| Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Nasal Polyps In brief, in today’s talk I am going to go over nasal polyps, present an interesting patient that I saw in Ben Taub Clinic and what sparked me to this topic. I would like to give a brief overview of the history of nasal polyps, epidemiology. Nasal polyposis has interesting clinical associations, and I would like to briefly discuss those, current research on etiologies. As many of us know, we do not know what nasal polyps are caused from. A brief overview on the current thoughts today of medical management versus surgical management for nasal polyps and where future research is going to be taking us in this field, and I would like to conclude with how my patient did. I would like to start off with the case presentation. RA is a 22-year-old Latin American female with a past medical history significant only for allergic sinusitis. She was referred to Ben Taub General Hospital Otolaryngology Clinic for evaluation of right-sided nasal congestion. Patient had been taking fluticasone and fexofenadine previously but stopped secondary to no relief of symptoms. Her review of symptoms was positive for complaints of nasal pressure, obstruction, rhinorrhea and a postnasal drip. She denied any history of fevers, chills, purulent drainage and in addition she denied any history of asthma or aspirin sensitivity. On physical exam with investigation with nasal speculum, when you looked inside her nose you would see a polyp change extending from the medial meatus back. On the oral cavity exam, you look in the posterior oropharynx you did not see any evidence of nasal polyp. Endoscopic exam you could see nasal polyps hanging off the side. The remainder of her head and neck exam was unremarkable. Based on this history and physical, we elected to perform a clinic biopsy and actually we just got rongeur biopsy forceps, biopsied the polyp and sent them to Ben Taub pathology. These are my patient’s actual pathology slides that I was able to obtain from Ben Taub. It has a lot of stromal edema, not evident in these slides but in future slides that I will show you, you will see that more prominent and increased eosinophil infiltrations. The histopathologist labeled my patient’s slides as an inflammatory “allergic” polyp. Based on these nasal biopsies we also obtained CT scan to further evaluate her sinuses. The CT scan which is here, for my patient, showed a right maxillary sinus opacification and a mass extending from the nose into the posterior nasopharynx as well as a little retention cyst on the left side. Based on these, we elected to proceed with continuing her on her medical management. We saw her in followup four weeks later. She presented back to the clinic still complaining of nasal obstruction and right-sided fullness. Based on her refractory condition to medical management, we elected to proceed with surgical removal of this nasal polyp. We started her on a seven day course of oral corticosteroids and this is our actual patient on the day of her procedure. If you notice her speculum exam, the patient had a decrease in the actual size of the nasal polyp. We went ahead and proceeded with endoscopic removal of this polyp and grossly this is the polyp and the removal. The reason I chose this patient is because I thought she had an interesting history as well as physical exam findings and we saw how medical management was tried initially. She was refractory to that and we went on to surgery. It is obvious that she had an antrochoanal polyp. Interestingly she also asked me what caused her polyp. I did not know the answer and I referred to the medical literature to see if there was much information on nasal polyps and their causes. I stumbled onto the topic of nasal polyposis and there is a plethora of information in the literature with regards to research, on its etiologies and medical management. Based on this, I elected to proceed with this grand rounds topic. In brief, the history of nasal polyps goes very far back. It is first described in India as far as 1000 BC were they used these little curettes to remove these polyps from the nose. As stated by Dr. Spiros Manolidis in his latest grand rounds on the history of otolaryngology, Hypocrites in 400 BC began to describe nasal polyps and his medical management for these nasal polyps. He is accredited with developing sponge technique in which he actually gets a sponge, ties a string, passes it through the nose into the oral cavity and pulls them. He actually forcefully yanks this sponge through the nose and avulses the polyps. Hypocrites was very innovative. In addition, he developed a crude snare technique in which he used to loop around these polyps and just yank them out. In addition, he described using hot irons for cauterization of these polyps. Later in the middle ages, Philipius refined the snare technique in which he used a metal bar and harpsichord wire. This allowed for a more precise excision. In addition in the middle ages we begin seeing use of scalpels and curettes for nasal surgery. Fast