AFRS is usually identified in patients who are young adults with a long history of nasal congestion, immunocompetence, unilateral or asymmetric involvement of the paranasal sinuses, nasal casts, hyposmia or anosmia, and facial pressure without significant pain. These findings cannot be used for diagnosis of AFRS, but they are usually present in people who have AFRS [6, 7]. Studies have estimated that anywhere from 5 to 10 % of patients who have been diagnosed with CRS are actually suffering from AFRS. AFRS is much more common in the southeastern and southwestern portion of the United States, including the Mississippi River basin. This geographical predominance is linked to the areas with a temperate climate and increased humidity, which is more conducive for the fungus to flourish [8]. In the southeastern portion of the country, up to one third of the people undergoing functional endoscopic sinus surgery are found to have fungal sinusitis [6]. AFRS is associated with a type 1 hypersensitivity reaction and has been likened to allergic bronchopulmonary aspergillosis (ABPA) in that they are both chronic inflammatory conditions utilizing the same facets of the immune response. Both of these disease processes are set in motion by an allergic response to small numbers of fungus present in the respiratory tract [4].

Increasing evidence over the years indicates that allergens and fungus play a large role in the pathogenesis of CRS. However, many questions regarding the cause of nasal polyposis remain unanswered. The development of CRS with nasal polyps may be associated with allergens – a claim bolstered by immunological evidence that Th2 (helper T cells) and eosinophils are the predominant cell types present. In contrast, acute rhinosinusitis due to bacterial causes or mucociliary dysfunction (e.g., cystic fibrosis) is associated with a neutrophilic response [9–13]. In some cases, it is thought that fungus incites an inflammatory response that is a separate trigger for CRS in the absence of a type 1 IgE hypersensitivity reaction [14]. Although the exact mechanism of a noninvasive allergic response in AFRS is still uncertain, the most well-accepted theory on the development of the disease is as follows: (1) a previously atopic patient is exposed to a fungus, (2) the fungus incites an antigenic inflammatory response via type 1 and type 3 hypersensitivity reactions in the nasal airway leading to eosinophilic accumulation and mucosal hypertrophy, (3) the fungus is able to propagate in a closed system when coupled with previously present mechanical or anatomical obstructions (occluded ostia or polyposis), (4) the propagation of the fungus leads to the eosinophilic mucin that continues to obstruct the drainage of the paranasal sinuses, and (5) further proliferation of the fungus stimulates a vicious inflammatory cycle [8, 15]. In contrast to that theory, Ponikau [16] suggested that fungus was present in nearly all nasal mucosa of CRS patients. Further studies of these patients noted that they did not have a fungal-specific antigenic or inflammatory response and that the response did not depend on IgE-mediated reactions but instead was secondary to T-lymphocyte-mediated inflammatory cascades that ultimately incite eosinophilic chemotaxis and activation. Regardless of controversies over fungal etiology, individuals with classical AFRS have type I hypersensitivity to molds that are usually very robust and will be the focus of the current chapter.

The recurrence rate of AFRS is considered high in patients with incomplete treatment. Therapy consists of both surgical (where fungal load should be removed) and postoperative medical interventions [8]. Medical therapy alone may not be enough for treatment of AFRS.