Fungal sinusitis a review

FUNGAL SINUSITIS
A review
Dr.Malarvizhi.R
MBBS, DLO

Intro
• Rare - is it?
• Increased incidence in last 2 decades
• Presence of Fungi in 100% normal and 96% chronic RS
• Recent technology in serology, histology MYCOLOGY &
radiology contributed to detection
21-Apr-17 DR.R.Malarvizhi MBBS,DLO

Risks
• Diabetes mellitus
• Increased use of broad spectrum antibiotics
• Topical nasal spray – inadvertent and indicative use
• Acquired immunodeficiency states- viral,
immunosuppressive drug intake (post-organ
transplantation), chronic steroid users
• Defective immune response states- post-radiotheray and
chemotherapy

• Low granulocyte count
• Acute leukemia
• Lymphoma
• Aplastic anemia
• Multiple myeloma
• Renal failure
• Malnutrition
• Gastroenteritis
• Burn injury

Peak into Mycology
• Fungi grows well in
• Humid and wet environment
• High osmotic ( high glucose)
• Acidic environment
• Mucor, Rhizopus, Aspergillus sp
• Smears and culture

Aspergillus
• Aspergillus
• Longitudinally-
centrifugally in cultures,
tubular hyphae
• 45 degree Y- shaped
hyphae
• Does not require light
• Needs a host for metal
ions, glucose, nitrogen,
sulphur, calcuim, ZINC

Mucor
• Mucor
• Rhizopus, Mucor,
Absidia
• Hyphae vary in width,
branch off at 90 degree
• Propensity for vascular
invasion high ( higher
incidence in Diabetic
ketoacidosis)

Tissue sections showing Mucor

Some organisms
• Aspergillus fumigatus
• Aspergillus flavus
• Aspergillus niger
• Alternaria
• Bipolaris
• Candida
• Curvularia
• Fusarium
• Paeciomyces
• Penicillium
• Pseudoallescheria
boydii
• Rhizopus/Mucor
• Scedosporium
apiospermum
• Scopulariopsis
• Yeast not Candida

Spectrum of Disease
• Extramucosal (noninvasive) fungal rhinosinusitis
• Superficial sinomucosal mycosis
• Fungal ball
• Allergic fungal RS
• Invasive fungal rhinosinusitis
• Chronic invasive (indolent) fungal RS
• Granulomatous
• Non granulomatous
• Acute (fulminant) fungal RS

Signs and Symptoms
Major
• Nasal obstruction/ blockage
• Rhinorrhoea – purulent
nasal discharge/ discolored
post nasal discharge
• Olfactory disturbance
• Facial congestion / fullness
• Facial pain/ pressure
• Hyposmia / Anosmia
• Purulence in nasal cavity on
examination (anterior nasal)
• Fever (acute RS only)
Minor
• Headache
• Fever ( all non-acute)
• Halitosis
• Fatigue
• Dental pain
• Cough
• Ear pain/ pressure/
fullness

Other signs and symptoms
• Proptosis
• Visual impairment
• Focal neurologic deficits
• Seizures
• Altered sensorium

Superficial sinonasal mycosis
• NON-INVASIVE
• Mc in post surgical, immunosuppressed and such
• Aspergillus, Candida sp
• Part of flora of mucous membrane
• Arise when local systemic factors decrease resistance of
the patient
• Such as local mucous membrane continuity disruption-
ulcers, nasal sprays, radiation
• General risk factors

Foreign body
covered
superiorly by
fungi

Superficial
sinonasal
mycosis

• Smears to be taken – not miss out malignancy
• Mixed cultures
• Biopsy
• DD- Malignancy, TB
• Careful removal of crusts and debris by endoscopic
visualization
• Local irrigation with Clotrimazole / naftifine
• Milder cases Ketoconazole is valuable in Oral therapy

• In chronic Aspergillus or Candida, in extensive invasion of
mucous membrane or when specific complications are
expected , Ampho –B, with or without Flucytosine IV
• Both A.fumigatus and Candida sp can become inhaled
allergens and trigger or sustain specific rhinopathies and
asthma

Fungal ball
• NON-INVASIVE
• An overgrowth of fungal elements in the sinuses
• Most commonly molds such as Aspergillus are
responsible.
• The most commonly involved sinuses –
• maxillary and the sphenoid sinuses, where the fungus finds
favorable conditions such as warmth and humidity for growth.
• Sometimes, bacteria can cause super-added infection in the sinus
affected by the fungus ball.
• Typically, only a single sinus is involved, and the disease
has a classic appearance on CT or MRI scans.