forward almost 500 years and we have not advanced much. We are still using snare techniques, cauterization but now we have rigid endoscopes. Back then and even today, nasal polyposis is very common and often very tedious to treat because of the high recurrence rates. Looking at the epidemiology there has been very few studies reviewing epidemiology but the general literature tends to agree that the prevalence in the population is between 1 and 4%. It also increases with age and there is an interesting male predominance of nasal polyps. The study that I will go over later in my talk shows that asthmatic patients have an equal sex predominance. Several autopsy studies in the literature have noted an incidence between 26 and 42%. Nasal polyposis is associated with three specific entities that are very unique. Nasal polyposis has an association with asthma, cystic fibrosis and aspirin sensitivity. If the patient has any of these three conditions it is the likelihood that he or she will have concomitant nasal polyps. To briefly go over these, nasal polyp and asthma was studied and it shows that the literature tends to agree that 13-17% of asthma patients have nasal polyps. Regina in 2002 did an epidemiological study and multicenter study in which she found that there was an equal sex incidence in asthmatic patients as opposed to the general population. Larsen in 1997 did a med analysis of the literature and his review of nasal polyps with asthma was interesting to note that he found the majority of patients, after surgical removal of their polyps, had better control of their asthma or their asthma did not progress as much. The next clinical entity is nasal polyps and cystic fibrosis. Hatfield in 2000 noted that cystic fibrosis incidence were anywhere between 10-32%. He studied 211 adults with cystic fibrosis and in his particular study he quoted the incidence as 37%. Bernstein in 1995 did excellent basic science research on the cystic fibrosis receptor. It is basically a chloride transmembrane regulator. When this receptor is mutated, as in cystic fibrosis, you get electrolyte abnormalities as well as abnormalities in water conduction. He postulated that this abnormality led to the mucosal edema, water retention, and thus formation of nasal polyps. Irving out of University of San Francisco in 1997 took a general population of 55 patients with nasal polyps and he was interested to see if maybe nasal polyps was a mild form of cystic fibrosis. In these 55 patients, he looked for the most common mutations of the CFTR receptor. On conclusion of his study, only 5 of the 55 patients came out positive so based on this study it is obvious that we would not be screening just the general population of nasal polyps for cystic fibrosis. Moving on, in 1968 Max Sampter was the first to describe a clinical triad of asthma, nasal polyps, and aspirin allergy in a landmark study that he published in the Annals of Internal Medicine. Further research has shown that aspirin intolerance and asthma, these patients have a 36 to 95% prevalence of nasal polyps. With this clinical triad, the nasal polyps are unique in that they are often more widespread and diffuse and often more refractory to medical management and more difficult to treat. Moving on, the patient asked me particularly what caused nasal polyps. So a review of my literature, there has been several theories and I would like to go over a few of them now. Genetic – could nasal polyposis be a genetic mutation leading to this. The state of knowledge in this area is very limited. We are still developing our genetic techniques. Maloney and Oliver in 1980 interestingly enough found HLA A1, B, A association with aspirin intolerant patients. Further studies 20 years later, Luxonberger tried to find the same association but he was not successful. In his study, he noticed an HLA A74 association. What these genes do is still not known. Molnar and Gamore in 2000 found an association with HLA DR7 and they noted that when a patient had these genes they had a two to three times higher ratio of developing disease. As I stated, our state of knowledge is very limited in what these genes do and how they are affecting nasal polyposis still has yet to be unraveled. Now there are many people out there in the community that have noticed, and particularly Larsen noticed, that most of the nasal polyps enter from the medial meatus. People have tried hypothesizing why these polyps tend to stay from here. I borrowed these slides from our academy website and you see the turbinate perforated, this white here is where the academy generally states that these polyps tend to reside. You see coming back into the posterior nasopharynx and sometimes coming forward. Stramberger in 1991 postulated that maybe it is an anatomical problem causing these nasal polyps. He started to discuss the possibility that maybe mucosal-to-mucosal contact in the nose led to an inflammatory reaction which evolved into these nasal polyps. The reason why these nasal polyps continue to localize to this part of the body