Fungal SinusitisFungal Sinusitis

Anders CervinAnders Cervin

Department of Department of Otorhinolaryngology, Otorhinolaryngology,

Head and Neck surgeryHead and Neck surgery

Lund University HospitalLund University Hospital

SwedenSweden

HistoryHistory

1971 McCarthy and Pepys. 1971 McCarthy and Pepys. 1981 Millar et al. 1981 Millar et al. 1983 Katzenstein (allergic 1983 Katzenstein (allergic

aspergillus sinusitis)aspergillus sinusitis) 1989 Robson AFS1989 Robson AFS 1996 Pediatric AFS1996 Pediatric AFS 1998 AFS without fungus1998 AFS without fungus

ClassificationClassification

Fungal ball (Mycetoma, no Fungal ball (Mycetoma, no allergic mucin) allergic mucin)

Non invasive (AFS and Non invasive (AFS and Saprophytic)Saprophytic)

Invasive (chronic and acute - Invasive (chronic and acute - immunocompromised patient)immunocompromised patient)

AFS, Geographic DistributionAFS, Geographic Distribution

Memphis Tennesse 23% of CSMemphis Tennesse 23% of CS Southern States 10%Southern States 10% Northern States 0-4%Northern States 0-4%

How do you get AFS?How do you get AFS?

Injury to mucosa

Impaired MCT

Inhalation of fungal spores

Immunologic reaction

Infection

Atopy

Katzenstein at alKatzenstein at al

7 otherwise healthy patients 7 otherwise healthy patients with allergic mucin (cottage with allergic mucin (cottage cheese, peanut butter, green, cheese, peanut butter, green, brown or yellow)brown or yellow)– Laminated mucinLaminated mucin– EosinophilsEosinophils– Charcot-Leyden crystalsCharcot-Leyden crystals– Fungal hyphaeFungal hyphae

Diagnostic Criteria AFS Diagnostic Criteria AFS (deShazo 95)(deShazo 95)

Sinusitis CTSinusitis CT Allergic mucinAllergic mucin Fungal elements in secretions or Fungal elements in secretions or

tissuetissue Abscence of invasive fungal diseaseAbscence of invasive fungal disease Abscence of immuno-compromising Abscence of immuno-compromising

diseeasediseease

Data on 99 cases of AFSData on 99 cases of AFS (deSchazo 95, Alabama, USA)(deSchazo 95, Alabama, USA)

Age Age rangerange

SexSex AtopyAtopy Chronic Chronic sin.sin.

PolypsPolyps Bony Bony erosierosion on CTCT

Fungus Fungus culture culture pospos

RAST RAST pospos

ElevatElevat

ed IgEed IgE

Pos Pos skin skin prickprick

7-587-58 52% 52% MM

76%76% 75%75% 80%80% 36%36% 76%76% 89%89% 74%74% 73%73%

AFS, 67 consecutive casesAFS, 67 consecutive cases(Schubert 98, USA southwest)(Schubert 98, USA southwest)

Atopy 100%Atopy 100% Nasal polyposis 100%Nasal polyposis 100% Young age (33±13 years)Young age (33±13 years) Hypertrofic rhinosinusitis 100%Hypertrofic rhinosinusitis 100% Cast production 75%Cast production 75% Elevated S-IgE (668 IU/ml)Elevated S-IgE (668 IU/ml) Growth of Bipolaris 67%Growth of Bipolaris 67%

European experienceEuropean experience (Vennewald Germany 1998)(Vennewald Germany 1998)

132 samles from 117 patients were 132 samles from 117 patients were taken if granulomatous material taken if granulomatous material was found during surgerywas found during surgery

Fungus was found in 25% of Fungus was found in 25% of patientspatients

Aspergillus fumigatus and Aspergillus fumigatus and Sporanax in the majority of cases Sporanax in the majority of cases (80%)(80%)

No invasive casesNo invasive cases

Swedish experienceSwedish experienceYdreborg et al 2001Ydreborg et al 2001

23 patients nasal polyposis 23 patients nasal polyposis Culture from mucus 6 weeksCulture from mucus 6 weeks Positive culture 48% of pat. Positive culture 48% of pat.

