A Study on the Prevalence and Clinical Features of Fungal Sinusitis in Chronic Rhinosinusitis

Abstract

Chronic sinusitis is a common disorder worldwide a significant proportion of which is secondary to fungal aetiology contrary to popular belief that fungal sinusitis is a rare entity, more so in a country like India where warm moist climate in a number of states and ever rising incidence of diabetes mellitus gives the fungal organisms a perfect environment to grow. This study aims to find the incidence and clinical features of fungal rhinosinusitis in chronic rhinosinusitis reinstating the fact that it should be kept as a differential diagnosis in every patient presenting with symptoms of chronic rhinosinusitis. Aim of the study was to find out the incidence and clinical manifestations of fungal sinusitis in chronic rhinosinusitis. A prospective study was conducted in JSS Academy of Higher Education and Research, Mysore during a time period of 37 months i.e. November 2015 to December 2018. Total of 190 patients with chronic rhinosinusitis were evaluated with relevant investigations to reach the diagnosis. All patients were subjected to diagnostic nasal endoscopy and CT scan of paranasal sinuses. Patients were then subjected to functional endoscopic sinus surgery and sample collected was sent for KOH stain and fungal culture with histopathology. Fungal rhinosinusitis is on the rise now and it is important to evaluate all cases with caution and keep an eye out for features suggestive of fungal sinusitis as an accurate diagnosis is the key to proper management.

Introduction

Sinusitis refers to the inflammation of paranasal sinus mucosa. It can be divided into acute and chronic based on the duration of symptoms with acute being less than 12 weeks and chronic being greater than 12 weeks. Chronic rhinosinusitis represents a significant disease burden worldwide. Fungal infections are commonly associated with chronic rhinosinusitis and can be seen both in immunocompetent and immunocompromised patients. Plaignaud in 1791 reported the first case of a 22 years old soldier with maxillary pain and was said to have a fungal tumour. A more specific diagnosis of nasal and paranasal sinus aspergillosis (non-invasive) was reported by Schubert in 1885. Stammberger reported having treated 140 patients with massive fungal sinusitis during 1976–1985. Most of the landmark studies on fungal sinusitis have been done in European and American continents and of lack a data from the Indian subcontinent prompted us to undertake this study, more so because the warm, moist environment in a number of Indian states and an ever rising incidence of diabetes mellitus in this part of the globe provides the fungal organism a perfect environment to grow.

Fungal sinusitis can be categorized into two broad groups i.e. Invasive and non-invasive based on the presence or absence of fungus in tissue (mucosa, blood vessel or bone).

Non-invasive fungal rhinosinusitis includes saprophytic fungal infection, fungal ball and allergic fungal rhinosinusitis. Saprophytic fungal infections refers to visible fungal colonization of mucosal crusts seen within nose and paranasal sinuses on nasoendoscopy. Patients are usually asymptomatic or may present with foul smelling odour. Fungal ball is more common in immunocompetent, middle aged females often with a history of previous dental procedures and is a dense accumulation of extra-mucosal fungal hyphae, usually within one sinus i.e. Maxillary sinus. Allergic fungal rhinosinusitis results from the presence of extra-mucosal fungal hyphae in sinuses. It was recognised as an upper airway manifestation of allergic bronchopulmonary aspergillosis (ABPA) in the 1970’s. Numerous case series have shown the fungi like Bipolaris, Curvularis and Alternaria to be more common than aspergillus which was the presumed pathogen. The typical AFRS patient is a young immunocompetent adult with a mean age between 21 and 33 years. There is also a higher male to female ratio. In 1994, Bent and Kuhn described a diagnostic-criteria for AFRS based on 15 consecutive AFRS patients and had 5 major and 6 minor criteria. All major criteria were necessary to define AFRS while minor criteria were supporting features.

Bent and Kuhn’s diagnostic criteria for AFRS

Major criteria	Minor criteria
Evidence of type I IgE mediated hypersensitivity	Asthma
	Unilateral predominance
Nasal polyposis	Radiographic bone erosion
Characteristic CT findings	Fungal culture
Eosinophilic mucus	Charcot–Leyden crystals
Positive fungal smear	Serum eosinophilia

Presence of allergic mucin is considered to be a characteristic feature of AFRS and on nasoendoscopy inspissated thick yellow or brown peanut-butter like mucus may be seen among polyps. CT shows heterogenous signal intensities within the paranasal sinuses filled with allergic mucin called the ‘double density sign’ and expansion of paranasal sinuses with bony erosion.

