Coronavirus disease 2019 (COVID-19), a respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a worldwide pandemic in over 200 countries.

The nasal epithelium is enriched in angiotensin-converting enzyme 2 (ACE2) proteins, the key cell entry receptors for SARS-CoV-2, serve as the first barrier to protect the airway tract from viral infection. Recent studies have demonstrated detection of higher viral loads in the nasal cavity than in the pharynx of patients with COVID-19, and otolaryngologists should carefully consider the treatment of nasal conditions to prevent infection in clinical practice. Moreover, several studies have indicated that anosmia is one of the clinical characteristics of COVID-19, though its prevalence and mechanism remain unclear. Thus far, the comorbidity of allergic rhinitis does not seem to be a major risk factor for the severity of COVID-19. However, we should develop strategies in clinical practice for the treatment of nasal diseases such as allergic rhinitis during the pandemic.

This review summarizes the association between coronavirus disease (COVID-19) and allergic diseases. Allergic rhinitis and COVID-19 share common clinical symptoms as well as differences, which necessitates differentiating the two diseases when patients with allergic diseases have COVID-19. In patients who have bronchial asthma and COVID-19, the respiratory function is reduced. Typically, in patients with allergic diseases, the production of Th2 cytokines is dominant over that of Th1 cytokines. Hence, asthmatic patients with COVID-19 may be less likely to experience Th1 cytokine storms. However, these conclusions remain controversial. Anti-IgE antibody drugs, which are indicated for the treatment of Japanese cedar pollinosis, are also found to have antiviral activity. The mechanism of olfactory dysfunction in COVID-19 and the associations between severe acute respiratory syndrome coronavirus 2 viral titer and olfactory dysfunction have also been discussed in detail in this review.

Allergic rhinitis is commonly treated by pharmacotherapies, such as corticosteroids, antihistamines, and leukotriene receptor antagonists. However, pharmacotherapies are not causal treatments for allergic rhinitis. Allergen immunotherapy is the only causal treatment that induces long-lasting tolerance to allergens and prevents further allergen sensitization. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are frequently administered forms of allergen immunotherapy. Recent studies have reported that SLIT is an effective treatment for allergic rhinitis and a safe alternative to SCIT. Moreover, the percentage of regulatory T cells (Tregs) in the peripheral blood is increased by SLIT. Treg cells are mainly classified into two main groups: 1) CD4⁺ CD25⁺ Foxp3⁺ T cells (Foxp3⁺ Treg cells) and 2) IL-10-producing Foxp3^– CD4⁺ T cells (type 1 regulatory T [Tr1] cells). Recently, we demonstrated that the numbers of Foxp3⁺ Treg cells and Tr1 cells in peripheral blood were significantly increased by SLIT and that the SLIT-induced cell proliferation suppressed allergic reactions. Here, we have reviewed our current understanding of the immune mechanisms responsible for induction of Foxp3⁺ Treg cells and Tr1 cells by SLIT and the immune-suppressive role of Foxp3⁺ Treg cells and Tr1 cells in SLIT. Analysis of the mechanisms underlying the induction of Foxp3⁺ Treg cells and Tr1 cells and a search for compounds that induce the proliferation of cells may lead to the development of more efficient SLIT.

Stromal cells, including various immune cells, fibroblasts and endothelial cells dynamically interact with tumor cells in the tumor microenvironment (TME) and play an important role in tumor progression. Tumor-associated macrophages (TAM) represent a major component of the TME. TAMs are known to originate in the bone marrow; however, recent accumulating evidence indicates that tissue-resident macrophages are derived from primitive yolk sac precursors. Tumor-infiltrating TAMs show pro-tumoral features, including promotion of immunosuppression, angiogenesis, and tumor invasion. Based on these features, infiltration of TAMs and gene expression of TAM-related genes are considered potential biomarkers for diagnosis and prognosis of cancers. Moreover, TAM-targeting therapies, including reprogramming of TAMs, limiting recruitment, and promoting phagocytosis have attracted attention as new strategies of cancer immunotherapy. Clinical trials that target TAMs are currently underway. Further evidence is necessary to verify the potential and superiority of TAM-targeting therapies as an important component of cancer immunotherapy.

