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Allergic Fungal Sinusitis

Pathogenesis and Management Strategies

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Abstract

Allergic fungal sinusitis (AFS) is a noninvasive form of highly recurrent chronic allergic hypertrophic rhinosinusitis that can be distinguished clinically, histopathologically and prognostically from the other forms of chronic fungal rhinosinusitis. There are three invasive (acute necrotising, chronic invasive and granulomatous invasive) and two noninvasive (fungal ball and allergic fungal) forms of fungal rhinosinusitis currently recognised. Confusion in differentiating between the various forms of fungal rhinosinusitis and between other forms of chronic hypertrophic sinus disease (HSD) can be eliminated by adhering to strict diagnostic criteria. Although there are characteristic presenting clinical history and physical examination findings, laboratory test results, including elevated total serum IgE and positive inhalant allergy skin tests, and sinus computed tomography scans showing chronic rhinosinusitis (often with the presence of hyperattenuating sinus contents) diagnosis of AFS is essentially based on histopathology obtained from sinus surgery. Histopathology shows the presence of eosinophilic-lymphocytic sinus mucosal inflammation, extramucosal allergic mucin (that is also seen grossly at surgery as a characteristic ‘peanut-buttery’ material), and scattered silver stain positive fungal hyphae within the allergic mucin but not in the mucosa.

Treatment and follow up of AFS has been based on its immunopathological analogy to allergic bronchopulmonary aspergillosis, a similar noninvasive fungal hypersensitivity disorder of the lung, and its clinical and pathophysiological relationship to other forms of HSD and asthma. Treatment involves aggressive sinus surgery followed by medical management that includes allergen immuno-therapy, topical and systemic corticosteroids, antihistamines and antileukotrienes. Total serum IgE levels should be followed postoperatively as they can be prognostic for recurrent disease. Close follow up and coordination of treatment by both medical and surgical physicians as a team leads to the best clinical outcomes. Ongoing studies are being directed at furthering our understanding of the pathophysiological relationships and treatment options for AFS, and other common forms of chronic hypertrophic rhinosinusitis disorders.

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References

  1. de Shazo RD, Chapin K, Swain RE. Fungal sinusitis. N Engl J Med 1997; 337: 254–9

    Article  Google Scholar 

  2. Schubert MS. Medical treatment of allergic fungal sinusitis. Ann Allergy Asthma Immunol 2000; 85: 90–101

    Article  PubMed  CAS  Google Scholar 

  3. Choi SS, Milmoe GJ, Dinndorf PA, et al. Invasive aspergillus sinusitis in pediatric bone marrow transplant patients. Arch Otolaryngol Head Neck Surg 1995; 121: 188–92

    Article  Google Scholar 

  4. Ferguson BJ. Mucormycosis of the nose and paranasal sinuses. Otolaryngol Clin North Am 2000; 33: 349–65

    Article  PubMed  CAS  Google Scholar 

  5. Gillespie MB, O’Malley BW. An algorithmic approach to the diagnosis and management of invasive fungal rhinosinusitis in the immunocompromised patient. Otolaryngol Clin North Am 2000; 33: 323–34

    Article  PubMed  CAS  Google Scholar 

  6. Mitchell TG. Overview of basic medical mycology. Otolaryngol Clin North Am 2000; 33: 237–49

    Article  PubMed  CAS  Google Scholar 

  7. Ferreiro JA, Carlson BA, Cody DT. Paranasal sinus fungus balls. Head Neck 1997; 19: 481–6

    Article  PubMed  CAS  Google Scholar 

  8. Milroy CM, Blanshard JD, Lucas S, et al. Aspergillosis of the nose and paranasal sinuses. J Clin Pathol 1989; 42: 123–7

    Article  PubMed  CAS  Google Scholar 

  9. Dooley DP, Hollsten DA, Grimes SR, et al. Indolent orbital apex syndrome caused by occult mucormycosis. J Clin Neuroophthalmol 1992; 12: 245–9

