Fungal Rhinosinusitis

Introduction to Fungal Rhinosinusitis

Fungal infections of the paranasal sinuses are diverse, ranging from benign colonization to rapidly progressive, life-threatening invasive diseases. Although fungi are ubiquitous in our environment, and many are even normal commensals, certain factors can tip the balance, leading to infection. Notably, the liberal use of broad-spectrum antibiotics and a global increase in immunocompromised individuals have significantly contributed to the rising incidence of fungal rhinosinusitis. This is primarily due to the alteration of normal flora and a compromised host immune response. Furthermore, advancements in diagnostic imaging, such as CT scans and MRI, have dramatically improved our ability to detect and characterize these infections.

Etiology and Predisposing Factors

While numerous fungal species can cause rhinosinusitis, the majority of clinically significant infections from an ENT perspective are primarily caused by Candidiasis and Aspergillosis species. Additionally, Zygomycetes, including Mucor, Apophysomyces, Rhizomucor, Rhizopus, and Absidia, contribute to a substantial proportion, particularly in patients with compromised immune systems. These fungi are typically soil saprophytes.

Predisposing Factors for Fungal Rhinosinusitis:

Understanding the factors that predispose individuals to fungal rhinosinusitis is crucial for both diagnosis and management. These conditions impair the body’s natural defenses, allowing fungi to proliferate and invade tissues.

• • • Immunocompromised states: Patients with an impaired neutrophilic response are highly susceptible.
    • Uncontrolled Diabetes Mellitus & Ketoacidosis: This is a major risk factor, especially for Mucormycosis, as high glucose and acidic conditions enhance fungal growth.
    • Acquired Immunodeficiency Syndrome (AIDS): Weakened immune systems are vulnerable to various fungal infections.
    • Organ or Bone Marrow Transplantation: These patients are often on immunosuppressive medications.
    • Hematological Malignancies: Conditions like leukemia and lymphoma compromise immune function.
    • Chronic Renal Failure: This can lead to a general debilitated state and immune dysfunction.
    • Prolonged use of Corticosteroids: Steroids suppress the immune system.
    • Chemotherapy: Medications used in chemotherapy can severely reduce immune cell counts.
    • Broad-spectrum Antibiotic Use: These can alter the normal microbial flora, creating an environment conducive to fungal growth.
    • Traumatic cases with compound fractures: These can introduce fungi directly into tissues.
    • Occupational exposure: Farmers and garbage cleaners are more exposed to fungal spores in their environment.

Classification of Fungal Rhinosinusitis

The classification of fungal sinus disease is primarily based on the presence or absence of tissue invasion. A widely accepted classification, proposed by Chakravarti et al. (2009), categorizes fungal sinus disease into two broad types: invasive and non-invasive. This distinction is critical because it dictates the urgency and type of treatment required.

Table 1: Classification of Fungal Rhinosinusitis

Type	Characteristics	Subtypes	Key Feature
Invasive	Fungal hyphae present within tissue (mucosa, blood vessel, bone). Generally aggressive, life-threatening.	1. Acute Necrotizing Invasive FRS (ANIFRS) 2. Chronic Invasive FRS (CIFRS) 3. Chronic Granulomatous Invasive FRS (CGIFRS)	Tissue invasion, high morbidity/mortality if untreated.
Non-Invasive	Fungal colonization on epithelial surface without tissue invasion. Generally less aggressive.	1. Saprophytic Fungal Infection 2. Fungus Ball (Aspergilloma) 3. Allergic Fungal Rhinosinusitis (AFRS)	Fungal presence without active invasion; often allergic response.

Invasive Fungal Rhinosinusitis

Invasive fungal rhinosinusitis is characterised by the presence of fungal hyphae within the tissue (mucosa, blood vessels, or bone). These conditions are generally more severe and often require aggressive management.

Types of Invasive Fungal Rhinosinusitis:

• • 1. Acute Necrotizing Invasive Fungal Rhinosinusitis (ANIFRS) – Aspergillosis, Mucormycosis.
    2. Chronic Invasive Fungal Rhinosinusitis (CIFRS)
    3. Chronic Granulomatous Invasive Fungal Rhinosinusitis (CGIFRS)

1. Acute Necrotizing Invasive Fungal Rhinosinusitis (ANIFRS). This is a rapidly progressive and life-threatening condition characterized by hyphal invasion of sinus tissue with a time course of less than 4 weeks. Therefore, prompt diagnosis and aggressive treatment are paramount, as it can lead to death within days.

• • • Causative Organisms: Primarily Aspergillus and Mucorales (e.g., Mucor, Rhizopus).
    • Key Pathophysiology: Angioinvasion is a hallmark, particularly with Mucorales, leading to vascular thrombosis, tissue infarction, and necrosis.

Clinical Features of ANIFRS:

• • • Patients may present with symptoms of acute or subacute rhinosinusitis.
    • Mucosal changes and/or anesthesia are typical on endoscopic examination, often appearing pale or blackened due to necrosis.
    • Fever of unknown origin in immunocompromised patients, not improving with broad-spectrum intravenous antibiotics for 48 hours, should raise suspicion.
    • Black, crusted, and necrotic areas in the nasal cavity and sinuses are highly indicative.
    • Septal perforation and erosion of the septum and hard palate may occur.
    • Orbital involvement: Proptosis, ptosis, orbital fixation, and blindness (panophthalmoplegia) are ominous signs.
    • Cranial nerve palsies (III, IV, VI) due to extension to the cavernous sinus via the orbital apex.
    • Cerebral ischemia and death can result from carotid artery invasion.
    • Ethmoid sinuses are most commonly involved, while the frontal sinus is usually spared.

