Allergic Aspergillus Rhinosinusitis

Abstract

Allergic fungal rhinosinusitis (AFRS) is a unique variety of chronic polypoid rhinosinusitis usually in atopic individuals, characterized by presence of eosinophilic mucin and fungal hyphae in paranasal sinuses without invasion into surrounding mucosa. It has emerged as an important disease involving a large population across the world with geographic variation in incidence and epidemiology. The disease is surrounded by controversies regarding its definition and etiopathogenesis. A working group on “Fungal Sinusitis” under the International Society for Human and Animal Mycology (ISHAM) addressed some of those issues, but many questions remain unanswered. The descriptions of “eosinophilic fungal rhinosinusitis” (EFRS), “eosinophilic mucin rhinosinusitis” (EMRS) and mucosal invasion by hyphae in few patients have increased the problem to delineate the disease. Various hypotheses exist for etiopathogenesis of AFRS with considerable overlap, though recent extensive studies have made certain in depth understanding. The diagnosis of AFRS is a multi-disciplinary approach including the imaging, histopathology, mycology and immunological investigations. Though there is no uniform management protocol for AFRS, surgical clearing of the sinuses with steroid therapy are commonly practiced. The role of antifungal agents, leukotriene antagonists and immunomodulators is still questionable. The present review covers the controversies, recent advances in pathogenesis, diagnosis, and management of AFRS.

Literature review. Noninvasive fungal rhinosinusitis

“…Physical and chemical changes of nasal epithelial cells, caused by the negative consequences of fungal, bacterial and viral toxins action and the inhalation of air pollutants, affect the epithelial physical barrier and mucociliary clearance, generates the worsening of the rheological properties of mucus, mucus stasis and synthesis of inflammatory mediators (histamine, bradykinin, prostaglandins and cytokines, developing a chronic inflammatory process. All these changes associated with ostiomeatal obstruction, enhanced or not by the anatomical factors, cre-ate a hypoxic and anaerobic environment, by lowering the pH -a favourable and ideal condition for the proliferation and metabolism of fungi and increasing the possibility of allergic reactions 17,20 . The innate immunity involves a set of mechanisms of resistance, such as phagocytosis, which is not specific to a particular pathogen, while the acquired immunity presents a high degree of specificity, as the remarkable property of "memory".…”

“…The diagnosis of AFRS begins with a detailed anamnesis. There are some clinical aspects showing an alert sign for the clinician: patient age (usually young people, with the average age of 22 years), immunocompetent, with a long clinical picture of CRS 6,20,34,37 . During the clinical examination, nasal polyps are a universal endoscopic finding, but, in more severe cases, diplopia, ptosis and telecanthus may be identified 29,32,34 .…”

“…These cells accumulate when the fungi interact with rhinosinusal epithelial cells and produce antibodies, cytokines (interleukins -IL-1, IL-6, IL-8, IL-10, IL-12, TNF-α and interferons), chemokines, complement and various inflammatory mediators, which, in their turn, activate adaptive immunity. Interleukins (IL-4, IL-5, IL-9, IL-13) contribute to the secretion of IgE, are central mediators that play a key role in the chemotaxis, differentiation, activation and survival of eosinophils and promote independently eosinophilic inflammation with the development of FRS 15,17,20 . Together with the innate immune response, the acquired immune system contributes to chronic inflammation, observed in patients with CRS.…”

“…Fungi and inflammatory mediators (IL-5, eotaxin) contribute to the degranulation of eosinophils and the release of large quantities of major basic protein. The latter possesses local toxic effects and favours epithelial lesions of the superficial mucosa 15,20 . Thus, the results of recent studies of FRS have contributed to the elaboration of the following hypothesis.…”

“…Fungi on the sinus mucosa surface induce the production of cytokines that promote eosinophil migration through the epithelium towards the mucin. Eosinophils reach the mucin that contains fungi and releases high levels of cationic proteins (the major basic protein) to destroy fungi, favouring the appearance of epithelial lesions and aggravating the mucosal inflammation with the development of FRS 15,20,21 .…”