    PubMed  CAS  Google Scholar 

  10. Sandison AT, Gentles JC, Davidson CM, et al. Aspergilloma of paranasal sinuses and orbit in northern Sudanese. Sabouraudia 1967; 6: 57–69

    Article  Google Scholar 

  11. Milosev B, el-Mahgoub S, Aal OA, et al. Primary aspergilloma of paranasal sinuses in the Sudan: a review of seventeen cases. Br J Surg 1969; 56: 132–7

    Article  PubMed  CAS  Google Scholar 

  12. Veress B, Malik OA, el-Tayeb AA, et al. Further observations on the primary paranasal aspergillosis granuloma in the Sudan: a morphological study of 46 cases. Am J Trop Med Hyg 1973; 22: 765–72

    PubMed  CAS  Google Scholar 

  13. Gumaa SA, Mahgoub ES, Hay RJ. Post-operative responses of paranasal Aspergillus granuloma to itraconazole. Trans R Soc Trop Med Hyg 1992; 86: 93–4

    Article  PubMed  CAS  Google Scholar 

  14. Schubert MS, Goetz DW. Evaluation and treatment of allergic fungal sinusitis. I: demographics and diagnosis. J Allergy Clin Immunol 1998; 102: 387–94

    Article  CAS  Google Scholar 

  15. Schubert MS. Fungal rhinosinusitis: diagnosis and therapy. Curr Allergy Asthma Rep 2001; 1: 268–76

    Article  PubMed  CAS  Google Scholar 

  16. deShazo RD, O’Brien M, Chapin K, et al. Criteria for the diagnosis of sinus mycetoma. J Allergy Clin Immunol 1997; 99: 475–85

    Article  Google Scholar 

  17. Klossek JM, Serrano E, Peloquin L, et al. Functional endoscopic sinus surgery and 109 mycetomas of paranasal sinuses. Laryngoscope 1997; 107: 112–7

    Article  PubMed  CAS  Google Scholar 

  18. Millar JW, Johnston A, Lamb D. Allergic aspergillosis of the paranasal sinuses [abstract]. Thorax 1981; 36: 710

    Google Scholar 

  19. Gourley DS, Whisman BA, Jorgensen NL, et al. Allergic bipolaris sinusitis: clinical and immunopathologic characteristics. J Allergy Clin Immunol 1990; 85: 583–91

    Article  PubMed  CAS  Google Scholar 

  20. Bent III JP, Kuhn FA. Diagnosis of allergic fungal sinusitis. Otolaryngol Head Neck Surg 1994; 111: 580–8

    Article  PubMed  Google Scholar 

  21. de Shazo RD, Swain RE. Diagnostic criteria for allergic fungal sinusitis. J Allergy Clin Immunol 1995; 96: 24–35

    Article  Google Scholar 

  22. Ferguson BJ, Barnes L, Bernstein JM, et al. Geographic variation in allergic fungal rhinosinusitis. Otolaryngol Clin North Am 2000; 33: 441–9

    Article  PubMed  CAS  Google Scholar 

  23. Katzenstein AA, Sale SR, Greenburger PA. Allergic aspergillus sinusitis: a newly recognized form of sinusitis. J Allergy Clin Immunol 1983; 72: 89–93

    Article  PubMed  CAS  Google Scholar 

  24. Ence BK, Gourley DS, Jorgensen NL, et al. Allergic fungal sinusitis. Am J Rhinol 1990; 4: 169–78

    Article  Google Scholar 

  25. Collins MM, Nair SB, Wormald PJ. Prevalence of noninvasive fungal sinusitis in South Australia. Am J Rhinol 2003; 17: 127–32

    PubMed  Google Scholar 

  26. Manning SC, Vuitch F, Weinberg AG, et al. Allergie aspergillosis: a newly recognized form of sinusitis in the pediatric population. Laryngoscope 1989; 99: 681–5

    Article  PubMed  CAS  Google Scholar 

  27. McCann WA, Cromie M, Chandler F, et al. Sensitization to recombinant Aspergillus fumigatus allergens in allergic fungal sinusitis. Ann Allergy Asthma Immunol 2002; 89: 203–8