Diagnosis of ANIFRS:

• • • Endoscopy: Reveals characteristic changes such as pale or black, necrotic mucosa.
    • Histopathology: This is the gold standard for diagnosis. Biopsies from multiple sites (especially middle turbinate and septum) are crucial. It demonstrates invasive features and often distinguishes Mucorales (non-septate hyphae with wide-angle branching) from Aspergillus (septate hyphae with 45-degree angle branching).
    • Radiological Investigations: Both CT and MRI are highly helpful.
      • CT scan effectively detects bony destruction.
      • MRI is superior for detecting mucosal, skin invasion, and orbital or intracranial involvement.
      • Typically, CT shows focal bony erosions with limited sinus disease, suggesting the disease is more extensive outside the sinuses, particularly with intra-orbital or intra-cranial extension.

Treatment of ANIFRS:

Treatment must be swiftly instituted due to the fulminant nature of the disease.

• • • Aggressive Surgical Debridement: This is paramount to remove all necrotic and infected tissue. This may involve extensive debridement or even orbital exenteration in severe cases.
    • Systemic Antifungal Therapy: Intravenous Amphotericin B (conventional or lipid formulations) is considered the gold standard. Other drugs like Posaconazole or Isavuconazole may also be used, especially in mucormycosis.
    • Control of Underlying Predisposing Causes: This includes meticulous control of blood glucose in diabetic patients and reversal of acidosis.

(i) Aspergillosis (Invasive). Invasive Aspergillosis is a serious fungal infection, particularly common in immunocompromised individuals.

• • • • Causative Organisms: Aspergillus niger, A. fumigatus, or A. flavus. It is the second most common fungal infection after candidiasis in immunocompromised patients.
      • Typical Patient Profile: Often seen in individuals handling small birds, though immunocompromise is the primary risk factor.

Histopathology of Invasive Aspergillosis:

• • • • Shows septate hyphae of uniform diameter with 45-degree angle branching.
      • Mycotic infiltration of blood vessels (vasculitis), thrombosis, tissue infarction, hemorrhage, and acute neutrophilic infiltrate are characteristic.

Treatment of Invasive Aspergillosis:

• • • • Surgical debridement to remove infected tissue.
      • Antifungal drugs: Amphotericin B followed by oral voriconazole or itraconazole for prolonged periods to ensure eradication.
      • Repeated irrigation with 1% gentian violet can also be useful.

(ii) Mucormycosis (Zygomycosis or Phycomycosis). Mucormycosis is an opportunistic, fulminant fungal infection predominantly observed in uncontrolled diabetics or immunocompromised patients. Around 70% of cases occur in uncontrolled diabetic patients, largely because these organisms possess an active ketone reductase system, enabling them to thrive in high glucose and acidotic conditions. Consequently, hyperglycemia and acidosis significantly enhance tissue invasion and fungal growth. Mucormycosis exhibits a strong predilection for angioinvasion, rapidly invading arteries, causing endothelial damage and thrombosis.

• • • • Causative Organisms: Mucor, Rhizopus oryzae, and Absidia.
      • Pathogenesis: Inhaled fungal spores, in an immunosuppressed host, are not effectively phagocytized. This leads to germination and hyphae formation, subsequently invading mucosal tissues. The disease typically begins in the nose or sinuses and, if untreated, can rapidly spread along vascular channels to involve the orbital apex, then the cavernous sinus, and potentially the carotid arteries, leading to cerebral ischemia and death.

Histopathology of Mucormycosis:

• • • • Shows non-septate hyphae of irregular size and shape with 90-degree wide-angle branching. These are well-demonstrated in hematoxylin and eosin (H&E), PAS-, or GMS-stained sections.
      • Similar to aspergillosis, mycotic infiltration of blood vessels, vasculitis with thrombosis, tissue infarction, and hemorrhage are prominent, along with an acute neutrophilic infiltrate.

Treatment of Mucormycosis:

Treatment must be swiftly instituted due to its aggressive nature.

• • • • Intravenous Amphotericin B: This is the cornerstone of medical therapy.
      • Aggressive Surgical Debridement: Crucial for removing all devitalized tissue. This may necessitate extensive resections or even orbital exenteration in cases with widespread orbital disease.
      • Control of Underlying Predisposing Cause: Optimizing blood glucose control and correcting acidosis in diabetic patients is absolutely critical for successful treatment and preventing recurrence.

 

2. Chronic Invasive Fungal Rhinosinusitis (CIFRS). CIFRS shares clinical similarities with acute necrotizing invasive fungal rhinosinusitis but presents as a slowly destructive disease with a time course of more than 12 weeks.

• • • Causative Organism: Typically Aspergillus fumigatus or flavus.

Clinical Features of CIFRS:

• • • Early stages: Unilateral bloody nasal discharge, nasal obstruction, headache, cacosmia (foul smell), and purulent nasal discharge.
    • Later stages: Proptosis, orbital apex syndrome, and cranial nerve deficits due to orbital invasion. Erosion of the palate and facial swelling may also occur. Chronic headache, seizures, and focal neurological deficits indicate intracranial involvement.
    • Ethmoid and sphenoid sinuses are most commonly involved.

Histopathology of CIFRS:

• • • Fungal invasion into the sinonasal mucosa with a dense accumulation of fungal hyphae and occasional vascular invasion.
    • Characterized by a chronic or sparse inflammatory reaction with few inflammatory cells (unlike ANIFRS) and a lack of granulomas, which are often seen in chronic granulomatous invasive fungal sinusitis.

Radiology of CIFRS:

• • • CT imaging: May mimic malignancy, often showing a hyper-attenuating mass in one or more sinuses with destruction of the sinus bony walls. This makes differentiation from neoplastic lesions challenging.
    • MRI: Essential for assessing intracranial involvement.

Treatment of CIFRS:

Treatment is similar to acute invasive fungal rhinosinusitis.

• • • Surgery: Complete surgical removal of the disease.
    • Antifungal agents: Prolonged courses of systemic antifungals are typically required.

 

3. Chronic Granulomatous Invasive Fungal Rhinosinusitis (CGIFRS). This entity is defined by invasive fungal infection lasting more than 12 weeks, distinguished by the presence of non-caseating granulomas with Langhan’s type giant cells and fungal hyphae. It can coexist with other types of fungal sinusitis. The disease has a gradual onset.

