Role of local immunoglobulin E production in the pathophysiology of noninvasive fungal sinusitis

OBJECTIVES/HYPOTHESIS: Immunoglobulin (Ig)E-mediated hypersensitivity to fungi has been postulated to explain allergic fungal sinusitis (AFS). Not all patients suspected to have AFS demonstrate systemic evidence of allergy. Locally produced IgE might explain those patients with no systemic evidence of allergy but clinical features of AFS. The aim was to determine whether fungal-specific IgE could be demonstrated in sinus mucin in patients with eosinophilic mucin rhino-sinusitis. STUDY DESIGN: A prospective study was undertaken in a tertiary rhinology practice in Adelaide, South Australia. METHODS:: Eighty-six consecutive patients with nasal polyposis and thick, colored macroscopically "fungal-like" sinus mucin at time of surgery for chronic sinusitis were entered in the study. The sinus mucin was liquefied and underwent testing for fungal-specific IgE (Pharmacia UniCAP) and fungal culture. Serum fungal-specific and total IgE, eosinophil count, C-reactive protein (CRP), and eosinophilic cationic protein (ECP) were measured. RESULTS: Fifty-six (65%) patients were fungal culture positive, and 37% had a detectable fungal-specific IgE in sinus mucin. Data were available to classify 81 patients: AFS = 24 (30%), AFS-like = 6 (7%), nonallergic eosinophilic fungal sinusitis = 32 (40%), nonallergic, nonfungal eosinophilic sinusitis = 19 (23%). Patients with AFS were significantly more likely to have fungal-specific IgE in sinus mucin (17/24, 71%, P =.02). In all fungal culture-positive patients, positive mucin fungal-specific IgE was significantly associated with systemic fungal allergy (P =.005), but a raised total serum IgE was not. Six (19%) of the 32 patients with positive fungal cultures but negative serum fungal-specific IgE had a positive mucin fungal-specific IgE, suggesting that they may be reclassified as AFS. The mean ECP and total IgE were raised most significantly in the AFS subgroup. CONCLUSIONS: This is the first study to show that fungal-specific IgE may be demonstrated in sinus mucin. It was significantly associated with systemic fungal allergy and may play a role in a minority of fungal sinusitis patients in the absence of systemic fungal allergy.     

Effect of using multiple culture media for the diagnosis of noninvasive fungal sinusitis

BACKGROUND: This study was designed to assess the relative efficiency of three different culture media for isolating fungi in patients suspected of having noninvasive fungal sinusitis. METHODS: A prospective study was performed of 209 operative samples of sinus "fungal-like" mucin from 134 patients on 171 occasions and processed for microscopy and fungal culture in Sabouraud's dextrose agar, potato dextrose agar, and broth media. RESULTS: Ninety-three (69%) of 134 patients had evidence of fungal infection. Two-thirds of patients had negative microscopy samples yet 56% of these went on to positive cultures. Forty-five percent cultured Aspergillus genus. Discrepancy between the fungi cultured in different media and on different occasions was common. With a single culture medium up to 19% of patients and 15% of samples would have been falsely labeled fungal negative. CONCLUSION: Increasing the number and type of fungal culture media used increases the number and range of fungal isolates from mucin in patients with the features of fungal sinusitis. Negative specimen microscopy is unreliable. All specimens should be cultured in multiple media and on multiple occasions when fungal sinusitis is suspected.     

Non invasive fungal sinusitis: mycetoma and alergical fungal sinusitis

We have made a study about different cases of non-invasive fungal sinusitis (FS) treated at our hospital with surgery (endoscopic sinus approach) and medical treatment. We review two cases: Mycetoma and allergic fungal sinusitis, following the recent classification based on physiopathology, treatment and prognosis. We review the clinical presentation of the different types.     

