Invasive Fungal Rhinosinusitis Research Articles

Visual Outcome in Patients with Acute Invasive Fungal Rhinosinusitis

Visual Outcome in Patients with Acute Invasive Fungal Rhinosinusitis

A retrospective review of 46 cases of chronic invasive fungal rhinosinusitis

Objective To investigate the clinical characteristics of chronic invasive fungal rhinosinusitis. Methods Clinical features and outcomes of 46 proven cases of chronic invasive fungal rhinosinusitis admitted in Huashan Hospital, Fudan University from January 2009 to December 2016 were retrospectively reviewed. Results Of the 46 patients enrolled, left sphenoid sinus, ethmoid sinus and maxillary sinus were affected in 24, 23 and 20 cases, respectively, while right maxillary sinus, ethmoid sinus and sphenoid sinus were affected in 18, 16 and 15 cases, respectively. Left and right frontal sinus were affected in 9 and 6 cases, respectively. The central nervous system and orbit were the most commonly affected sites in external nasal involvements, noted in 22 cases respectively. Left sphenoid (17 cases) and ethmoid sinus (15 cases) involvements were most common in central nervous system affected patients. Left sphenoid (14 cases) and ethmoid sinus (13 cases) involvements were most common in orbit affected patients. Aspergillus species were the primary pathogens observed in 42 cases. Zygomycete, candida and dark filamentous fungus were observed in two, one and one case, respectively. Pathologically, 37 of the cases were chronic nongranulomatous type and the left 9 were chronic granulomatous type who were all immunocompetent hosts. The initial symptoms usually included headache, dizziness and nasal discomforts including nasal obstruction and purulent secretion. The chief complaints usually included headache, dizziness, and visual disturbances including blurred vision, vision loss or even blindness. Antifungal treatment combined with surgical interventions for removal or drainage focus lesions achieved significant effect, and 42 patients were cured. Conclusions Chronic invasive fungal rhinosinusitis should be taken into consideration in the presence of nasal discomforts or nonspecific symptoms such as headache and dizziness. The possibility of chronic invasive fungal rhinosinusitis should be cautious after the emergence of vision abnormalities. Key words: Chronic; Fungal rhinosinusitis; Clinical characteristics; Treatment

Multimodal management for acute invasive fungal rhinosinusitis

Acute invasive fungal rhinosinusitis (IFRS) is an aggressive sinonasal infection that is associated with a high risk of morbidity and mortality. Acute IFRS typically affects individuals with a deficient immune system and is characterized by a fulminant proliferation of tissue invasion by opportunistic fungal species. The early diagnosis and management of acute IFRS play important roles in improving the disease prognosis. The management of acute IFRS requires a multimodal approach that relies on both medical and surgical interventions. This article highlights general considerations for both the medical and surgical strategies for treatment of acute IFRS as a rhinologic emergency.

Invasive fungal sinusitis: treatment of the orbit.

To summarize diagnostic techniques for invasive fungal rhinosinusitis and provide a review of treatment options once disease has spread to the orbit. Improved imaging criteria, polymerase chain reaction and other serologic tests show promise in advancing our ability to accurately diagnose invasive fungal disease. Currently, there exists three treatment options for infected orbital tissue: exenteration, conservative debridement and transcutaneous retrobulbar injection of amphotericin B. Exenteration, the most frequently reported intervention, has not been proven to enhance survival. Conservative debridement and transcutaneous retrobulbar injection of amphotericin B are increasingly considered reasonable first-line options. Although investigative tools are improving, invasive fungal rhinosinusitis can still pose a diagnostic challenge. No one treatment option for the orbit has been proven superior to another. Therefore, it is justified to initiate therapy by prioritizing less morbid procedures. If deterioration is continually noted, more invasive interventions can then be employed. The treatment algorithm established at our institution is provided.

Identification of fungal causative agents of rhinosinusitis from Mashhad, Iran.

