Fungal infections of paranasal sinuses Mucormycosis

1. Fungal sinusitis
DR GRACE VANDANA
ENT PG
NMC NELLORE

2. Introduction
 Fungal rhinosinusitis (FRS) can be categorized into two broad groups
 Invasive
 non-invasive
 This is based on the presence or absence of fungus in the tissue (mucosa, blood vessel or
bone) respectively.

3. Non invasive Invasive
Saprophytic fungal infection
Fungal ball
Allergic fungal rhinosinusitis (AFRS)
Acute (fulminant) invasive FRS
Granulomatous invasive FRS
Chronic invasive FRS
Fungal sinusitis

4. SAPROPHYTIC FUNGAL INFECTION
 visible fungal colonization of mucus crusts seen within the nose and paranasal sinuses on
nasoendoscopy.
 mechanism
dysfunction in mucociliary transportation from surgery
crust formation
platform for growth of fungal spores
 precursors to fungal balls if left untreated.
 patients are usually asymptomatic or may present with a foul smelling odour
 Endoscopic cleaning of the infected crust with or without continued self-irrigation with saline is
usually the only treatment required

6. Fungal ball
 dense accumulation of extramucosal fungal hyphae, usually within one sinus, most
commonly the maxillary sinus.
 most common organism Aspergillus
 Fungal balls are seen more commonly in immunocompetent, middle-aged and
elderly females,
 often with a history of previous dental procedure, especially dental fillings.

7.  diagnosis
 radiological findings
 sinus opacification often with areas of
hyperattenuation
 cheesy or clay-like debris within the sinus
 accumulation of fungal hyphae without
evidence of tissue fungal invasion seen
microscopically
 non-specific chronic inflammation of the
sinus and the absence of eosinophil
predominance, granuloma or allergic
mucin

8.  Management wide opening of the involved sinus and complete removal of the
fungal debris.
 Examination of the involved sinuses with angled scopes is crucial to ensure
complete surgical extirpation.
 Subsequent regular surveillance in the clinic is necessary.
 Oral or topical antifungals are not necessary

9. FUNGUS-RELATED EOSINOPHILIC
FRS INCLUDING ALLERGIC FUNGAL
RHINOSINUSITIS (AFRS)
 AFRS is a non-invasive fungal sinusitis resulting from an allergic and immunologic response to the
presence of extramucosal fungal hyphae in the sinuses.
 It was first recognized as an upper airway manifestation of allergic bronchopulmonary aspergillosis
(ABPA) in the 1970s.
 Aspergillus along with dematiaceous fungi such as Bipolaris, Curvularis and Alternaria were more
common causative organisms.
 AFRS is the most common form accounting for between 56 and 72% of patients with FRS.
 The typical AFRS patients are young immunocompetent adults
 mean age at presentation is 21 and 33 years old.
 higher male to female ratio

10. Pathophysiology
 underlying pathophysiology remains unknown and controversial.
 number of popular theories have evolved.
 Manning et al. proposed a mechanism derived from the ABPA model
 Demonstrating raised fungal-specific IgE antibodies and IgG antibodies in AFRS patients, it is believed that
an atopic host exposed to fungi resulted in antigenic stimulation by a combination of Gell and Coombs
type I and type III hypersensitivity.
 alternative theory was later proposed by Panikou et al stating that eosinophilic chemotaxis in response to
extramucosal fungi was the hallmark of the inflammatory reaction in AFRS.
 eosinophilic theory does not explain the triggering factor for eosinophil chemotaxis.
 The term eosinophilic mucin rhinosinusitis (EMRS) was used to describe non-allergic fungal sinusitis.
 These patients were felt to have histological features similar to AFRS but without the presence of fungus.
 The underlying mechanism was believed to be a systemic dysregulation of immunologic controls resulting
in upper and lower airway eosinophilia.

