Allergic fungal sinusitis: clinicopathological characteristics

Allergic fungal sinusitis is a comparatively new disease entity in paranasal sinus mycoses. It is not a very rare condition, but diagnosis is difficult to establish. Of 28 consecutive cases of allergic nasal polyposis during a 2-year period, 11 patients had allergic fungal sinusitis and the diagnosis was based on the presence of type I hypersensitivity, eosinophilic mucus without tissue invasion of fungi on histopathology and detection of septate hyphae on direct microscopy. On culture, Aspergillus flavus was isolated from nine patients and A. fumigatus and A. niger from one patient each. Among patients with allergic fungal sinusitis, five had asthma, four had proptosis, of whom two had impaired vision, and all 11 patients had nasal obstruction. Eight patients described a history of recurrence. All patients underwent surgical clearance of the diseased sinuses and were given post-operative topical steroids to prevent recurrence.     

Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis

BACKGROUND: Few cases of allergic fungal sinusitis have been systematically evaluated to conclusively confirm working clinical, histopathologic, and serologic diagnostic criteria. OBJECTIVES: The objective of this study was to describe 67 consecutive cases of allergic fungal sinusitis, the largest number of cases yet published. METHODS: Cases from 1 practice over 8 years were evaluated with a consistent protocol, including skin testing, serum chemistries and serologies, and surgical specimen analysis. RESULTS: All patients were atopic (100 %) and had nasal polyposis (100%). They tended to be young (33.3+/-13.1 years, mean +/-SEM), immunocompetent (92 %; remaining 8 % with low quantitative immunoglobulin but normal function), have slight female preponderance (58%), have a history of hypertrophic rhinosinusitis (100%), report nasal cast production (75%), and have developed their disease in the southwestern United States. Bipolaris spicifera was the most prevalent fungus involved (67%). Total serum IgE (mean 668 IU/mL) and fungal-specific IgG were generally elevated, whereas fungal-specific precipitins and specific IgE were generally negative despite positive fungal-specific immediate hypersensitivity skin tests. CONCLUSIONS: Patients with allergic fungal sinusitis tend to have elevated total serum IgE and fungal-specific IgG at diagnosis but not fungal-specific IgE or precipitins. Histopathologic criteria for allergic fungal sinusitis diagnosis are discussed. The southwestern United States appears to be a "hot spot" for the disease, particularly caused by B spicifera.     

Chronic mycoses of the paranasal sinuses--value of endonasal paranasal sinus surgery

BACKGROUND: Many host factors even in immunocompetent patients may have an influence on development of a fungal diseases within the paranasal sinuses. Fungal sinusitis can occur in an acute form or more often to a chronic type of the disease. These mainly relatively asymptomatic chronic forms and further divided into a chronic noninvasive, chronic allergic, and chronic invasive disease. Endonasal microsurgery has significantly changed the management of chronic fungal sinusitis and allows adequate removal of pathologic tissue even in advanced situations. The aim of this study was to analyze the efficacy of endonasal surgery in chronic fungal sinusitis. MATERIAL AND METHODS: In a retrospective study we assessed a group of 40 patients who had endonasal surgery for chronic fungal sinusitis. Patient records, CT and MRI scans, microbiology and histology as well as the postoperative clinical follow-up including endoscopic photo documentation were evaluated over a period of 5 years. All patients underwent endonasal surgery using endoscopic techniques. The microscopic was of additional help in a few cases with extended disease and multiple dehiscences of the skull base. RESULTS: Twenty-four patients had a chronic noninvasive of fungal sinusitis and 16 patients had a chronic invasive form. All these patients underwent endonasal surgery without external incision. The fungal disease was erradicated in 39 cases, and revision surgery was required in only one case in which involvement of the contralateral side was not initially detected. in two cases scar tissue in the middle meatus was later excised but without evidence of residual fungal disease. Only in 6 cases was antifungal chemotherapy required, where the disease had spread into surrounding tissue or the patient had severe symptoms. CONCLUSIONS: Endonasal microsurgical techniques are today the appropriate approach for managing chronic fungal sinus disease even in severe cases with radiologic evidence of expansion or invasion of surrounding tissue. Additional antifungal chemotherapy is only rarely indicated, specifically when the fungal disease invades surrounding tissue.     

Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma

Aspergillus sp. sinusitis is not uncommon in immunocompromised patients but is unusual in patients who are not immunocompromised. The disease may occur as a saprophytic condition, as an allergic sinusitis or as a potentially lethal invasive disease. The differentiation between non-invasive and invasive Aspergillus sp. sinusitis is crucial and this distinction is fully discussed. The treatment options are also considered. Invasive disease requires aggressive treatment with long-term antifungal agents in sufficient doses combined with wide surgical excision. We present a patient who presented with invasive Aspergillus fumigatus sinusitis and subsequently developed cranial neuropathies and skull base osteitis. She was initially treated with oral itraconazole (400 mg daily) for 18 months but due to lack of response this was changed to a new experimental oral azole (voriconazole) which was continued for a further 14 months. She has since remained well for the last five years.     

APOM-project: a survey of pharmacy organization and management

Allergic fungal sinusitis (AFS) is a recently described entity that has been frequently misdiagnosed in the past. AFS is now felt to be the most common cause of fungal sinusitis. There is now a sufficient experience to make the diagnosis and the causative organisms have been elucidated. However, controversy continues to surround the pathophysiology and treatment of this challenging disease.     

Further evidence for allergic pathophysiology in allergic fungal sinusitis

Controversy continues over whether allergic fungal sinusitis represents a true allergy, an infection, or a point somewhere along a spectrum between allergy and infection. The present study describes two experiments that add weight to the argument that allergic fungal sinusitis (AFS) is truly an immunologically mediated hypersensitivity and not a form of infection. In the first experiment, eight patients with Bipolaris culture-positive AFS were prospectively evaluated with Bipolaris antigen skin testing and with inhibition radioallergosorbent (RAST) and enzyme-linked immunosorbent assay (ELISA) for Bipolaris-specific IgE and IgG antibodies. The Bipolaris AFS cases were compared with 10 control patients with no history of AFS. All eight AFS cases demonstrated positive skin testing to Bipolaris and in addition, all tested positive by RAST and ELISA for IgE and IgG Bipolaris antibodies, respectively. In the control group one patient had a positive skin test, ELISA, and RAST and one additional patient had a positive ELISA only. Good correlation was noted between skin test, RAST, and ELISA results. In the second experiment, sinus mucosa from 14 AFS patients and 10 control patients with other forms of surgical sinus disease was analyzed by immunohistocytochemistry for the eosinophilic inflammatory mediators major basic protein (MBP) and eosinophil derived neurotoxin (EDN) and the neutrophil mediator neutrophil elastase. All AFS cases demonstrated evidence of eosinophilic mediator release, and MBP and EDN predominated over neutrophil elastase. In the control group eosinophil and neutrophil mediator release in sinus mucosa was equal. The two experiments support the concept that AFS is an antigen-triggered, IgE- and IgG-mediated hypersensitivity response with a late-phase inflammatory reaction involving release of eosinophilic mediators.     

Fungal sinusitis: progression of disease in immunosuppression--a case report

Fungal sinusitis is a disease which can be grouped into invasive and noninvasive forms. The invasive entities include the acute/fulminant and chronic/indolent forms. The noninvasive entities include the fungus ball and allergic forms. The noninvasive forms, however, can develop into invasive disease under certain immunosuppressive states. The patient in this case report had the fungus ball form of fungal sinusitis which evolved into chronic, and then the acute/fulminant form approximately two weeks after undergoing cadaver-donor kidney transplantation. Due to the patient's immunosuppressed state, the fungus spread beyond the sinus region and eventually lead to fulminant disseminated disease. The severity of the fungal disease corresponded directly to the severity of the patient's immunosuppression.     

Report of the first case of invasive fungal sinusitis caused by Scopulariopsis acremonium: review of scopulariopsis infections

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.     