Background and Purpose:Rhinosinusitis is a common disorder, influencing approximately 20% of the population at some time of their lives. It was recognized and reported with expanding recurrence over the past two decades worldwide. Undoubtedly, correct diagnosis of fungi in patients with fungal rhinosinusitis affects the treatment planning and prognosis of the patients. Identification of the causative agents using the standard mycological procedures remains difficult and time-consuming.Materials and Methods:Based on clinical and radiological parameters, 106 patients suspected of fungal rhinosinusitis were investigated in this cross-sectional prospective study from April 2012 to March 2016 at an otorhinolaryngology department. In this study, internal transcribed spacer (ITS) and calmodulin (CaM) sequencing were respectively validated as reliable techniques for the identification of Mucorales and Aspergillus to species level (both agents of fungal rhinosinusitis).Results:Of these, 63 (59.4%) patients were suspected of allergic fungal rhinosinusitis (AFRS), 40 (37.7%) patients suspected of acute invasive fungal rhinosinusitis (AIFRS), and 3 (2.8%) patients suspected of mycetoma. In patients suspected of AFRS, AIFRS, and mycetoma only 7, 29, and 1 had positive fungal culture, respectively. After ITS and CaM sequencing, Aspergillus flavus was the most common species isolated from non-invasive forms, and A. flavus and Rhizopus oryzae were more frequently isolated from invasive forms.Conclusion: A spergillus flavus is the most common agent of fungal rhinosinusitis in Iran, unlike most other reports from throughout the world stating that A. fumigatus is the most frequent causative agent of this disease.

A seven-year retrospective analysis of the clinicopathological and mycological manifestations of fungal rhinosinusitis in a single-centre tropical climate hospital.

To evaluate the clinicopathological and mycological manifestations of fungal rhinosinusitis occurring in the Tengku Ampuan Rahimah Hospital, in Klang, Malaysia, which has a tropical climate. Records of patients treated from 2009 to 2016 were analysed retrospectively. Data from the records were indexed based on age, gender, clinical presentations, symptom duration, clinical signs and mycological growth. Of 80 samples, 27 (33.75 per cent) had fungal growth. Sixteen patients were classified as having non-invasive fungal rhinosinusitis and 11 as having invasive fungal rhinosinusitis. The commonest clinical presentation was nasal polyposis in non-invasive fungal rhinosinusitis patients (p < 0.05) and ocular symptoms in invasive fungal rhinosinusitis patients (p < 0.05). The commonest organism was aspergillus sp. (p < 0.05) in non-invasive fungal rhinosinusitis and mucorales in invasive fungal rhinosinusitis. There is an almost equal distribution of both invasive and non-invasive fungal rhinosinusitis, as seen in some Asian countries. Invasive fungal rhinosinusitis, while slightly uncommon when compared to non-invasive fungal rhinosinusitis, is potentially life threatening, and may require early and extensive surgical debridement. The clinical presentation of nasal polyposis was often associated with non-invasive fungal rhinosinusitis, whereas ocular symptoms were more likely to be associated with invasive fungal rhinosinusitis.

Endoscopic sinus surgery for the treatment of invasive fungal sinusitis

Objective:To explore the early diagnosis, the treatment and theprognosis of invasive fungal rhinosinusitis.Method:By summarizing the clinical data of 18 patients, CT and MRI images, pathological diagnosis and follow-up results to analysis the early diagnosis and the treatment.Result:All 5 patients with invasive fungal sinusitis were infected with mucor, 3 of whom died of intracranial complications. Among 13 patients with chronic invasive fungal rhinosinusitis, 9 were aspergillus, 3 were mucor, and 1 was negative. There were 9 cases of diabetes, 1 cases of ankylosing spondylitis, 3 cases of hypoproteinemia, 1 cases of organ transplantation, and 1 cases of leukemia. There were 3 cases of death who unenforced the operation, 15 patients received enlarged endoscopic surgery, postoperative antifungal therapy. Followed up 1-3 years, relapse in 3 cases, 1 case of death.Conclusion:The diagnosis of FRS needs to be combined with clinical manifestations, imaging features and pathological findings. The treatment requires surgery to completely remove diseased tissue (enlarged sinus open surgery) combined with antifungal use in sufficient quantities.