    Article  PubMed  Google Scholar 

  28. Ponikau JU, Sherris DA, Kern EB, et al. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin Proc 1999; 74: 877–84

    Article  PubMed  CAS  Google Scholar 

  29. Kupferberg SB, Bent III JP. Allergic fungal sinusitis in the pediatric population. Arch Otolaryngol Head Neck Surg 1996; 122: 1381–4

    Article  PubMed  CAS  Google Scholar 

  30. Kuhn FA, Javer AR. Allergic fungal sinusitis: a four year follow-up. Am J Rhinol 2000; 14: 149–56

    Article  PubMed  CAS  Google Scholar 

  31. Dibbern DA, Dreskin SC. Allergic fungal sinusitis [letter]. Mayo Clin Proc 2000; 75: 122

    Article  PubMed  Google Scholar 

  32. Page EH. Allergic fungal sinusitis [letter]. Mayo Clin Proc 2000; 75: 122

    Article  PubMed  CAS  Google Scholar 

  33. Ramadan HH, Quraishi HA. Allergic mucin sinusitis without fungus. Am J Rhinol 1997; 11: 145–7

    Article  PubMed  CAS  Google Scholar 

  34. Ferguson BJ. Eosinophilic mucin rhinosinusitis: a distinct clinicopathological entity. Laryngoscope 2000; 110: 799–813

    Article  PubMed  CAS  Google Scholar 

  35. Lara JF, Gomez D. Allergic mucin with and without fungus: a comparative clinicopathologic analysis. Arch Pathol Lab Med 2001; 125: 1442–7

    PubMed  CAS  Google Scholar 

  36. Greenberger PA, Patterson R. Diagnosis and management of allergic bronchopulmonary aspergillosis. Ann Allergy 1986; 56: 444–8

    PubMed  CAS  Google Scholar 

  37. Greenberger PA. Allergic bronchopulmonary aspergillosis. In: Grammer LC, Greenberger PA, editors. Patterson’s allergic diseases. 6th ed. Philadelphia (PA): Lippincott Williams & Wilkins, 2002

    Google Scholar 

  38. Venarske DL, de Shazo RD. Sinobronchial allergic mycosis. Chest 2002; 121: 1670–6

    Article  PubMed  Google Scholar 

  39. Khan DA, Cody III TC, George TJ, et al. Allergic fungal sinusitis: an immunohistologic analysis. J Allergy Clin Immunol 2000; 106: 1096–101

    Article  PubMed  CAS  Google Scholar 

  40. Gleich GJ, Adolphson CA, Leiferman KM. Eosinophils. In: Gallin JI, Goldstein IM, Snyderman R, editors. Inflammation: basic principles and clinical correlates. New York: Raven Press, 1992: 663–700

    Google Scholar 

  41. Chrzanowski RR, Rupp NT, Kuhn FA, et al. Allergenic fungi in allergic fungal sinusitis. Ann Allergy Asthma Immunol 1997; 79: 431–5

    Article  PubMed  CAS  Google Scholar 

  42. Ricketti AJ, Greenberger PA, Patterson R. Serum IgE as an important aid in the management of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1984; 74: 68–71

    Article  PubMed  CAS  Google Scholar 

  43. Schubert MS, Goetz DW. Evaluation and treatment of allergic fungal sinusitis. II: treatment and follow-up. J Allergy Clin Immunol 1998; 102: 395–402

    CAS  Google Scholar 

  44. Schubert MS, Hutcheson PS, Graff RJ, et al. High-resolution HLA class II DNA haplotyping in allergic fungal rhinosinusitis and hypertrophic sinus disease: the role of HLA DQ3 [abstract]. J Allergy Clin Immunol 2003; 111: S123

    Article  Google Scholar 

  45. Chauhan B, Santiago L, Kirschmann DA, et al. The association of HLA-DR alleles and T cell activation with allergic bronchopulmonary aspergillosis. J Immunol 1997; 159: 4072–6

    PubMed  CAS  Google Scholar 

  46. Schubert MS. A superantigen hypothesis for the pathogenesis of chronic hypertrophic rhinosinusitis, allergic fungal sinusitis, and related disorders. Ann Allergy Asthma Immunol 2001; 87: 181–8