remains a mystery to science. To refute Stramberger’s hypothesis of mucosal-to-mucosal contact therapy, many endoscopists see mucosal-to-mucosal contacts on every patient that they evaluate so whether it is this or not we have no idea. Histology in nasal polyps is very interesting. In fact I think in future research the histologic clues are going to give us ideas as to what causes these nasal polyps. To start off with cystic fibrosis is different from common polyps in that it is infiltrated by neutrophils, plasma cells, and lymphocytes. If you recall, my patient’s histology is more infiltrated with eosinophils. It has been hypothesized that cystic fibrosis, the reason they have more neutrophilic infiltration is because of recurrent infection. Also noted that they are often resistant to this corticosteroid treatment. Future research currently is ongoing for other medical solutions other than corticosteroids for treating this neutrophil-predominant cystic fibrosis. This slide provided to me is just showing a PAF staining and cystic fibrosis is more of an acidic mucinous staining blue. Regular, every day, nasal polyposis is more of a lighter staining blue. As stated, current research is focused on trying to find different medical treatments for this unique histologic clues in cystic fibrosis. Proceeding on, this is a typical inflammatory “allergic” type polyp. If you notice, it is infiltrated with more eosinophils, macrophages, and mass cells. All these cellular clues are consistent with characteristics of that of an inflammatory disease. If you search the literature, you will see that basic science has shown many times numerous inflammatory mediators, growth factors, and adhesion molecules involved in this nasal polyp. Again, this is showing the standing textbook nasal polyp and this is my patient. This shows better the edema and eosinophilic infiltration in normal respiratory mucosa. So histopathologists continue to label these as allergic type polyps. The presence of eosinophils, mass cell degranulation, and high levels of IgE also suggest an allergic basis to these polyps, so many would say, “Well Gabe, don’t you think allergic polyps are due to allergies?” When I reviewed the literature, actually, there has been several studies that there is no correlation between allergies and nasal polyps. In the largest study Septin in 1976 reviewed 6,000 patients and showed that systemic allergies, as measured by skin prick test, was no more common in patients with nasal polyps than in the general public. This has been followed up with several studies by Kaplan in 1971, Banog in ’83, and Jamal in 1987. Each of these studies also provided evidence to support that nasal polyposis was not more common in allergic versus nonallergic patients. Interestingly when I reviewed the literature, as of recent, there has been new findings suggesting that maybe local allergies or systemic allergies may still play a role. Park in 1997 studied an in vitro release of GM CSF factor and IL-8 from polyp tissue from allergic type patients. He noted that when you present allergen to these patients’ polyps, it prolonged the eosinophilic survival by increasing these two factors. I will later talk about how medical management is targeting this IL-8. Based on Park’s study, maybe there is after all some type of systemic allergy contributing to these nasal polyps. Bacterial – can these polyps be caused by bacteria? As of recent in 1993, Kenalof showed that nasal polyps possess bacterial specific IgG in this serum versus allergic rhinitis patients that he studied did not. Bactor in 2001 again provided more evidence supporting a possible bacterial etiology by showing the presence of increased levels of specific IgE to staph excellent enterotoxins A and B. Again, pointing out the possibility of bacterial etiology in nasal polyps. A hot topic today is whether or not fungal infection are causing nasal polyps. Firestein in 1976 was the first to note a syndrome of nasal polyps in positive Aspergillus cultures. Here on my slide you can see the hyphae of these fungi. Allergic fungal sinusitis is a grand rounds talk in itself. The literature is very vast and it is a very popular topic currently. The diagnosis depends on these three main factors in brief. Polyposis sinus disease, allergic mucin from these polyps has to show fungal elements and there has to be an absence of invasive disease. The current theory is that fungal colonization in the mucosa results in an allergic inflammatory reaction and thus leads to the nasal polyps. I will later talk about some interesting modalities in treating this type of allergic fungal polyp. Now coming back to the etiology viral. Kozak was one of the first to study this in 1991. He studied several patients and he used DNA hybridization to try to detect viruses in nasal polyps. He scanned for adenovirus, herpes virus, and EBV. He was unable to identify and viruses. Again in 1994, Becker further added use of poor man’s chain reaction to try to identify these viruses. He, too, failed to isolate any viruses. Out