Pharmacokinetics of caspofungin acetate to guide optimal dosing in cats.

Cats are the most common mammal to develop invasive fungal rhinosinusitis caused by cryptic species in Aspergillus section Fumigati that are resistant to azoles but susceptible to caspofungin. In this study nonlinear mixed-effects pharmacokinetic modeling and simulation was used to investigate caspofungin pharmacokinetics and explore dosing regimens in cats using caspofungin minimum effective concentrations (MECs). Plasma concentrations in healthy cats were determined using HPLC-MS/MS after administration of a single and seven consecutive daily intravenous doses of 1 mg/kg caspofungin. In the final pharmacokinetic model an optimum maximum concentration (Cmax): MEC ratio of 10–20 was used to guide caspofungin efficacy. Simulations were performed for dosing regimens (doses 0.25–2 mg/kg and 6–72 h dosing intervals) with and without inclusion of a loading dose. Using a 1 mg/kg dose Cmax first dose was 14.8 μg/mL, Cmax at steady state was 19.8 μg/mL, Cmin was 5 μg/mL and Cmax: MEC was >20 in 42.6% of cats after multiple doses. An optimal Cmax: MEC ratio was achieved in caspofungin simulations using 0.75 mg/kg q 24 h or 1 mg/kg q 72h. However, at 1 mg/kg q 72h, Cmin was < MEC (<1 μg/mL) in over 95% of the population. Using a loading dose of 1 mg/kg and a daily dose of 0.75 mg/kg thereafter, the Cmax: MEC was optimal and Cmin was > 2.5 μg/mL for 98% of the population. Based on the modeling data this dosing regimen is likely to achieve target therapeutic concentrations, meet the proposed Cmax: MEC window and provide consistent exposure between doses.

Pediatric invasive fungal rhinosinusitis: An investigation of 17 patients

PurposeTo investigate outcomes of pediatric patients at a single institution with invasive fungal rhinosinusitis (IFRS) and to determine variables that impact overall survival. MethodsAll pediatric patients at a large tertiary children's hospital diagnosed with IFRS confirmed by surgical pathology from 2009 to 2015 were retrospectively reviewed. Demographics, underlying diseases, symptoms, antifungal therapy, absolute neutrophil count (ANC), surgical management,and outcomes were analyzed. ResultsSeventeen patients were identified with IFRS with an average age of 8.7 years and 53% male. Hematologic malignancy was the most common (n = 13) underlying disease. The most common presenting symptoms were fever (82%) and congestion (41%). 15 patients had severe neutropenia (Absolute Neutrophil Count (ANC) < 500) within 2 weeks prior to diagnosis. The average ANC at time of diagnosis was 1420 cells/uL. 16 patients were treated with serial nasal endoscopy and debridement, while 1 patient was treated with an open approach. 16 received combination antifungals while 1 was treated with amphotericin monotherapy. The most common genus cultured was Fusarium (n = 6). The average number of surgical interventions was 3.4, with the average interval between interventions 6.2 days. 13 of 17 (76%) were cleared of IFRS. Overall survival at 6 months was 41%. ConclusionPediatric IFRS is a life-threatening disease that requires a coordinated surgical and medical approach. Despite a relatively high local control rate, overall mortality remains disappointingly high, reflecting the disease's underlying pathogenesis - lack of host defense and risk of disseminated fungal infection. Further investigation is necessary to reveal optimal management with regards to antifungal therapy, surgery, and utility of labs.

One-health pathogens in the Aspergillus viridinutans complex.

