Rhino-Orbito-Cerebral Mucormycosis in Diabetic Disease Mucormycosis in Diabetic Disease.

The authors present their experience about clinical evidences that include patients with an untreated diabetes who developed rhino-orbito-cerebral mucormycosis (ROCM). They were treated with endoscopic sinus surgery and medical treatment with intravenous, intradural therapy, and sinus washes with amphotericin B. The ROCM is a disease with a rapid evolution and an increase in mortality rate, especially if the fungus enters the cranial cavity. Therefore, it would be necessary in all diabetic patients with sinus symptoms, headaches, visual changes, suspect a mucormycosis, and perform a careful radiology assessment and a nasal endoscopy. Often, despite an early diagnosis and rapid treatment for ROCM, it is not possible to stem the disease, which ends with the patient's death.

Giant isolated transcranial Rosai-Dorfman disease with diffuse involvement of nasal and paranasal tissues: case report and literature review.

Rosai-Dorfman disease (RDD) is an uncommon systemic histioproliferative disease process characterized by sinus histiocytosis with massive lymphadenopathy, and isolated transcranial RDD (ITRDD) is extremely rare. We report a patient with giant ITRDD with diffuse involvement of nasal and paranasal tissues, showing favorable response to postoperative steroid therapy.

The accessibility of topical treatment in the paranasal sinuses on operated cystic fibrosis patients assessed by scintigraphy.

BACKGROUND: Nasal irrigations with antibiotics are used to eradicate Pseudomonas aeruginosa from the upper airways in patients with cystic fibrosis (CF) and thereby avoid lung colonisations; nevertheless, the efficacy is uncertain. METHODOLOGY: The aim of this study was to investigate the accessibility and durability of solutions in the sinuses before and after sinus surgery. The participants irrigated their noses with radioactively marked saline and were evaluated using a dynamic SPECT/CT scan. The preoperative and postoperative (after 30 days) examinations were compared. RESULTS: Twelve CF patients were included. In 10 out of the 24 scanned maxillary sinuses an improvement was seen postoperatively compared with the preoperative fluid volume. Notably, in 7 out of the 24 sinuses the mucosa was so swollen postoperatively that no fluid was detected. Ten patients had developed their frontal sinuses. We observed no fluid in the frontal or sphenoid sinuses, neither before nor after surgery. At best, a mean of 23% of the maxillary sinuses were filled with fluid; thus, all sinuses had postoperatively areas of the mucosa that did not have contact with the fluid. A mean of 76% of the initial volume was present after 30 min in the maxillary sinuses. CONCLUSION: Fluid-depositing using nasal irrigation will not sufficiently or not at all get in contact with all the sinus mucosa despite of sinus surgery. Thus, the efficacy of topical deposition of antibiotics is presumably reduced.

Septic thrombosis of cavernous sinus extended to the ipsilateral internal jugular vein and transversal sinus with favorable outcome: Clinical and radiological features of a Lemierre syndrome.

An 86-year-old patient was hospitalized for fever and left acute orbital syndrome (red eye with moderate visual impairment, chemosis, ophthalmoplegia without proptosis, or any fundus involvement). CT scan showed superior ophthalmic vein and cavernous sinus enlargement complicating ipsilateral sphenoidal sinusitis. Magnetic resonance imaging (MRI) demonstrated the left cavernous sinus thrombosis extended to the ipsilateral jugular vein and transversal sinus (Lemierre syndrome). Intravenous broad-spectrum antibiotics and curative anticoagulation were prescribed. Blood cultures allowed the identification of Streptococcus intermedius and Staphylococcus warneri species. Evolution was favorable and the patient was discharged 3 weeks after. Antibiotics and anticoagulation were carried out for a total duration of 4 and 12 weeks, respectively. Lemierre syndrome is a potentially life-threatening emergency rarely encountered; thus, ophthalmologists should be cognizant of clinical and radiological features. Broad-spectrum antibiotics are the mainstay of treatment. Curative anticoagulation may be added if no blood coagulation disorder nor bleeding on neuroimaging has been identified.

Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution.

Chronic invasive aspergillosis of the sinus is frequently fatal in the absence of early surgical and chemotherapeutic intervention because of its invasion of vascular tissue. We attempted to control a case of inoperable invasive aspergillosis of the sinus with micafungin and itraconazole oral solution. We prescribed a daily oral dose of 400 mg of itraconazole, which is twice the usual dose, and monitored the serum concentration of the drug. Finally, we were able to control the spread of the lesion. This case indicates that combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution is an alternative treatment strategy for inoperable invasive aspergillosis of the sinus.

The Role of Adjunctive Therapies in the Management of Invasive Sino-Orbital Infection.

OBJECTIVE: Invasive sino-orbital fungal infections are life-threatening complications of immunonosupression that are difficult to treat. Currently there are no standard treatment guidelines. The most widely accepted therapy includes parenteral anti-fungal therapy and surgical debridement of sinuses with orbital exenteration, a procedure that is not only disfiguring, but may increase morbidity. Injection of retrobulbar Liposomal Amphotericin B (L-AMB) is an alternative approach that provides local administration to infected tissues. The adjunct use of anti-fungal retrobulbar injections not been extensively reviewed in treating sino-orbital infection. We are reporting the multimodal approach of using L-AMB retrobulbar injections in combination with sinus debridement, intravenous (IV) anti-fungal therapy, and hyperbaric oxygen (HBO) for the management of sino-orbital infection. METHOD & RESULTS: Review of literature of 12 cases and retrospective evaluation of one patient with sino-orbital Aspergillus flavus infection on chemotherapy for T-cell acute lymphocytic leukemia treated with retrobulbar Amphotericin B, IV anti-fungal agents, and hyperbaric oxygen therapy. Clinical characteristics, radiographic features, management techniques, and clinical outcomes are described. CONCLUSION: Retrobulbar Amphotericin B injection may be an effective adjunct to hyperbaric oxygen and parenteral anti-fungals in the control of sino-orbital fungal infections.

Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation.

BACKGROUND: Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated. OBJECTIVE: The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease. DESIGN: Observational study. PARTICIPANTS: Twelve patients with cystic fibrosis and a G551D-CFTR mutation. METHODS: Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor. OUTCOME MEASURES: Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared. RESULTS: Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy. CONCLUSIONS: Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

Is sinus disease the cause of my headaches? An update on sinus disease and headache.

The interplay between head pain caused by sinus disease and primary headaches is complex. Classification of secondary headaches, attributed to disorders of the nose or paranasal sinuses has been recently updated. New treatments including office- based procedures are emerging for patients with chronic sinusitis. This paper briefly reviews sinus disease and headache.

[Liposomal local therapy of sinunasal symptoms in ANCA associated vasculitis]. / Sinunasale Symptome ANCA-assoziierter Vaskulitiden und deren Therapie mit Liposomen.

BACKGROUND: GPA, eGPA and MPA constitute the group of AAV. ENT manifestations are part of the typical clinical picture of these diseases. Usually, patients are treated with systemic immunomodulatory drugs, mostly based on organ affection. In clinical routine, an insufficient decrease of sinunasal manifestations during a solely systemic therapeutic concept can repeatedly be -observed. MATERIAL AND METHODS: Between February 2009 and November 2012, 20 patients with AAV were diagnosed in or referred to our department for further treatment. Clinical symptoms and manifestations were measured by the use of international accepted activity scores. The effect of a local therapy with liposomes for a period of 2 months on sinunasal symptoms was prospectively evaluated by using visual analogue scales and standardized questionnaires. RESULTS: Within the described collective 100% of patients did show ENT-symptoms at the time of initial diagnosis. Every patient did receive immunomodulatory therapy, but in 61.1% of cases there was just slight or no improvement on sinunasal symptoms. After a 2-month period of liposomal local therapy, a significant reduction of sinunasal complaints could be observed, both evaluated via visual analogue scales (p<0.001 to p=0.014, depending on the evaluated symptom) and standardized questionnaires (p<0.001). CONCLUSIONS: The local application of liposomes in addition to a systemic therapy is effective in alleviating sinunasal manifestations in patients with AAV.

How Does Oxymetazoline Change Nasal Aerodynamics and Symptomatology in Patients with Turbinate Hypertrophy?

OBJECTIVES: Oxymetazoline relieves nasal obstructive symptoms via vasoconstriction, however, the changes in nasal structures and aerodynamics that impact symptoms the most remain unclear. METHODS: This prospective, longitudinal, and single blinded cohort study applied Computational Fluid Dynamic (CFD) modeling based on CT scans at baseline and post-oxymetazoline on 13 consecutive patients with chronic nasal obstruction secondary to inferior turbinate hypertrophy from a tertiary medical center. To account for placebo effect, a sham saline spray was administered with subject blindfolded prior to oxymetazoline, with 30 min rest in between. Nasal Obstruction Symptom Evaluation (NOSE) and unilateral Visual Analogue Scale (VAS) scores of nasal obstructions were collected at baseline, after sham, and 30 min after oxymetazoline. RESULTS: Both VAS and NOSE scores significantly improved from baseline to post-oxymetazoline (NOSE: 62.3 ± 12.4 to 31.5 ± 22.5, p < 0.01; VAS: 5.27 ± 2.63 to 3.85 ± 2.59, p < 0.05), but not significantly from baseline to post-sham. The anatomical effects of oxymetazoline were observed broadly throughout the entire length of the inferior and middle turbinates (p < 0.05). Among many variables that changed significantly post-oxymetazoline, only decreased nasal resistance (spearman r = 0.4, p < 0.05), increased regional flow rates (r = -0.3 to -0.5, p < 0.05) and mucosal cooling heat flux (r = -0.42, p < 0.01) in the inferior but not middle turbinate regions, and nasal valve Wall Shear Stress (WSS r = -0.43, p < 0.05) strongly correlated with symptom improvement. CONCLUSION: Oxymetazoline broadly affects the inferior and middle turbinates, however, symptomatic improvement appears to be driven more by global nasal resistance and regional increases in airflow rate, mucosal cooling, and WSS, especially near the head of the inferior turbinate. LEVEL OF EVIDENCE: 3: Well-designed, prospective, single blinded cohort trial. Laryngoscope, 134:1100-1106, 2024.

Successful treatment of invasive rhinopulmonary mucormycosis with an indolent presentation by combined medical and surgical therapy.

In many cases of mucormycosis, immediate surgical treatments are necessary because of its fulminant course and destructive characteristics in an immunocompromised patient. However, a chronic indolent type is also observed in a healthy group of people. We experienced rhinomucormycosis in a 56-year-old woman with diabetes who previously had pulmonary mucormycosis. She was treated successfully through endoscopic sinus surgery and nasal irrigation with antifungal agent. Herein, we report the clinical courses and symptoms of this patient with literature review.

Fungal disease of the nose and paranasal sinuses.

Fungal infections of the nose and paranasal sinuses represent a spectrum of diseases ranging from colonization to invasive rhinosinusitis. Clinical manifestations are largely dependent on the immune status of the host, and given the ubiquitous nature of these organisms, exposure is unavoidable. Noninvasive disease includes asymptomatic fungal colonization, fungus balls, and allergic fungal rhinosinusitis. Invasive disease includes indolent chronic rhinosinusitis, granulomatous fungal sinusitis, and acute fulminant fungal rhinosinusitis. A differentiation of these somewhat overlapping syndromes and the disparate treatment regimens required for effective management are the focus of this review.

Primary odontogenic onset invasive mucormycosis-an under recognized clinical entity.

