Introduction
Allergic fungal rhinosinusitis is a form of paranasal mycosis that often causes bone destruction with extension into the orbit and anterior skull base.Reference Liu, Schaefer, Muscatello and Couldwell1
Five basic diagnostic categories of fungal rhinosinusitis disorder are currently recognised, differentiated by their characteristic clinical presentation and histopathological findings. Three types of fungal rhinosinusitis are true, tissue-invasive, infectious diseases: acute necrotising (acute invasive) fungal rhinosinusitis, chronic invasive fungal rhinosinusitis and granulomatous invasive (indolent) fungal rhinosinusitis. The two non-invasive fungal rhinosinusitis disorders are fungal ball (sinus mycetoma) and allergic fungal rhinosinusitis.Reference Shubert2 Allergic fungal rhinosinusitis usually follows a slow, nonaggressive course. However, extension of the disease process outside the confines of the sinuses can lead to massive bone destruction. Kinsella et al. have proposed a new diagnostic entity, ‘skull base allergic fungal sinusitis’, which incorporates the histological diagnostic criteria of allergic fungal sinusitis with the computed tomography (CT) criteria for bone erosion. Biopsy is necessary to exclude invasive fungus or tumour. Otolaryngologists, ophthalmologists and neurosurgeons should be familiar with skull base allergic fungal sinusitis so that systemic antifungal agents, craniotomy and dural resection (which may initially appear necessary) can be avoided.Reference Kinsella, Rassekh, Bradfield, Chaljub, McNee and Gourley3
Allergic fungal rhinosinusitis is managed using pre-operative corticosteroids and antibiotics for 10 to 14 days, prior to surgery, to decrease intranasal inflammation and post-obstructive bacterial sinusitis.
Endoscopic sinus surgery (ESS) is accepted to be the most appropriate surgical procedure for allergic fungal rhinosinusitis. Weekly follow-up visits are required in the first post-operative month to allow regular inspection of the operative site and cleaning of crusts and retained debris. To attain best results, systemic corticosteroids are continued for three to four weeks in the post-operative period, and are then gradually tapered. Topical steroids are also administered for six months post-operatively. Allergic fungal rhinosinusitis is more prevalent in temperate regions with high humidity, such as Karachi; thus the number of cases presenting to our department is ever-increasing.
The diagnosis and treatment of allergic fungal rhinosinusitis remains difficult and controversial, despite the increasing number of publications in the international literature. As very few local studies were available, we conducted this study in our department to evaluate the presentation and management of allergic fungal rhinosinusitis, with special reference to orbital and skull base erosion. This study serves not only to emphasise the seriousness of this condition, but also to propose a management strategy aiming to minimise complications, morbidity and recurrence.
Materials and methods
Forty-seven proven cases of allergic fungal sinusitis (using fungal culture and sensitivity, and/or fungal staining) were selected for this study, irrespective of age, sex, socioeconomic status and geographical area. This descriptive study was conducted from April 2003 to March 2006 in the department of otorhinolaryngology – head and neck surgery, Dow Medical College and Civil Hospital, Karachi, a 1837-bed, tertiary care hospital. A non-probability sampling technique was used.
We used a proforma to record: patient demographic data (including name, age, sex, address and socioeconomic status); signs and symptoms, laboratory investigation results (especially immunoglobulin (Ig) E and eosinophil count); and imaging results (CT and/or magnetic resonance imaging (MRI)).
The following criteria were used for case selection: (1) clinical picture of nasal polyposis, along with characteristic CT findings depicting marked polyposis involving the nose and paranasal sinuses means maxillary, frontal, ethmoidal & sphenoidal sinuses, with orbital and skull base erosion; (2) identification of allergic fungal mucin (grossly at surgery or on histopathological analysis); and (3) absence of invasive fungal disease.
We also recorded details of: surgical procedures performed; pre- and post-operative treatment; follow-up results (assessed weekly for the first month and then monthly for two years); detection of residual disease (within six months of surgery); recurrence of disease (more than six months after surgery); and revision surgery for residual or recurrent disease.
