Understanding hereditary hemorrhagic telangiectasia: From genetic anomalies to systemic manifestations, quality of life, and epistaxis management-Exploring the otolaryngologist's integral role.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber syndrome, is a rare autosomal dominant disorder characterized by vascular malformations. This comprehensive review aimed to provide an overview and summarize various aspects of HHT, including the genetic abnormalities, complications associated with visceral arteriovenous malformations (AVMs), prognosis of HHT, quality of life (QOL), and treatment of epistaxis. In addition, this review highlights the challenges in diagnosing HHT and emphasizes the critical role of otolaryngologists in the early detection of HHT. Otolaryngologists can refer patients with refractory epistaxis for AVM screening to expedite intervention. Mutation of the genes involved in the transforming growth factor-ß signaling pathway leads to the incidence of HHT, resulting in the formation of abnormal blood vessel formation. These vascular malformations commonly manifest as telangiectasia on the skin and mucous membranes; however, epistaxis remains the hallmark symptom of HHT. The impact of HHT goes beyond the visible symptoms and often includes the formation of life-threatening visceral AVMs in the lungs, liver, and brain. The prognosis of patients with HHT is closely related to the development of these complications, necessitating timely diagnosis and intervention. Refractory epistaxis diminishes the QOL of patients with HHT. The management of epistaxis ranges from conservative measures to advanced interventions such as prevention, conservative treatments, ablation, surgical procedures, and the administration of anti-angiogenic agents. However, effective management requires a multidisciplinary approach. The diagnosis of HHT remains challenging due to its variable presentation and lack of awareness among physicians. This review highlights the importance of reducing the duration between symptom onset and diagnosis. Otolaryngologists who are experienced in the management of refractory epistaxis can aid in identifying potential cases of HHT. They can facilitate the initiation of screening for visceral AVMs via prompt recognition of the signs and symptoms of HHT, contributing to improved patient outcomes. Early detection and intervention through screening can extend the life expectancy of patients with HHT to levels comparable with that of the general population. In conclusion, this review provides insight into various aspects of HHT and emphasizes the importance of timely diagnosis and intervention in the mitigation of the potentially life-threatening complications associated with this disorder. Otolaryngologists play a critical role in this process, serving as gatekeepers to the identification of cases of HHT and implementation of appropriate screening and management pathways, thereby improving the life expectancy and QOL of patients.

Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study.

OBJECTIVE: To determine if tokishakuyakusan (TSS) is effective for treating post-infectious olfactory dysfunction (PIOD) compared with vitamin B12 (mecobalamin). METHODS: We conducted a randomized, nonblinded clinical trial. Patients with PIOD enrolled in 17 hospitals and clinics from 2016 to 2020 were randomly divided into two groups, and we administered TSS or mecobalamin for 24 weeks. Their olfactory function was examined using interviews and T&T olfactometry. The improvement of olfactory dysfunction was assessed following the criteria of the Japanese Rhinologic Society. RESULTS: Overall, 82 patients with PIOD were enrolled in this study. In the TSS and mecobalamin groups, 39 patients completed the medication regimen. In the TSS and mecobalamin groups, olfactory dysfunction was significantly improved based on self-reports and olfactory test results. The improvement rate of olfactory dysfunction was 56% in the TSS group and 59% in the mecobalamin group. Early intervention within 3 months produced a better prognosis than the treatment initiated after 4 months. Furthermore, age and sex differences were not observed. Both medications produced no severe adverse events. CONCLUSION: The present study showed that TSS and mecobalamin might be useful for treating PIOD.

Percutaneous Transluminal Angioplasty and Stenting for Progressive Intracranial Carotid Artery Stenosis Secondary to Invasive Sphenoid Sinus Aspergillosis: A Case Report.

We report a case of invasive sphenoid sinus aspergillosis with progressive internal carotid artery (ICA) stenosis and contralateral carotid occlusion that was successfully treated with percutaneous transluminal angioplasty and stenting (PTAS). A 70-year-old man presented with right-sided visual disturbance, ptosis, and left hemiparesis. Magnetic resonance imaging of the head revealed a space-occupying lesion within the sphenoid sinus with infiltration of the bilateral cavernous sinuses, right ICA occlusion, and multiple watershed cerebral infarcts involving the right cerebral hemisphere. The patient was diagnosed with invasive sinus aspergillosis based on transnasal biopsy findings. Despite intensive antifungal therapy using voriconazole, rapidly progressive aspergillosis led to a new stenotic lesion in the left ICA, which increased the risk of bilateral cerebral hypoperfusion. We performed successful PTAS to prevent critical ischemic events. Finally, aspergillosis was controlled with voriconazole treatment, and the patient was discharged. He showed a favorable outcome, with a patent left ICA observed at a 3-year follow-up. PTAS may be feasible in patients with ICA stenosis and invasive sinus aspergillosis.

