Diagnosis Of Invasive Fungal Sinusitis Research Articles

The preliminary application of mNGS in the diagnosis of invasive fungal sinusitis

Objective: By conducting a retrospective analysis of the clinical data of 14 patients diagnosed with invasive fungal rhinosinusitis (IFRS) confirmed by metagenomics next generation sequencing (mNGS) technology, we aim to explore the rapid diagnosis value of mNGS in IFRS. Methods: The clinical data of 14 IFRS patients admitted to TianJin First Central Hospital were retrospectively analyzed from February 2021 to October 2023. The study cohort comprised 8 males and 6 females, with ages ranging from 14 to 77 years. All patients were diagnosed as IFRS by performing mNGS sequencing technology of nasal sinus lesion biopsy specimens. Clinical data such as laboratory examination, imaging examination, histopathological examination results, treatment plan and prognosis were summarized and analyzed. Results: All 14 patients were diagnosed as IFRS, with mNGS detecting pathogens such as Rhizopus (7 cases), Aspergillus (5 cases), Trichoderma (1 case), and Scedosporium apiospermum (1 case). Follow-up evaluations were conducted for a period ranging from 2 months to 2 years post-treatment. At the end of follow-up, 11 out of 14 IFRS patients achieved a complete cure with no signs of recurrence, while the symptoms of the remaining 3 patients significantly improved with comprehensive treatment. Conclusion: mNGS emerges as a highly effective diagnostic tool for IFRS, providing valuable microbiological evidence for clinical diagnosis and demonstrating promising clinical utility.

P426 Interleukins—a non-invasive biomarker for invasive fungal sinusitis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesInvasive fungal infection is estimated to cause around 1.5 million deaths each year. But the true burden is estimated to be even more due to the lack of reliable diagnostic methods. Invasive fungal sinusitis (IFS) is the emerging infection leading to high morbidity and mortality (80%). Both clinical suspicion and reliable diagnostic tests available to diagnose an IFS are less. As a result, most patients are diagnosed only in the later stages. Nasal swabs for IFS are less useful and the most appropriate sample for the diagnosis will be the deep tissues involved, which are obtained after an invasive procedure. The gold standard test for diagnosis of IFS is the isolation of fungus in culture media but its sensitivity is ˂50%. Hence a non-invasive procedure to help in the diagnosis of invasive fungal sinusitis is needed. The role of Interleukins (IL) in fungal infections, especially IL-10 and IL-17 has been documented in various research in the past. Hence this research was carried out to study the role of IL-10 and IL-17 in invasive and non-invasive fungal sinusitis (NIFS).MethodsThe study was carried out in the Department of Microbiology, SRIHER, Chennai. A total of 60 samples collected from patients suspected to have fungal sinusitis and sent to the laboratory for fungal culture were considered for the study. All the samples which grew fungus were categorized as IFS and NIFS. ELISA was performed with the serum samples of patients for IL-10 and IL-17 based on manufacturer's instruction (Human IL-10 ELISA Kit, Thermofisher and Human IL-17 ELISA Kit, Thermofisher), and reading is taken in a spectrophotometer (Thermo Fisher Scientific).ResultsAmong the 60 serum samples tested, 30 were categorized as IFS and the rest as NIFS. A total of 90% (n = 27/30) of IFS patients expressed interleukins in serum samples whereas none of the NIFS expressed both the interleukins tested. Among IFS, IL-10 was seen in 63.3% (n = 19/30) patients, IL-17 in 46.7% (n = 14/30) patients and 20% (n = 6/30) patients expressing both IL-10 and IL-17. In IFS the mean value of IL-10 and IL-17 were 6.657 and 4.259 respectively. Among the 30 IFS, 13 were positive for COVID-19. IL-17 was expressed in 84.6% (n = 11/13) of COVID-19 positive IFS patients. But only 23.1% (n = 3/13) of COVID-19 positive IFS patients expressed IL-10. A total of 15.4% (n = 2/13) of the COVID-19 positive patients did not express any interleukins. Surprisingly the expression of IL-10 among COVID-19 negative IFS was 94.1% (n = 16/17). The specificity of both IL-10 and IL-17 was 100% in the case of IFS.ConclusionThus, interleukins look to be a promising biomarker for IFS. Further studies will help in establishing interleukins as a potential non-invasive biomarker for IFS. IL-17 can be used as a biomarker for COVID-19 patients suspected to have IFS. Also looking for more than one cytokine preferably a combination of IL-10 and IL-17 should be done in patients with NIFS, which will help in the early prediction of patients progressing into IFS and can be managed accordingly.

