Chronic Invasive Fungal Sinusitis Research Articles

Monocular Vision Loss and Headache in a 60-Year-Old Liver Transplant Patient

Monocular Vision Loss and Headache in a 60-Year-Old Liver Transplant Patient

Comparison of Efficacy of Amphotericin B and Itraconazole in Chronic Invasive Fungal Sinusitis

Management of invasive fungal sinusitis includes both surgery and antifungal chemotherapy. To compare the efficacy of amphotericin B and itraconazole used alone in the management of chronic invasive fungal sinusitis. A prospective randomized unblinded study was conducted in the Department of Otolaryngology, Postgraduate Institute of Medical Education and Research, Chandigarh, India during December 2006 to June 2008. 26 immunocompetent patients were randomly divided into two groups-group A-received amphotericin B and group I-received itraconazole in conventional doses. The response to treatment was judged on the basis of symptomatic and radiologic resolution. Seven patients had complete cure (5/16-gr I; 2/10-gr A); Eleven patients had persistent disease (7/16-group-I; 4/10 in group A); four relapses were noted (3/16 in group I and 1/10 in group A); 3 deaths occurred; one patient was lost to follow up. Relative risk analysis did not show any statistically significant difference between the two drugs as regards their efficacy. Itraconazole and amphotericin B both have been found to be equally efficacious in the management of invasive fungal sinusitis. Itraconazole however, has fewer side effects compared to amphotericin B.

Should Voriconazole be the Primary Therapy for Chronic Invasive Sinus Aspergillosis (CISA)?

ABSTRACT Introduction Invasive sinus aspergillosis infection has been reported with increasing frequency in the last decade, especially, in immunocompromised patients with chronic invasive sinus aspergillosis (CISA). The gold standard for treatment has been wide surgical debridement, intravenous administration of antifungal agents, such as amphotericin B, but the prognosis remains poor. Newer antifungal agents are being tried but no standard treatment option with new antifungal agents has yet been established for chronic invasive fungal sinusitis. Therefore, we undertook this study to evaluate the efficacy of voriconazole in patients of chronic invasive sinus aspergillosis. Materials and methods This study is a prospective randomized unblinded study with primary aim of evaluating the feasibility and effectivity of voriconazole in patients of chronic invasive sinus aspergillosis with intraorbital or intracranial extension, and secondarily to compare voriconazole with amphotericin B therapy in patients with chronic invasive sinus aspergillosis. Observations and results Thirty-three patients who fulfilled the eligibility criteria were included in this study. There were 18 patients enrolled in group I who received amphotericin therapy and 15 patients in group II who received voriconazole therapy. Out of 33 patients, 9 patients had complete response, 10 had partial response, in eight patients disease became stable and there were seven failures. Overall 50% patients had a successful outcome in group I, whereas 60% had a successful outcome in group II receiving oral voriconazole. On comparing only in extradural group, 5/10 had a successful outcome in group I receiving amphotericin B, whereas 8/12 (66.7%) had a successful outcome in group 2 receiving voriconazole. There was significant difference between adverse reactions of the two drugs, with amphotericin B having a significant renal and cardiotoxicity as compared to voriconazole; though patients on voriconazole developed skin rashes which were transient and disappeared on completion of the therapy. Conclusion The present series demonstrates that oral voriconazole can be the primary line of therapy in chronic invasive sinus aspergillosis in carefully monitored immunocompetent cases. Multicentric, randomized studies are required to define disease definition, duration and successful outcome.

Should Voriconazole be the Primary Therapy for Chronic Invasive Sinus Aspergillosis (CISA)?

ABSTRACT Introduction Invasive sinus aspergillosis infection has been reported with increasing frequency in the last decade, especially, in immunocompromised patients with chronic invasive sinus aspergillosis (CISA). The gold standard for treatment has been wide surgical debridement, intravenous administration of antifungal agents, such as amphotericin B, but the prognosis remains poor. Newer antifungal agents are being tried but no standard treatment option with new antifungal agents has yet been established for chronic invasive fungal sinusitis. Therefore, we undertook this study to evaluate the efficacy of voriconazole in patients of chronic invasive sinus aspergillosis. Materials and methods This study is a prospective randomized unblinded study with primary aim of evaluating the feasibility and effectivity of voriconazole in patients of chronic invasive sinus aspergillosis with intraorbital or intracranial extension, and secondarily to compare voriconazole with amphotericin B therapy in patients with chronic invasive sinus aspergillosis. Observations and results Thirty-three patients who fulfilled the eligibility criteria were included in this study. There were 18 patients enrolled in group I who received amphotericin therapy and 15 patients in group II who received voriconazole therapy. Out of 33 patients, 9 patients had complete response, 10 had partial response, in eight patients disease became stable and there were seven failures. Overall 50% patients had a successful outcome in group I, whereas 60% had a successful outcome in group II receiving oral voriconazole. On comparing only in extradural group, 5/10 had a successful outcome in group I receiving amphotericin B, whereas 8/12 (66.7%) had a successful outcome in group 2 receiving voriconazole. There was significant difference between adverse reactions of the two drugs, with amphotericin B having a significant renal and cardiotoxicity as compared to voriconazole; though patients on voriconazole developed skin rashes which were transient and disappeared on completion of the therapy. Conclusion The present series demonstrates that oral voriconazole can be the primary line of therapy in chronic invasive sinus aspergillosis in carefully monitored immunocompetent cases. Multicentric, randomized studies are required to define disease definition, duration and successful outcome.

Treatment of chronic invasive fungal sinusitis with voriconazole in an HIV patient

Purpose of the study: Chronic invasive fungal sinusitis is a rare condition, and the conventional treatment surgical debridement and systemic antifungal therapy such as amphotericin B. Recently, voriconazole has demonstrated superior efficacy in the treatment of invasive aspergillosis, compared to amphotericin B. However, its use in invasive fungal sinusitis in an HIV patient has not been reported. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P190 Cite this article as: Ho et al.: Treatment of chronic invasive fungal sinusitis with voriconazole in an HIV patient. Journal of the International AIDS Society 2010 13(Suppl 4):P190. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112972/

Imaging of granulomatous and chronic invasive fungal sinusitis: Comparison with allergic fungal sinusitis

Objective To study the radiological features of chronic/granulomatous invasive fungal sinusitis (IFS) and identify differentiating characteristics, if any, from allergic fungal sinusitis (AFS). Study design Prospective radiological study. Setting Tertiary hospital in northern India. Subjects and methods Subjects were nonacute fungal sinusitis patients with orbital involvement presenting between January 1999 and December 2003. Seventeen IFS and 12 AFS patients with mean age 27 years (range 7-59 years) underwent computed tomographic scan (CT) and magnetic resonance imaging (MRI) of paranasal sinuses with contrast. These were operated within one month of doing the scans and had histologically confirmed fungal sinusitis. Outcome measures were characteristics of opacity produced by the diseased tissue on CT and MRI, side and number of sinuses involved, expansion of sinuses, areas of bone erosion, and extra-sinus extension. Results IFS showed homogenous opacity (isodense or hyperdense to muscle tissue) on CT and isointense and hypointense signal on T1- and T2-weighted MR images respectively. IFS showed involvement of one or two sinuses only, homogenous contrast enhancement, lack of expansion of sinuses, and bone erosion localized to the area of extra-sinus extension, and the extra-sinus component of the disease was more than the intra-sinus component. AFS showed heterogenous opacities with hyperattenuation areas on CT, isointense/hypointense to signal void on T1- and T2-weighted MR images. Expansion of sinuses, extensive bone erosion, lack of contrast enhancement, multiple sinus involvement, and major bulk of disease being intra-sinus rather than extra-sinus were other characteristics of AFS. Conclusion Radiological features of IFS are described that are different from AFS.

