INTRODUCTION

The ascent of man has been accompanied by the birth of science,

resulting in the emergence of various inventions and discoveries. The
concomitant development of sophisticated technology coupled with
mankinds thirst for knowledge and his curiosity to seek the ultimate truth
has enabled him to diagnose and treat serious diseases previously
thought to be incurable.
However certain diseases continue to prove a challenge to him.
One such condition is fungal infection. More than ever, fungal diseases
have emerged as a major challenge for physicians, clinical microbiologists
and scientists. The incidence of mycotic infection and the number and
diversity of pathogenic fungi have increased dramatically in the recent
years. Both imrnunocompetent and immunocompromised individuals are
at risk.
The growing breadth, complexity and significance of mycological
disease needs an in depth study of treatment of fungal rhinosinusitis that is
increasing in incidence and often difficult to diagnose and manage.
Fungal rhinosinusitis follows inhalation of fungal spores into the
nasal passages. Occasionally, however the fungal cells can invade from
the pre-existing infection in the lungs or elsewhere in the body. Most
infections of the sinuses affect not only the paranasal sinuses but also the
nose.

The American academy Of Otolaryngologys task force on

rhinosinusitis

suggested

the

term

rhinosinusitis

more

accurately

describing the disease process than the term sinusitis. A number of

conditions and disease modalities are recognized to increase susceptibility
to mycotic infections. In general, people with impaired cell mediated
immunity are more susceptible to mycotic infections. This condition may
be congenital or induced by other diseases such as AIDS, Diabetes
mellitus or hematogenous dyscrasias or by administration of cytotoxic
drugs to manage cancer or transplantation. It is important to classify fungal
rhinosinusitis to accurately predict diagnosis and optimize effective
therapy.
In 1997, deShazo classified it into invasive and non-invasive forms. 1
Then he characterized five major types .The first of the non-invasive forms
were allergic fungal sinusitis as well as sinus fungal ball. Of the invasive
forms the most common form is what he described as acute or fulminant
invasive sinusitis. Then he described chronic invasive fungal rhinosinusitis,
and finally granulomatous invasive fungal rhinosinusitis. All these
manifestations overlap or progress from a non-invasive form to an invasive
form, if the immunogenic status of the patient changes. This prognosis is
less dependent on a particular fungus causing the infection than on
immunogenic status of the host.
Knowledge of fungal organisms is important in directing appropriate
antifungal therapy and possibly in selecting the correct antigens for postsurgical immunotherapy in allergic fungal rhinosinusitis. For the diagnosis
of fungal rhinosinusitis, a thorough clinical examination, KOH mount of
2

nasal discharge, fungal cultures, histopathological examination, serological

and skin tests and coronal CT scans of the patients are necessary. Various
approaches to manage fungal rhinosinusitis include surgical debridement,
topical and systemic corticosteroids, topical and systemic antifungals and
immunotherapy.
This study aims at highlighting the presently available modalities of
treatment depending upon the type of fungal infection and host-immune
status.

AIMS AND OBJECTIVES

The study was carried out with the following aims in mind.
1. To carry out a clinical study of fungal rhinosinusitis in its various
presentations.
2. To correlate various factors pertaining to etiology of the disease with
reference to:
Age
Sex
Predisposing factors
Immunological status
3. To evaluate the criteria for selection of patients for surgery.
4. To study various treatment modalities.
5. To compare and evaluate the efficacy of various medical and surgical
treatment modalities in our tertiary health-care centre.

ANATOMY OF NOSE AND PARANASAL SINUSES2

External nose is a surface projection of the face. It is a triangular
pyramid shaped structure with its root above and base directed
downwards. The nose has two openings, the anterior nares separated by
the columella. The apex is connected to the root by septum, upper part of
which is termed bridge. Each side of the nose ends in a rounded
eminence, the ala-nasi which forms the outer boundary of anterior nares.
The supporting framework of external nose consists of a bony
pyramid and a number of paired and unpaired cartilages. The bone
consists of the anterior part of the body of maxilla with its frontal process,
the nasal spine of frontal bone and the nasal bones. The cartilages which
complete the framework of the nose are a single central septal cartilage,
two upper nasal cartilages and two lower nasal alar cartilages.
The muscles bringing about the movement of the ala and the lower
part of the septum are the procerus, the nasalis consisting of a transverse
part (compressor naris) and an alar part (dilator naris); and the depressor
septi. The muscles are either attached to the cartilage, or pass across the
nose from the maxilla to a central aponeurosis. The muscles are
rudimentary in man. The upper buccal branches of facial nerve innervate
all of the above muscles. The skin of the dorsum and sides of the nose is
thin and loosely connected with the subjacent part; but over the ala it is
thicker and more firmly adherent, and is furnished with numerous large
sebaceous glands, the orifices of which are usually very distinct.

Nasal cavity:
It extends from the external nares or nostrils to the posterior
choanae, where it becomes continuous with the nasopharynx and is
narrower anteriorly than posteriorly. Vertically it extends from the palate to
the cribriform plate, being broader at its base than superiorly where it
narrows at the olfactory cleft. The nasal cavity is divided in two by a
septum. Each half has a floor, a roof, a lateral wall and a medial (septal)
wall.
Floor:
The floor is concave from side to side, anteroposteriorly flat and
almost horizontal. Its anterior three quarters are composed of palatine
process of maxilla, its posterior one quarter by the horizontal process of
the palatine bone. About 12 mm behind the anterior end of the floor is
slight depression in the mucosa overlying the incisive canals. It contains
the terminal branches of the nasopalatine nerve, the greater palatine
artery and a short mucosal canal (Stensons organ).
Roof:
The roof is narrow from side to side, except posteriorly and may be
divided into frontonasal, ethmoidal and sphenoidal parts, related to the
respective bones. As both the sphenoidal and frontonasal parts of the roof
slope downwards, the highest part of the nasal cavity relates to the
cribriform plate of the ethmoid which is horizontal. This area is covered by
olfactory epithelium (Schneiderian membrane) which spreads down a little

distance onto the upper lateral and medial walls of the nasal cavity. The
rest of the nasal cavity (with the exception of the nasal vestibule) is lined
by respiratory mucous membrane and is continuous with that of the
paranasal sinuses, nasolacrimal duct and nasopharynx.
Nasal septum:
The nasal septum is composed of a small anterior membranous
portion, a single quadrangular cartilage and several bones: the
perpendicular plate of ethmoid, the vomer and two bony crests of maxilla
and palatine bones.
The cartilaginous portion is composed of a quadrilateral cartilage
with a contribution from the lower and upper lateral alar cartilages forming
the anterior nasal septum. Its upper margin is expanded and connected to
the upper lateral cartilages, forming the anterior septal angle, just cranial
to the domes of the lower lateral cartilages. It abuts the maxillary spine at
the inferior septal angle. Anteriorly, it is attached by a thin membranous
septum to the medial crura of lower lateral cartilages.
The perpendicular plate of the ethmoid forms the superior and
anterior bony septum and is continuous above with the cribriform plate and
crista galli. The vomer forms the posterior and inferior bony nasal septum
and articulates by its two alae with the rostrum of sphenoid. The inferior
border of the vomer articulates with the nasal crest formed by the maxillae
and palatine bones. The anterior border articulates with the perpendicular
plate above and the quadrilateral cartilage inferiorly. The posterior edge of
the vomer forms posterior free edge of the septum.
7

The lateral nasal wall:

Inferior meatus:
Inferior meatus is that part of the lateral wall of the nose which lies
lateral to the inferior turbinate. 3It is the largest meatus extending almost
the length of the nasal cavity. The meatus is highest at the junction of the
anterior and the middle third. In adults this ranges from 1.6 to2.3mm at
1.6cm along the bony lateral wall. The nasolacrimal duct opens into the
inferior meatus usually just anterior to its highest point. 4 There is no true
valve, the opening being guided by small folds of mucosa. It can be
identified by gentle massage of the lacrimal sac at the medial canthus.
Inferior turbinate:
This structure is composed by a separate bone, the inferior concha
which has an irregular surface and is perforated and grooved by the
vascular channels to which the mucoperiosteum is firmly attached. The
bone has a maxillary process which articulates with the inferior margin of
the maxillary hiatus. It also articulates with the ethmoid, palatine and
lacrimal bones, completing the medial wall of the nasolacrimal duct.
Middle meatus:
The middle meatus is that portion of the lateral wall lying lateral to
the middle turbinate. It receives drainage from the frontal, maxillary and
anterior ethmoidal sinuses.

Middle turbinate:
The middle turbinate is much larger and extends from atrium to the
level of choana. It is crucial to understand the anatomy of the ethmoid
complex. Most anteriorly the turbinate attaches to the maxilla just anterior
to which is the bulge of the agger nasi. The anterior third attaches to the
skullbase vertically at the lateral border of the cribriform niche with the
frontal bone forming the root of the ethmoids. The posterior third attaches
horizontally to the lamina papyracea and the medial wall of the maxilla.
Between the two portions of the turbinate, there is an obliquely disposed
plate of bone, the basal lamella of the middle turbinate, attaching laterally
to the lamina papyracea.
The uncinate process:
This thin crescent of bone curves posteriorly, parallel to the curve of
the anterior face of the ethmoidal bulla.
Hiatus semilunaris:
The Hiatus semilunaris is a two dimensional space lying between
the posterior edge of the uncinate process and the anterior surface of the
ethmoidal bulla.
Ethmoidal infundibulum
The ethmoidal infundibulum is a three dimensional funnel
connecting the natural ostium of the maxillary sinus to the middle meatus
via the Hiatus semilunaris. The natural ostium of the maxillary sinus lies at
the floor of the ethmoidal infundibulum, usually at its middle and posterior
9

third so is not usually visualized until the uncinate process has been
removed.
The frontal recess:
The frontal recess is found in the anterosuperior-most portion of the
middle meatus. The term frontonasal duct has been generally abandoned
as no true duct exists histologically or topographically in most people. The
natural ostium of frontal sinus is somewhat variable in its configuration but
most frequently it presents as an hourglass narrowing opening directly into
the recess.
The ethmoidal bulla:
This is one of the most constant features in the middle meatus
containing the anterior ethmoidal cell but it may be poorly aerated or
completely unpneumatised in 8% of patients. 5 The anterior face forms the
posterior margin of the Hiatus semilunaris and ethmoidal infundibulum.
Posteriorly the bulla may fuse with the basal lamella of the middle
turbinate and superiorly it may reach the roof of the ethmoids forming the
posterior wall of the frontal recess.
Superior meatus:
This meatus is again defined by its relation to the superior turbinate.
The posterior ethmoidal cells open into this region.

10

Supreme turbinate:
A Supreme turbinate is discernible above the superior meatus in 6067%of patients.
Sphenoethmoidal recess:
Sphenoethmoidal recess lies medial to the superior turbinate and is
the location of the ostium of the sphenoidal sinus.
The Maxillary sinus:
The maxillary sinus is the largest of the paranasal sinuses. It is a
pyramidal cavity within the body of the maxilla. The apex is directed
laterally and extends into the zygomatic process of maxilla. The base is
directed medially and is formed by lateral wall of the nose. Floor of the
sinus is formed by alveolar process of maxilla. The roof is formed by
orbital surface of maxilla and is ridged by canal of the infraorbital nerve.
The floor lies about 1-1.2cms below the level of nasal cavity in
adult. The average measurements are height 3.5cms, breadth2.5cms and
depth 3.2cms.The sinus communicates with the lower part of the hiatus
semilunaris through an opening in the anterosuperior part of its base.
Accessory ostia if present lie behind the main one.
The Ethmoidal sinus:
It consists of number of thin walled cavities within the lateral
masses of ethmoid bones, and sometimes in agger nasi and middle
turbinate. The ethmoidal sinus is divided into anterior and posterior cell

11

groups by the basal or ground lamella of the middle turbinate. Cells

anterior to the middle meatus are generally smaller and open into middle
meatus, whereas the larger cells open posteriorly through the superior or
supreme meatus into the sphenoethmoidal recess. The anterior cells are
generally smaller and more numerous (2-8) than the posterior group (1-5).
The largest form the bulla ethmoidalis and most anterior cells form the
agger nasi opening directly into the middle meatus. The posterior cells are
large and pyramidal in shape, pointing towards the orbital apex. They are
closed posteromedially by the sphenoid bone.
The posterior-most ethmoidal cells can extend supero-lateral to the
sphenoid upto 1.5cms posterior to the anterior wall of sphenoid. This
configuration was originally described by Adolf Onodi in 1903, and bears
his name. The ethmoidal cells may pneumatise the orbital floor, forming
Haller cells which can encroach upon the ethmoidal infundibulum.
The roof of ethmoid sinus is formed by the floor of the anterior
cranial fossa and may be horizontal or sharply down-sloping medially. The
floor of the anterior cranial fossa creates a large difference between the
height of the cribriform plate medially and the ethmoidal roof laterally. The
roof is also thin medially and may have a significant area of dehiscence
adjacent to the ethmoidal vessels.
The Frontal sinus:
The frontal sinuses are found in the frontal bone deep to the
superciliary ridges. The two sinuses are unequal in size and have the
shape of the pyramid with its apex upwards. They are separated by a thin
12

septum of bone which is seldom in midline and may occasionally be

deficient. Their average height is 2cms, breadth 2.5cms and depth 2cms.
The anterior wall is formed by diploic bone and is the thickest of the walls.
The posterior wall is thinner but is composed of more compact bone. The
floor slopes medially downwards and backwards towards the opening of
frontonasal duct. The duct runs down through the front of the ethmoidal
labyrinth and enters either the infundibulum or opens independently into
the anterior end of the middle meatus.
The Sphenoidal sinus:
They are two in number contained within the body of the sphenoid
bone and placed posterior to the upper part of nasal cavity. Laterally it is
related to the optic nerve and the cavernous sinus and its contents,
superiorly it is related to the undersurface of the frontal lobes and to the
olfactory tracts. The pituitary gland lies above and posteriorly. The sinuses
are separated by a septum which is seldom in midline, so they are rarely
symmetrical. Average measurements of the size of the adult sinus have
been given as height 2cms, breadth 1.8cms and depth 2cms. Occasionally
the sinus spreads laterally to invade the greater and lesser wing and
medial and lateral pterygoid plates of sphenoid and occasionally into the
basilar part of the occipital bone. Each sinus communicates with the
sphenoethmoidal recess in the superior meatus by an opening in the
upper part of the anterior wall.