OBJECTIVES: The primary source of facial mucormycosis is through inhalation of fungal sporangiospores, resulting in invasive disease in paranasal sinuses. However, dental onset mucormycosis has not been well documented in literature. The aim of this study was to describe the clinical characteristics and outcomes of patients with odontogenic onset mucormycosis. METHODS: From a large cohort of mucormycosis involving the face between July 2020 and October 2021, we selected patients who had dental symptoms at onset and predominant alveolar involvement with little to no paranasal sinus disease as shown by baseline imaging. All patients had a confirmed diagnosis of mucormycosis through histopathology, with or without the growth of Mucorales in fungal culture. RESULTS: Out of 256 patients with invasive mucormycosis of the face, 8.2% (21 patients) had odontogenic onset. Uncontrolled diabetes was a common risk factor, affecting 71.4% (15/21) of the patients, while recent COVID-19 illness was noted in 80.9% (17/21) of patients. The median duration of symptoms at presentation was 37 days (IQR, 14-80 days). The most common symptoms were dental pain with loose teeth (100%), facial swelling (66.7% [14/21]), pus discharge (28.6% [6/21]), and gingival and palatal abscess (28.6% [6/21]). Extensive osteomyelitis was found in 61.9% (13/21) of the patients, and 28.6% (6/21) had oroantral fistulas. The mortality rate was low, at 9.5% (2/21), with only 9.5% (2/21) of the patients having brain extension and 14.2% (3/21) in the orbit. CONCLUSION: This study suggests that odontogenic onset invasive mucormycosis may be a separate clinical entity with its own distinct clinical features and prognosis.

Rare pediatric rhino-orbital infection caused by Saksenaea vasiformis.

Rhinosinusitis infection due to Saksenaea vasiformis is extremely rare. The present case describes a rhino-orbital infection in a 21-month-old Chadian immunocompetent male child with a 2-month history of excessive tearing from the right eye, followed by swelling of the right upper and lower eye lids, associated with right facial swelling and dark coloration surrounding the lower eye lid. Coronal computed tomography (CT) scan of the paranasal sinuses showed opacification of the right nasal cavities with extension to the orbit. Non-septate fungal hyphae were diagnosed by tissue sections and a Blankophor P fluorescent stain microscopy. The culture grew zygomycetes, S. vasiformis that failed to sporulate on Sabouraud dextrose agar, the organism was sporulated after 1 week on Czapek agar medium, and produced flask-shaped brown pigmented sporangium with lateral rhizoids and hemispherical columella filled with spores. The patient underwent a right functional endoscopic sinus surgery, where debridement of both right maxillary and ethmoid sinuses was done. Treatment with amphotericin B lipid complex was started and continued for 41 days. The patient was clinically doing better with decreased eye and facial swelling, and his erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were decreased to normal values. The patient continued with treatment on posaconazole after his discharge, and his condition resolved without further sequelae. Rhinosinusitis due to mucormycosis should be considered in any patient, even in young children, presenting with progressive rhinosinusitis infection, whether immunocompromised or not. Early diagnosis may lead to a successful treatment and good prognosis.

[Mucormycosis. An emergent mycosis]. / Mucormicosis. Una micosis emergente.

Mucormycosis is an opportunistic infection caused by fungi of the order Mucorales. It is characterized by rapid progression and high morbidity and mortality in the absence of early diagnosis and prompt treatment. It was an infrequent disease, but in recent years, its incidence appears to have increased. The aim of this paper is to report the cases of mucormycosis diagnosed from 1982 to 2010 at the Hospital de Clinicas José de San Martín, University of Buenos Aires. We diagnosed 10 cases of mucormycosis; the first three between 1982 and 2004 and the last 7 between 2005 and 2010. The incidence from 1980 to 2004 was 0.13 patient-years and the frequency 0.1/10 000 discharges (95% CI 0.00- 0.3). In the period 2005 to 2010, the incidence was 0.86 patients per year with 1.1/10 000 discharges (95% CI 0.5-2.4). There was a pulmonary mucormycosis case (in a patient treated with corticosteroids) and nine rhinocerebral cases, two in neutropenic and seven in diabetic patients. The diagnosis was made by observation of cenocytic hyphae in 10/10 patients. Mucorales were recovered in 8/9 cultures (5 Rhizopus spp and 3 Mucor spp.). In one case diagnosis of pulmonary mucormycosis was made post-mortem. Nine patients were treated with amphotericin B deoxycholate (in 3 patients supplemented with liposomal amphotericin B) and surgery. Three patients underwent hyperbaric chamber. Seven patients had favorable outcome. In conclusion, mucormycosis is a rare disease, but its incidence has increased over the past five years. A good evolution of the patients is linked to early diagnosis and treatment.

