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Nasal polyposis: Role of subclinical delayed food hypersensitivity
Nasal polyposis: Role of subclinical delayed food hypersensitivity YOKE-TEEN PANG, FRCSEd(ORL), FRCS(Glasg), FAMS, ORHAN ESKICI, MD, and JANET A. WILSON, MSc, FRCS,
Singapore, Singapore, and Newcastle-upon-Tyne, United Kingdom
Nasal polyposis is a common problem in otolaryngology. The cause remains unclear, and treatment with medication and surgery is often unsatisfactory. We present our controlled study, which suggests a strong association between food allergy and nasal polyposis. The study was conducted in 2 parts. A postal survey of 900 patients with nasal polyps showed 53 respondents (5.9%) had a known food allergy. In the prospective study, 80 nasal polyp patients and 36 control subjects completed intradermal tests for food allergy. Sixty-five nasal polyp patients (81%) and 4 control subjects (11%) had positive intradermal food test results. This is highly significant. We believe that food allergy may play a significant role in the pathogenesis of nasal polyposis and should be further studied. (Otolaryngol Head Neck Surg 2000;122:298-301.)
Nasal polyposis has been recognized for more than 3000 years,1 and it is the most common mass lesion in the nose.2 During the past decade there has been a resurgence of interest in nasal polyps, primarily because of advances in modalities of treatment. These include the use of local and systemic steroids as well as endoscopic and microscopic ethmoidectomy. Despite these advances, the cause of nasal polyps remains unresolved. Suggested causes include chronic infection, allergy, immunologic factors such as aspirin idiosyncrasy,3 and cystic fibrosis.4 None of these causes has been proved with certainty. Mygind5 and more recently Slavin6 found no increase in the prevalence of atopy or allergic disorders in patients with nasal polyps compared with the general population. This is supported From the Department of Otolaryngology, National University Hospital, Singapore (Dr Pang); the Department of Otolaryngology–Head and Neck Surgery, Freeman Hospital, Newcastleupon-Tyne (Drs Pang and Eskici); and Otolaryngology–Head and Neck Surgery, University of Newcastle (Dr Wilson). Reprint requests: Yoke-Teen Pang, FRCSEd(ORL), Department of Otolaryngology, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore. Copyright © 2000 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2000/$12.00 + 0 23/77/98177 298
by the work of Caplin et al,3 who found only 0.5% of a group of 3000 atopic patients had nasal polyps. DrakeLee et al7 found no increased incidence of allergic disorders in 200 consecutive patients admitted for polypectomies. King8 and Yeoh (personal communication, 1990) observed a more frequent relationship with polyps and delayed food allergies than polyps and typical IgE-mediated inhalant allergies. In Yeoh’s unpublished data, he observed that more than 90% of nasal polyp patients have food allergy. Treatment of delayed food allergy in nasal polyp patients has led to decreased symptoms and has slowed the progress of nasal polyps. The diseasefree interval is increased after polypectomy. This study aims systematically to compare the prevalence of delayed food hypersensitivity (non-IgE mediated) in nasal polyposis patients with the prevalence in healthy volunteers without nasal polyps. In addition, a postal questionnaire was also used to determine the prevalence of food allergy and other associated conditions in patients with nasal polyposis. METHODS AND MATERIAL The study was conducted in 2 parts. First, postal questionnaires were sent to 1000 patients who had undergone 1200 nasal polypectomies between 1991 and 1995 in the Department of Otolaryngology–Head and Neck Surgery at Freeman Hospital, Newcastle-upon-Tyne, UK. Nine hundred replies were received and analyzed. The questionnaire provided a detailed clinical profile, which included demographic data as well as information on associated conditions and habits of the patient. Second, intradermal tests were carried out to determine delayed food hypersensitivity as validated by King et al.9,10 The intradermal tests were conducted according to the method described by the American Academy of Otolaryngic Allergy. In this study we conducted only the provocation part of the test (ie, the first dilution, which is of the highest concentration). Intradermal food allergy tests were conducted on an unselected group of 80 patients with evidence of ongoing nasal polyposis. These included patients awaiting nasal polypectomies and new referrals. Thirty-six control subjects were also studied. The control subjects had no history of any allergy and were nonasthmatic. After confirmation of the nasal polyposis, the patients were recruited for the study. Each patient completed a 14-day food diary to indicate the range of foods normally consumed.