13

Mucous membrane of Nose and Paranasal sinus:

The Mucous membrane of nose is of two types:
1. Respiratory:
This lines the lower two-third of the nasal septum, the lateral wall of
the nose below the superior turbinate and the floor of the nasal fossa. It is
pink in colour, moist and is covered by a ciliated columnar epithelium. This
consists of tall ciliated epithelium which narrows in its deeper part.
Irregular basal cells fill in the intervening spaces. Goblet cells containing
thick mucus lie among the ciliated cells. Thin fluid comes from compound
acinar secreting glands of two types, serous and mucinous. Both types of
mucus are spread thin over the epithelium and propelled by cilia at a
density of 5 million per square mm. Cilia move at 14 beat per second and
in a healthy adult the mucociliary stream carries about a pint and half of
nasal mucus to the throat every 24 hrs.
A fibroblastic basement separates the epithelium from the
subepithelial tissue, which is loose and highly vascular and contains many
mucous and serous glands. Its deeper portion is firmly blended with the
underlying periosteum and perichondrium. The respiratory membrane
extends from the limen nasi throughout the nose and into the upper half of
the nasopharynx. It also extends into the sinuses through their ostia, and
is thinner there. It is also continuous with the epithelia of nasolacrimal duct
and Eustachian tube. Above it is continuous with the olfactory mucosa of
the nose. Anteriorly at the limen nasi it becomes continuous with the skin
of the nasal vestibule.
14

2. Olfactory:
This (Schneiderian) membrane lines the upper one third of the
nasal septum, the roof of the nose, and the lateral walls above including
the superior turbinate. The olfactory epithelium is made up of non-ciliated
columnar epithelium and is yellowish in colour. It contains the serous
glands of Bowman. The cells are:
Olfactory: Bipolar-The superficial process end at the surface of the
mucous membrane in bulbous process which bears the olfactory hairs.
The central process passes to the olfactory bulb through the cribriform
plate.
Supporting.
Basal: contain yellow pigment.
Blood supply of nasal cavity and paranasal sinuses:
Arterial supply:
The blood supply of the nasal cavity and paranasal sinuses is derived from
the branches of external and internal carotid arteries.
(1) Branches of external carotid artery:
Sphenopalatine artery: via the internal maxillary artery supplies
the turbinates and meatus of the nose and most of the septum.
Greater palatine artery: a branch of maxillary artery contributes
branches to the lateral nasal wall and to the anterior part of the
septum.
15

 Superior labial artery: a branch of facial artery, sends branches to

the tip of the septum and the ala-nasi. Its anastomosis with the
branch of sphenopalatine artery and the greater palatine artery (the
artery of epistaxis) forms Kiesselbachs plexus.
Pharyngeal branches of internal maxillary artery: supplies the
sphenoidal sinus.
(2) Branches of internal carotid artery:
Anterior and posterior ethmoidal arteries: Branches of the
ophthalmic arteries. They supply the roof of the nose, anterior part of the
septum and lateral wall of the nose, and the ethmoidal and frontal sinuses.
Bleeding from these vessels is seen above the level of the middle
turbinate.

Venous drainage:
The veins form the cavernous plexus beneath the mucous membrane.
They open into Sphenopalatine vein and anterior facial vein from the plexus.
Ophthalmic veins from the ethmoidal veins.
Veins on the orbital surface of the frontal lobe of the brain, through
foramina in the cribriform plate.
Superior saggital sinus, through the foramen caecum.

16

Nerve supply of the nose and paranasal sinuses:

Autonomic nerve supply:
This controls the vascular reactions of nasal mucous membrane.
Sympathetic fibres: Postganglionic fibres pass from the superior cervical
ganglion to the plexus around the internal carotid artery. They then form
the deep petrosal nerve which with the greater superficial petrosal nerve
becomes the nerve of pterygoid canal(Vidian nerve).They are distributed
without relay via the sphenopalatine ganglion .They maintain a constant
tonic vasoconstrictor action. Section of cervical sympathetic nerves cause
vasodilatation and results in stuffy nose.
Parasympathetic fibres: These are secretomotor to the glands via
branches from pterygopalatine ganglion

Nerve supply of the paranasal sinuses:

The ethmoidal sinuses are innervated by the anterior and posterior
ethmoidal nerves and orbital branches of pterygopalatine ganglion. The
sphenoid sinuses are supplied by posterior ethmoidal nerves and orbital
branches of pterygopalatine ganglion. The frontal sinuses are supplied by
supraorbital nerve. The maxillary division of the trigeminal nerve supplies
the maxillary sinus via the infraorbital, superior alveolar and greater
palatine nerves.

17

Olfactory nerves:
The sense of smell is supplied by the 1st cranial nerve. Fibres arise
from bipolar cells in the olfactory mucosa. They are non-medullated and
pass through foramina in the cribriform plate. They enter the undersurface
of the olfactory bulb.

Lymphatic drainage of nose and paranasal sinuses:

The lymphatic vessels arise from a continuous network in the
superficial part of the mucous membrane. This is best developed at the
posterior end of the superior turbinate. Submandibular lymph nodes collect
lymph from the external nose and anterior part of the nasal cavity. Upper
deep cervical lymph nodes drain the rest of the nasal cavity, either directly
or through the retropharyngeal nodes.

DEVELOPMENT OF NOSE AND PARANASAL SINUSES

The external nose and paranasalcavity: 2
The nose develops from a number of mesenchymal processes
around the primitive mouth.6 The nasal cavity is first recognizable in the 56 mm embryo in the 4 th intrauterine week as the olfactory or nasal placode,
a thickening of the ectoderm above the stomatodeum. This placode sinks
to form the olfactory pits lying between the proliferating mesoderm of the

18

medial and lateral nasal folds of the frontonasal process. This deepens to
form the nasal sac by the fifth week.
In the 12.5 mm embryo, the maxillary process of the first branchial
arch grows anteriorly and medially to fuse anteriorly with the medial nasal
folds and the frontonasal process which closes the frontonasal pits off to
form widely separated primitive nasal cavities. The primitive nasal cavity
and mouth are separated initially by a bucconasal membrane. This
gradually thins as the nasal sac extends posteriorly and eventually breaks
down at the 14-15 mm stage to form the primitive choanae. These are
more anteriorly placed than the definitive posterior growth of the
palate.7The floor anterior to the choanae forms from the mesenchymal
extensions of the medial nasal folds to produce the premaxilla and
ultimately the upper lip and medial crus of the lower lateral cartilages.
The palate and nasal septum:
The primitive palate begins to form anteriorly with fusion of the
maxillary and frontonasal processes by the 13.5 mm stage. A midline ridge
develops from the posterior edge of the frontonasal process in the roof of
the oral cavity and extends posteriorly to the opening of Rathkes pouch.
This becomes the nasal septum which is continuous anteriorly with the
partition between primitive nasal cavities enlarge, the palatal processes
derived from the lateral maxillary mesoderm grow medially towards each
other and the septum. Initially they lie lateral to the tongue, but as this
moves ventrally with further growth the palatal processes wing medially
and fuse horizontally. The fusion begins along the posterior margin of the
19

primitive palate and is complete except for a midline dehiscence at the

future site of the incisive canal. Fusion continues between the palatal
processes and the septum from anterior to the posterior, separating the
nasal and oral cavities and most posteriorly the nasopharynx and the oral
cavity as the palatal process complete the soft palate and uvula. Failure of
fusion between a maxillary process and the corresponding premaxilla
causes a cleft lip. Non fusion between palatal process and nasal septum
results in cleft palate. Failure of the oronasal membrane to rupture results
in choanal atresia.
On either side of the anterior septum, in relation to the paraseptal
Jacobsons cartilage, an invagination of the ectoderm forms the
vomeronasal organ, which largely disappears in man leaving only a blind
tubular pouch.8
The primitive septum is initially made entirely of cartilage. The
superior part ossifies to form perpendicular plate of ethmoid and the vomer
in the posterioinferior portion, leaving the anteroinferior quadrilateral
cartilaginous plate.
The turbinate bones:
A series of elevations appear on the lateral wall of the nose from the
sixth fetal week which will ultimately form the turbinates. The most inferior
or maxilloturbinal forms the inferior turbinate. The middle, superior and
supreme turbinates result from reduction of the complete ethmoturbinal
system. The primitive nasoturbinal is represented by the agger nasi region
and the uncinate process of the ethmoid.
20

The maxillary sinus:

The maxillary sinus appears first and is initially represented as a
depression in the nasal wall below the middle turbinate. The depression
rapidly becomes a groove which grows laterally and invades the body of
the maxilla. The sinus grows in spurts associated with eruption of the
molar teeth and reaches its full size after the time of eruption of the
permanent dentition.
Ethmoid sinuses:
The ethmoidal sinuses are well delineated, fluid filled structures in a
new born child. During fetal development the anterior cells form first,
followed by the posterior cells. The cells grow gradually and are of adult
size by age 12 years. They are not seen on radiographs usually until age
of 1. Septa gradually thin and pneumatisation spreads as the child ages.
Ethmoidal sinuses are the most variable and can often be found above the
orbit, lateral to the sphenoid, into the roof of maxillary sinus, and anteriorly
above the frontal sinus. These cells have been named. A cell above the
orbit i.e. called supraorbital cell and is found in 15% patients. Invasion of
an ethmoidal cell into the floor of frontal sinus is called frontal bulla.
Extension into the middle turbinate is called concha bullosa. Cells in the
roof of maxillary sinus are called Hallers cells, found in 10% population.
These cells can obstruct the maxillary ostia and narrow the infundibulum
and result in disruption of normal sinus function. Finally a cell which
extends posterolaterally to the sphenoid sinus is called an Onodi cell

21

(10%).The common variability of these cells makes preoperative imaging

essential to determine a patients individual anatomy.
Frontal sinus:
The frontal sinus develops as an upgrowth from the diverticulum
that is to form the anterior ethmoidal sinus. Growth begins at about sixth
months of intrauterine life, but the developing sinus invades the frontal
bone within the first year after birth. The sinus grows steadily for about 10
years, but shows a more rapid growth at puberty.
Sphenoid sinus:
The sphenoid sinus appears before birth. It is small but definite
cavity at birth. After five years it invades the pre-sphenoid bone and there
are successive periods of rapid growth at about age of 10 years and later
at puberty.

22

PHYSIOLOGY OF NOSE AND PARANASAL SINUSES9

The principle functions of the nose and paranasal sinuses are following1. Respiratory channel.
2. Heat exchange
3. Humidification
4. Filtration and ciliary mechanism
5. Nasal resistance
6. Nasal neurovascular reflexes
7. Voice modification
8. Olfaction
The main function of the nose is to purify the inspired air, so as to make it
ideal for gaseous exchange inside the alveoli.
1. Respiratory channel:
The nasal passage constitutes the uppermost part of the conducting
passages along which the ventilation of the pulmonary alveolar surface is
maintained. They serve as a natural airway, distinct from the buccal cavity,
enabling respiration to proceed during mastication.
The tidal air drawn in and forced out through the nose in the
inspiratory and expiratory phases of normal respiration appears to traverse
in the main, fairly well defined pathways through the nasal passages.

23

The inspired air entering through the anterior nares is directed

upwards in the narrow stream medial to the middle turbinate and then
downwards and backwards in high parabolic curves. The stream fans out
somewhat as it traverse the posterior choanae. In expiration the air enters
the choana from the nasopharynx and follows the same route, as do the
inspiratory air currents. Anteriorly on meeting the constriction at upper limit
of the vestibule the air current divides. A portion passes through the nostril
and the remainder forms a large central eddy, whirling back through the
inferior meatus and rising to join the main stream from the nasopharynx.
Part of this central eddy passes under the middle turbinate.
2. Heat exchange:
The temperature of the inspired air can vary from -50deg C to
50deg C. The different racial groups have become modified to suit the
local ambient temperatures. The rich vascular arrangements of the nasal
mucosa allow the inspired air to be warmed in its passage through the
nose. The extensive plexus, especially in the inferior turbinates, provide an
efficient radiating system.
3. Humidification:
Adequate saturation of the inspired air is essential for the
maintenance of the efficient functioning and the integrity of the ciliated
epithelium. Moisture is also essential for the proper cleaning of the
pharyngeal mucosa and for the protection from drying of the lining of the
pulmonary alveoli.