• • • Causative Organism: Aspergillus flavus.
    • Predisposing Host Factors: Similar to acute (fulminant) invasive fungal rhinosinusitis.

Clinical Features of CGIFRS:

• • • Often presents with proptosis and a large mass in the cheek, nose, paranasal sinus, and orbit.

Histopathology of CGIFRS:

• • • Demonstrates fungal tissue invasion and a prominent granulomatous reaction with considerable fibrosis, including the presence of non-caseating granulomas.

Treatment of CGIFRS:

• • • Surgery: Resection of involved tissues to bleeding margins is crucial.
    • Antifungal agents: Voriconazole is commonly used.

Table 2: Differentiating Key Invasive Fungal Rhinosinusitis Types

Feature	Acute Necrotizing Invasive FRS	Chronic Invasive FRS	Chronic Granulomatous Invasive FRS
Time Course	< 4 weeks (rapidly progressive)	> 12 weeks (slowly destructive)	> 12 weeks (gradual onset)
Causative Org.	Aspergillus, Mucorales	Aspergillus fumigatus/flavus	Aspergillus flavus
Histopathology	Extensive angioinvasion, thrombosis, tissue infarction, acute neutrophilic infiltrate. Fungal hyphae present.	Invasion of fungi with dense hyphae, occasional vascular invasion, chronic/sparse inflammation (few cells).	Fungal tissue invasion + non-caseating granulomas with Langhan's type giant cells, fibrosis.
Prognosis	Grave, life-threatening	Better than ANIFRS but can be destructive	Better than ANIFRS
Primary Rx	Aggressive surgical debridement + IV Amphotericin B	Surgical removal + systemic antifungals	Surgical resection + Voriconazole
Typical Patient	Severely immunocompromised, uncontrolled diabetics	Immunocompromised, but less fulminant onset	Immunocompromised

Non-Invasive Fungal Rhinosinusitis

Non-invasive fungal rhinosinusitis refers to conditions where there is colonization of the surface of epithelial tissues without invasion into the underlying mucosa, blood vessels, or bone. These conditions are generally less aggressive but still require appropriate management.

Types of Non-Invasive Fungal Rhinosinusitis:

• • 1. Saprophytic Fungal Infection
    2. Fungus Ball (Mycotic Mass/Aspergilloma)
    3. Allergic (Eosinophilic) Fungal Rhinosinusitis (AFRS)
  • 1. Saprophytic Fungal Infection

This involves fungal colonization of mucus crusts in the nose and paranasal sinuses. It is typically a superficial infection and can often be visualized on nasal endoscopy.

• • • Etiology: Often arises due to dysfunction in mucociliary transportation from prior surgery, leading to crust formation that provides a suitable platform for fungal spore growth.
    • Significance: If left untreated, these can potentially serve as precursors to fungus balls.
    2. Fungus Ball (Mycotic Mass/Aspergilloma)

A fungus ball is an accumulation of a dense mass of sequestered fungal hyphae within a sinus, typically separating easily from the sinus mucosa. Crucially, there are no invasive or granulomatous changes in the surrounding tissue.

• • • Appearance: Clay-like or cheesy material, which can be green, yellow, brown, or black.
    • Causative Organism: Primarily Aspergillus species.
    • Coexistence: Can coexist with other forms of fungal sinusitis.

Clinical Features of Fungus Ball:

• • • Patients can be asymptomatic, with the fungus ball often discovered incidentally on imaging.
    • The maxillary sinus is most commonly involved (94%), causing headache or facial pain, post-nasal drip, and cacosmia.
    • Involvement of the ethmoid sinus can lead to retro-orbital pain at the vertex.

Histopathology of Fungus Ball:

• • • Shows abundant fungal hyphae without any evidence of mucosa, vessel, or bone invasion.
    • Absence of eosinophils, granulomas, or allergic mucin differentiates it from AFRS.

Radiology of Fungus Ball:

• • • CT scan is the investigation of choice. Characteristic findings include:
      • Heterogeneous soft tissue density in a single, unilateral sinus.
      • No air-fluid level.
      • Inner wall of the sinus may be eroded due to pressure effects from the mass.
      • Lateral sinus wall may show sclerosis (thickening).
      • Calcification is a hallmark, resulting from the deposition of calcium salts within the fungal ball, often appearing as hyperdense spots.

Treatment of Fungus Ball:

• • • Complete surgical removal of the fungal ball from the affected sinus is the mainstay of treatment.
    • Medical management and systemic antifungals are usually not required as there is no tissue invasion.
    3. Allergic (Eosinophilic) Fungal Rhinosinusitis (AFRS)

AFRS is an allergic and immunologic response to extramucosal fungal growth within the sinuses. It is more prevalent in warm, humid environments and in younger, immunocompetent patients with a history of atopy or asthma.

• • • Fungi commonly seen in eosinophilic mucin: Alternaria, Bipolaris, Cladosporium, Curvularia, Drechslera, Helminthosporium (from the dematiaceous family), and Aspergillus species.

Diagnostic Criteria for AFRS:

Two commonly used criteria are:

• • • Bent and Kuhn Diagnostic Criteria for AFRS: This is widely adopted.
      • 5 Major Clinical Features (all must be met):
        1. Evidence of Type I IgE–mediated hypersensitivity (e.g., positive skin prick test or RAST to fungi).
        2. Nasal polyposis.
        3. Characteristic CT findings (e.g., heterogeneous sinus opacity, hyperdense foci).
        4. Eosinophilic mucin (allergic mucin).
        5. Positive fungal smear from the allergic mucin.
      • 6 Minor Clinical Features (supporting features):
        1. Asthma
        2. Unilateral predominance
        3. Radiographic bone erosion
        4. Positive fungal culture
        5. Charcot-Leyden crystals
        6. Serum eosinophilia
    • DeShazo et al. Diagnostic Criteria for AFRS: A slightly revised criterion aiming to reduce controversy regarding the role of atopy.
      • Sinusitis confirmed on CT scanning.
      • Presence of allergic mucin.
      • Demonstration of fungal hyphae within the allergic mucin.
      • Absence of fungal invasion.
      • Absence of diabetes or immunodeficiency states.