Invasive fungal rhinosinusitis includes acute, granulomatous and chronic invasive fungal rhinosinusitis. Acute or fulminant invasive disease is a life threatening condition usually present in immunocompromised patients with an impaired neutrophilic response such as those with uncontrolled diabetes mellitus, AIDS, organ transplantation and haematological malignancies. It is characterised by a time course of less than 4 weeks and the presence of hyphal invasion of sinus tissue.

Most commonly implicated fungi includes Aspergillus species and Mucorales (Rhizopus, Rhizomucor, Mucor). Commonly reported symptoms include fever, cough, crusting of nasal mucosa, epistaxis and headaches. Often fever that has failed to respond to 48 h of broad spectrum antibiotics may be the initial presenting symptom. The disease is not extensive within the sinuses and usually presents with intra-orbital or intra-cranial extension. Granulomatous FRS is defined as lasting for more than 12 weeks with a more gradual onset and causative agent almost exclusively being aspergillus flavus. It is more commonly seen in countries like India, Pakistan, Sudan. It can present as proptosis with enlarging mass in the cheek and there is presence of non-caseating granulomas with Langerhans type vasculitis and sparse hyphae. Chronic FRS is a slow destructive process with a course of more than 12 weeks with most common fungi being Aspergillus fumigatus. Most commonly involved sinuses are ethmoid and sphenoid with clinical features being similar to granulomatous FRS. Fungal sinusitis should be considered as a differential diagnosis in all patients of chronic sinusitis especially in association of intractable symptoms despite adequate treatment for bacterial sinusitis, allergic rhinitis, asthma, nasal polyposis etc. due to an increasing prevalence of immunocompromised patients across the globe.

Aims and Objectives

To find the incidence and clinical manifestations of fungal sinusitis in chronic rhinosinusitis.

Materials and Methods

A Cross sectional study was conducted in the department of otorhinolaryngology and head and neck surgery, JSS Academy of Higher Education and Research, Mysuru for a period of 37 months from November 2015 to December 2018. Study included 190 patients within the age group of 16–60 years of chronic rhinosinusitis, recurrent sinusitis, chronic rhinosinusitis in patients with diabetes mellitus and immunocompromised patients that attended OPD in department of otorhinolaryngology, JSS hospital. Cases of antrochoanal polyp, sinonasal tumours and those that don’t fall within the age bracket of 16–60 years were excluded.

Data Collection

During the study period, patients who were willing to give a written informed consent were enrolled in the trial. Diagnosis was based upon a detailed history and clinical assessment noted from each patient on admission and the data entered in proforma, CT scan of nose and paranasal sinuses (axial and coronal view). Microscopic examination of material i.e. Sinus mucosa and nasal polyp in wet KOH mount preparation, mucin examination for Charcot–Leyden crystals, histopathological examination of biopsy material with special stain and fungal culture in Sabouraud’s dextrose agar.

Statistical Analysis

Descriptive statistics were applied and data analysed by proportions and percentages. Relevant preferential statistical tests were applied.

Discussion

Fungal sinusitis which was previously not considered in the common spectrum of sinonasal diseases has seen an increasing incidence due to varying reasons.