Otolaryngology– Head and Neck Surgery Volume 122 Number 2
Table 1. Food allergens used in the intradermal skin tests Apple Beef Corn Haddock Oat Pea Pork Soybean Wheat Banana Chicken Egg Milk Orange Peanut Potato Tomato
Foods that were not eaten at least twice a week were not selected from the panel of 16 allergens available to us (Table 1). Any food considered to be potentially anaphylactic was also excluded. The test allergens (Biodiagnostics) were supplied in 1:10 wt/vol strength with 50% glycerine as a solvent. The solution was diluted 5 times with saline solution used for the intradermal test described below. The negative control used is 50% glycerine, which is present in that strength as a solvent in the test solution. A 0.05 mL dose of each test allergen selected was injected intradermally on the flexor surface of the forearm. This produces an approximate wheal size of 7 mm diameter. The exact size of the wheal was measured and documented. The process was repeated for each selected food allergen as well as for the negative control (the test sites should be at least 4 cm apart to avoid overlapping of wheals and thereby interfering with the results recorded). The size of the wheal was read at 20 minutes. A growth of 2 mm in diameter in excess of the negative control was considered a positive test result. Throughout the procedure the patient was not told the nature of the test solution at each site. Hydrocortisone cream (1%) was applied to the test area to stop further reaction after the final reading. Adrenaline 1/1000 was always available for resuscitation purposes, and a member of the medical team was always present to attend to any problems that might arise. The study had the approval of the local ethical committee, and informed consent was obtained from each patient. RESULTS Postal Survey
In the 900 responses analyzed, there were 593 men and 307 women, approximately a 2:1 ratio. The mean
PANG et al
299
Table 2. Prevalence of associated conditions in 900 nasal polyp patients Condition
No. of patients (%)
Asthma Allergic rhinitis Bronchitis Aspirin intolerance Asthma and aspirin intolerance Known food allergy Irritable bowel syndrome
321 (35.7) 287 (31) 135 (15) 101 (11.2) 64 (7.1) 53 (5.9) 87 (9.6)
Table 3. Sex and age distribution of the nasal polyp patients and control subjects
Men Women Age (y) Mean ± SD Range
Patients
Controls
48 32
21 15
49 ± 11 26-70
44 ± 14 19-65
age of the respondents was 56 ± 14 years (1 SD), with a range from 18 to 91 years. The mean age of first nasal polyp presentation was 45 ± 15 years (1 SD), range 11 to 89 years. The number of polypectomies in the respondents ranged from 1 to 25 operations, with a mean of 2.4 (median 1). Associated conditions in this survey are listed in Table 2. The subgroup with asthma and aspirin intolerance had an approximately equal sex distribution, 30 men to 34 women. The mean age of this subgroup of patients was similar to that of the total sample, 51 ± 13 years (1 SD), range 25 to 74 years. In this group the mean number of operations was higher at 4 per patient (median 3.5, range 1-20). This was statistically significant with a t test (P = 0.033). Among the patients, 469 of 900 (52.1%)—354 men and 115 women—had histories of smoking. The duration of smoking ranged from 1 to 72 years, with a mean of 25 ± 13.5 years (1 SD). The average number of polypectomies in this group was 2.17 ± 2.2. This was not statistically different from the number in the nonsmoking population. There was no correlation between the number of polypectomies and alcohol intake. The mean intake per week was 9 units, with a range of 0 to 112 units (median 5 units, mode 0 units) (1 unit of alcohol = 1/2 pint of beer or 1 glass of wine). Forty-three percent of the surveyed population had relatives with a known history of nasal polyposis.
