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FUNGAL SINUSITIS

Pravin Amin
 Physician and Intensivist, Bombay Hospital & Medical Research Centre, Mumbai 400 020.
Fungal sinusitis may occur in patients with chronic sinusitis, who usually have a predisposing cause such as neutropenia, AIDS, prolonged use of corticosteroids / broad spectrum antibiotics, uncontrolled diabetes or are immunosuppressed. Occasionally it may also be seen in immunocompetent patients. It is of utmost importance that physicians suspect the possibility of fungal sinusitis in theses patients if they do not respond to medical treatment or have any complication of sinusitis. A variety of different causative organisms could be responsible for fungal sinusitis. Aspergillus and mucor mycosis are the commonest. Non-invasive fungal sinusitis is usually due to aspergillosis. It mimics sinusitis but there is no response to antibiotics. Local clearance of fungus is required with medical treatment. In invasive fungal sinusitis, patients will complain of fever, local pain, swelling, discharge and foul smell. Fungal sinusitis is often detected after the onset of an orbital complication or cranial nerve palsy and the sinus involvement seen on CT scan. While imaging will undoubtedly help in the diagnosis and assessment of the extent of fungal involvement, nasal swabs or tissue must be sent for fungal culture in all patients with the slightest doubt of fungal infection to confirm the diagnosis. Early diagnosis, correction of any underlying cause and aggressive treatment is the key to a successful outcome. Treatment will require wide debridement of the affected areas and anti-fungal medication.

Allergic fungal sinusitis (AFS) is present in those patients in whom fungal hyphae can be demonstrated in allergic mucin and occurs in immunocompetent individuals.

Over the last decade, the incidence of fungal infections has increased dramatically. Fungi are ubiquitous in the environment, hence we are constantly exposed to them. Resident bacterial flora probably inhibit colonization by fungi through a number of mechanisms, primarily by competition for nutrients. Bacteria might also produce antifungal substances, further limiting colonization. Thus antimicrobial therapy predisposes to both the overgrowth of normal fungal flora, e.g., Candida species, and growth of opportunists like Aspergillus. The mucociliary action of the mucous membrane is probably the prime clearance mechanism active against inhaled fungal spores. For most fungi, cellular immunity is the mainstay of host defences. In the setting of granulocytopenia induced by chemotherapy for malignancy, the most rapidly progressive and potentially devastating opportunistic fungal infections may occur, namely disseminated candidiasis, aspergillosis, and mucormycosis. Acquired immunodeficiency syndrome (AIDS) because of abnormal T-cell function is a hallmark of the illness leading to a host of fungal infections. Diabetes mellitus, lymphomas, leukaemias, organ transplants antibacterial and corticosteroid therapy, are other predisposing factors for fungal infections.

Fungal sinusitis should be considered in all patients with chronic sinusitis. Patients with non-invasive forms have intractable sinusitis that fails to respond to repeated courses of antibiotics before the diagnosis is recognised. Invasive fungal sinusitis usually occurs in immunocompromised patients with fever, local pain, swelling, discharge, foul smell, cough, nasal mucosal ulceration, eschars, epistaxis and headache. More chronic forms of invasive disease may present as proptosis or orbital apex syndrome. While imaging will undoubtedly help in the diagnosis and assessment of the extent of fungal involvement, nasal swabs or tissue must be sent for fungal culture in all patients with the slightest doubt of fungal infection to confirm the suspicion. Early diagnosis, correction of any underlying cause and aggressive treatment is the key to a successful outcome. Untreated, the invasive form can lead to fungal invasion of cerebral blood vessels, with ischaemic infarction or direct infection of the brain.

Invasive and non-invasive sinusitis
The pathophysiology of fungal sinusitis probably involves compromised sinus aeration and altered immune responses to fungi. Invasive and non-invasive syndromes of fungal sinusitis have certain common features. They both may occur in immunocompetent or immunocompromised persons, may have an acute or chronic course, and may spread to the orbit, structures of the eye, and the brain. Purulent, pasty, often foul-smelling material is present within the affected sinuses.