This study was conducted in JSS Academy of Higher Education and Research, Mysore over a period of 37 months and included 190 patients between 16 and 60 years showing features of chronic rhinosinusitis clinically and radiologically who visited the department of otorhinolaryngology, head and neck surgery (Table 1). All 190 patients were subjected to undergo diagnostic nasal endoscopy and CT-PNS. FESS was performed for all patients and samples obtained were sent for KOH testing, fungal culture and histopathological examination. 58% cases of fungal sinusitis were females and 42% males. 26% cases of fungal sinusitis were diagnosed in patients with agriculture as their occupation. 44% cases of fungal sinusitis had diabetes mellitus making it the most common co-morbidity in our study comparable to the study by Pannathat et al. [1] where it was found in 29.7% of cases. One patient who was HIV positive was diagnosed to have oculorhinocerebral mucormycosis. 100% cases of invasive fungal rhinosinusitis in our study had compromised immune system like uncontrolled diabetes or HIV whereas 63% cases were immunocompromised as per study by Rajiv et al. [2] and 40% cases in a study by Navya et al. [3]. Diabetes mellitus and compromised immune status were found to have very strong correlation and were statistically significant for the incidence of fungal sinusitis cases in our study. The most common clinical symptoms with which patient of fungal sinusitis presented was nasal obstruction (82%) and headache (74%), others being excessive sneezing (8%), post nasal discharge (12%), facial pain (11%), nasal bleed (16%) and olfactory disturbances (7%) (Fig. 1). Nasal obstruction, headache and nasal bleed were found statistically significant in our study. In a study by Celso et al. [4] predominant symptoms of fungal rhinosinusitis were found to be nasal obstruction (92%), nasal secretion (88.7%), post nasal drip (82.2%) and cough (69.35%). According to study by Pannathat et al. [1] the predominant symptoms of fungal rhinosinusitis were nasal stuffiness (27.9%), nasal discharge (27.9%), facial pain (27.9%), fever (24.3%) and headache (19.8%). Diagnostic nasal endoscopy showed polypoidal changes in 71 patients (37.3%), blackish debris in 14 patients (7.4%), and mucopurulent discharge in middle meatus in 49 cases (25.8%) out of 81 cases of fungal sinusitis (Table 2, Fig. 2). In a study by Karthikeyan et al. [5] on diagnostic nasal endoscopy 44 cases showed polypoidal changes, 13 showed mucopurulent discharge and 1 case showed black crusting out of 67 patients. CT PNS was done for all cases and sinus involvement, metal dense deposits and bone erosion was noted. Unilateral sinus involvement of fungal sinusitis was seen in 52% cases in our study (Table 2) as compared to a study by Sandeep et al. [6] where unilateral involvement was seen in 83.3% cases. The most common sinus involved was maxillary sinus (86%) followed by ethmoid (74%), sphenoid (28%) and frontal (44%). Maxillary sinus is most commonly involved probably because the sinus ostium is located lowest in the middle meatus compared with other sinus ostia providing as easy access to microorganisms. Maxillary sinus was most commonly involved in the study by Sandeep et al. [6] as well (46.6%), followed by ethmoid (40%) and sphenoid (36.6%). In our study 33.3% cases of fungal rhinosinusitis showed features of metal dense deposits (Fig. 3) and 30.9% cases of bony erosion. 34.2% of the total number of cases which were subjected to KOH mount came positive for fungal sinusitis i.e. 80.2% cases of fungal sinusitis (Table 2). The other could be false negatives due to delay in processing or drying up of the sample. According to our study incidence of fungal sinusitis in chronic rhinosinusitis was found to be 42.6% (Table 2) which is similar to a study by Granville et al. [7] in 2004 and Das et al. [8] in 2009. Allergic mucin (Fig. 4) was found in 13 out of 81 cases of fungal sinusitis and these were found to satisfy Bent and Kuhn’s criteria for allergic fungal rhinosinusitis. Thus, 16% of our cases belonged to Allergic fungal sinusitis in our study. Even though our study wasn’t conducted in coastal region we found an incidence of fungal sinusitis as high as 42.6% which is contrary to the previous belief that it is more prevalent in coastal areas. 81.5% were found to be non-invasive and 18.5% to be invasive (Table 3) but according to a study conducted by Navya et al. [3] 53% were invasive and 47% were non-invasive which is conflicting with our finding. Aspergillus species was found to be the most common fungus isolated which accounted for 79% of total fungal sinusitis cases out of which Aspergillus flavus (64.2%) was most commonly isolated followed by Aspergillus fumigatus (13.6%), Mucormycosis (11.1%), Rhizopus (7.4%), Aspergillus niger (1.2%) and Scopularis (2.5%) (Table 4). Aspergillus flavus was also the most common in study by Rajiv et al. [2] in 2008. Aspergillus fumigatus is found to be more common in USA and Aspergillus flavus to be more common in India, this can be attributed to difference in climate and geographic conditions. As per our study 65.2% of the samples sent for histopathological examination gave results suggestive of chronic inflammation, 26.8% came as allergic polyp and 22.1% showed features suggestive of fungal sinusitis (Table 2). In the study conducted by Celso et al. [4] in USA definite histopathological examination showed non-specific chronic inflammation in 40.3% cases, allergic chronic inflammation in 33.8% cases, suppurative chronic inflammation in 19.3% cases and fungal invasion in 6.4% cases. Thus, the findings in both are quite comparable. 13 cases (16%) of fungal sinusitis were diagnosed to have complications which included orbital apex syndrome, superior orbital fissure syndrome, meningoencephalitis, orbital cellulitis, cavernous sinus thrombosis, ophthalmoplegia and proptosis. Complications were more common in immunocompromised patients.

