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Background: The prevalence of allergic rhinitis (AR) is increasing worldwide, mainly due to an increase in antigen exposure. We conducted an epidemiological study involving the staff of the University of Fukui Hospital and its associated hospital in 2006. There were 1540 participants aged ≥20 years, and the rates of Japanese cedar (JC) pollinosis and mite-induced perennial allergic rhinitis (PAR) were 36.8% and 15.8%, respectively. In 2016, we conducted a second survey. Methods: The rate of sensitization to JC pollen and mites and the prevalence of JC pollinosis and mite-induced PAR were analyzed based on data from questionnaires and antigen-specific immunoglobulin E (IgE) levels. Results: In the present study, we analyzed data of 1472 participants aged between 20 and 59 years. Total sensitization to JC pollen and total prevalence of JC pollinosis were 57.8% (851/1472) and 40.8% (601/1472), respectively. Total sensitization to mites and total prevalence of mite-induced PAR were 41.4% (610/1472) and 18.8% (276/1472), respectively. Total prevalence of JC pollinosis and mite-induced PAR increased significantly over a decade. Among the 334 people who participated in the 2006 and 2016 cross-sectional studies, 13% of JC pollinosis and 36% of mite-induced PAR experienced remission. However, since the number of new onset cases was higher that the number of remission cases, a slight increase in prevalence was observed over a decade. Conclusions: The prevalence of JC pollinosis and mite-induced PAR continues to show increasing trends, accompanied by an increase in antigen exposure. The remission rate of JC pollinosis was particularly low.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by diverse organ damages resulting from various autoantibodies, such as antinuclear or anti-DNA antibodies. Neuropsychiatric lupus (NPSLE) refers to the neurological and psychiatric disorders complicated with SLE and can be challenging for physicians to manage. NPSLE has a broad spectrum and high heterogeneity of clinical phenotypes, including headaches, psychiatric symptoms and peripheral neuropathy. Additionally, various immune effectors have been reported to contribute to the pathogenesis, including cytokines, cell-mediated inflammation and brain-reactive autoantibodies. In some patients with SLE, neuropsychiatric symptoms develop for the first time after the initiation of the steroid treatment, hindering the differentiation from steroid psychosis. The administration of high doses of steroids in patients with SLE is believed to trigger psychiatric symptoms. No clear evidence has yet been found regarding the treatment of NPSLE. Therefore, NPSLE-specific markers need to be developed, and treatment guidelines should be established. This article provides an overview of NPSLE as well as its pathogenesis and treatment.

Strategic Outlook toward 2030: Japan's Research for Allergy and Immunology (Strategy 2030) is the national research strategy based on Japan's Basic Law on Measures Against Allergic Diseases, a first of its kind worldwide. This strategy was established by a multi-disciplinary committee consisting of administrators of the Ministry of Health, Labour and Welfare of Japan, young and senior experts from various research societies and associations, and representatives of patient and public groups. Whereas the issues of transition, integration, and international collaboration have yet to be solved in this research realm in Japan, identification of unmet needs, digitization of information and transparent procedures, and strategic planning for complex problems (a process dubbed MIERUKA by the Toyota Way) are crucial to share and tackle the same vision and goals. The committee developed three specific actions focusing on preemptive treatment, interdisciplinarity and internationality, and life stage. The real success of Strategy 2030 is made by the spontaneous contributions of doctors, dentists, veterinarians, and other medical professionals; basic and clinical research scientists, research supporters, and pharmaceutical/medical device companies; manufacturers of food, healthcare, and home appliances; and patients, their families, and the public. The hope is to establish a stable society in which people can live long, healthy lives, as free as possible from allergic and immunological diseases, at each individual life stage. This article is based on a Japanese review first reported in Arerugi, introduces the developmental process and details of Strategy 2030.