24

It is generally assumed that the water for humidification comes

directly from the capillaries through the surface epithelium. However the
fluorescent studies showed that except during acute inflammation, little
water comes directly through the surface epithelium. Water comes from
the serous glands, which are extensive throughout the nose. Additional
water is extracted from the expired air, the nasolacrimal duct and the oral
cavity.
The relatively small nasal cavities achieve nearly full saturation of
the inspired air with remarkable efficiency, which becomes 75-95%
saturated in the nose. It has been shown that the daily volume of
secretions and transudate is about 1litre. Some 700 ml are used in
saturating the inspired air; the excess is used in the ciliary cleaning
processes and is finally swallowed.
4. Filtration and ciliary mechanism:
The nose is able to remove particles of 30 micrometer or more from
the inspired air. The inspired air changes direction by 180 degree in
passage through the nose and during this period the velocity decreases
considerably as a consequence of the nasal valve. Turbulence
encountered in the flow increases the deposition of the particles. Fine
particles including bacteria stick to the mucus over the cilia, which is
impelled as a continuous conveyer belt into the nasopharynx when they
are swallowed. Lysozymes are bacteriolytic enzymes found in the nasal
mucus and tears. Lactoferrin produced by glandular epithelium is
responsible for removing the heavy metal and by this they prevent the
25

growth

of

the

certain

bacteria,

particularly

Staphylococcus

and

Pseudomonas. Reflex sneezing helps to expel the inhaled foreign

particles.
A

number

of

different

anti-proteases,

phospholipids

and

triglycerides are present. Their exact function is unknown. All components

of complements have been identified in the nose. It has a variety of
functions including the lysis of microorganisms and enhancement of
neutrophilic functions as well as leucotaxis.
All classes of irnmunoglobulins are found in the nasal secretions.
IgA and IgE have been found in greater quantities than in serum.
5. Nasal resistance:
Narrowest part of the nose is the nasal valve, which physiologically
is less well defined than the anatomical structures, which constitute it. It
comprises the lower edge of the upper lateral cartilage, the anterior end of
the inferior turbinate and the adjacent nasal septum, together with the
surrounding soft tissues. The nasal resistance is high in infants as they are
obligate nose breathers at least initially. Adults breathe preferentially
through the nose at rest even though significant resistance occurs there.
The resistance is important during expiration since the positive pressure is
transmitted to the alveoli and keeps the lungs expanded.
6. Nasal neurovascular reflexes:
The nasal mucous membrane is the specific receptive field for a
large variety of reflex responses affecting particularly the alimentary,
26

cardiovascular and respiratory system. The reflexes may be broadly

divided into two groups, according to the receptors and afferent nerves
involved. They are olfactory and trigeminal. The olfactory group of reflexes
follows stimulation of olfactory receptors and influences chiefly the
secretions of salivary, gastric and pancreatic glands.
The second group includes reflex responses of receptors by touch,
pressure, temperature, pH and chemical irritant. Trigeminal neurons form
the afferent limb of these reflex arcs. These nasal reflexes include, among
others, reflex changes in pulmonary ventilation, changes in laryngeal and
bronchial muscle, and changes in heart rate and blood vessels. The
sneeze is a physiological neuromuscular response to irritation and
autonomic alteration, central nervous system seizures or paroxysmal
psychological response.
7. Voice modification:
The voice is produced by modifying the vibrating column of air from
the Slarynx. The larynx produces the vowel sounds and the pitch of the
voice. High frequency sounds, the consonants, are added by the pharynx,
tongue, lips and teeth. The nose adds quality to this by allowing some air
to escape through it. The sound resonates within the nose and mouth.
8. Olfaction:
Olfactory function of the nose is very complicated. Olfactory
components must contact the nasal mucosa in order to produce a smell
and have to be soluble in water and lipids The human has 200-400 square

27

mm of sensory epithelium with a cellular density of about 5x10 4 receptor

cells per square mm. Odours are accepted into the water fraction of mucus
and the lipid reacts with the lipid bilayer of the receptor cells at specific
sites. This causes K+ and Cl- to flow out and thereby depolarize the
sensory cells. After a latent period of 400ms, a low compound action
potential may be recorded from the olfactory mucosa which Ottoson called
the electro-olfactogram.
Olfaction is important in regulating behavior in all animals. Smell is
used in four main areas of behavior: the detection and consumption of
food, recognition, territorial marking and sexual behavior.

FUNCTIONS OF PARANASAL SINUSES:

The physiology and function of paranasal sinuses has been the
subject of much research. Multiple theories of function exist. These include
the functions of warming, humidification of air, assisting m regulation of
intranasal pressure and serum gas pressures, contributing to immune
defense, increase mucosal surface area, lightening the skull, giving
resonance to the voice, absorbing shock and contributing to facial growth.
The nose is an amazing humidifier and warmer of air. Even at 7 litres per
minute of air flow the nose has not reached its maximum ability to perform
this function. Nasal humidification has been shown to contribute as much
as 6.9 mmHg on serum p02. Although the nasal mucosa is best adapted
to perform this task, the sinuses contribute to mucosal surface area and
warming ability.
28

Because of the copious mucus production the sinuses contribute

heavily to the immune defense performed by the nose. The nasal and
sinus mucosa is ciliated and functions to move mucus. The thickened
superficial layer of nasal mucus serves to trap bacteria and particulate
matter in a substance rich with immune cells, antibodies and antibacterial
proteins. The underlying layer is much thinner and serves to provide a
thinner substrate in which the cilia are able to beat. Unless obstructed by
disease or anatomical variance, the sinuses move mucus through their
cavities and out of their ostia towards the choanae. The most recent
research on sinus function has focused on molecule nitrous oxide (NO).
Studies have shown that the production of intranasal NO is primarily in the
sinuses. NO has been toxic to bacteria, fungi and viruses at levels as low
as 100ppb.Nasal concentration of this substance can reach upto
30,000ppb. NO has also been shown to increase ciliary motility

29

REVIEW OF LITERATURE
The study of nose is as old as civilization. Prominent structure being
in the middle of nose has acquired a unique status socially, sexually,
aesthetically and physiologically. Various conditions affecting its structure
and function have been documented in Edwin Smith Papyrus in
hieroglyphic script, an Egyptian writing system of the mid 4th Millennium
BC. The major contribution for the complete reconstruction of the nose
originated in India by Shushruta in and around 600 BC. He discovered
Netiyantra to examine the nose. Greek physicians, Hippocrates and
Galen, and at the birth of Christianity, Celsus wrote eight books of medical
encyclopedia,

which

described

various

conditions

affecting

nose.

Hippocrates in 460 BC described sponge method of nasal polypectomy.

The presence of paranasal sinuses is documented in ancient Egypt.
Sinus surgery probably originated there as instruments were used to
remove brain through the ethmoidal sinuses as a part of mummification
process.
Andreas Vesalius in 1537 described maxillary sinus as an air
containing cavity. Highmore named it as Antrum of Highmore in 1651. Pere
Dionis described first nasal speculum in 1714. A New York surgeon
George Caldwell in 1893 described the procedure of entering the maxillary
sinus through the canine fossa, removing the mucous membrane and
making a permanent opening in the inferior meatus to drain the sinus.
Incidentally another surgeon in France named Henry Luc was also working
on the same operation which then was described as Caldwell Luc
30

operation. The quest to look into the sinuses continued with Wertheim in
1896 designing a conchoscope to look deeper into middle meatus.
With better visualization of the nasal cavity, Parson Schaffer in
1912-1923 described the intricate anatomy of the lateral wall of nose and
paranasal sinuses. Harris Mosher emphasized the importance of Agger
nasi cells in frontal sinus surgery.
In the late 20th century, Prof. Messerklinger in 1967 studied and
documented genetically determined pathways of mucociliary mechanism
in all sinuses and any obstruction to its natural drainage was responsible
for continued sinus dysfunction. He emphasized that the anterior ethmoid
and osteomeatal complex was the key to chronic sinus disease. This
formed the basis of chronic recurrent sinusitis. This event along with the
nasal endoscopy described by Prof. Draf with the development of fibre
optics and CT imaging heralded a new era, which evolved in functional
endoscopic sinus surgery. Later on Prof. H. Stammberger popularized the
technique and published his experience of functional endoscopic sinus
surgery in 1991.5 This new technology further enhanced the scope of
endoscope being used around and beyond the nose.
However certain diseases continue to prove a challenge to
mankind. One such condition is fungal infection. This discussion
emphasizes issues that relate to fungal rhinosinusitis. The American
academy Of Otolaryngologys task force on rhinosinusitis suggested the
term rhinosinusitis more accurately describing the disease process than
the term sinusitis. As the linings of nose and paranasal sinuses are
31

continuous, inflammatory processes tend to involve both areas to a greater

or lesser extent.
Fungal sinusitis as an entity was described in the late 1700s. 10 By
mid-1800 to late 1800s; it was described in both invasive and non-invasive
forms. Non-invasive Aspergillosis of the nose and paranasal sinuses was
first described by Schubert in 1855 and invasive fungal rhinosinusitis was
first reported by Oppe in 1897. It was in1965 when Hora actually put the
whole picture together and described Fungal rhinosinusitis as a spectrum
of disease ranging from non-invasive to invasive. If one looks at the
literature over the history of this disease, it has had some confusing
nomenclature, and up until recent years, it has not really had a standard
nomenclature.
In 1997, deShazo reviewed the literature on fungal rhinosinusitis
and proposed a standard classification by which to look at these cases.
He, as before broke it down into invasive and non-invasive forms. Then he
characterized five major types. The first of the non-invasive forms was
allergic fungal sinusitis as well as sinus fungal ball. Of the invasive forms
the most common form is what he described as acute or fulminant invasive
sinusitis. Then he described chronic invasive fungal rhinosinusitis, and
finally granulomatous invasive fungal rhinosinusitis. Berrylin J. Fergusson
described saprophytic colonisation as a subtype of non-invasive fungal
sinusitis.11
All these manifestations overlap or progress from a non-invasive
form to an invasive form if immunogenic status of the patient changes.
32

This prognosis is less dependent on a particular fungus causing the

infection than the manifestation of fungal infection in the host which is
dependent on immunogenic status of the host.

Overview

of

vast

medical

mycology

in

relation

to

fungal

rhinosinusitis12
Fungi are eukaryotes that evolved shortly before plants and
animals. The number of fungal species probably exceeds 50,000, but only
a few hundred species of fungi are implicated in human disease, and 90%
of human infections can be attributed to a few dozen fungi. Although many
cases of fungal rhinosinusitis are caused by species of Aspergillus,
Dematiaceous moulds or Zygomycetes, the range of confirmed and
potential fungal elements is extensive and expanding.
Each fungal cell possesses at least one nucleus and nuclear
membrane,

endoplasmic

reticulum,

mitochondria,

and

secretory

apparatus. Most fungi are facultative or obligate aerobes. Fungi grow as

yeasts and moulds.
Yeasts are single cells, usually spherical to elliptoid in shape
varying in diameter from 3 to15 microns. Most yeasts reproduce by
budding. Under certain conditions some pathogenic yeasts produce buds
that characteristically fail to detach and become elongated, producing a
chain of elongated yeast cells called pseudohyphae. All fungi have rigid
cell walls that determine their shape. Cell walls are composed of

33

carbohydrate layers and long chains of polysaccharides as well as

glycoproteins and lipids.
Pathobiotic properties of cell walls:
1. Surface components of cell wall mediate attachment of the fungus to
host cells.
2. Cell wall polysaccharides may activate the alternative pathway of
complement cascade to stimulate the inflammatory reaction.
3. Fungal cell wall is degraded poorly by the host and can be detected with
special stains.
4. Cell wall release immunodominant antigens that may elicit cellular
immune responses. In addition to their vegetative growth as yeasts or
moulds, fungi can produce spores to enhance their survival. Spores can
be readily airborne and dispersed, are more resistant to adverse
conditions, and can germinate when conditions for growth are favorable.
Spores can derive from asexual or sexual reproduction, which are called
anamorphic and teleomorphic states, respectively.
The medical fungi produce two types of asexual spores, conidia and
sporangiophores. In the zygomycetes, sporangiophores are produced by
mitotic replication and spore formation within a sac like structure called a
sporangium, which is supported by sporangiophores. The ever changing
classification of fungi is based upon the process of sexual reproduction.
Some fungal genera and species implicated in fungal rhinosinusitis.

34

Category

Genera

Zygomycetes

Absidia,

Mucor

Cunninghamella
Rhizomucor

Hyaline moulds

Rhizopus
Aspergillus
Blastomyces dermatitidis
Chrysosorim
Fusaium
Penicillum
Pseudallescheria boydii
Scedosporium
Scopulariopsis
Alternaria

Dematiaceousmoulds

Bipolaris
Curvularia
Exserohilum
Cladosporium
Candida
Coprinus

Ascomycetous yeasts
Basidiomycetes

Cryptococcus neoformans
Schizophyllum
Ustilago

Rhinosinusitis follows inhalation of nasal spores into nasal passages. The

outcome of inhaling an innoculum of spores depends upon several factors:
1. The number of spores inhaled.
2. The size of fungal particles.
35

3. The immunity of the host.

4. The pathobiologic potential or virulence of the particular fungus.

Diagnosis of mycotic infections:

Specimens:
While examining a patient with rhinosinusitis, any exudate, infected
material or necrotic tissue should be rapidly transported to the laboratory
for direct examination and culture. Swabs should be avoided.
Microscopic examination:
The ideal stain for histopathological direct examination is a mixture
of KOH and Calcofluor white.
Histopathological examination of specimens:
Exudates or specimens can be stained with:
Hematoxylin and Eosin (H and E)
Gomori Methenamine Silver (GMS)
Periodic Acid Schiff (PAS)
GMS and PAS stains are superior to H & E and stain the cell wall black or
red respectively. The melanin of dematiaceous fungi is often present on H
and E slides. The Fontana Masson melanin stain is useful in differentiating
these fungi from non melanin containing fungi such as Aspergillus.

36

Culture identification:
The traditional medium is Sabourauds agar which contains glucose
and beef extract. Their identification is based upon morphology of their
conidia.PCR methods can be employed to detect various taxa and genera
based upon ribosomal DNA.
Serologv and skin tests:
Precipitins and specific lgG and igE antibodies are detected in
serum by various enzyme immunoassay and radioimmunoassay. The
antibody class and skin tests can help to differentiate among invasive,
non-invasive and allergic fungal rhinosinusitis.
Management of fungal infections:
Various

approaches

to

manage

fungal

infections

include

endoscopic surgery, systemic corticosteroids, topical and systemic

antifungal antibiotics and immunotherapy.