Aspergillus is the most common reported cause of fungal sinusitis. Invasive fungal sinusitis can be distinguished from non-invasive disease with the use of clinical criteria, [2] radiological diagnosis of sinusitis and histopathological examination of tissues from sinuses. [3] Radiological findings in fungal sinusitis are those also seen with isolated bacterial sinusitis, such as air-fluid levels or more than 8 mm of mucoperiosteal thickening and those more specific for fungal sinusitis such as calcifications and loss of bony sinus margins (Fig. 1). Fungal cultures of the nasal mucus are dubious in the diagnosis of any form of fungal sinusitis. Stainable hyphae are not present in the mucosa of patients with chronic bacterial sinusitis; they are present solely in mucopurulent material within the sinus in non-invasive disease. Hyphae penetrate the sinus mucosa into submucosa, blood vessels, or bone in invasive disease. To distinguish between these two forms, ample quantities of sinus contents and biopsy specimens of diseased and healthy mucosa and bone bordering the area of frank necrosis must be obtained for histopathological analysis. Since fungi do not stain well with routine stains (such as haematoxylin and eosin), silver impregnation fungal stains and fungal cultures of surgical specimens are necessary whenever fungal sinusitis is considered.

Non-invasive Fungal Sinusitis

Allergic Fungal Sinusitis (AFS)
Allergic fungal sinusitis should be suspected in patients with atopy, chronic often intractable sinusitis and nasal polyposis. AFS has a slow mild course and there is no tissue invasion, expansion or erosion of the sinus wall. Sinuses contain brown or greenish black material. This material contains laminated accumulations of intact and degenerating eosinophils, Charcot- Leyden crystals, cellular debris, and sparse hyphae rarely visualised without fungal stains. Sinus mucosa has a mixed cellular infiltrate of eosinophils, plasma cells, and lymphocytes.

 
Fig 1: Coronal CT scan showing right fungal sinusitis.

The most common causes of allergic fungal sinusitis are the dematiaceous moulds including curvularia lunata, pseudallescheria boydii, bipolaris species, and the hyaline moulds such as aspergillus species and fusarium species. These fungi are also common causes of allergic rhinitis. Patients with allergic fungal sinusitis often have asthma, allergic rhinitis, eosinophilia and elevated total and fungus specific IgE concentrations. The diagnostic criteria for allergic fungal sinusitis consist of five features: radiologically confirmed sinusitis; the presence of allergic mucin within a sinus; the demonstration of fungal hyphae in the allergic mucin; the absence of fungal invasion of submucosa, blood vessels, or bone; and the absence of diabetes, immunodeficiency state. Allergic fungal sinusitis does not become invasive.

The treatment is with systemic steroids or local steroid sprays with surgical clearance of the affected sinus. Surgical intervention consists of endoscopic removal of polyps and inflammatory material to establish aeration and drainage of involved sinuses is imperative for adequate therapy. Open surgical procedures may be necessary in some patients. Amphotericin B with its attendant toxicity is not indicated, and newer, less toxic antifungal agents have not been shown to be useful. Daily sinus irrigation with warm isotonic saline can prevent impaction of mucus. Postoperatively oral prednisone in a dose of 10 to 20 mg per day is given for a minimum of two weeks, followed by the same dose on alternate days for an additional two weeks or longer. Full dose, short acting intranasal corticosteroids are prescribed on a long term basis. Postoperatively patients benefit from regular nasal endoscopy to remove any synechiae or polyps that may develop. [4,5] The neurophysician and surgeon must be aware of skull base AFS (SBAFS), where erosion of the skull base bone is seen on CT scan. [6] Biopsy will confirm the diagnosis and rule out a tumour. Treatment is again with steroids with clearance of the affected sinus.

Sinus Mycetoma
Patients with sinus mycetomas or fungus balls usually seek medical attention because of nasal obstruction, chronic sinusitis, facial pain, or foul smell. Mycetomas principally involve the maxillary sinus and may be associated with nasal polyps and bacterial sinusitis. Fungi may not grow from the hyphae rich material obtained at surgery since fungal elements in mycetomas have a low viability. Aspergillus fumigatus is the most common cause of mycetomas. Diagnosis of sinus mycetoma consists of five features. Radiological studies show sinus opacification often associated with fluffy calcifications (Fig. 2). Mucopurulent, cheesy or clay like material is present at the time of surgery. Histopathological assessment shows, dense aggregation of hyphae separate from but adjacent to the respiratory mucosa of the nongranulomatous, inflammatory response of variable intensity to adjacent fungal elements. [7] There is no fungal invasion of mucosa, associated blood vessels or bone. Allergic conditions and fungus specific IgE are less common in patients with mycetoma than in those with allergic fungal sinusitis, but like patients with allergic fungal sinusitis they are immunocompetent. Radiological findings are often interpreted as showing bony erosion which actually reflect pressure induced necrosis of bone like that seen in allergic fungal sinusitis rather than invasiveness. Removal of the fungus ball with aeration and drainage of the affected sinus usually resolves this condition without the need for antifungal agents.