Non-invasive fungal sinusitis: allergic fungal sinusitis and sinusal mycetomas

We review non-invasive fungal sinusitis (FS) cases treated at our Unit following the recent SF classification, based on physiopathology, treatment and prognosis. We report 7 FS cases treated during 2 years and followed a minimum of 24 months. They are two allergic FS, one of them related to an allergic bronchopulmonary aspergillosis, and five mycetomas, two of them without a sinusal foreign body, sphenoidal and maxillary respectively, and three caused by a maxillary foreign body. All were treated by endoscopic sinus surgery (ESS). The two allergic cases were also treated with systemic corticoids in the postoperative period. We review the clinical presentation of the different types of non-invasive FS, the importance of endoscopy and imaging techniques in their management, the usefulness of ESS, the common association of FS to foreign bodies, and their prognosis.     

Allergic fungal sinusitis

Allergic fungal sinusitis is a non-invasive disease, first described in the early 1980s. We review our experience with 25 patients treated at the University of Texas Medical Branch, Galveston. All patients were treated surgically, using endoscopic techniques in 17, and combined endoscopic and external procedures in eight. Histological evidence of tissue invasion was absent in all 25 patients, in spite of extensive destruction of the skull base in four. Dematiaceous fungi were the most common cultural isolate. Fifteen patients were available for more than 6 months post-operative follow-up. None of the eight patients who developed recurrent disease had been treated with post-operative systemic steroids. Four of the seven patients who remained disease-free had received steroids. Clinical trials to test the efficacy of systemic steroids in the prevention of disease recurrence are clearly warranted.     

Allergic fungal sinusitis

AFS is an increasingly recognized form of HSD, now reported throughout the world. It is probably the most frequently occurring fungal rhinosinusitis disorder. The term fungal sinusitis is no longer appropriate because the five categories of fungal rhinosinusitis can now be differentiated. Each category of fungal rhinosinusitis disorder carries different treatment approaches and prognosis. Diagnostic error can be minimized by adhering to strict diagnostic criteria. The analogy (but not identity) of AFS to ABPA has been supported by histopathology, immunopathology, and the clinical response to OCS treatment. AFS represents a true medical surgical disorder in which both surgery and postoperative medical treatment, if properly coordinated between medical and surgical specialists, leads to the best patient outcomes. Continued advances in the understanding of the immunogenetics and immunopathogenesis of AFS may provide fundamental insights into molecular mechanisms operant in other chronic inflammatory disorders, including other chronic eosinophilic-lymphocytic respiratory mucosal disorders such as common forms of HSD and chronic severe asthma.     

Allergic fungal sinusitis

Allergic fungal sinusitis (AFS) is considered an allergic inflammation against fungus, and has been reported to be refractory, with very high recurrence. In Europe and the United States, AFS incidence is reported from 4% to 7% in patients with chronic sinusitis undergoing endoscopic sinus surgery (ESS). In Japan, however, only 5 patients, including ours have been reported, making AFS very rare in Japan. We prospectively studied the incidence, pathogenesis and diagnosis of AFS in Japan among 102 patients with chronic sinusitis who underwent ESS. Four cases (3.9%) were diagnosed with AFS based on the criteria of Bent and Kuhn. This incidence is slightly lower than that reported in Europe and the United States. We report the diagnosis, treatment, and course in 4 AFS patients. Of these, an allergen provocation test against detected fungus was conducted in 2 from whom informed consent was obtained. In the immediate phase, positive reactions were observed. Immunoglobulin E (IgE) antibody-mediated type I allergy may be involved in the pathogenesis of AFS.     

Allergic fungal sinusitis

Allergic fungal sinusitis is a recently described clinical entity that has gained increased attention as a cause of chronic sinusitis. Consist in a benign noninvasive sinus disease related to a hypersensitivity reaction to fungal antigens. It should be suspected in any atopic patient with refractory nasal polyps. Computed tomography (CT) findings are characteristics, but not diagnostic. Diagnosis requires show allergic mucin in the histopathologic examination and hiphae in special fungal stains. The suitable treatment includes the allergic mucin removal and sinus aeration accomplished endoscopically, perioperative systemic steroids and immunotherapy with fungal antigens. We present a case of this kind of chronic sinusitis describing the characteristic histopathologic and radiologic findings, the pathogenic theories and recent advances in immunotherapy.     

