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Introduction: Hyponatremia is one of the most common electrolyte abnormalities in clinical practice. Syndrome of inappropriate antidiuretic hormone (SIADH) accounts for the majority of hyponatremia cases. In some cases, it may be challenging to find an underlying etiology. Case Presentation: We present a 76-year-old male patient with complaints of altered consciousness, disorientation, and relapsing hyponatremia. The final evaluation of hyponatremia showed a diagnosis of SIADH. As the patient’s hyponatremia was unresponsive to fluid restriction, tolvaptan was started at a 7.5 mg/day dose. Following detailed investigations to find an etiology of SIADH, sphenoidal sinusitis was detected, and sinus biopsy culture yielded Aspergillus flavus/oryzae. Voriconazole (IV 6 mg/kg loading followed by 4 mg/kg) commenced, and tolvaptan was discontinued during the follow-up. Conclusion: Fungal infections should be kept in mind after excluding other causes of central nervous system-related hyponatremia in immunocompetent individuals without alarming symptoms suggestive of malignancy. [ABSTRACT FROM AUTHOR]

Penicillium brasilianum is an environmental filamentous fungus with useful applications in biotechnology. However, human infections caused by P. brasilianum are rare and not well understood. We present the case of a woman in her sixties with poorly controlled diabetes mellitus who was diagnosed with invasive fungal rhinosinusitis (IFRS) and orbital apex syndrome. She underwent endoscopic sinus surgery and received treatment with liposomal amphotericin B. Notably, β-tubulin gene sequencing identified the filamentous fungus as P. brasilianum, and long-term itraconazole administration suppressed IFRS flares. Our findings underscore the need for increased awareness and understanding of rare fungal pathogens in clinical practice. [ABSTRACT FROM AUTHOR]

Invasive fungal sinusitis is a life-threatening form of fungal rhinosinusitis. Due to the aggressive clinical presentation and radiological appearance, there is diagnostic difficulty in differentiating invasive fungal sinusitis from a malignant process. This is even more challenging in oncological patients who have undergone previous head and neck radiotherapy, due to possibility of a recurrence of primary malignancy and radiation-induced neoplasms. We report a rare case of invasive fungal sinusitis mimicking a malignancy in a post-radiotherapy patient. Our patient was a 68-year-old male, 25-years post-radiotherapy for nasopharyngeal carcinoma. He presented with a 3-month history of purulent sputum and right facial paraesthesia. Magnetic resonance imaging showed an irregular destructive enhancing mass of the greater wing of right sphenoid and pterygoid bone with extensive extension into nearby structures. In view of extensive local and bony invasion, and a history of radiotherapy, initial suspicions were that of primary malignancy, specifically radiation-induced sarcoma, and recurrence of nasopharyngeal carcinoma. He underwent transpterygoid biopsy of the lesion, and histopathology demonstrated Aspergillus species, with no malignancy identified. Our report highlights the diagnostic difficulties in the post-radiotherapy cancer patient presenting with symptoms suggestive of aggressive sino-nasal disease. Invasive fungal sinusitis closely mimics the clinical and radiological findings of several neoplastic processes. We discuss the clinical and radiological characteristics of pathologies that may mimic invasive fungal sinusitis. Histological examination remains the gold standard for diagnosis, and early fungal staining is crucial. Furthermore, one should not presume the initial histopathological diagnosis to be confirmatory of isolated fungal disease. Repeat radiological investigations for disease resolution and histopathologic re-evaluation if required should be performed, keeping in mind possibility of coexisting malignancy. [ABSTRACT FROM AUTHOR]

