Sublingual immunotherapy (SLIT) was first reported for perennial allergic rhinitis by Scadding in 1986. We conducted the SLIT open study in cedar pollinosis between 2000 and 2003 with the approval of the Ethics Committee of Nippon Medical School. In 2004, a double-blind comparative study on SLIT for cedar pollinosis was conducted by the Ministry of Health, Labour and Welfare (MHLW) as part of the Immunology Research Project funded by the Grant-in-Aid for Scientific Research on Immunological Diseases (Grant-in-Aid for Scientific Research on Immunology). In 2005, we reported that SLIT was effective against cedar pollinosis during heavy cedar pollen dispersal. The efficacy of SLIT for cedar pollinosis, which has already become a common treatment, is clear. We also reported the post-effect of SLIT on actual drugs after 3 years of SLIT in tablet form in a double-blind, controlled study; we found differences in IgE and IgG4. Further studies on the production of these antibodies are required.

In 1991, a humanized monoclonal antibody rhuMAbE25 (omalizumab) was developed, which has specificity for Cε3, the receptor to which human IgE binds to Fcε receptor I. It is currently indicated worldwide for severe bronchial asthma and severe urticaria. Clinical trials on omalizumab for cedar pollinosis began in 2002. In 2018, a clinical trial was conducted for severe cedar pollinosis resistant to existing therapies. The antihistamine and nasal spray steroid significantly improved nasal and ocular symptom scores over placebo in patients with severe cedar pollinosis who remained symptomatic, leading the world to obtain a 2019 indication for omalizumab for severe hay fever. We will continue researching so that drug development can provide a new treatment method in general clinical practice.

Eosinophilic rhinosinusitis and allergic rhinitis are typical eosinophilic and allergic inflammatory diseases of the upper respiratory tract.

Eosinophilic rhinosinusitis is often recurrent even after surgery and is treated as a refractory disease. Moreover, eosinophilic sinusitis is known to be strongly associated with the innate immune response that induces type 2 inflammation without antigen sensitization. Epithelial-derived cytokines (TSLP, IL-25, IL-33) produced by epithelial cells are thought to induce large amounts of type 2 cytokine production via type 2 innate lymphoid cells (ILC2) and pathogenic memory Th2 cells, forming the characteristic histology of eosinophilic rhinosinusitis, including eosinophil infiltration, mucin production, and goblet cell hyperplasia.

Allergic rhinitis is a disease that affects almost half of the Japanese population. Allergen immunotherapy (AIT) has been shown to be highly effective in treating allergic rhinitis and is the only method that can be expected to provide long-term remission and cure. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cells. However, the mechanism by which AIT induces long-term remission has not been elucidated.

Both diseases are characterized by type 2 inflammation or IgE-dependent allergic inflammation, and managing these inflammations may lead to effective treatments.

This report describes the pathophysiology of eosinophilic chronic rhinosinusitis and novel mechanisms of AIT based on our studies.

Japanese cedar (JC) pollinosis is the most common type of seasonal allergic rhinitis (AR) prevalent in Japan, and the number of patients with JC pollinosis has markedly increased recently. Sublingual immunotherapy (SLIT) has been shown to significantly improve severe symptoms. In addition, SLIT can have a long-term effect despite discontinuation. Although most patients with AR respond favorably to SLIT, this therapy is ineffective in ~30% patients. Moreover, it can take ≥2 years to confirm the effectiveness of SLIT in treated patients. Therefore, an assay that identifies the treatment response of patients, as responders or non-responders prior to the implementation of SLIT, could be of great value. However, a predictive biomarker for SLIT efficacy is not available for patients with AR. We previously reported that amino acid changes in the allergen-binding pocket of HLA-DPβ1 were associated with sensitization to JC pollen, and subsequent development of JC pollinosis. This study aimed to investigate whether HLA-DPB1 gene is associated with SLIT responsiveness in patients with JC pollinosis. In total, 203 peak-symptomatic patients with JC pollinosis in the second season were considered eligible for the study; there were 160 responders and 43 non-responders. A non-responsive association with SLIT was observed among HLA-DPB1*05:01 carriers. Genotyping of HLA-DPB1 might serve as a predictive biomarker for response to SLIT among patients with JC pollinosis.