The Statistical Package for the Social Sciences version 10.0 software was used for statistical analysis. Data analysis used: the male to female ratio to indicate sex distribution; mean ± standard deviation (SD) for age distribution; and frequencies and percentages for all categorical variables (e.g. socioeconomic status, CT findings, clinical features and treatment).
Results
Forty-seven cases of proven allergic fungal sinusitis were evaluated. The majority of patients (78.71 per cent) were in their second or third decade (Table I). The mean age±SD was 23.44±10.34 years; the age range was 11 to 60 years.
Table I Age distribution
* n = 47. Age mean ± standard deviation = 23.44 ± 10.34 years (yrs); age range = 11–60 yrs.
Males comprised 70.21 per cent of the patients and females 29.78 per cent; the male to female ratio was 2.3:1 (Figure 1).
Fig. 1 Sex distribution for patients with allergic fungal rhinosinusitis (AFS) and with allergic fungal rhinosinusitis plus erosion. Total patients n = 47. Male to female sex ratios: AFS = 2.3:1; AFS + erosion = 6.8:1
The majority of patients (63.83 per cent) were of lower socioeconomic status (Table II).
Table II Socioeconomic status
*Income ≥ Rs 10 001 per person/month; †income = Rs 5001 to 10 000 per person/month; ‡income = ≤Rs 5000 per person/month; where Rs = Pakistani rupees
Histopathological analysis showed aspergillus to be the commonest type of fungus identified (59.57 per cent). In the remaining (40.42 per cent) cases, allergic mucin was seen but no fungal spores were identified.
Computed tomography scanning demonstrated double density signs on CT Scan is due to magnesium deposition, showing hyperdense areas on isodense back ground indicating fungal infestation in 37 cases (78.72 per cent), while orbital erosion (Figure 2) was noted in 29.78 per cent of cases and skull base erosion (Figure 3) in 19.14 per cent (Table III).
Fig. 2 Coronal computed tomography scan of patient with allergic fungal rhinosinusitis, showing orbital erosion.
Fig. 3 Coronal computed tomography scan of patient with allergic fungal rhinosinusitis, showing skull base erosion. 25Y/N = Years old male; R = right; L = left
Table III Prevalence of orbital & skull base erosion
Due to financial constraints, MRI was performed only in 14 cases (29.78 per cent) suspected of having intracranial and/or orbital involvement.
Nasal obstruction was the most common clinical feature, being observed in all cases (100 per cent), while nasal discharge (89.36 per cent) and postnasal drip (89.36 per cent) were the next commonest findings (Table IV).
Table IV Prevalence of nasal signs and symptoms
Of the extranasal and paranasal sinus symptoms, headache (29.78 per cent), telecanthus (29.78 per cent) and facial disfigurement (29.78 per cent) were the most common, while proptosis (19.14 per cent) and facial pain (10.63 per cent) were also encountered. The most common positive laboratory findings were raised eosinophil counts (80 per cent) and increased IgE levels (80 per cent). Unilateral involvement of the nose and paranasal sinuses was seen in 59.57 per cent of cases, while nasal polyps and allergic rhinitis were present in all cases (100 per cent).
Orbital and skull base erosion was observed in 30.04 per cent of cases, orbital erosion alone in 29.78 per cent and skull base erosion alone in 19.14 per cent (Table III). Interestingly, orbital and/or skull base erosion was notably more common in males than in females (with a ratio of 6.8:1) (Figure 1).
All patients were managed surgically using ESS.
Residual or recurrent disease was seen in only nine patients (in two years); revision ESS was performed for these cases.
