Allergic Fungal Sinusitis/Polyposis John P. Bent III, M.D. and Frederick A. Kuhn, M.D.* ABSTRACT ACUTEIFULMINANT (INVASIVE) FUNGAL In the last decade, the medical community has recognized SINUSITIS allergic fungal sinusitis as an unique clinical entity strongly as- ulminant (invasive) fungal sinusitis is the only form of sociated with nasal polyps. We will review the differential diag- Facute fungal sinusitis. It occurs exclusively in diabetic or nosis, clinical features, diagnosis, treatment, and prognosis. Ap- immunosuppressed patients, most typically among oncol- propriate management requires distinguishing allergic fungal ogy or transplant patients. The patient generally presents sinusitis from other forms of chronic fungal and bacterial sinusitis. with ischemic tissue in the paranasal region, but not with Surgical treatment initially results in dramatic improvement, and polyps. Fungal penetration progresses rapidly, within hours oral steroids help maintain postoperative success. However, re- or days, destroying mucosa and bone while invading blood current disease eventually prevails, leaving a glaring need for vessels, orbit, brain, and skin. Histologic exam demon- improved medical treatment. (Allergy and Asthma Proc 17:259- strates vascular occlusion and necrosis (Fig. I), and fungal 268, 1996) cultures usually reveal Phycomycetes (Mucor or Rhizopus) or Aspergillus species. The term "mucormycosis," which llergic fungal sinusitis (AFS) is a newly appreciated describes acute fungal sinusitis caused by Mucor, frequently A diagnosis, first described in the early 1980s. Over the appears in the medical literature. last decade, it has come to be acknowledged as a significant This condition requires emergency surgical attention. Ne- cause of nasal polyposis and the most common form of crotic tissue should be debrided until viable tissue is en- fungal sinusitis in the United States. Although much has countered, which may require orbital enucleation or crani- been learned about AFS since its discovery, it remains a otomy. The goal is to minimize the number of fungal mysterious and chronic condition for which there exists no organisms present, but complete fungal eradication is usu- effective long-term treatment. ally not possible with surgery alone. Adjuvant antifungal In order to properly diagnose and treat AFS, the full therapy with amphotericin B helps improve survival, but spectrum of fungal sinusitis must be understood. Currently, morbidity and mortality rates are quite high. Outcome does most rhinologists recognize four types of fungal sinusitis: not appear to be dependent on whether the etiologic organ- acute/fulminant (invasive), chronic/indolent (invasive), fun- ism is Mucor or AspergiLLus. Survival rates range from gus ball, and allergic fungal sinusitis (AFS).i-3 This system 20%-75% and correlate with the control of underlying can be broken down into two invasive and two noninvasive, disease.4 Aggressive correction of any metabolic or immune or one acute and three chronic (Table I). Other forms of disorder is therefore of paramount importance. Diabetics fungal sinusitis may exist that have not yet been described. tend to fare better than patients with more refractory sys- This article will outline the four recognized types of fungal temic disorders, such as leukemia and chronic renal failure,4 sinusitis, highlighting the differences among each category. probably because diabetes can be more readily controlled. Emphasis will be placed on the pathophysiology, diagnosis, HIV-related immunosuppression does not predispose pa- and treatment of AFS. tients to acute fungal sinusitis, but AIDS victims may be at risk for fungal sinusitis caused by PseudaLLesc/Zeria boydit', Cryptococcus, or Histoplasma.s From the Department of Otolaryngology, University of Iowa Hos- CHRONICIINDOLENT (INVASIVE) FUNGAL pitals and Clinics, Iowa City, Iowa, and *the Georgia Ear Insti- SINUSITIS tute, Savannah, Georgia Address correspondence and reprint requests to Dr. John A. Bent hronic invasive fungal sinusitis features insidious 1II, Department of Otolaryngology, University of Iowa Hospitals C symptomatology complicated by fungal penetration and Clinics, Iowa City, IA 52242-1078 into tissue. It occurs in immunocompetent individuals who usually have a longstanding history of rhinosinusitis. The Allergy and Asthma Proc. 259 ALLERGIC FUNGAL SINUSITIS TABLE I Classification of Fungal Sinusitis Historical Background FS was first appreciated in the early 1980s because of Acute its histologic resemblance to allergic bronchopulmo- acute fulminant invasive A nary aspergillosis (ABPA). This connection was first appre- Chronic chronic indolent InvasIve ciated in 1981 by Millar et al., who noted a similarity fungus ball noninvasive between the