(Aspergillus 81%, Candida 19%)(Aspergillus 81%, Candida 19%) PAS staining negative for HyphaePAS staining negative for Hyphae All had benign polyposis on All had benign polyposis on

histologyhistology

When to suspect AFS When to suspect AFS SymptomsSymptoms

Chronic sinusitisChronic sinusitis Refractory to traditional Refractory to traditional

treatmenttreatment History of atopyHistory of atopy PolypsPolyps

When to suspect AFS When to suspect AFS SignsSigns

PolypsPolyps Tenacious Tenacious

secretionssecretions Cheesy materialCheesy material Fungus ballsFungus balls

How to diagnose How to diagnose CultureCulture

Culture from mucus Culture from mucus Sampling technique Sampling technique Culture technique Culture technique (mucolytic (mucolytic

treatment, medium, time)treatment, medium, time)

How to diagnose How to diagnose Radiology Radiology

CT shows high or variable attenuationCT shows high or variable attenuation MRI T1, Mucosal lining high signalMRI T1, Mucosal lining high signal MRI T2 Fungal infection; voidMRI T2 Fungal infection; void

How to diagnose How to diagnose Radiology Radiology

CT shows calcificationCT shows calcification

How to diagnose How to diagnose HistologyHistology

Onion skin layering Onion skin layering of fungal masses of fungal masses (HE)(HE)

Aspergillu Fumigatus, Aspergillu Fumigatus, fruit head, spores fruit head, spores and hyphae (PAS)and hyphae (PAS)

Silver stainingSilver staining

Observe; Histology on mucus

How to diagnose How to diagnose ImmunologyImmunology

Skin Prick testSkin Prick test Serum IgESerum IgE RAST (specific IgE)RAST (specific IgE) ISH ISH (Aspergillus and Penicillum rRNA)(Aspergillus and Penicillum rRNA)

Specific IgE in mucus?Specific IgE in mucus?

Diagnostic criteria Diagnostic criteria (summary)(summary)

CSCS (with Nasal polyposis) (with Nasal polyposis) Histological evidence of Histological evidence of

eosinophilic mucuseosinophilic mucus Positive fungal stain and / or Positive fungal stain and / or

positive culturepositive culture Type I hypersensitivity (skin or RAST)Type I hypersensitivity (skin or RAST) Typical Radiological findingsTypical Radiological findings

TreatmentTreatment

SurgerySurgery Topical steroidsTopical steroids Systemic steroidsSystemic steroids Anti-fungal therapy Anti-fungal therapy (amfotericin B or (amfotericin B or

itraconazole)itraconazole)

ImmunotherapyImmunotherapy Anti-HistaminesAnti-Histamines Anti-LeukotriensAnti-Leukotriens Anti-IgE?Anti-IgE?

Systemic steroidsSystemic steroids

Start with 1 mg/kg/day of Start with 1 mg/kg/day of prednisoneprednisone

Taper down to 5 - 10 mg per Taper down to 5 - 10 mg per dayday

Forever !?Forever !?

Immunotherapy Immunotherapy (Folkers 1998)(Folkers 1998)

22 patients with AFS, surgery and 22 patients with AFS, surgery and steroids and antibiotics.steroids and antibiotics.

11 patients specific immunotherapy 11 patients specific immunotherapy for 33 monthsfor 33 months

Significant improvement in Sinus Significant improvement in Sinus specific QoL, endoscopic scoring specific QoL, endoscopic scoring and less use of steroidsand less use of steroids

Symptom improvement maintained Symptom improvement maintained after cessation of IT (2000)after cessation of IT (2000)

Pediatric AFSPediatric AFS

Does not differ from adults, Does not differ from adults, Avoid long-term systemic Avoid long-term systemic

steroidssteroids

SammanfattningSammanfattning

Allergisk, infektiös eller båda?Allergisk, infektiös eller båda? Incidens i Sverige?Incidens i Sverige? Diagnoskriterier?Diagnoskriterier? Hur skall AFS behandlas?Hur skall AFS behandlas? Hur misstänksamma skall vi Hur misstänksamma skall vi

vara i refraktära fall av sinuit?vara i refraktära fall av sinuit?

Allergic Mucin Sinusitis Allergic Mucin Sinusitis without Funguswithout Fungus

Eosinophilic Mucin RhinosinusitisEosinophilic Mucin Rhinosinusitis Ferguson, Laryngoscope 1998Ferguson, Laryngoscope 1998

To sum upTo sum up

Allergic, Infectious or both?Allergic, Infectious or both? Incidens in Sweden?Incidens in Sweden? High Suspicion in Refractory casesHigh Suspicion in Refractory cases How to diagnoseHow to diagnose Which treatment? Skin prick test Which treatment? Skin prick test

available?available?