ALLERGIC FUNGAL RHINOSINUSITIS13

37

It is a term introduced by Robson et al in 1989 to describe a

constellation of unusual findings in a unique group of patients suffering
from chronic sinusitis.14
Epidemiology of Allergic Fungal Rhinosinusitis:
The prevalence of allergic fungal rhinosinusitis in chronic
rhinosinusitis patients who require surgery is between 5% to 10%. Allergic
fungal rhinosinusitis is noted more commonly in a younger group of
patients varying from 23 to 42.4 yrs of age. 15,16 Some studies have noted a
fairly equal sex predilection for AFRS whereas Manning and Holeman
noted a male preponderance of 1.6 males per female. 16,17 The diseases
seem more common in warmer, humid climate. The first to report the
incidence of AFRS was Katzenstein in 1983 with an incidence of 6.2%
from St.Louis, Missouri, which lies along the central Mississippi river. One
third to one half of AFRS patients have asthma.16,17
Deshpande, Shukla and M V Kirtane found that the incidence of
AFRS of all sinus surgeries in Mumbai in a 4 year study is 8.2% which is
the highest reported incidence in literature. 18
Pathophysiology of Allergic Fungal Rhinosinusitis:
Miller demonstrated Type-1 hypersensitivity to Aspergillus fumigatus
in a group of patients with a constellation of symptoms and findings that
can be labelled as AFRS. Members of the dematiaceous family are
actually the most common agents involved in AFRS.
Symptoms of AFRS:
38

The patient typically has a history of nasal polyposis and may have
had previous sinonasal surgery. The incidence of nasal polyposis in AFRS
is almost 100%.15 They may have documented atopic disease. Children
with AFRS commonly have proptosis.1675% patients diagnosed as having
AFRS describe expelling dark coloured rubbery nasal casts. 17
Bent and Kuhn diagnostic criteria for AFRS:
1. Type-1 hypersensitivity.
2. Nasal polyps.
3. Characteristic CT scan findings.
4. Positive fungal stain or culture.
5. Allergic mucin with fungal elements and no tissue invasion.
Marple uses the same diagnostic criteria though he excludes the
requirement of fungal culture because a negative culture may be caused
by laboratory inexperience, and a positive culture may represent a
saprophytic growth of fungi.
In actuality an atopic individual who lacks nasal polyps, a
characteristic CT,or positive fungal cultures, but has the characteristic
histopathology of allergic mucin with hyphal elements is still diagnosed as
having AFRS.
Preoperative steroids may reduce the nasal polyps and facilitate the
identification of surgical landmarks, but may obfuscate the diagnosis of
AFRS. Graham and Ballas described such a case in which preoperative
39

high dose steroids resolved the eosinophilic mucin. The pathologists saw
only a matte of fungal hyphae and diagnosed it as a fungal ball. When
steroids were tapered off post operatively, the AFRS recurred and the
diagnosis was confirmed by characteristic histopathology.
Examination of acid mucin by H and E stain reveals eosinophils,
Charcoat laden crystals, and possibly fungal hyphae within a background
of eosinophilic or basophilic mucinous material. The Charcoat laden
crystals are composed of lipophospholipase and range in size from 2 to 60
micrometers. The crystals are depicted especially well with a Brown Brenn
stain.19 GMS stain is typically used to visualize the fungal elements within
the allergic mucin. Fontana masons stain actually may allow the
microscopist to more easily distinguish the dematiaceous fungi from other
septate fungi, as it stains the melanin that is characteristic of the former
group.
AFRS CT scans show characteristic findings:
Central areas of hyperattenuation within the sinus cavity on CT
scan correspond to areas of hypointensity on T-1 weighted MR images
and signal void on T2 weighted MR images.
Central areas of hyperattenuation within the sinus cavity on CT
scan may take on various patterns including a star filled sky, ground glass
or serpiginous pattern. Bony loss is common as the expanding
inflammatory lesion pushes and thins the surrounding bone. The disease
may progress from frontal sinus into the orbit below, or posterior through
the posterior table to involve the anterior skull base. Disease may spread
40

laterally from ethmoid region to erode the lamina papyracea. Although

exposed, the soft tissue barriers of dura or periorbita are not involved by
the fungus.
Role of surgery in management of AFRS: 20
Surgery has been the single invariable component of combination
therapy for AFRS. An aggressive approach initially was adopted because
of perceived risk of fungal infections.
Increased acceptance of the disease as of a specific immunologic
hypersensitivity has led to changes in its management. Radical surgery for
AFRS has given way to more conservative, tissue sparing approaches.
Mabry et al refer to this surgery as conservative 21but complete, relying
almost completely upon endoscopic techniques. Nasal polyposis is
inherent to AFRS and can cause distortion of local anatomy and loss of
surgical landmarks.
Aside from these problems, polyps can provide an important
intraoperative role by serving as a marker of the disease. AFRS causes a
relatively consistent configuration of the disease. Because of the noninvasive nature of the disease, it may be removed in a blunt fashion,
leaving the involved sinus completely lined with intact mucosa.
Preservation of mucosa provides protection of adjacent anatomical
structures, even in the face of large areas of anatomical dehiscence.
The next goal of the surgery is to impart permanent drainage and
ventilation to the affected sinuses. Postoperative care begins immediately

41

following surgery in the form of nasal saline irrigation. Weekly clinical visits
are requested initially to allow regular inspection of operative areas as well
as debridement of crusts and retained fungal debris if necessary. Systemic
corticosteroids are continued postoperatively.
Complications:
In addition to fungal or bacterial seeding, penetration of dura or
periorbita may lead to injury of the structures within it. It can result in
diplopia, blindness, haemorrhage, stroke, intracranial hemorrhage, or CSF
rhinorrhea. Erosion of osseous boundaries may increase the risk of
formation of encephalocele.
Role of steroids, antifungals and immunotherapy in the management
of AFRS:22
Waxman et al suggested the use of systemic corticosteroids in the
treatment of AFRS23 based on the treatment modalities used in ABPA.
Kuhn and Javer recommend beginning oral prednisolone in a dose of 0.4
mg/kg for 4 days. The dose is then decreased by 0.1 mg/kg/day in cycles
of 4 days until a dose of 20mg/day or 0.2mg/kg/day whichever is greater is
reached. This is continued until the 1 month postoperative visit when it is
adjusted to 0.2mg/kg/day. This dose is then maintained and the patient is
then followed monthly with both nasal endoscopy and total serum IgE
levels. Intranasal steroid spray is simultaneously started in a dose of one
spray in each nostril 3 times daily. Endoscopy and total serum IgE levels
are measured monthly for 6 months and then bimonthly for 3 to 5 years.

42

The adverse effects of systemic steroids:

Accelerated Osteoporosis, Cataracts, Glaucoma and Avascular
necrosis of hip.
Kupferberg and Bent cautioned that systemic corticosteroids should
be weaned aggressively in children with AFRS to minimize possible long
term growth retardation. Topical and systemic antifungal therapy for AFRS
has been studied by Kuhn and colleagues with mixed to poor results.
Mabry
investigating

and

colleagues

immunotherapy

have
for

made

AFRS.

They

considerable
have

stated

effort
that

immunotherapy produced a decreased amount of crusting and polyposis

as well as a reduction in the need of systemic and topical corticosteroids in
these patients.
A retrospective review by Fergusson of 7 patients who received
immunotherapy without adequate surgical and medical management
indicated that 5 patients did not improve or worsened with immunotherapy.
Issues not in favour of immunotherapy are:
It may incite a Gell and Coombs Type-3 Arthus reaction with
immune complex mediated tissue damage. There may be possible
worsening of the disease with introduction of extraneous fungal antigens to
patients with AFRS. Antigens of many common fungal allergens are not
available commercially. Laboratories capable of measuring fungal specific
serum IgE levels for all fungi are not available. Immunotherapy may be a

43

promising direction in which to develop a supplemental treatment option

for surgery and steroid therapy of this difficult disease.

FUNGAL BALLS OF THE PARANASAL SINUSES24

44

Fungus balls of the paranasal sinuses are composed of matted

fungal hyphae. In the literature the term mycetoma is frequently used to
describe these paranasal sinuses fungal ball. In older literature the term
Aspergilloma or Aspergillosis was often used for paranasal sinus Fungus
balls even if fungal cultures are not performed or fail to grow. In 1893
Mackenzie reported the first case published in English of a non-invasive
fungal sinusitis. deShazo and colleagues in the review of English literature
cases through 1996 identified 20 patients in 11 reports that met their
criteria for paranasal sinus Fungus balls and added 5 cases of their own. 25
Subsequently large series from Mayo clinic with 29 cases 26 and France
with 109 cases27 added to the clinical characterization of this fungal
manifestation.
Epidemiology:
Older individuals appear more susceptible. The average age
reported in an American retrospective series of 29 cases was 64 years,
ranging from 28 to 86 years. A comprehensive review by deShazo and
Klossek also showed a similar age range with the youngest reported being
18 years.25,27 No pediatric cases have been reported. In all English
language literature available for review, there is consistently a female
preponderance of about 64%.25,26

Clinical presentation:

45

The common symptoms include nasal obstruction, purulent nasal

discharge, cacosmia or facial pain. Unusual symptoms include onset of
seizures, epistaxis, proptosis, fever, cough and blurred vision. Ten percent
of the patients have polyps.27
Radiographs:
The most commonly infested sinus is the maxillary followed by the
sphenoid. 102 of 109 cases (94%) had only a single sinus involved. 27A
radiographic imaging most commonly shows complete or subtotal
opacification of the involved sinuses. On sinus CT, 97 of 109 cases show
heterogenous opacity. Upto half the cases demonstrate radiodensities
within the central portion of the soft tissue mass. 27These represent
calcifications or dense hyphae. Occasionally a mucocele or foreign body
or even an antrochoanal polyp may be seen.
Histopathology:
Fungus balls are extra mucosal fungal infestations. No invasion is
present. Granulomatous reaction is absent. A tangled mat of hyphae is
present on histopathology. Grossly the fungus is gritty, occasionally
cheesy, often fragmenting easily into clay like particles. Colour can range
from brown to black to green or yellow.

Fungal cultures:

46

Fungi reported to cause fungal balls include A.fumigatus, flavus,

Alternaria sp., and P.boydii. Failure ofthe fungus to grow on fungal cultures
is common with only 23 to 50% of cultures resulting in fungal growth.
Immunology:
Immunologically

most

patients

appear

to

be

normal.

If

immunosuppression develops these patients are at high risk for

developing invasive fungal rhinosinusitis.
Pathogenesis:
The most likely cause of fungal balls is the persistence of fungal
spores within the nasal cavity, or entrance of the fungal spores into the
maxillary or the other sinus through accessory ostia, and subsequent
germination and growth.
Treatment:
The treatment of paranasal sinus fungal balls is surgical removal. In
the past these patients were approached externally. This has been largely
replaced with endoscopic techniques. No recurrences were found in
patients treated with Caldwel Luc technique in the Mayo clinic series. 26

SAPROPHYTIC FUNGAL INFESTATION11

47

Saprophytic fungal infestation refers to the presence of fungal

spores on mucous crusts within the nose and paranasal sinuses. The
incidence of this phenomenon is unknown. It is frequently seen upon
endoscopic examination of the nose and the paranasal sinuses. It may be
more frequent in patients who have undergone previous endoscopic sinus
surgery, because such surgery may disrupt the mucociliary transport
pathways and allow the formation of crusts upon which fungus can grow.
Histopahologically, if the mucocrusts were sampled, the hyphae could be
seen. Culture would reveal a variety of fungi. This if left undisturbed would
become a fungus ball. At this stage, the only therapy required is
endoscopic cleaning. If fungal mucocrusts continue to accumulate, instruct
the patient in mechanical cleaning with saline irrigation using a water pilk
or a baby bulb syringe on a weekly basis to resolve the problem.
Saprophytic fungal colonization is defined as the visible growth of fungus
within the nasal cavity of an asymptomatic individual and does not refer to
fungi that are not visibly growing but present by culture alone. This is
important because fungus can be cultured from virtually any individuals
nose, if one uses elaborate washes and culturing methods.

ACUTE FULMINANT INVASIVE FUNGAL SINUSITIS

48

28

Acute fulminant invasive fungal rhinosinusitis is a disorder

characterized by mycotic infiltration of the mucosa of the nasal cavity and
paranasal sinuses. In the absence of treatment the disease is rapidly fatal
in 50% to 80% of the orbit an of the patients secondary to the invasion of
the orbit and intracranial cavity.29,30,31The primary risk factor for the
development of acute fulminant invasive fungal rhinosinusitis is an
immunocompromised state. The disorder always occurs in patients with an
impaired neutrophilic response secondary to disorders such as

Poorly controlled Type 1 diabetes mellitus

AIDS
Hemochromatosis
Aplastic anemia
Iatrogenic immunosuppression
Organ transplantation
Hematologic malignancy.

Clinical features:
The most common symptom in upto 90% of patients is fever of
unknown origin that has not responded to 48 hrs of broad spectrum
intravenous antibiotics.30 Absence of fever does not rule out the disorder
especially in patients with localizing symptoms such as facial or periorbital
pain, nasal congestion and rhinorrhea and headache which are invariably
present in 20% to 60% of patients. 29,30,32 Late signs and symptoms include
loss of visual acuity, opthalmoplegia, proptosis, and change in mental
status, focal neurological signs and seizures.
On a thorough rigid endoscopic nasal examination, the most
consistent physical finding is an alteration in appearance of the nasal

49

mucosa. Mucosal discoloration is variable and may be grey, green white or

black. White discoloration of the mucosa indicates tissue ischaemia
secondary to angiocentric invasion whereas black discoloration is a late
finding signifying tissue necrosis.
A thorough head and neck examination is also mandatory. The
patients level of consciousness and awareness to person, place and time
provides the rough evaluation of the central nervous system function. The
face is palpated tor paranasal sinus tenderness. A full cranial nerve
evaluation, with particular attention to facial sensation, extraocular muscle
function, afferent pupillary reflex and visual acuity is performed.
Radiology:
CT of the paranasal sinuses:
Fine cut (1 mm) CTscan of the paranasal sinuses should be
obtained in both the coronal and axial views in order to maximize
anatomical details. CT findings in invasive fungal rhinosinusitis are nonspecific and do not correlate well with surgical and pathologic findings. The
CT scan can document the presence of sinusitis and demonstrate which
sinuses are to be addressed surgically. A scan can demonstrate individual
variations in bony architecture, which may prevent potential surgical
complications. This ability of the scan makes it the imaging study of
choice. CT scans may have findings suggestive of an invasive sinonasal
disorder.

