Development of an Oral Immunotherapy-Related Parental Burden Scale.

INTRODUCTION: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT-PB and verified its reliability and validity. METHODS: A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey. RESULTS: The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: "burden caused by adherence to treatment plan," "anxiety about symptom-induced risk," "burden due to patient's eating behavior," and "anxiety about treatment effect." The Cronbach's α for all 16 items of the OIT-PB was 0.893; Cronbach's α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720-0.937, p < 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422-0.747], p < 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306-0.687], p < 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the "anxiety about treatment effect" score (R = -0.355 [95% CI: -0.558-0.112], p < 0.001). Parents of children on the hen's egg OIT treatment scored higher on the "burden due to patient's eating behavior" subscale than did parents of children on the milk and wheat OIT treatment. CONCLUSION: The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents.

Comparison of rush-subcutaneous and sublingual immunotherapy with house dust mite extract for pediatric allergic rhinitis: A prospective cohort study.

BACKGROUND: We aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for allergic rhinitis. METHODS: Participants with allergic rhinitis selected their treatment between HDM SCIT or HDM SLIT, according to their wishes. We prospectively followed symptoms of allergic rhinitis using the allergic rhinitis symptom medication score (ARSMS), along with adverse reactions, during the dose escalation and maintenance phases for two years. We compared the outcomes between propensity score-matched groups to adjust the confounding factors. RESULTS: After propensity score matching, 88 patients in the HDM SCIT (n = 44) and HDM SLIT groups (n = 44) remained for analysis. The HDM SCIT group showed significantly earlier effectiveness than the HDM SLIT group (median time to decrease in ARSMS [≥2 points]: 5.5 vs. 18.0 months, p < 0.001). The incidence of systemic reactions was not significantly different between the two groups in the dose escalation phase (68.2% vs. 56.8%, p = 0.379). In the maintenance phase, the incidence of systemic reactions was higher in the HDM SCIT group than in the HDM SLIT group (18.2% vs. 0%, p < 0.006). All 44 patients in the HDM SCIT group completed two years of treatment, while nine patients in the HDM SLIT group discontinued treatment. CONCLUSIONS: The HDM SCIT group showed an earlier onset of therapeutic effect and a lower discontinuation rate than the HDM SLIT group, although more severe systemic reactions were observed during the maintenance phase.

[EVALUATION OF PROTOCOLS FOR RUSH SUBCUTANEOUS IMMUNOTHERAPY WITH STANDARDIZED HOUSE DUST MITE EXTRACTS].

BACKGROUND: Widely accepted loading protocols for rush subcutaneous immunotherapy (rSCIT) have not been established. Our aim was to evaluate the loading protocols of rSCIT. METHODS: In the low initial dose group (33 patients), the initial dose of standardized house dust mite extract was 1 JAU or less. The target dose at the end of the rush build-up phase was 500 JAU. Next, the initial dose was increased to 10 JAU with the same target dose in the high initial dose group (18 patients). Furthermore, in the modified high initial dosage group (17 patients), the initial dose was 10 JAU but the target dose at the end of the rush phase was 300 JAU. Then, the maintenance dose of 500 JAU was administered at 9 or 10 days after rSCIT initiation. We retrospectively evaluated these protocols. RESULTS: A systemic reaction (SR) occurred in 28 out of 33 (84.8%) patients in the low initial dosage group and in 12 out of 18 (66.7%) patients in the high initial dosage group, on the other hand significantly reduced in 4 out of 17 (23.5%) patients in the modified high-dosage group. The amount of antigen reached 339.3±19.0 JAU in the low initial dosage group and 358.3±24.9 JAU in the high initial dosage group at the end of the rush phase, significantly increased 452.9±20.6 JAU in the modified high-dosage group at 9 or 10 days. CONCLUSION: In rSCIT using standardized house dust mite extract, lowering the target dose at the end of the rush phase and delaying the administration of the maintenance dose may reduce SR and increase the reached amount of antigen.

Juvenile polymyositis associated with anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody in a 13-year-old girl.

A 13-year-old girl was admitted for persistent thigh pain and remittent fever and was diagnosed as having juvenile polymyositis. Although the initial treatment with 2 cycles of methylprednisolone pulse therapy failed to achieve full remission, the second-line treatment with intravenous cyclophosphamide pulse therapy was effective. Anti-OJ antibody, which is one of anti-aminoacyl-tRNA synthetase (ARS) antibodies and is rare in adult polymyositis, was detected. Assessment of anti-ARS autoantibodies may facilitate diagnosis and management of juvenile polymyositis.

Effectiveness of allergen immunotherapy with house dust mite extract for pediatric bronchial asthma.