两性霉素B鼻腔冲洗在非侵袭性真菌性鼻窦炎术后的应用

目的观察在鼻内镜手术治疗非侵袭性真菌性鼻窦炎后，应用0．05％两性霉素B冲洗鼻腔的临床效果。方法鼻内镜手术治疗的非侵袭性真菌性鼻窦炎患者16例，术后常规生理盐水冲洗鼻腔，临床症状改善不满意，术腔黏膜恢复不良，后改用0．05％两性霉素B冲洗鼻腔。结果随访6个月～2年，14例术腔上皮化，症状缓解或消失，2例术腔未上皮化，症状不能缓解，有效率87．5％。结论对于非侵袭性真菌性鼻窦炎术后恢复不良的患者给与两性霉素B冲洗鼻腔，能促进术腔黏膜上皮化，可作为降低患者术后复发率的一种治疗方法。     

血清TIgE及SIgE在非侵袭性真菌性鼻窦炎中的表达及临床意义

目的：研究血清中TIgE、SIgE在非侵袭性真菌性鼻窦炎的2个亚型（真菌球型和变态反应型）中的表达及临床意义。方法：回顾性分析非侵袭性真菌性鼻窦炎患者23例,用Unicap法检测患者血清中TIgE及SIgE的表达水平,X^2检验及Fishers精确概率计算法对血清中TIgE、SIgE的表达水平与各亚型之间的关系进行分析。结果：血清TIgE阳性10例（43％）,SIgE阳性7例（30％）。14例真菌球型中,血清TIgE阳性2例（14％）,SIgE阳性1例（7%）;9例变态反应型中,血清TIgE阳性8例（89％）,SIgE阳性6例（67％）。血清TIgE和SIgE在非侵袭性真菌性鼻窦炎的2个亚型之间的表达水平不同,差异有统计学意义（P〈0．05）。结论：变态反应型真菌性鼻窦炎中血清TIgE和SIgE的表达明显高于真菌球型,其检测指标可以作为非侵袭性真菌性鼻窦炎术前鉴别2个亚型的客观指标应用于临床,进而指导临床的治疗。     

Allergic fungal sinusitis in children

Allergic fungal sinusitis (AFS) is a subtype of eosinophilic chronic rhinosinusitis (CRS) characterized by type I hypersensitivity, nasal polyposis, characteristic computed tomography scan findings, eosinophilic mucus, and the presence of fungus on surgical specimens without evidence of tissue invasion. This refractory subtype of CRS is of the great interest in the pediatric population, given the relatively early age of onset and the difficulty in managing AFS through commercially available medical regimens. Almost universally, a diagnosis of AFS requires operative intervention. Postoperative adjuvant medical therapy is a mainstay in the treatment paradigm of pediatric AFS.     

Allergic fungal sinusitis.

In summary, AFS is a newly recognized form of sinusitis, appearing in otherwise healthy young adults with a history of chronic bacterial or polypoid rhinosinusitis refractory to conventional therapy. Radiologic study may show patchy opacification or calcifications of the sinuses on CT. The patients have an elevated total IgE, peripheral eosinophilia, and positive skin tests for fungal antigens. They may also have elevated serum fungal allergen-specific IgE and IgG and precipitating antibodies to Aspergillus, Curvularia, or other fungi. Diagnostic and therapeutic surgical drainage of the sinuses will establish a definitive diagnosis by identifying the typical allergic mucin with eosinophils, Charcot-Leyden crystals, few fungal hyphae on silver stain, and a lack of tissue invasion. Treatment, other than surgical drainage, consists of systemic corticosteroids to prevent recurrence of disease.     