Abstract Background Malrotation is a congenital anomaly during the development of the embryonic intestine. Although it is generally considered a pediatric surgical condition, it can have significant implications for adult surgery in terms of reconstruction. Case presentation The patient was an 85-year-old man with pancreatic cancer and intestinal malrotation. He underwent pancreaticoduodenectomy with modified Child’s reconstruction. Because the ascending colon and efferent loop twisted easily, we fixed the ascending colon to the abdominal wall. Thereafter, right twist and stenosis of the efferent loop occurred. On the 22nd day after the initial surgery, detorsion and Braun anastomosis were performed for efferent loop fixation. Postoperative oral intake was good, and the patient was discharged from our hospital on the 24th day after the reoperation. Conclusions This is a rare case of pancreaticoduodenectomy with malrotation following reoperation due to a complication after Child’s reconstruction. In similar cases of intestinal malrotation, it is important to consider avoiding coaxial positioning of intestinal parts and an upper abdominal space while selecting a reconstruction method.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today.To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.

Background: Oral allergy syndrome (OAS) is an immediate allergy caused by a cross-reaction of highly homologous common antigens (pan-allergens) contained in fruits/vegetables and pollen. Methods: A questionnaire was provided to 6824 outpatient visitors and serum levels of specific IgEs against crude antigens and pan-allergen components were measured to study the relationship between the prevalence of OAS and pollinosis in the Fukui Prefecture where there is almost no dispersal of birch pollen. Results: The prevalence of OAS was 10.8%. The rate of pollinosis complication in the OAS group was 67.4%, and OAS was observed in 16.8% of pollinosis patients. Causative foods in order of frequency were melon, pineapple, kiwi fruit, peach, and apple. A significantly higher number of patients from the OAS group were positive for birch, alder, and timothy grass-specific IgE. The rate of positivity for anti-component IgE corresponding to pollen in OAS group was also significantly higher. Of 34 patients with OAS caused by eating apples, 28 (82.4%) were positive for Mal d1-specific IgE. Of the 52 patients with peach-induced OAS, 41 (78.8%) were positive for Pur p1-specific IgE. The concordance rates between crude antigen-specific IgE and anti-PR-10 component-specific IgE were 87.1% and 93.3% for apple and peach respectively. Conclusions: In regions where birch pollen is not dispersed, OAS patients have a significant association with the onset of Bet v1-associated allergy. Anti-PR-10 component IgE was useful in diagnosing OAS, and crude antigen-specific IgE was also associated with apple and peach allergies. Keywords: Allergen component, LTP, Oral allergy syndrome, Pollen-food allergy syndrome, PR-10

Interleukin (IL)-4 and IL-13, signature type 2 cytokines, exert their actions by binding to two types of receptors sharing the IL-4R α chain (IL-4Rα). Since IL-4 and IL-13 play important and redundant roles in the pathogenesis of allergic diseases, blocking both the IL-4 and IL-13 signals would be a powerful and effective strategy for treating allergic diseases. Dupilumab (Dupixent®) is a fully human monoclonal antibody recognizing IL-4Rα and blocking both the IL-4 and IL-13 signals. Dupilumab was first prescribed for atopic dermatitis (AD) patients and has been widely approved for adult patients with moderate to severe AD since 2018. Dupilumab has since been used for asthma, receiving approval for uncontrolled asthma in 2019. A phase 3 study using dupilumab for chronic rhinosinusitis with nasal polyps (CRSwNP) has been just completed, with positive results. Several clinical trials of dupilumab for other diseases in which type 2 inflammation is dominant are now underway. It is hoped that dupilumab will open the door to a new era for treating allergic patients with AD, asthma, and CRSwNP, and for more patients with type 2 inflammations. Keywords: Asthma, Atopic dermatitis, Chronic rhinosinusitis with nasal polyps, Interleukin-4, Interleukin-13

