Majority of fungal infections from the ENT point of view are caused by Candidiasis and Aspergillosis species. Zygomycetes including Mucor, Apophysomyces, Rhizomucor, Rhizopus, and Absidia, also contribute to a significant proportion, especially in immunosuppressed patients such as uncontrolled diabetes and malignancy.
Most of the fungi are ubiquitous soil saprophytes or even normal human commensals. But due to liberal use of broad-spectrum antibiotics and increase in the number of immunocompromised individuals has contributed to fungal growth via alteration in the normal flora. Recently advanced imaging with CT scans and MRI has improved the diagnostic capabilities.
It is characterized by inflammation of the sinus mucosa due to a fungal infection. It occurs mostly in uncontrolled diabetics, debilitated patients, such as carcinoma, and in patients on immunosuppressants, antibiotics, or steroids, and in traumatic cases with compound fractures.
- Immunocompromised patients with impaired neutrophilic response.
- Uncontrolled diabetes mellitus & ketoacidosis.
- Acquired immunodeficiency syndrome (AIDS).
- Organ or bone marrow transplantation.
- Hematological malignancies
- Chronic renal failure
- Prolonged use of corticosteroids.
- Occupational farmers, garbage cleaners
- Potassium hydroxide solution (KOH) test – It is a rapid test. It dissolves non-fungal elements in a sample and yeast cells and fungal hyphae can be visualized directly on a microscope slide.
- Fungal culture test – It is commonly used when there is persistent fungal infections or penetration into deeper tissues or cause systemic infections. Fungal culture test identifies the specific fungi but may take several weeks.
- Histopathology is the gold standard for diagnosis. It shows the fungal mycelia along with inflammatory cells.
- Treat underlying pathology.
- Treatment of acidosis and dehydration in diabetic patients.
- Systemic antifungal therapy. It is given in invasive or disseminated diseases. Amphotericin B is the gold standard. Other drugs used are 5-Flucytosine.
- Oral antifungal therapy. Ketoconazole and fluconazole.
- Aeration and drainage of infected sinuses, removal of contaminated indwelling catheters.
Chakravarti et al (2009) classified the fungal sinus disease based on tissue (mucosa, blood vessel or bone) invasion into two types (invasive and non-invasive).
- Invasive Fungal Rhinosinusitis. There is presence of fungus in the tissue (mucosa, blood vessel or bone). It is further divided into three types : (i) Acute necrotizing invasive Fungal Rhinosinusitis (ii) Chronic invasive Fungal Rhinosinusitis (iii) Chronic granulomatous invasive Fungal Rhinosinusitis.
- Non-invasive Fungal Rhinosinusitis. There is colonization of the surface of epithelial tissues, rather than invasion. It is also further divided into three types : (i) Saprophytic fungal infection. (ii) Fungus ball. (iii) Allergic Fungal Rhinosinusitis
INVASIVE FUNGAL RHINOSINUSITIS.
1. Acute Necrotizing Invasive Fungal Rhinosinusitis.
This condition is characterized by the presence of hyphal invasion of sinus tissue and a time course of less than 4 weeks. It is a rapidly progressive life-threatening condition that can result in death within days. Causative organisms are Aspergillus & Mucorales.
- Changes in mucosal appearance and/or sensation (anaesthesia) are typical on endoscopic examination.
- Histopathology examination in potassium hydroxide. – This is gold standard for diagnosis. This allows the identification of invasive features, and can often distinguish Mucorales from Aspergillus fungi. Biopsies are taken from multiple sites, particularly the middle turbinate and septum in order to confirm the diagnosis and the causal fungal organism.
- Radiological investigations – Both CT and MRI are helpful for diagnosis. CT allows detection of bony destruction while MRI is better at detecting mucosal, skin invasion, orbital or intracranial involvement. CT shows more focal bony erosions, less expansion of the sinuses, has more limited sinus disease as compared to AFRS. The disease is more outside the sinuses than within, when there is intra-orbital or intra-cranial extension.
A. Aspergillosis. It is mainly seen in persons handling small birds. Causative organisms are Aspergillus niger, A. fumigatus or A. flavus. After candidiasis, it is the second most common fungal infection seen in immunocompromised patients.
Clinical Features –
- There will be symptoms of acute or subacute rhinitis or sinusitis.
- Black or greyish membrane is present in the nasal mucosa.
- Characteristic green-brown discharge.
- Fungus ball containing semisolid cheesy-white or blackish material may be present in maxillary sinus.
Histopathology – Septate hyphae of uniform diameter with 45-degree angle branching. There is mycotic infiltration of blood vessels, vasculitis with thrombosis, tissue infarction, haemorrhage and acute neutrophilic infiltrate.
Treatment – Surgical debridement and antifungal drugs, e.g. Amphotericin B, followed by an oral ketaconazole or itraconazole to ensure eradication. Repeated irrigation with 1% gentian violet is also useful.
B. Mucormycosis (Zygomycosis or Phycomycosis). It is an opportunistic fulminant fungal infection mainly seen in uncontrolled diabetics or immunocompromised patients. Around 70% of cases are seen in uncontrolled diabetic patients as these organisms have an active ketone reductase system and thrive in high glucose acidotic conditions. Presumably, hyperglycemia and acidosis enhance tissue invasion and fungal growth. Mucormycosis has a predilection for angioinvasion. It rapidly invades the arteries and causes endothelial damage and thrombosis. Causative organisms are Mucor, Rhizopus oryzae, and Absidia.
Fungal spores are inhaled and immunosupressed host is not unable to phagocytize the spores, germination and hyphae formation occur, leading to invasion of the mucosal tissues. The disease usually starts from the nose or sinuses and, if not treated, may rapidly spread along vascular channels to involve first the orbital apex and then the cavernous sinus. Invasion of the carotid arteries can lead rapidly to cerebral ischemia and death.
Clinical features –
- There will be symptoms of acute or subacute rhinitis or sinusitis, similar to aspergillosis.
- Fever, cough, crusts formation, epistaxis and headache.
- Fever of unknown origin in immunocompromised patients, not improving with broad-spectrum intravenous antibiotics for 48 hours may be the initial presenting symptom.
- Anterior rhinoscopy or nasal endoscopy may demonstrate pale mucosa initially, but later black crusted and necrotic areas is present in the nasal cavity and sinuses. Septal perforation may also be present.
- Erosion the septum and hard palate.
- Signs of ear involvement such as sensorineural and conductive hearing loss may occur. It may occur from direct extension of the infection via the eustachian tube or the meninges, or by hematogenous spread.
- Frontal sinus is usually not involved and ethmoid sinuses are most commonly involved.
- Signs of orbital involvement such as proptosis, ptosis, orbital fixation, and blindness (panophthalmoplegia) portend a grave prognosis.
- Infection can extend to the cavernous sinus via the orbital apex, causing III, IV and VI cranial nerves palsy.
Mucormycosis – Endoscopic view in nasal cavity
Histopathology – It shows non-septate hyphae of irregular size and shape with 90-degree wide angle branching, well demonstrated in hematoxylin and eosin, PAS- or GMS-stained sections. There is mycotic infiltration of blood vessels, vasculitis with thrombosis, tissue infarction, haemorrhage and acute neutrophilic infiltrate.
Treatment – It should be swiftly instituted.
- IV amphotericin B
- Aggressive surgical debridement or even orbital exenteration is required because of extensive orbital disease
- Control of underlying predisposing cause.
2. Chronic Invasive Fungal Rhinosinusitis.
Chronic invasive Fungal Rhinosinusitis is similar to Acute necrotizing invasive Fungal Rhinosinusitis in clinical features but it is a slowly destructive disease with a time-course of more than 12 weeks duration. Causative organism are Aspergillus fumigatus or flavus.
Clinical features –
- Initially, there is unilateral bloody nasal discharge, nasal obstruction, headache, cacosmia, and purulent nasal discharge.
- In later stages, patients may present with proptosis, orbital apex syndrome, and cranial nerve deficits reflecting invasion into the orbit. Erosion of palate and facial swelling. Chronic headache, seizures, and focal neurological deficit due to intracranial involvement.
- The ethmoid and sphenoid sinuses are most commonly involved.
Histopathology – There is invasion of fungi into the sinonasal mucosa with a dense accumulation of fungal hyphae, occasional vascular invasion, and chronic or sparse inflammatory reaction. There are few inflammatory cells (unlike AIFS) and CIFS lacks granulomas often witnessed in granulomatous invasive fungal sinusitis.
Radiology – CT imaging may mimic the features of malignancy, which is the primary differential in most cases. CT shows a hyper-attenuating mass in one or more of the sinuses with destruction of the sinus bony walls. MRI is helpful in intracranial involvement.
Treatment – It is similar to Acute (fulminant) invasive Fungal Rhinosinusitis. Surgery for disease removal and antifungal agents.
3. Chronic Granulomatous Invasive FRS.
This disease entity is defined by invasive fungal infection lasting more than 12 weeks. There is presence of non-caseating granulomas with Langhan’s type giant cells and fungal hyphae. It may coexist with other types of fungal sinusitis. The disease is gradual in onset. Causative organism is Aspergillus flavus. The predisposing host factors are same as acute (fulminant) invasive fungal rhinosinusitis.
Clinical features – Proptosis with large mass in the cheek, nose, paranasal sinus and orbit.
Histopathology – There is fungal tissue invasion and a granulomatous reaction with considerable fibrosis (presence of non-caseating granulomas).
- Surgery (resection of involved tissues to bleeding margins) followed by antifungals.
- Antifungal Voriconazole is used.
NON-INVASIVE FUNGAL RHINOSINUSITIS.
1. Saprophytic fungal infection.
There is fungal colonization of mucus crusts in the nose and paranasal sinuses. It can be seen on nasal endoscopy. It is due to dysfunction in mucociliary transportation from surgery leading to crust formation which acts as a platform for growth of fungal spores. It may be precursors to fungal balls if left untreated.
2. Fungus ball.
There is accumulation of dense mass of sequestered fungal hyphae (fungal ball) within the sinus which separates easily from the sinus mucosa, without invasive or granulomatous changes. On appearance, it is clay-like or cheesy material which is green, yellow, brown or black. It may coexist with other forms of fungal sinusitis. Causative organism is Aspergillus.
Clinical features –
- Patient can be asymptomatic and may be discovered accidentally.
- Maxillary sinus (94%) is most commonly involved causing headache or facial pain, post-nasal drip and cacosmia.
- Ethmoid sinus when involved causes retroorbital pain at the vertex.
Histopathology – Shows fungal hyphae without evidence of mucosa, vessels or bone invasion with absence of eosinophils, granuloma or allergic mucin.
Radiology – CT scan is the choice of investigation. Findings:
- Heterogenous soft tissue density in a single unilateral sinus.
- No air- fluid level.
- Inner wall of the sinus eroded,
- Lateral sinus wall sclerosed.
- Calcification. It is due to the deposition of calcium salts within the fungal ball.
Treatment: Complete surgical removal of fungal ball from the affected sinus. Medical management and systemic antifungals are usually not required.
3. Allergic (Eosinophilic) Fungal Rhinosinusitis.
It occurs due to allergic and immunologic response to extramucosal fungal growth within the sinuses. It is more commonly seen in warm, humid environment and lower socioeconomic status. younger population. Usually patients are young, immunocompetent with a history of atopy or asthma.
The fungi most commonly seen in the eosinophilic mucin include Alternaria, Bipolaris, Cladosporium, Curvularia, Drechslera and Helminthosporium from the dematiaceous family and Aspergillus species.
Bent and Kuhn diagnostic criteria for AFRS:
This is the most commonly used and adopted criteria for diagnosis. There are 11 important clinical features, 5 major and 6 minor. All 5 major criteria must be met in order to make AFRS diagnosis. While the minor criteria were considered supporting features.
5 Major clinical features are:
- Evidence of type I IgE–mediated hypersensitivity.
- Nasal polyposis
- Characteristic CT findings
- Eosinophilic mucus
- Positive fungal smear
6 minor clinical features are:
- Unilateral predominance
- Radiographic bone erosion
- Fungal culture
- Charcot-Leyden crystals
- Serum eosinophilia
De Shazo et al diagnostic criteria for AFRS
It is a slightly revised criteria in order to avoid controversy related to the role of atopy in AFRS. He suggested:
- Sinusitis confirmed on ct scanning;
- The presence of allergic mucin;
- Demonstration of fungal hyphae within the allergic mucin;
- The absence of fungal invasion
- The absence of diabetes or immunodeficiency states.
- Recurrent nasal congestion, post-nasal drip, and a thick dark nasal discharge.
- Patients usually responds well to oral corticosteroids, but not antibiotics.
- Proptosis and telecanthus may be present if there is bony erosion and involvement of the orbit.
- Classical yellow/green peanut butter and axle-grease type thick mucin is present.
- Unilateral or bilateral nasal polyposis.
- Symptoms are similar to chronic sinusitis with nasal polyposis.
Histopathology – Allergic mucin consists of an eosinophilic mucin with necrotic eosinophils, inflammatory cells, Charcot-Leyden crystals (the by-product of eosinophil) and fungal hyphae.
- IgE antibodies and IgG antibodies – Raised.
- Non Contrast CT Scan is investigation of choice. There is 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 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 mucin.
- Contrast MRI is required when there is intra-cranial or intra-orbital complications or suspected.
Surgery is the mainstay of treatment although adjunctive medical management is important to keep the disease under control.
1. Surgical (Functional endoscopic sinus surgery). Complete removal of polypoid disease and allergic mucin. It re-establishes ventilation and drainage of the sinuses. Polyps and allergic mucin should be sent to microscopy and culture to exclude invasion.
- Oral steroids – It reduces intra-operative bleeding when given in pre-operative period. In postoperative period, oral steroids in a tapering dose causes reduction in post-operative mucosal disease and inflammatory markers.
- Topical nasal steroids – Following endoscopic sinus surgery, there are open sinus cavities and middle meatus, topical nasal steroids achieves the highest and effective drug concentration in the sinonasal mucosa with little systemic side effects.
- Immunotherapy – Few studies have shown reduced dependence on post-operative steroids and need for revision surgery.
OTHER FUNGAL INFECTIONS
- Candidiasis (Moniliasis or thrush).
1. Candidiasis (Moniliasis or thrush).
Causative organism is Candida albicans. Oral candidiasis is the most common form seen in head and neck region. It is commonly seen in very young and the very old patients. AIDS patients with oral thrush and odynophagia demonstrate a high likelihood of having esophageal candidiasis. When esophagitis is suspected, a barium swallow is indicated to reveal the characteristic “cobblestone” pattern.
Clinical features –
- White curd-like pseudo membrane in the oropharynx, which, when wiped away, reveals red, inflamed underlying mucosa.
- White patches are present in oral cavity, though it is also seen in larynx, nasal cavity, external ear canal, vagina and gastrointestinal tract.
Fungal stain – Oral smears or scrapings for Gram’s stain or KOH preparation shows broad pseudohyphae (actually budding yeast forms) and small yeast forms.
- Maintain oral hygiene
- Discontinue antibiotics.