Clinical Features of AFRS:

• • • Recurrent nasal congestion, post-nasal drip, and a thick, dark nasal discharge.
    • Patients often respond well to oral corticosteroids, but not antibiotics.
    • Proptosis and telecanthus may be present if there is bony erosion and orbital involvement.
    • Classical yellow/green “peanut butter” or “axle-grease” type thick mucin is a pathognomonic finding.
    • Unilateral or bilateral nasal polyposis.
    • Symptoms are similar to chronic sinusitis with nasal polyposis.

Histopathology of AFRS:

• • • Allergic mucin consists of an eosinophilic mucin with necrotic eosinophils, inflammatory cells, Charcot-Leyden crystals (by-product of eosinophil degranulation), and fungal hyphae.

Investigation of AFRS:

• • • IgE and IgG antibodies: Often raised.
    • Non-Contrast CT Scan: This is the investigation of choice. It reveals characteristic pansinusitis, heterogeneous sinus opacity with focal or diffuse areas of hyperdense spots due to calcium and manganese deposits in the thick allergic mucin. This often results in a ‘double density’ or ‘rail-track sign’. There can be expansion of the affected paranasal sinuses/nasal cavity, with or without bony erosion, due to local inflammation and the expansive nature of the mucin.
    • Contrast MRI: Required when intracranial or intra-orbital complications are suspected.

Treatment of AFRS:

• • • Surgery: This is the mainstay of treatment. Functional Endoscopic Sinus Surgery (FESS) is performed to achieve complete removal of polypoid disease and allergic mucin, thereby re-establishing ventilation and drainage of the sinuses. Importantly, all polyps and allergic mucin should be sent for microscopy and culture to exclude invasive disease.
    • Medical Management (Adjunctive): Crucial for controlling the disease post-operatively.
      • Oral Steroids: Administered pre-operatively to reduce intra-operative bleeding and post-operatively in a tapering dose to reduce mucosal disease and inflammatory markers.
      • Topical Nasal Steroids: Following FESS, open sinus cavities allow topical nasal steroids to achieve high, effective drug concentrations in the sinonasal mucosa with minimal systemic side effects.
      • Immunotherapy: Some studies have shown that immunotherapy (allergen-specific or anti-IgE antibodies like Omalizumab) can reduce dependence on post-operative steroids and the need for revision surgery.

Table 3: Differentiating Key Non-Invasive Fungal Rhinosinusitis Types

Feature	Saprophytic Fungal Infection	Fungus Ball (Aspergilloma)	Allergic Fungal Rhinosinusitis (AFRS)
Description	Fungal colonization of mucus crusts	Dense mass of sequestered hyphae within sinus, easily separable from mucosa	Allergic/immunologic response to extramucosal fungal growth
Causative Org.	Various fungi	Aspergillus species (most common)	Alternaria, Bipolaris, Aspergillus etc.
Clinical Features	Mucus crusts, may be asymptomatic	Often asymptomatic, headache, facial pain, cacosmia. Maxillary sinus common.	Nasal polyposis, thick dark discharge ("peanut butter" mucin), post-nasal drip, recurrent congestion. Atopy.
Histopathology	Fungi in mucus, no tissue invasion	Fungal hyphae without invasion, no eosinophils/granulomas/allergic mucin	Eosinophilic mucin with necrotic eosinophils, Charcot-Leyden crystals, fungal hyphae. No tissue invasion.
CT Findings	Crusts	Heterogeneous density, calcification, no air-fluid level, sinus wall sclerosis/erosion.	Pansinusitis, heterogeneous opacity, hyperdense foci (double density/rail-track sign), sinus expansion.
Treatment	Mucociliary clearance, possibly local antifungals	Surgical removal of fungus ball. No systemic antifungals.	Surgical debridement + systemic/topical steroids, immunotherapy.

High-Yield Points for NEET PG & University Exams

• • • Gold Standard Diagnosis: Histopathology is the gold standard for diagnosing fungal rhinosinusitis, especially for distinguishing invasive from non-invasive forms and identifying specific fungal morphology.
    • Amphotericin B: The gold standard systemic antifungal for invasive fungal rhinosinusitis, particularly Mucormycosis.
    • Mucormycosis Predilection: Strong association with uncontrolled diabetes mellitus (ketoacidosis) and a characteristic of angioinvasion. Histopathology shows non-septate hyphae with 90-degree wide-angle branching.
    • Aspergillosis Histopathology: Shows septate hyphae with 45-degree angle branching.
    • Fungus Ball: Characterized by calcification on CT scan and usually does not require systemic antifungals; surgical removal is curative. Maxillary sinus is most commonly involved.
    • AFRS CT Features: Heterogeneous sinus opacity with hyperdense spots (double density/rail-track sign) and expansion of sinus walls. “Peanut butter” mucin is classic.
    • AFRS Treatment: Surgical debridement + prolonged oral/topical steroids + potentially immunotherapy.
    • Saprophytic Fungal Infection: Colonization of mucus crusts, precursor to fungus balls if untreated.
    • Acute vs. Chronic Invasive FRS: Distinguished by time course (<4 weeks vs. >12 weeks).

Other Fungal Infections in ENT

While rhinosinusitis is a primary focus, medical students and ENT PGs should be aware of other fungal infections that can affect the head and neck region.

