Fungal Rhinosinusitis

Fungal Rhinosinusitis

Robert T. Adelson

Bradley F. Marple

Matthew W. Ryan



Fungi are increasingly recognized as etiologic agents in a diversity of disease states in the nose and paranasal sinuses. Over the past 30 years our enhanced understanding of the role of fungi in sinus disease and the complex interactions between host and pathogen has led to a logical classification of fungal rhinosinusitis with improvements in treatment outcomes. At the same time, the development of endoscopic surgical techniques has improved our diagnosis and treatment of all forms of rhinosinusitis. One distinction between fungal rhinosinusitis and other forms of rhinosinusitis is that all forms of fungal rhinosinusitis require some level of endoscopic assessment or surgery.

Basic Mycology

Fungi are eukaryotic organisms ubiquitous in our environment. Scientists estimate the total number of these different fungal species to be between 20,000 and 1.5 million, of which only a fraction of a percent are responsible for human illnesses, perhaps with only a few dozen species responsible for over 90% of infections (1,2). Fungi can exist either as yeast or molds. Characteristically, molds produce hyphae, multicellular, branching tubular extensions (2 to 10 µm in diameter), which coalesce as a colony known as a mycelium. Yeast are unicellular, from 3 to 15 µm in diameter, and reproduce asexually via budding. Failure of buds to detach can result in a characteristic chain of fungal cells known as pseudohyphae. The spore represents an evolutionary solution to fungal survival problems posed by unfavorable conditions. These derivatives of sexual or asexual fungal reproduction disperse easily into the environment, can withstand adverse surroundings, and retain their germinative abilities until a more receptive milieu is encountered. Inhalation of spores is thought to be the most common route by which fungal rhinosinusitis is initiated (3). Once the nasal mucosa has been accessed, development of a pathologic condition is determined not only by the inherent characteristics of the fungus, but by the host’s immune system and the complex host-pathogen interaction that ensues.

Classification of Fungal Rhinosinusitis

Fungal disease of the nose and paranasal sinuses can be classified based on the clinical, radiologic, and histologic manifestations of the host-pathogen relationship. Most classification schemes divide fungal rhinosinusitis into invasive and noninvasive diseases based on histopathologic evidence of fungus penetrating host tissue (4) (Table 37.1). Recent adjustments to the nomenclature regarding fungal rhinosinusitis reflect the evolving knowledge in this area of Rhinology (5). The full spectrum of invasive and noninvasive fungal rhinosinusitis is considered below.

Invasive Fungal Sinusitis

The unchecked incursion of omnipresent fungal pathogens are among the most impressive infections to which humans are susceptible. While an intact immune system provides sufficient defense against the development of invasive fungal disease, the proliferation of organ transplant procedures and the greater prevalence of diabetes mellitus have led to significant increases in the incidence of invasive fungal infections reported over the last 10 years (6). The growing population of patients with conditions that predispose them to invasive fungal disease, in combination with dramatic disease velocity and considerable morbidity and mortality, has made invasive fungal sinusitis (IFS) a topic of particular interest within the Otolaryngology literature. Previously, tissue-invasive fungal disease was commonly
referred to by a variety of terms including “zygomycosis,” “mucormycosis” and “invasive aspergillosis,” which encompassed almost all of the pathogens associated with human-invasive fungal disease. Revisions of the phylogenetic classification within the kingdom Fungi have eliminated the phylum Zygomycota and therefore the pathologic term Zygomycosis has been made obsolete (7). Mucor, Rhizopus, and many of the organisms responsible for invasive disease of the Order Mucorales are instead assigned to the subphylum Mucoromycotina until further study better delineates the relationship between these organisms (8). Finally, it has become clear that the various forms of fungal rhinosinusitis are primarily determined by host factors; thus the current classification scheme does not include the names of the organism.







Localized Fungal Colonization of the Nasal or Paranasal Sinus Mucosa

Sinus FB


Modified from Chakrabarti A, Das A, Panda NK. Controversies surrounding the categorization of fungal sinusitis. Med Mycol 2009;47:S299-S308; Chakrabarti A, Denning DW, Ferguson BJ, et al. Fungal rhinosinusitis: a categorization and definitional schema addressing current controversies. Laryngoscope 2009;119:1809-1818.






– Invasive fungal hyphae are sparse and found within noncaseating granulomas

– Immunocompetent


– Dense fibrosis and mild inflammatory cell infiltrate in surrounding tissue

– Diabetic cases reported rarely

Fungal Rhinosinusitis

A. flavus is most common

Chronic Invasive

– Invasive fungal hyphae and necrotic tissue with mixed acute and chronic inflammatory cellular response.

– Diabetes Mellitus

Fungal Rhinosinusitis

– Matted hyphae can resemble sinus FB

A. fumigatus, many others


– Invasive fungal hyphae with prominent angioinvasion, thrombosed vessels, and necrotic tissue.