sinus contents removed from five chronic si- allergic fungal sinusitis noninvasive nusitis patients and the typical pathologic appearance of ABPA.IO Two years later, Katzenstein et al. independently made the same observation, stimulating a retrospective re- disease progresses slowly, producing chronic granuloma- view of 119 chronic sinusitis surgical specimens in which tous inflammation and extension beyond sinus walls. Polyps they identified seven patients (5.9%) with septate fungal may be present. It has been compared to a locally aggressive hyphae scattered among necrotic eosinophils and amor- neoplasm.6 Plasmocytes and eosinophils may be seen in phous mucin. They termed this condition "allergic Aspergil- sinus mucosa, a finding also seen in AFS. Many of these lus sinusitis" based on the assumption that Aspergillus spe- patients have allergic histories,7 making differentiation from cies were the causative organisms. II Gourley et aI.' s AFS difficult. Fungi must be microscopically visualized retrospective review of 200 patients demonstrated a 7% within sinus tissue to distinguish this entity from the two prevalence of AFS among chronic sinusitis patients requir- noninvasive forms of fungal sinusitis. ing surgery,'4 corroborating Katzenstein et al.'s study. No Aspergillus species and members of the Dematiaceous prospective data exists regarding true disease prevalence, family are the usual causative organisms. Chronic invasive but the 6-7% rate established in retrospective studies may fungal sinusitis is virtually endemic in some areas, such as be an underestimate. As it became apparent that Dematia- Sudan6 and northern India.7 Reports of this disease have ceous fungi, not Aspergillus species, were the primary eti- 12 decreased significantly in the United States over the last ologic agents, the name was changed to AFS. ,13 decade. We have seen no cases since 1980 and believe that it is quite rare, certainly the least common of the fungal Clinical Characteristics sinus infections. arm humid climates, typified by the southeastern When pathologic examination confirms fungal invasion, WUnited States, seem to foster fungal proliferation. the physician is obligated to treat the patient aggressively. AFS patients are usually adolescents or young adults. We Complete surgical excision with wide exposure and gener- have now diagnosed over 40 cases in the last 4 years, with ous bone removal is indicated. Extensive antifungal therapy, an age range of 9 to 69 years, but have observed no sexual directed by in vitro fungal culture sensitivities, should also or ethnic predilection. Atopy and asthma have been present be used. Although recurrences commonly occur, some pa- in most reported cases. Patients typically give a history of tients achieve cure,s and the prognosis is much better than sinonasal polyposis, recurrent sinusitis, and multiple previ- for acute fungal sinusitis. ous surgeries. Usually, the inflamation affects all paranasal sinuses, but asymmetrically involves one side. FUNGUS BALL Computerized tomography (CT) scans have a character- lder names for this noninvasive form of chronic fungal istic appearance (Fig. 2). Fungal elements release ferromag- O sinusitis include mycetoma and aspergilloma. It af- netic elements (magnesium and calcium), creating a serp- fects immunocompetent, nonatopic patients and usually inginous area of high attenuation.20 CT scans often produces either no symptoms or a mild sensation of pres- demonstrate bone erosion and deviation of adjacent struc- sure. The disease may involve any sinus, but usually occurs tures. Investigators have reported bone destruction ranging in a single sinus, most frequently the maxillary antrum. from 19%27 to 80%16 of AFS cases. Such a CT appearance Bone erosion and mucosal invasion does not occur. Fungal in an allergic patient complaining of chronic sinus obstruc- proliferation produces a tangled and tightly packed mass tion is highly suggestive of AFS. Magnetic resonance im- with a clay-like appearance. The lack of sinus inflammation aging (MRI) also has a characteristic appearance, as the distinguishes this disorder from other forms of chronic ferromagnetic elements have a decreased signal intensity, fungal sinusitis. leading to a hypointense T1 image and a markedly hypoin- The etiologic organism is almost always Aspergillus fu- tense T2 image (Figs. 3 and 4). Some surgeons recommend migatus.9 Treatment consists of debridement of the fungus MRI as the optimal imaging method?1 but we believe that and sinus aeration; cure rates should approach 100%. In our CT adequately displays AFS while providing superior bone recent review of 20 consecutive cases of chronic fungal definition. sinusitis, 2 had fungus balls, equating to an incidence of Nasal endoscopy demonstrates