Allergic fungal rhinosinusitis presented by Wantida Chuenjit, MD. Jan8, 2014

1. Allergic fungal rhinosinusitis
Wantida Chuenjit; MD
Allergy & Immunology Unit, Department of Pediatrics,
Faculty of Medicine, Prince of Songkhla University

2. Outlines
• Background of allergic fungal rhinosinusitis
• Pathophysiology of allergic fungal
rhinosinusitis
• Approach to allergic fungal rhinosinusitis
• Management of allergic fungal rhinosinusitis

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. Fungal rhinosinusitis
C. A. Callejas et al, Clinical & Experimental Allergy 2013;43:835–849

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. Classification of fungal rhinosunusitis
Kathleen T. Montone et al, International Journal of Otolaryngology 2012, Article ID 684835, 9 pages

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. 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. 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. Criteria for diagnosing
non-invasive fungal rhinosinusitis
F.A. Ebbens et.al, Rhinology 2007; 45, 178-189

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. 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. Kathleen T. Montone et al, International Journal of Otolaryngology 2012, Article ID 684835, 9 pages

14. Pathophysiology of allergic fungal rhinosinusitis
Marple, Laryngoscope 2001; 111: 1006-1019

15. Comparison between allergic fungal rhinosinusitis (AFRS) and
allergic bronchopulmonary aspergillosis (ABPA)
C. A. Callejas et al, Clinical & Experimental Allergy, 43 : 835–849

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. Fungal rhinosinusitis in patients with
chronic sinusal disease
Celso Dall’Igna et al, Rev Bras Otorrinolaringo2005;6:712-20

18. Clinical manifestation

19. Diagnosis of Allergic Fungal Sinusitis
Asthma
Charcot-Leyden crystals
Eosinophilia
Unilaterality of disease
Evidence of osseous erosion
Positive sinonasal fungal culture.

20. Endonasal endoscopic;
allergic mucin
Nasal polyps
Brian D. Thorp et.al, Otolaryngol Clin N Am 45 (2012) 631–642

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. 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. Granville et al , Human pathology 2004 ; 35(4): 474-481

24. Charcot-Leyden crystal displayed on a
hematoxylin and eosin stain of allergic mucin.

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. Alexander E. Stewart et al, Otolaryngology Head and Neck Surgery 2002; 127: 324-332

27. Management of Allergic Fungal Sinusitis
Marple, Laryngoscope 2001; 111: 1006-1019

28. Management of Allergic Fungal Sinusitis
Marple, Laryngoscope 2001; 111: 1006-1019

29. Approach to management of
allergic fungal rhinosinusitis
M.P. Silva et al, Ann Allergy Asthma Immunol 2013; 110: 217-222

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. 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. 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. Allergen immunotherapy
Ashley G. et al, Curr Opin Allergy Clin Immunol 2012; 12;629-634

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. 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. 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. Thank you