    Article  PubMed  CAS  Google Scholar 

  47. Kotzin BL, Leung DYM, Kappler J, et al. Superantigens and their potential role in human disease. Adv Immunol 1993; 54: 99–166

    Article  PubMed  CAS  Google Scholar 

  48. Kappler J, Kotzin B, Herron L, et al. V beta-specific stimulation of human T cells by staphylococcal toxins. Science 1989; 244: 811–3

    Article  PubMed  CAS  Google Scholar 

  49. Krakauer T. Immune response to staphylococcal superantigens. Immunol Res 1999; 20: 163–73

    Article  PubMed  CAS  Google Scholar 

  50. Bachert C, Gevaert P, Holtappels G, et al. Total and specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy Clin Immunol 2001; 107: 607–14

    Article  PubMed  CAS  Google Scholar 

  51. Bachert C, Gavaert P, Howarth P, et al. IgE to Staphylococcal aureus enterotoxins (SAEs) in patients with asthma [abstract]. J Allergy Clin Immunol 2003; 111: S268

    Article  Google Scholar 

  52. Hauk PJ, Wenzel SE, Trumble AE, et al. Increased T-cell receptor V Beta 8+ T cells in bronchoalveolar lavage fluid of subjects with poorly controlled asthma: a potential role for microbial superantigens. J Allergy Clin Immunol 1999; 103: 37–45

    Article  Google Scholar 

  53. Frenkel L, Kuhls TL, Nitta K, et al. Recurrent bipolaris sinusitis following surgical and antifungal therapy. Pediatr Infect Dis J 1987; 6: 1130–2

    PubMed  CAS  Google Scholar 

  54. Washburn RG, Kennedy DW, Begley MG, et al. Chronic fungal sinusitis in apparently normal hosts. Medicine 1988; 67: 231–47

    Article  PubMed  CAS  Google Scholar 

  55. Corey JP, Delsuphene KG, Ferguson BJ. Allergic fungal sinusitis: allergic, infectious, or both? Otolaryngol Head Neck Surg 1995; 113: 110–9

    Article  PubMed  CAS  Google Scholar 

  56. Bent III JP, Kuhn FA. Allergic fungal sinusitis/polyposis. Allergy Asthma Proc 1996; 17: 259–68

    Article  PubMed  Google Scholar 

  57. Morpeth JF, Rupp NT, Dolen WK, et al. Fungal sinusitis: an update. Ann Allergy Asthma Immunol 1996; 76: 128–40

    Article  PubMed  CAS  Google Scholar 

  58. Bent III JP, Kuhn FA. Antifungal activity against allergic fungal sinusitis organisms. Laryngoscope 1996; 106: 1331–4

    Article  PubMed  Google Scholar 

  59. Andes D, Proctor R, Bush RK, et al. Report of successful prolonged antifungal therapy for refractory allergic fungal sinusitis. Clin Infect Dis 2000; 31: 202–4

    Article  PubMed  CAS  Google Scholar 

  60. Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med 2000; 342: 756–62

    Article  PubMed  CAS  Google Scholar 

  61. Ponikau JU, Sherris DA, Kita H, et al. Intranasal antifungal treatment in 51 patients with chronic rhinosinusitis. J Allergy Clin Immunol 2002; 110: 862–6

    Article  PubMed  CAS  Google Scholar 

  62. Vaughan WC, Carvalho G. Use of nebulized antibiotics for acute infections in chronic sinusitis. Otolaryngol Head Neck Surg 2002; 127: 558–68

    Article  PubMed  Google Scholar 

  63. Scheinberg PA, Otsuji A. Nebulized antibiotics for the treatment of acute exacerbations of chronic rhinosinusitis. Ear Nose Throat J 2002; 81: 648–52

    PubMed  Google Scholar 

  64. Desrosiers MY, Salas-Prato M. Treatment of chronic rhinosinusitis refractory to other treatments with topical antibiotic therapy delivered by means of a large-particle nebulizer: results of a controlled trial. Otolaryngol Head Neck Surg 2001; 125: 265–9