The intestinal environment, which is formed from dietary components and intestinal bacteria, plays an important role in maintenance of our health. Specifically, fatty acids in food are converted into functional lipid metabolites by mammalian or intestinal bacterial enzymes and affect various physiological functions, including the immune response associated with allergies and inflammatory diseases. Lipid metabolism is affected by several factors including enzymatic activity of our body, as well as the actions of intestinal microbiota. Differences in the degree of health benefits are attributable to disparities in the production of beneficial metabolites via intestinal environment. In this study, we describe the immunoregulatory mechanisms underlying lipid metabolite generation from omega-3 fatty acids. We have also discussed our recent findings regarding the development of a stratified and personalized nutrition system, considering inter-individual variations in the intestinal environment.

Based on the results of the CheckMate 141 trial, nivolumab, an antiprogrammed cell death-1 (PD-1) antibody, was approved for management of unresectable recurrent and/or metastatic head and neck cancer in Japan in 2017. Subsequently, pembrolizumab was approved in 2019 for treatment of the aforementioned cancer and is now widely used in clinical settings. This review describes the current status of immune checkpoint inhibitor therapy for recurrent and/or metastatic head and neck cancer.

Since the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was reported as a pneumonia of unknown cause in Wuhan, China in December 2019, its infection has spread worldwide. In Japan, the first case was reported on January 16, 2020, and although the number of infected people has increased and decreased with the emergence of mutant strains and outbreaks since then, prevention, infection control measures, and treatment, including vaccines, are being established. On the other hand, some patients with coronavirus disease 2019 (COVID-19) have been reported to experience various sequelae, the pathogenesis of which remains unclear, and there is no established treatment for these sequelae. Recently, the usefulness of epipharyngeal abrasive therapy (EAT), a treatment method for chronic nasopharyngitis, has been reported for this sequela, and therapeutic intervention by otolaryngologists for the sequela has been attracting attention.

We performed EAT on patients post-COVID-19 or with long COVID and conducted a questionnaire survey on subjective symptoms. As a result, 79.6% of patients showed improvement in subjective symptoms before and after EAT, and 20.4% of patients showed improvement of more than 70% of symptoms, while only 4.1% of patients were completely cured.

Since no clear treatment for post-COVID-19 or long COVID-19 has been established yet, and people are still experiencing the effects of COVID-19 in their social life, EAT is a simple and safe method that can be performed during routine medical treatment. It may also be an option for the treatment of post-COVID conditions. However, few patients are completely cured, and we hope that novel, more effective treatment methods will be elucidated in the future.

Eosinophil- and interleukin-5-targeted therapies are being utilized in clinical settings in recent years. It is important to understand the mechanisms underlying the behavior of eosinophils in vivo. Eosinophils are important etiopathogenetic contributors to otolaryngological diseases, such as allergic rhinitis, eosinophilic granulomatosis with polyangiitis, eosinophilic chronic rhinosinusitis, and eosinophilic otitis media. The recognition of programmed eosinophil death, which results in release of granule proteins and formation of extracellular traps and Charcot-Leyden crystals leads our research forward to gain deeper insight into the pathogenesis of eosinophil-mediated diseases.

The typical cedar pollinosis in Japan was first reported in 1964. In the 1980s, measures were taken to address the problem as a national issue. The treatment guidelines were developed for otolaryngologists and other medical specialists in 1993, and they have been revised and updated. More treatment types have arisen, indicating an increase in the prevalence and severity of hay fever. The effectiveness of sublingual cedar pollen immunotherapy is assured, and the range of indications has been expanded. Antigen pollen survey results mainly mention the cypress family, tree pollens such as birch and beech, herbaceous spring grass pollen, and autumn Asteraceae. Long-term survey results show that pollen fronts in the genus cedar are moving northwards. The number of Cupressaceae pollen collections is increasing nationwide with repeated annual fluctuations, correlating with higher temperatures due to climate change. The number of Fagaceae pollen collections is also increasing.