50

MR imaging is however superior to CT in delineating intracranial

extent of the disease.29,31 A mortality rate of 100% has been demonstrated
in patients with intracranial involvement. 29,30 MR imaging may prevent
unnecessary procedures in patients who are unlikely to benefit from
surgery.
Diagnosis:
Histopathological evaluation of tissue biopsies is required to confirm
the diagnosis of invasive fungal rhinosinusitis. Fungal disease is
determined to be invasive if it meets the following criteria on
histopathological examination:
1) Hyphal forms within the submucosa with or without angiocentric
invasion.
2) Tissue necrosis with minimal host inflammatory cell infiltration.
Ideally tissues should be sent for frozen and permanent sections.
Permanent sections with GMS staining confirm the diagnosis and provide
important morphologic information for determining the fungal species. The
most common site of invasion is the middle turbinate in approximately twothird of the patients.28

Treatment:
Mainstay of treatment continues to be a combination of antifungal
antibiotics and aggressive surgical debridement. Surgical approach for
invasive fungal rhinosinusitis has been changed over years from radical
51

surgeries to endoscopic sinus debridement. Clear bleeding margins should

be achieved during endoscopic sinus debridement. The patient should be
scheduled for a second look procedure in 48 to 72 hours if there is
concern of residual disease in the sinonasal cavity.
Surgery does not prolong survival in neutropenic patients who do
not recover their white blood cell counts. 29,30 Granulocyte colony
stimulating factor has been shown to be efficacious for promoting bone
marrow recovery in neutropenic patients. These patients are more likely to
become disease survivors. They should continue to receive weekly nasal
endoscopy until reversal of neutropenia, and once a month for 6 months
thereafter.

Role of antifungals in the treatment of acute invasive fungal

sinusitis:33
It was discovered by Gold and coworkers who were studying the
strains of Streptomyces nodosus, an aerobic actinomycetes, obtained from
the Orinoko river valley of Venezuela. 34 In 1958, Chick described the
effectiveness of Amphotericin against Rhizopus infections in rabbits and
rats.32In 1961, Gass described the first human survival treated with this
drug.
Since the sixties, surgical treatment combined with Amphotericin B
has become the mainstay of therapy.

52

Andrew Blitzer et al in 1980 in the study of 9 cases of sinonasal

infection had shown that with surgical debridement or radical resection
survival rate is 78% as compared to 57% with medical line of
management.35 Analysis of patients having combined Amphotericin B and
surgery showed an overall survival of 81%. Amphotericin B remains the
standard drug for most life threatening systemic fungal infections. It is a
polyene macrolide. Its antifungal activity is caused by its ability to bind
preferentially to ergosterol, a major component of fungal cell membrane.
Cell membrane permeability is then increased following attachment of this
lipophilic structure to the fungal cell wall, with leakage of intracellular
components and ultimately cell death.
Unfortunately, Amphotericin B also binds to a lesser degree to
cholesterol in mammalian cell membranes, which probably accounts for its
toxic effects on human cells.
Intravenous doses in the range of 0.25 to 1 mg/kg once daily in 5%
Dextrose solutions usually are recommended. Maximum daily doses of 1.2
mg/kg/day in adult and 1.5m/ kg/day in children are generally are reserved
for serious invasive mycoses.36,37

Hazards of Amphotericin B:
Infusion related reactions: chills, rigors, fever, headaches, nausea and
generalized aches. Premedication with acetaminophen, diphenhydramine,
aspirin or ibuprofen may help diminish this reaction.

53

Nephrotoxicity may occur in upto 80% of patients receiving

Amphotericin B therapy. It is manifested by azotemia, electrolyte wasting
(Mg and K), and a decrease in urinary concentrating ability. Patients
receiving a total dose of 4 to 5grams of Amphotericin B may have
permanent renal impairment. An approach to minimize nephrotoxicity
includes sodium supplementation to maintain intravascular volume and
inhibit tubuloglomerular feedback system.

Lipid based combinations of Amphotericin B:

Recently lipid based formulations of Amphotericin B have been
added to the armamentarium of antifungal agents. Amphotericin B lipid
complex, Amphotericin B cholesterol complex and liposomal Amphotericin
B use a variety of lipid carriers.37,38
The

pharmacodynamics

of

Lipid

based

combinations

of

Amphotericin B differs significantly from that of Amphotericin B

deoxycholate. They are preferentially delivered to reticuloendothelial
system such as the liver and the spleen. 37,38 Dose for liposomal
Amphotericin B is 1 to 5 mg/kg. Their use is associated with fewer
breakthrough fungal infections and less infusion related toxicity and
nephrotoxicity.
Future directions in antifungal therapy:

54

In developing new agents, the challenge remains in targeting

compounds that are effective in killing the fungal organism, yet limit the
toxicity to human cells.
Voriconazole is a new triazole and a derivative of Fluconazole.
Voriconazole has demonstrated two to eight-fold more activity against
C.crusei and C.glabrata strains than itraconazole. Other fungal pathogens
in which Voriconazole has demonstrated highly potent in vitro activity are
Aspergillus species, C.neoformans, C.immitis, H.capsulatum.
Studies evaluating the pharmacokinetics of Voriconazole have
demonstrated a relatively high (90%) bioavailability and a mean half life of
6 hours. Like Fluconazole, Voriconazole is metabolized by the hepatic p450 enzymes. It is in clinical trial with oral and intravenous preparations.
Clinical trials till date have indicated that Voriconazole is a
promising drug against acute and chronic Aspergillosis. In the setting of
invasive Aspergillosis intravenous doses of 6mg/kg every 12hrs for two
doses, then 3 mg/kg every 12 hrs for upto 30 days has been studied. This
regimen was followed by the course of oral therapy 200mg twice daily to
complete a total of 24 weeks. Side effects have been very limited and
include mild elevations in liver function tests and transient but reversible
visual impairment.
MUCORMYCOSIS11
Upper airway mucormycosis was first described in 1885 by Paltauf
who coined the term mycosis mucorina, which subsequently became

55

mucormycosis.39In 1943 the more typical findings of advanced rhinocerebral mucormycosis, proptosis and opthalmoplegia were reported in a
series of three fatal cases in patients with diabetic ketoacidosis by Gregory
et al.40
In 1955 the first cure of mucormycosis was shown by Harris 41 with
increasing recognition of the typical features of mucormycosis and the
development of Amphotericin B in 1956 the universal mortality of the
disease has been decreased dramatically. In diabetic patients the
survivorship ranges from 60% to 90%, whereas in leukemic patients and
those in whom the source of immunocompromise is not easily reversible,
survivorship is 20% to 50%.35,42
Taxonomy:
Mucormycosis is a term to refer to any fungal infections of the order
Mucorales, which belongs to the class Zygomycetes. Rhizopus oryzae is
the prominent pathogen that accounts for 60% of all forms of
mucormycosis

and

90%

of

rhinocerebral

cases

of

mucormycosis.43,44Apohycomyces elegans is the most recently recognized

agent in immunocompromised patients. 11 Assessment of the exact species
is limited by lack of fungal culture information in over half of reported
cases. Regardless of the agent, the clinical presentation & management
are identical.
Important members of the class Zygomycetes are:
CLASS

ORDER

FAMILY

56

GENUS

SPECIES

Zygomycetes
Mucorales
Mucoraceae
Absidia
Mucor
Rhizomucor
Rhizopus
Oryzae
Epidemiology and pathogenesis
Diabetics in ketoacidocis are classically affected. In the largest single
series to date of 126 patients with rhino-cerebral mucormycosis, 70% were
diabetic. Rhizopus has an active ketone reductase system and thrives in
high glucose and acidotic conditions. 35 Diabetics also have decreased
phagocytic activity because of an impaired glutathione pathway. Normal
serum inhibits Rhizopus growth, whereas serum from patients in diabetic
ketoacidocis stimulates growth.

Other risk factors include neutropenia, systemic steroids, protein

calorie malnutrition, solid organ and bone marrow transplant patients,
immunodeficiency, leukemia, and intravenous drug abusers who may
57

inject spores of Mucorales with their drugs and present with space
occupying lesions of the central nervous system. The relative infrequency
of mucormycosis, in patients with AIDS probably reflects the ability of
neutrophils to prevent growth of the fungus. 11 Patients reported infected
with rhino-cerebral mucormycosis range in age from 16 days to 75 years.
At least 14 cases of mucormycosis involving the paranasal sinuses have
occurred in patients without any predisposing factors.
Clinical features:
Depending upon the degree of immunocompromise, the disease
process can be indolent or fulminant. Yohia and colleagues reviewed 208
cases of rhino-orbito-cerebral mucormycosis from the literature between
1970 and 1993.45114 cases from their literature review and experience
were used to provide an estimate of the relative frequency of signs and
symptoms that occur within 72 hours of first symptom.
The leading symptom is fever, which occurred in less than half of
the individuals, followed by nasal ulceration and necrosis, periorbital or
facial swelling, or decreased vision; each occurred in approximately onethird of cases. An elevated white blood cell count is an early sign in less
than 20% of reported cases. Ultimately, 80% of patients developed a
necrotic lesion on either the nasal or oral mucosa. Facial numbness was
reported as an early symptom in only 7% of cases, which is an under
representation of an early symptom that is not usually assessed.
Yohia and colleagues also correlated survival relative to ophthalmic
signs and symptoms and non-ophthalmic signs and symptoms. Only a
58

third of patients who developed periorbital necrosis and 40% of the

cavernous sinus thrombosis patients have survived. Over half of the
patients with visual impairment or ophthalmoplegia however survived. 72%
of the patients with facial numbness survived. Low survivorship is seen
with hemiplegia (28%), facial necrosis (31%), mental changes (32%) and
fever (41 %). Yohia also found a decline in the survival when the interval to
treatment was greater than 6 days.46
Histopathology:
A presumptive

diagnosis

of

mucormycosis

can

be

made

histopathologically based on the broad ribbon-like hyphae, 10 to 20

microns across, haphazardly branched, and absence or paucity of hyphal
septations. The etiological agents of mucomycosis are readily stained with
hematoxyline and eosin stain and special fungal stains such as GMS.
Once invasive, the organism shows a markedly predilection for
vascular invasion. The propensity of these fungi to invade arteries and
arterioles contributes to an ischemic and acidotic environment, which
stimulates further growth.

Radiographs:
In early disease radiographs may be normal. As invasion continues,
one sees the typical findings of early infectious rhinosinusitis.

59

Only late in progression of the disease, bony erosion is appreciated.

Treatment:
Mainstays for treatment of mucormycosis of the paranasal sinuses
are reversal of immunocompromise, systemic Amphotericin B, and surgical
debridement.
Hyperbaric oxygen therapy is theoretically attractive in treating this
disease because it reverses the ischaemic acidotic conditions that
perpetuate fungal growth. There are no controlled studies regarding its
use. Hyperbaric oxygen treatments are usually given at two atmospheres
for 1 hour on a daily basis upto 30 treatments.

CHRONIC INVASIVE FUNGAL SINUSITIS:

60

Berrylin J Fergusson defines chronic invasive fungal sinusitis as

invasive fungal rhinosinusitis of greater than four weeks duration in which
vascular invasion is minimal or absent.47
deShazo et al has subdivided chronic invasive fungal sinusitis into
cases with granulomatous and non-granulomatous histopathology. But no
difference in prognosis or therapy is yet apparent based on his distinction.
The disease is characterized by a prolonged clinical course with slow
disease

progression,

sinusitis

on

radiological

imaging,

and

histopathological evidence of hyphal forms within sinus mucosa,

submucosa, blood vessels and bone.
Clinical features:
Chronic invasive fungal sinusitis occurs in healthy individuals,
though many have a history of chronic rhinosinusitis, upper airway
allergies, or nasal polyposis. Symptoms directly related to the invasive
disease may take months or years to appear and may only develop once
the orbit or skullbase are involved. Erosion into the orbit from the
paranasalsinuses may produce proptosis. Invasion of the maxillary floor
may produce palatal erosion. Erosion of the cribriform plate may produce
chronic

headache,

seizures,

decreased

mental

status,

or

focal

neurological findings. Extension through the sphenoid sinus may lead to

orbital apex syndrome or cavernous sinus syndrome. Extension in to the
pterygopalatine fossa may cause cranial nerve deficits. Some catastrophic
complications may occur such as mycotic aneurysm, internal carotid artery
rupture, and cavernous sinus thrombosis.
61

On intranasal examination, severe nasal congestion and polypoidal

mucosa may be noted. There may be a soft tissue mass that can be either
mucosally covered or ulcerated with overlying debris or dried secretions.
Diagnostic Imaging:
A sinus CT scan is an appropriate initial step in the evaluation of
suspected fungal rhinosinusitis. Mucosal thickening may be noted. Focal
or diffuse areas of hyper attenuation within a sinus are a clue to fungal
colonization, thick mucin plugs, infection, or Allergic fungal sinusits. Soft
tissue infiltration of peri-antral fat planes around the maxillary sinus
provides early evidence of invasive fungal rhinosinusitis in the appropriate
clinical setting. MR imaging is useful for assessing the dural involvement
and the intradural extension of the disease. The ultimate distinction
between invasive and non-invasive fungal rhinosinusitis and neoplasm is
best made histologically.
Although Aspergillus species were originally identified as the
causative organism of chronic invasive fungal rhinosinusitis, it is now
recognised that chronic invasive fungal rhinosinusitis can be caused by a
variety of organisms. At least 23 different species have been reported in all
types of fungal rhinosinusitis. Chronic invasive fungal rhinosinusitis has
specifically been associated with Mucor, Alternaria, Curvularia, Bipolaris,
Candida, Drechslera, Sporothrix schenckii, and Pseudallescheria boydii.
Pathophysiology:

62

Most patients with chronic invasive fungal rhinosinusitis are

immunologically intact. Chakrabarty showed that in patients with
Aspergillus

causing

invasive

disease,

only

29%

patients

with

granulomatous type disease had cutaneous Type 4 hypersensitivity to

aspergillus antigen (delayed skin reaction), whereas none of the nongranulomatous patients showed Type 4 reactions. 48deShazo has reported
that al cases of non-granulomatous chronic invasive fungal rhinosinusitis
occurred in patients with diabetes. 1Many of the organisms that cause
chronic invasive fungal rhinosinusitis were previously identified as
saprophytic organisms. The specific virulence factors that are responsible
for the development of invasive disease in most species have not been
completely elucidated.
Sandison speculated that a hot, dry, warm climate with nasal
obstruction is responsible for aspergillus infection, and A. flavus seems
more common in the environment of Northern Sudan. Others propose
mechanical obstruction of the natural sinus ostia as a result of
inflammation, allergic rhinitis, nasal polyposis, septal deviation, or chronic
sinusitis as the ultimate predisposing factor. Milosev believed that
anaerobic conditions in the sinus because of repeated inflammation or
polyps predisposed to invasive fungal disease.
Pathology:
Veress et al described the gross appearance of granulomatous
chronic invasive fungal rhinosinusitis as firm, hard, rubbery, fibrous,
grayish-white masses with an irregular surface. 49 Periarterial inflammation
63

without direct involvement of fungal elements and no true vascular

invasion were noted. They described three variants: proliferative
(granulomatous pseudotubercles in a fibrous tissue stroma), exudativenecrotizing (with prominent foci of necrosis), and a mixed form. deShazo
typified

granulomatous

chronic

invasive

fungal

rhinosinusitis

as

granulomas composed of eosinophilic material surrounded by fungus,

giant cells and palisading nuclei, variable numbers of lymphocytes and
plasma cells.1 Non-granulomatous chronic invasive fungal rhinosinusitis
was characterized by tissue necrosis with little inflammatory infiltrate and
dense hyphal accumulation resembling a fungal ball (mycetoma). The
fungi in this form may breach mucosal barriers to invade blood vessels or
simply cause an arteritis without vascular invasion, although both
granulomatous and non-granulomatous forms may result in tissue
necrosis.
Treatment:
Most published cases have been treated with a combination of
surgery and antifungal chemotherapy. Much of the advice previously
published for treating sinus aspergillosis is no longer valid because of lack
in specificity of diagnosis. Some suggest that cure can be achieved with
surgical debridement alone or with a combination of debridement followed
by a short course of antifungal therapy. deShazo feels that nongranulomatous chronic invasive fungal rhinosinusitis should be treated
with an aggressive surgical approach similar to that for fulminant invasive
fungal rhinosinusitis.

64

Washburn has noted that chronic invasive fungal rhinosinusitis

frequently recurs despite surgical debridement and recommends a
prolonged course of Amphotericin B exceeding 2 gm for adults after
surgery.50 In contrast, deShazo feels that granulomatous invasive fungal
rhinosinusitis responds well to surgery alone without need of antifungal
antibiotic therapy. Zieske, in a mixed series of patients, some of whom
today would be classified as having AFS, recommended that for patients
with histologic invasion and extension beyond sinus confines, sinus
debridement and wide aeration should be followed by 1 to 2 grams of
amphotericin B. If persistent or recurrent disease develops, Itraconazole
200 to 400mg per day for 6 to 12 months may be added. Fungal cultures
are necessary because not all fungi are sensitive to amphotericin B or
itraconazole.45

PREVENTION AND PROPHYLAXIS OF INVASIVE FUNGAL SINUSITIS

IN THE IMMUNOCOMPROMISED PATIENTS51
Prevention by decreasing environmental exposure:

65

These interventions apply to Aspergillus as well as other

filamentous fungi and have been described as being useful most often in
the setting of allogenic bone marrow transplantation and prolonged
granulocytopenia after chemotherapy for leukemia.
Because many patients are hospitalized during the period when
they are at highest risk of infection, nosocomial acquisition of aspergillosis
has been described many times. Hospital associated outbreaks are
usually related to contamination of the ventilation system supplying the
hematology or the transplant unit or passive transmission of large number
of conidia aerosolised into the ventilation system by demolition or
construction projects. Other sources of Aspergillus and filamentous fungi in
the hospital include potted plants, food stuffs, and fire proofing and
insulating materials.
All hospitals caring for immunosuppressed patients should establish
general policies to decrease the fungal burden to which patients are
exposed. Potted plants and flowers should not be allowed on the unit and
ground pepper should not be used as seasoning. Regular cleaning of air
ducts and maneuvers to discourage birds from nesting on seels and roofs
should be carried out. Patients at greatest risk should minimize time spent
outside their room; when they do leave many centres advocate use of a
mask.
The ideal environment in terms of decreasing the number of conidia
to which patients are exposed, is a specially constructed room that
incorporates laminar air flow and high efficiency particulate air filtration
66

(HEPA).These measures diminish the airborne filamentous fungus burden

and have been shown to decrease infections in neutropenic patients.
Prevention with prophylactic antifungal drugs:
Several principals require consideration when selecting an effective
prophylactic regimen.

Targeting pathogens most likely to cause the infection.

Identifying subsets of patients at highest risk for fungal sinusitis.
Limiting prophylaxis to the period of time when risk is highest.
Choosing a safe, well tolerated drug with minimal toxicity and

interactions.
Monitoring patients for drug related side effects and development of

resistance to the agents.

Evaluating the cost of regimen in relation to its efficacy.

Because Aspergillus species are the most common cause of invasive

fungal sinusitis in immunocompromised patients, drugs active against this
pathogen should be an integral part of any successful regimen. Invasive
Candida infection is rare and should not be a target of prophylaxis.
Infections caused by Zygomycetes, Alternaria, Bipolaris and the others are
uncommon enough that antifungal prophylaxis is not feasible.
Prophylaxis should be limited to patients likely to develop infection
and should be given only during the period of highest risk. If all
immunocompromised patients received prophylaxis against filamentous
fungi, drug related side effects and the development of resistance to
antifungal agents would undoubtedly overshadow the benefit seen for a
few individuals with neutropenia.

67

.MATERIALS AND METHODS

A prospective study of 30 cases of fungal rhinosinusitis was carried
from July 2009 to October 2011.
A detailed study of history and clinical presentation, thorough
clinical examination, investigations including CT PNS was done. Following

68

diagnostic endoscopy, patients were subjected to the appropriate surgery.

Surgical specimens were sent for KOH mount, fungal culture and
histopathological examination. Patients were treated with appropriate
antifungals, topical or systemic steroids accordingly. A record of follow up
of these patients weekly for 1 month, fortnightly for 3 months, and monthly
for 6 months was also kept.

CASE RECORD FORM

MANAGEMENT OF FUNGAL RHINOSINUSITIS IN A TERTIARY
HEALTHE CARE CENTRE.
Name:

IPD No:

Age:

Address:

Sex:
Chief complaints:
Nasal symptoms:
Excessive sneezing
Occasional/Cascade
Nasal blockage
Duration, Onset: Days/ Weeks /Months /Years
Laterality: unilateral/bilateral

69

Latency: constant/intermittent
Severity
Character: during inspiration/expiration
Aggravating/Ameliorating factors:
Nasal discharge:
Duration/ Onset: Days/Weeks /Months /Years
Duration/ Onset: Days/Weeks /Months /Years
Laterality:Unilateral/Bilateral
Latency: constant/intermittent
Severity
Character: Watery/ Mucoid/ Mucopurulent/ Purulent/ Blood stained

Nasal mass
Duration/ Onset: Days/Weeks /Months /Years
Duration/ Onset: Days/Weeks /Months /Years
Laterality: Unilateral/Bilateral
Related nasal obstruction
Enlarging/ Static/ Regressing

Associated symptoms:
Facial pain:
70

Onset/ Duration
Spontaneous/Induced
Aggravating/Ameliorating factors
Associated fever
Nature of pain: Stabbing/ cutting/dull aching
Spread
Postural/ Diurnal variation
Dental hygiene
Facial swelling;
Duration/ Onset: Days/ Weeks/ Months /Years
Laterality: Unilateral/ bilateral
Static / progressive/ regressive
H/O trauma
Disturbances in smell
Nasal crusting:
Duration/ Onset: Days/ Weeks /Months /Years
Laterality: Unilateral/ Bilateral
Type/colour
Epistaxis:
71

Fresh /clotted/ blood stained discharge

Amount of blood
H/O Trauma
H/O Taking drugs
H/O Bleeding from any site
H/O Bleeding in family
Postnasal drip
Associated symptoms:
Disturbances in vision
Drooping of eyelid
Headache
Deviation of angle of mouth
Past history
H/O similar illness in past
H/O any childhood illness
H/O any exposure
H/O major illness in past
H/O surgery in past
Personal history:
72

Family history:

General examination:
Level of consciousness:

Orientation:

Built:

Temperature:

PR

RR

BP

Pallor/ icterus/ cyanosis /clubbing/ edema/ Lymphadenopathy

ENT examination:
Nose:
Inspection: deformity/swelling of nose or face
Palpation:
Anterior Rhinoscopy:
Vestibule:

Septum:

Spur:

Turbinates:

Nasal mucosa:

Nasal secretions:

Crusts: Type/ Colour

Nasal mass:

Posterior Rhinosopy:
PNS examination:
73

Sinus tenderness: maxillary/ frontal/ ethmoidal

Cold spatula test:
Oral cavity and throat examination:
Oral hygiene:

Oral mucosa;

Tongue:

Teeth:

Hard palate:
Posterior pharyngeal wall:
Indirect Laryngoscopy:
Ear examination:
Neck examination:
Ophthalmic examination:
Lids:

Sclera:

Conjunctiva:

Cornea:

Iris:

Pupil:

Proptosis: mild/moderate/severe
Vision: normal/decreased
Fundus Exam:
CNS examination:
Higher functions:
74

Consciousness/behaviour/intelligence
Memory/speech
Signs of cranial nerve involvement:
Pupillary changes/ visual disturbances
Corneal/conjunctival reflex
Sensation over face
Deviation of angle of mouth
Difficulty in eye closure
Motor system:
Nutrition /tone/ power/ataxia/involuntary movements
Sensory system:
Touch/pain/temperature
Signs of raised ICT:
Bradycardia/

neck

rigidity/

Kernigs sign/

Brudzinskis

sign/

papilloedema
Respiratory system:
Gastrointestinal system:
Investigations:
Haemogram:

BSL:
75

Serum electrolytes:

LFT:

RFT:

Urine:

Radiological investigations:
X ray PNS Caldwells and Waters view:
CT-PNS:
MRI-PNS:
Nasal endoscopy:
Discharge/crusts/eschar/fungal balls
Microbiological examination:
KOH Mount
Fungal culture:
Histopathological examination:
Diagnosis:
Treatment:
Medical
Surgical:
Intra-operative findings:
Follow up after discharge:1 Month/3month/6months

76

OBSERVATIONS AND RESULTS

TABLE NO. 1: DIAGNOSTIC ANALYSIS
Diagnostic Analysis

NON-INVASIVE
FUNGAL
RHINOSINUSITIS

Allergic fungal rhinosinusitis

Fungal Ball
Saprophytic colonisation

77

No. of cases
out of 30
16
2
1

Percentage
53.34%
6.67%
3.33%

INVASIVE FUNGAL
RHINOSINUSITIS

Acute fulminant invasive fungal

rhinosinusitis
Chronic invasive fungal
rhinosinusitis
Chronic Granulomatous invasive
fungal rhinosinusitis

30%

3.33%

3.33%

Chart no .1 :Diagnostic analysis

no.of cases

Chronic Granulomatous invasive fungal rhinosinusitis 1

Chronic invasive fungal rhinosinusitis 1

Acute fulminant invasive fungal rhinosinusitis 1

Saprophytic colonisation 1

Fungal Ball

Allergic fungal rhinosinusitis

16

TABLE NO. 2: AGE DISTRIBUTION

Age (years)

10-20
21-30
31-40
41-50

No. of cases with

non-invasive
fungal sinusitis
4
5
3
5

No. of cases with

invasive fungal
sinusitis
0
0
1
3
78

Total no. of cases

Percentage

4
5
4
8

13.33%
16.67%
13.33%
26.67%

51-60
61-70

1
1

4
3

5
4

16.67%
13.33%

Chart no. 2: Age Distribution

7
3
6

0
1

4
5

4
3

10 to 20

21 to 30

31 to 40

41 to 50

Non-invasive fungal rhinosinusitis

79

51 to 60

61 to 70

Invasive fungal sinusitis

TABLE NO. 3: SEX DISTRIBUTION

Sex

Male
Female

No. of cases with

non-invasive
fungal sinusitis
8
11

No. of cases with

invasive fungal
sinusitis
8
3

Total no. of cases

Percentage

16
14

53.33 %
46.66 %

Chart no. 3: Sex Distribution

Females

Males

0
Non-invasive fungal sinusitis

Invasive fungal sinusitis

TABLE NO. 4: PRESENTING SYMPTOMS

80

Symptom

Excessive
sneezing
Nasal
obstruction
Nasal
discharge
Facial pain
Headache
Fever
Facial
swelling
Deviation of
angle of
mouth
Diminution
of vision
Paraesthesia

No. of
cases
with
noninvasive
fungal
sinusitis
12

Percentage
out of 19

No. of
cases with
invasive
fungal
sinusitis

Percentage
out of 11

Total
no. of
cases

Percentage
out of 30

63.15

12

40

19

100

10

90.90

29

96.67

10

52.63

45.45

15

50

5
14
0
0

26.31
73.68
0
0

5
7
6
8

45.45
63.63
54.54
72.72

10
21
6
8

33.33
70
20
26.67

36.36

13.33

63.63

23.33

72.72

26.67

81

Chart no. 4: Presenting Symptoms

8

Paraesthesia

Diminution of vision
Deviation of angle of mouth

4
8

Facial swelling
Fever

Non-invasive fungal
sinusitis

Invasive fungal sinusitis

Headache
Facial pain

Nasal discharge 3

5
10

Nasal obstruction
Excessive sneezing 0
0

10

82

15

20

TABLE NO. 5: SIGNS

Signs

Nasal polyposis
Proptosis
Opthalmoplegia
Ptosis
Palatal erosion

No. of
cases
with
noninvasive
fungal
sinusitis
12
1
0
0
0

Percentage
out of 19

No. of
cases
with
invasive
fungal
sinusitis

Percentage
out of 11

Total
no.
of
cases

Percentage
out of 30

63.15
5.26
0
0
0

0
7
7
7
3

0
63.63
63.63
63.63
27.27

12
8
7
7
3

40
26.67
23.33
23.33
10

Chart no. 5: Signs

3

Palatal erosion
0

Ptosis
0

Non-invasive fungal sinusitis

Invasive fungal sinusitis

7

Opthalmoplegia
0

Proptosis

7
1

0
Nasal polyposis

12

TABLE NO. 6: ASSOCIATED DISEASES

Associated
diseases

No. of
cases

Percentage
out of 19
83

No. of
cases

Percentage
out of 11

Total
no. of

Percentage
out of 30

Bronchial
asthma
Diabetes
mellitus
Renal
Failure

with
noninvasive
fungal
sinusitis
2

with
invasive
fungal
sinusitis

cases

10.52

6.67

5.26

10

90

11

36.67

9.09

3.33

Chart No.6: Associated Diseases

10

Bronchial asthma

Diabetes mellitus

Renal Failure

2
1

Invasive
0 fungal sinusitis

0
Non-invasive fungal sinusitis

84

TABLE NO. 7: CT FINDINGS

CT Findings

Heterogenous
opacity in
sinonasal
compartments
Radiodensity in
sinonasal
compartments
Bony invasion &
destruction
Polypoidal mass
Mucosal
thickening
Hetergenous
enhancing lesion
Proptosis
Orbital invasion
Intracranial
extension