Descending necrotizing mediastinitis is a severe life-threatening disease with a high mortality rate that requires systemic management, including antibiotics, and prompt and accurate surgical intervention. We present 22 patients (12 men and 10 women) who were treated for descending necrotizing mediastinitis between 2008 and 2019 in our hospital. Their median age was 61 years (range: 41–85 years). Nine patients had diabetes mellitus, but 13 patients did not have an underlying disease causing immunocompromise. Regarding drainage, all patients underwent transcervicotomy. Mediastinal drainage was performed in 2 out of 10 cases of type I, 1 out of 3 cases of type IIA and 7 out of 9 cases of type IIB, all by thoracoscopic drainage. Thoracoscopic mediastinal drainage was considered useful because of its progress-specific approach and the possibility of minimally invasive, appropriately positioned drainage. There were some cases in which initial surgery alone did not result in a cure, and multiple surgical treatments were performed. Appropriate postoperative evaluation using computed tomography with the possibility of reoperation in mind is essential.

Deep neck abscesses may cause dysphagia as a late complication. We retrospectively reviewed the charts of 28 patients who underwent surgery for deep neck infections between July 2012 and April 2019 at the Department of Otolaryngology at Gifu University Hospital to investigate the role of swallowing rehabilitation and surgery in improvement of swallowing function in these patients. Patients’ age range was 19 to 85 years (61±17 years) with a male:female ratio of 17:11. Deep cervical infections were classified as follows: stage 1: 7 cases, stage 2: 5 cases, stage 3: 12 cases, and stage 4: 4 cases. Dysphagia occurred in 10 patients (35.7%). The Hyodo scores ranged from 5 to 11 points (8.0±2.0), and the Penetration Aspiration Scale scores ranged from 1 to 7 points (6.0±2.5). A high serum C-reactive protein level (p=0.003) and tracheostomy (p=0.038) were identified as risk factors. Of the 10 patients with dysphagia, 5 and 4 patients showed improved swallowing function after rehabilitation and surgical intervention, respectively. The mean length of hospitalization was longer in the dysphagia group than in the non-dysphagia group (69 days vs. 17 days, p<0.001). Dysphagia occurred in patients with severe deep cervical abscesses, who underwent tracheostomy; however, our results suggest that swallowing function could recover, following swallowing rehabilitation and surgical intervention.

Introduction: Eosinophilic chronic rhinosinusitis (ECRS) is a common disease that recurs easily but often difficult to treat. Recently, sensitization to Staphylococcus aureus and fungi in pathophysiology of ECRS has been reported. S. aureus is known to secrete several toxins including, enterotoxins which exhibit super antigenic activity. Studies have implicated that triggering of Type 2 inflammation by this bacterium is an important pathogenic factor in endotype of ECRS. Though several reports have explored the relationship between Type 2 inflammation and S. aureus secreted enterotoxins (SE), only a few have documented sensitization to SE in ECRS within clinical settings.

In this study, we examined the sensitization to SE-IgE in blood from patients with ECRS. The baseline characteristics of patients in specific SE-IgE positive and negative groups, were studied along with the clinical course of SE-IgE positive case having moderate and severe ECRS.

Subjects: Forty-eight patients with ECRS at the outpatient clinic at the Department of Otorhinolaryngology, General Hospital, Kansai Medical University, Osaka, Japan were included. Specific SE-IgE levels from blood samples were measured in all.

Period: August 1, 2019 to December 31, 2019

Methods: Patients were divided into two groups: SE-IgE positive and SE-IgE negative. At the time of initial diagnosis, the sensitization rate to serum SE-IgE ([enterotoxinA, B(SEA, SEB)] and, to potential inhalant allergens (such as pollen, fungi, mites, insects; ImmunoCAP > Class 1) were examined. In addition, total IgE levels and eosinophil count from peripheral blood, sinus computed tomography score, percent force expiratory volume were also measured. The obtained values and the clinical course of patients, were compared between the two groups. Based on the severity classification of ECRS, any significant differences in the sensitization rate between the groups were also analyzed.