Paranasal Schwannomas: A Comprehensive Study of 2 Cases.

Paranasal sinus tumors are a heterogeneous group of neoplasms (with paranasal schwannomas being a rare subtype) that are often present with non-specific symptoms, such as nasal obstruction and epistaxis. Thus, early diagnosis is crucial for optimal management. This study presents 2 cases of paranasal schwannomas, detailing their clinical presentation, diagnostic methods, and treatment approaches. Both patients underwent endoscopic sinus surgery with successful tumor excision and had no significant complications or recurrences during follow-up. Diagnosis was based on a combination of clinical examination, radiological imaging (computed tomography and magnetic resonance imaging), and histopathological confirmation with immunohistochemical staining. Treatment consisted primarily of endonasal resection, with consideration of frontal craniotomy if necessary. This study aims to contribute to the understanding of paranasal schwannomas and emphasizes the importance of early detection and treatment to improve patient outcomes.

Buccal Abscess Caused by Toothbrush Trauma: A Case Report of a Two-Year-Old.

Children often experience impalement trauma when they fall while holding objects in their mouths. While most cases heal without complications, here we report a case of buccal abscess formation after toothbrush trauma. A two-year-old boy fell while running with a toothbrush in his mouth, which punctured his right buccal mucosa. The following day, he presented to a pediatrician with a fever and buccal swelling and was treated with oral antibiotics. However, the buccal swelling did not improve, and the patient was referred to our department. Four days after the visit, the buccal swelling and fever worsened, requiring hospitalization, intravenous antibiotics, and drainage. The inflammation quickly disappeared following treatment, with no recurrence. Prophylactic antibiotic administration for oral impalement trauma is controversial. Our results suggest that prophylactic antibiotics covering both anaerobic and aerobic bacteria are necessary in cases of toothbrush-related oral trauma, where multiple bacterial infections may occur.

S100A8 enhances IL-1ß production from nasal epithelial cells in eosinophilic chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. METHODS: We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. RESULTS: S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1ß secretion in human nasal epithelial cells. CONCLUSIONS: Our data demonstrate that S100A8 results in production of interleukin-1ß in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Pseudo-malignant paranasal invasive aspergillosis showing bone destruction and FDG uptake on PET/CT: A case report.

RATIONALE: Aspergillosis is a rare disease that often occurs in patients with diabetes mellitus or compromised hosts. This study describes a 60-years-old woman with unusual pseudo-malignant paranasal invasive aspergillosis with 18F-fluorodeoxyglucose (18F-FDG) uptake treated by endoscopic sinus surgery. To the best of our knowledge, there are few reported cases of paranasal fungal infection with 18F-FDG uptake. PATIENTS CONCERNS: A 60-years-old woman was presented with headache and nasal obstruction. DIAGNOSES: Computed tomography (CT) showed a shadow with bone destruction in the sinus cavity and accumulation of 18F-FDG uptake. The patient was diagnosed with a malignant tumor or pseudo-malignant paranasal invasive aspergillosis. INTERVENTIONS: The patient underwent endoscopic sinus surgery; no neoplastic lesions were detected in the areas with CT shadows. All the observed fungal mass reservoirs were removed. OUTCOMES: The patient remained hospitalized for 1 week after the surgery with no significant postoperative abnormalities. There was no recurrence of the disease for 6 months, and the patient's symptoms resolved, indicating a good course of follow-up. LESSONS: Invasive aspergillosis should be considered a differential disease when positron emission tomography (PET)/CT scans show FDG uptake, CT shows bone destruction, and T2-weighted MRI scans show a low signal.

Co-Treatment with Steroid and Dupilumab for Eosinophilic Chronic Rhinosinusitis after Eosinophilic Pneumonitis Caused by Dupilumab.