No. of
cases with
noninvasive
fungal
sinusitis
6

Percentage
out of 19

No. of
cases with
invasive
fungal
sinusitis

Percentage
out of 11

Total
no. of
cases

Percentage
out of 30

31.57

18.18

26.66

15.78

9.09

13.33

10

90.90

10

33.33

13
9

68.42
47.36

0
9

0
81.81

13
18

43.33
60

81.81

30

1
0
0

5.26
0
0

6
6
2

54.54
54.54
18.18

7
6
2

23.33
20
6.66

ChartNo. 7: CT
findings
Intracranial extension 02
Orbital invasion 0

Proptosis 1

Hetergenous enhancing lesion 0

9
9

Mucosal thickening

13

Polypoidal mass
Bony invasion & destruction 0
Radiodensity in sinonasal compartments
Heterogenous opacity in sinonasal compartments

9
0

10
3 1
6

0 2 4 6 8 1012141618
Non-invasive fungal sinusitis

Invasive fungal sinusitis

TABLE NO. 8: ENDOSCOPIC FINDINGS

85

Endoscopic
findings

Grey fungal
debris
Polyposis
Thick clay like
material in
sinuses
Mucopus
Fungal
colonisation on
nasal crusts
Pallor of middle
turbinate
Black eschar
Nasal crusts
Allergic mucin

No. of
cases with
noninvasive
fungal
sinusitis
8

Percentage
out of 19

No. of
cases with
invasive
fungal
sinusitis

Percentage
out of 11

Total
no. of
cases

Percentage
out of 30

42.10

18.18

10

33.33

12
2

63.15
10.52

0
0

0
0

12
2

40
6.66

3
1

15.78
5.26

1
0

9.09
0

4
1

13.33
3.33

45.45

16.66

0
2
11

0
10.52
57.89

5
4
0

45.45
36.36
0

5
6
11

16.66
20
36.66

Chart No. 8: Endoscopic Findings

non-invasive fungal sinusitis

invasive fungal sinusitis

0
Allergic mucin

11

Nasal crusts

Black eschar
0

Pallor of middle turbinate

0
0
Fungal colonisation on nasal crusts
Mucopus

1
1

0
Thick clay like material in sinuses

3
2

0
Polyposis

12
2

Grey fungal debris

TABLE NO. 9: MEDICAL TREATMENT

86

Medical
treatment

Topical
steroids
Systemic
steroids
Oral
Itraconazole
Topical
Amphotericin
B
Systemic
Amphotericin
B

No. of
cases
with
noninvasive
fungal
sinusitis
18

Percentage
out of 19

No. of
cases
with
invasive
fungal
sinusitis

Percentage
out of 11

Total
no.
of
cases

Percentage
out of 30

94.73

18

60

18

94.73

18

60

17

89.47

17

56.66

81.81

30

11

100

11

36.66

Chart No. 9: Medical Treatment

non-invasive fungal sinusitis
0
18

0
18

invasive fungal sinusitis

0
17
9
0

87

11
0

TABLE NO. 10: SURGICAL TREATMENT

Sugical
treatment

FESS
Endoscopic
debridement
DNE
Endoscopic
debridement
with
maxillectomy
Endoscopic
debridement
with orbital
exentration

No. of
cases
with
noninvasive
fungal
sinusitis
18
0

Percentage
out of 19

No. of
cases
with
invasive
fungal
sinusitis

Percentage
out of 11

Total
no.
of
cases

Percentage
out of 30

94.73
0

0
8

0
72.72

18
8

60
26.66

1
0

5.26
0

0
1

0
9.09

1
1

3.33
3.33

18.18

6.66

Chart No. 10: Surgical treatment

non-invasive fungal sinusitis

invasive fungal sinusitis

0
18
8
0

0
1

88

1
0

2
0

TABLE NO. 11: CULTURE REPORTS

Culture Reports

Aspergillusfumigat
us
Aspergillusflavus
Aspergillusniger
Rhizopus
Others
Negative

No. of
cases
with
noninvasiv
e
fungal
sinusiti
s
1

Percentag
e out of
19

No. of
cases
with
invasiv
e
fungal
sinusiti
s

Percentag
e out of
11

Total
no.
of
case
s

Percentag
e out of
30

5.26

18.18

10

3
2
0
1
12

15.78
10.52
0
5.26
63.15

2
1
4
1
1

18.18
9.09
36.36
9.09
9.09

5
3
4
2
13

16.66
10
13.33
6.67
43.33

Chart No. 11: Culture Reports

non-invasive fungal sinusitis

Negative

Others

1
12
1
1
4

Rhizopus
0

Aspergillus niger

1
2
2

Aspergillus flavus

Aspergillus fumigatus

invasive fungal sinusitis

3
2
1

89

TABLE NO. 12: HISTOPATHOLOGICAL REPORTS

Histo-

No. of

Percentage

No. of

Percentage

Total

Percentage

Pathological

cases

out of 19

cases with

out of 11

no. of

out of 30

reports

with

invasive

non-

fungal

invasive

sinusitis

cases

fungal
Inflammatory

sinusitis
14

73.68

14

46.67

0
0

0
0

3
8

27.27
72.72

3
8

10
26.66

polyp without
fungal invasion
Aspergillosis
Mucormycosis

Chart No. 12: Histopathological reports

Inflammatory polyp without fungal invasion
Aspergillosis
Mucormycosis
14

0
non-invasive fungal
sinusitis
0

0
invasive fungal sinusitis

90

TABLE NO. 13: PROGNOSIS

Prognosis

Disease free
Recurrence
Death

No. of

Percentage

No. of

Percentage

Total

Percentage

cases

out of 19

cases

out of 11

no. of

out of 30

with non-

with

invasive

invasive

fungal

fungal

sinusitis

sinusitis

17
2
0

89.47
10.52
0

7
0
4

cases

63.63
0
36.36

Chart No. 13: Prognosis

17

18
16
14
12
10
8
6

4
2

2
4

0
non-invasive fungal sinusitis
0
0
invasive fungal sinusitis
Disease free

Recurrence

DISCUSSION

91

Death

24
2
4

80
6.67
13.33

In this prospective study, the clinical profiles, investigations and

management of patients with fungal rhinosinusitis were studied from July
2009 to October 2011.
Diagnostic analysis:
In this present study which included 30 patients of fungal
rhinosinusitis 19 (63.33%) patients were diagnosed to have non-invasive
fungal rhinosinusitis of which 16 patients (53.33%) had allergic fungal
rhinosinusitis, 2 patients (6.67%) had fungal balls and 1 patient (3.33%)
had saprophytic fungal colonisation. The remaining 11 patients (36.67%)
had invasive fungal rhinosinusitis. Out of 11 patients, 9 (30%) were of
acute fulminant variety while 1 case (3.33%) was of chronic invasive type
and 1 (3.33%) was of chronic granulomatous type.
Age:
In our study of the 30 patients, majority of cases were between 41
to 50 years of age forming 26.67% of cases. The youngest patient was 15
years old and the oldest being 65 years. Of all the cases of non-invasive
fungal sinusitis, the cases with allergic fungal rhinosinusitis were from 15
to 65 years of age. The cases with fungal balls were from 33 to 35 years of
age and the cases with acute fulminant invasive fungal rhinosinusitis were
from 33 to 65 years of age and both the cases of chronic invasive fungal
rhinosinusitis were between 55 to 65 years. The mean ages of various
series of allergic fungal rhinosinusitis ranged from 23 to 42.4 years of
age.15,16 The average age reported for patients with fungal ball in an
American retrospective series of 29 cases was 64 years, ranging from 28
92

to 86 years.26 A comprehensive review by deShazo and Klossek also

showed a similar age range, with the youngest reported age being 18
years.25,27 Patients reported infected with rhino-cerebral mucormycosis
range in age from 16 days to 75 years according to Berrylin J. Ferguson. 11
Sex:
In our study males were almost equally affected with fungal
rhinosinusitis compared to females. Of the 30 patients studied 16 were
males (53.33%) and 14 were females (46.66%). Of the 19 cases of noninvasive fungal rhinosinusitis 11 patients were females and 8 patients were
males. Of the 11cases of invasive fungal rhinosinusitis 8 patients were
males and 3 patients were females. Of the 16 cases of allergic fungal
rhinosinusitis, 10 were females and 6 were males with a female
preponderance of 1.6 females per males. Some studies have noted a fairly
equal sex predilection for AFRS whereas Manning and Holman noted a
male predominance of 1.6males per female.16,17
Signs and symptoms:
In the present study nasal obstruction was the most common
presenting symptom noted in 29 patients i.e. 96.67% of cases. 15 out of
30 patients (50%) had nasal discharge. 21 out of the 30 (70%) patients
had headache. Nasal polyposis was the most common finding on local
examination in patients with non-invasive fungal rhinosinusitis. 12 out of 16
(75%)of the patients of our study with AFRS had polyposis.

93

The incidence of polyposis in AFRS reported in literature is almost

100%.17 According to Berrylin J. Ferguson the most common symptoms of
fungal ball are nasal obstruction, nasal discharge and facial pain. These
symptoms were present in both the patients having fungal ball in the
present series. The literature has reported that 10% of patients with fungal
ball have polyp27 which was present in both these patients in this series.
In our study comprising 11 patients of invasive fungal rhinosinusitis,
6 patients had fever (54.54%), 8 had facial swelling (72.72%) 4 had
deviation of angle of mouth (36.36%), 7 had diminution of vision (63.63%)
and paraesthesia (72.72%) was present in 8 patients. These symptoms
were absent in cases with non-invasive fungal rhinosinusitis. Proptosis
(63.63%), opthalmoplegia (63.63%), ptosis (63.63%) and palatal erosion
(27.27%) were also seen in invasive fungal rhinosinusitis.
According to Kennedy, Adams and Neglia the most common
symptom in acute fulminant invasive fungal rhinosinusitis is fever present
in upto 90% of patients. Facial pain, nasal discharge and headache are
variably present in 20% to 60% of such patients. 29,30,32
Berrylin J. Ferguson has reported facial numbness as an early
symptom in 7% of cases.11 He believes that it is an under representation of
an early symptom that is not usually assessed.
According to Yohia and colleagues who reviewed 114 cases of
rhino-orbital-cerebral mucormycosis from the literature, nasal ulcerations
occurred in approximately one third of cases. 46 Opthalmoplegia was
present in 29% of patients, proptosis in 16% of patients, nasal discharge in
94

18% of patients and palatal necrosis in 14% of patients. Harold et al found

decreased vision in 92% of patients and cranial nerve palsies in 77% of
patients of rhino- orbital-cerebralmucormycosis. 52
In our study, out of 19 cases of non-invasive fungal rhinosinusitis, 2
patients (10.52%) had history of Bronchial Asthma. Studies have revealed
that one-third to one-half of the patients with allergic fungal rhinosinusitis
have asthma.17
In our series, 11 out of 30 patients (36.67%) had associated
Diabetes mellitus, in which 1 (5.26%) case was on non-invasive variety
and 10 (90%) were of invasive fungal rhinosinusitis. In the largest series
to date 126 patients with rhino-cerebral-mucormycosis, 70% of patients
were diabetic.11 Uncontrolled diabetes was the commonest underlying
disease in 30 (88.2%) of the 34 patients with histopathological diagnosis of
rhino-orbito-cerebral mucormycosis studied by Nithyanandam S et al. 53
None of our patients in the present series had HIV or AIDS. The
literature has only 12 reported cases of mucormycosis for all organs in
AIDS patients.53
Radiological finding:
In our study, mucosal thickening was the most common finding
(60%) in CT-PNS of the patients with fungal rhinosinusitis.
Polypoid masses were seen in 13 of the 19 (68.42%) patients with
non-invasive fungal rhinosinusitis. Heterogenous opacity in sinonasal
compartments was seen in 6 (31.57%) patients of non-invasive fungal
95

rhinosinusitis while radiodensity in sinonasal compartments was seen in 3

(15.78%) patients with non-invasive fungal rhinosinusitis.
In the series by Klossek et al, on CT-PNS, 97 of 109 cases of fungal
balls showed heterogenous opacities and upto half of the cases
demonstrated radiodensities with central portion of the soft tissue mass. 39
One of the 2(50%) patients of fungal ball in the present series had
antrochoanal polyp. Presence of antrochoanal polyp in fungal ball patients
has been reported by B. J.Ferguson. 24 Both patients with fungal ball had
heterogenous opacities in sinonasal compartment in our series.
Heterogenous enhancing lesion (81.81%), bony invasion and
destruction (90.90%), orbital invasion (54.54%) and intracranial extension
(18.18%) were present exclusively in CT scans of patients with invasive
fungal rhinosinusitis in our study.
Andrew Blitzer et al had observed mucosal thickening in 60% of the
patients and bony erosion in 50% of patients with rhino-orbital-cerebral
mucormycosis.9
Endoscopic findings:
In our study, the most common endoscopic finding in cases with
non-invasive fungal rhinosinusitis was polyposis found in 12 patients
(63.15%) followed by gray fungal debris with clay like consistency found in
8 (42.10%) patients. Allergic mucin was present in 11 out of 16 (68.75%)
patients with allergic fungal rhinosinusitis Both patients of fungal ball had
thick clay-like material in sinuses. Fungal colonisation on nasal crusts was

