|Year : 2015 | Volume
| Issue : 1 | Page : 120-124
Fungal rhinosinusitis: A clinicomycological perspective
K Usha Krishnan1, D Agatha1, R Selvi2
1 Department of Microbiology, Institute of Microbiology, Madras Medical College, Chennai, India
2 Department of Microbiology , Stanley Medical College, Chennai, Tamil Nadu, India
|Date of Submission||19-Oct-2013|
|Date of Acceptance||23-Jan-2014|
|Date of Web Publication||5-Jan-2015|
K Usha Krishnan
Department of Microbiology, Institute of Microbiology, Madras Medical College, Chennai
Source of Support: None, Conflict of Interest: None
Purpose: Chronic rhinosinusitis (CRS) is a widely prevalent condition globally as well as in India. The spectrum of fungal involvement in CRS runs from benign colonisation to potentially life-threatening invasive disease. Successful treatment of such mycotic infections largely depends on the accurate identification of the pathogen, early and appropriate intervention by surgical clearance, supported with antifungal medication as per standard regimen. Thus, this study was undertaken to determine the prevalence of fungal rhinosinusitis (FRS), and to analyse its clinicomycological profile. Materials and Methods: Fifty-two patients with clinical suspicion of CRS attending a tertiary care hospital during a one-year period were included in this retrospective analysis. The sinonasal specimens were subjected to microscopy by KOH mount and fungal culture as per standard mycological technique. Tissue specimens were also subjected to histopathological examination. Results: Male to female ratio was 1.25:1; age varied from 14 years to 62 years with majority of patients (37%) belonging to age group 21-40 years. The prevalence of FRS was 44%, and 74% of it was caused by Aspergillus sp. Aspergillus flavus (A. flavus) (52%) was the most prevalent fungus isolated. Allergic fungal rhinosinusitis (AFRS) was the most common presentation (79%). Conclusion: FRS is a continuous spectrum of disease varying in presentation, treatment and long-term sequelae. Correct identification of the fungus remains essential for appropriate treatment.
Keywords: Aspergillus, allergic fungal rhinosinusitis, chronic rhinosinusitis, fungal rhinosinusitis, invasive fungal infections
|How to cite this article:|
Krishnan K U, Agatha D, Selvi R. Fungal rhinosinusitis: A clinicomycological perspective. Indian J Med Microbiol 2015;33:120-4
|How to cite this URL:|
Krishnan K U, Agatha D, Selvi R. Fungal rhinosinusitis: A clinicomycological perspective. Indian J Med Microbiol [serial online] 2015 [cited 2019 Jul 17];33:120-4. Available from: http://www.ijmm.org/text.asp?2015/33/1/120/148407
| ~ Introduction|| |
The kingdom of fungi is ubiquitous and omnipresent. In general numerous fungi of medical importance thrive as an indolent saprophyte or turn into a virulent invasive pathogen, depending on the host and environmental conditions.
Since the past two decades, fungi are increasingly recognized as a significant cause of morbidity and mortality among the patients  because of the wider use of broad-spectrum antibiotics, immunosuppressive therapy, cancer chemotherapy, increased incidence of immunodeficiency diseases and increased use of intensive care interventions.
Fungal colonization of the nose and paranasal sinuses appears to be a common finding in both normal and diseased states. Fungal rhinosinusitis (FRS) is increasing in prevalence; it causes significant physical symptoms, negatively affects quality of life and it can substantially impair daily functioning.
It presents in five clinicopathological forms, each with distinct diagnostic criteria, treatment and prognosis. The invasive forms are acute fulminant, chronic and granulomatous invasive fungal rhinosinusitis (IFRS). The non-invasive forms are fungal ball and allergic fungal rhinosinusitis (AFRS).
Early diagnosis and accurate classification of fungal rhinosinusitis which depends on demonstration of fungus may help in deciding the treatment protocol and preventing multiple surgical procedures, and may lead to effective treatment. Despite advances in medical and surgical treatment, it remains a major health burden and in many cases it is extremely challenging to treat.
Hence, this study was undertaken to determine the prevalence of fungal agents involved in chronic rhinosinusitis (CRS) and to correlate it with the various clinical presentations.
| ~ Materials and Methods|| |
In this retrospective analytical study, a total of 52 sinonasal specimens from patients with clinical suspicion of CRS collected from a tertiary care hospital in Chennai from April 2010 to March 2011 were evaluated.