Discussion
Allergic fungal rhinosinusitis is probably the endpoint in a spectrum of sinonasal diseases caused by fungi, eosinophils and other inflammatory mediators. The affected nasal mucosa ceases to function properly, resulting in a cycle of chronic oedema, stasis and bacterial super-infection.Reference Khun and Swain4 Allergic fungal rhinosinusitis usually accounts for the majority of fungal sinusitis cases, although a study in Taiwan found fungal ball to be the commonest form.Reference Granvilla, Chirala, Cernoch, Ostrowski and Truong5–Reference Hsiao, Li, Wang and Liu7
Allergic fungal rhinosinusitis usually follows a slow, nonaggressive course. However, if the disease process extends outside the confines of the sinuses, massive bone destruction can occur.Reference Kinsella, Rassekh, Bradfield, Chaljub, McNee and Gourley3 Bony erosion with intracranial and intra-orbital extension is more common in allergic fungal rhinosinusitis than in all other types of inflammatory sinusitis combined.Reference Ghegan, Lee and Schlosser8 Recognition of this possibility is important, because bone erosion can be interpreted as an indication of invasive disease.Reference Nussenbaum, Marple and Schwade9 This unique form of fungal disease may mimic anterior skull base and paranasal sinus tumours.Reference Liu, Schaefer, Muscatello and Couldwell1
Most cases of allergic fungal rhinosinusitis can be successfully managed with transnasal and/or transmaxillary endoscopic techniques. A craniotomy is very rarely indicated, unless there is a suspicion of dural invasion or extensive intracranial and/or orbital involvement inaccessible from below.Reference Liu, Schaefer, Muscatello and Couldwell1
The current study findings suggest that allergic fungal rhinosinusitis is a disease of young, immunocompetent individuals. The majority of our patients (78.71 per cent) were in their second or third decade; this is comparable with previous reports.Reference Shubert2, Reference Gupta, Ghosh and Gupta10–Reference Akhtar, Ishaque and Saadat15 Our patients' mean age was 23.44 years (SD 10.34 years), and their ages ranged from 11 to 60 years. These findings are similar to those of Mian et al. and Liu et al. In contrast, Ghegan et al. and Iqbal et al. reported a mean age of 28.6 years.Reference Liu, Schaefer, Muscatello and Couldwell1, Reference Ghegan, Lee and Schlosser8, Reference Mian, Kamal, Senthilkumaran, Abdullah and Pirani13, Reference Iqbal, Saqlain and Jalisi14
The male to female ratio of our patients was 2.3:1; this was comparable to the findings of Liu et al. (3.75:1), Ghegan et al. (4:1) and other local studies.Reference Liu, Schaefer, Muscatello and Couldwell1, Reference Ghegan, Lee and Schlosser8, Reference Mian, Kamal, Senthilkumaran, Abdullah and Pirani13–Reference Akhtar, Ishaque and Saadat15 In contrast, Rashid et al. reported a female preponderance.Reference Rashid, Ahmed, Muhammad, Hydri and Fungal16
On histopathological analysis, aspergillus was found in 59.57 per cent of our cases; this is similar to McCann and colleagues' and Panda and colleagues' findings.Reference McCann, Cromie, Chandler, Ford and Dolen17, Reference Panda, Sharma, Chakrabarti and Mann18 However, this percentage is much higher than most findings from the western world.Reference Schubert and Goetz19, Reference deShazo, Chapin and Swain20 In our remaining 40.42 per cent of allergic fungal rhinosinusitis cases, allergic mucin was seen but no fungal spores were identified; this emphasises the importance, in this condition, of surgical sinus fungal culture, and the difficulty of accurately identifying the fungal genus or species from allergic mucin histopathology alone. This was also reported in a study conducted in the southern US.Reference McCann, Cromie, Chandler, Ford and Dolen17