Eosinophilic chronic rhinosinusitis (ECRS) is a Type 2 inflammatory disease that manifests as chronic inflammation of the paranasal sinus. IL-4/IL-13 receptor monoclonal antibodies (dupilumab) to suppress Type 2 inflammation have become a good treatment option for patients who are refractory to surgery. Most patients respond normally, although significant side effects such as eosinophilic pneumonia may occur, requiring discontinuation of dupilumab. Here, we present a case in which dupilumab administration caused a side-effect of eosinophilic pneumonia. A 65-year-old woman presented with nasal obstruction and olfactory dysfunction due to a nasal polyp. Her symptoms temporarily improved with dupilumab; however, dupilumab was discontinued due to eosinophilic pneumonia. Discontinuation of dupilumab resulted in the rapid resolution of eosinophilic pneumonia and reappearance of nasal polyps. We, therefore, resumed dupilumab treatment in combination with low-dose steroids; eosinophilic pneumonia did not flare up, and the nasal polyps shrank steadily. There is no established treatment strategy in cases where a side effect of eosinophilic pneumonia arises while treating ECRS with dupilumab. Based on the described case, we recommend that a combination of a low-dose steroids and dupilumab be considered as a treatment option to counter the side-effect of eosinophilic pneumonia induced by dupilumab alone.

Organized Hematoma after Intra-Arterial Chemoradiotherapy for Maxillary Sinus Cancer: A Case Report.

An organized hematoma (OH) is a relatively rare benign lesion of the paranasal sinuses. Traditionally, it has been reported to occur following trauma, surgery, and sinus hemorrhagic lesions and in various bleeding predispositions. OHs are sometimes difficult to differentiate from malignancy because of the similar clinical symptoms and bone destruction. It is especially difficult when OHs occur in the same location as the primary tumor after treatment of a malignant tumor. In this paper, we report two cases of OH that occurred after intra-arterial chemoradiotherapy (IACRT) for maxillary sinus cancer. In one case, FDG accumulation was found in PET/CT and suspected to be a cancer recurrence. However, the postoperative pathology showed no malignant findings. This suggests that OH may show accumulation on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). In both cases, bleeding from the maxillary sinus continued after surgery. In one case, recurrence was observed, and in the other, nasal irrigation prevented the pooling of blood in the maxillary sinus, and no recurrence was observed. These cases suggest that OH after IACRT may easily recur because the bleeding continues even after surgery. In such cases, nasal irrigation or preoperative embolization may be helpful to avoid recurrence.

Validation of epistaxis severity score for hereditary hemorrhagic telangiectasia in Japan.

OBJECTIVE: This study aimed to assess the health-related QoL (HR-QoL) of patients with hereditary hemorrhagic telangiectasia (HHT), with emphasis on the role/social aspects, and validate the Japanese version of the epistaxis severity score (ESS) in these patients. METHODS: The Japanese version of the ESS was created through forward and reverse translation, and consultation with the original author. A validation analysis was performed by comparing ESS severity with the invasiveness of previous treatments for epistaxis and assessing the correlation between the ESS and HR-QoL. Medical history forms, ESS questionnaires, and the Medical Outcomes Study Short Form 36 (SF-36) were distributed to participants with HHT in August 2020. The relation between the ESS and summary scores of SF-36 was assessed by performing analysis of variance and Spearman's correlation. RESULTS: In total, 73 participants were included in this study. The average ESS was 5.02; there were mild (32.9%), moderate (45.2%), and severe (21.9%) epistaxis groups. Patients with higher ESS received a significantly more invasive treatment (Fisher's exact test, p < 0.05). The ESS was also negatively correlated with the physical component score (PCS) (r = -0.489, p < 0.001). Comorbid liver and gastrointestinal arteriovenous malformations significantly reduced the PCS (p < 0.05). Multiple regression analysis revealed that the ESS was a significant variable (p < 0.01). The role/social component score was significantly lower in the severe ESS group than in the mild or moderate group. CONCLUSION: The Japanese version of the ESS was considered valid and may be useful as an outcome measure of future HHT-associated epistaxis trials in Japan.

A Case of Endonasal Endoscopic Surgery for Intraorbital Metastasis of Gastric Ring Cell Carcinoma.

Gastric signet ring cell carcinoma has well-known metastatic features, including peritoneal dissemination and carcinomatous lymphangitis of the lung, but no intraorbital metastases were reported previously. A woman in her 60s developed left eye pain, sudden vision loss, and headache 12 years after gastric cancer treatment. Symptoms did not improve despite steroid pulses. Craniotomy showed no malignant findings. The patient was referred to our department for symptomatic relief and biopsy due to the lack of a definitive diagnosis and no improvement in her ocular pain. Endonasal endoscopic surgery was performed for diagnostic purposes and to relieve symptoms through orbital decompression. Preoperative computed tomography examination revealed a tumor at the left medial orbit, extending to the orbital apex. Orbital decompression through the open left medial orbital wall was performed with biopsy of the intraorbital tumor. Pathological findings were consistent with metastatic signet ring cell carcinoma. Pain and subjective improvement of visual acuity were noted the day after surgery. Twelve months postoperatively, diplopia remains, but there has been no worsening of symptoms.