Information regarding age, gender, associated co-morbid diseases, clinical presentation and immune status of the patient were retrieved from records.
Samples collected were allergic mucin, mucopurulent exudate at sinus cavity, nasal exudate and tissue specimens collected by endoscopic sinus surgery. A portion of surgically excised specimens was received in sterile normal saline from mycology laboratory and another part of the specimens was received in 10% formalin in the histopathology laboratory.
Details about sample collection, processing and final microbiological and histopathological report were obtained from archived documents.
The tissue specimens received at mycology laboratory were minced. Direct 10% KOH mount examination was performed for all these tissue specimens.
Histopathological examination of the specimens was done by haematoxylin and eosin and periodic acid-Schiff stain [Figure 1].
|Figure 1: H and E stained tissue section of the nasal mucosa showing slender septate fungal hyphae with necrosis|
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Irrespective of direct KOH positivity, the specimens were subjected to fungal culture. According to the standard mycological practice, the specimens were inoculated into two sets of Sabouraud's Dextrose Agar (SDA), in duplicates, one set with gentamicin and cycloheximide and another set without cycloheximide. One set was incubated at 37°C and another set at 25°C for 30 days. 
In culture-positive samples, the isolate was identified by detailed macroscopic morphology of colonies and microscopic morphology by performing lactophenol cotton blue tease mount and slide culture technique.
Results of fungal cultures were reviewed and correlated with clinical and histopathological findings. A clinicomycological approach was taken in arriving at a final diagnosis and categorization of FRS.
| ~ Results|| |
Age of the patients varied from 14 years to 62 years. Majority of patients (37%) belonged to an age group 21-40 years, and male to female ratio was 1.25:1.
All the patients presented with symptoms of nasal obstruction and nasal discharge, followed by headache and facial fullness in 82% and 64% of patients, respectively.
KOH smear positivity in this study was 48% [Figure 2]. Out of the 52 sinonasal specimens, 23 (44%) were culture-positive for fungus.
|Figure 2: KOH mount of the sinonasal polyp tissue showing slender septate fungal hyphae|
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On the basis of histopathological findings, 19 cases were found to be non-invasive FRS and five were IFRS [Figure 3].
|Figure 3: Flow chart showing detailed breakup of FRS patients based on histopathology|
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The distribution of isolated fungi from specimens of clinically diagnosed FRS patients is given in [Table 1].
Seventeen out of 23 culture-positive fungal pathogens was Aspergillus species (74%) and 12 belong to A. flavus (52%) [Figure 4].
Out of 16 cases of AFRS, Aspergillus flavus (A. flavus) was the most common fungus isolated (seven cases). In fungal ball, A. flavus was isolated in two cases and Aspergillus niger (A. niger) was isolated in one case.
From the five cases of IFRS, A. flavus was isolated in three cases; Scopulariopsis sp. was isolated in one case. In one patient with chronic IFRS, there was histopathological and direct KOH evidence for mucormycosis but culture was negative.
| ~ Discussion|| |
Rhinosinusitis is defined as the inflammation of nasal and paranasal sinus mucosa, and it is a common disorder affecting approximately 20% of the population at sometime of their lives.  The prevalence is even greater in tropical countries like India.
CRS is characterised by sinonasal mucosal inflammation with a history of atleast 12 weeks of persistent symptoms and signs despite maximal medical therapy. 
There is emerging evidence that fungi play an important role in exacerbation and perpetuation of mucosal inflammation in CRS, and only in more recent times has the categorization of FRS been more fully defined.
A significant number of patients diagnosed with CRS often tend to have a final diagnosis of fungal rhinosinusitis. In a study by Chakrabarti et al. 56% fungal smear positivity has been reported  ; 48% KOH smear positivity was reported in this study.
Some studies have reported 10% and 40% prevalence of sinonasal mycotic infections. , In the present study, the prevalence of fungal rhinosinusitis by fungal culture was 44% among patients with CRS. This correlates well with a study by Das et al. which reported 42.7% of fungal rhinosinusitis of all 665 cases of CRS over a period of five years.  In an another five-year study from south India, there were 63 biopsies diagnosed as FRS (45.7%) out of 138 biopsies of CRS in the study period. 