The post-operative clinical course of refractory patients with moderate and severe ECRS who were positive for specific SE-IgE with or without systemic steroid administration or introduction of biologics were also studied. The postoperative clinical course of SEA/SEB positive cases at our hospital was examined too.

Results: SE-IgE positive group had elevated levels (p<0.05) of total IgE and blood eosinophil counts, and presented with severe form of ECRS. This group also showed more sensitization to multiple allergens; however, these were not significantly different between severe, moderate, and mild cases. The number of patients who required systemic steroids within 1 year after surgery was significantly higher in the SE-IgE group. In addition, as compared to SEB-positive patients, the post-operative lower airway management in SEA-positive patients were more complicated, and were more likely to have received systemic steroids earlier. Therefore, it can be concluded that specific SE-IgEis a good clinical indicator of refractory cases of ECRS and post-operative lower airway management.

Emedastine fumarate-containing tape (trade name: Aresaga Tape) has been on the market since April 2018, and its use as a transdermal patch has become widespread. Regarding antihistamine medications for patients with allergic rhinitis, we investigated the patients’ satisfaction and usage rate of this transdermal patch. Emedastine fumarate-containing tape (4 mg) was administered to 49 patients (26 males and 23 females) with allergic rhinitis who were taking antihistamines during outpatient visits for four weeks. A questionnaire survey was conducted on the usage and the stability of the symptom-suppressing effects of the patches.

It was found that the patients that were more than satisfied were 88.7% with regard to usability, 92.4% with regard to ease of continuation, and 83.0% with regard to satisfaction with the effects of the patch.

The frequencies of the patients forgetting to apply the patches over four weeks were: 73.5% for “None”, 18.8% for “1 to 3 days”, and 7.5% for “4 to 7 days”, and on the other hand, the frequencies of the patients forgetting to take the antihistamine drug over four weeks were: 43.4% for “None”, 33.9% for “1 to 3 days”, and 15.0% for “4 to 7 days”. The patch was therefore found to have significantly better medication compliance.

When we evaluated the presence or absence of diurnal variation in the effects of the patch, the frequencies of “feeling that the drug was not working in the day” were 69.2% for “none”, 19.2% for “somewhat”, and 11.5% for “sometimes”.

It was suggested that the use of antihistamine patches for patients with allergic rhinitis had good patient satisfaction, medication compliance, and stable symptom-suppressing effects.

The drug susceptibility was retrospectively examined for the so-called three major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). Isolates were identified in otorrhea, myringotomy fluid, nasal discharge, pharyngeal specimens, etc., taken from otorhinolaryngological patients with acute exacerbations of infectious diseases who visited my clinic over the past 10 years.

Looking at the susceptibility of the three major strains against aminobenzylpenicillin (ABPC), M. catarrhalis is almost 100% resistant due to production of β-lactamase in all strains, and the low susceptibility rate of H. influenzae is increasing gradually from ~70%. In contrast, the resistance of S. pneumoniae is decreasing.

The susceptibility rate of H. influenzae is increasing not only against ABPC, but also against tosufloxacin (TFLX) and tebipenem pivoxil (TBPM-PI), which are considered to be highly effective agents. All 81 H. influenzae strains detected in 2020 were CDTR-PI-resistant.

Actinomycosis is a chronic suppurative disease caused by the Actinomyces species. We treated two patients with actinomycosis occurring in the hypopharynx and epiglottis, respectively.

Case 1: A 74-year-old man presented to our university hospital complaining of hoarseness, dysphagia, and sore throat. He had been taking methotrexate for the treatment of rheumatoid arthritis. Endoscopic examination revealed a mass with an ulcerative lesion in his right pyriform sinus. Positron emission tomography–computed revealed ¹⁸F-fluorodeoxyglucose accumulation in the hypopharynx, right cervical lymph node, left upper lobe of the lungs, and right adrenal gland. Endoscopic biopsy revealed a histopathological diagnosis of hypopharyngeal actinomycosis. Methotrexate treatment was discontinued, and the patient was treated with intravenous ampicillin for 6 weeks, oral amoxicillin for 2 weeks, and oral clindamycin for 10 months. All lesions were eliminated, and no recurrence was observed during the 3-month follow-up period.