Cryptic species in Aspergillus section Fumigati are increasingly recognised as pathogens in humans and animals. The A.viridinutans complex (AVC) has recently expanded to comprise 10 species, of which six are known to be pathogenic, including A.udagawae, A. felis, A. pseudofelis, A. parafelis, A. pseudoviridinutans, and A.wyomingensis. They cause locally invasive and disseminated invasive disease syndromes, including chronic pulmonary aspergillosis and invasive aspergillosis in humans, invasive fungal rhinosinusitis in cats, and disseminated invasive aspergillosis in dogs. In contrast to A.fumigatus, AVC species are characterized by higher minimum inhibitory concentrations (MICs) of antifungal drugs and the infections they cause are typically more chronic and more refractory to therapy. This review, of relevance for one-health practitioners, explores the history of the AVC as well as current phylogenetic relationships, secondary metabolite production, environmental distribution, clinical syndromes, and antifungal susceptibility patterns.

Complete surgical resection and short-term survival in acute invasive fungal rhinosinusitis.

Acute invasive fungal rhinosinusitis (AIFR) is a fulminant fungal infection seen in patients who are immunocompromised. Due to its rarity, there is little evidence regarding the appropriate antifungal treatment regimen, especially the degree of surgical intervention. To assess factors that impact short-term survival in AIFR as defined by survival to hospital discharge and to develop a staging system to predict survival and complete surgical resection. Fifty-four patients with histopathologically diagnosed AIFR who met inclusion criteria were identified between 1984 and 2014. Patient characteristics, disease extent, treatment modality, and short-term survival data were collected. Univariate analysis was performed to assess for factors associated with survival and increased likelihood of surgical resection. Of 52 patients with adequate documentation, 36 (69.2%) survived their hospital stay. Complete surgical resection was the only factor associated with improved survival (survival, 95.5%; p < 0.01). A surgical staging system was proposed to guide probability of complete resection and overall prognosis, with stage I disease limited to the nasal cavity, stage II involving the paranasal sinuses, stage III involving the orbit, and stage IV with skull base or intracranial extension. The χ2 analyses showed a decreased likelihood of complete surgical resection with stage III or IV disease compared with stage I (resection, 90.9%) (stage III resection, 37.5% [p = 0.01]; stage IV resection, 16.7% [p = 0.002]). There was a decreased likelihood of survival associated with increasing disease stage compared with stage I (survival, 100%) (stage II survival, 60% [p = 0.009]; stage III survival, 62.5% [p = 0.02]; stage IV survival, 54.6%, [p = 0.006]). Although further studies are needed to define specific treatment protocols, analysis of these data indicated that endoscopic sinus surgery with the goal of complete surgical resection may provide the best survival outcomes in select patients when complete surgical resection can be performed. Our staging system represents the first attempt to predict surgical success and prognosis in patients with AIFR.

Utility of intraoperative frozen sections in surgical decision making for acute invasive fungal rhinosinusitis.

Acute invasive fungal rhinosinusitis (AIFRS) represents a fulminant, potentially fatal, disease process in immunocompromised patients. The diagnosis often rests on high index of clinical suspicion, with relative paucity of data on the diagnostic and therapeutic implications of intraoperative frozen sections. Retrospective review was performed for 18 cases undergoing endoscopic sinus surgery for AIFRS. Reliability of intraoperative frozen section diagnosis was evaluated for all patients using final pathology as the gold standard. A total of 66 frozen sections were performed. Diagnostic accuracy of frozen sections illustrated sensitivity of 72.7% (95% confidence interval [CI], 0.57 to 0.85), specificity of 100% (95% CI, 0.85 to 1.00), positive predictive value (PPV) of 100% (95% CI, 0.89 to 1.00), and negative predictive value (NPV) of 64.7% (95% CI, 0.46 to 0.80). There was no statistically significant difference in sensitivity of frozen sections in cases of Mucor and Aspergillus at 68.8%% and 76.2%, respectively (p = 0.61). This study represents the largest series assessing the diagnostic accuracy of frozen section analysis in AIFRS. Frozen section analysis is an effective tool for guiding intraoperative decision making in patients with AIFRS with a high PPV. A Low NPV underscores the importance of clinical suspicion and intraoperative decision making based on endoscopic findings when negative frozen section results are encountered. Further, frozen section analysis appears to be equally effective in detecting either Mucor or Aspergillus.