뇌기저부 골수염으로 진행된 만성 침습성 진균성 부비동염 1예

Chronic invasive fungal sinusitis is a life-threatening disease, but encompasses a more unhurried progression of illness, in contrast with acute invasive fungal sinusitis. This case is a fungal sinusitis with skull base osteomyelitis and meningitis progressed from fungal ball past years. Fungal ball is easily treated by endoscopic sinus surgery and rarely progress to invasive type. If invasive fungal sinusitis is not timely diagnosed by histopathologic evidence of fungal hyphae, it makes clinicians embarrassing and face poor clinical course of patient like this case. It should be noted that chronic invasive fungal sinusitis may be developed from even fungal ball in a diabetes mellitus patient and may extend to skull base osteomyelitis and meningitis. (J Clinical Otolaryngol 2010;21:89-94)

A Case of Chronic Invasive Fungal Sinusitis Invading Pterygopalatine Fossa

Chronic invasive fungal sinusitis is a slowly destructive process that most commonly affects the ethmoid and sphenoid sinus, but may involve any paranasal sinus. The disease typically has a time course over 12 weeks. Pathologically, it is characterized as a dense accumulation of hy-phae, occasional vascular invasion and sparse inflammatory reaction with involvement of local structures. Aspergillus fumigates is the most common pathogen. In this report, we present a patient with chronic invasive fungal sinusitis invading pterygopalatine fossa, which was pre-sented as only mild thickening of posterior wall of maxillary sinus at initial CT scan

An atypical case of chronic invasive fungal sinusitis and its management

An atypical case of chronic invasive fungal sinusitis and its management

New treatment for invasive fungal sinusitis: Three cases of chronic invasive fungal sinusitis treated with surgery and voriconazole

Invasive fungal sinusitis is a relatively rare disease and can be divided into acute fulminant, chronic, and granulomatous invasive fungal sinusitis. The conventional treatment is radical surgery combined with systemic amphotericin B administration, but the poor prognosis and unestablished treatment options require a better therapeutic strategy. We report three cases of chronic invasive fungal sinusitis successfully treated with a combination of surgery and voriconazole, a new antifungal agent, with good responses in all patients. Voriconazole administration could form the basis for a new standard treatment for invasive fungal sinusitis.

Syndromes of invasive fungal sinusitis

Invasive fungal sinusitis should be suspected in immunocompromised or diabetic patients who present with acute sinusitis, inflammation of nasal septal mucosa, unexplained fever or cough, or the orbital apex syndrome. Histopathological studies are required to differentiate among these syndromes. Acute (fulminant) invasive fungal sinusitis has been called mucormycosis, zygomycosis and fulminant invasive sinusitis. Fever, cough, crusting of nasal mucosa, epistaxis, and headache are the most common presenting symptoms. Histopathological studies show hyphal invasion of blood vessels, vasculitis with thrombosis, and tissue infarction. Reports of granulomatous invasive fungal sinusitis come primarily from Sudan, but also from India, Pakistan, and the United States. Patients usually present with proptosis, appear to be immunocompetent and are infected almost exclusively with A. flavus. Chronic invasive fungal sinusitis can be distinguished from the two other forms of invasive fungal sinusitis by its chronic course, dense accumulation of hyphae resembling a mycetoma, and association with the orbital apex syndrome, diabetes mellitus, and corticosteroid treatment. Biopsy and orbital exploration show vascular invasion by fungal elements and only a sparse chronic inflammatory infiltrate.

