radiological findings and the management of invasive FRS

1. Radiological findings
and
management of invasive
fungal rhinosinusitis

2. Radiological findings
Axial CT scan shows right ethmoid and sphenoid sinusitis with destruction of
the lateral wall of the right sphenoid sinus (arrow).

3. Axial unenhanced CT scan shows sinus disease in
the ethmoid, maxillary, and sphenoid sinuses. Note
the left-sided facial swelling.
Axial contrast-enhanced CT scan shows lack of
enhancement in the left cavernous sinus (arrows)
secondary to thrombosis from invasive fungal sinusitis.

4. Axial unenhanced CT scans (1 obtained craniad to 2) show soft-tissue thickening in the left posterior ethmoid air
cells, which is destroying the medial wall of the orbit and extending into the retro-orbital soft tissues (arrow).

5. Axial unenhanced CT scan shows increased attenuation in the right anterior and posterior ethmoid air cells and right
sphenoid sinus with soft-tissue thickening in the orbital apex (arrow). (b) Coronal unenhanced CT scan shows
destruction of the medial wall and floor of the right orbit and disease extension into the orbit (arrows). (c) Axial
unenhanced CT scan obtained caudad to a shows destruction of the posterior wall of the right maxillary sinus and
obliteration of the periantral fat plane immediately posterior to the sinus (arrows).

6. (a) Axial contrast-enhanced CT scan shows increased attenuation in the left anterior and posterior ethmoid
air cells with destruction of the medial wall of the left orbit (arrow). (b) Coronal contrast-enhanced CT scan
shows a subperiosteal abscess occupying the inferomedial aspect of the left orbit and displacing the medial
and inferior rectus muscles laterally (arrows). Note also the destruction of the orbital floor (arrowhead) and
the increased attenuation in the adjacent left maxillary sinus.

7. Chronic invasive fungal sinusitis. unenhanced CT scans show bilateral mucosal thickening in the maxillary
sinuses. Bone invasion is noted in the form of mottled areas of low attenuation in the zygomatic process of the
right maxillary bone; this finding is best visualized on the images obtained with bone windows (arrows
in b and d). There is also invasion into the soft tissues of the right cheek (arrowheads in a and c).

8. Chronic invasive fungal sinusitis due to zygomycosis in a 47-year-old woman. Axial unenhanced CT scans
(a obtained caudad to b) show increased attenuation in the left maxillary sinus. Note the absence of the
normal fat planes along the posterior wall of the left maxillary sinus. There is extension of infection beyond
the walls of the maxillary sinus into the anterior and posterior periantral soft tissues (arrows). Corresponding
images obtained with bone windows showed osseous sclerotic changes in the left maxillary sinus, findings
consistent with chronic sinus inflammatory changes.

9. Axial unenhanced CT scans show expansion of and increased attenuation in the anterior ethmoid, posterior
ethmoid, sphenoid, and frontal sinuses bilaterally. There is characteristic hyperattenuating material within these
sinuses (black arrows). Note also the smooth thinning of the posterior wall of the left frontal sinus (white arrows
in b).

10. (a obtained posterior to b) show characteristic expansile, hyperattenuating material in the sphenoid, ethmoid, and
right maxillary sinuses (arrows). Extension into the nasal cavity (*) from the bilateral ethmoid sinuses and right
maxillary sinus is noted. (c, d) Corresponding images obtained with bone windows show smooth erosion of the roofs
of the posterior ethmoid sinuses (arrowheads in c) with intracranial extension, which is possibly limited by the dura.
There is also smooth erosion of the medial wall of the right orbit (arrows in d) with intraorbital extension, which is
possibly limited by the periosteum.

11. Management of invasive fungal
Rhinosinusitis
 Without early treatment, rapid progression of disease with 50-80%
mortality rates from intra orbital and intra cranial extension have been
reported.
 Improvement of the host immune system is paramount for survival.
 Surgery is necessary to halt or slow progression of the disease (allowing
time for bone marrow recovery), to reduce fungal load and to provide a
tissue for culture.