of Japan, Tao in 1996 was the first successful to isolate Epstein-Barr virus in these nasal polyps. Of 13 patients he studied, he was able to identify 2 positives with Southern blots, 9 with PCR, 11 with in-situ hybridization, and 7 with immunohistochemistry staining which is this slide and you see the virus sliding up. Tao did not necessarily state that the EBV was the cause of these nasal polyps, more that the nasal polyps harbored EBV which has been speculated to cause nasopharyngeal tumors. Management is a very broad topic in nasal polyps. The reason being nasal polyposis is both a medical disease as well as a disease of surgery. It is treated by surgeons like ourselves, otolaryngologists, as well as allergy/immunology doctors. So there is two ways to tackle these nasal polyposis. Homberg in 1996 pulled up an interesting way of summarizing what the current thought is. Early stage of polyps versus advanced stage. On the medicine side, you could try topical cortical steroids and systemic steroids for more advanced disease. On the surgical side, you could do simple polypectomy; say in your clinic versus functional endoscopic sinus surgery versus ethmoidectomies and more radical surgeries for advance stage. Overall, from gathering the consensus of the literature, management should be geared to restoring the main functions of the nose including ventilation, sinus drainage as well as try to prevent recurrence of disease. Talk about topical corticosteroids. These have been the gold standard of treatment since the early 1970s and the literature is abundant with well thought out, well planned surgeries. There have been several double blind studies that show these topical intranasal corticosteroids both reduce the size, prevent and delay recurrences, as well as decrease the need for repeated surgery. Batty in 2001 in the Journal of Drugs published an excellent overview of all the major studies on topical corticosteroids. It has been well supported that this is an excellent primary as well as postoperative management. Systemic steroids, often called medical polypectomy. This was obvious in my patient when we gave her a seven-day course of oral corticosteroids, it dramatically shrinked the size of her polyps. Reinholt in 1989 reviewed 53 patients where he compared surgical removal versus oral steroids. He noted that both had similar outcomes in relief of symptoms, thus, he endorsed medical management using systemic and topical corticosteroids. Then Van Camp followed up the study in 1993 in which he studied 25 patients and he gave them oral steroids to see how they reacted. Seventy-two percent had a clinically relief of symptoms and he actually saw that 52% of them were relieved by CT scan. The scene that Van Camp noticed was the high rate of recurrence once oral steroids were stopped. At five months, the majority of then relapsed. He was one of many to describe the use of oral steroids as preoperative therapy to facilitate the surgical removal. Overall Reinholt in 1997 had a randomized double blind study that was excellent that showed that most patients with nasal polyps did well with medical treatment and only a select few needed surgery. Now, proceeding on to surgical management. You can go from simple polypectomies with these little snares. Larsen and House in 1997 published their 243 patients that they did simple polypectomies on. They noticed 70% relief of symptoms at 56 months out and only 80% required to or more polypectomies. The thing with nasal polyposis is that recurrence rates are high. That is why endoscopic sinus surgery is so beneficial. It allows for accurate removal of these nasal polyps while preserving landmarks. Since the recurrences are so high, so patient require multiple procedures and this endoscopic surgery is key in preserving landmarks for our future surgeons. Now radical endoscopic sinus surgery has been advocated by many, but there are a few well controlled trials to describe the outcomes of conservative versus extensive surgery. In particular, there are two entities in nasal polyposis that radical endoscopic sinus surgery is endorsed for. Diffuse polyposis in aspirin intolerant patients with polyposis. Wigandgin in 1989 showed that with aggressive surgery, he only had a recurrence rate of 18%. Jankoski in 1997 evaluated 76 of his patients that her performed radical surgery on and noted the decreased need for corticosteroids. McFadden in 1990 had an 11 year old retrospective study of his 25 patients that he operated on that had this aspirin intolerance and nasal polyposis. He noted that out of 16 patients that had simple surgeries, 9 of them recurred and needed further surgeries. Nine of his patients in which he performed a more radical and more extensive surgery, none of those patients needed re-operation. So McFadden also endorsed this radical type of surgery. Overall I think the consensus should be the surgeon should balance the risks of performing the more extensive surgery for the extent of disease. Now where is the future research heading us? In my opinion, the