Significance of MUC5B antibody in differential diagnosis between Aspergillus species and Mucorales of fungal sinusitis

To differentiate between Aspergillus species and Mucorales of fungal sinusitis by immunohistochemistry. Formalin-fixed paraffin-embedded tissue blocks of 66 cases of fungal sinusitis were retrieved from the archival files of Department of Pathology of Beijing Tongren Hospital during the period from 2001 to 2006. The samples included 29 cases of fungal balls, 12 cases of allergic fungal sinusitis, 24 cases of chronic invasive fungal sinusitis and 1 case of acute invasive fungal sinusitis. The types of fungi were 44 Aspergillus species (31 cases of A. fumigatus, 7 cases of A. flavus and 6 cases of A. terreus) and 22 Mucorales (14 cases of Mucor species and 8 cases of Rhizopus species). Immunohistochemistry was performed with MUC2, MUC5AC and MUC5B antibodies. The results were compared with histochemical study for periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stains. Immunohistochemical study for MUC5B showed that the positive rate of Aspergillus species was 90.9%, in contrast to 4.5% in Mucorales (P < 0.001). The expression of MUC2 and MUC5AC was completely negative, whereas PAS and GMS stains were positive in all cases. MUC5B antibody appears to be a useful immunohistochemical marker for identifying fungal types in tissue sections, especially in distinguishing between Aspergillus species and Mucorales in fungal sinusitis.

Imaging Features of Invasive and Noninvasive Fungal Sinusitis: A Review

Fungal sinusitis was once considered a rare disorder but is now reported with increasing frequency throughout the world. The classification of fungal sinusitis has evolved in the past two decades, and this entity is now thought to comprise five subtypes. Acute invasive fungal sinusitis, chronic invasive fungal sinusitis, and chronic granulomatous invasive fungal sinusitis make up the invasive group, whereas noninvasive fungal sinusitis is composed of allergic fungal sinusitis and fungus ball (fungal mycetoma). These five subtypes are distinct entities with different clinical and radiologic features. The treatment strategies for the subtypes are also different, as are their prognoses. An understanding of the different types of fungal sinusitis and knowledge of their particular radiologic features allow the radiologist to play a crucial role in alerting the clinician to use appropriate diagnostic techniques for confirmation. Prompt diagnosis and initiation of appropriate therapy are essential to avoid a protracted or fatal outcome.

CT and MRI diagnosis of chronic invasive fungal sinusitis

目的 探讨慢性侵袭性真菌性鼻窦炎的CT和MRI表现及诊断价值.方法回顾性分析经手术、组织病理学证实的10例慢性侵袭性真菌性鼻窦炎的影像学资料.结果慢性侵袭性真菌性鼻窦炎发生于蝶窦5例,上颌窦3例,筛窦2例.CT表现:受累窦腔内充以软组织影,其中1例伴斑点状钙化;窦壁骨质破坏,同时伴周围骨质增生肥厚.MRI表现:T1WI为低信号(与脑实质比较,以下相同)2例,等信号7例;T2WI信号不均匀, 7例以低信号为主,2例以高信号为主;增强后病变明显强化.侵犯邻近结构:眼眶9例,其中6例累及眶尖区,可见不规则软组织肿块影,与邻近眼外肌分界不清楚,7例包绕视神经;6例侵犯海绵窦,可见形态不一的软组织影;脑膜增厚、强化5例,3例侵犯脑实质,表现为水肿1例,肉芽肿2例;4例侵犯翼腭窝及颞下窝;3例鼻咽部软组织增厚;2例上颌神经和1例下颌神经明显增粗、强化;3例面颊部软组织肿胀;1例硬腭骨质破坏.结论窦壁骨质破坏伴硬化、MR T2WI低信号、易侵犯眶尖及海绵窦为本病特征性影像学表现.结合CT和MRI 2种检查方法能够对本病的诊断、鉴别和治疗提供更可靠的信息。

Clinicopathologic and immunohistochemical characteristics of fungal sinusitis.