12.  Empirical treatment by I/V Amphotericin B is started prior to definitive
identification of the causative fungi. Then we can switch to triazoles which
is less nephrotoxic than amphotericin, but lacks effectivenes against the
mucorales ( rhizopus, rhizomucor, ) so there presence should be ruled out
prior to its use.
 Four formulations of Amphotericin B are available:
1. conventional amphotericin B (C-AMB)
2. amphotericin B colloid dispersion (ABCD)
3. liposome amphotericin B (L-AMB)
4. amphotericin B lipid complex (ABLC)

13. Amphotericin B
 Amphotericin B is a naturally occurring polyene antifungal
produced by Streptomyces nodosus.
 It is a polyene and All polyenes are insoluble in water and
unstable in aqueous medium.
 Polyene antibiotics have high affinity for ergosterol present in
fungal cell membrane.
 They combine with it, get inserted into the membrane and
several polyene molecules together orient themselves in such a
way as to form a 'micropore'.
 The hydrophilic side forms the interior of the pore through which
ions, amino acids and other water-soluble substances move out.
The micropore is stabilized by membrane sterols which fiII up the
spaces between the AMB molecules on the lipophilic side. Thus,
cell permeability is markedly increased .

14. S/E
 Acute reaction:- This occurs with each infusion and consists of chills, fever, aches ,
nausea, vomiting. Usually the intensity of reaction decreases with continued
medication.
 Injection of hydrocortisone 0.6 mg/kg with the AMB infusion may reduce the
intensity of reaction.
 Thrombophlebitis of the injected vein can occur. Adding heparin to the infusion can
alleviate this problem.
 Long-term toxicity:- Nephrotoxicity is the most important. It occurs fairly uniformly
and is dose related.
 Sodium loading with infusions of normal saline prior to administration minimizes the
risk of nephrotoxicity.
 Manifestations are- azotemia, reduced g.f. r. , acidosis, hypokalaemia and inability to
concentrate urine.
 Nephrotoxicity reverses slowly and often incompletely after stoppage of therapy.
 Anaemia: Most patients develop slowly progressing anaemia which is due to bone
marrow depression. This is largely reversible.

15. interactions
 Flucytosine (5-FC) has supra additive action with AMB in the case of fungi
sensitive to both (AMB increases the penetration of 5-FC into the fungus).
 Aminoglycosides, vancomycin, cyclosporine and other nephrotoxic drugs
enhance the renal impairment caused by AMB.

16.  Liposomal (L-AMB)- It consists of 10% AMB incorporated in uniform sized (60- 80 nM) unilamellar
liposomes made up of lecithin and other biodegradable phospholipids.
 The special features of this preparation are:
 It produces milder acute reaction on i.v. infusion.
 It can be used in patients not tolerating infusion of conventional AMB formulations.
 It has lower nephrotoxicity.
 It causes minimal anaemia.
 The liposomal-AMB produces equivalent blood levels,has similar clinical efficacy.
 It can be infused at higher rates (3-5 mg/kg/day)
 amphotericin B colloid dispersion (ABCD) :- cholesteryl sulfate complex
 amphotericin B lipid complex (ABLC):- as a lipid complex

17. Conventional Amphotericin B (C-AMB)-
sodium deoxycholate
 50 mg , vial.
 It is first suspended in 1O ml water and then diluted to 500 ml with
glucose solution (saline makes the suspension coarse, should be avoided).
 Initially 1 mg test dose is injected i.v. over 20 minute~. If no serious
reaction follows, 0.3 mg/kg is infused over 4- 8 hours.
 Daily dose may be gradually increased to 0. 7 mg/kg depending on
tolerance of the patient. The total dose of AMB for majority of cases is 3-4
g given over 2- 3 months.

18.  There are insufficient data presently available to define total dosage
requirements and duration of treatment necessary for eradication of
specific mycoses.
 The optimal dose is unknown.
 Total daily dosage may range up to 1.0 mg/kg per day or up to 1.5 mg/kg
when given on alternate days.
 Under no circumstances should a total daily dose of 1.5 mg/kg be
exceeded