Paranasal sinus mycoses in north India

Recognizing the high incidence of paranasal sinus mycoses in north India, we analysed retrospectively the clinical, mycological and management aspects of 178 patients with proven disease attending our institute. On the basis of clinical, radiological, histopathological and mycological findings, the patients could be categorized into those with allergic (8), non-invasive (92) and invasive (78) disease types. Bony erosion without mucosal invasion by fungi was seen in 16 patients with non-invasive disease. Young men from rural areas were the most commonly affected. Rhinorrhoea with nasal polyposis (45.8%) and proptosis (46.4%) was the most common presentation. Concurrent involvement of the maxillary and ethmoid sinuses was common in these patients, whereas isolated sphenoid and frontal sinuses were involved in the invasive variety only. Orbital and intracranial extensions were detected in 100% and 13.2%, respectively, of patients with the invasive type of disease. Aspergillus flavus (79.7%) was the most common isolate. Surgical debridement and sinus ventilation were adequate for the effective management of the non-invasive disease. However, adjuvant medical therapy was included in treatment of the semi-invasive and invasive varieties of the disease. Itraconazole was found to be most useful in prevention of recurrence in the invasive type. Mortality was highest (33.3%) among patients with zygomycotic infection. Invasive fungal granuloma with orbital and intra-cranial invasion is a distinct entity in terms of its clinical course and treatment compared with non-invasive fungal sinusitis, and it needs to be treated aggressively with surgical excision and postoperative itraconazole.     

Therapy of sinuorbital aspergillosis with amphotericin B colloidal dispersion

Invasive aspergillosis is a feared complication in the management of patients with malignancies. We report a 13-year-old boy with acute myelogenous leukaemia and chronic sinusitis who developed a sinuorbital fungal infection during cytostatic and prolonged antibiotic treatment. The clinical findings, diagnostic measures and treatment and its adverse effects are described and discussed. Special emphasis is given to our experience of the use of colloidal dispersed amphotericin B (Amphocil).     

Invasive mold sinusitis: 17 cases in immunocompromised patients and review of the literature

A 10-year retrospective analysis of invasive mold infections in hospitalized patients was performed to characterize the epidemiology and clinical features of invasive fungal sinusitis. Seventeen cases of invasive mold sinusitis were identified. Eleven cases were caused by Aspergillus flavus, three were caused by unspecified species, and one each was caused by Aspergillus fumigatus, Rhizopus species, and Alternaria species, respectively. Fifteen patients had hematologic malignancies, and two had end-stage liver disease. The most common presenting symptom was periorbital swelling (seven patients). Sinusitis was diagnosed a median of 19 days after admission. Eight patients (47%) survived; six of these patients were treated with both amphotericin B and surgery. Postmortem examination of six patients showed evidence of disseminated disease; the brain was the most common extrapulmonary site (four patients). To our knowledge, this is the largest currently reported series on invasive mold sinusitis; our report extends the information on invasive mold sinusitis and shows that aggressive therapeutic and surgical interventions are needed to prevent rapid progression of disease in immunocompromised patients.     

Chronic sinusitis: characterization of cellular influx and inflammatory mediators in sinus lavage fluid

Chronic sinusitis is a recurrent disorder commonly found in atopic individuals, yet few studies have explored the role of inflammatory mediators in sinusitis. Sinus lavage fluid from ten patients with chronic sinusitis obtained during endoscopic surgery was analyzed for total cell counts and then assayed for histamine, immunoreactive leukotriene C4/D4/E4 (LTC4/D4/E4), and prostaglandin D2 (PGD2). All ten patients had been unresponsive to medical treatment, including oral corticosteroids in most cases. High concentrations of histamine, LTC4/D4/E4 and PGD2 were found in sinus fluid and were comparable to levels seen in nasal secretions of allergic rhinitis patients following allergen challenge. In the sinus fluid, inflammatory cells were predominantly neutrophils with only low percentages of mast cells, basophils or eosinophils. On the basis of the histamine and PGD2 concentrations in sinus fluid, we conclude that mast cell/basophil activation does occur in chronic sinusitis and may contribute to the persistent inflammation present in sinusitis.     