300
Otolaryngology– Head and Neck Surgery February 2000
PANG et al
Food Allergy Skin Tests
In the prospective study 80 nasal polyp patients and 36 control subjects completed the food allergy tests. The sex and age distribution is shown in Table 3. Sixtyfive nasal polyp patients (81%) and 4 healthy volunteers (11%) had positive food reactions (P = 0.00, χ2). The mean number of skin tests in both groups was 11 (median 11). The number of skin tests with positive results in nasal polyp patients ranged from 0 to 13 (median 2), whereas in the control subjects the range was 0 to 5 (median 0). The difference in the number of food reactions was also statistically significant (P = 0.000, Mann-Whitney test). The most common reactions were to wheat, potato, and tomato; other reactions were to corn, chicken, egg, milk, pork, pea, and orange. Of these commonly reacting foods only orange, tomato, and to a lesser degree, pea contain salicylate. DISCUSSION
A review of the literature suggests that this is one of the largest retrospective surveys of nasal polyp patients reported to date (1966-1996). The age and sex distribution in our survey is similar to that of previous studies. Nasal polyps predominantly affect middle age adults (>40 years old), with a male predominance of 2:1 to 3:1.7,11 The association with asthma has been widely recognized and is reported to range from 20% to 70%,7,12,13 which is similar to the findings in this study (35.7%). Aspirin intolerance has been observed in 13.8% to 14.2% of nasal polyp patients,14,15 which is similar to our survey incidence of 11.2%. Because this was a postal survey, we were unable to determine the extent and nature of the reported aspirin intolerance. Samter and Beers16 reported the incidence of the triad of nasal polyposis, asthma, and aspirin intolerance as 8%, a figure relatively close to our own findings (7.1%). Two thirds of those with aspirin intolerance and nasal polyps had asthma. In this subgroup, disease was more aggressive, as reflected by the significantly higher frequency of polypectomies. Smoking and alcohol consumption do not appear to affect the frequency of polypectomies when patients in these groups were compared with patients in the nonsmoking and nondrinking groups, respectively. Maloney and Oliver17 found an association of HLA Al and HLA B8 in patients with asthma and nasal polyps, which they suggested might be due to an underlying abnormality in the immune response. The high frequency of first- and second-degree relatives with histories of nasal polyps would support this observation. This study showed a significant association of delayed food hypersensitivity and nasal polyposis.
There was a striking excess of positive skin test results in 80% of the patients. Food hypersensitivity can be broadly divided into immediate and delayed reactions. Immediate reaction is IgE mediated, manifesting as an anaphylactic-type reaction. It is estimated to constitute 5% of food allergy reactions.18 In this study we were interested in non-IgE-mediated delayed food hypersensitivity. These reactions are labeled as type II, III, or IV hypersensitivity and comprise 95% of all immune food reactions.18 Foods causing delayed hypersensitivity are commonly eaten and may be part of the daily diet. They can be eaten whole or as “hidden foods” in prepared foodstuffs. The number of positive reactions per patient varied from 1 to 15. It is conceivable that the varying reactivity may relate to the fluctuations in clinical behavior in nasal polyposis. However, the numbers in this study are too small to test this hypothesis. From the questionnaire, only 6% of patients were aware of food allergy. This is certainly an underestimation compared with the percentage prevalence of positive skin test results. Similarly, the 4 control subjects with positive skin reactions in this study were not aware of any food allergy. Comparison of the 2 groups shows that there is a significant association of delayed food hypersensitivity with the nasal polyp population. Many recent studies have described a host of mediators in nasal polyp tissues.2 Delayed food hypersensitivity being immunologically mediated may be the trigger for the migration and release of mediators in the polyp tissues. Whether delayed food hypersensitivity is a major cause of nasal polyposis needs to be proved. It