Allergic fungal rhinosinusitis

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Allergic fungal rhinosinusitis

presented by Wantida Chuenjit, MD.

Jan8, 2014

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  • In 1983, Katzenstein et al identified Aspergillus species in mucus obtained from the nose and paranasal sinuses of patients suffering form CRS with NP, and introduced the term“allergicAspergillus sinusitis” because of its histopathological similarity to allergic bronchopulmonaryaspergillosis (ABPA)-presence of “allergic mucin” (thick, tenaciousand darkly coloured (peanut butter like) mucus containingaggregates of necrotic eosinophils, nuclear debris, freeeosinophil granules, sloughed respiratory tract epithelial cells,and Charcot-Leyden crystals within an otherwise amorphous,pale eosinophilic or basophilic mucinous background) andscattered fungal hyphae of Aspergillus species
  • Ponikau Fungal cultures of nasal secretions were positive in 202 (96%) of 210 consecutive CRS patients. Allergic mucin was found in 97 (96%) of 101 consecutive surgical cases of CRS. Allergic fungal sinusitis was diagnosed in 94 (93%) of 101 consecutive surgical cases with CRS, based on histopathologic findings and culture results. Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients.-Ferguson described a form of CRS histologically similar toAFS (as described by DeShazo et al(7)) except for the absenceof fungal hyphae, which she called eosinophilicmucinrhinosinusitis(EMRS). It was postulated that AFS is an allergicresponse to fungi in predisposed individuals, while EMRS isthe result of a systemic dysregulation in immunological controls
  • AFRS was diagnosed in 27 patients, and 15/27 (56%) had bony skull base or orbital erosion. Non-AFRS chronic sinusitis required surgery in 158 patients, but only 8 (5%) had bony skull base or orbital erosion (P < 0.01)
  • Allergic fungal rhinosinusitis

