wrong.
A. Antibodies or lack thereof
Everyone is exposed to fungi in daily living and, therefore, antibodies to fungi are found in nearly everyone. They have been shown to be protective, except for patients whose immune systems are inadequate in response. These patients are extremely susceptible to fungal infection. In such cases, e.g., AIDS patients, cancer patients (especially if on chemotherapy), transplant recipients on immunosuppressive drugs, and patients with acquired or congenital immune deficiency, especially involving cellular immunity, fungal colonization can be life threatening. In most healthy individuals, the constant exposure to ambient fungal spore levels is handled easily by normal mucosal cleansing mechanisms and the ever-vigilant immune system. Ill effects do not generally occur in the normal population. However, this statement is not true for all otherwise “healthy” individuals. The extreme example of this is seen in certain occupational fungal diseases, e.g., farmer’s lung (Emanuel et al., 1964), malt workers pneumonitis (Riddle et al., 1968), etc. where enormous exposures occur on a daily basis and virtually everyone can be symptomatic. In such cases the inflammatory changes produced in the lungs can cause severe destruction of lung tissue, extensive colonization of lungs with fungi and bacteria, and slow progression to respiratory deficiency and death (Pepys, 1969). Such patients must be treated aggressively with complete cessation of further exposure, high doses of systemic and inhaled antifungals (Stevens et al. 2000) (Nark et al., 2003) and the judicious use of systemic steroids to reduce inflammation and arrest the progressive damage or remodeling of the lungs (Kaltreider, H.B., 1993). Steroids actually encourage fungal growth by suppressing the inflammatory reaction and their use must be carefully monitored to walk the tightrope between too much steroid encouraging fungal growth and too little allowing progressive destruction of lung tissue.
B. Individual Variations in Response
The levels of fungi in contaminated homes and office buildings may be quite high but are generally not nearly as high as encountered in the special occupational situations previously mentioned above. Still they are high enough to cause serious illness in non-immuno-compromised individuals (Burr, 2001). A considerable variation in response to moldy homes among members of the family is common. In some cases all members of the family are affected with some small variations in severity and in the organs infected, e.g., skin, lungs, sinuses, gastrointestinal tract, headaches, etc. In other instances the variation in severity of illness can be considerable among family members, one person at one extreme may be quite ill, even disabled, while another at the other extreme has little to show for the exposure. This is understandable in that not all rooms in the house may be equally contaminated and those sleeping in the rooms with highest levels of contamination are likely to have more severe symptoms. Variations may be seen in the amount of time each individual spends at home. And then there is genetic polymorphism where each individual is endowed with his own unique immune responsiveness and two individuals in the same family or bloodline may respond quite differently to the same exposure. In studies done with serum sickness where normal, healthy individuals were given different volumes of horse serum intravenously, some individuals developed symptoms (Von Pirquet, 1951) with relatively low volumes of serum while others required ten times more serum to show the same symptoms. The conclusion of these studies was that everyone was susceptible, but there is a dose dependent susceptibility among different individuals.
Sustained exposure to airborne fungal spores at levels far below the occupational disease levels in otherwise normal healthy individuals will produce symptoms in some percentage of patients. The exact percentage of susceptible individuals is likely to be low, perhaps under 1% of the population. But with the widespread contamination of home and workplaces in this country, with perhaps 30% of the schools, homes and offices involved, the actual number of affected individuals can easily reach one million. One percent of the population is about three million individuals and a third of these would be one million. This is an epidemic. Unfortunately, many of these cases are not recognized by the medical community and go undiagnosed and untreated. Thanks to the Internet and the media publicizing the results of litigation involving mold cases, the public’s awareness of the problem has grown. Hopefully, this will induce more health caregivers to learn about fungal illness.
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.