The following is based on a lecture given by Dr. Tichenor at the Functional Endoscopic Sinus Surgery course in Jackson, Mississippi on October 19, 2000 and subsequently given at several other meetings with modifications. It is a guide for otolaryngologists as to when the allergist should be called for patients with chronic sinusitis.
I would like to establish today for otolaryngologist the kinds of circumstances when an allergist should be called for consultation in patients with chronic sinusitis. We need to establish at what point the allergist needs to be called when treating a patient with chronic sinusitis . We would also like to decide whether this is before surgery, after surgery, or under what other circumstances, as well as what tests the allergist needs to perform.
An allergist will take an extensive history with regard to exposure to environmental agents. This may take an extended amount of time, depending on the patient. For example in patients with sinusitis, mold exposure should be extensively explored, and may in some cases require an home visit and mold sampling to be done, as many patients are unaware of mold contamination.
As most of you know there are numerous symptoms that identify allergic rhinoconjunctivits including patients who have thin, watery mucus, blue cobblestoned boggy mucosa; and itchy, red eyes with watering and sneezing. These patients will also typically have seasonal or perennial symptoms and will have symptoms with exposure to the usual allergens.
These patients typically need to have allergy testing done. You should note that many patients with chronic sinusitis may need to have testing for agents such as fungi which the allergist may not typically test for. We will talk later about the importance of these fungi.
Environmental controls must also be utilized in order to reduce patient's allergies. My nurse spends a great deal of time reviewing what must be done, based on the allergens. It often takes a large amount of time spent coaxing patients to do the things that must be done, from obtaining mattress and pillow covers to getting rid of carpeting.
A further discussion of environmental changes may be found later in this website in the allergy section
Antihistamines have a controversial role in patients with sinusitis. Although they are helpful in patients with allergic rhinitis, they may cause drying of the mucus, making it difficult to get the mucus out of the sinuses. At the same time they may give relief to patient's allergic symptoms, and as a result they can be a two-edged sword. Other medications including nasal sprays, eye drops, and for patients with asthma, inhalers, are also important to use. Antileukotriene agents, either topically or orally may be helpful, and lastly immunotherapy may be important.
We need to ask the question: Do all patients with chronic sinusitis need an evaluation for immunodeficiency?
I believe that if a patient with sinusitis doesn't completely resolve with either medication or surgery within a relatively short period of time, they should have an evaluation for immunodeficiency.
It is important to recognize that the most common immunodefiency which I see, antibody deficiency, typically will manifest itself only with sinusitis, bronchitis, and/or pneumonia. It is impossible to tell a priori which patients need to have an immunodeficiency evaluation because there is no distinguishing characteristics other than frequent infection. As a result, any patient with chronic sinusitis which does not completely resolve should have an immunological evaluation.
Although it is theorectically possible for the otolaryngologist to perform the immunological tests, interpretation can be difficult, and should probably be left to the allergist/immunologist. Immunoglobulin levels, including possibly IgG subtypes, need to be done. Also isohemagglutinins need to be done. One must remember, however, that when making a decision to start treatment for an immunodeficiency, the decision must be made not the basis of the immunoglobulin levels, but on the basis of specific antibody levels.
To determine specific antibody levels, we challenge patients with the Pneumovax vaccine as well as diphtheria and tetanus and then do matched-pair antibody levels before and four weeks after the injections. This will determine if they are able to respond to a bacterial challenge and form antibodies. It is important to have facilities to store the bloods in your office for at least one month so that a matched pair can be sent to the laboratory. It is also critically important to save a specimen of the blood taken before the immunizations so that if the laboratory loses the blood you will still have some of the pre-immunization specimen. You must assume that the lab will lose the specimen, since they will about 25% of the time.
Interpretation of results can be extremely difficult. We typically use Specialty Laboratories in Santa Monica, California .
I recently saw a patient who had an immunological evaluation for chronic sinusitis approximately eight years ago. Unfortunately the evaluation which was done at that point was inadequate. Since then the patient has had numerous endoscopic surgeries which probably could have been avoided if an adequate evaluation was done.
The patient had antibody levels done for diphtheria and tetanus toxoid at the original evaluation by another physician. Despite the fact that she had received a vaccination approximately 6-8 months prior to the original evaluation, the tetanus antibody levels were less that therapeutic. In addition the diphtheria titer was just above therapeutic level. The combination of these tests suggest an inadequate response. In addition, although the IgG subclass levels were listed as normal, the IgG-3 level was barely above adequate levels.
The pneumococcal titers which were done at the original evaluation showed a slight amount of activity, but in a subtherapeutic range. But they were done without having had a Pneumovax vaccination so that they are difficult to interpret.
At this point, the patient should have been started on IVIG, but the evaluating physician was apparently unaware of the correct protocol, so that as a result, the patient got inadequate treatmnt. She also had to have multiple sinus surgeries which could have been avoided if she had received IVIG.
The Pneumovax vaccination contains antigens for 23 different subtypes of Streptococcus pneumoniae. Of those 23 serotypes, it is now possible to measure antibody levels to all of them. In this particular patient, however, only 4 were measured. As a result, interpretation was even more difficult.