Microendoscopic treatment of the hypopharyngeal diverticulum with the CO2 laser

BACKGROUND AND OBJECTIVE: The hypopharyngeal (Zenker's) diverticulum is a herniation of mucosa and submucosa on the posterior wall of the pharynx. The only treatment is surgical. STUDY DESIGN/MATERIAL AND METHODS: Between 1976 and 1993, 109 patients with a hypopharyngeal diverticulum were operated on at the Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, either transcutaneously combined with a cricopharyngeal myotomy (n = 76), or microendoscopically (n = 37) using the CO2 laser. Results and complications of both techniques were evaluated and compared. RESULTS: With both surgical procedures, > 90% of the patients were treated successfully. The rate of postoperative complications was generally low. In comparison to the microendoscopic procedure, serious complications were found to be more frequent in patients treated with the conventional transcutaneous diverticulectomy. CONCLUSION: The laser surgical tissue bridge dissection is a less invasive, quick, relatively safe, and effective procedure requiring only short hospitalisation. Therefore, the laser surgical tissue bridge dissection can be considered as the method of choice for the treatment of the hypopharyngeal diverticulum.     

Orbital rhinocerebral mucormycosis associated with diabetic ketoacidosis: report of survival of a 10-year-old boy

Cerebral mucormycosis is a rare fungal infection that occurs mostly in association with diabetic ketoacidosis. This central nervous system infection is characterized by a rapid decline in clinical status, and has been recognized as a uniformly fatal event if aggressive therapy is not instituted. We report a diabetic child who presented with blurred vision, chemosis, and pain in the left periorbital region noted for about 1 week during an episode of ketocidosis. Neurologic examinations revealed that there was a decreased range of motion in the upward and lateral gaze, along with incomplete pupillary dilatation and papilledema of the left eye. Imaging studies demonstrated left-side orbital cellulitis, paranasal sinusitis, and a large lobulated abscess in the left frontal lobe. Two surgical procedures, including functional endoscopic sinus surgery for sinus debridement and a subsequent open craniotomy for abscess resection were performed. Pathologic specimens obtained from the abscess wall revealed necrotic inflammation and wide, nonseptate hyphae with right angle branching, which are typical characteristics of the family Mucoraceae. Postoperatively, the patient was treated with 1.5 g of amphotericin B over a 7-week period, and aggressive diabetic control for 2 months. Through the combination of medical and surgical treatment the child made an uneventful recovery.     

Age differences in behaviors leading to completed suicide

Nonclostridial necrotizing soft-tissue infections are usually polymicrobial, with greater than 90 per cent involving beta-hemolytic streptococci or coagulase-positive staphylococci. The remaining 10 per cent are usually due to Gram-negative enteric pathogens. We describe the case of a 46-year-old woman with bilateral lower extremity fungal soft tissue infections. She underwent multiple surgical debridements of extensive gangrenous necrosis of the skin and subcutaneous fat associated with severe acute arteritis. Histopathological examination revealed Aspergillus niger as the sole initial pathogen. Despite aggressive surgical debridement, allografts, and intravenous amphotericin B, her condition clinically deteriorated and she ultimately died of overwhelming infection. Treatment for soft-tissue infections include surgical debridement and intravenous antibiotics. More specifically, Aspergillus can be treated with intravenous amphotericin B, 5-fluorocytosine, and rifampin. Despite these treatment modalities, necrotizing fascitis is associated with a 60 per cent mortality rate. Primary fungal pathogens should be included in the differential diagnosis of soft-tissue infections.     

Overview of diagnosis and management of allergic rhinitis

Allergic rhinitis remains an important problem that affects people of all ages. Although allergic rhinitis is considered a trivial disease by the public and medical community alike, the evidence of allergic rhinitis as a risk factor to the development of associated diseases such as asthma, sinusitis, otitis media with effusion, and nasal polyps is better appreciated. Pathophysiology and current therapy of allergic rhinitis is reviewed.     