Invasive aspergillosis of orbit in immunocompetent patients: treatment and outcome.

OBJECTIVE: Invasive sino-orbital aspergillosis in immunocompetent patients is a rare clinical entity and often misdiagnosed. Invasive sino-orbital aspergillosis is potentially fatal; however, mortality may be avoided with timely treatment. Presently, there are no universal guidelines for its treatment. We present the clinical features, treatment, and outcome in 15 cases of invasive sino-orbital/orbital aspergillosis in healthy individuals. DESIGN: Retrospective case series. PARTICIPANTS: Fifteen cases of invasive sino-orbital/orbital aspergillosis in immunocompetent individuals. METHODS: We retrospectively analyzed all patients with sino-orbital/orbital aspergillosis who were treated at the Dr. Rajendra Prasad Center for Ophthalmic Sciences between June 1999 and September 2009. Diagnosis was based on histopathologic documentation of tissue invasion by septate fungal hyphae with acute angle branching and presence of granulomatous inflammation. MAIN OUTCOME MEASURES: Treatment outcome in terms of patient survival, resolution of symptoms, and resolution of orbital mass on imaging. RESULTS: Fifteen patients (11 male and 4 female) were studied. Mean age of patients was 35 years. One patient declined treatment. Surgery was performed for orbital disease in 6 patients. Medical therapy consisted of intravenous amphotericin B followed by itraconazole in 10 patients, itraconazole alone in 2 patients, and voriconazole followed by itraconazole in 2 patients. Eleven patients are alive without recurrence at a median follow-up of 20 months. Of these patients, 5 had residual mass on imaging at last follow-up. One patient died of progressive disease. CONCLUSIONS: This is a large case series of orbital aspergillosis reported in healthy individuals. The role of orbital surgery is not clear in treatment of this entity and requires further evaluation. Newer antifungal agents alone seem to be effective in controlling the infection.

The effects of repetitious topical use of mitomycin C on antrostomy patency in maxillary antrostomy created rabbit model.

The aim of our study was to investigate the effect of the topical use of mitomycin C (MMC) intraoperatively in single dose and intra-postoperatively in two doses on the narrowing of antrostomy in maxillary rabbit sinus antrostomies created experimentally. And also to determine the local and systemic side effects of topical MMC. With this objective, 0.6 mg/ml MMC was used to the first group at single dose and to the second group intraoperatively and on third day postoperatively in two doses topically for 5 min. After 8 weeks, although the mean area of antrostomy was larger than that in the control side in the first group, which received single dose MMC, the difference was not statistically significant (p = 0.287). The second group received two doses, and the antrostomy areas were found to be significantly larger than the controls (p = 0.05). Overall, the sides that received MMC were significantly larger (p = 0.029). From the point of histopathological examination of the tissue, it was seen that two-dose MMC increased the edema indicating inflammation and antrostomy resolved with normal respiratory tract epithelium. It was shown by measuring the blood values that nephrotoxic and myelosupressant effect of MMC occurring in systemic use did not occur with single or double dose topical use. Our results demonstrate that even if the number of cases was low, two doses of topical MMC usage prevent the narrowing of antrostomy while single dose MMC does not. And two-dose topical MMC usage does not have local and systemic side effects.

A case of rhinoorbital mucormycosis in a leukemic patient with a literature review from Turkey.