As it turned out, after immunization by me to the Pneumovax, the patient developed a good antibody response to the vaccine. Since the patient did not respond to the Tetanus and Diphtheria vaccination, however, she is still a candidate for intravenous immunoglobulin. We will not attempt to discuss intravenous immunoglobulin in this session today as it is a topic in and of itself. Suffice it to say at this point that it is very expensive and insurance approval is often difficult to obtain
In summary, relating to the immunoglobulin levels, it is important to check that the normal values which your laboratory is using are correct, that at least 12 and preferably all 23 antibodies are tested by the lab, and that the values are high enough to be protective. If it has been over five years since administration of the pneumovax or ten years for diphtheria and tetanus, the immunizations should be redone. We like to have values for the antibody titers over 1.3 micrograms/ml. Values for the post exposure antibodies should be three times prior to those done prior to the injection. In addition, adult patients should respond to at least 17/23 or 8/12 of the serotypes.
So in conclusion, I think that that all patients who have chronic sinusitis which does not resolve within a reasonable period of time should be evaluated for an immunodeficiency.
I would next like to talk about use of IV antibiotics in patients with chronic sinusitis. It has been found that guided endoscopic cultures from the middle meatus and/or sinuses as acdurate as sinus puncture and are helpful in treatment of chronic sinusitis. In addition, Xomed makes a sinus secretion collector which can be very helpful in obtaining good cultures. One can base antibiotic treatment on the culture results as long as bacterial sensitivities are done. It is important to recognize that laboratories may describe "normal flora" on culture when in fact it may not be normal. So make sure that you insist that the laboratory determines tha actual bacteria. Some workers now believe that "normal flora" like Staph epidermidis may be pathogenic or can cause antigenic stimulation.
You may wish to consider using IV antibiotics in patient with osteitis, cystic fibrosis, immunodeficiency, Wegeners granulomatosis, in patients who would prefer not to have surgery, who have resistant organisms, or who are not surgical candidates. You may also wish to consider IV antibiotics prior to surgery in patients who you think may be difficult to treat.
It is important to recognize that, in our experience, at least 80% of patients will commonly have side effects as a result of IV antibiotics including, in order of decreasing frequency: mild hepatitis, rash, anemia, leukopenia, urticaria, hyperglycemia, chest pain, palpitations, diarrhea, cholecystitis, hemolysis, pruritus, and thrombocytopenia. Obviously, most of these problems are ones that the patient will complain about, or can be easily picked up by a weekly blood test. As a result, we believe that weekly office visits are required as well as complete exams and blood work. Most otolaryngologists are not comfortable doing all these tests including a complete physical exam. You also must recognize that patients must be taken care of by your associates when you are in the operating room. We have had numerous circumstances where the partner of the treating otolaryngologist did not want to take care of problems with IV antibiotics when the partner was in the OR or on vacation.
Evaluation of side effects can be particularly difficult when patients are on multiple different IV drugs. One must determine which antibiotic is likely to be causing the problem, which can be difficult to do. As a result of all of the above, you may wish to consider having an allergist or infectious disease specialist render this care.
It is important that you carefully choose the allergist that you will be working with. Much of the time the allergist may not be used to dealing with the problems that we have discussed previously. Allergy testing with fungi, immunodeficiency testing and IV antibiotics may be foreign to them.
One of my professors in medical school said that you have educate the surgeon. He said to make sure that when patients are taken to the operating room, the surgeon does all of the things that you need him to do. I will tell you the same thing. You must educate the allergist, as he/she may very well just want to give allergy shots.
It is important to remember that we do not cure chronic sinusitis. When I first see a patient, I will introduce this concept early in course of treatment. I would suggest that you may do a similar thing in patients that you treat and say that they may need an allergy/immunologic evaluation and management by 2 or more medical specialties.
I have found that patients are often resistant to seeing another doctor, particularly about chronic sinusitis. In the patients that I see, they may initially refuse to even consider having surgery. In the patients that you see who have surgery, they may persist in believing that the surgery will cure them. As a result, if they are told several times about the chronicity of the disease, they may eventually be convinced that this is a disease that should probably be taken care of by multiple doctors.
You may wish to suggest to patients that they may need to see an allergist unless you are positive you will cure the patient. As we know, patients with chronic sinusitis are usually not cured of their disease.
I like to ask the patients the following question after they have been treated for several weeks or months. "If you had the level of symptoms that you have right now before I ever saw you would you still need to see a doctor."
If the answer to that question is yes, indicating that they still have a significant level of symptoms,then you need to have them see somebody else to evaluate whether there can be anything more done - usually an allergist. We often find that having a fresh look by another physician will often elucidate problems that were not previously discovered.
I would like to next talk about the concept of eosinophilic fungal rhinosinusitis: Is this fact or fiction?
At the recent Nose 2000 course, the findings that were published in the September 1999 issue of Mayo Clinic Proceedings by Ponikau and Kern were confirmed by Stammberger. They found that 95% of both normals as well as controls had fungi which could be cultured from the sinus. Over 90% of patients with chronic sinusitis had activated eosinophiles which had released their eosinophilic granules, and these granules were released in a different way than stimulation by other agents.
What appears to happen is that major basic protein is released by eosinophiles as they attack the fungi in the sinuses. As a result of this, the fungi are injured or killed, but it is actually a pyrrhic victory because the major basic protein injures the mucosa. As a result, a bacterial infection ensues. In the data from the Mayo Clinic there were a total of approximately 2.7 fungi in each patient with chronic sinusitis. The results in normal patients were similar. Remember, however, that most labs are poor at performing fungal cultures. Allergists will note that the first four fungi are commonly tested as allergens. The fungi that were found included, in order of significance:
| Alternaria | 44% | Ustilago | 6% |
| Cladosporium | 39% | Epicoccus | 6% |
| Penicillium | 43% | Geotrichum | 5% |
| Aspergillus | 30% | Trichoderma | 4% |
| Candida | 21% | Aureobasidium | 4% |
| Fusarium | 16% | Others (28) | <3% |
| Pithomyces | 7% |
Although many of the more common fungi may be tested by allergists, you may have to ask that the allergist test for a larger number of fungi than usual. Unfortunately, however, many of the fungi are not available for testing, especially Bipolaris, which is a very common cause of allergic fungal sinusitis in the Southwest. (Not surprisingly this was not found in a significant number of the cultures from the Mayo Clinic).
Also presented at the Nose 2000 meeting were the Mayo clinic's report on treatment. In the patients who were treated with topical Amphotericin B, there was a 75 % effecacy. The problem with Amphotericin is that is extremely inconvenient. It must be kept refrigerated, away from the light, and approximately a ¼ of patients find that since it must be diluted in sterile water, it burns. Itraconazole can also be used for irrigation, but it cannot be mixed by your local pharmacy without probable inactivation of the drug, but rather by Anazao or Sinucare, two specialty pharmacies. Treatment needs to be continued indefinitely. We must continue to kill the fungi because we don't fully understand the basic pathological process which causes the problem in the first place. The place of oral antifungal agents is not clear, although a paper by Silver et. al. presented at the 2000 American College of Allergy, Asthma and Immunology meeting suggested that oral Diflucan may have a place in treatment of chronic sinusitis. A clinical trial on the use of Amphotericin B is currently underway by Accentia Pharmeuticals
We also need to ask the question of what allergic management should take place. Mabry has found that in patients with allergic fungal sinusitis, allergy immunotherapy can be extremely helpful. Lavigne found that patients with allergic rhinitis and chronic sinusitis who had endoscopic sinus surgery did not have as good an outcome as non-allergic patients and as a result needed allergic management. Asero found that patients with nasal polyposis had a 44% incidence of allergy to Candida vs. 1% of atopic controls. They were also more sensitive to dust mites. ( Note control patients with chronic sinusitis were also less likely to be allergic but only limited information was supplied in that group, and only a limited number of molds were tested.)
Although only 43% of the group from Mayo were allergic, they only tested a total of 18 allergens. Santilli found that 70% of patients with allergic rhinitis and sinusitis were allergic to at least 1 of 30 molds. Our experience is similar, and we are now testing for 30+ molds. Because there are hundreds or thousand of allergenic molds, we suspect that we are still missing many allergies to molds, because only a limited number can be tested.
So we still have numerous questions which have been partially answered but still need to be worked on including: What is the role of antihistamines? When do I start antifungal therapy and for how long? Which patients need IV antibiotics? Do all patients with chronic sinusitis need immunotherapy?
In conclusion, I think that most patients with chronic sinusitis should be seen as a team effort by the otolaryagologist, allergist/immunologist, and possibly infectious disease specialist.
Remember to choose someone who will compliment you so that you have someone to ask to help take care of your headaches.
The take home information which you should have is:
If patients do not get better you may wish to do what my ancestors did, which is to give them a bottle of Dr. Tichenor's mouthwash
(For those of you who do not know, Dr. G. H. Tichenor, a very distant relative, developed Dr. Tichenor's mouthwash in the 19th century. It is still the number one selling mouthwash in New Orleans and is marketed throughout the southeast and selected parts of the United States).
At what point in time should I introduce the idea of seeing an allergist?
I think that it depends on the patient. I will typically introduce to patients the idea that they may need to see a surgeon very early in the course of treatment so that I don't have to surprise them later with new information. If a patient still has symptoms 6 weeks after surgery, that patient should have an allergy immunology evaluation.
The Mayo Clinic Study ( published in September, 1999 in The Proceedings of the Mayo clinic) showed that everyone has fungus in their sinuses. I looked at that study and couldn't see any significance to a fungus in the sinuses.
The Mayo Clinic found that 95% of patients with chronic sinusitis had a fungus grow out of their sinuses versus 100% of normals. The difference was that the patients with sinusitis had activated eosinophiles in their sinuses, which had released Major Basic Protein, and damaged the mucosa which caused a superimposed bacterial infection.
Should all patients with sinusitis have allergy tests and start shots?
I think that if a patient has chronic sinusitis and it doesn't completely resolve, we should do everything we can to resolve symptoms. That means surgery, allergy and immunology evaluation, environmental controls, allergy shots and possibly IV antibiotics.
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