Computed tomography scanning is a primary imaging modality, and is probably more accurate than MRI in terms of diagnostic specificity and determination of the extent of bone erosion. Magnetic resonance imaging should be used to supplement CT when intracranial or intra-orbital extension is suspected.Reference Lund, Lloyd, Savy and Howard21 In our study, CT scanning was performed in all cases (100 per cent), and MRI in 14 cases (29.78 per cent) suspected of intracranial and/or orbital involvement. Orbital and skull base erosion was detected in 34.04 per cent of cases. This is comparable to the results of Liu et al., who observed bony erosion in 38.09 per cent of cases.Reference Liu, Schaefer, Muscatello and Couldwell1 In contrast, Ghegan et al. reported bony skull base or orbital erosion in 56 per cent of cases, Nussenbaum et al. noted bony erosion in 20 per cent, and Kinsella et al. reported skull base erosion in 21.42 per cent.Reference Kinsella, Rassekh, Bradfield, Chaljub, McNee and Gourley3, Reference Ghegan, Lee and Schlosser8, Reference Nussenbaum, Marple and Schwade9 Orbital erosion alone was detected in 29.78 per cent of our patients; this result is similar to that of Liu et al. (28.57 per cent) but higher than that of Kinsella et al. (21.42 per cent).Reference Liu, Schaefer, Muscatello and Couldwell1, Reference Kinsella, Rassekh, Bradfield, Chaljub, McNee and Gourley3 Skull base erosion alone was detected in 19.14% of our patients, whereas Liu et al. observed intracranial extension in 38.09 per cent of their patients.Reference Liu, Schaefer, Muscatello and Couldwell1
In the current study, prominent clinical features comprised nasal obstruction, nasal discharge, postnasal drip, hyposmia or anosmia, facial pain, headache, and proptosis. Corresponding results in the local and international literature differed little.Reference Shubert2, Reference Mian, Kamal, Senthilkumaran, Abdullah and Pirani13–Reference Rashid, Ahmed, Muhammad, Hydri and Fungal16 However, we observed raised IgE levels in 80 per cent of our patients, a higher proportion than that reported in other studies.Reference Schubert and Goetz19, Reference Schubert22, Reference Mabry and Manning23
Another important finding of our study was a male to female ratio of 6.8:1 in patients with orbital and skull base erosion. This represents a significant male predominance, and further research is required, with more patients and longer follow-up times, in order to confirm this finding and to investigate its cause.
• The paper explains allergic fungal rhinosinusitis and its classification
• Diagnosis of this condition requires: positive computed tomography findings; a clinical picture of nasal obstruction, discharge and postnasal drip; and identification of allergic fungal mucin
• Skull base and orbital erosion are not uncommon in cases of allergic fungal rhinosinusitis, and such cases show a significant male predominance
• The preferred treatment comprises corticosteroids plus endoscopic sinus surgery for complete removal of allergic fungal mucin and debris, together with regular follow up
Prednisolone (0.5–1 mg/kg/day) plus clarithromycin (250–500 mg twice daily) and topical steroids were given to all our patients for 10 to 14 days in the pre-operative period. This was intended to reduce inflammation by controlling infection and allergy, resulting in reduced bleeding and better surgical clearance of disease. Oral steroids were continued for three to four weeks and topical steroids for six months after surgery to prevent recurrence. No steroid toxicity was noted over two years of follow up.
Endoscopic sinus surgery was performed in all our patients to achieve complete surgical removal of allergic mucin and debris, in order to greatly decrease the antigenic load, to ensure permanent drainage with ventilation of sinuses, and to access previously diseased sinuses, as previously reported.Reference Liu, Schaefer, Muscatello and Couldwell1, Reference Kinsella, Rassekh, Bradfield, Chaljub, McNee and Gourley3, Reference Nussenbaum, Marple and Schwade9
Conclusion
Skull base and orbital erosion is not uncommon in cases of allergic fungal rhinosinusitis, and such cases have a significant male dominance; however, orbital erosion is more common than skull base erosion. The use of ESS plus pre- and post-operative steroid treatment facilitates good results. The use of pre-operative steroids decreases inflammation and helps clear disease, while post-operative steroids prevent recurrence. Regular follow up is the key to success. Endoscopic assessment of the operative site and clearance of crusts and retained debris should be conducted at every follow-up visit.