Revised workflow practices in the management of acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic.

To document changes in evaluation protocols for acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic, and to analyse concordance between clinical and histopathological diagnoses based on new practice guidelines. Protocols for the evaluation of patients with suspected acute invasive fungal sinusitis both prior and during the coronavirus disease 2019 period are described. A retrospective analysis of patients presenting with suspected acute invasive fungal sinusitis from 1 May to 30 June 2021 was conducted, with assessment of the concordance between clinical and final diagnoses. Among 171 patients with high clinical suspicion, 160 (93.6 per cent) had a final histopathological diagnosis of invasive fungal sinusitis, concordant with the clinical diagnosis, with sensitivity of 100 per cent, positive predictive value of 93.6 per cent and negative predictive value of 100 per cent. The study highlights a valuable screening tool with good accuracy, involving emphasis on 'red flag' signs in high-risk populations. This could be valuable in situations demanding the avoidance of aerosol-generating procedures and in resource-limited settings facilitating early referral to higher level care centres.

Curvularia Sinusitis in Leukemic Patients

Abstract Curvularia species are dematiaceous filamentous fungi that can cause a variety of infections in both immunocompetent and immunocompromised hosts. We present 2 cases of severely immunosuppressed patients with acute invasive fungal sinusitis due to Curvularia species. Both patients had a history of hematologic malignancy with refractory disease and prolonged neutropenia. They presented with facial and sinus pain, which prompted maxillofacial computed tomography that showed acute sinusitis. Subsequently, they underwent nasal endoscopy with a biopsy that revealed a definitive diagnosis of invasive fungal sinusitis. Dematiaceous fungi are responsible for most fungal sinusitis cases, with Curvularia being one of the most common species isolated. Generally, invasive fungal rhinosinusitis may follow a relatively innocuous and nonspecific course. In addition, fungal infections may complicate chronic allergic sinusitis. Computed tomography scan is the first imaging modality of choice, and magnetic resonance imaging has a role in prognostication in acute invasive fungal rhinosinusitis. Endoscopic sinus surgery with biopsy yields a definitive diagnosis and is therapeutic. Management typically includes a combination of surgery and antifungal agents. Severe neutropenia is a significant risk factor for infection and is associated with poor outcomes. Aggressive surgical debridement, combined with antifungal therapy, should be emphasized in leukemic patients despite their prolonged neutropenia and bleeding tendency.

Revisiting rhino-orbito-cerebral acute invasive fungal sinusitis in the era of COVID-19: pictorial review.

COVID-19 patients have been found to have an increased incidence of superadded fungal infections because of multiple factors such as impaired cell-mediated immunity, immunosuppressive therapy, and coexistent diabetes mellitus. Recently, there has been a significant rise in the COVID-19-associated mucormycosis and aspergillosis cases involving the sinonasal cavity and the lungs. Rhino-orbito-cerebral acute invasive fungal rhinosinusitis (AIFR) is a potentially life-threatening, invasive fungal infection. Early diagnosis followed by prompt medical management and surgical intervention is crucial for patient survival. The role of cross-sectional imaging (CT/MRI) is not only to suggest a diagnosis of invasive fungal sinusitis but also to delineate the complete extent of disease. Mapping the extent of orbital and intracranial disease has prognostic as well as management implications, as involvement of these sites marks a worse prognosis. A stepwise approach to evaluation of imaging of AIFR along with a pictorial depiction of the key imaging findings is presented.