IL-5 is the most potent activator of eosinophils and is produced by Th2 cells and ILC2s. A role for IL-5 in eosinophil extracellular trap cell death, i.e., a proinflammatory cell death, has also been reported. Mepolizumab and benralizumab are humanized mAbs that target IL-5 and the IL-5 receptor α, respectively, and their therapeutic efficacy for severe asthma has been established. Although consistent differences in the efficacies of those drugs have not been proven, benralizumab extensively depleted eosinophils via Ab-dependent cell-mediated cytotoxicity. Blood eosinophil count, but not FeNO or IgE, is the best-established predictive biomarker of the efficacy of anti-IL-5 treatment. Regarding the choice of biologics, the balance between blood eosinophil count and FeNO, indication of comorbidities, longitudinal safety, and interval of injection should be considered. Mepolizumab was also effective in maintaining the remission of refractory eosinophilic granulomatous polyangiitis. Moreover, mepolizumab decreased the proportion of patients who required surgery and lowered the nasal polyp score in patients with chronic rhinosinusitis with nasal polyps; a further extensive trial is currently under way. In a phase II benralizumab study performed in Japan, no significant effect on nasal polyp score at week 12 was observed, suggesting a requirement for longer treatment. In this review, the role of IL-5 in eosinophil biology and the current status of anti-IL-5 therapy are discussed. The longitudinal safety of anti-IL-5 therapy has been increasingly established, and this strategy will be continuously indicated for eosinophilic diseases as a specific treatment for eosinophilic inflammation. Keywords: Benralizumab, Chronic rhinosinusitis with nasal polyps, Eosinophils, IL-5, Mepolizumab

Abstract Background Intraperitoneal arterial hemorrhage without trauma is extremely rare. We report two infant cases of intraperitoneal arterial hemorrhage due to intestinal duplication. Case presentation In case 1, a 2-month-old girl experienced sudden intraperitoneal hemorrhage from the middle colic artery with no apparent trauma. Hemostasis was achieved with suturing of the hemorrhage point, but the cause of hemorrhage was still unknown. Computed tomography after the first operation revealed a duodenal duplication cyst and a pseudopancreatic cyst. Percutaneous drainage of the pseudopancreatic cyst was performed, and the contents had high pancreatic amylase. As the size of the duodenal duplication cyst also decreased with this drainage, we suspected that the duodenal duplication cyst was connected to the pseudopancreatic cyst and the arterial hemorrhage. We hypothesized that the pancreatic juice inside the duplication cyst leaked into the intraperitoneal cavity and caused rupture of the arterial wall. Therefore, marsupialization of the duodenal duplication was performed to evacuate the pancreatic juice contained in the cyst toward the native duodenum. The postoperative course was uneventful. In case 2, a 6-month-old boy experienced sudden intraperitoneal hemorrhage without trauma. The hemorrhage site was identified as the ileocecal artery, and hemostasis was achieved with sutures. Tissue near the hemorrhage point was biopsied, because the cause of arterial wall rupture was still unknown. The biopsied tissue was found to be intestinal mucosa. The patient had recurrent abdominal pain after the first operation, and computed tomography showed a duplication cyst located near the hemorrhage point. Therefore, we resected the intestinal duplication. Pathology results showed that the intestinal duplication contained intestinal mucosa, ectopic gastric mucosa, and pancreatic tissue. The postoperative course was uneventful. Conclusion Intraperitoneal arterial hemorrhage without trauma is an extremely rare condition, and identifying its cause is difficult. To our knowledge, this is the first report of intraperitoneal arterial hemorrhage due to intestinal duplication. In cases of unexplained intraperitoneal arterial hemorrhage in infants, intestinal duplication near the hemorrhage point should be suspected.

Background: There have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets. Methods: This was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (≥0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded. Results: The percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively. Conclusions: Dual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses. Keywords: Allergic rhinitis, Dual therapy, Immunological response, Safety, Sublingual immunotherapy

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated.Objective: To determine whether the serum levels of leptin are altered in patients with ECRS.Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient’s serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression.Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05).Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.