Seventy-four percent of fungal rhinosinusitis was caused by Aspergillus sp., and A. flavus (52%) was the most common isolate, a finding that is supported by a study from Iran  and by various studies from other parts of India. , In a similar study by S. Prateek et al., Aspergillus sp. (76.19%) was the most common isolated species and A. flavus (57.14%) being the most common fungal isolate among all cases of fungal rhinosinusitis. 
Aspergillus sp. is a chronic colonizer of paranasal sinuses and ears as well as associated with a variety of different clinical conditions. 
From most-invasive to least-invasive, these infections are classified into IFRS, AFRS and fungal ball. , The clinical presentations are also usually characteristic of each type.
Various studies have reported AFRS as the most common form of fungal rhinosinusitis and it is more commonly seen in tropical climates such as that seen in India. , In a seven-year study, 63% had AFRS among 211 patients, with 24% and 10% presenting with acute and chronic invasive sinusitis, respectively.  In this study, 66.6% of fungal rhinosinusitis patients presented as AFRS, and 12.5% of patients presented as sinus fungal ball; 21% of CRS were categorized as IFRS.
AFRS patients are frequently atopic individuals clinically presenting as pansinusitis and nasal polyposis,  which is due to the allergic response to the fungus colonizing the mucin in their sinonasal cavities. 
Patients with sinus fungal ball often clinically present as unilateral nasal obstruction, nasal polyp and discharge and is caused by the overgrowth of fungus in the nose and paranasal sinuses without an eosinophillic inflammatory reaction. 
Demonstration of fungal hyphae with characteristic cellular response or fungal culture positivity in properly collected sinus content in an otherwise characteristic patient is an important diagnostic criterion in these conditions. 
IFRS patients presented with diagnostic and therapeutic challenges. The histopathology of surgical sinus specimen played a major role in categorizing the IFRS patients.
Scopulariopsis sp. was isolated from the nasal biopsy specimen of a diabetic ketoacidotic patient presented clinically as acute IFRS with facial swelling and proptosis. Even though the patient was started on empirical systemic amphotericin, he succumbed to illness before the fungus could be isolated by culture.
Scopulariopsis sp. is a saprophytic fungus, and it has been reported to cause invasive infections in immunocompromised host. Deep infections caused by this fungus are associated with a high mortality rate. 
Chronic granulomatous FRS is exclusively a histopathological diagnosis in which granulomatous response is seen with considerable fibrosis. It is primarily caused by Aspergillus sp. and is mainly located in Africa and Southeast Asia. 
In this study, an immunocompetent adult male chronic FRS patient presented with signs and symptoms of bony erosion involving osteomyelitis of left maxilla with unilateral proptosis. Histopathology showed non-caseating granulomas in the involved bone and tissue and A. flavus was isolated in culture.
Of the three chronic IFRS patients who clinically presented as nasal obstruction with proptosis A. flavus was isolated from tissue biopsy specimen of two patients. Another patient had histopathological diagnosis of mucormycosis, but the fungus could not be isolated by culture.
Due to the reduced viability of non-septate zygomycetes hyphae, the causative agents of mucor mycosis have been isolated by culture in only small proportions of patients. 
Various authors propose fungal rhinosinusitis to be a continuous spectrum of disease starting from the non-invasive to the acute invasive varieties with considerable overlap and transition from one form to another in the same patient. 
Therefore, continuous surveillance of prevalent sinonasal fungal infection and periodical monitoring of changing disease pattern of FRS patients are essential. A multi-disciplinary approach involving surgery and medical department with appropriate anti-fungals and immunotherapy is more successful in treating these patients. 
| ~ Conclusion|| |
CRS not responding to standard therapy should be investigated for FRS.
Mycological identification plays a crucial role in diagnosing and categorizing CRS. It also provides therapeutic guidance for the other specialities, principally in the case of atypical presentation and in infection with less common agents.
As each of the clinicopathological variants of FRS is associated with unique geographical and host-related risk factors and different etiological agents, knowledge of the prevalent fungal agents is important. Hence, a regular monitoring of fungal infections is required to study the prevalent pattern and monitor the emerging pattern of these infections.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]