The Trend of Changes in Paranasal CT Scan in Patients with Hematologic Malignancy Under Chemotherapy

ObjectivesThe aim of this study was to evaluate the clinical significance of early screening of computerized tomography scan of paranasal sinuses (PNS CT) in hematologic malignancies before chemotherapy and evaluation of changes after chemotherapy and during neutropenia.MethodsAll 40 new cases of hematologic malignancies with febrile neutropenia in a teaching referral hospital between 2018 and 2019 were enrolled in this study. All of these patients underwent paranasal sinus (PNS) CT scan before chemotherapy, along with other preliminary investigations. Symptoms and signs indicating the infectious process were meticulously followed and monitored before and during chemotherapy as well as the occurrence of febrile neutropenia. All patients were clinically and radiologically evaluated regarding the presumptive diagnosis of invasive fungal sinusitis during prolonged febrile neutropenia (more than 4 days). PNS CTs before and after chemotherapy of all patients were compared by two radiologists and were evaluated based on histopathologic findings of nasal and or paranasal biopsies.ResultsAround 50% of patients with PNS CT scan abnormality suspected inflammatory process including microbial and fungal sinusitis during prolonged febrile neutropenia (more than 4 days) were confirmed that have had similar involvement before starting chemotherapy and these abnormalities have been stable with no significant changes after chemotherapy. The histopathologic examination of sinuses also showed no evidence of invasive fungal infection by endoscopic biopsy. Therefore, the abnormal findings including mucosal thickening in PNS CT during prolonged febrile neutropenia were not consistent with the confirmed invasive fungal infection. The rate of mortality was 2.5% without association with invasive fungal sinusitis.ConclusionsA considerable number of patients with underlying hematologic malignancies have paranasal sinus involvement such as mucosal thickening that may be misdiagnosed as invasive fungal sinusitis during the hazardous phase of prolonging febrile neutropenia. Thus, performing PNS CT scan before initiation of chemotherapy even though in asymptomatic patients could be helpful to decrease the number of suspected and probable cases of fungal sinusitis based on abnormal findings in PNS CT scan followed by the number of cases undergoing sinus endoscopic surgery.

The Sensitivity and Specificity of Touch Preparation for Rapid Diagnosis of Invasive Fungal Sinusitis: A Pilot Study

Invasive fungal sinusitis is a morbid pathology that typically affects immunocompromised patients and may quickly progress to fulminant disease. The purpose of this study was to measure the sensitivity and specificity of touch preparation of nasal debridement specimens as a rapid diagnostic tool for invasive fungal sinusitis. A retrospective chart review was performed of 22 patients undergoing nasal debridement due to suspicion for invasive fungal sinusitis over a 10-year period. Thirteen patients had touch preparation of nasal specimens followed by routine histologic processing; 2 of these patients underwent two and 1 patient had three separate debridements, for a total of 17 touch preparations performed. The sensitivity and specificity of touch preparation were calculated by correlating the initial results with the presence of fungal invasion on final pathologic analysis. The sensitivity of touch preparation was 56% (95% confidence interval [CI]: 0.23 to 0.85), specificity was 100% (95% CI: 0.60 to 1.00), positive predictive value was 100% (95% CI: 0.46 to 1.00), and negative predictive value was 67% (95% CI: 0.35 to 0.89). This procedure may be a useful adjunct in situations requiring rapid diagnosis of invasive fungal sinusitis but should not be used as the sole criterion for determining the need for surgical intervention.

Clinical Manifestation and Diagnosis of Invasive Fungal Sinusitis in Patients with Hematological Malignancy

Background: Invasive fungal sinusitis (IFS) is a potentially deadly infection especially in patients with immunocompromising conditions. Objectives: The current study aimed to evaluate the clinical manifestations, outcomes and factors that may affect survival of patients with IFS. Methods: A cross sectional descriptive study was performed on hospitalized patients admitted to Taleghani hospital affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran, from October 2012 to October 2013. The clinical data of 24 patients with IFS were reviewed. All patients had hematologic malignancies, and received broad spectrum chemotherapy. Demographic data, clinical characteristics, presented symptoms and signs, underlying diseases and outcomes of the patients were studied. Results: The age range of patients was 15 - 60 years. The IFS was proven, probable and possible in 25%, 66.7% and 8.3% of the cases, respectively. Serum galactomannan antigen was positive in 41.6% of the cases; 15 out of 24 cases with IFS had received antifungal chemoprophylaxis before diagnosis, 54% fluconazole and 8.3% itraconazole. Aspergillus flavus (33%), Aspergillus fumigatus (20.8%), Aspergillus niger (16.7%) and Mucor spp. (16.7%) were responsible for incidence of IFS; 54% of IFS cases occurred in summer and 91.6% of occurred during hospital construction; a risk factor in 91.6% of the cases. Conclusions: Current study revealed that A. flavus was the most common isolated pathogen. Moreover, A. fumigatus was the second commonisolated pathogen in patients with IFS. Additionally, the hospital construction was an important environmental risk factor for acquisition of infection in patients with hematological malignancy. The most common season for IFS incidence was summer. Additionally, the common causes of death in patients with IFS were primary disease and also resistance to chemotherapy (37.5%).