Objective To study the etiological and anatomical factors in pathophysiology of invasive fungal rhinosinusitis affecting the skull base. Design Retrospective clinical study over 5 years. Setting Single-center tertiary referral hospital. Materials and Methods All cases of invasive fungal rhinosinusitis with clinicoradiological and/or operative evidence of anterior and central skull base, orbit, and orbital apex involvement with or without intracranial disease were included in the study. Patients with a sinonasal-palatal disease without the involvement of the skull base or orbit were excluded from the study. In addition, we assessed the risk factors such as coronavirus disease 2019 (COVID-19) infection, diabetes mellitus (DM), and other immunocompromised conditions. Results There were 79 patients, of which 65.8% had skull base rhino-oribitocerebral mucormycosis (ROCM), and 34.2% had Aspergillus infection. The mean duration from onset of the symptom to presentation of ROCM was 36.75 ± 20.97 days, while for the Aspergillus group was 21 weeks. The majority of patients (66%) with ROCM presented after 30 days of symptom onset. Among ROCM patients, 88.7% had a history of COVID-19 infection, and 96% had DM. In 40.8% of patients with Aspergillus infection, the tissue diagnosis was unavailable, and galactomannan assay and clinicoradiological assessment were used for diagnosis. The most common area of the skull base involved was the pterygopalatine fossa (88.5%), followed by the infratemporal fossa (73.1%). The most common neurovascular structure (75%) involved was the pterygopalatine ganglion and the infraorbital nerve. Conclusion With the increasing incidence of invasive fungal infections worldwide, particularly after the COVID-19 pandemic, it is crucial to understand the evolving nature of this disease. ROCM, documented in the literature to cause fulminant disease, became a chronic illness, possibly due to the improvement of the patient's immunity during the disease course. [ABSTRACT FROM AUTHOR]

Introduction: Hyponatremia is one of the most common electrolyte abnormalities in clinical practice. Syndrome of inappropriate antidiuretic hormone (SIADH) accounts for the majority of hyponatremia cases. In some cases, it may be challenging to find an underlying etiology. Case Presentation: We present a 76-year-old male patient with complaints of altered consciousness, disorientation, and relapsing hyponatremia. The final evaluation of hyponatremia showed a diagnosis of SIADH. As the patient’s hyponatremia was unresponsive to fluid restriction, tolvaptan was started at a 7.5 mg/day dose. Following detailed investigations to find an etiology of SIADH, sphenoidal sinusitis was detected, and sinus biopsy culture yielded Aspergillus flavus/oryzae. Voriconazole (IV 6 mg/kg loading followed by 4 mg/kg) commenced, and tolvaptan was discontinued during the follow-up. Conclusion: Fungal infections should be kept in mind after excluding other causes of central nervous system-related hyponatremia in immunocompetent individuals without alarming symptoms suggestive of malignancy.

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1β and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

Iron is an important micronutrient involved in cell biology through vital reactions. We examined the correlations between iron metabolism parameters and the course of invasive fungal sinusitis. Patients with invasive fungal sinusitis were enrolled. Serum iron and ferritin levels, total iron-binding capacity, and transferrin saturation were measured at the initiation of treatment. Patients were followed for 6 months, and the clinical course was categorised as improvement or worsening/death. A total of 35 patients were enrolled. The average ferritin levels in mucormycosis patients was 944.9 ng/ml, versus 110.7 ng/ml for aspergillosis patients. Iron levels were significantly lower in mucormycosis than in aspergillosis (29.14 µg/dl vs. 68.55 µg/dl). Total iron-binding capacity was significantly different between the two groups (16.76 µg/dl vs. 330.36 µg/dl). After 6 months, improvement, worsening, and death were noted for 18, 8, and 9 patients, respectively. Higher iron levels and lower ferritin levels were linked with improvement. Total iron-binding capacity was significantly higher in improved patients (2314 vs. 151). Iron metabolism parameters play significant roles in the preemptive judgment of the course of fungal sinusitis. Based on these findings, studies on drugs affecting iron metabolism should be conducted. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are uncommon in an immunocompetent host and pose a real diagnostic dilemma. As they have a propensity for locoregional destruction, clinic-radiological findings can mislead to a faulty diagnosis of a malignancy. Here we present a case of Primary Aspergillus dacryocystitis in an immunocompetent individual initially thought to be an orbital malignancy until the histopathological examination. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis is a rare but severe fungal infection primarily affecting immunocompromised individuals. The Coronavirus Disease-2019 (COVID-19) pandemic has introduced new complexities in managing aspergillosis due to the widespread use of corticosteroids for treating COVID-19-related respiratory distress, which can increase susceptibility to fungal infections. Here, we present a challenging case of progressive cerebral aspergillosis complicated by cavernous sinus thrombosis (CST) in a 67-year-old male with a history of COVID-19. The patient, initially misdiagnosed with temporal arteritis, received pulse corticosteroid therapy twice before presenting with persistent left-sided headaches and vision loss. Cranial imaging revealed findings consistent with fungal sinusitis, Tolosa–Hunt syndrome, and orbital pseudotumor, which progressed despite initial antifungal therapy. Subsequent magnetic resonance imaging indicated an invasive mass extending into the left cavernous sinus and other intracranial structures, raising suspicion of aspergillosis. A transsphenoidal biopsy confirmed Aspergillus infection, leading to voriconazole therapy. Despite aggressive treatment, follow-up imaging revealed significant progression, with extension to the right frontal region and left cavernous sinus. The patient then developed visual impairment in the right eye and was diagnosed with CST secondary to fungal sinusitis. Management included a combination of systemic antifungals and antibiotics; however, the patient declined surgical intervention. This case underscores the diagnostic challenges and rapid progression associated with cerebral aspergillosis in post-COVID-19 patients treated with corticosteroids. This report highlights the need for heightened clinical suspicion and prompt, targeted interventions in similar cases to improve patient outcomes. Further research is required to understand the optimal management of invasive fungal infections.