Table 1.

The relevant examination findings and sinus involvement in CT PNS

	Count	Column N %
Anterior rhinoscopy mucosa
Congested	25	13.1
Normal	110	58
Pale	55	28.9
Anterior rhinoscopy nasal discharge
Blackish debris	10	5.2
Mucoid	26	13.6
Mucopurulent	36	18.9
No	118	62.1
Maxillary sinus tenderness
No	161	84.7
Yes	29	15.3
Frontal sinus tenderness
No	176	92.6
Yes	14	7.4
Ethmoidal sinus tenderness
No	173	91.0
Yes	17	9.0
Palatal involvement
No	186	97.9
Yes	4	2.1
Oroantral fistula
No	187	98.43
Yes	3	1.57
Proptosis
No	174	91.6
Yes	16	8.4
Eyes chemosis
No	178	93.7
Yes	12	6.3
Swelling over medial canthus
No	189	99.5
Yes	1	0.5
Periorbital swelling
No	169	89
Yes	21	11
Decreased vision
No	187	98.43
Yes	3	1.57
Ptosis
No	181	97.1
Yes	9	4.7
Maxillary sinus involvement CT PNS
No	15	7.9
Yes	175	92.1
Ethmoidal sinus involvement CT PNS
No	28	30.6
Yes	132	69.4
Frontal sinus involvement CT PNS
No	92	48.4
Yes	98	51.6
Sphenoid sinus involvement CT PNS
No	64	71.0
Yes	55	29.0

Fig. 1.

Distribution of cases based on diagnostic nasal endoscopy findings

Table 2.

Distribution of cases based on CT PNS features, diagnostic nasal endoscopy findings, KOH, fungal culture and histopathology findings

	Count	Column N %
Laterality of sinus involvement
Bilateral	91	48
Unilateral	99	52
Metal dense deposits CT PNS
No	163	85.8
Yes	27	14.2
Bony erosion CT PNS
No	165	86.9
Yes	25	13.1
DNE polypoidal changes
No	119	62.7
Yes	71	37.3
DNE blackish debris
No	176	92.6
Yes	14	7.4
DNE mucopurulent discharge
No	141	74.2
Yes	49	25.8
KOH
No	125	65.8
Yes	65	34.2
Fungal culture
No	109	57.4
Yes	81	42.6
HPE chronic inflammation
Yes	124	65.2
HPE allergic polyp
Yes	51	26.8
HPE fungal sinusitis
Yes	42	22.1

Fig. 2.

Symtomatology of fungal sinusitis

Fig. 3.

A CT scan, coronal view of the paranasal sinuses showing fungal rhinosinusitis of the left maxillary sinus with metal dense deposits

Fig. 4.

Allergic mucin in the left nasal cavity

Table 3.

Distribution fungal sinusitis cases into invasive and non invasive

	N	%
Type of fungal culture
Non invasive	66	81.5
Invasive	15	18.5

Table 4.

Percentage of various cultured fungi

Cultured fungus	n	%
Aspergillus flavus	52	64.2
Aspergillus fumigatus	11	13.6
Aspergillus niger	1	1.2
Mucormycosis	9	11.1
Rhizopus	6	7.4
Scopularis species	2	2.5

Conclusion

In our study the prevalence of fungal rhinosinusitis among chronic rhinosinusitis was as high as 42.6% (Table 2) with most patients being above the age of 41 years with majority of them being from an agricultural background. Most common fungal agent found was aspergillus flavus. This study has helped to tackle the popular belief that fungal sinusitis is a rare entity and establishes the fact that all cases of clinical rhinosinusitis should be evaluated with KOH mount, fungal culture and histopathological examination to rule out fungal rhinosinusitis not just in immunocompromised patients but also in immunocompetent patients where non-invasive fungal sinusitis is more commonly seen and treated appropriately with surgical debridement and antifungal therapy. Diabetes was found to be the major predisposing factor for fungal sinusitis. This increase in knowledge regarding the topic helps us to increase the precision of our diagnosis and accuracy of treatment.

Compliance with Ethical Standards

Conflicts of interest

All the authors declare they have no conflict of interest and have not received any funding.

Ethical Approval

All procedures performed in this study were in accordance with the ethical standards of the institute.