    Article  PubMed  CAS  Google Scholar 

  65. Moss RB, King VV. Management of sinusitis in cystic fibrosis by endoscopie surgery and serial antimicrobial lavage: reduction in recurrence requiring surgery. Arch Otolaryngol Head Neck Surg 1995; 121: 566–72

    Article  PubMed  CAS  Google Scholar 

  66. Safirstein B. Allergic bronchopulmonary aspergillosis with obstruction of the upper respiratory tract. Chest 1976; 70: 788–90

    Article  PubMed  CAS  Google Scholar 

  67. Goldstein MF, Atkins PC, Cogen FC, et al. Allergic aspergillus sinusitis. J Allergy Clin Immunol 1985; 76: 515–24

    Article  PubMed  CAS  Google Scholar 

  68. Waxman JE, Spector JG, Sale SR, et al. Allergic aspergillus sinusitis: concepts in diagnosis and treatment of a new clinical entity. Laryngoscope 1987; 97: 261–6

    Article  PubMed  CAS  Google Scholar 

  69. Sher TH, Schwartz HJ. Allergic aspergillus sinusitis with concurrent allergic bronchopulmonary aspergillosis: report of a case. J Allergy Clin Immunol 1988; 81: 844–6

    Article  PubMed  CAS  Google Scholar 

  70. Shah A, Khan ZU, Chaturvedi S, et al. Concomitant allergic Aspergillus sinusitis and allergic bronchopulmonary aspergillosis associated with familial occurrence of allergic bronchopulmonary aspergillosis. Ann Allergy 1990; 64: 507–12

    PubMed  CAS  Google Scholar 

  71. Goldstein MF, Dvorin DJ, Dunsky EH, et al. Allergic rhizomucor sinusitis. J Allergy Clin Immunol 1992; 90: 394–403

    Article  PubMed  CAS  Google Scholar 

  72. Roth M. Should oral steroids be the primary treatment for allergic fungal sinusitis? Ear Nose Throat J 1994; 73: 928–30

    PubMed  CAS  Google Scholar 

  73. Kinsella JB, Bradfield JJ, Gourley WK, et al. Allergic fungal sinusitis. Clin Otolaryngol 1996; 21: 389–92

    Article  PubMed  CAS  Google Scholar 

  74. Mabry RL, Marple BF, Folker RJ, et al. Immunotherapy in the treatment of allergic fungal sinusitis: three years’ experience. Otolaryngol Head Neck Surg 1998; 119: 648–51

    Article  PubMed  CAS  Google Scholar 

  75. Quinn J, Wickern G, Whisman B, et al. Immunotherapy in allergic Bipolaris sinusitis: a case report [abstract]. J Allergy Clin Immunol 1995; 95: 201

    Google Scholar 

  76. Goldstein MF, Dunskey EH, Dvorin DJ, et al. Allergic fungal sinusitis: a review with four illustrated cases. Am J Rhinol 1994; 8: 13–8

    Article  Google Scholar 

  77. Parnes SM, Chuma AV. Acute effects of antileukotrienes on sinonasal polyposis and sinusitis. Ear Nose Throat J 2000; 79: 18–25

    PubMed  CAS  Google Scholar 

  78. Dahlen B, Nizankowska E, Szczeklik A, et al. Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics. Am J Respir Crit Care Med 1998; 157: 1187–94

    PubMed  CAS  Google Scholar 

  79. Schubert MS. Antileukotriene therapy for allergic fungal sinusitis. J Allergy Clin Immunol 2001; 108: 466–7

    Article  PubMed  CAS  Google Scholar 

  80. Marple B, Newcomer M, Schwade N, et al. Natural history of allergic fungal rhinosinusitis: a 4–10-year follow-up. Otolaryngol Head Neck Surg 2002; 127: 361–6

    Article  PubMed  Google Scholar 

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Schubert, M.S. Allergic Fungal Sinusitis. Drugs 64, 363–374 (2004). https://doi.org/10.2165/00003495-200464040-00002

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