Fungal Ball in
Sphenoid sinus
Differentail Diagnosis
Rhinoscleroma

Fungal Ball
Sphenoid

Fungal Ball
Maxilla

• Surgical removal of the fungus ball through endoscopic
sinus surgery.
• Characteristic ‘peanut-butter’- like appearance of the
fungal ball
• Most have excellent results from surgery, and may not
require any further treatment

Allergic Fungal RS- NON-INVASIVE
• Immunocompetent patients
• Allergy to fungi
• The causative fungi resides in the mucin and provides
continued allergic reaction
• Similar ABPA

• Allergic mucin
• Type 1 hypersensitivity
• <30 years, no gender predominance
• May associate wit polyps
• Mucin – hyphae
• Culture necessary
• RAST, total IgE, antigen specific IgE or IgG

Diagnostic criteria (Bent & Kuhn)
• Major
• Type I hypersensitivity confirmed by history, skin tests or serology
• Nasal polyposis
• Characteristic CT scan signs
• Positive Fungal stain or culture
•

• Minor
• Asthma
• Eosiophilic mucus with fungal elements and no tissue invasion
• Unilateral predominance
• Radiographic bone erosion
• Charcot- Leyden crystals (Lysophospholipase)
• Peripheral Eosinophilia

Diagnostic criteria
• Kupferberg – Endoscopic (for the purpose of post
operative management)
• Stage 0- no mucosal oedema or allergic mucin
• Stage 1- Mucosal oedema with or without allergic mucin
• Stage 2- polypoid oedema with or without allergic mucin
• Stage 3- sinus polyps with fungal debris or allergic mucin

Allergic fungal
RS
Landmarks maintained

Treatment
• Removal of all mucin
• Recurrence is common
• Prednisone in oral – during entire treatment regimen (
start before surgery and continue after surgery and taper
and stop as per response)
• No use for systemic and topical anti-fungals ( Mabry et al)
• Immunotherapy with fungal antigens and positive non-
fungal antigens – reduces necessity for systemic &/ local
steroids and chances of recurrence. (Mabry et al)

INVASIVE

Chronic invasive (indolent) fungal RS
• Two variants based on presence of granulomas within
tissue
• Granulomatous
• Non-granulomatous
• Healthy individuals with previous history Chronic RS
• An asymptomatic period occurs only when orbit or skull
base are involved

Chronic Fungal RS
• Slower destructive process
• Rarely causes vascular invasion, sparse inflammatory
reaction and limited involvement of surrounding
structures.
• Common in HIV, Diabetes mellitus and long term use of
steroid
• Most commonly affects Ethmoid and Sphenoid
• The typical time course of the disease is over 3 months.
• Tissue cultures show fungus in over half the patients, and
Aspergillus fumigatus is the most commonly grown
fungus.

Granulomatous Chronic Fungal RS
• Present with an enlarging mass in the cheek, orbit, nose,
and sinuses.
• Microscopically, it is characterized by formation of
granulomas, and this differentiates it.
• Aspergillus flavus is usually the causative organism.
• Treatment may involve surgery in combination with
antifungal agents.

Chronic
invasive Fungal
rhinosinusitis
Lamina papyracea
breached

• Treatment
• Surgery in combination with medical therapy
• Anti-fungal drugs and
• Measures to restore the patient’s immune system

Acute (fulminant) fungal RS
• Most dangerous and life-threatening form of fungal sinusitis.
• Very rare
• usually only affects severely immunocompromised patients
• leukemia, aplastic anemia, uncontrolled diabetes mellitus, and
hemochromatosis.
• anti-cancer chemotherapy or organ/ bone-marrow transplantation are
especially susceptible.
• Aspergillus or Mucor, Rhizopus are the most frequent causative
agents.
• Has an aggressive course, with fungus rapidly growing through
sinus tissue and bone to extend into the surrounding areas of
the brain and eye.

• Endoscopically areas of dead tissue and eschar are
noted.
• Microscopic examination shows invasion of blood vessels
by the fungus, leading to necrosis.
• Treatment - aggressive surgical and medical therapy.
• Repeated surgery may be necessary to remove all dead
tissue.
• Anti-fungal drugs and restoring the immune status of the
patient are key to improving survival, as this disease is
frequently fatal

Fungal rhinosinusitis with orbital and cranial invasion (yellow
arrows) References: Dept. of Radiology, Hospital Clinic
Barcelona - Barcelona/ES

Assessment of immune status
• Complete blood count with differential
• Blood chemistry
• Liver function enzymes
• Autoimmune enzymes
• Anergy panel for cellular and humoral immunity
• HIV testing

Management
• Investigations and Treatment with Follow-up
• Clinical
• Laboratory
• MYCOLOGY LAB
• Radiological

• Before starting treatment
• Usg pelvis with abdomen
• Renal function tests with all electrolytes
• Liver unction tests
• PT, activated PTT
• BT, CT
• Blood counts and ESR
• Chest X ray, ECG

Monitor
• Serum / blood glucose, urine glucose and urine ketones
everyday
• Blood urea, creatinine, Na and k on alternate days
• Mg and Ca with serum bilirubin and Albumin every 3rd day
• ECG every 3rd day
• Input and output charts