may be that nasal polyps are the uniform local manifestation of a systemic disorder that has yet to be fully defined. Work is now in progress to determine whether the exclusion of relevant food allergens from the diet alters the clinical course of nasal polyposis. Salicylate sensitivity has long been associated with nasal polyposis. In the panel of 16 foods that we have selected, only apple, tomato, and pea have been found to contain salicylate. In this study, only 1 patient reacted positively to pea and/or tomato alone. These results appear to suggest that the presence of salicylates in food may not be a significant factor in the pathogenesis of nasal polyposis, as previously thought. A controlled study comparing salicylate hyperactivity in nasal polyp patients and healthy control subjects would, however, be needed to settle this issue conclusively. CONCLUSION
A controlled study of delayed food hypersensitivity and nasal polyps is reported. The results indicate a highly significant difference in the prevalence of posi-
Otolaryngology– Head and Neck Surgery Volume 122 Number 2
tive intradermal food test results in nasal polyp patients. Because only a small minority is clinically apparent, intradermal tests are necessary to substantiate the diagnosis. Delayed food hypersensitivity may have been underestimated, whereas the importance of salicylate may be overestimated. We thank Sister Pauline Davidson for her assistance in the study. REFERENCES 1. Vancil ME. A historical survey of treatment of nasal polyposis. Laryngoscope 1969;79:435-45. 2. Jordanna M, Dolovich J, Ohno I, et al. Nasal polyposis: a model for chronic inflammation. In: Bruce W, Holgate W, editors. Asthma & rhinitis. Boston: Blackwell Scientific; 1995. p. 15664. 3. Caplin I, Hayes TJ, Spahn J. Are nasal polyps an allergic phenomenon? Ann Allergy 1971;29:631-4. 4. Schraum VL Jr, Bifrom MZ. Nasal polyps in children. Laryngoscope 1980;90:1488-95. 5. Mygind N. Nasal allergy. Oxford: Blackwell; 1978. p. 233-8. 6. Slavin RG. Allergy is not a significant cause of nasal polyps [letter]. Arch Otolaryngol Head Neck Surg 1992;118:343.
PANG et al
301
7. Drake-Lee AB, Lowe D, Swanston A, et al. Clinical profile and recurrence of nasal polyps. J Laryngol Otol 1984;98:783-93. 8. King WP. Food hypersensitivity in otolaryngology. Otolaryngol Clin North Am 1992;25:163-79. 9. King WP, Rubin WA, Fadal RG, et al. Provocation-neutralization: a two-part study. Part 1. The intracutaneous provocative food test: a multicenter comparison study. Otolaryngol Head Neck Surg 1988;99:263-71. 10. King WP, Moles JM. The intracutaneous progressive dilution multi-food test. Otolaryngol Head Neck Surg 1991;104:235-8. 11. Salvin RG. Nasal polyps and sinusitis. Allergy: principles and practice. 3rd ed. St Louis: Mosby; 1988. p. 1291-303. 12. Maloney JR. Nasal polyps, nasal polypectomy, asthma and aspirin sensitivity. J Laryngol Otol 1977;91:837-46. 13. Settipane GA, Chaffee FH, Klein DE. Aspirin intolerance: a prospective study in an atopic and normal population. J Allergy Clin Immunol 1974;53:200-4. 14. Schenk N. Nasal polypectomy in aspirin sensitive asthmatic. Trans Am Acad Ophthalmol Otolaryngol 1974;78:109-19. 15. Settipane GA, Charles FH. Nasal polyps and rhinitis: A review of 6037 patients. J Allergy Clin Immunol 1971;59:17-21. 16. Samter M, Beers RF. Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med 1968;68:975-83. 17. Maloney JR, Oliver RTD. HLA antigen, nasal polyps and asthma. Clin Otolaryngol 1980;5:183-9. 18. Breneman JC. Basics of food allergy. Springfield (IL): Charles C Thomas; 1978. p. 8-15, 155-6.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of Otolaryngology–Head and Neck Surgery are available to subscribers (only) for the 2000 issues from the Publisher, at an individual cost of $118.00 ($146.59 for Canadian, $137.00 for international subscribers) for Vols. 122 (January-June) and 123 (JulyDecember). Shipping charges are included. Each bound volume contains subject and author indexes, and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable blue buckram with the Journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Inc., Subscription Services, 11830 Westline Industrial Drive, St. Louis, MO 63146-3318, USA; phone, 800-453-4351 or 314-453-4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular Journal subscription.