Fungal sinusitis (FS) is a common disease in Taiwan. Histologically, there are 4 types of FS, i.e., acute invasive, chronic invasive, fungal ball and allergic FS. Among the various fungal pathogens, Aspergillus is the most important. This study analyzed results of antibody staining against Aspergillus species on tissue sections of FS to identify fungal elements and evaluated the role of Aspergillus in different types of FS. We retrospectively reviewed 140 cases with a pathologic diagnosis of FS in our hospital from 1995 to 2003. The clinical information, hematoxylin and eosin staining, and Gomori methenamine silver staining results for each patient were analyzed. Patients were reclassified into 4 categories of FS according to histologic presentation. The causative fungi were divided into Aspergillus and non-Aspergillus groups according to the results of immunoreactivity against anti-Aspergillus antibody. Fungal ball was diagnosed in 126 patients (90%), 66.6% of whom were females. Only 3 patients died of underlying disease not related to the fungal infection. Immunohistochemical staining demonstrated Aspergillus infection in 108 out of 119 patients (90.7%). Thirteen patients were categorized as having acute invasive FS due to the presence of vascular and stromal invasion. All but 1 patient had underlying diseases associated with immunocompromised status and 11 out of the 13 patients died of sepsis. Immunohistochemical study revealed 5 of these patients were infected with Aspergillus species, and the other 8 were infected with non-Aspergillus fungi. Allergic FS was diagnosed in 1 patient based on the presence of allergic mucin containing numerous eosinophils and few fungal hyphae. The fungal elements were negative for anti-Aspergillus antibody. None of the patients had chronic invasive FS. Fungal ball and acute invasive FS were the 2 most common types of FS in this study from Taiwan. However, both allergic FS and chronic invasive FS are rare. Immunohistochemical staining was useful in identifying specific species of fungus in tissue sections. Aspergillus accounted for 90.7% of fungal ball infections and 38.4% of acute invasive FS infections. It is important to differentiate among the categories of FS because the clinical course, etiology, treatment and prognosis are quite different.

Correlation between Preoperative Clinical Diagnosis and Histopathological Findings in Patients with Rhinosinusitis

The diagnosis of chronic rhinosinusitis (CRS) or chronic rhinosinusitis with polyposis (CRSP) is typically clinical and based on the combination of medical history, physical examination, and imaging. The recommendation to perform surgery and the type of surgery is tailored to the diagnosis. The objective of this study is to determine the accuracy of preoperative clinical CRS or CRSP diagnosis in patients who underwent endoscopic sinus surgery. This is a retrospective review of a case series of 380 consecutive patients who underwent endoscopic sinus surgery for the preoperative clinical diagnosis of CRS or bilateral CRSP. Data regarding symptoms, nasal endoscopy, computed tomography findings, preoperative diagnosis, and postoperative histopathology results were collected. The preoperative diagnoses were CRS (n = 180) and CRSP (n = 200). Two of the 180 patients (1.1%) with the preoperative diagnosis of CRS had a different postoperative histopathological diagnosis. The histopathology in both patients showed noncaseating granulomata, leading to a diagnosis of sarcoidosis. Nine of the 200 patients (4.5%) with the preoperative diagnosis of CRSP had a different postoperative histopathological diagnosis. Of these nine patients, five had inverted papilloma (bilaterally in one instance); one had adenocarcinoma; one had squamous-cell carcinoma; one had chronic invasive granulomatous fungal sinusitis; and one had sinonasal sarcoidosis. The preoperative clinical diagnosis can be inaccurate in patients with CRS and bilateral CRSP. The misdiagnosis is more common in CRSP, including patients with recurrent polyposis.

