Allergic fungal rhinosinusitis

Wantida Chuenjit; MDAllergy & Immunology Unit, Department of Pediatrics,

Faculty of Medicine, Prince of Songkhla University

Outlines

• Background of allergic fungal rhinosinusitis• Pathophysiology of allergic fungal

rhinosinusitis• Approach to allergic fungal rhinosinusitis• Management of allergic fungal rhinosinusitis

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)

Fungal rhinosinusitis

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

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

Classification of fungal rhinosunusitis

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

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

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 andKuhn proposed 5 criteria for the diagnosis of AFS1. Nasal polyposis 100 %2. Allergic mucin 40 %3. CT findings consistent with CRS 100 %4. Positive fungal stain or culture 100 %, 73%5. Type I hypersensitivity to fungi diagnosed

by history, a positive skin prick test or serology 100 %

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?

Criteria for diagnosing non-invasive fungal rhinosinusitis

F.A. Ebbens et.al, Rhinology 2007; 45, 178-189

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;6:712-20C. A. Callejas et al, Clinical & Experimental Allergy 2013;43:835–849

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

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

Pathophysiology of allergic fungal rhinosinusitis

Marple, Laryngoscope 2001; 111: 1006-1019

Comparison between allergic fungal rhinosinusitis (AFRS) and allergic bronchopulmonary aspergillosis (ABPA)

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

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)

Fungal rhinosinusitis in patients with chronic sinusal disease

Celso Dall’Igna et al, Rev Bras Otorrinolaringo2005;6:712-20

Clinical manifestation

Diagnosis of Allergic Fungal Sinusitis

Asthma Charcot-Leyden crystals Eosinophilia Unilaterality of disease Evidence of osseous erosion Positive sinonasal fungal culture.

Endonasal endoscopic;allergic mucin Nasal polyps

Brian D. Thorp et.al, Otolaryngol Clin N Am 45 (2012) 631–642

Investigation

1Scott C. Manning et al, Laryngoscope 1997; 107:170-176 2Ghegan, Mark D. et al, Otolaryngology - Head & Neck Surgery 2006; 134(4):592-595

-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

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

Medial orbital wall thinned and expanded laterally by the ethmoidsinus content

Erosion of the skull base (arrow) and lateral expansion of the thinned medial orbital wall (arrowheads)

T2-weighted image showing central void signal (asterisks) and peripheral enhancement of right-side sinuses (arrowheads)

T1-weighted image showing central hypointensity (asterisks) and peripheral enhancement of right-side sinuses (arrowheads)

MRISinus CT

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

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

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

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

Management of Allergic Fungal Sinusitis

Marple, Laryngoscope 2001; 111: 1006-1019

Management of Allergic Fungal Sinusitis

Marple, Laryngoscope 2001; 111: 1006-1019

Approach to management of allergic fungal rhinosinusitis

M.P. Silva et al, Ann Allergy Asthma Immunol 2013; 110: 217-222

V. Rupa, Mary Jacob, Mary Somini Mathews, Mandalam S. Seshadri

V. Rupa et al, Eur Arch Otorhinolaryngol 2010; 267: 233–238

Oral steroid group•Prednisolone, 50 mg OD x 6 weeks, tapered for period of 6 weeksControl group •PlaceboAll patients received fluticasone propionate nasal spray and oral itraconazole at a dose of 200 mg once daily for 12 weeks.

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 monthswith short course of oral steroids at 0.5 mg/kg/day for 1 to 2 weeks if nasal mucosa swellingHistorical 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

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 A oral itraconazole Group B fluconazole nasal spray Group C combined oral itraconazole and nasal fluconazoleGroup D irrigation with fluconazole solution through the nasal fossa Group 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 (39.0%)•group A 6 /9 patients (66.7%)•group B 1/10 patients (10.0%)•group C 1/7 patients (14.3%)•group D 2/7 patients (28.6%)•group B 6/8 patients (75.0%)

Y. Khalil, ENT-Ear, Nose & Throat Journal 2011; 90(8): E1-7

Allergen immunotherapy

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

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;117:35-47Schubert MS, (J Allergy Clin Immunol 1998;102:395-402

Follow up

A. Ragab et al, Eur Arch Otorhinolaryngol 2014; 271:93–101

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 testAFRS with HFL •Additionally cheesy or clay-like materials•Scattered fungal hyphae together with dense conglomerations of hyphae

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

Thank you