Aim: We compared the effectiveness of rush subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) using standardized house dust mite (HDM) extract for pediatric bronchial asthma (BA). Methods: We followed the pediatric BA treatment score during 3 years of treatment. We assessed the median time to no longer requiring long-term control pharmacotherapy (LTCP) for BA (LTCP-free). We compared the outcomes after adjustment for confounding factors and propensity score matching. Results: Patients in the HDM SCIT group achieved the LTCP-free status significantly earlier than those in the HDM SLIT group after adjustment for confounding factors and propensity score matching. Conclusion: Patients treated for pediatric BA with rush HDM SCIT had earlier onset of therapeutic effects than those with HDM SLIT.

Effectiveness of continuous allergenic food intake for acute food protein-induced enterocolitis syndrome.

Continuous intake of allergenic food is a safe and efficient treatment strategy for patients with a prolonged course of acute food protein-induced enterocolitis syndrome. The initial dose, dose escalation rate, and starting age for continuous allergenic food intake need further clarification.

Parents' Fears about Hospital Visits and Trait Anxiety in the COVID-19 Pandemic.

Anxiety in parents of children with allergic diseases during the COVID-19 pandemic may impact hospital visits. This study explored the effect of the pandemic on parents' fears about hospital visits and their relationship with their personality traits. A cross-sectional, questionnaire-based study was conducted between September 2020 and March 2021, with parents of children aged 0-15 years, who regularly visited 24 outpatient facilities for allergic disease. The survey included patient information, fears about hospital visits, desired information, and the State-Trait Anxiety Inventory. Responses were compared between parents with high and low trait anxiety. The response rate was 97.6% (2439/2500). The most common fear was "Fear of getting medical care as usual (85.2%)" and "Fear of COVID-19 infection during hospital visits (87.1%)". High trait anxiety showed a significant association with "Fear of worsening of children's allergies" (adjusted OR: 1.31, 95%CI: 1.04 to 1.65, p = 0.022), and "Fear of worsening of COVID-19 due to allergy" (adjusted OR: 1.52, 95%CI: 1.27 to 1.80, p < 0.01). Healthcare professionals should share updates on COVID-19 and healthcare system to reduce parents' fear. Subsequently, they should communicate the importance of continuing treatment to prevent worsening of COVID-19 and avoid emergency visits, considering parental trait anxiety.

Pediatric allergies in Japan: Coronavirus disease pandemic-related risk factors.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies. Objective: This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures. Methods: Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic. Results: A valid response was obtained from 2302 parents; 1740 of them had children with food allergies. Approximately 4% (62/1740) of the parents reported accidental food allergen ingestion was increased compared to that before the COVID-19 pandemic. Accidental ingestion during school closures was associated with increased contact with meals containing allergens meant for siblings or other members of the family at home. The exacerbation rate during the pandemic was highest for atopic dermatitis at 13% (127/976), followed by allergic rhinitis at 8% (58/697), and bronchial asthma at 4% (27/757). The main risk factors for worsening atopic dermatitis, allergic rhinitis, and bronchial asthma were contact dermatitis of the mask area (34/120 total comments); home allergens, such as mites, dogs, and cats (15/51 total comments); and seasonal changes (6/25 total comments), respectively. Conclusion: The main factors affecting allergic diseases were likely related to increased time at home, preventive measures against COVID-19, and refraining from doctor visits. Children with allergies were affected by changes in social conditions; however, some factors, such as preventing accidental ingestion and the management of allergens at home, were similar to those before the COVID-19 pandemic. Patients who had received instructions on allergen avoidance at home before the pandemic were able to manage their disease better even when their social conditions changed.

Oropharyngeal symptoms without systemic reactions as a risk factor for food allergen intolerance: a longitudinal pediatric study.

BACKGROUND: The determinants of tolerance to food allergens are not fully understood. We aimed to elucidate the longitudinal association between oropharyngeal symptoms without systemic reactions (OSw/oS) and tolerance to food allergens. METHODS: We included all patients diagnosed with single food allergy to egg (n = 121), milk (n = 55), and wheat (n = 41) using the oral food challenge test (OFC) from 2014 to 2017. These patients received oral immunotherapy at home and/or in the hospital after diagnosis by OFC. We compared the incidence proportion of tolerance within 2 years by OSw/oS and other variables for 217 patients with food allergy. We defined OSw/oS as isolated symptoms of oropharyngeal discomfort that occurred after ingestion of a safe dose of the allergenic food determined by the OFC in the first 6 months. RESULTS: Of the 217 patients (median age 37.5 months, male 64.5%), 53 developed OSw/oS (24.4%), and 151 (egg, 85 milk, 36 and wheat, 30) attained tolerance in 2 years. Patients without OSw/oS showed a significantly higher incidence of tolerance than those with the symptoms (crude hazard ratio [HR] 5.62, 95% confidence interval [CI] 3.58-8.82, p < 0.001). The association was consistently significant in the multivariable model (adjusted HR 9.50, 95% CI 5.25-17.20, p < 0.001) independent of other risk factors for intolerance, such as concomitant bronchial asthma (adjusted HR 3.33), history of anaphylaxis (adjusted HR 2.16), milk allergy (adjusted HR 2.02), and allergic symptoms with low dose OFC (adjusted HR 1.52). CONCLUSION: Our results suggest that OSw/oS may be a risk factor for intolerance to food allergens. To reveal a high risk of food allergen intolerance may help patients and their families as well as healthcare professionals prepare for the challenge of continuing oral immunotherapy.