    1. 1. Allergic fungal rhinosinusitis Wantida Chuenjit; MD Allergy & Immunology Unit, Department of Pediatrics, Faculty of Medicine, Prince of Songkhla University
    2. 2. Outlines • Background of allergic fungal rhinosinusitis • Pathophysiology of allergic fungal rhinosinusitis • Approach to allergic fungal rhinosinusitis • Management of allergic fungal rhinosinusitis
    3. 3. Fungal rhinosinusitis • Both inflammatory and infectious conditions of nose and paranasal sinuses caused by fungi • Two categories – Non-invasive disease • Fungal ball • Allergic fungal rhinosinusitis (AFRS) – Invasive disease • Acute invasive fungal rhinosinusitis (AIFRS) • Chronic invasive fungal rhinosinusitis (CIFRS) • Granulomatous invasive fungal rhinosinusitis (GIFRS)
    4. 4. Fungal rhinosinusitis C. A. Callejas et al, Clinical & Experimental Allergy 2013;43:835–849
    5. 5. • • • Fungal ball Heterogeneous opacities within the involved sinus cavity Most probably due to the accumulation of haemosiderin and metals Local calcification in the centre of the hyphae masses Allergic fungal rhinosinisitis • Medial orbital wall thinned and expanded laterally by ethmoidal sinus content Invasive fungal rhinosinusitis • Complete opacification of lumen of right maxillary sinus with bony erosion/destruction medially extending through the lamina papyracea
    6. 6. Classification of fungal rhinosunusitis Kathleen T. Montone et al, International Journal of Otolaryngology 2012, Article ID 684835, 9 pages
    7. 7. Allergic Fungal Rhinosinusitis • Young, Atopic, Immunocompetent patients • Present as CRS with polyps which usually recalcitrant to conventional treatment • Patients may discharge allergic mucin • Severe cases may present with facial deformity
    8. 8. Historical Prospective • In 1983, Katzenstein et al identified term "allergic Aspergillus sinusitis” because of its histopathological similarity to allergic bronchopulmonary aspergillosis (ABPA) Later the disease name “allergic fungal sinusitis” (AFS) • In 1994, based on clinical findings in 15 patients, Bent and Kuhn proposed 5 criteria for the diagnosis of AFS 1. 2. 3. 4. 5. Nasal polyposis Allergic mucin CT findings consistent with CRS Positive fungal stain or culture Type I hypersensitivity to fungi diagnosed by history, a positive skin prick test or serology 100 % 40 % 100 % 100 %, 73% 100 %
    9. 9. Historical Prospective • In 1995, DeShazo and Swain, review 98 AFS cases, observed that only 3/4 of patients were atopic. point of debate, the criterion “type I hypersensitivity” necessary for the diagnosis?
    10. 10. Criteria for diagnosing non-invasive fungal rhinosinusitis F.A. Ebbens et.al, Rhinology 2007; 45, 178-189
    11. 11. Epidemiology • Prevalence of fungal rhinosinusitis was 6.7% of CRS • Most common among adolescents and young adults: mean age at diagnosis is 21.9 years • Environment factors and host genetics have shown to play a role • Increase incidence in warm and humid areas (southern US, India) and low socioeconomic status Celso Dall’Igna et al, Rev Bras Otorrinolaringo2005;6:712-20 C. A. Callejas et al, Clinical & Experimental Allergy 2013;43:835–849
    12. 12. Prevalence and microbiology of fungi in AFRS • Fungi can be detected in the nose and paranasal sinuses of all CRS patients and all healthy controls • Most common organism in AFRS – Aspergillus – Dematiaceous moulds e.g. Curvularia, Penicillium, Alternaria, Bipolaris, and Fusarium
    13. 13. Kathleen T. Montone et al, International Journal of Otolaryngology 2012, Article ID 684835, 9 pages
    14. 14. Pathophysiology of allergic fungal rhinosinusitis Marple, Laryngoscope 2001; 111: 1006-1019
    15. 15. Comparison between allergic fungal rhinosinusitis (AFRS) and allergic bronchopulmonary aspergillosis (ABPA) C. A. Callejas et al, Clinical & Experimental Allergy, 43 : 835–849
    16. 16. Clinical manifestation • Nasal congestion • Some degree of nasal airway obstruction • Purulent and clear rhinorrhea, postnasal drainage, thick, tenacious and darkly coloured (peanut butter like) mucus • Headaches • Present with difficult-to-treat sinusitis and nasal polyposis (massive polyposis)
    17. 17. Fungal rhinosinusitis in patients with chronic sinusal disease Celso Dall’Igna et al, Rev Bras Otorrinolaringo2005;6:712-20
    18. 18. Clinical manifestation
    19. 19. Diagnosis of Allergic Fungal Sinusitis Asthma Charcot-Leyden crystals Eosinophilia Unilaterality of disease Evidence of osseous erosion Positive sinonasal fungal culture.
    20. 20. Endonasal endoscopic; allergic mucin Nasal polyps Brian D. Thorp et.al, Otolaryngol Clin N Am 45 (2012) 631–642
    21. 21. Investigation -AFRS patients were 12.6 times (P < 0.01) more likely to have bony erosion than non-AFRS patients -African American males were 15.0 times (P < 0.01) more likely to have bony erosion than whites and African American females combined 2 1Scott C. Manning et al, Laryngoscope 1997; 107:170-176 2Ghegan, Mark D. et al, Otolaryngology - Head & Neck Surgery 2006; 134(4):592-595