 
Fig 2 : Coronal CT scan showing left maxillary sinus mycetoma.

Invasive Fungal Sinusitis

Acute Invasive Fungal Sinusitis
Rhinocerebral mucormycosis is a syndrome characterised by sinusitis and a painless, necrotic black palatal or nasal septal ulcer or eschar. Without early treatment, the fungus may rapidly propagate by the vascular route, causing death within days. [8] Although most common in patients with diabetes and other immunosuppressed patients it occasionally occurs in previously healthy patients. [9]

Histopathological studies show hyphal invasion of blood vessels, including the carotid arteries and cavernous sinuses; vasculitis with thrombosis; haemorrhage and tissue infarction. Nasal septal ulceration has been described with aspergillus species, fusarium species, and Pseudallescheria boydii and Zygomycetes like Rhizopus aryzae, Cunninghamella bertholettiae infections and has been called fulminant invasive sinusitis. The condition usually involves patients who are immunocompromised. The syndromes of fulminant invasive sinusitis and rhinocerebral mucormycosis are the same, and are termed fulminant invasive fungal sinusitis. Immediate surgical intervention should be achieved to obtain material for histopathology and to debride aggressively. Treatment with amphotericin B (1.0 to 1.5 mg per kilogram of body weight per day) should be initiated immediately. Total dose of 2500 of amphotericin B may be necessary if the patients are immuno suppressed. Liposomal amphotericin B10, azole antifungal agents, and combinations of antifungal agents will also probably prove useful in the treatment of invasive fungal sinusitis.

Granulomatous Invasive Fungal Sinusitis
Paranasal granuloma is a peculiar syndrome of chronic sinusitis associated with proptosis that has been also called indolent fungal sinusitis. In patients who appear to be immunocompetent, the causative organism is A flavus. There is exuberant fungal growth with regional tissue invasion, noncaseating granulomas with giant cells and plasma cells. This has to be removed surgically to prevent spread into the orbit and brain. Itraconazole at a dose of 8-10 mg/kg/day is very effective.

Chronic invasive fungal sinusitis
The condition has a chronic course wherein there is a thick aggregation of hyphae resembling a mycetoma and is associated with an immunocompromised state. These infections act as locally malignant conditions by invading, eroding and spreading beyond the sinus walls. It may be associated with the orbital apex syndrome resulting in diminished vision. It usually spreads from the ethmoid or sphenoid sinus (Fig. 3). Orbital exploration shows vascular invasion by fungi and has a poor prognosis particularly if the cavernous sinus is involved.

 
Fig 3 :

Axial CT scan showing fungal involvement of the ethmoid sphenoid sinuses.

An early diagnosis with endoscopic guided biopsy, culture and CT scan is imperative in managing invasive fungal sinusitis. Screening for an immunocompromised state is warranted. Aggressive early surgical intervention is of paramount importance with appropriate medical therapy of which Amphotericin B is the premier drug. Long term oral antifungals like itraconazole (or newer azoles like voriconazole) may also be needed. Despite all efforts, mortality figures remain high for invasive fungal sinusitis.

REFERENCES

  1. DeShazo RD, Chapin K Current concepts of fungal sinusitis. NEJM 1997;337:254-9
  2. Bent JP, Kuhn FA. Diagnosis of allergic fungal sinusitis. Otolaryngol Head Neck Surg 1994;111:580-8
  3. Blitzer A Lawson W. Fungal infections of the nose and paranasal sinuses. Otolaryngol Clin North Am 1993;26:1007-35
  4. Loftus BC General principles of management of fungal infections of the head and neck. Otolaryngol Clin North Am 1993;26:1115-21
  5. Graybill JR The future of antifungal therapy. Clin Infect Dis 1996;22:Suppl 2:S166-S178
  6. Kinsella JB, Rassekh CH et al. Allergic fungal sinusitis with cranial base erosion. Head and Neck May-Jun. 1996; 18(3): 211-7.
  7. Brandwein M. Histopathology of sinonasal fungal disease. Otolaryngol Clin North Am 1993;26:949-81
  8. Blitzer A, Lawson W. Patient survival factors in paranasal sinus mucormycosis. Laryngoscope 1980;90:635-48
  9. Radner AB, Witt MD et al, Acute invasive rhinocerebral zygomycosis in an otherwise healthy patient: case report and review. Clin Infect Dis 1995;20:163-6
  10. Weber RS, Lopez-Bernstein G. Treatment of invasive Aspergillus sinusitis with liposomal-amphotericin B. Laryngoscope 1987;97:937-41

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