Clinical manifestation and diagnosis of invasive fungal sinusitis in patients with hematological malignancy

Clinical manifestation and diagnosis of invasive fungal sinusitis in patients with hematological malignancy

Invasive fungal sinusitis of the sphenoid sinus.

ObjectiveThis study was conducted to present the clinical outcome of invasive fungal sinusitis of the sphenoid sinus and to analyze clinical factors influencing patient survival.MethodsA retrospective review of 12 cases of invasive fungal sphenoiditis was conducted.ResultsCases were divided into acute fulminant invasive fungal spheonoidits (n=4) and chronic invasive fungal sphenoiditis (n=8). The most common underlying disease was diabetes mellitus (n=9). The most common presenting symptoms and signs included visual disturbance (100%). Intracranial extension was observed in 8 patients. Endoscopic debridement and intravenous antifungals were given to all patients. Fatal aneurysmal rupture of the internal carotid artery occurred suddenly in two patients. The mortality rate was 100% for patients with acute fulminant invasive fungal sphenoiditis and 25% for patients with chronic invasive fungal sphenoiditis. In survival analysis, intracranial extension was evaluated as a statistically significant factor (P=0.027).ConclusionThe survival rate of chronic invasive fungal sphenoiditis was 75%. However, the prognosis of acute fulminant invasive fungal sphenoiditis was extremely poor despite the application of aggressive treatment, thus, a high index of suspicion should be required and new diagnostic markers need to be developed for early diagnosis of invasive fungal sinusitis of the sphenoid sinus.

A Strategy For Early Diagnosis Of Invasive Mold Infections In Children With Hematologic Malignancies

Infections with invasive molds are an important cause of morbidity and mortality with published mortality rates of 21-48% among pediatric cancer patients infected by these organisms. Diagnosing invasive fungal infections is difficult because signs and symptoms are non-specific, and delays in diagnosis limit successful debridement of infected tissues. Despite this, there are no uniform guidelines for the diagnosis of invasive fungal infections. The deaths of three teens, at our institution, with leukemia and widespread mold, lead to the creation of a screening protocol for invasive fungal infection in November 2006. Neutropenic patients with persistent fever at 5 days or recurrent fever after defervescing were evaluated with a non-contrast computed tomography (CT) of the chest, abdominal ultrasound, and nasal endoscopy, performed at the bedside, by an otorhinolaryngologist. Initially the screen included CT of the abdomen, but the proclivity of mold for solid organ involvement supported the use of ultrasound as a screening tool. Additional studies were obtained as clinically indicated.To determine the impact of this screening protocol on mortality associated with invasive mold, we performed a retrospective chart review of patients receiving intensive therapy for hematologic malignancies from 2004-2011 who were diagnosed as having proven, probable, or possible invasive mold (candida excluded) infections (N=52) using the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Of the 20 mold infections in the pre-protocol group, 14 were classified as proven, 6 as possible. Among the 32 infections in the post-protocol group, 22 were proven, 4 probable, and 6 possible. Organisms included Aspergillus, Bipolaris, Curvalaria, Exserohilum, Fusarium, Rhizopus, and Scedosporium. Clinically indicated evaluations among the 20 patients in the pre-protocol group included, 16 chest CTs, 20 abdominal CTs or ultrasounds, and 7 underwent evaluation of their sinuses by direct nasal endoscopy. The lungs were the most common site of infection, with involvement detected in 15/20 patients (75%). Five patients (25%) had sinus involvement; in 1 patient this was the only site of disease. All 5 were symptomatic with rhinorrhea, congestion, facial pain, or facial numbness. Of the 32 patients in the post-protocol group, 30 had chest CTs, 32 had abdominal imaging (5 CT, 27 ultrasound), and 31 had direct nasal endoscopy. One patient did not have an ENT evaluation or chest CT because fungal disease was only detected post-mortem, and in 1 patient, cardiovascular instability precluded CT imaging. The lungs were again the most common site affected, with fungal pneumonia seen in 23/32 patients (72%). Fourteen patients (44%) had sinus involvement; in 4 patients this was the only site of disease. Nine patients with sinus involvement had no nasal symptoms or findings on routine physical exam.Mortality specifically associated with invasive mold infection decreased significantly after initiation of the screening protocol. Before implementing the screening protocol, 8/20 patients (40%) who developed invasive mold infections died from the infection; afterward 4/32 (12.5%), (Fisher's exact p=0.04). Prior to routine evaluation of the sinuses by direct nasal endoscopy, 5/20 patients with mold infections had demonstrable disease in the sinuses and all had symptoms referable to sinus disease prior to evaluation. Once direct nasal endoscopy was implemented as part of the screening protocol, 14/32 patients with invasive mold infection were found to have sinus disease; 9 had no symptoms other than fever. Age, gender, race and length of hospital stay did not differ significantly before and after implementing the screening protocol. Before implementation, 8/20 patients (40%) died from all causes; afterward 6/32 (19%), (Fisher's exact p=0.12).A screening protocol for the evaluation of neutropenic patients with persistent or recurrent fever led to early detection of invasive fungal infections in patients with hematologic malignancies and a significant decrease in infection associated mortality. Non-invasive, direct nasal endoscopy, performed at the bedside, is an effective tool for diagnosis of invasive fungal sinusitis and often detects fungal sinusitis before specific symptoms develop. Disclosures:No relevant conflicts of interest to declare.