    22. 22. Sinus CT MRI Medial orbital wall thinned and expanded laterally by the ethmoid sinus content Erosion of the skull base (arrow) and lateral expansion of the thinned medial orbital wall (arrowheads) T1-weighted image showing central hypointensity (asterisks) and peripheral enhancement of right-side sinuses (arrowheads) T2-weighted image showing central void signal (asterisks) and peripheral enhancement of right-side sinuses (arrowheads) C. A. Callejas et al, Clinical & Experimental Allergy, 43 : 835–849
    23. 23. Granville et al , Human pathology 2004 ; 35(4): 474-481
    24. 24. Charcot-Leyden crystal displayed on a hematoxylin and eosin stain of allergic mucin.
    25. 25. Serum total and specific IgE concentrations of patients with AFRS versus non-AFRS CRSwNP and control subjects Tineke Dutre et.al, J Allergy Clin Immunology 2013; 132(4):487-489
    26. 26. Alexander E. Stewart et al, Otolaryngology Head and Neck Surgery 2002; 127: 324-332
    27. 27. Management of Allergic Fungal Sinusitis Marple, Laryngoscope 2001; 111: 1006-1019
    28. 28. Management of Allergic Fungal Sinusitis Marple, Laryngoscope 2001; 111: 1006-1019
    29. 29. Approach to management of allergic fungal rhinosinusitis M.P. Silva et al, Ann Allergy Asthma Immunol 2013; 110: 217-222
    30. 30. V. Rupa, Mary Jacob, Mary Somini Mathews, Mandalam S. Seshadri Oral steroid group •Prednisolone, 50 mg OD x 6 weeks, tapered for period of 6 weeks Control group •Placebo All patients received fluticasone propionate nasal spray and oral itraconazole at a dose of 200 mg once daily for 12 weeks. V. Rupa et al, Eur Arch Otorhinolaryngol 2010; 267: 233–238
    31. 31. Patients Allergic fungal sinusitis patients who undergo endoscopic sinus surgery Intervention and control Steroid group • 33 treated with surgery plus steroid therapy •Oral prednisone (0.5 mg/kg) for 1 month, followed by topical beclamethasone (2 sprays in each side twice daily) for 5 months with short course of oral steroids at 0.5 mg/kg/day for 1 to 2 weeks if nasal mucosa swelling Historical Control group •30 treated with surgery plus placebo Outcome Allergic fungal sinusitis recurred in •15/30 no-steroid patients (50.0%), compared with •5/33 steroid patients (15.2%) (p = 0.008) No patient in the steroid group reported any serious side effects of steroid therapy Ikram M. et al, Ear Nose Throat J. 2009; 88(4):E8-11
    32. 32. The role of antifungal therapy in the prevention of recurrent allergic fungal rhinosinusitis after functional endoscopic sinus surgery: A randomized, controlled study Patients Allergic fungal sinusitis patients who undergo endoscopic sinus surgery Intervention and control Group Group Group Group Group A oral itraconazole B fluconazole nasal spray C combined oral itraconazole and nasal fluconazole D irrigation with fluconazole solution through the nasal fossa E 10 controls received CMT only •Prednisone 60 mg/day for 6 wks tapered over 3 wks •Fluticasone nasal spray at 2 puff s/day for 6 months •Amoxicillin/clavulanic acid (500/125 mg) 1x3 for14 days •An alkaline nasal wash (borax, sodium chloride, or sodium bicarbonate at 5 g/50 ml 3 times/day 2 weeks •loratadine at 10 mg 1x1 for 2 weeks Outcome Recurrence rates •All 16/41 patients •group A 6 /9 patients •group B 1/10 patients •group C 1/7 patients •group D 2/7 patients •group B 6/8 patients (39.0%) (66.7%) (10.0%) (14.3%) (28.6%) (75.0%) Y. Khalil, ENT-Ear, Nose & Throat Journal 2011; 90(8): E1-7
    33. 33. Allergen immunotherapy Ashley G. et al, Curr Opin Allergy Clin Immunol 2012; 12;629-634
    34. 34. Follow up • High recurrence • Patient symptoms do not collerate with extend of disease, physical finding match the progression of stages of recurrence • Total serum IgE correlated significantly with severity of disease • Importantly, an increase ≥ 10% of total serum IgE during follow up “strong predictor of recurrence and need for surgery Kupferberg et al, Otolaryngo head and neck surg 1997;117:35-47 Schubert MS, (J Allergy Clin Immunol 1998;102:395-402
    35. 35. Follow up AFRS without high fungal loads (HFL) •Allergic fungal mucin (thick tenacious colored mucus at the time of surgery) •Viable and degranulating eosinophils with scattered fungal hyphae •Allergy to any fungi determined by a positive skin prick test AFRS with HFL •Additionally cheesy or clay-like materials •Scattered fungal hyphae together with dense conglomerations of hyphae A. Ragab et al, Eur Arch Otorhinolaryngol 2014; 271:93–101
    36. 36. Conclusion • Young, Atopic, Immunocompetent patients • Present as CRS with polyps which usually recalcitrant to conventional treatment and may discharge allergic mucin • Pathogenesis include hypersensitivity and T-cell mediated reactions as well as humoral immune response • Treatment is largely surgical with role of oral and intranasal corticosteroid and an emerging role for IT • High recurrent rate, need long term follow up
    37. 37. Thank you

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