future research will be in alternative medical treatments to corticosteroids. There is a lot of interesting data coming out of Japan, a study on macrolides. Yamada in 2000, in the American Journal of Rhinology published his results of long-term macrolide treatment. He noted that it decreased the amount of IL-8 production in nasal polyps as well as decreased the size of the polyps. If you noticed here are some of his case presentations of macrolide treatment. Polyps here after treatment resolved and this was is a little bit better and case 18 did not improve. What was interesting about Yamato’s research is that he noted a decreased in IL-8 with macrolide treatment. IL-8 is particularly common in the neutrophilic type of polyps as in cystic fibrosis. Based on his research, it patients have a high IL-8 preop, pre-treatment the macrolide seemed to work better. Again, moving on to other alternative forms of treatment. Topical antifungals are very common and commonly being reported in the literature now. The most recent shows current cure rates around 30% with simple polyps and even higher cure rates in patients who have undergone endoscopic sinus surgery and treated with these antifungals. Other medical treatments have been suggested including intranasal aspirin, interferon, leukotriene receptor antagonists, Capzasin and furosemide. Overall, what we have to do is take these with a grain of salt. All require further evaluation before being considered viable alternatives to these corticosteroids. Again, in my opinion, the future research on etiology is going to exploit the differences between the neutrophilic polyps, say in cystic fibrosis, versus eosinophilic polyps. In summary, the keys I would like everybody to take home from my grand rounds talk today is as follows: nasal polyps are very common and their cause remains unknown. There is a clear association with three distinct entities: asthma, aspirin sensitivity, and cystic fibrosis. Histologically while they demonstrate large quantities of extracellular fluid, mass cell degranulation, inflammatory cells, and eosinophils, there is very little conclusive evidence to support allergies as the main etiology of these nasal polyps. In addition, there is good evidence, since the 1970s, to support corticosteroids as the primary choice of treatment, both as primary and postop treatment, in the majority of patients. Lastly, that surgical treatment for nasal polyposis has declined recently in the years because of the benefits of medical treatment. I believe, in the future, that surgical treatment of these nasal polyposis will continue to decline as we get better at treating these medically and particularly with all the research being done with alternative medications. In my case conclusion, at two months followup, RE is seen back in our clinic. She has no complaints of nasal obstruction, tolerating her topical corticosteroids well and endoscopic exam reveals no evidence of recurrence of her nasal polyps. Case Presentation: Physical exam revealed a single large right sided nasal polyp extending from the middle meatus to the nasal vault. The nasal mucosa showed evidence of congestion, but no purulence from the osteomeatal complex was appreciated. The left side of the nose was clear and the oral cavity showed no evidence of polyp in the oropharynx. The remainder of the patient’s head and neck physical exam was negative for abnormalities. Patient was diagnosed as having an antrochoanal polyp. Patient was restarted onfexofenadine and fluticasone and a nasal biopsy as well as CT scan was obtained. In follow up, pathologic findings were consistent with an inflammatory polyp. CT scan revealed a right maxillary sinus opacification with a soft tissue mass extending into the posterior nasopharynx and a small left maxillary sinus retention cyst. Despite medical management, the patient continued to complain of nasal congestion and obstruction. Patient was started on a seven day course of oral corticosteroid treatments prior to undergoing endoscopic sinus surgery for removal of a right antrochoanal polyp. Bibliography: Bachert C, Gevaert P, Holtappels G, Johansson S, Cauvwenberge P. Total and specific IgE in nasal polyps is related to local eosinophilic inflammation. Allergy Clin Immunol 2001;107:607-614. Badia L, Lund V. 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Vento S, Ertama L, Hytonen M, Wolff J, Malmberg C. Nasal polyposis: clinical course during 20 years. Ann Allergy Asthma Immunol 2000;85:209-214. Weshta M. Rimek D. Formanek M. Polzehl D. Riechelmann H. Local production of aspergillus fumigatus specific immunoglobulin E in nasal polyps. Laryngoscope 2003;113:1798-1802. Wigand ME, Hosemann W. Microsurgical treatment of recurrent nasal polyposis. Rhinol 1989;(Suppl 8):25-29. Yamada, Takechiyo, Fujieda Shigeharu, Mori Shigehito. Macorlide treatment decreased the size of the nasal polyps and IL-8 levels in nasal lavage. Am J Rhinol 2000;14:143-148. BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2005
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