Singapore, Singapore, and Newcastle-upon-Tyne, United Kingdom
Nasal polyposis is a common problem in otolaryngology. The cause remains unclear, and treatment with medication and surgery is often unsatisfactory. We present our controlled study, which suggests a strong association between food allergy and nasal polyposis. The study was conducted in 2 parts. A postal survey of 900 patients with nasal polyps showed 53 respondents (5.9%) had a known food allergy. In the prospective study, 80 nasal polyp patients and 36 control subjects completed intradermal tests for food allergy. Sixty-five nasal polyp patients (81%) and 4 control subjects (11%) had positive intradermal food test results. This is highly significant. We believe that food allergy may play a significant role in the pathogenesis of nasal polyposis and should be further studied. (Otolaryngol Head Neck Surg 2000;122:298-301.)
Nasal polyposis has been recognized for more than 3000 years,1 and it is the most common mass lesion in the nose.2 During the past decade there has been a resurgence of interest in nasal polyps, primarily because of advances in modalities of treatment. These include the use of local and systemic steroids as well as endoscopic and microscopic ethmoidectomy. Despite these advances, the cause of nasal polyps remains unresolved. Suggested causes include chronic infection, allergy, immunologic factors such as aspirin idiosyncrasy,3 and cystic fibrosis.4 None of these causes has been proved with certainty. Mygind5 and more recently Slavin6 found no increase in the prevalence of atopy or allergic disorders in patients with nasal polyps compared with the general population. This is supported From the Department of Otolaryngology, National University Hospital, Singapore (Dr Pang); the Department of Otolaryngology–Head and Neck Surgery, Freeman Hospital, Newcastleupon-Tyne (Drs Pang and Eskici); and Otolaryngology–Head and Neck Surgery, University of Newcastle (Dr Wilson). Reprint requests: Yoke-Teen Pang, FRCSEd(ORL), Department of Otolaryngology, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore. Copyright © 2000 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2000/$12.00 + 0 23/77/98177 298
by the work of Caplin et al,3 who found only 0.5% of a group of 3000 atopic patients had nasal polyps. DrakeLee et al7 found no increased incidence of allergic disorders in 200 consecutive patients admitted for polypectomies. King8 and Yeoh (personal communication, 1990) observed a more frequent relationship with polyps and delayed food allergies than polyps and typical IgE-mediated inhalant allergies. In Yeoh’s unpublished data, he observed that more than 90% of nasal polyp patients have food allergy. Treatment of delayed food allergy in nasal polyp patients has led to decreased symptoms and has slowed the progress of nasal polyps. The diseasefree interval is increased after polypectomy. This study aims systematically to compare the prevalence of delayed food hypersensitivity (non-IgE mediated) in nasal polyposis patients with the prevalence in healthy volunteers without nasal polyps. In addition, a postal questionnaire was also used to determine the prevalence of food allergy and other associated conditions in patients with nasal polyposis. METHODS AND MATERIAL The study was conducted in 2 parts. First, postal questionnaires were sent to 1000 patients who had undergone 1200 nasal polypectomies between 1991 and 1995 in the Department of Otolaryngology–Head and Neck Surgery at Freeman Hospital, Newcastle-upon-Tyne, UK. Nine hundred replies were received and analyzed. The questionnaire provided a detailed clinical profile, which included demographic data as well as information on associated conditions and habits of the patient. Second, intradermal tests were carried out to determine delayed food hypersensitivity as validated by King et al.9,10 The intradermal tests were conducted according to the method described by the American Academy of Otolaryngic Allergy. In this study we conducted only the provocation part of the test (ie, the first dilution, which is of the highest concentration). Intradermal food allergy tests were conducted on an unselected group of 80 patients with evidence of ongoing nasal polyposis. These included patients awaiting nasal polypectomies and new referrals. Thirty-six control subjects were also studied. The control subjects had no history of any allergy and were nonasthmatic. After confirmation of the nasal polyposis, the patients were recruited for the study. Each patient completed a 14-day food diary to indicate the range of foods normally consumed.