• • 1. Candidiasis (Moniliasis or Thrush)
  • • Causative Organism: Candida albicans.
    • Common Form: Oral candidiasis is the most frequent presentation in the head and neck, seen often in very young, very old, or immunocompromised patients (e.g., AIDS patients with oral thrush and odynophagia often have esophageal candidiasis).
    • Clinical Features: White, curd-like pseudomembranes in the oropharynx, which, when wiped away, reveal red, inflamed underlying mucosa. Can also affect the larynx, nasal cavity, external ear canal, and other mucosal surfaces.
    • Diagnosis: Oral smears or scrapings for Gram’s stain or KOH preparation show broad pseudohyphae (budding yeast forms) and small yeast forms.
    • Treatment: Maintain oral hygiene, discontinue broad-spectrum antibiotics if possible, local cleaning, and topical antifungal medications (e.g., oral nystatin rinses or clotrimazole troches). IV medication is needed if swallowing is impossible or in disseminated disease.
    • Laryngeal Candidiasis: Suspect in patients with unexplained hoarseness or dysphagia. Laryngoscopy shows edema, ulcerations, and sometimes pseudomembranes. Biopsy confirms tissue invasion.
    2. Actinomycosis (Chronic Granulomatous Infestation)
  • • Causative Organism: Actinomyces species (a bacterium, though historically referred to as “ray fungus”).
    • Patient Profile: Mainly seen in farmers.
    • Lesions: Often affect the maxilla or sinuses (e.g., granuloma of the antrum), with potential secondary nasal involvement.
    • Appearance: Characterized by “sulfur granules” on examination.
    • Histopathology: Shows polymorphs, endothelial cells, foreign body giant cells, and branching acidophilic fibers radiating outwards.
    • Treatment: Penicillin in large doses for 6 to 8 weeks.
    3. Blastomycosis
  • • Causative Organism: Blastomyces dermatitidis.
    • Primary Involvement: Primarily a pulmonary disease from spore inhalation; however, laryngeal involvement can occur.
    • Clinical Features: Usually mild and self-limiting, but can cause severe pneumonia and distinctive skin lesions (large verrucous ulcers with indurated borders that can mimic squamous cell carcinoma).
    • Histopathology: Pseudoepitheliomatous hyperplasia and microabscesses or giant cells. Fungal culture on Sabouraud’s agar confirms diagnosis by demonstrating thick-walled refractile yeasts with single broad-based buds inside giant cells.
    • Treatment: Surgical drainage of abscesses (if present) followed by systemic antifungals (e.g., IV Amphotericin B). Oral Itraconazole/ketoconazole for subacute or chronic progressive disease.
    4. Coccidioidomycosis
  • • Causative Organism: Coccidioides immitis.
    • Primary Involvement: Primarily a lung disease, but laryngeal involvement can occur.
    • Clinical Features: Cough, fever, headache, sore throat, and chest pain. Most cases are self-limiting. However, a few progress to disseminated disease, potentially leading to meningitis or destructive ulcerative facial lesions.
    • Diagnosis: Tissue biopsy demonstrates double-walled spherules of C. immitis filled with endospores. Fungal cultures confirm diagnosis.
    • Treatment: IV Amphotericin B for severe pulmonary or rapidly progressing disease. Oral Itraconazole and Fluconazole for most other forms. Surgical debridement may also be necessary.
    5. Rhinosporidiosis
  • • Causative Organism: Rhinosporidium seeberi (now classified as an aquatic protozoan, not a fungus, belonging to Protistaozoa, closely related to fish pathogens).
    • Mode of Infection: From dust or animal dung containing spores, or contaminated water (e.g., ponds frequented by cattle). It is a chronic granulomatous disease affecting both humans and animals.
    • Common Sites: Most commonly seen in the nose and nasopharynx, but can involve the lip, palate, conjunctiva, epiglottis, larynx, trachea, bronchi, skin, vulva, and vagina.
    • On Examination: Presents as a pedunculated, friable, pink to purple, vascular polypoidal mass arising from the lateral or medial wall of the nose. It bleeds very easily on touch and often extends into the nasopharynx. The mass is studded with subepithelial spores or sporangia, appearing as white dots, resembling a strawberry. Spores may also be visible in nasal discharge.
    • Symptoms: Nasal obstruction, epistaxis, and nasal discharge.
    • Histopathology: Shows round or oval-shaped cells with thick walls containing multiple sporangia. Sporangia may be seen bursting through their chitinous walls.
    • Management: Complete wide excision of the mass with a diathermy knife and cauterization of its base. Recurrence is common, often requiring re-excision. Medical treatment is generally not effective, though Dapsone and antimony compounds have been tried.

Mnemonics and Learning Aids

Mnemonics for AFRS Major Criteria (Bent & Kuhn):

Think of “P-FACES” for the Positive fungal smear, Fungal (Type I hypersensitivity), Allergic mucin, CT findings, Eosinophilic mucin, Sinus Polyposis. (Note: This mnemonic combines A and E from the actual list into ‘allergic mucin’ for simplicity and includes ‘S’ for sinus polyposis.)

A simpler one: “MICE-F”

• • • Mucin (Eosinophilic)
    • IgE-mediated hypersensitivity (Type I)
    • CT findings (characteristic)
    • Eosinophilic (mucin) – redundant but helps reinforce
    • Fungal smear (positive)

 

———- End of the chapter ———–

NEET PG Style MCQs

Here are 10 NEET PG-style MCQ’s to test your understanding:

1. Which of the following is considered the gold standard for diagnosing fungal rhinosinusitis? a) Fungal culture test b) Potassium hydroxide (KOH) test c) Histopathology d) CT scan of paranasal sinuses
2. A 55-year-old diabetic patient presents with rapidly progressive facial pain, proptosis, and a black eschar on the nasal septum. Which of the following fungal organisms is most likely responsible? a) Aspergillus fumigatus b) Candida albicans c) Rhizopus oryzae d) Alternaria alternata
3. Characteristic CT findings of Allergic Fungal Rhinosinusitis (AFRS) include: a) Air-fluid level in the sinus b) Homogeneous soft tissue density with bone expansion c) Heterogeneous sinus opacity with hyperdense spots (“double density” sign) d) Complete opacification with calcifications within the sinus
4. A 30-year-old immunocompetent patient presents with unilateral headache and cacosmia. CT scan shows a heterogeneous mass with calcifications in the maxillary sinus, which on endoscopy, appears clay-like and separates easily from the mucosa. What is the most appropriate management? a) Long-term oral antifungals b) Intravenous Amphotericin B c) Complete surgical removal of the mass d) Observation and symptomatic treatment
5. Which of the following histopathological findings is characteristic of Mucormycosis? a) Septate hyphae with 45-degree angle branching b) Non-septate hyphae with 90-degree wide-angle branching c) Pseudoepitheliomatous hyperplasia d) Charcot-Leyden crystals
6. According to Bent and Kuhn’s diagnostic criteria, which of the following is NOT a major criterion for Allergic Fungal Rhinosinusitis? a) Nasal polyposis b) Type I IgE-mediated hypersensitivity c) Asthma d) Eosinophilic mucin
7. A 60-year-old patient on prolonged corticosteroids for rheumatoid arthritis develops chronic unilateral nasal obstruction and bloody discharge. CT scan shows a hyper-attenuating mass with bony erosion in the ethmoid sinus. Biopsy reveals fungal invasion with a sparse inflammatory reaction. What is the most likely diagnosis? a) Acute Necrotizing Invasive FRS b) Chronic Granulomatous Invasive FRS c) Chronic Invasive FRS d) Fungus Ball
8. Which of the following is the primary treatment for Rhinosporidiosis? a) Oral Itraconazole b) Intravenous Amphotericin B c) Wide surgical excision with diathermy cauterization d) Penicillin in large doses
9. Angioinvasion leading to thrombosis and tissue infarction is a hallmark of which fungal infection? a) Allergic Fungal Rhinosinusitis b) Fungus Ball c) Mucormycosis d) Saprophytic Fungal Infection
10. Which drug is considered the gold standard for systemic antifungal therapy in invasive fungal rhinosinusitis, especially Mucormycosis? a) Ketoconazole b) Fluconazole c) Amphotericin B d) Voriconazole

MCQ Answers and Explanations:

1. c) Histopathology. Explanation: While other tests are useful, histopathology is crucial for confirming tissue invasion and specific fungal morphology, which dictates treatment.
2. c) Rhizopus oryzae. Explanation: The clinical picture (diabetic, rapidly progressive, black eschar, proptosis) is classic for Mucormycosis, which is caused by Mucorales, including Rhizopus.
3. c) Heterogeneous sinus opacity with hyperdense spots (“double density” sign). Explanation: This is a classic radiological finding in AFRS due to the presence of thick, mineralized allergic mucin.
4. c) Complete surgical removal of the mass. Explanation: The description (clay-like, calcifications, easily separable) points to a fungus ball, which is non-invasive and cured by surgical removal without the need for systemic antifungals.
5. b) Non-septate hyphae with 90-degree wide-angle branching. Explanation: This is the characteristic histological feature of Mucorales (Mucormycosis).
6. c) Asthma. Explanation: Asthma is a minor criterion in Bent and Kuhn’s diagnostic criteria for AFRS.
7. c) Chronic Invasive FRS. Explanation: The time course (>12 weeks), immunocompromised state, bony erosion, and fungal invasion with a sparse inflammatory reaction fit the description of CIFRS.
8. c) Wide surgical excision with diathermy cauterization. Explanation: Rhinosporidiosis lesions are typically excised with cauterization to reduce recurrence; medical treatment is generally ineffective.
9. c) Mucormycosis. Explanation: Mucormycosis has a strong predilection for invading blood vessels, leading to thrombosis, infarction, and necrosis.
10. c) Amphotericin B. Explanation: Amphotericin B (especially lipid formulations) remains the cornerstone of systemic antifungal therapy for invasive fungal rhinosinusitis, particularly for Mucormycosis. Voriconazole is the drug of choice for invasive aspergillosis.

 

Practical Tips for Viva and Clinical Exams

How to Present a Case of Fungal Rhinosinusitis:

When presenting a case of fungal rhinosinusitis, especially invasive forms, emphasize the urgency and multisystem involvement.

1. Start with the Chief Complaint & History: “This is a 45-year-old male, a known diabetic with poorly controlled sugars, presenting with unilateral facial pain, black nasal discharge, and rapidly progressive proptosis over the last 5 days.”
2. Highlight Predisposing Factors: Immediately mention the patient’s immunocompromised status (e.g., uncontrolled diabetes, chemotherapy, prolonged steroid use).
3. Clinical Examination Findings: Describe local signs (black turbinate, septal perforation, periorbital edema, ophthalmoplegia), as well as any signs of systemic involvement (fever, altered sensorium).
4. Investigations: “CT scan showed extensive bony erosion of the paranasal sinuses extending into the orbit. MRI revealed cavernous sinus involvement. Endoscopy showed a black, necrotic middle turbinate.”
5. Crucial Diagnostic Step: “A biopsy was taken, which on histopathology showed broad, non-septate hyphae with 90-degree branching, confirming Mucormycosis.”
6. Management Plan: “Immediate and aggressive management was initiated with intravenous Amphotericin B, surgical debridement of all necrotic tissue, and strict glycemic control.”
7. Prognosis: “Despite aggressive measures, the prognosis remains guarded given the rapid progression and extensive involvement.”

Common Examiner Questions in Viva:

• “What is the gold standard for diagnosing fungal rhinosinusitis?” Answer: “Histopathology, as it confirms tissue invasion and distinguishes specific fungal types.”
• “Differentiate between invasive and non-invasive fungal rhinosinusitis.” Answer: “Invasive involves fungal hyphae within the tissue (mucosa, bone, vessels), while non-invasive is colonization on the surface without tissue invasion.”
• “What are the characteristic CT findings in a fungus ball?” Answer: “Heterogeneous soft tissue density with calcifications, often with sinus wall thickening/sclerosis, without an air-fluid level.”
• “How do you manage a case of Mucormycosis?” Answer: “Prompt and aggressive surgical debridement of all necrotic tissue, high-dose intravenous Amphotericin B, and strict control of underlying predisposing factors like diabetes.”
• “What are Charcot-Leyden crystals and in which condition are they seen?” Answer: “They are by-products of eosinophil degranulation and are characteristic of allergic mucin in Allergic Fungal Rhinosinusitis (AFRS).”
• “What is the significance of “black crusts” in the nasal cavity?” Answer: “Highly suspicious for invasive fungal rhinosinusitis, particularly acute necrotizing forms like Mucormycosis or Invasive Aspergillosis, indicating tissue necrosis.”
• “When would you use Voriconazole over Amphotericin B?” Answer: “Voriconazole is primarily used for Invasive Aspergillosis, while Amphotericin B is the first-line for Mucormycosis. Voriconazole may also be used in chronic granulomatous invasive FRS.”