Skull Base Metastasis of Breast Cancer With Oculomotor and Trochlear Nerve Palsy.

Skull base metastatic tumors are rare. Breast cancer in particular can cause bone metastases after a long period of time. A 70-year-old woman presented with multiple cranial nerve palsy. Magnetic resonance imaging revealed a lesion that extended from the orbit to the base of the skull, and the patient was referred to our department. Ophthalmological evaluation showed left visual acuity impairment, left oculomotor nerve palsy, and left trochlear nerve palsy. Endoscopic biopsy performed 5 years after the completion of breast cancer treatment revealed skull base metastases. In unilateral multiple cranial nerve palsy, the possibility of skull base metastases should be considered.

Isolated sphenoid sinus opacification is often asymptomatic and is not referred for otolaryngology consultation.

Isolated sphenoid sinus opacifications (ISSOs) are clinically important because they can lead to serious complications. However, some patients with ISSOs are asymptomatic, and not all patients are properly referred to the otolaryngology department. Because past studies of ISSOs focused only on patients who received treatment, in this study we selected ISSO cases based on radiology reports, then determined whether these patients had symptoms and were appropriately referred for specialty care. We conducted a retrospective analysis of data collected from patients who underwent computed tomography or magnetic resonance imaging from January 2007 to March 2017 at Osaka General Medical Center. We searched for the terms "sphenoid" or "sphenoidal" using F-REPORT to identify patients who had a sphenoid disease. We checked all selected images and diagnosed ISSOs. Examination of 1115 cases revealed 223 cases of ISSOs, of whom 167 (74.9%) were asymptomatic. We categorized patients with ISSOs into four groups: inflammation, mucocele, fungal diseases, and unclassifiable; the final category was used when edges were irregular or complete opacity was encountered. In the unclassifiable group, the majority of cases required otolaryngology consultation, but 37 of 47 unclassifiable patients did not have an otolaryngology visit. ISSOs are often identified by chance on imaging tests performed by non-otolaryngologists. However, our study revealed that many patients with ISSOs who should be treated by otolaryngologists were not referred to the otolaryngology department. Accordingly, it is important to promote awareness of the disease among other types of clinicians.

An Unusual Case of Maxillary Sinus Cholesterol Granuloma Showing FDG Uptake on PET/CT.

ABSTRACT: Cholesterol granuloma (CG) occurs primarily in the middle ear and rarely in the paranasal sinus. We report an unusual case of paranasal sinus CG with 18F-FDG uptake. A 76-year-old man presented with right refractory epistaxis. PET/CT showed FDG uptake in the maxillary sinus. CT findings are typically uncharacteristic, whereas MRI scans are characterized by a high signal on both T1-weighted and T2-weighted images. Nasal endoscopy from the ostium revealed a granulomatous lesion with hemorrhage at the base of the maxillary sinus. After pathological examination by endoscopic sinus surgery, the patient was diagnosed with CG.

[Two Cases of Venous Malformation of the Orbit Treated by Endoscopic Endonasal Surgery].

Venous malformation of the orbit(VMO), previously called orbital cavernous hemangioma, has been classified as a vascular malformation according to the International Society for the Study of Vascular Anomalies. Among various surgical approaches for VMO, endoscopic endonasal surgery(EES)has recently been developed, especially for those in the inferomedial quadrant of the orbit. Two 67-year-old and 69-year-old women presented with decreased visual acuity and visual field deficit, respectively. Their CT and MRI scans revealed retrobulbar masses, suggestive of the inferomedial type of VMO. The first case was diagnosed as an intraconal VMO, and subtotal removal was achieved through binostril EES using a two-surgeon four-handed technique after palliative partial resection through a prior frontal craniotomy. In the second case, diagnosed as an extraconal VMO, total en bloc removal was achieved using the same surgical technique as above. In both cases, the visual functions improved after the procedures, with uneventful postoperative courses. Although the inferomedial VMO is an uncommon type, EES is well indicated for this condition. The international consensus of surgical techniques and staging from a surgical point of view should be established in the near future.