Otolaryngology– Head and Neck Surgery Volume 122 Number 2
Table 1. Food allergens used in the intradermal skin tests Apple Beef Corn Haddock Oat Pea Pork Soybean Wheat Banana Chicken Egg Milk Orange Peanut Potato Tomato
Foods that were not eaten at least twice a week were not selected from the panel of 16 allergens available to us (Table 1). Any food considered to be potentially anaphylactic was also excluded. The test allergens (Biodiagnostics) were supplied in 1:10 wt/vol strength with 50% glycerine as a solvent. The solution was diluted 5 times with saline solution used for the intradermal test described below. The negative control used is 50% glycerine, which is present in that strength as a solvent in the test solution. A 0.05 mL dose of each test allergen selected was injected intradermally on the flexor surface of the forearm. This produces an approximate wheal size of 7 mm diameter. The exact size of the wheal was measured and documented. The process was repeated for each selected food allergen as well as for the negative control (the test sites should be at least 4 cm apart to avoid overlapping of wheals and thereby interfering with the results recorded). The size of the wheal was read at 20 minutes. A growth of 2 mm in diameter in excess of the negative control was considered a positive test result. Throughout the procedure the patient was not told the nature of the test solution at each site. Hydrocortisone cream (1%) was applied to the test area to stop further reaction after the final reading. Adrenaline 1/1000 was always available for resuscitation purposes, and a member of the medical team was always present to attend to any problems that might arise. The study had the approval of the local ethical committee, and informed consent was obtained from each patient. RESULTS Postal Survey
In the 900 responses analyzed, there were 593 men and 307 women, approximately a 2:1 ratio. The mean
PANG et al
299
Table 2. Prevalence of associated conditions in 900 nasal polyp patients Condition
No. of patients (%)
Asthma Allergic rhinitis Bronchitis Aspirin intolerance Asthma and aspirin intolerance Known food allergy Irritable bowel syndrome
321 (35.7) 287 (31) 135 (15) 101 (11.2) 64 (7.1) 53 (5.9) 87 (9.6)
Table 3. Sex and age distribution of the nasal polyp patients and control subjects
Men Women Age (y) Mean ± SD Range
Patients
Controls
48 32
21 15
49 ± 11 26-70
44 ± 14 19-65
age of the respondents was 56 ± 14 years (1 SD), with a range from 18 to 91 years. The mean age of first nasal polyp presentation was 45 ± 15 years (1 SD), range 11 to 89 years. The number of polypectomies in the respondents ranged from 1 to 25 operations, with a mean of 2.4 (median 1). Associated conditions in this survey are listed in Table 2. The subgroup with asthma and aspirin intolerance had an approximately equal sex distribution, 30 men to 34 women. The mean age of this subgroup of patients was similar to that of the total sample, 51 ± 13 years (1 SD), range 25 to 74 years. In this group the mean number of operations was higher at 4 per patient (median 3.5, range 1-20). This was statistically significant with a t test (P = 0.033). Among the patients, 469 of 900 (52.1%)—354 men and 115 women—had histories of smoking. The duration of smoking ranged from 1 to 72 years, with a mean of 25 ± 13.5 years (1 SD). The average number of polypectomies in this group was 2.17 ± 2.2. This was not statistically different from the number in the nonsmoking population. There was no correlation between the number of polypectomies and alcohol intake. The mean intake per week was 9 units, with a range of 0 to 112 units (median 5 units, mode 0 units) (1 unit of alcohol = 1/2 pint of beer or 1 glass of wine). Forty-three percent of the surveyed population had relatives with a known history of nasal polyposis.