96

found in 1 patient (5.26%) who was diagnosed to have saprophytic

colonisation.
The incidence of polyposis in AFRS reported in literature is almost
100%.17
In our series, pallor of middle turbinate (45.45%) and black eschar
(45.45%) were the most common findings in cases with invasive fungal
rhinosinusitis, followed by nasal crusts (36.36%), black necrotic debris with
coal-tar like consistency (18.18%) and mucopus(9.09%).
According to Christopher N. Prichard pallor of middle turbinate is
the

earliest

endoscopic

finding

in

patients

with

invasive

fungal

rhinosinusitis.10 Gillespie and O Malley have examined the role of middle

turbinate biopsy for the diagnosis of invasive fungal rhinosinusitis with 75%
sensitivity and 100% specificity.28
Surgical treatment:
Functional endoscopic sinus surgery (FESS) was the surgical
treatment in 18 out of 19 (94.43%) patients with non-invasive fungal
rhinosinusitis. Endoscopic removal of nasal crusts was done in 1 patient
with saprophytic colonization.
Mabry et al call FESS as a conservative but complete surgery
relying upon it completely.48
2 of the 19 (10.52%) patients with non-invasive fungal rhinosinusitis
had recurrence at 6 months follow-up of which one was treated by revision
surgery and the other was treated conservatively.
97

None of the two patients with fungal ball had recurrence after
surgery.
Waxman et al reported 3 groups of AFRS patients, those with
immediate recurrence within a matter of months after treatment, delayed
recurrence after a year or more and cured patients who were free of
symptoms with the follow up to 2 years. 23
In our study, all the 8 patients with invasive fungal rhinosinusitis
were treated by endoscopic debridement. Orbital exenteration was done in
addition to endoscopic debridement in 2 patients- 1 (11.11%) with acute
invasive fungal rhinosinusitis and other with chronic granulomatous
disease. The patient with chronic invasive fungal rhinosinusitis required
additional maxillectomy for palatal involvement and antrocutaneous fistula.
After 6 months of disease free follow-up, the patient with chronic
invasive disease was treated with Left facial reconstruction and palatal
prosthesis and the orbital defect of the patient with chronic granulomatous
disease was reconstructed using free antero-lateral thigh flap. Both these
patients are still under follow-up.
In our present study 4 out of the 10 (40%) patients who underwent
endoscopic debridement with achievement of disease free bleeding
margins died. All of these 4 patients who died had orbital involvement and
one patient had intracranial involvement. In a series of Kennedy et al all 6
patients with orbital and intracranial involvement died of invasive fungal
disease.30

98

Orbital exenteration was once advocated for ocular involvement if

blindness had occurred. This is now controversial and there are several
case reports of patients surviving episodes of mucormycosis with ocular
involvement and blindness who did not undergo orbital exenteration.
These cases must be individualized according to Berrylin J. Ferguson. 11
We feel that surgery should be tailor-made to suit the extent of the
disease in each patient.
Medical treatment:
In our study, topical steroids and systemic steroids were used in 18
out of 19 patients (94.73%) with non-invasive fungal rhinosinusitis. 1
(3.33%) patient with saprophytic colonization was not given steroids. Oral
Itraconazole was used in 17 (89.47 %) patients with non-invasive fungal
rhinosinusitis with a success rate of about 88.23%.
Agarwal et al recommend the use of oral Itraconazole in a dose of
400mg per day for 10 days.55 Rains et al reported retrospectively on 139
patients with AFRS treated with steroids and post-operative Itraconazole,
where they found that this regime may reduce the need for revision
surgery.56 Topical and systemic antifungal therapy for AFRS patients has
been studied by Kuhn et al with mixed to poor results. 22 Waxman et al
suggested the use of systemic corticosteroids post-operatively.23 10 out of
26 patients studied by Kupferberg et al, who after surgery received
prednisolone therapy, reported lesser incidence of endoscopically
confirmed disease, on follow up. 57 A 4-year follow up study of 11 AFRS
patients by Kuhn and Javer demonstrated a reduction in mucosal stage
99

and IgE level post operatively while the patients were on systemic
steroids.22
In our study, topical Amphotericin B douches were used in 7 out of 9
(77.77%) cases of acute invasive fungal rhinosinusitis with success rate of
77.77% and in both cases (2) of chronic invasive fungal rhinosinusitis with
success rate of 100%. None of the patients with non-invasive fungal
sinusitis were treated with Amphotericin B douches.
As reported by A Helbling et al Amphotericin B nasal spray has no
effect on nasal polyp. 58 Trigg et al have reported decrease in the incidence
of invasive fungal disease from 13.8% to 1.8% in neutropenic patients by
the use of Amphotericin B in the spray form. 26Berrylin et al has
recommended topical application of Amphotericin B with 15mg vial of the
drug and 10ml sterile water.11
In our series, systemic Amphotericin B was used in all 9 patients
with acute invasive fungal rhinosinusitis, in a dose of 0.5mg/ kg/day over a
period of 6 weeks, with a success rate of about 55.55% as compared with
a 79% survival rate quoted by Andrew Blitzer et al. 352 patients of chronic
invasive variety also received systemic Amphotericin B with a success rate
of 100%. Randal S. Weber et al reported excellent results with liposomal
Amphotericin B i.e. 71% in cases of invasive fungal infections. 64 High dose
Amphotericin B is an important adjunct in the treatment of invasive fungal
rhinosinusitis. However Amphotericin B alone without surgery is thought be
insufficient in treatment of invasive fungal rhinosinusitis.

100

KOH mounts and culture reports:

In our study, intraoperative KOH mounts of all patients of fungal
sinusitis patients were positive.
Aspergillus flavus was the most common organism (16.66%) grown
on fungal culture of all patients with fungal rhinosinusitis. According to
case reports of paranasal sinus mycoses from India and Sudan,
Aspergillus flavus is the most common isolated organism on fungal
cultures.55
Rhizopus was the commonest organism (36.36%) grown on fungal
culture of all patients with acute invasive fungal rhinosinusitis in our study.
As reported by A Daudia et al the commonest causes of acute
fulminant fungal sinusitis are moulds of the mucorales order, including
rhizopus and rhizomucor species.59Aspergillusfumigatus is the most
frequently isolated species in both invasive arid non-invasive fungal
sinusitis in immunocompetent as well as immunocompromised patients. 56
Other pathogens include those belonging to the family Mucoraceae
including the genera Mucor, Rhizopus and Absidia.
Negative cultures were found in 63.15% of patients with noninvasive fungal rhinosinusitis and in 9.09% of patients with acute invasive
fungal rhinosinusitis.

101

Histopathological findings:
Inflammatory polyp without evidence of fungal invasion but with
eosinophilic infiltrate was the most common histopathological finding in 14
out of 19 (73.68%) cases with non-invasive fungal rhinosinusitis. 3 of the
14 (21.42%) patients with non-invasive fungal rhinosinusitis who had
inflammatory polyp on histopathological examination showed positive
fungal culture. Aspergillus flavus was isolated in two of these cultures and
Aspergillus niger in 1 culture.In a study of 100 polyposis patients by
Kordbacheh et al, 9 cultures yielded pure growth of fungi with Aspergillus
flavus as the most common organism.60
Absence of allergic mucin in histopathological examination of these
patients may be due to preoperative treatment with topical and systemic
steroids in our study. Pre-operative steroids cause resolution of
eosinophilic mucin and may obscure the diagnosis of AFRS according to
Graham and Ballas.61
In our study, of all the 11 patients of invasive fungal rhinosinusitis 5
patients (45.45%) had Aspergillosis on histopathological examination.
Prognosis:
Of all the 19 cases with non-invasive fungal rhinosinusitis 17
patients (89.47%) were disease free at 6 months follow up, whereas 2
patients (10.52%) had recurrence.
Of the 9 cases with acute invasive fungal rhinosinusitis 5 patients
(55.55%) were disease free at 6 months follow-up, while 4 patients
102

(44.44%) succumbed to death. All of these 4 patients had intraorbital

extension while one patient had intracranial extension of the disease.
Out of the 11 cases with invasive fungal rhinosinusitis 4 had only
sinonasal disease, all of which survived with a success rate of 100%.
Both the cases of chronic invasive variety were disease free after 6
months follow-up with 100% success rate.
In a series by Nithyanandam S et al, a success rate of 91% was
found in patients with sinonasal invasive fungal disease. 53 Andrew Biitzer
et al reported 78% survival in cases with paranasal mucormycosis. 35
Out of the 2 cases with intracranial extension 1 has survived and is
on regular follow-up. Thus we had a 50% survival rate in rhino-orbitocerebral mucormycosis cases. In our study we had about 63% survival
rate with medical and surgical line of treatment in mucormycosis
comparable with 84% survival rate reported by Harold Pillsbury et al. 42
According to Gillespie and OMalley a mortality rate of 100% has been
demonstrated in patients with intracranial involvement. 26 In a series of
Kennedy et al, all 6 patients with orbital and intracranial involvement died
of invasive fungal disease.28

103

SUMMARY AND CONCLUSIONS

This was a prospective study comprising of 30 patients suffering
from Fungal Rhinosinusitis. Following conclusions were drawn from the
study.
1. Fungal Rhinosinusitis was found to be more common between
the age group 40 to 50 years (8 out of 30; 26.67%). Non-invasive fungal
rhinosinusitis was more common in younger age group between 2050years (13 out of 19; 68.42%) whereas invasive fungal rhinosinusitis was
more common in the older population between 40-70 years (10 out of 11;
90.90%).
2. There was a slight male preponderance as compared to females
in the overall incidence of fungal rhinosinusitis (16 males & 14 females;
53.33%). Non-invasive fungal rhinosinusitis was more common in females
(11 out of 19; 57.89%) whereas invasive fungal rhinosinusitis was more
common in males (8 out of 11; 72.72%).
3. The common clinical features of fungal rhinosinusitis were nasal
obstruction, nasal discharge, and headache and were present in both
invasive and non-invasive forms. Excessive sneezing was seen only in
cases with non-invasive fungal rhinosinusitis, whereas fever, facial
swelling, deviation of angle of mouth, diminution of vision and
paraesthesia was seen only in cases with invasive fungal rhinosinusitis.
Nasal polyposis was the most common finding on local examination in
patients with non-invasive fungal rhinosinusitis (12 out of 19; 63.15%),

104

whereas proptosis, opthalmoplegia, ptosis and palatal erosion were seen

in invasive fungal rhinosinusitis.
4.

Invasive

fungal

infection

was

commonly

seen

in

immunosuppressed and immunocompromised patients such as patients

with diabetes mellitus (10 out 0f 11; 90%), renal failure (1 out of 11; 9.09%)
etc. Bronchial asthma may be associated with non-invasive fungal
rhinosinusitis.
5. Computed Tomography and Magnetic Resonance Imaging are of
utmost importance to know the extension of the disease and also in the
management of the patients. Mucosal thickening was the most common
finding in CT-PNS of all the patients with fungal rhinosinusitis (18 out of 30;
60%). Polypoidal masses (13 out of 19; 68.42%), heterogenous opacity
and radiodensity in sinonasal compartments (6 out of 19; 31.57%) were
seen in patients with non-invasive fungal rhinosinusitis. Heterogenous
enhancing lesion, bony invasion and destruction, orbital invasion and
intracranial extension were present exclusively in CT scans of patients
with invasive fungal rhinosinusitis.
6. The most common endoscopic finding in cases with non-invasive
fungal rhinosinusitis were polyposis (12 out of 19; 63.15%), allergic mucin
(11 out of 19; 57.89%) and grey fungal debris (8 out of 19; 42.10%). Pallor
of middle turbinate (5 out of 11; 45.45%) and black eschar were the most
common findings in cases with invasive fungal rhinosinusitis.
7. Aspergillus flavus was the most common organism grown on
fungal culture of all patients with fungal rhinosinusitis (5 out of 30;
105

16.66%). Rhizopus was the commonest organism grown on fungal culture

of all patients with acute invasive fungal rhinosinusitis (4 out of 11;
36.36%).
8. Inflammatory polyp without fungal invasion but with eosinophilic
infiltrate was the most common histopathological finding in patients of noninvasive fungal sinusitis (14 out of 19; 73.68%) while mucormycosis was
the most common histopathological finding in invasive fungal sinusitis (8
out of 11; 72.72%).
9. Treatment of choice was surgical debridement along with either
oral or systemic antifungals. Topical and systemic steroids were used only
in non-invasive fungal rhinosinusitis. Systemic Amphotericin B was used in
all cases of invasive fungal rhinosinusitis.
10. Cases with non-invasive fungal rhinosinusitis had good
prognosis as compared with those of invasive fungal rhinosinusitis with a
cure rate of 89.47% (17 out of 19) and 63.63% (7 out of 11) respectively.
Acute invasive cases has poorer success rate (5 out of 9; 55.55%) while
chronic invasive cases had 100% success rate. A combination of medical
and surgical line of treatment improved the prognosis significantly.
11. Currently novel regimes for the treatment of invasive and noninvasive fungal rhinosinusitis include oral Voriconazole, combination of
liposomal Amphotericin B and either an Echinocandin or Itraconazole or
both.

106

Finally, prompt diagnosis, reversal of predisposing conditions and

aggressive surgical debridement remain cornerstones of therapy for this
deadly disease.

107

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KEY TO MASTERCHART
p: present
a: absent
FESS: Functional endoscopic sinus surgery
IP: inflammatory polyp without fungal invasion
AS: Aspergillosis
AFRS: Allergic fungalrhinosinusitis
Aifs: Acute invasive fungal sinusitis
Cifs: Chronic invasive fungal rhinosinusitis
Cgfs: Chronic Granulomatous fungal rhinosinusitis
U: used
OI: oral itraconazole
IAB: Injectable Amphotericin B
SC: Saprophytic colonisation
BSL: Blood sugar level
Arf: Acute renal failure
Crf: Chronic renal failure
BUN: Blood urea nitrogen
NA: Not Applicable
115