Evaluation of subcutaneous immunotherapy with birch pollen extract for pollen-food allergy syndrome.

Some patients with pollen-food allergy syndrome (PFAS) develop systemic symptoms along with oral allergy syndrome upon ingesting processed foods as well as raw fruits and vegetables. This study aimed to investigate the efficacy of subcutaneous immunotherapy with birch pollen extract for patients with PFAS associated with soybean allergy. Subcutaneous immunotherapy with birch pollen extract was introduced in 6 patients with PFAS caused by alder/birch pollen and soybean allergy. An oral food challenge for ingestible amount of soy milk was performed before and 1 year after initiating subcutaneous immunotherapy with birch pollen extract. Before the treatment, the median intake of soy milk was 1.5 mL (interquartile range [IQR], 1-2 mL). One year after the treatment initiation, the median intake of soy milk increased significantly to 150 mL (IQR, 20-200 mL). Systemic reactions occurred in 4 of 6 patients in the rapid escalation phase of the treatment. The results thus suggest that subcutaneous immunotherapy with birch pollen extract could be beneficial for patients with PFAS associated with soybean allergy despite concerns regarding systemic reactions.

Progress of Home-Based Food Allergy Treatment during the Coronavirus Disease Pandemic in Japan: A Cross-Sectional Multicenter Survey.

The coronavirus disease 2019 (COVID-19) pandemic's impact on food allergy treatment such as home-based oral immunotherapy (OIT) is not known. This cross-sectional, questionnaire-based anonymized survey screened 2500 parents of children with allergic diseases and was conducted in the pediatric outpatient clinics of 24 hospitals. Basic clinical data of the children were collected along with the degree of allergy control, parental anxiety about emergency visits, and the risk of COVID-19 in the first state of emergency. A total of 2439 (97.6%) questionnaires were collected, and 1315 parents who were instructed to initiate home-based OIT for their children were enrolled (OIT group). Subjective OIT progress compared to before the COVID-19 pandemic was ascertained as "Full", "Middle", "Low", "Little", and "Stop" in 264 (20.1%), 408 (31.0%), 384 (29.2%), 203 (15.4%), and 56 (4.3%) participants, respectively. Anxiety about emergency visits and the risk of COVID-19 were negatively associated with the subjective OIT progress. In Japan, approximately half of the children continued smoothly the home-based OIT during the COVID-19 pandemic. Parents with high levels of anxiety about the disruption of the medical care system due to COVID-19 and the risk of COVID-19 did not experience a smooth continuation of home-based OIT.

Association between fruit and vegetable allergies and pollen-food allergy syndrome in Japanese children: a multicenter cross-sectional case series.

BACKGROUND: Recently, the prevalence of food allergies during childhood is increasing, with fruits being common allergens. However, data on allergens that cause fruit and vegetable allergies and pollen-food allergy syndrome (PFAS) in childhood are relatively few. This study aimed to examine the allergens in fruit and vegetable allergies in pediatric patients and to determine the association between fruit and vegetable allergies and PFAS. OBJECTIVE: This study aimed to examine the current status of fruit and vegetable allergies in Japanese children. METHODS: This was a multicenter case series observational study. The participants included children aged <15 years who developed allergic symptoms after eating fruits and vegetables and subsequently received treatment in the Pediatric Department of 6 hospitals in the Osaka Prefecture in Japan during the study period from August 2016 to July 2017. Participants' information was obtained using a questionnaire, and data were obtained by performing several types of allergy tests using blood samples. RESULTS: A total of 97 children (median age, 9 years; 56 males) were included in the study. Apple was the most common allergen, followed by peach, kiwi, cantaloupe, and watermelon. A total of 74 participants (76%) exhibited allergic symptoms due to PFAS; moreover, pathogenesis-related protein-10 (PR-10) was the most common allergen superfamily. On the contrary, in the group where neither PR-10 nor profilin was sensitized, kiwi and banana were the most common allergens, and the age of onset was lower than that in the PFAS group. Specific antibody titer was significantly associated with Birch for Bet v1 and latex for Bet v2 (r = 0.99 and r = 0.89). CONCLUSION: When we examine patients with fruit and vegetable allergies, we should first consider PFAS even in childhood specifically for children greater than 4 years old.