Anatomical variations in the maxillary sinus pneumatisation are limited unlike the ethmoids. We present rare variations of the maxillary sinus along its floor other than septations and includes wide pneumatisation of alveolar and palatal recess with cell formation. An intra-maxillary cell that opens into the maxillary infundibulum well within the sinus is described here and our senior author has coined the new term-alveolar recess cell. Its involvement in the sinus pathologies and additional surgical approaches for the disease clearance is discussed here. [ABSTRACT FROM AUTHOR]

Orbital abscesses are primarily seen in children as complication of ethmoid bacterial sinusitis. We report a case of invasive aspergillosis causing orbital abscess in an immunocompetent child which resolved with surgery followed by antifungal therapy. This case highlights need for histopathological, and microbiological examination, including fungal culture in such cases. [ABSTRACT FROM AUTHOR]

A Gentleman in his 40s presented to us with left-sided hemifacial pain and nasal discharge for the last three days. He has been on immunosuppressive therapy for Wegener's Granulomatosis for over five years. Crusting was seen in the Left middle meatus upon clinical examination. Based on the post-covid status, steroid therapy, KOH mount, and radiologic imaging, a provisional diagnosis of Sinonasal mucormycosis was considered. He was posted for emergency debridement followed by Liposomal Amphotericin B and steroid therapy. Surgical histopathological specimens were suggestive of Mucormycosis. Limited sinonasal disease with no intracranial, orbital, or palatal involvement was seen in a background of Wegener's Granulomatosis, Covid, and immunosuppressive therapy. Steroids are condemned as a predisposing factor to mucormycosis. Still, the combination of Liposomal Amphotericin B and steroids was used, opening new avenues for managing mucormycosis in patients with vasculitis. The patient is well nine months post-surgery with no signs of disease relapse. [ABSTRACT FROM AUTHOR]

Rhino- orbital-cerebral mucormycosis is a rapidly progressive life-threatening fungal infection which primarily affects the nose, paranasal sinuses and orbit. It is an opportunistic fungal infection caused by fungi of order Mucorales. They are a group of ubiquitous fungi which grow on decaying vegetation and a wide variety of organic compounds, and they pose a huge threat to life by direct invasion of the vital structures in the body. Early identification and treatment of this disease is therefore of paramount importance for a better outcome. We report a case of a 65-year-old man with a background history of poorly controlled type 2 diabetes mellitus, hypertension and chronic kidney disease, who presented with a diffuse headache of 5 days along with left sided facial oedema, redness of left eye and visual disturbance. Imaging studies revealed sinusitis involving multiple sinuses and the nasal mucosal biopsy showed fungal hyphae. Considering the clinical presentation and the overall findings from the investigations a diagnosis of rhino-cerebral mucormycosis was made. Medical management was done with administration of intravenous Amphotericin B and IV itraconazole along with other supportive medication. Patient had a successful recovery after a lengthy hospital stay which included surgical debridement of affected tissues and the medical treatment even with challenges faced due to unavailability of drugs due to economic constraints on health.