12. Investigation
 IMMUNOLOGIC TEST
 Patients with AFRS have an elevated IgE level 50 and >1000 IU/ml.
 The average total IgE level was about 550 IU/mL.
 total serum IgE level may be useful in monitoring clinical activity in
 the management of AFRS.
 An in-vivo (skin prick) or invitro (RAST) test can be utilized to demonstrate fungal
specific IgE as a diagnostic criteria for AFRS

15. Histology
 hallmark of AFRS is the presence of
allergic mucin.
 Grossly, it is thick, tenacious and highly
viscous in consistency.
 Hence, the terms ‘peanut butter’ and
‘axle-grease are often used to
describe the characteristic appearance
of the mucus.
 Histologically, allergic mucin consists
of an eosinophilic mucin with necrotic
eosinophils, inflammatory cells,
Charcot-Leyden crystals (the by-
product of eosinophil) and fungal
hyphae.

16. FUNGAL CULTURE
 A positive fungal culture provides supporting evidence in the diagnosis of AFRS. However, its
absence does not exclude the diagnosis of AFRS.
 The presence of a positive fungal culture in AFRS patients ranged from 49 to 100%

17. Management
 SURGICAL TREATMENT
 Unlike the management of classical CRS, surgery is usually the first line treatment in the management
of AFRS.
 Meticulous and complete endoscopic sinus surgery is the gold standard for the surgical extirpation of
polypoid disease and allergic mucin in an attempt to restore ventilation and drainage of the sinuses
 Removal of allergic mucin and fungal debris eliminates the antigenic factor that incites the disease in
an atopic host.
 Surgery also provides wide access for surveillance, clinical debridement and application of topical
medication

19. Medical treatment
 SYSTEMIC MEDICATIONS
 I. Corticosteroids
 Oral steroids are useful in the perioperative period ofpatients with AFRS. In the pre-operative period, a short
course of coritcosteroids reduce intra-operative bleeding and size of the polyps
 II. Antifungals
 Oral antifungals are considered a viable treatment option for patients with recalcitrant AFRS. They are also
used as a steroid-sparing medication, allowing some patients to be weaned off from long-term oral
corticosteroid therapy
 oral itraconazole (200–400 mg daily) has potential benefits as a steroid sparing alternative and in prolonging
time to disease recurrence.
 Oral itraconazole is associated with risk of elevated liver enzymes, congestive heart failure, nausea, rash,
headache, malaise, fatigue and oedema
 Cessation of treatment is usually sufficient for the elevated liver enzymes to revert back to normal.

20. TOPICAL MEDICATION
 I. Corticosteroid
 Topical corticosteroids are used as standard treatment for patients with AFRS.
 They are most effective in the postoperative period when open sinus cavities and
middle meati allow access to the paranasal sinuses.
 The benefit of topical over systemic steroid lies in the ability of topical steroid to
achieve the highest drug concentration in the target tissue (sinonasal mucosa) without
the undesirable systemic side effects
 These include metered-dose nasal sprays such as mometasone furoate, fluticasone
propionate, fluticasone furoate, budesonide, beclomethasone dipropionate
monohydrate, ciclesonide, flumisolide and triamcinolone acetonide.

21.  II. Antifungals
 As AFRS is a different disease entity resulting from an immunologic hyperreaction to extramucosal
fungus, topical antifungals should hypothetically reduce the immunologic reaction of an atopic host
decreasing the antigenic load.
 fluconazole nasal spray, combined oral itraconazole and fluconazole nasal irrigation
 larger RCTs will be required to establish the role of topical antifungals in the management of AFRS.
 Non-standard topical nasal steroid (e.g. budesonide), oral antifungals and immunotherapy are
in cases of refractory AFRS.
 Future treatment strategy
 ANTI-IMMUNOGLOBULIN E (IGE) THERAPY
 Omalizumab (Xolair) is a humanized monoclonal anti- IgE antibody that has been used as an
adjuvant treatment in severe atopic asthma, allergic rhinitis and CRS with nasal polyposis