Clinical-Based Questions for Practical & Viva Exams

1. A 68-year-old male, recently discharged after chemotherapy for lymphoma, presents to the emergency department with severe right-sided facial pain, headache, and sudden onset of blurring vision in the right eye. On examination, you notice periorbital edema, proptosis, and ophthalmoplegia of the right eye. Nasal endoscopy reveals a pale, dusky-looking middle turbinate on the right side.
   • What is your immediate differential diagnosis, considering the patient’s history and symptoms?
   • What urgent investigations would you order to confirm your diagnosis?
   • Outline the definitive management strategy for this patient.
2. A 25-year-old female, known asthmatic and atopic, presents with chronic nasal obstruction, thick yellowish-green nasal discharge, and multiple nasal polyps bilaterally. She reports that her symptoms temporarily improve with oral steroids but recur when steroids are stopped. Her CT scan shows pansinusitis with heterogeneous, hyperdense material within the maxillary and ethmoid sinuses, causing expansion of the sinus walls.
   • What is the most probable diagnosis? Justify your answer based on the clinical and radiological findings.
   • What key histopathological finding would you expect from a biopsy of the polyps and sinus contents?
   • Describe the comprehensive management plan for this patient, including both surgical and medical aspects.
3. A 40-year-old female with poorly controlled diabetes mellitus presents with a history of left-sided facial swelling, purulent nasal discharge, and fever for two months. She denies any visual symptoms or rapid progression. On examination, a firm, non-tender swelling is noted over the left cheek. Nasal endoscopy shows purulent discharge and some granulations in the left middle meatus. CT scan reveals a hyper-attenuating mass in the left maxillary sinus with mild bony erosion. A biopsy from the sinus shows fungal hyphae with a granulomatous reaction and Langhan’s giant cells.
   • What specific type of fungal rhinosinusitis is most likely in this case?
   • How does this condition differ from acute necrotising invasive fungal rhinosinusitis in terms of clinical course and histopathology?
   • What are the mainstays of treatment for this condition?

Answers to Clinical-Based Questions:

Patient Scenario 1 (Immunocompromised, Rapidly Progressive):

• a) Immediate Differential Diagnosis: Given the history of chemotherapy (immunocompromised state), rapid progression of symptoms (facial pain, proptosis, ophthalmoplegia), and the dusky/pale middle turbinate, the immediate differential diagnosis is Acute Necrotizing Invasive Fungal Rhinosinusitis, most likely Mucormycosis or severe Invasive Aspergillosis.
• b) Urgent Investigations:
  • Urgent Nasal Endoscopy and Biopsy: Crucial to obtain tissue for histopathological examination (gold standard) to confirm fungal invasion and identify fungal morphology (e.g., non-septate 90° branching hyphae for Mucor, septate 45° branching for Aspergillus).
  • Contrast-enhanced CT and MRI of Paranasal Sinuses, Orbit, and Brain: To delineate the extent of the disease, including bony destruction (CT), and orbital/intracranial extension (MRI).
  • Blood tests: Complete blood count, blood glucose (HbA1c if diabetic), renal function tests, liver function tests, and inflammatory markers (ESR, CRP).
• c) Definitive Management Strategy: This is a medical emergency.
  • Aggressive Surgical Debridement: Immediate and complete removal of all necrotic and involved tissue, potentially including orbital exenteration if vision is lost and orbital involvement is extensive.
  • Systemic Antifungal Therapy: High-dose intravenous Amphotericin B (preferably lipid formulations due to better safety profile) started immediately after suspicion. Posaconazole or Isavuconazole could be considered based on fungal type and patient tolerance.
  • Optimisation of underlying condition: Aggressive correction of immunosuppression, including management of underlying malignancy and careful attention to fluid and electrolyte balance.

Patient Scenario 2 (Atopic, Polyps, “Peanut Butter” Mucin on CT):

• a) Most Probable Diagnosis: Allergic Fungal Rhinosinusitis (AFRS).
  • Justification: The patient’s history of asthma and atopy, recurrent nasal polyps, thick yellowish-green nasal discharge, temporary response to oral steroids, and characteristic CT findings (pansinusitis with heterogeneous, hyperdense material causing sinus expansion) are all hallmarks of AFRS. The hyperdense material on CT often signifies fungal elements and calcium/manganese deposits within the allergic mucin.
• b) Key Histopathological Finding:
  • The biopsy of polyps and sinus contents would reveal eosinophilic mucin containing necrotic eosinophils, Charcot-Leyden crystals (by-products of eosinophil degranulation), and fungal hyphae, importantly, without evidence of tissue invasion.
• c) Comprehensive Management Plan:
  • Surgical: Functional Endoscopic Sinus Surgery (FESS) is the cornerstone. The goal is complete removal of all allergic mucin and polypoid disease, re-establishing sinus ventilation and drainage. Specimens should always be sent for histopathology and fungal culture.
  • Medical (Adjunctive):
    • Oral Corticosteroids: Pre-operative to reduce inflammation and intra-operative bleeding, and post-operative (tapering dose) to minimise recurrence.
    • Topical Nasal Steroids: Long-term post-operatively to control inflammation and prevent recurrence.
    • Immunotherapy: Consider allergen-specific immunotherapy or biologics (e.g., Omalizumab, an anti-IgE antibody) for refractory cases or to reduce steroid dependence, especially in patients with severe asthma and high IgE levels.
    • Regular follow-up: Essential for debridement of any residual mucin and monitoring for recurrence.

Patient Scenario 3 (Diabetic, Chronic, Granulomatous):

• a) Specific Type of Fungal Rhinosinusitis: This strongly suggests Chronic Granulomatous Invasive Fungal Rhinosinusitis (CGIFRS). The chronic nature (two months), the presence of a mass/swelling, granulomatous reaction, and Langhan’s giant cells on biopsy, along with the immunocompromised state (poorly controlled diabetes), are characteristic.
• b) Differentiation from Acute Necrotizing Invasive Fungal Rhinosinusitis (ANIFRS):
  • Clinical Course: CGIFRS is a slowly progressive disease lasting more than 12 weeks, as opposed to the rapidly progressive and fulminant nature (<4 weeks) of ANIFRS. The patient in this scenario presents with symptoms for two months.
  • Histopathology: The key differentiator is the prominent granulomatous reaction with non-caseating granulomas and Langhan’s type giant cells in CGIFRS, which are typically absent or sparse in ANIFRS. While both show fungal invasion, ANIFRS is characterized by marked angioinvasion, thrombosis, and acute neutrophilic infiltrate.
• c) Mainstays of Treatment:
  • Surgical Excision: Complete surgical resection of involved tissues to healthy, bleeding margins is crucial.
  • Antifungal Therapy: Systemic antifungal agents are required. Voriconazole is often the drug of choice for Aspergillus species, which is the common causative organism for CGIFRS.
  • Control of Underlying Predisposing Factors: Meticulous control of blood glucose in diabetic patients is essential for successful treatment and preventing recurrence.

FAQ Section (Optimized for Google Rich Snippets)

• Q: What is Fungal Rhinosinusitis? A: Fungal Rhinosinusitis is an inflammation of the sinus lining caused by a fungal infection, ranging from superficial colonization to aggressive tissue invasion.
• Q: How is Fungal Rhinosinusitis diagnosed? A: Diagnosis primarily involves clinical examination, imaging (CT/MRI), and critically, histopathological examination of biopsy samples from the affected sinuses.
• Q: What are the main types of Fungal Rhinosinusitis?A: It is broadly classified into Invasive (Acute Necrotizing, Chronic Invasive, Chronic Granulomatous) and Non-Invasive (Saprophytic, Fungus Ball, Allergic Fungal Rhinosinusitis).
• Q: What is a Fungus Ball and how is it treated? A: A Fungus Ball is a dense mass of fungal hyphae within a sinus without tissue invasion, often appearing calcified on CT; it is typically treated by complete surgical removal without systemic antifungals.
• Q: What are the warning signs of invasive fungal rhinosinusitis? A: Warning signs include rapidly progressive facial pain, black nasal discharge/eschar, proptosis, ophthalmoplegia, and fever in immunocompromised patients.
• Q: Is Allergic Fungal Rhinosinusitis an invasive condition? A: No, Allergic Fungal Rhinosinusitis is a non-invasive condition characterized by an allergic response to fungal elements within the sinus, without fungal hyphae invading the tissue.
• Q: Which underlying conditions increase the risk of Fungal Rhinosinusitis? A: Poorly controlled diabetes mellitus, immunocompromised states (e.g., AIDS, organ transplant, chemotherapy), and prolonged corticosteroid use are significant risk factors.

———— End of the chapter ————

Download full PDF Link:

Reference Textbooks.

• • • Scott-Brown, Textbook of Otorhinolaryngology-Head and Neck Surgery.
    • Glasscock-Shambaugh, Textbook of Surgery of the Ear.
    • P L Dhingra, Textbook of Diseases of Ear, Nose and Throat.
    • Hazarika P, Textbook of Ear Nose Throat And Head Neck Surgery Clinical Practical.
    • Mohan Bansal, Textbook of Diseases of Ear, Nose and Throat Head and Neck Surgery
    • Hans Behrbohm, Textbook of Ear, Nose, and Throat Diseases With Head and Neck Surgery.
    • Salah Mansour, Middle Ear Diseases – Advances in Diagnosis and Management.
    • Logan Turner, Textbook of Diseases of The Nose, Throat and Ear Head And Neck Surgery.
    • Rob and smith, Textbook of Operative surgery.
    • Anirban Biswas, Textbook of Clinical Audio-vestibulometry.
    • Arnold, U. Ganzer, Textbook of  Otorhinolaryngology, Head and Neck Surgery.

Author:

Dr. Rahul Bagla
MBBS (MAMC, Delhi) MS ENT (UCMS, Delhi)
Fellow Rhinoplasty & Facial Plastic Surgery.
Renowned Teaching Faculty
Mail: msrahulbagla@gmail.com
India

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Keywords: Fungal Rhinosinusitis is a significant and increasingly prevalent condition encountered in clinical ENT practice. This comprehensive chapter aims to equip MBBS and ENT PG students with a thorough understanding of fungal rhinosinusitis, covering its etiology, classification, clinical features, diagnosis, and management. Aligned with the CBME curriculum, this resource is meticulously designed to be your sole guide for university theory exams, viva questions, practical exams, and NEET PG MCQs. Therefore, mastering the concepts discussed here will ensure strong conceptual clarity and boost your confidence in various examination settings. Fungal Rhinosinusitis, ENT topics for NEET PG, MBBS ENT notes, ENT viva questions, Mucormycosis symptoms, Aspergillosis in sinuses, Allergic Fungal Rhinosinusitis (AFRS) treatment, Fungus ball in maxillary sinus, Invasive fungal sinusitis diagnosis, Non-invasive fungal sinusitis, Amphotericin B for fungal infections, CBME curriculum ENT, Rhinosporidiosis management, Chronic Invasive Fungal Rhinosinusitis, Acute Necrotizing Invasive Fungal Rhinosinusitis, ENT exams preparation, Sinus fungal infection symptoms, Treatment of Fungal Sinusitis, Differential diagnosis of sinusitis, Immunocompromised patients ENT infections