Culture-positive allergic fungal sinusitis

Allergic Aspergillus sinusitis is a well-defined clinical and histologic entity, although surprisingly few reported cases have yielded any fungal growth on culture. Taking advantage of recent changes in the identification and classification of certain groups of fungi, we were able to identify a specific fungal organism in 19 of 22 consecutive patients with a histologic diagnosis of allergic fungal sinusitis over the past 2 1/2 years. Aspergillus was found in only one patient, while an organism in the family of dematiaceous fungi was found in 18 patients. Of these patients, the genus Bipolaris was the most commonly represented, while Exserohilum, Curvularia, and Alternaria species were seen with less frequency. Thus, it appears that Aspergillus may not be the most common etiologic agent in allergic "Aspergillus" sinusitis. Allergic fungal sinusitis is not unusual and its incidence may be increasing. On initial clinical evaluation it may be easily mistaken for malignancy or invasive fungal disease with the potential for overly aggressive treatment. Preoperative suspicion of allergic fungal sinusitis based on clinical and roentgenographic findings along with careful communication with the mycology laboratory about the possibility of dematiaceous fungal growth are necessary for proper diagnosis.     

急性爆发性真菌性鼻窦炎

目的　探讨急性爆发性真菌性鼻窦炎 (acutefulminantfungalsinusitis ,AFFS)的临床特征、诊断标准及治疗原则。方法　回顾收治的 6例较典型的AFFS病例诊断和治疗过程。其中结合全身疾病病史 ,发热伴颜面部、眼部及鼻部症状 ,影像学 ,鼻内镜及鼻腔分泌物真菌涂片检查 ,在患者就诊的 2 4h内做出初步诊断 5例。在此基础上鼻内镜下行全组鼻窦开放术 ,切除全部坏死组织至露出新鲜创面 5例。根据临床及影像学表现 ,进行眶内容物切除 1例。术后同时进行原发病治疗以及全身抗真菌治疗 5例。结果　 6例病例经过病理、真菌涂片及培养证实为鼻窦黏膜侵袭性真菌感染 ,其中毛霉菌 1例 ,根霉菌 2例 ,链隔孢霉菌 1例 ,曲霉菌 1例 ,毛霉菌根霉菌混合 1例。 1例未在第一时间诊断 ,且未经抗真菌治疗的患者于住院第 7天死亡 ,1例抗真菌治疗及清创术后 88d死亡 ,2例分别于治疗后 3 2个月和 6个月死于白血病 ,2例经上述治疗后分别随访 9个月和 11个月无复发 ,后者为本组唯一进行眶内容物摘除者。结论　根据病史 ,眼或颜面症状 ,鼻腔内干痂以及影像学尤其是磁共振成像 ,分泌物真菌涂片检查 ,可以在患者到鼻科就诊的 2 4h内做出AFFS的诊断。包括及时彻底的根治性清创 ,足量静脉内二性霉素B注射 ,完全控制原发病以及足够的全身支     

IgE‐mediated fungal allergy in allergic fungal sinusitis

This review will address the current knowledge of the pathogenic mechanisms in allergic fungal sinusitis (AFS) and the basis for the current classification of a subgroup of chronic rhinosinusitis patients. Special attention is directed to the role of immunoglobulin E (IgE)‐mediated fungal allergy in the pathogenesis of AFS. Concepts relating to the mucosal inflammatory response are introduced, as a knowledge of the reactions of the sinus mucosal cells can lead to a better understanding of the mechanisms perpetuating and maintaining the chronic inflammation. Laryngoscope, 2009     

变应性真菌性鼻窦炎的综合治疗

目的 探讨内、外科综合治疗手段对变应性真菌性真窦炎的治疗作用。方法 对31例变应性真菌性鼻窦炎进行了以手术治疗为中心的综合治疗．其中鼻内镜手术24例,柯-陆氏手术7例,术前、术后进行抗生素、皮质类固醇激素和抗真菌药物治疗。结果 术后均随访1年以上,无手术并发症发生．采用鼻内镜手术的患者无复发．3例采用柯-陆氏手术治疗的患者复发行二次手术。结论 本研究表明鼻内镜外科手术对变应性真菌性鼻窦炎是一种有效的微创治疗手段．手术结合内科用药对变应性真菌性鼻窦炎的治疗具有良好的效果。