Black fungus, also known as mucormycosis, is one of the most serious infections affecting immunocompromised individuals. Invasive fungal sinusitis due to mucormycosis is quite rare globally. Hence, this article presents a case report of invasive fungal sinusitis in a 53-year-old diabetic female who presented to the emergency department with a severe case of diabetic ketoacidosis secondary to acute sinusitis, which was confirmed by histopathology to be mucormycosis. An extensive surgical debridement and liposomal amphotericin B were the mainstay of treatment. The treatment of mucormycosis consists of treating the underlying disease, antifungal therapy, and surgical debridement. Also, previous studies have discussed the use of medical therapy alone, surgical therapy alone, and combination therapy. It was found that the combination of medical and surgical therapy was the most effective method in treating this condition. However, the high mortality rate of this disease indicates the need for a possible adjuvant therapy which could increase the survival rate. Therefore, recent studies have proposed new adjuvant modalities, such as hyperbaric oxygen therapy and local treatment with amphotericin B. In this study, we propose a new adjuvant therapy using local miconazole cream which showed a good prognosis with the combination of oral amphotericin B and surgical debridement. This highlights the necessity for extensive future clinical trials to validate its effectiveness in treating isolated sinus mucormycosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aljubran et al.)

Fungal sphenoiditis is a rare case in clinical practice. Usually affecting just one sinus, Aspergillus is the most common cause of fungal sinusitis. Atypical headache with unresponsive to analgetics is one of symptom from Isolated Sphenoid sinusitis. This case report presents a 37 year old female with isolated sphenoiditis fungal. The patient came with atypical headache as the major symptom. Based on the morphology of the sphenoid sinus and its surrounding structures, diagnosis is often challenging. After some medicine, the chief complaint did not disappear. A functional endoscopic sinus surgery was performed to remove the fungal ball, and the patient get good result. • Atypical headache have numerous causes. • Because of high costs, neurologists in developing countries do not perform CT scans when patients arrive • This leads to a delayed or incorrect diagnosis. • Isolated Sphenoid Fungal Sinusitis is a rare case, seen in fewer than 3% of all sinusitis patients. • Its optimal management is endoscopic intranasal transphenoidal approach without the need for antifungal therapy [ABSTRACT FROM AUTHOR]

Background: Allergic fungal sinusitis (AFS) is a form of paranasal mycosis that often involves bone destruction and can extend into the orbit and anterior skull base. Intracranial and intraorbital involvement are published but not both in each included patient of a series. The purpose of the present study was to review cases of extensive AFS with orbital or/and skull base erosion, including the presenting symptoms, patient socioeconomic background, imaging features, surgical technique, and post-operative outcomes., Methods: The records of 30 patients with the histological diagnosis of AFS and both intracranial and intraorbital involvement were reviewed., Results: The average age of the patients was 25.2 years. 83 % of patients were male. 70 % were African American. 66 % of patients had Medicaid or were uninsured. Presenting symptoms were headaches (80 %), nasal obstruction (33 %), proptosis (40 %), vision change (23 %), facial pressure (10 %), and decreased sense of smell (7 %). 100 % of patients had bone erosion observed on computerized tomography scans with disease extending intracranially through the anterior skull base or posterior wall of the frontal sinus along with disease that eroded through the lamina papyracea. All patients had failed medical management. All patients underwent surgery by Otolaryngology, Ophthalmology, and Neurosurgery with transnasal endoscopic approaches and orbitotomy. 80 % also underwent a bifrontal craniotomy for removal of intracranial extradural disease with cranialization. 53 % of patients had orbital implants remaining after surgery; 23 % had nasal stents. There were no postoperative cerebrospinal fluid leaks. Average hospital stay was 4.8 days. Preoperatively, 13 % of patients underwent allergy testing. 94 % saw an Allergist postoperatively. 21 % required follow up surgery., Conclusions: A team approach of Otolaryngologists, Ophthalmologists, and Neurosurgeons is recommended for this slowly growing but locally destructive disease. Most patients with AFS will present with headaches and nasal obstruction. While most cases of AFS can be successfully managed with transnasal endoscopic techniques, orbitotomy and craniotomy represents an effective treatment for severe AFS cases with extensive intracranial and intraorbital involvement. This disease is found most commonly in young African American males and in the underinsured., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus -induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1β and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus -induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P =0.021) , hemorrhagic cystitis after transplantation ( P =0.012) , delayed platelet engraftment ( P =0.008) , and lower transplant mononuclear cell count ( P =0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P <0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.