Glycemic control
• Diabetologist
• Insulin analogues best
• With sliding scale / fixed dose (former better during active
management)

Don’t hesitate
• To seek opinion
• Microbiologist
• Mycology – DERMA
• Nephrology
• Hepatology
• DIABETOLOGY

Surgery
• Endoscopic removal
• Aggressive in invasive lesions
• Dictum- remove till fresh bleeding points
• Saline flush and remove technique for fungal balls

Amphotericin-B
• THE drug
• Various forms
• Regimen to be completed for success in therapy
• No difference in liposomal and convential except finish the
course earlier

MOA
• Amphotericin B binds with ergosterol, a component of
fungal cell membranes, forming pores that cause rapid
leakage of monovalent ions (K+, Na+, H+and Cl− ) and
subsequent fungal cell death.
• This is amphotericin B's primary effect as an antifungal
agent.
• It has been found that the amphotericin B/ergosterol
bimolecular complex that maintains these pores is
stabilized by Van der Waals interactions

Bioavalability 100% (IV)
Metabolism kidney
Biological half-life initial phase : 24 hours,
second phase : approx. 15 days
Excretion 40% found in urine after single
cumulated over several days
biliar excretion also important

• Very often, it causes a serious reaction soon after infusion
(within 1 to 3 hours)
• high fever, shakingchills,
• hypotension,
• anorexia,
• nausea, vomiting, headache, dyspnea and tachypnea, drowsiness,
and generalized weakness.
• The violent chills and fevers have been nicknamed "shake and
bake"

• This reaction sometimes subsides with later applications of the
drug, and may be due to histamine liberation.
• An increase in prostaglandin synthesis may also play a role.
• This nearly universal febrile response necessitates a critical
(and diagnostically difficult) professional determination as to
whether the onset of high fever is a novel symptom of a fast-
progressing disease, or merely the effect of the drug.
• To decrease the likelihood and severity of the symptoms, initial
doses should be low, and increased slowly.
• Paracetamol, pethidine, diphenhydramine
and hydrocortisone have all been used to treat or prevent the
syndrome, but the prophylactic use of these drugs is often
limited by the patient's condition.

• S/E
• Renal failure
• Hypokalemia
• Hypomagnesimia
• Heapatotoxicity and fulminant liver failure
• Anemia and blood dyscrasias
• Severe cardiac arrhythmias (VF)
• Cardiac failure
• Sever skin reactions

Amphotericin B
• During every dose
• One pint Normal saline before infusion and one pint
Normal saline after infusion
• Dose 0.25-0.5mg/kg/day body weight
• Start with test dose MUST DAY 1
• 50mg in 50 ml DEXTROSE containing solution and use 1 ml in 100
ml d5 over 30 minutes
• Discard remaining (though cost effective measure is use it for nasal
douching)

• DAY 2
• 50mg in 50 ml D5 , infuse 5ml in 100 ml D5 over 1 hour
• DAY 3
• 50mg in 50ml D5, infuse 10 ml in 300 ml D5 over 1 hour

• DAY 4 - 25ml
• DAY 5 - 50ml
• DAY 6 – 50ml
• 50ml is 50 mg (avg dosage used 50mg per day-
conventional preparations of Ampho-B)
• Course to be completed within 3-4weeks with patient
compliance often hindering completion
• Cumulative dose of 800-1000mg by the time course
completed
• Liposomal preparations 1-5mg/kg/day
• Lipid complex and Conventional preparations 0.25-1
mg/kg/day

Anti-fungals Used
Non- invasive
• Clotrimazole ( outdated)
for superficial
• Ketoconazole for
superficial
Invasive
• Amphotericin – B
• Itraconazole
• Voriconazole
• Posaconazole
• Of these Only Ampho-B
and Posaconazole used
in Mucor

Other Measures supplementary
• Granulocyte colony stimulating factor
• Hyperbaric oxygen therapy
• Echinocandins: Caspofungin, Micafungin, Anidulafungin

Posaconazole
• Wonder drug, Expensive
• But cannot be used to initiate or used as solo drug
• Must be started after Ampho B course
• Anti-Mucor

Prognosis
• Excellent in non-invasive
• Very poor in invasive ( acute > chronic)

Realistic approach
• Patient compliance
• Patient education and self awareness of disease and
realistic expectations
• Patient caregiver (attender/ FAMILY) education and
realistic HOPE
• Frequent counselling to adhere to strict glymic control and
FINISH the course of Ampho B
• Some aspects cannot be predicted and some
eventualities must be explained to patient and family
BEFORE the start as well as during the course of
treatment with AmphoB

• FOLLOW up is the dictum

• Multidisciplinary approach and management
• Your role
• Patient compliance- foremost in successful outcome
• What and how much to give
• Know when to stop
• FOLLOW UP- for safe patient and Otolaryngologist

Fungal sinusitis a review

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