Mucormycosis (Zygomycosis) is a rare, invasive, opportunistic fungal infection of the paranasal sinuses, caused by a fungus of the order Mucorales. We report a case of rhinoorbital mucormycosis caused by Rhizopus oryzae in an acute lymphoblastic leukemia patient and review the 79 Mucormycosis cases reported in the last decade from Turkey. In our case, the diagnosis was made with endoscopic appearance, computerized tomography of the paranasal sinuses, and culture of the surgical materials. Following aggressive surgical debridement and parenteral amphotericin B therapy, the patient recovered completely. In Turkish literature, rhinocerebral manifestations were the most common form of the mucormycosis (64 cases), followed by pulmonary form (6 cases). The most common risk factor was hematologic malignancies (32 cases) and diabetes mellitus (32 cases), similar to those reported from the rest of the world. The etiologic agents responsible for the review cases were Rhizopus sp., Mucor spp., Rhizomucor spp., Rhizopus oryzae, Mucor circinelloides, and Lichtheimia corymbifera. Although various treatment modalities were used, amphotericin B was the mainstay of therapy. Mortality rate was found to be 49.4% in review cases. It seems that strong clinical suspicion and early diagnosis, along with aggressive antifungal therapy and endoscopic sinus surgery, have great importance for better prognosis in mucormycosis.

Rhinocerebral mucormycosis: five cases and a literature review.

OBJECTIVE: In this retrospective study, we describe our experience in the diagnosis and management of rhinocerebral mucormycosis (RCM), a rapidly lethal fungal infection. METHODOLOGY: Between 1997 and 2007, five patients hospitalized for suspicion of RCM. Computed tomography was performed in all cases, and diagnosis was confirmed after anatomopathological or mycological examination. All patients underwent medical and surgical treatment. Follow-up was clinical and radiological with a mean period of 17 months. RESULTS: All patients were diabetic. Exophthalmia, rhinorrhea, and ophthalmoplegia were the most frequent symptoms observed. One patient had loss of visual acuity and another exhibited peripheral facial palsy. One patient had extensive hemifacial cutaneous necrosis. Nasal endoscopy revealed black necrotic lesions in one case, and another patient had a tumefaction localised in the left middle meatus. Necrotic lesions were most often found in the orbit, the maxillary and the ethmoidal sinuses on computed tomography (four cases for each site). One patient had thrombophlebitis of the cavernous sinus, and another had an intracranial extension. All patients were administered ordinary insulin and intravenous amphotericin B. Surgical debridement of the nasal cavity and the involved sinuses was performed through lateral rhinotomy (four cases) or endoscopy (one case). Unilateral orbital exenteration was associated in two cases. Progression was favourable in four cases; one patient died from sepsis despite aggressive treatment. CONCLUSION: Early diagnosis is crucial for the management of RCM. Treatment of underlying disorders, use of intravenous amphotericin B, and aggressive surgical intervention are key in reducing morbidity and mortality rates.

Effect of highly effective modulator treatment on sinonasal symptoms in cystic fibrosis.

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator for cystic fibrosis (CF) patients homozygous or heterozygous for F508del. Effects of the drug on sinonasal symptoms have not been studied. METHODS: Adult participants were prospectively evaluated at baseline and after three months of treatment using validated questionnaires assessing sinonasal symptoms (SNOT-22) and CF-related quality of life (CFQ-R). RESULTS: Forty-three participants completed the study; 23 were taking other CF transmembrane conductance (CFTR) modulators at the time of study participation. There was a significant improvement in mean SNOT-22 from 34.8 (29.4-40, 95% confidence interval) to 24.4 (19.9-29.0) (p = 0.000003) and in the Respiratory domain of the CFQR from 60.6 (57.1-64.1) to 83.3 (79.4-87.2) (p = 0.0000002), both achieving a minimal clinically important difference. Patients previously taking CFTR modulators experienced a greater benefit in sinonasal and respiratory symptoms. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor is associated with significant improvement in sinonasal symptoms; previous use of CFTR modulators is associated with greater benefit.