300
Otolaryngology– Head and Neck Surgery February 2000
PANG et al
Food Allergy Skin Tests
In the prospective study 80 nasal polyp patients and 36 control subjects completed the food allergy tests. The sex and age distribution is shown in Table 3. Sixtyfive nasal polyp patients (81%) and 4 healthy volunteers (11%) had positive food reactions (P = 0.00, χ2). The mean number of skin tests in both groups was 11 (median 11). The number of skin tests with positive results in nasal polyp patients ranged from 0 to 13 (median 2), whereas in the control subjects the range was 0 to 5 (median 0). The difference in the number of food reactions was also statistically significant (P = 0.000, Mann-Whitney test). The most common reactions were to wheat, potato, and tomato; other reactions were to corn, chicken, egg, milk, pork, pea, and orange. Of these commonly reacting foods only orange, tomato, and to a lesser degree, pea contain salicylate. DISCUSSION
A review of the literature suggests that this is one of the largest retrospective surveys of nasal polyp patients reported to date (1966-1996). The age and sex distribution in our survey is similar to that of previous studies. Nasal polyps predominantly affect middle age adults (>40 years old), with a male predominance of 2:1 to 3:1.7,11 The association with asthma has been widely recognized and is reported to range from 20% to 70%,7,12,13 which is similar to the findings in this study (35.7%). Aspirin intolerance has been observed in 13.8% to 14.2% of nasal polyp patients,14,15 which is similar to our survey incidence of 11.2%. Because this was a postal survey, we were unable to determine the extent and nature of the reported aspirin intolerance. Samter and Beers16 reported the incidence of the triad of nasal polyposis, asthma, and aspirin intolerance as 8%, a figure relatively close to our own findings (7.1%). Two thirds of those with aspirin intolerance and nasal polyps had asthma. In this subgroup, disease was more aggressive, as reflected by the significantly higher frequency of polypectomies. Smoking and alcohol consumption do not appear to affect the frequency of polypectomies when patients in these groups were compared with patients in the nonsmoking and nondrinking groups, respectively. Maloney and Oliver17 found an association of HLA Al and HLA B8 in patients with asthma and nasal polyps, which they suggested might be due to an underlying abnormality in the immune response. The high frequency of first- and second-degree relatives with histories of nasal polyps would support this observation. This study showed a significant association of delayed food hypersensitivity and nasal polyposis.
There was a striking excess of positive skin test results in 80% of the patients. Food hypersensitivity can be broadly divided into immediate and delayed reactions. Immediate reaction is IgE mediated, manifesting as an anaphylactic-type reaction. It is estimated to constitute 5% of food allergy reactions.18 In this study we were interested in non-IgE-mediated delayed food hypersensitivity. These reactions are labeled as type II, III, or IV hypersensitivity and comprise 95% of all immune food reactions.18 Foods causing delayed hypersensitivity are commonly eaten and may be part of the daily diet. They can be eaten whole or as “hidden foods” in prepared foodstuffs. The number of positive reactions per patient varied from 1 to 15. It is conceivable that the varying reactivity may relate to the fluctuations in clinical behavior in nasal polyposis. However, the numbers in this study are too small to test this hypothesis. From the questionnaire, only 6% of patients were aware of food allergy. This is certainly an underestimation compared with the percentage prevalence of positive skin test results. Similarly, the 4 control subjects with positive skin reactions in this study were not aware of any food allergy. Comparison of the 2 groups shows that there is a significant association of delayed food hypersensitivity with the nasal polyp population. Many recent studies have described a host of mediators in nasal polyp tissues.2 Delayed food hypersensitivity being immunologically mediated may be the trigger for the migration and release of mediators in the polyp tissues. Whether delayed food hypersensitivity is a major cause of nasal polyposis needs to be proved. It