INCIDENCE AND PRESENTATION OF ALLERGIC FUNGAL RHINOSINUSTIS (AFRS)

IN PATIENTS DIAGNOSED WITH CHRONIC RHINOSINUSITIS.

INTRODUCTION:
Allergic fungal rhinosinusitisis defined as immunocompetent patients with an allergy to
fungus.The fungi which are the cause of the hypersensivity reside in the mucin &
provide continued stimulation.
1
AFRS was first reported as a distinct clinical entity in
1976
2
. AFRS is coupled with the clinical entity of fungus ball (mycetoma) as a form of
non-invasive fungal sinus disease, separate from & unrelated to invasive fungal sinus
pathology. AFRS is a truly unique pathologic entity, defined largely by the presence of
allergic fungal mucin , which is a thick ,tenacious eosinophilic seceration with
characteristic histologic findings.
The diagnostic criteria are still under debate. However in 1994,Bent & Kuhn published
their diagnostic criteria based on histologic , radiographic and immunologic
characteristics of disease
3
.The major criteria included type 1 hypersensivity , nasal
polyposis, characteristic CT-scan findings, esoinophilic mucin without invasion ,positive
fungal stain while minor criteria included asthma , unilateral disease , bone erosion ,
fungal cultures, charcot-leyden crystals & serum eosinophilia.
Approximately 7% of all CRS cases requiring surgery have been diagnosed as AFRS in
UK
4
.The overall incidence of AFRS is estimated at 5% to 10% of all patients with
CRS
5
.Patient with AFRS commonly presents with CRS with naal polys,inhalant atrophy,
elevated total serum immunoglobulin E (IgE level) & sinus obstructing inspissates of a
characteristic extramucosal peanut buttery eosinophil-rich material called allergic
mucin
6,7
.Allergic mucin typically culture as biploris spicifera or curvularia lunata or
aspergillus species such as A.fumigatus flavus or Niger
5
.However , up to 13 % of AFRS
fungal cultures return negative despite histopathologic confirmation of AFRS
8
.Treatment
options to achieve relief from symptoms of AFRS included avoidance measures , oral
antihistamines , corticosteroids nasal spray , leukotrienes receptor antagonists and
allergen immunotherapy
9
.
RATIONALE
The rationale of this study is to determine various presentations of patients
with AFRS who were initially treated as CRS.& to explore the characteristics of
Allergic fungal rhinosinusitis occurring in our part of country. The result of this
study would help us to detect patients with AFRS early and help to start early
directed treatment.


OBJECTIVE : TO DETERMINE INCIDENCE AND PRESENATION OF ALLERGIC FUNGAL
RHINOSINUSTIS IN PATIENTS DIAGNOSED WITH CHRNOIC RHINOSINUSTITIS
OPERATIONAL DEFINATIONS;
Allergic Fungal Rhinosinusitis; immunocompetent patients with allergic to fungus.
BENT AND KUHN DIAGNOSTIC CRITERIA;
MAJOR MINOR
Type 1 hypersensivity Asthma
Nasal polyposis Unilateral disease
Characteristic CT findings Bone erosion
Eosinophilic mucin without invasion Fungal culture
Positive fungal stain Charcot-leyden crystals
Serum eosinophilia

1. TYPE 1 HYPERSENSIVITY: Determined by serum IgE level (>1,000U/mL)

2. Nasal Polyposis; Diagnosed by anterior rhinoscopy , nasal endoscopy /CT-scan
findings.

3. CT-scan findings; will be demonstrate unilateral or asymmetric involvement of
sinus , presence of double density sign , presence of bone erosion/expansion of
the fungal mucin .The remodeling & thining of bony walls specially of orbit .

4. Eosinophilic mucin without invasion; Determined by histopathological
specimen
eosinophilic mucin without invasion.
5. Positive fungal stain; It will be taken as positive if the mucin take chondroid
appearance with sheets of eosinophils frequently with the presence of esophilia
breakdown products or charcot- leyden crystals that can easily be seen with H&
E staining.
6. FUNGAL CULTURES; will be done for following fungus;
For aspergillus : Aspergillus species are reliably demonstrated by silver stains, e.g.,
Gridley stain or Gomori methenamine-silver. These give the fungal walls a gray-black
colour. The hyphae of Aspergillus species range in diameter from 2.5 to 4.5 m. They
have septate hyphae,even one hyphea will be taken as positive.