Structure-based design of ligands for protein basic domains: application to the HIV-1 Tat protein

OBJECTIVES: to describe the clinical, microbiological and pathological features of invasive sinus aspergillosis affecting immunocompetent hosts, and to identify the risk factors for mortality. METHODS: we report three apparently immunocompetent patients with invasive sinus aspergillosis, and review all cases reported in the English literature since 1987, the year in which the triazole antifungal agents were introduced. RESULTS: twenty-nine patients (including three of our own) were identified. The presenting symptoms were non-specific and indistinguishable from viral, bacterial or allergic causes of sinusitis. The findings on computed tomography scan were also non-specific, and histopathology and culture of sinus tissue biopsy had low yield. These factors, along with the mistaken impression that Aspergillus can only affect immunocompromised hosts, frequently delayed the diagnosis. Fifty-nine percent of patients either failed therapy or died. The following factors were associated with a poor prognosis: delayed diagnosis, intracranial extension of infection, and histopathology demonstrating hyphal invasion of blood vessel or tissue. Complete surgical extirpation was the key element of successful therapy; antifungal agents played an adjunctive role. CONCLUSIONS: invasive sinus aspergillosis carries high morbidity and mortality, even in immunocompetent hosts. To improve outcome, the diagnosis must be recognized early, before the organism can invade the central nervous system or vascular structures. Aggressive surgical resection of the infected areas is of utmost importance in the management of this infection.     

Is there a role for induction androgen deprivation prior to radical prostatectomy?

The potential advantages of neoadjuvant androgen deprivation include decreased prostatic size, reduced vasculature, and reduced incidence of positive margins. The potential disadvantages are the side effects of hormonal medication, cost, tissue reaction, treatment "delay," and progression of androgen-independent clones. Many theories have been postulated to explain the observed reduction in the incidence of positive margins with neoadjuvant hormonal treatment. It is possible that the reduced prostate size and the frequently found periprostatic tissue reaction facilitate dissection, allowing better cancer clearance. It is possible, however, that the fibrosis may also increase the surgical difficulty, which critics argue may increase the risk of a positive margin. It is difficult to conceive of a research methodology that could resolve this issue. The occurrence of tumor cell death is likely a more significant explanation for the improved results. Whether tumor cells beyond the prostatic capsule are consistently affected to pathologically downstage the disease is unknown. The careful pathologic assessment in the randomized trials discussed previously suggests that pathologic downstaging is not as common as earlier reports have suggested. Difficulty in interpreting pathologic specimens after neoadjuvant treatment must be considered. At this point, neoadjuvant hormonal treatment prior to surgery would appear appropriate for those patients at high risk of having a positive surgical margin. Specifically, this includes clinical stage T2b, PSA elevation greater than 10 to 20 ng/mL, and a high Gleason score on the prostatic biopsy. Research to date suggests that neoadjuvant hormonal therapy prior to radical prostatectomy has a significant effect in reducing the incidence of positive surgical margins. The treatment is well tolerated with minimal side effects. Whether this will translate into improved disease-free survival remains to be determined. Fortunately, the randomized trials have been completed and follow-up data will be forthcoming.     

Inhibition of perioperative platelet aggregation using toradol (ketorolac)

Traditionally, aspirin is used as an inexpensive and usually well-tolerated agent to accomplish inhibition of platelet aggregation after microvascular surgery. Occasionally, however, aspirin is contraindicated. We have successfully used Toradol (ketorolac) after microvascular tissue transfer to inhibit platelet aggregation postoperatively, and documented this in our laboratory. We present two individuals on our surgical service requiring microvascular free tissue transfer with documented allergic reactions to aspirin. Platelet function was successfully suppressed while on the Toradol regimen, and this function returned to normal within 24 hours after stopping this therapy. We believe this agent may have some use for the microvascular surgeon for the population of patients in which aspirin is contraindicated or difficult to administer.