– Immunocompromised as a result of hematologic malignancies, therapeutic immunosuppression, diabetes mellitus

– Moderate inflammatory cell infiltrate (predominantly neutrophils)

Aspergillus and Family Mucoraceae are common

– Immunocompetent cases reported rarely

Modified from Chakrabarti A, Das A, Panda NK. Controversies surrounding the categorization of fungal sinusitis. Med Mycol 2009;47:S299-S308; Das A, Bal A. Chakrabarti A, et al. Spectrum of fungal rhinosinusitis: histopathologist’s perspective. Histopathology 2009;54:854-859; DeShazo RD. Syndromes of invasive fungal sinusitis. Med Mycol 2009;47:S309-S314.

General Description of IFS

IFS is defined by fungal elements invading host sinonasal tissue. A diagnosis of IFS hinges upon histopathologic evidence of fungi invading nasal tissue: hyphal forms within sinus mucosa, submucosa, blood vessel, or bone. Specific histopathologic features, immunocompetence of the host, and disease progression allow further classification of invasive fungal sinus disease into three forms: acute invasive fungal rhinosinusitis (AIFR), chronic invasive fungal rhinosinusitis (CIFR), and granulomatous invasive fungal rhinosinusitis (GIFR) (see Table 37.1). In brief summary, a time course of 4 weeks separates acute from chronic disease, AIFR and CIFR typically occur in patients with some degree of immunocompromise while GIFR is limited to the apparently immunocompetent (see Table 37.2). Accurate classification of these different disease entities is an important step in discussing each with regard to their clinical presentation, pathogenesis, diagnosis, and treatment.



Diagnostic imaging of the paranasal sinuses is often performed in the workup of patients with presumed or proven AIFR. Although no radiographic imaging findings have been found to be pathognomonic for AIFR, such studies assist in the differential diagnosis, treatment planning, and monitoring of the condition. CT images will document the presence of radiographic changes consistent with sinus disease and define the sinonasal anatomy both for surgery and as a baseline exam for future comparison. Fine-cut, noncontrasted CT scans of the sinuses in axial and coronal planes can detect paranasal sinus bony erosion and screen for extrasinus soft tissue involvement. Magnetic resonance imaging (MRI) (with or without gadolinium) delineates the degree of orbital involvement and/or intracranial spread. These findings provide key information regarding the feasibility of surgery and ultimately patient prognosis.

Although bone erosion and extrasinus extension are often cited as classic radiographic findings of AIFR, these results are not typically found in the incipient case of AIFR but instead are ominous signs of advanced disease. The radiographic findings with the greatest positive predictive values are also those that are indicative of late and often irreversible disease: osseous erosion, facial soft tissue thickening, extrasinus involvement. Soft tissue infiltration with loss of the fat planes anterior and posterior to the maxillary sinus is considered an early indicator of AIFR (21). Another subtle finding, severe sinonasal edema without evidence of bone erosion, is emerging as a consistent and early radiographic finding amongst many cases of invasive disease (16,22). Severe unilateral thickening of nasal cavity mucosa is the most consistent CT characteristic suggestive of early IFS, albeit nonspecific for invasive fungal disease (23) (Fig. 37.3).

Physicians should not become overly dependent upon radiographic information alone when considering the diagnosis of AIFR. AIFR may present without significant radiographic evidence of sinusitis and there is poor correlation between surgical specimens and radiographic demonstration of the extent of disease (23). While some studies report a normal CT scan in 12% of patients with histopathologic evidence of IFS, other reviews found no patient afflicted with the disease to have a normal CT scan (11,16). Care should be taken in the interpretation of CT scans in cases suspicious for AIFR as imaging studies are supportive, but not diagnostic, of AIFR.


Aspergillus and the members of the Subphylum Mucoromycotina (Mucor, Rhizomucor, Absidia) are the fungi most frequently implicated in AIFR, though unusual cases involving Candida, Bipolaris, Cunninghamella, Conidiobolus, Scytalidium, Fusarium, and Exserohilum have been reported (2,12).

The clinical manifestations of AIFR develop as a result of the propagation of angioinvasive and neuroinvasive fungi within the sinonasal cavity and facial tissues. AIFR
is defined by fungal forms invading into the submucosal tissue, often associated with angioinvasion resulting in vascular thrombosis, infarction, and necrosis. Areas of coagulative tissue necrosis are extensive and the total numbers of hyphae can be relatively sparse at times, with an associated neutrophilic infiltration (9). The acidotic environment of tissue ischemia and necrosis provide an ideal medium for fungal growth and further propagation of the fungal infestation (12).

Figure 37.3 AIFR Axial on contrast CT scan shows right maxillary sinus opacification and right nasal cavity mucosal thickening. There is loss of normal fat planes within the pterygopalatine fossa, a sign of invasive disease. Image and caption: Jeffrey Bennett, MD. Department of Radiology, University of Florida College of Medicine, Gainesville, FL.

May 24, 2016 | Posted by in OTOLARYNGOLOGY | Comments Off on Fungal Rhinosinusitis

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