Case 2: A 64-year-old man presented to our university hospital complaining of sore throat and halitosis. Endoscopic examination revealed a mass with an ulcerative lesion in the epiglottis. Endoscopic biopsy revealed a histopathological diagnosis of laryngeal actinomycosis. The mass decreased in size one week after the biopsy. The patient was treated with oral amoxicillin for 3 months. Laryngeal actinomycosis was eliminated, and no recurrence was observed during the 15-month follow-up period.

We report a case of post-streptococcal reactive arthritis (PSReA) and its management in a 39-year-old woman who presented to the emergency outpatient department of our hospital with fever and pharyngitis on Y–17 days in month X. Physical examination revealed pus adherent to the palatine tonsils; therefore, the patient was prescribed oral amoxicillin for a diagnosis of bacterial tonsillitis and was instructed to return home. However, she observed persistent fever and pharyngitis 1 week before day Y of month X and returned to our department with generalized arthritis. Physical examination showed disappearance of the pus adherent to the palatine tonsils, and routine blood test results showed only a slightly elevated white blood cell (WBC) count. Her serum C-reactive protein and anti-streptolysin O (ASO) levels were within normal limits, and the rapid strep test result was negative. In light of the patient’s severe pharyngitis and arthritic symptoms, we measured serum complement levels to screen for possible acute rheumatic fever (ARF), and the patient was prescribed analgesics. However, on day Y+5 of month X, the patient returned with severe sore throat and neck pain. Blood test results showed only a slightly elevated WBC count and a negative erythrocyte sedimentation rate. However, the ASO titer was elevated, and the patient was diagnosed with PSReA based on the development of arthritic symptoms approximately 10 days after a hemolytic streptococcal infection. The symptoms and laboratory test findings observed in PSReA are often indistinguishable from those of ARF; however, the inflammatory response and erythrocyte sedimentation rate elevation are milder than these findings observed in patients with ARF, and cardiac complications are not known to occur. Therefore, PSReA and ARF are categorized as distinct entities. Nonetheless, otolaryngologists should consider PSReA in the differential diagnosis in patients with hemolytic streptococcal tonsillitis/pharyngitis, which is frequently encountered in routine medical practice.

We report two cases of eosinophilic granulomatosis with polyangiitis (EGPA) that acutely developed postoperatively in patients with eosinophilic chronic rhinosinusitis (ECRS).

A 74-year-old man with nasal obstruction was diagnosed with moderate ECRS (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis [JESREC] score 13 points; peripheral blood eosinophils 6.0%, bronchial asthma [+]) and underwent bilateral endoscopic sinus surgery (ESS, type IV) in December 20xx. The patient’s sinonasal symptoms improved without recurrent polyps for 9 months after ESS. However, during the 10th month after ESS, he observed sudden onset of purpura and reduced leg muscle strength along with numbness. Laboratory investigations revealed significant eosinophilia (58.5%, 11,296/μL). A nerve conduction study revealed mononeuritis multiplex with axonal disorder involving the right median, tibial, and sural, as well as the bilateral peroneal nerves. Therefore, he was definitively diagnosed with EGPA.

A 45-year-old woman with anosmia was diagnosed with moderate ECRS (JESREC score 15 points; peripheral blood eosinophils 11.4%, bronchial asthma [+]) and underwent bilateral ESS (type IV) in May 20xx. The patient’s sinonasal conditions were maintained without recurrent polyps for one year postoperatively. She had sudden onset of generalized fatigue and arthralgia, 13 months after ESS, and laboratory investigations showed significant eosinophilia (46.5%, 9,984/μL). Echocardiography revealed hypokinesia of the posterior wall of the left ventricle, apical thickening, and pericardial effusion. Histopathological evaluation of a myocardial biopsy specimen showed significant eosinophilic infiltration in the myocardial connective tissues leading to a definitive diagnosis of eosinophilic myocarditis and EGPA.

Thorough clinical evaluation is warranted for diagnosis of EGPA in patients with ECRS, who present with severe eosinophilia, muscle weakness, numbness, and skin lesions.