Hay fever has multiple target organs and has been considered a systemic disease since its discovery. Pollen food allergy syndrome (PFAS) have been attracting attention since around 2000. A high co-morbidity of birch pollinosis and food allergy to rosacea fruits has been reported in Hokkaido. In our department, located in Kyushu, a small number of cases diagnosed with PFAS were sensitized to Cupressaceae, Quercus spp., and Poaceae and induced by foods from Cucurbitaceae, Solanaceae, and Rosaceae families, showing regional differences.

Cultures of aerobic and anaerobic bacteria were analyzed in a case of unilateral sinusitis involving purulent nasal discharge with a foul-smelling odor emanating from one side of the middle nasal passage. The relationship between sinus lesions and dental infection was examined for the presence of dental maxillary sinusitis using cone-beam computed tomography. Seventy-two strains were isolated and identified from 50 cases.

Aerobic bacteria were found in 3 cases (3 strains) and microaerophilic Streptococci in 10 cases (10 strains). There were 59 strains of obligatory anaerobes, 78.8% of which were gram-negative rods (Fusobacterium nucleatum, 45.8%; Prevotella, 30.5%) and gram-positive cocci (Parvimonas, 22%). Based on a report by Japanese oral surgeons (Muroki, 1986), gram-positive Veillonella and Peptostreptococcus accounted for 80% and gram-negative bacilli Bacteroides accounted for 2.9%.

In addition, Kaneko (2015) reported that anaerobes are less common, while facultative anaerobic bacteria are more common. The reason for the apparent differences between the author’s data and historical data is that Fusobacterium and Bacteroides are oxygen-sensitive and take longer to form colonies, leading to gram-negative bacteria and a low detection rate if the culture conditions are not ideal. Fifty patients received a diagnosis of dental sinusitis. Dental infection, apical periodontitis, foreign bodies such as dental implants, and oroantral fistulae were diagnosed as the causes of dental maxillary sinusitis. In vitro antibacterial activity was favorable for CVA/AMPC in 3 kinds of bacteria, and purulent nasal discharge ceased in 22 of 25 patients treated with CVA/AMPC at the first visit.

Japanese cedar pollinosis is the most common seasonal disease in Japan and has been considered a national affliction. The predictions of the dispersion and counts of Japanese cedar pollen are important for self- and medical care. We previously reported models for predicting the first days of pollen dispersion and total pollen counts during the pollen dispersal seasons based on meteorological data for the past 20 years. However, there could have been changes in factors related to the environment, climate, and forest, among others. Therefore, we reconsidered that the use of data from the recent 10 years, rather than the past 20 years, would be more suitable for accurate predictions and verified the results obtained by the previous and newly constructed models. Regarding the predictions of the first days of pollen dispersion from 2011 to 2020, the mean differences between the actual day and the days predicted by the previous and new models were 2.40 and 2.00 days, respectively. Retrospective investigation of the total pollen counts from 2012 to 2022 showed that the correlation coefficients for the actual counts and those predicted by the new model (r=0.962) were higher than those for the previous model (r=0.922). In summary, the new prediction models based on the data collected over the recent 10 years more accurately predicted the first day of pollen dispersion and total pollen count than the previous models based on the past 20-year data. Therefore, prediction models should be updated periodically.

Most cases of otomycosis can be cured by topical treatment, but recently intractable types with progressive tympanic membrane perforation have appeared. Moreover, their characteristics are unknown. We present three cases of progressive tympanic membrane perforation secondary to otomycosis caused by aspergillus despite topical treatment. Each case presented different symptoms (otalgia, otorrhea, and itching) like normal otomycosis. There was no change in the score of β-D-glucan that would be expected with invasive fungal infection. We closed the perforation with oral antifungal medicine immediately after detection. Early invasive aspergillus otitis externa can be successfully treated with oral antifungal medicine without the need for surgical debridement, although in some cases it persists, resulting in bone exposure despite medical treatment.