Fungal sinusitis: histologic spectrum and correlation with culture

Fungi are important etiologic agents of sinusitis. However, features of fungal sinusitis including the histologic spectrum, diagnostic mishaps, incidence, and fungal types have not been systematically studied. From 1996 through 2001, a total of 788 surgical pathology sinus specimens from 384 cases was retrieved. Fungal sinusitis was diagnosed in 58 specimens (7%) from 47 cases (12%). Four histologic categories of fungal sinusitis were identified: (1) allergic fungal sinusitis in 34 cases (copious mucin, abundant eosinophils, Charcot-Leyden crystals (so-called allergic mucin), with rare noninvasive fungal hyphae); (2) mycetoma/fungus ball in 11 cases (tightly packed fungal hyphae without allergic mucin or tissue invasion); (3) chronic invasive fungal sinusitis in 1 case (tissue granulomas with fungal hyphae); and (4) acute fulminant fungal sinusitis in 1 case (fungal vascular invasion). The diagnosis was initially missed in 16/34 (47%) cases of allergic fungal sinusitis despite typical features; incorrect classification was noted in 47% of cases. Sixty-seven percent of cases had positive fungal cultures, dematiaceous fungi being the most common. Allergic fungal sinusitis accounted for the majority of fungal sinusitis. Although misdiagnosis or incorrect classification is rather frequent for fungal sinusitis, awareness of the distinctive morphologic features of this entity may prevent these errors.

Chronic Invasive Fungal Sinusitis: A Report of Two Atypical Cases

The purpose of this article is to describe a chronic variant of invasive fungal sinusitis (IFS) and discuss its management. This is a retrospective review of two cases of IFS that were characterized by atypical clinical courses. Patient 1 was a 75-year-old man with noninsulin-dependent diabetes mellitus who came to us with a 5-month history of headache. Computed tomography detected an opacified left sphenoid sinus. After the man failed to respond to medical therapy, he underwent a left endoscopic sphenoidotomy. Pathologic examination revealed that septate, branching fungal hyphae had invaded the soft tissues. The patient was started on oral itraconazole, but later switched to intravenous amphotericin B in response to intracranial extension. The man's disease stabilized, but he died a little more than 1 year later of unrelated causes. Patient 2 was an otherwise healthy 41-year-old woman who came to us with nasal congestion and unilateral nasal polyps. She underwent endoscopic sinus surgery. Pathologic examination identified granulomatous sinusitis and septate, branching fungal hyphae that had invaded the soft tissue of the middle turbinate. The patient was not treated with systemic antifungal medications because of the localized nature of the fungal invasion and the lack of bone invasion or erosion. She has now been symptom-free for 5 years. These two cases demonstrate that IFS can appear in a chronic variant form that is characterized by an indolent course and histologic evidence of tissue invasion by fungal hyphae. The type of treatment is dependent on the extent of the disease on initial examination and the rapidity of its progression.

Primary Paranasal Aspergillus Granuloma: Case Report and Review of the Literature

Primary paranasal aspergillus granuloma (PPAG) is a slowly progressive chronic infection of the sinus extending beyond the confines of the sinus. It has been reported only in patients from the Sudan and India. Microscopically, it differs from chronic invasive fungal sinusitis in that there are pseudotubercles containing giant cells, histiocytes, lymphocytes, plasma cells, newly formed capillaries, eosinophils, and Aspergillus fungal elements. We describe the first case of PPAG in the United States in an immunocompetent nonatopic woman who had never left Missouri.

Invasive and Allergic Fungal Sinusitis.

Fungal sinusitis encompasses a wide range of clinical syndromes. Disease is classified into four major categories: 1) acute invasive fungal sinusitis, 2) chronic invasive fungal sinusitis, 3) mycetoma, and 4) allergic fungal sinusitis. Acute disease is most often a fulminant, life-threatening process seen in immunocompromised patients. Treatment requires prompt antifungal therapy and extensive surgical debridement. Other types of fungal sinusitis are more indolent. For chronic invasive sinusitis, a combination of surgical debridement and antifungal agents is the cornerstone of treatment. Mycetomas can usually be extirpated surgically and do not require therapy with antifungal agents. Treatment of allergic fungal sinusitis remains controversial, but most current management regimens utilize surgical debridement combined with corticosteroid therapy, rather than antifungal agents.