A Case of Relapse of Invasive Fungal Sinusitis after Endoscopic Sinus Surgery

Invasive fungal sinusitis is considered to have a poor prognosis. We report herein on a case of invasive fungal sinusitis successfully treated with endoscopic sinus surgery (ESS) but which relapsed 4 months after surgery. A 65-year-old man presenting with left cheek pain was found on computed tomography to have a heterogeneously enhanced mass in the anterior wall of the maxillary sinus and bone defects. We suspected a malignant tumor and performed diagnostic ESS. Fungus and necrotic mucosa were observed in the posterior wall of the maxillary sinus while necrotic mucosa and bone destruction were observed in the anterior wall. Endoscopic findings indicated a diagnosis of invasive fungal sinusitis and the patient underwent removal of the mucosa of the maxillary sinus with a modified endoscopic medial maxillectomy. Pathology confirmed invasive fungal sinusitis and Aspergillus fumigatus was detected on bacterial testing. The patient’s left cheek pain disappeared after surgery and micafungin was systemically administered for one month. However, follow-up CT at 4 months after surgery revealed recurrence in the orbit. Voriconazole was systemically administered and ESS was performed to confirm the diagnosis. Since we suspected that the fungus had invaded the lateral aspect of the maxillary bone, a total maxillectomy was performed, followed by systematic administration of voriconazole for 2 months. The patient was free from recurrence at the one-year follow up. This case suggests that, depending on the clinical course, aggressive surgery such as a total maxillectomy might be required for invasive fungal sinusitis.

S283 – Invasive Fugal Sinusitis: Pathognomic Presentation in MRI

Objectives The aim of this study was to evaluate the pathognomic findings of magnetic resonance image(MRI) and determine the benefit of MRI in early diagnosis of invasive fungal sinusitis(IFS). Methods We retrospectively reviewed 15 cases of biopsy-proven IFS. The preoperative MRI was reviewed to identify the pathognomic findings and correlation between radio-graphic and surgical findings were investigated. Results The MRI findings included decreased signal intensity on T1-weighted images with no enhancement on contrast-enhanced images and markedly decreased signal intensity on T2-weighted images in all cases. In our series, the interval between the onset of symptom and timing of MRI was from 48 hours to 2 weeks. Radiographic findings were correlated with histopathologic findings in 13 of 15 patients. Conclusions We could find typical MRI findings in IFS. MRI should be considered early in patients at high risk for IFS.