Allergic fungal rhinosinusitis (AFRS) is a highly recurrent and refractory sinusitis with marked eosinophilic infiltration. This report described a case of AFRS, presenting with extensive cranial base bone defects on sinus computed tomography (CT) scan. This disease needs to be differentiated from invasive fungal sinusitis or a malignant sinus tumor. The patient was a 21-year-old male, who developed a severe headache and fever while receiving treatment for chronic sinusitis at another hospital. He visited the emergency department of a general hospital. Physical examination revealed exophthalmos, and the CT scan revealed bone defects in the anterior skull base, right orbital wall, and sphenoid sinus. The patient was, therefore, transported to our department as an emergency case, and subsequently, underwent an endoscopic sinus surgery under general anesthesia. A large fungal mass was found in the right posterior ethmoidal cells and the sphenoid sinus. Defects were also observed in the sphenoid sinus septum and the roof of the right posterior ethmoid sinus. Histopathological examination revealed eosinophilic mucin and fungi. Based on the absence of fungal infiltration into the sinus mucosa, the patient was diagnosed with AFRS. The CT scan showed the characteristic findings of bone remodeling, which are specific for AFRS. The patient was treated effectively with sphenoid sinus singularization and steroid nasal drop therapy in the suspended head position. Postoperative recurrence was not observed, and the patient is being followed up.

Bilateral facial nerve palsy is a rare condition accounting for approximately 5% of all facial palsies. Various systemic diseases may cause bilateral facial nerve palsy, one of which is sarcoidosis. Sarcoidosis is a systemic granulomatous disease that commonly affects the lungs, heart, and eyes, and may also involve the nervous system. The facial nerve is the most frequently affected cranial nerve in patients with neurosarcoidosis, with 40–60% of cases manifesting with facial paralysis.

A 50-year-old man presented with right-sided facial weakness and consulted another hospital the next day. Bell’s palsy was diagnosed and treated with prednisolone. However, a week later, the facial palsy extended to the left side of the face. He was admitted to our hospital and was diagnosed with bilateral facial nerve paralysis. We investigated the cause of bilateral facial nerve palsy but were unable to reach a conclusive diagnosis. Sarcoidosis was believed to be the cause of bilateral facial palsy, given the disease’s progression and the presence of bilateral hilar lymphadenopathy. He was given steroids, and his palsy improved five months later. This study highlights that the involvement of systemic disease should be considered in patients with bilateral facial nerve palsy.

Hard ticks (Acari: Ixodidae) may carry pathogens causing various infectious diseases. We report two cases of tick bites that presented with different clinical features.

The first patient is a 69-year-old woman who presented with vertigo. One week after mountain climbing, she developed general fatigue, headache, high fever, vertigo, and a generalized rash. She was suspected of having vestibular neuritis, and admitted to our institution. Blood tests revealed thrombocytopenia, and increased levels of C-reactive protein, aspartate aminotransferase, alanine transaminase, and lactate dehydrogenase. Upon consultation with the Department of Internal Medicine, she was suspected of having Japanese spotted fever. Her condition improved upon initiation of minocycline management. The diagnosis of Japanese spotted fever was confirmed via a polymerase chain reaction test of the eschar on her back, which was believed to be the spot where she was bitten.

The second patient is a 78-year-old woman who presented with right otalgia, one day after working in a bamboo forest. A white spherical mass attached to the external auditory canal entrance was observed. Due to the suspicion of a tick bite, she was referred to a dermatologist. The dermatologist noted the presence of a blood-sucking Amblyomma testudinarium on the right external auditory canal. The tick was completely removed.

Although tick bites are not commonly observed by otolaryngologists, these bites present with various pathologies. Thus, it is recommended to know the features and treatments of tick bites.