Visual evaluation of blood coagulation during mural thrombogenesis under high shear blood flow.

Mural thrombus generation at sites of damaged vessel walls is essential for both physiological haemostasis and pathological intravascular thrombosis. While thrombi are established by the concerted action of platelet aggregation and blood coagulation, most previous in vitro coagulation assays have evaluated fibrin clot formation in a closed stirring situation that lacks blood cells including platelets. We describe here a modified flow chamber system, established originally for platelet functional studies, that enables real-time observation of intra-thrombus fibrin accumulation during platelet thrombogenesis under flow conditions. Analysis by confocal laser scanning microscopy during perfusion of whole blood anticoagulated to various extents revealed that the size and shape of mural thrombi can depend on the intra-thrombus fibrin development under high shear rate conditions. These observations were confirmed by perfusion of heparinized blood or blood from haemophilia patients with or without addition of activated factor VII. Thus, our experimental system provides visual evidence supporting the concept of "cell-based coagulation under whole blood flow", which might be the most physiologically relevant model of comprehensive thrombogenicity in vivo to date. This system promises to help formulate strategies for haemostatic management of congenital coagulation disorders as well as for antithrombotic therapy targeting fatal arterial thrombosis.

[Membranous nephropathy following allogeneic peripheral blood stem cell transplantation in a boy with anaplastic large cell lymphoma].

We report the case of 13-year-old boy who had been diagnosed as having anaplastic large cell lymphoma (ALCL) when he was 11 years old. He suffered a relapse despite the chemotherapy regimens he had been subjected to. Since anaplastic lymphoma kinase (ALK), one of the important prognostic factors of ALCL, was not expressed in the tumor cells, allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched elder brother was performed. Eleven months after PBSCT, the patient developed nephrotic syndrome as a consequence of chronic graft-versus-host disease (GVHD). He was diagnosed as having membranous nephropathy (MN) based on the results of histological examinations. Soluble interleukin-2 receptor and anti-nuclear antibody closely reflected the clinical course of MN, therefore some immune mechanisms closely related to chronic GVHD seemed to contribute to the occurrence of MN after PBSCT.

Antithrombotic properties of pravastatin reducing intra-thrombus fibrin deposition under high shear blood flow conditions.

In addition to lowering cholesterol, the 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have a range of pleiotropic effects that help reduce the risk of adverse cardiovascular events. We sought to understand the molecular mechanisms by which statins could exert anti-platelet actions under physiologic whole blood flow conditions. Using an in vitro perfusion chamber system, we examined the anti-platelet effects of pravastatin under whole blood flow conditions with high or low shear rates. We determined that pravastatin significantly suppressed platelet activation-dependent procoagulant activity, decreasing P-selectin membrane expression, tissue factor accumulation, and thrombin binding within platelet thrombi generated on a von Willebrand factor-surface under high shear rate conditions. These effects resulted in reductions of intra-thrombus fibrin deposition. These antithrombotic properties of pravastatin, which were comparable to those of atorvastatin, could be abrogated by mevalonate. Our experimental approach revealed a novel mechanism mediating the anti-platelet action of statins. Shear rate-dependent antithrombotic activity may explain the favourable effect of pravastatin on the reduction in cardiovascular events that typically occur in vivo under whole blood flow conditions with high shear rates.

Functional imaging of shear-dependent activity of ADAMTS13 in regulating mural thrombus growth under whole blood flow conditions.

The metalloprotease ADAMTS13 is assumed to regulate the functional levels of von Willebrand factor (VWF) appropriate for normal hemostasis in vivo by reducing VWF multimer size, which directly represents the thrombogenic activity of this factor. Using an in vitro perfusion chamber system, we studied the mechanisms of ADAMTS13 action during platelet thrombus formation on a collagen surface under whole blood flow conditions. Inhibition studies with a function-blocking anti-ADAMTS13 antibody, combined with immunostaining of thrombi with an anti-VWF monoclonal antibody that specifically reflects the VWF-cleaving activity of ADAMTS13, provided visual evidence for a shear rate-dependent action of ADAMTS13 that limits thrombus growth directly at the site of the ongoing thrombus generation process. Our results identify an exquisitely specific regulatory mechanism that prevents arterial occlusion under high shear rate conditions during mural thrombogenesis.

Cardiac metastasis from Merkel cell skin carcinoma.

A 54-year-old woman presented with cardiac metastasis of a Merkel cell carcinoma. Chemotherapy was not effective for the metastasis sites; therefore, radiotherapy was performed for the metastatic cardiac tumors, and it reduced the volume of the cardiac tumors. Cardiac metastasis from Merkel cell carcinoma is rare. Radiotherapy for metastatic cardiac tumors from Merkel cell carcinoma is useful as palliative treatment when the response to chemotherapy is poor.