Acute Invasive Fungal Rhino-sinusitis: Clinical, Microbiological and Pathological Diagnosis

Acute Invasive Fungal Rhino-sinusitis: Clinical, Microbiological and Pathological Diagnosis

Fungal Rhinosinusitis: Microbiological and Histopathological Perspective.

On the basis of histopathology Fungal Rhinosinusitis (FRS) is categorized into non-invasive (allergic fungal rhinosinusitis, fungal ball) and invasive (acute invasive, chronic invasive and granulomatous invasive fungal sinusitis). This differentiation helps to decide the treatment. Role of latest molecular methods such as PCR and conventional methods such as KOH microscopy and culture also needs to be evaluated. Therefore, in this study we planned to categorise fungal rhinosinusitis on the basis of histopathology and compare it with other methods such as PCR, culture and KOH microscopy. To analyse fungal rhinosinusitis cases by both histopathologically and microbiologically. A total of 76 clinically suspected fungal rhinosinusitis cases were included in the study. The tissue of suspected cases were processed and examined by KOH microscopy, histopathologically, culture and PCR. Histopathological examination was done by PAS, GMS and H&E stain. FRS was diagnosed in 37 (48.68%) cases out of 76 clinically suspected cases of FRS. In which 17 (22.3%) cases were positive by direct microscopy, 21 (27.6%) by culture, 27 (35.5%) by PCR and 14 (18.42%) by histopathology. Approximately 14 cases of FRS were classified according to histopathology; 10 (71.3%) as non-invasive FRS. Out of these 10, 9 (64.2%) were classified as AFRS and 1 (7.14%) as fungal ball. Only 4 cases (28.5%) were diagnosed with invasive FRS. Out of these 4 cases, 2 (14.2%) were of chronic invasive fungal rhinosinusitis, 1 (7.14%) was of granulomatous invasive fungal rhinosinusitis and 1 (7.14%) was of acute fulminant invasive fungal rhinosinusitis. Allergic Fungal Rhinosinusitis (AFRS) is the most common type of FRS. Aspergillus flavus was found to be the most common fungi causing FRS. Diagnosis should not be based on the single method. It should be done by both histopathological and microbiological methods, especially for those cases which are difficult to diagnose.

浸潤型副鼻腔真菌症の臨床的特徴と予後

浸潤型副鼻腔真菌症の臨床的特徴と予後

Expression of maspin in invasive fungal rhinosinusitis.

This study aimed to test the expression of maspin in invasive fungal rhinosinusitis and explore its value in diagnosing invasive fungal rhinosinusitis. Forty-two fungal rhinosinusitis cases (12 invasive and 30 non-invasive) were selected as the experimental group, and 30 chronic rhinosinusitis cases comprised the control group. Maspin expression was assessed in nasal mucous membrane specimens by immunohistochemical staining. Compared with the control group, maspin expression was down-regulated in the fungal rhinosinusitis group (p < 0.05). Furthermore, the staining score for maspin was lowest in the invasive fungal rhinosinusitis group, as compared with both the non-invasive fungal rhinosinusitis group and the control group (p < 0.05). A maspin staining score of 5.70 was the critical value for diagnosis of invasive fungal rhinosinusitis, with sensitivity and specificity of 91.7 per cent and 88.3 per cent, respectively. The results of this study suggest that the maspin staining score may be a biomarker for effective and rapid diagnosis of invasive fungal rhinosinusitis.

Clinical implications of serum galactomannan measurement in patients with acute invasive fungal rhinosinusitis.

Acute invasive fungal rhinosinusitis (AIFR) is an aggressive opportunistic infection with a high mortality rate. Recently, non-invasive techniques have been introduced for diagnosis of invasive fungal disease. The purpose of this study is to evaluate the diagnostic significance of serum galactomannan measurement in patients with AIFR. We conducted a retrospective case-control study of 28 patients with AIFR and 36 fungus ball (FB) patients. We evaluated clinical, laboratory, and pathologic findings along with disease course. In 28 patients with AIFR, there were 21 cases of invasive aspergillosis (IA) and 7 cases of invasive mucormycosis (IM). The control group was comprised of 36 patients with FB. The three-group analysis showed a statistically significant difference among the groups. At the cut-off value of 0.48, the sensitivity and specificity were 71.4% and 93.0%, respectively. Comparison of mean serum galactomannan levels in 5 non-survivors and 9 survivors at initial measurement showed no significant difference, but that became significantly different 1 week later. Statistical analysis showed that the levels of serum galactomannan decreased significantly according to the measurement-point in within survivor-group analysis. The difference in between survivor-groups analysis was also significant. Serum galactomannan measurement seems useful for early diagnosis and discrimination of fungal species in patients with AIFR. In addition, clinical outcomes may be related to the levels and patterns of serum galactomannan, especially in IA. The appropriate measurement of galactomannan might be helpful in treating the patients at high risk for AIFR.

Clinical implications of serum galactomannan measurement in patients with acute invasive fungal rhinosinusitis

Acute invasive fungal rhinosinusitis (AIFR) is an aggressive opportunistic infection with a high mortality rate. Recently, non-invasive techniques have been introduced for diagnosis of invasive fungal disease. The purpose of this study is to evaluate the diagnostic significance of serum galactomannan measurement in patients with AIFR. We conducted a retrospective case-control study of 28 patients with AIFR and 36 fungus ball (FB) patients. We evaluated clinical, laboratory, and pathologic findings along with disease course. In 28 patients with AIFR, there were 21 cases of invasive aspergillosis (IA) and 7 cases of invasive mucormycosis (IM). The control group was comprised of 36 patients with FB. The three-group analysis showed a statistically significant difference among the groups. At the cut-off value of 0.48, the sensitivity and specificity were 71.4% and 93.0%, respectively. Comparison of mean serum galactomannan levels in 5 non-survivors and 9 survivors at initial measurement showed no significant difference, but that became significantly different 1 week later. Statistical analysis showed that the levels of serum galactomannan decreased significantly according to the measurement-point in within survivor-group analysis. The difference in between survivor-groups analysis was also significant. Serum galactomannan measurement seems useful for early diagnosis and discrimination of fungal species in patients with AIFR. In addition, clinical outcomes may be related to the levels and patterns of serum galactomannan, especially in IA. The appropriate measurement of galactomannan might be helpful in treating the patients at high risk for AIFR.

Acute Invasive Fungal Rhinosinusitis: Presentation of 19 Cases, Review of the Literature, and a New Classification System.

The aim of this study was to determine the correlation between acute invasive fungal rhinosinusitis (AIFRS) and underlying diseases, micro-organisms, presenting symptoms, extent of disease, radiologic findings, and outcomes and propose a new classification system. The data of 19 AIFRS cases were analyzed retrospectively. Magnetic resonance imaging and computed tomography were performed in all patients preoperatively. All patients underwent at least 1 surgical debridement. Hematologic diseases were the most common (52%) underlying diseases. Patients with type 2 diabetes and those with multiple etiologies causing immunosuppression had the lowest survival. Aspergillus and Mucoraceae species were isolated in 9 patients but were not associated with poor prognosis. Headache and nasal discharge or crusting were the most common presenting symptoms. Premaxillary involvement was significantly correlated with poor prognosis (P= .001). Unilateral involvement was correlated with poor prognosis, although this finding was not significant (P= .111). The overall mortality rate was 61.2%. Patients with neutropenia that was corrected had 80% survival (P= .014). Cessation of corticosteroids and regulating blood glucose levels in patients with immunosuppression from corticosteroid use resulted in 75% survival. There is no single curative treatment for AIFRS. For a favorable prognosis, underlying conditions must be treated in addition to surgical debridement and antifungals.

The effect of nasal endoscopic surgery in the treatment of acuteinvasive fungal rhino-sinusitis in 5 cases

The effect of nasal endoscopic surgery in the treatment of acuteinvasive fungal rhino-sinusitis in 5 cases