For curvularia:
PCR amplification of the internal transcribed spacer (ITS) region specific to Curvularia
lunatus and subsequent sequencing of the PCR amplification product will be used to
identify.
For Bipolaris spicifer : Histological examinations of formalin-fixed and paraffin-
embedded tissue and mucus samples will be performed. Hematoxylin and eosin (H&E)
staining will reveal inflammatory sinonasal polyps and clusters of eosinophilic
granulocytes within the mucus. Gomoris methenamine silver (GMS) staining will show
separate fungal hyphea within the mucus, where the hyphae will be impacted or
embedded within the clusters of eosinophils.
Chronic rhinosinustitis : is rhinosinusitis of atleast 12 consecutive weeks duration.For
diagnosis of rhinosinusitis sign and symptoms requires two major factor, or one major
and two minor factor.

MAJOR SYMPTOMS MINOR SYMPTOMS
Nasal obstruction/blockage Headache
Nasal discharge /purulence/discoloured
posterior drainage
Halitosis
Hyposmia/anosmia Fever(non acute)
Purulence on nasal examination Fatique
Facial pain/pressure Dental pain
Facial congesion cough
Fever(acute RS) only Ear pain/pressure/fullness


All the above mentioned symptoms will be asked and noted in pre- designed pro
forma .



MATERIAL AND METHORS;
Department of ENT Head & Neck surgery and Department of Histopathology,
Liaquat National Hospital, Karachi.
DURATION OF STUDY;
One year after the approval of synopsis by the CPSP.
STUDY DESIGN;
Cross-sectional study.
SAMPLE TECHNIQUE: Non-Probability consecutive sample technique
SAMPLE SIZE;
By using WHO calculator, taken prevalence of AFRS p=7%, margin of error
(d)=5 %,level of significance alpha=5% the estimated sample size will be at
least n = 101


SAMPLE SELECTION;

Inclusion Criteria:
1. All patients full filling Bent and Kuhn diagnostic criteria as defined in operational
definition
2. Either gender
3. Urban and rural population
4. Age 10-50
5. Patients presenting with chronic rhinosinusitis fulfilling major and minor criteria
as defined in operational definition.











Exculsion Criteria:
1. Patients on steroids, diabetes mellitus or immune compromised will not be
included in the study.
2. Cases of Acute sinusititis, nasopharyngeal carcinoma, foreign body will not be
included in the study.
3. All fungus showing invasion will not be included e.g. granulomatous & non
granulomatus , myotic infilteration of fungus in mucus membrane as seen in
histopathology sample.





DATA COLLECTION TECHNIQUE:

After the approval of synopsis from CPSP, patients who will be presenting in OPD of
ENT- Head & Neck department of liaquat national hospital with chronic rhinosinusitis
diagnosed on basis of history, examination, nasal endoscopy, CT-scan findings will be
enrolled in the study. An approval from ethical and review committee will be taken
before commencement of the study. Verbal and written consent will be taken from each
patient. Patients demographic data, clinical sign and symptoms , detailed examination
and CT-scan findings will be recorded by the principle investigators. Nasal biopsy will be
taken from patients diagnosed with CRS and immedialy sent to well equipped and 24
hours working histopathology laboratory of Liaquat National Hospital.fungal will be
isolated and subjected to different staining such as aspergillus will be stained by silver
stainse.g.gridley stain and even one fungal hypae will be taken as positive. Similarly for
curvularia PCR amplification of the internal transcribed spacer (ITS) region will be used
to identify. For Bipolaris spicifer ,histological examinations of formalin-fixed and paraffin-
embedded tissue and mucus samples will be performed. Hematoxylin and eosin (H&E)
staining will reveal inflammatory sinonasal polyps and clusters of eosinophilic
granulocytes within the mucus.The histopathological result will be confirmed by the
senior histopathologist and by researcher herself.
Confunding variables as well as bias will be controlled by strictly following the inclusion
and exclusion criteria.All the data will be entered into the pre-designed proforma.












DATA PROCESSING & ANALYSIS:

Data will be compiled and analyzed in a Statistical Package of Social Sciences(SPSS)
version 17.The descriptive analysis will be calculated. The quantitative variable
e.g.age,gender,residential area will be presented throught mean +-SD.The incidence &
presentation of patients with AFRS will be calculated for qualitative variable i.e. nasal
polyp, nasal obstruction, anosmia, presence of fungi (aspergillus).Stratification of age,
gender, AFRS, will be done to see effect of these modifiers by using Chi square test
considering p <_ 0.05.


REFERENCES:
1. Gleeson M,Browning GG.BurtMJ,Clarke ,R,Hibbert,J,NicholasS,et al.Scott browns
otorhinolaryngology,Head and Neck surgery,7
th
ed.London:Hodder
Arnold;2008.p.11452

2. Safirstein BH. Allergic bronchopulmonary aspergillosis with obstruction of the upper
respiratory tract. Chest. 1976 Dec;70(6):788-90.