22. ACUTE (FULMINANT) INVASIVE FRS
 Acute or fulminant invasive FRS is a life-threatening disease present usually in
immunocompromised patients with impaired neutrophilic response.
 These patients include those with uncontrolled diabetes mellitus, acquired immunodeficiency
syndrome (AIDS), iatrogenic immunosuppression, organ transplantation and haematological
malignancies.
 This condition is characterized by the presence of hyphal invasion of sinus tissue and a time course
of less than 4 weeks
 Histological features include mycotic infiltration of blood vessels, vasculitis with thrombosis, tissue
infarction, haemorrhage and acute neutrophilic infiltrate.
 Aspergillus species and the fungi in the order of mucorale (e.g. Rhizopus, Rhizomucor and Mucor)
are the most commonly implicated species

23.  clinical symptoms include fever, cough, crusting of the nasal mucosa, epistaxis and headaches,a
high index of suspicion of this disease entity should be present in any immunosuppressed
patients with localizing sinonasal symptoms.
 In the early stages, nasoendoscopic findings may be as subtle as the presenting symptoms.
 Alteration in mucosal appearance such as a discoloration, granulation and ulceration are the
most consistent physical findings.
 CT scan is the initial radiologic investigation of choice
 Compared to AFRS, invasive FRS tends to have more focal bony erosions, lacks expansion of
the sinuses, has more limited sinus disease and has more disease outside of the sinuses than
within when there is intra-orbital or intra-cranial extension.

24. Treatment
 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 culture.
 Prior to definitive identification of the causative fungi, empirical treatment with intravenous
amphotericin B, a broad-spectrum antifungal agent, has been recommended.
 Once a causative fungal species has been identified, the use of the triazoles (fluconazole,
itraconazole and variconazole) can be considered
 The triazoles are effective in the treatment of invasive FRS without the associated nephrotoxicity
seen in standard amphotericin B

25. GRANULOMATOUS INVASIVE FRS
 This disease entity is defined by invasive fungal infection lasting more than 12 weeks.
 The causative agent is almost exclusively Aspergillus flavus.
 Patients are typically immunocompetent and the predominant clinical features include proptosis
with an enlarging mass in the cheek, nose, paranasal sinus and orbit
 CT findings are not different to that of chronic invasive FRS although they have a tendency for
multiple sinus involvement
 The distinguishing feature from chronic invasive FRS is histological findings of fungal tissue
invasion and a granulomatous reaction with considerable fibrosis.
 This is evident from the presence of non-caseating granulomas with foreign body or Langerhans-
type giant cells, occasional vasculitis and sparse hyphae
 Treatment includes complete surgical removal and antifungal agents.

26. CHRONIC INVASIVE FRS
 Chronic invasive FRS is a slowly destructive disease with a time-course of more than 12 weeks
duration.
 Patients are usually immunocompetent or have subtle abnormalities in the immune system from
diabetes mellitus, chronic low dose corticosteroid use and AIDS.
 The most common fungi implicated is Aspergillus fumigatus
 The clinical picture of chronic invasive FRS is similar to that of granulomatous invasive FRS.
 The ethmoid and sphenoid sinuses are most commonly involved.
 On histology, chronic invasive FRS demonstrates invasion of fungi into the sinonasal mucosa with a
dense accumulation of fungal hyphae, occasional vascular invasion, and chronic or sparse
inflammatory reaction.
 There is no difference in the prognosis or the management of both chronic invasive and
granulomatous invasive FRS.

27. Complication of fungal
sinusitis

28.  Complications of rhinosinusitis result from progression of acute or chronic
infection beyond the paranasal sinuses, potentially causing significant morbidity
from either local or distant spread.
 Complications of rhinosinusitis are more accentuated in children and adolescents
because of their thinner, more porous bony septa and sinus walls, open suture
lines and larger vascular foramina.

29. CLASSIFICATION
 Orbital
 intra-cranial
 bony or chronic.
 Complications may be caused by either local progression or distant spread via the
bloodstream.
 Local progression is typically through areas where the surrounding bone is thin such as
the porous lamina papyracea, where there is a direct anatomical connection or through
osteitic bone.

31.  Direct routes of spread occur through neurovascular foramina such as the infraorbital canal, or via
the valveless diploeic veins of Breschet of the frontal, ethmoid and sphenoid bones.
 The venous drainage of the sinus mucosa is via these diploeic veins,which communicate with the
dural venous plexus, the absence of valves facilitates retrograde spread of infection.

32. Frontal
 Anterior spread of acute frontal sinusitis through the outer table of the skull may
cause a boggy subperiosteal abscess and osteomyelitis. (Pott’s puffy tumour)
 Posterior spread of infection can cause acute intracranial complications such as
subdural empyema, meningitis, cerebritis and intracranial abscess.
 Subdural empyema is the most common intracranial complication of sinusitis, and the
most common cause of subdural empyema is frontal sinusitis.
 Spread of infection inferiorly can lead to orbital cellulitis.

33. Ethmoid
 Orbital cellulitis is by far the most frequent acute complication of ethmoid
sinusitis.
 It can vary in degree and severity and is typically graded with the Chandler
classification

34. Maxillary
 Isolated maxillary rhinosinusitis rarely gives rise to acute complications.
 Acute cheek swelling usually results from complications of dental disease
 Sphenoid
 Isolated sphenoid sinusitis is rare, but complications can result in meningitis or cavernous sinus
thrombosis by direct spread.
 In cavernous sinus thrombosis infection may spread through veins from the paranasal sinuses
and orbit to the cavernous sinuses as thrombophlebitis or by septic emboli.
 Bacteria themselves are pro-thrombotic, the thrombus provides good conditions for growth and
bacteria within the thrombus are shielded by the outer layers from antibiotics which they can
later re-infect.

35. Orbital complications
 The onset is noted by swelling around the eye. Oedema results from congestion of veins draining the eyelid and
can be present when the infection is still confined to the sinus.
 Cellulitis from untreated sinusitis represents stage 1 of the disease with local spread of inflammatory elements to
the lid.
 Postseptal cellulitis (stage 2) is confined to the orbit but has extended through the orbital septum, potentially with
intraconal involvement.
 Patients will have eyelid swelling, chemosis and proptosis, potentially with impaired extraocular muscle function
and diplopia
 Postseptal cellulitis typically results from transmitted pressure from the sinus to orbital veins with leakage of
inflammatory elements into the orbit.
 It is difficult to clinically differentiate postseptal cellulitis from subperiosteal abscess (stage 3)
 CT scanning is mandatory here and reflects the fact that the classification system pre-dates the ready availability of
scanning.

39. EXAMINATION
 Clinical endoscopic examination of the nose should be performed to help determine the site and extent
of disease.
 In the case of orbital cellulitis, a formal assessment of the
 degree of chemosis
 range of eye movements
 degree of proptosis
 relative afferent pupillary defect
 visual acuity (using a Snellen chart)
 colour vision (using Ishihara plates)
 inspection of the optic disc should be made.
 For intracranial complications a full neurological examination should be completed.

40. INVESTIGATIONS
 Radiological
 The aim of these investigations is to:
• confirm the diagnosis of the complication
• define the extent and site of the complication
• help plan treatment including surgical approach
• confirm that there is no other covert complication
present
• Monitor the response to treatment.

41.  Contrast enhanced computed tomography (CT) is advised as first-line imaging
because of its superiority in demonstrating bony anatomy and pathology of the
orbit and sinuses with its speed and ease of examination.
 MRI provides outstanding soft tissue detail without radiation

42.  Below are some of the common signs to look out for each stage of the Chandler classification.
 1. Preseptal cellulitis – eyelid swelling and thickening of the preseptal tissues with possible
posterolateral extension to the temporal fossa.
 Importantly, CT will not distinguish between oedema, preseptal cellulitis and allergy.
 2. Postseptal cellulitis – the findings as above often with induration of the extraconal, intraconal
and retrobulbar fat without abscess.
 3. Subperiosteal abscess – CT scans show a typical lenticular rim-enhancing collection adjacent
to the lamina papyracea with a fat plane between it and the displaced medial rectus muscle
 Lateral deviation and proptosis of the globe may be visible on axial images.
 Sight threatening complications of optic neuritis or optic nerve ischemia may also be present
without radiological signs. Subperiosteal abscess secondary to frontal sinusitis typically forms an
abscess superiorly with anteroinferior globe displacement

44.  4. Orbital abscess – Scans may show multiple rimenhancing orbital abscesses
with surrounding cellulitis and a resultant proptosis.
 5. Cavernous sinus thrombosis – It is important to note that in the early stages
CT scans appear normal.
 CT and MR venography are complementary in the diagnosis of cavernous sinus
thrombosis.
 There may also be thickening and increased signal intensity in the extraocular
muscles in T2-weighted MRI

45. Treatment
 Medical management
 Unless an abscess is demonstrated by radiological or other investigation, non-surgical
management of rhinosinusitis complications is normally first choice.
 The exception is when vision is affected by pressure on the optic nerve from surrounding
inflammation without abscess formation.
 The aim of medical management is to control and eliminate both the disease process of the
complication and of the primary rhinosinusitis.
 Antibiotics form the mainstay of medical treatment
 Broad-spectrum antibiotics are advised for severe complications of sinusitis to cover the likely
organisms including S. pneumonia, S. anginosus and other Streptococcus species, H.
influenzae, S. aureus, Moraxella catarrhalis and anaerobic bacteria (Prevotella,
Porphyromonas, Fusobacterium and Peptostreptococcus species

46. Surgical management
 If there is no significant clinical improvement in the first 24 hours of medical
treatment, or there is any clinical deterioration surgical intervention should be
considered.
 The surgical treatment of patients with complications of rhinosinusitis can be
divided into procedures necessary to manage the complication and surgery for
the rhinosinusitis.

48. INTRACRANIAL COMPLICATIONS
 Brain abscess
 complication of either local or distant spread.
 The frontal sinuses are the most common source followed by the ethmoid,
sphenoid and maxillary sinuses.
 Haematogenous spread is the most likely mechanism of distant spread.

49.  Subdural empyema
 one of the commonest intracranial complications of rhinosinusitis, typically from haematogenous
spread
 Subdural empyemas present with meningeal irritation and neurological signs such as seizures or
focal deficits.
 Serious neurological injury can occur if not treated rapidly and aggressively with combined
treatment and neurosurgical drainage to decompress the brain and evacuate the empyema.
 Extradural empyema
 Extradural empyemas tend to be less symptomatic as the brain is protected by the dura mater.
signs are less marked and specific and are often only present when the collection reaches a size to
cause mass effect.

50.  Brain infarction
 Cerebral ischaemia and infarction are rare vascular complications of sinusitis
either dural venous thrombosis secondary to adjacent empyema, or cavernous
carotid artery occlusion
 Investigations
 MRI scanning has been shown to be superior to CT in the diagnosis of
complications and is the investigation of choice for the diagnosis of suspected
intracranial extension.

52. BONY COMPLICATIONS
 Pott’s puffy tumour
 Subperiosteal cellulitis or abscess of the frontal bone associated with frontal
osteomyelitis and presenting with headache, swelling and, on occasion, a
discharging frontal fistula.
 The infection can spread posteriorly giving rise to intracranial sepsis either by
erosion of the posterior table or more likely by septic thrombophlebitis via the
diploeic veins
 Management requires drainage of pus from the frontal sinuses, achieved either
endoscopically or conventionally through a frontal sinus trephination via an
incision in the superomedial aspect of the orbit.

54. CHRONIC COMPLICATIONS
 Mucoceles are chronic, slowly expanding lesions in any of the sinuses that may
result in bony erosion and can extend beyond the sinus

55. Rhino orbital mucormycosis
 Rhino-orbital mucormycosis is a rare but life threatening infection that generally occurs in
patients with diabetes mellitus and other immune deficiency conditions.
 Rhino-orbital and Rhino-cerebral are two form of the disease.
 As such the condition is a medical emergency.
 Early recognition and treatment are essential because it may lead to death in few days.
 Fungal infection of nasal cavity is uncommon but is being seen with increasing frequency
in patients with immune deficiency.

56. Etiology
 Mucormycosis are a group of invasive infections which are caused by filamentous fungi of the order,
Mucorales of the Mucoraceae Family.
 Rhino-orbital mucormycosis is an aggressive, angioinvasive fungal infection which is seen
inimmunocompromised hosts.
 The risk factors are poorly controlled Diabetes mellitus, haematological malignancies and a prolonged
corticosteroid treatment.
 The infections which are caused by members of the order mucorales are primarily opportunistic
infections and they represent the third leading cause of invasive fungal infections
following Aspergillus and Candida species.

57.  It is an acute opportunistic infection which is caused by a broad, non septate,
saprophytic fungus which is found in soil, air, bread mould, rotten fruit and
vegetables.
 It can be cultured from the mouth, nasal tract, throat and the faeces of healthy
persons.
 The fungus belongs to the Phycomycetes class, whose most common genera
are Mucor, Rhizopus, Absidia and Basidiobolus.
 Contact with the micro organism occurs through spore inhalation.

58. Pathophysiology
 The reduced ability of serum to bind iron at a low pH may be the basic defect in the body’s defense
systems.
 The high iron, glucose-rich acid medium facilitates fungal growth
 The human resistance to fungal infections rests on the body’s ability to restrict the availability of iron
to the invading fungus, by binding it to proteins such as apotransferrin.
 The fungal hyphae produce a substance called rhizoferrin, which binds iron avidly.
 This iron-rhizoferrin complex is then taken up by the fungus and it becomes available for the vital
intracellular processes.
 Diabetic patients are predisposed to mucormycosis because of the decreased ability of their
neutrophils to phagocytose and adhere to the endothelial walls.
 Furthermore, the acidosis and hyperglycaemia provide an excellent environment for the fungus to
grow

59.  The infection spreads along the vascular and neuronal structures and it infiltrates
the walls of the blood vessels.
 It causes erosion of the bony walls of the ethmoid sinuses and it may spread into
the orbit and the retro-orbital area and in the brain (cerebro-rhino-orbital
mucormycosis).
 Death may occur due to the cerebral abscesses.

60. Clinical features
 Fever > 48 hrs despite adequate medical therapy
 Blood stained nasal discharge
 Facial pain, facial swelling
 Orbital swelling opthalmoplegia, decreased vision
 Proptosis CN VI palsy
 Cavernous sinus thrombosis is a late sign of intracranial extension
 Pulmonary mucormycosis – cough hemoptysis,SOB
 Gastrointestinal mucormycosis – abdominal pain, hematemesis
 Renal mucormycosis – fever, flank pain
 Cutaneous mucormycosis – painful blackish hardened areas

61.  Anterior rhinoscopy
 Alteration of nasal mucosa appearance
 White discoloration of pale mucosa indicates tissue ischemia secondary to
angiocentric invasion
 Black discoloration indicates tissue necrosis
 Decreased mucosal bleeding
 Anaesthetic regions

62. Investigations
 Biopsy of polyp or unhealthy mucosa to make definitive diagnosis
 Ct and MRI scans with contrast of the sinuses inclusive of orbit and brain.
 Opthal opinion for visual acquity and fundus examination
 Neurosurgeon to rule out intracranial and cavernous sinus involvement

63. Treatment
 Emergency surgical debridement is the treatment of choice
 In some cases surgery may be disfiguring because it may involve removal of
palate, nasal cavity or eye structures
 Medial maxillectomy may be necessary
 Anti fungal agents
 Amphotericin B
 Derived from streptomyces nodosus
 It is poorly absorbed orally hence given intravenously

64.  Mechanism of action
 It gets bound to ergosterol in the cell membrane of fungus and increases the
permeability of cell membrane andcell contents leak out leading to death of cell
 Dose: 1-3 mg/kg/bodyweight given as slow IV
 Test dose of 1mg in 50 ml of 5% dextrose given IV over 20-30 min
 30 mins later 20 mg IV is given
 Next day 40 mg IV is administered.

65. Side effects

66.  Renal – increased creatinine and blood urea
 Prevented by sodium supplementation to maintain intravascular volume.
 Bone marrow depression

67.  Voriconazole
 Dosage IV 6 mg/kg every 12th hrly for 2 doses
 Oral preparations of 400 mg twice daily for 2 doses
 Posaconazole
 Dosage 400 mg twice daily

68. Thank you