- Local cleaning and application of nystatin locally or clotrimazole solution
- Topical antifungal medications (e.g. oral nystatin rinses or clotrimazole troches)
- IV medication is required when swallowing is impossible
Laryngeal candidiasis should be suspected in patients who develops unexplained hoarseness or dysphasia. Laryngoscopy reveals edema, ulcerations, and sometimes pseudomembranes. The diagnosis is confirmed by a biopsy that demonstrates tissue invasion by Candida organisms. Treatment consists of systemic and topical antifungal agents, with careful observation for the possible development of airway obstruction.
2. Actinomycosis (Chronic granulomatous infestation).
Causative organism is Actinomyces or ray fungus. It is mainly seen in farmers. Lesions are mainly seen in maxilla or sinuses (granuloma of antrum). Nose may get infected later.On examination, it looks like sulphur granules.
Histopathology – It shows polymorphs, endothelial cells and foreign body giant cells with branching acidophilic fibres radiating out are seen.
Treatment – Penicillin in large doses for 6 to 8 weeks.
Causative organism is Blastomyces dermatitidis. It is primarily pulmonary disease caused by inhalation of fungal spores but laryngeal involvement is also seen. Blastomycosisis usually mild and self-limiting, although occasionally severe pneumonia and skin lesions are seen. Skin lesions are large verrucous ulcers with indurated borders, which may impersonate squamous cell carcinoma.
Histopathology – It shows pseudoepitheliomatous hyperplasia and microabscesses or giant cells. Fungal culture confirms the diagnosis by demonstrating thick-walled refractile yeasts with single broad-based buds inside giant cellson Sabouraud’s agar medium.
- Surgical drainage of any abscess if present, followed by systemic antifungals (e.g. IV Amphotericin B)
- Oral Itraconazole/ ketoconazole for subacute or chronic progressive disease.
- IV Amphotericin B in patients with meningitis or evidence of respiratory compromise.
Causative organism is Coccidioides immitis. It is primarily lung disease but laryngeal involvement is also seen. Cough, fever, headache, sore throat, and chest pain is seen, though most of times it is self-limiting. But a few go on to have disseminated disease with the possibility of developing meningitis or destructive ulcerative facial lesions.
Tissue biopsy demonstrate double-walled spherules of C. immitis filled with endospores. Fungal cultures can confirm the diagnosis.
- IV amphotericin B for severe pulmonary or rapidly progressing disease.
- Oral Itraconazole and fluconazole are used for most other forms.
- Surgical debridement.
Causative organism is aquatic protozoan (not fungus), Rhinosporidium seeberi, which is closely related to protoctistae fish pathogens.Mode of infection is from dust or dung of animals which carries the spores of the fungus. The disease can also be acquired through contaminated water of ponds, often visited by cattle’s and other animals. It is a chronic granulomatous disease and affects both man and animals. It is commonly seen in the nose and nasopharynx. Though other sites like lip, palate, conjunctiva, epiglottis, larynx, trachea, bronchi, skin, vulva and vagina may also be involved.
On examination – There is pedunculated, friable, pink to purple colour vascular polypoidal mass arising from lateral or medial wall of the nose. It bleeds very easily on touch and often extends into nasopharynx, where it can be seen hanging behind the soft palate. The mass is studded with subepithelial spores or sporangia seen as white dots and resembles like a strawberry. Spores can also be seen in the nasal discharge. Usually symptoms are nasal obstruction, epistaxis, and nasal discharge. It should be differentiated from growth in the nose.
Histopathology – It shows round or oval shaped cells with thick walls, containing multiple sporangium. The sporangium may be seen bursting through its chitinous wall.
Management – Complete wide excision of the mass with diathermy knife and cauterisation of its base. Recurrence is common, and requires re-excision. Medical treatment not of much use but dapsone and antimony compounds have been tried.
———- End of the chapter ———–
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Dr. Rahul Kumar Bagla
MS & Fellow Rhinoplasty & Facial Plastic Surgery.
Associate Professor & Head
GIMS, Greater Noida, India
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