may be that nasal polyps are the uniform local manifestation of a systemic disorder that has yet to be fully defined. Work is now in progress to determine whether the exclusion of relevant food allergens from the diet alters the clinical course of nasal polyposis. Salicylate sensitivity has long been associated with nasal polyposis. In the panel of 16 foods that we have selected, only apple, tomato, and pea have been found to contain salicylate. In this study, only 1 patient reacted positively to pea and/or tomato alone. These results appear to suggest that the presence of salicylates in food may not be a significant factor in the pathogenesis of nasal polyposis, as previously thought. A controlled study comparing salicylate hyperactivity in nasal polyp patients and healthy control subjects would, however, be needed to settle this issue conclusively. CONCLUSION
A controlled study of delayed food hypersensitivity and nasal polyps is reported. The results indicate a highly significant difference in the prevalence of posi-
Otolaryngology– Head and Neck Surgery Volume 122 Number 2
tive intradermal food test results in nasal polyp patients. Because only a small minority is clinically apparent, intradermal tests are necessary to substantiate the diagnosis. Delayed food hypersensitivity may have been underestimated, whereas the importance of salicylate may be overestimated. We thank Sister Pauline Davidson for her assistance in the study. REFERENCES 1. Vancil ME. A historical survey of treatment of nasal polyposis. Laryngoscope 1969;79:435-45. 2. Jordanna M, Dolovich J, Ohno I, et al. Nasal polyposis: a model for chronic inflammation. In: Bruce W, Holgate W, editors. Asthma & rhinitis. Boston: Blackwell Scientific; 1995. p. 15664. 3. Caplin I, Hayes TJ, Spahn J. Are nasal polyps an allergic phenomenon? Ann Allergy 1971;29:631-4. 4. Schraum VL Jr, Bifrom MZ. Nasal polyps in children. Laryngoscope 1980;90:1488-95. 5. Mygind N. Nasal allergy. Oxford: Blackwell; 1978. p. 233-8. 6. Slavin RG. Allergy is not a significant cause of nasal polyps [letter]. Arch Otolaryngol Head Neck Surg 1992;118:343.
PANG et al
301
7. Drake-Lee AB, Lowe D, Swanston A, et al. Clinical profile and recurrence of nasal polyps. J Laryngol Otol 1984;98:783-93. 8. King WP. Food hypersensitivity in otolaryngology. Otolaryngol Clin North Am 1992;25:163-79. 9. King WP, Rubin WA, Fadal RG, et al. Provocation-neutralization: a two-part study. Part 1. The intracutaneous provocative food test: a multicenter comparison study. Otolaryngol Head Neck Surg 1988;99:263-71. 10. King WP, Moles JM. The intracutaneous progressive dilution multi-food test. Otolaryngol Head Neck Surg 1991;104:235-8. 11. Salvin RG. Nasal polyps and sinusitis. Allergy: principles and practice. 3rd ed. St Louis: Mosby; 1988. p. 1291-303. 12. Maloney JR. Nasal polyps, nasal polypectomy, asthma and aspirin sensitivity. J Laryngol Otol 1977;91:837-46. 13. Settipane GA, Chaffee FH, Klein DE. Aspirin intolerance: a prospective study in an atopic and normal population. J Allergy Clin Immunol 1974;53:200-4. 14. Schenk N. Nasal polypectomy in aspirin sensitive asthmatic. Trans Am Acad Ophthalmol Otolaryngol 1974;78:109-19. 15. Settipane GA, Charles FH. Nasal polyps and rhinitis: A review of 6037 patients. J Allergy Clin Immunol 1971;59:17-21. 16. Samter M, Beers RF. Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med 1968;68:975-83. 17. Maloney JR, Oliver RTD. HLA antigen, nasal polyps and asthma. Clin Otolaryngol 1980;5:183-9. 18. Breneman JC. Basics of food allergy. Springfield (IL): Charles C Thomas; 1978. p. 8-15, 155-6.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of Otolaryngology–Head and Neck Surgery are available to subscribers (only) for the 2000 issues from the Publisher, at an individual cost of $118.00 ($146.59 for Canadian, $137.00 for international subscribers) for Vols. 122 (January-June) and 123 (JulyDecember). Shipping charges are included. Each bound volume contains subject and author indexes, and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable blue buckram with the Journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Inc., Subscription Services, 11830 Westline Industrial Drive, St. Louis, MO 63146-3318, USA; phone, 800-453-4351 or 314-453-4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular Journal subscription.