Synonyms: Allergic Fungal Sinusitis (AFS), Allergic Aspergillus sinusitis (AAS), Allergic Aspergillosis of paranasal sinuses.
This is an increasingly recognized type of hypertrophic sinus disease or chronic rhinosinusitis though lot of confusion exists in its definition and understanding of aetiopathogenesis. The disease occurs in immunocompetent host with higher prevalence in regions with high humidity and estimated to be 5-10% of patients affected by chronic rhinosinusitis. The disease is common among adolescents and young adults.
AFRS presents with signs and symptoms of nasal airway obstruction, allergic rhinitis nasal congestion, purulent rhinorrhoea, postnasal drainage, headache. Pain is uncommon and, if present suggests the concomitant presence of bacterial rhino-sinusitis. Though the presentation of the disease is usually subtle and takes a course of over three months, occasional dramatic presentations are seen in the form of acute visual loss, gross facial dysmorphia or complete nasal obstructions.
No consensus exists among ENT specialists concerning the diagnostic criteria of AFRS. However, Bent and Kuhn’s criteria are the best accepted. The criteria include type I hypersensitivity, nasal polyposis, characteristic findings on CT scan, presence of fungi on direct microscopy or culture, allergic mucin containing fungal elements without tissue invasion. However, mycology laboratories vary in sample handling and in their capability of detection of fungi. Therefore, the presence of allergic mucin has been given more importance. Nasal polyposis may be absent especially with the history of previous surgery. Atopy is characteristic of the disease with demonstration of elevated specific IgE to one or more fungal antigens in more than 90% of these patients. The important fungi responsible for AFRS include Bipolaris, Curvularia, Exserohilum, and Alternaria among mechanized fungi andAspergillus, Fusarium in hyaline fungi. Melanized fungi are more commonly isolated from western world and Aspergillus flavus from eastern world.
The definition of AFRS has faced challenge with the demonstration of fungi in eosinophilic mucin independently from Type I hypersensitivity in most cases of chronic rhinosinusitis (Ponikau et al. 1999; Braun et al. 2003). Ponikau et al proposed a new name for this condition as Eosinophilic Fungal Rhinosinusitis (EFRS) highlighting the role of eosinophil. Though these findings raised several questions, it appears that AFRS is a separate entity under chronic rhinosinusitis that require not only the presence eosinophilic/allergic mucin with hyphae but also presence of atopy.
The comprehensive approach to manage AFRS depends on complete removal of all allergic mucin and long-term prevention of recurrence using corticosteroids and/or immunotherapy. The role of antifungal therapy is not yet clearly established. In spite of adherence to this management protocol, recurrence is not uncommon. Therefore, the management protocol is still evolving in patients with AFRS.
During surgery an aggressive posture was adopted initially because of the consideration of possible fungal invasion. Though rare histologic tissue invasion has been reported in AFRS cases in recent years, relapse rate remained high in spite of aggressive surgery and most patients required multiple surgical procedures. The most accepted protocol now is to achieve three goals during surgery: a) complete extirpation of allergic mucin and fungal debris, b) permanent drainage and ventilation of affected sinus while preserving the integrity of underlying mucosa, c) post-operative access to previously diseased areas. Some surgeons prefer to use pre-operative systemic corticosteroids therapy (prednisolone dosed at 0.5 –1 mg/kg/d) for one week before surgery to decrease intranasal inflammation and the volume of nasal polyp. The surgery may be a challenge in some cases due to extensive nasal polyposis and bleeding during surgical manipulation of the polyp. The choice of surgical approach depends on the experience and training of the surgeon. Most surgeons now prefer endoscopic surgery. However care should be taken in undertaking this surgery, as erosion of bone is well known fact in patients with AFRS leading to occasional inadvertent sinus perforation. The mucin collected during surgery should be included along with the other tissue removed while sending it to the laboratory for investigation including fungal culture and microscopy specifically for fungal elements in mucin.
Systemic corticosteroids, which were initiated before surgery or if started fresh, are continued usually for 2-12 months post-surgical period and are slowly tapered. A lower recurrence rate has been observed in patients on longer course of therapy. However, the optimal dosing regimen and length of corticosteroid therapy are still not clear. Topical corticosteroids along with systemic corticosteroid therapy are accepted as standard regimen in the post–operative treatment of AFRS in controlling local inflammation. Topical corticosteroids provide limited benefit pre-operatively due to nasal blockage. Immunotherapy may be beneficial as recurrence is markedly diminished in some studies among patients compliant with the regimen. A common misconception is that only immunotherapy for those fungi identified by culture from allergic mucin should be included in the treatment regimen. Rather a wide of variety of moulds prevalent in the local area should be tested and all positive reactors may be included in the treatment set. However, clinical data supporting this approach is still limited to draw any definite conclusion.
Due to high rate of relapse following surgery, some clinicians recommend the use of antifungal agents in patients with AFRS to prevent recurrence. The results of different anecdotal or randomized trials using antifungal agents are conflicting. To certain extent it may be due to lack of consensus in defining AFRS and EFRS patients in those studies. Therefore confident recommendation on either side cannot be done till systematic clinical trials are conducted on defined patient groups. Some authorities believe that bacterial superantigens playing an important role in the pathogenesis of AFRS, and so a few clinicians recommend the use of supplementary azythromycin or clarithromycin post-operatively. Supportive data for the recommendation of antibacterial therapy are still pending. Though the patients are atopic, they do not respond to antihistamine therapy.
In conclusion, controversy still exists regarding the exact criteria for diagnosis and proper regimen in patients with AFRS. Recent evidence support that AFRS is an immunological disease process. Further understanding of the pathogenesis of the disease would allow a more evidence-based management protocol to evolve. Though immuno-modulation through steroid use or immunotherapy may play an adjunct role, surgery is still the mainstay of management of AFRS. Surgical management has shifted from radical to conservative endoscopic complete removal of allergic mucin including fungal debris.
Professor Arunaloke Chakrabarti
Postgraduate Institute of Medical Education & Research, Chandigarh
Chandigarh 160012, India