3.Bent JP 3
RD
, Kuhn FA, Diagnosis of allergic fungal sinusitis Otolaryngol Head Neck
Surg 1994;111(5):580-588

4.Ferguson BJ.Defination of fungal rhinosinusitis .Otolaryngologic clinics of North
America .2000;33:227-35

5. Glass D,Amedee R.G.Allergic fungal rhinosinusitis:A review.The Oschnser Journal
2011:11:271-275

6. Michael RC, Michael JS, Ashbee RH, Mathews MS Mycological profile of fungal
sinusitis: An audit of specimens over a 7-year period in a tertiary care hospital in Tamil
Nadu. Indian J Pathol Microbiol. 2008 Oct-Dec;51(4):493-6.

7. Khan AR, Ali Farman, Din SE, Khan NS and Dawar A.Frequency of Allergic Fungal
Chronic Rhinosinusitis.Pak J of Otolaryngol 2011; 27: 12-14.





8. Azar S, Mansour B, Parivash K and Babak B; Fungal Rhinosinusitis in Hospitalized
Patients in Khorramabad, Iran Middle-East Journal of Scientific Research 7 (3): 387-
391, 2011

9.Kamal MS, Ahmed KU,Humayan P, Atiq T, Hossain A & Rasel MA.Association
between allergic rhinitis and sinonasal polyposis . Bangladesh Journal of
Otorhinolaryngology Vol 17, No 2 (2011) .







































PROFORMA

INCIDENCE AND PRESENTION OF ALLERFIC FUNGAL RHINOSINUSITIS IN
PATIENTS DIAGNOSED WITH CRONIC RHINOSINUSITIS.
Name __________________ AGE_____ MR#__________ TEL #_____________
ADDRESS_____________ ETHINICITY__________
HISTORY:
1) NASAL OBSTRUCTION: Y/N___ IF YES, UNILATERAL _____BILATERAL______,
INTERMITTENT_________, PERSISTENT__________.
2) NASAL DISCHARGE Y/N , IF YES COLOUR_________.
3) FACIAL PAIN, Y/N________4) HYPOSMIA Y/N ________
5) FEVER Y/N____________6) FACIAL HEAVINESS Y/N
7) VISISON LOSS Y/N _________8) PURULENCE ON NASAL EXAMINATION
Y/N____
9) HALITOSIS Y/N______10) DENTAL PAIN Y/N_____11) COUGH Y/N _______
12) ASTHMA Y/N________

CLINICAL EXAMINATION:
1) DEVIATED NASAL SEPTUM Y/N_______
2) POLYP Y/N_________ UNILATERAL_______ , BILATERAL ________,
3) TURBINATE HYPERTROPHY Y/N_______________
4) EXTERNAL NASAL DEFORMITY Y/N_______
5) PROPTOSIS Y/N__________
6) TELECANTHUS Y/N_____________
RADIOLOGICAL INVESTIGATIONS
CT-SCAN FINDINGS: RT LFT
MAXILLARY SINUS(0-2)
ANTERIOR ETHMOID(0-2)
POSTERIOR ETHMOID(0-2)
OSTIOMEATAL COMPLEX (0-2)
SPHENOID(0-2)
FRONTALS (0-2)
**CT-SCAN SCORE 0= no abnormality 1=partial opacification 2= total opacification
LABORTARY INVESTIGATIONS :
1) Serum IgE LEVEL: ________________
2) POSITIVE FUNGAL STAIN /CULTURE Y/N, IF YES THEN
1)ASPERGILLUS_______2)BIPOLARIS_____________3)CURVULARIA________

ENDOSCOPIC FINDINGS; (SELECT ONE)
STAGE 0: NO MUCOSAL EDEMA OR ALLERGIC MUCIN _________
STAGE 1 MUCOSAL EDEMA WITH OR WITHOUT ALLERGIC MUCIN___________
STAGE 2 POLYPOID EDEMA WITH OR WITHOUT ALLERGIC MUCIN ___________
STAGE 3 SINUS POLYPOSIS WITH FUNGAL DEBRIS OR ALLERGIC MUCIN










CONSENT FORM

The undersigned patient and/or responsible relative or person here by consent to & authorize
Liaquat National Hospital and medical personnel to perform medical examination, ear culture &
sensitivity investigations.



The undersigned also consent to the use of medical information for research purpose.



The undersigned also consent to the Hospital contacting him/her if needed regarding
appointment & follow up as required.






____________ ______________
Signature of Signature of
Witness Patient/Guardian
Dated: