To further complicate matters, anatomical factors may predispose the patient to CRS, and the disease can affect just one of the paranasal sinuses, a few at one time, or all of them, he added.
Explore This IssueSeptember 2006
Most people get an infection, which the immune response gets rid of, and then they get better. But in patients with CRS, there’s obviously some sort of ongoing stimulus. – -Joel M. Bernstein, MD, PhD
An allergic reaction to fungal antigens may be one reason why patients develop CRS. It is likely that some patients have a sensitivity or allergy to fungi, and this leads to an immune response that results in chronic sinusitis, said Marilene Wang, MD, Professor in the Division of Head and Neck Surgery at the University of California at Los Angeles David Geffen School of Medicine.
Whether the fungi are actually infecting the sinus tissue in patients with allergic fungal sinusitis is unclear, she added. It is more likely that this is not a true infection [that] requires antifungal therapy, but rather an allergic or immune response to the fungi, she said.
A non-allergic muscinous eosinophilic form of CRS caused by fungi, which may respond to antifungal treatment, is being studied by Dr. Ponikau and his colleagues at the Mayo Clinic. Research indicates that fungi, specifically Alternaria, are present in CRS patients and healthy controls.
However, CRS patients, unlike controls, react with cytokine production, which is crucial for eosinophilic inflammation. The fascinating fact was that all the CRS patients were reacting but not healthy persons, said Dr. Ponikau of his research.
Eosinophils appear to target fungi in the paranasal mucus, explaining why these inflammatory cells appear in the sinuses, he said. One reason why determining CRS etiology has been challenging is because physicians did not appreciate the kind of inflammatory process underlying the disease, namely eosinophilic inflammation, said Dr. Ponikau.
Alternaria induces eosinophil degranulation, which means that the inflammatory cells release their toxic mediators, such as major basic protein, he explained. We have already found the actual antigen, meaning the substance coming out of the fungus, which the inflammatory cells react to, he said.
It is now possible to sensitize mice to fungi, which produces the same kind of eosinophilic inflammation resulting in CRS, he said.
We also found that lymphocytes regulate eosinophilic inflammation, he said. We can reproduce this disease process in the Petri dish, and we found that a signal coming from those lymphocytes is necessary to induce the attack of the eosinophils against the fungi. Lymphocytes from healthy people are lacking this signal; thus, eosinophils were not attacking the fungi.