Regular intake of cow's milk with oral immunotherapy improves statures of children with milk allergies.

BACKGROUND: Children who avoid cow's milk (CM) because of food allergy may show disturbed growth. Calcium insufficiency, in particular, was reported among those who completely avoided dairy products. We retrospectively examined whether oral immunotherapy (OIT) affected the stature of patients who had completely avoided CM owing to their severe CM allergy. METHODS: The CM-OIT group included subjects who had completely avoided milk their entire lives and were administered OIT between 2009 and 2013. The complete milk avoidance (CM-Avoid) group included subjects who were diagnosed with a CM allergy using oral food challenges between 2013 and 2014 who subsequently avoided CM completely. By examining clinical records and questionnaires, we investigated patient height changes over time. We calculated age- and sex-stratified height standard deviation scores (HtSDS) and analyzed changes in HtSDS retrospectively. The observation period was 1-2 years. To exclude pubertal growth spurts, we set the age criteria as less than 11 years in boys and less than 9 years in girls. RESULTS: We recruited 29 patients (19 boys) for the CM-OIT group and 20 (9 boys) for the CM-Avoid group. The patients' median ages at the start of the observation period were 7.5 years (6.1-9.6) for boys and 6.8 years (5.8-7.8) for girls in the CM-OIT group, and 5.4 years (5.0-7.5) for boys and 5.7 years (5.0-7.1) for girls in the CM-Avoid group. The initial HtSDS in the CM-OIT group was -0.31 (median) and increased to -0.22 (median) after OIT (p = 0.016). In contrast, there was no significant change in HtSDS for the CM-Avoid group. CONCLUSIONS: Physical growth of pediatric patients with severe CM allergies, who have avoided CM completely, could be improved by OIT for CM allergy.

[ASSESSMENT OF QOL BY URTICARIA ACTIVITY SCORE IN PEDIATRIC PATIENTS WITH CHRONIC URTICARIA].

BACKGROUND: There is no standard for assessing pediatric chronic urticaria in Japan. UAS7, weekly total values of the Urticaria Activity Score (UAS), has correlation with Dermatology Life Quality Index (DLQI) which assesses Quality of Life (QOL). The current European Academy of Allergy and Clinical Immunology (EAACI) guidelines recommend assessing disease activity in chronic urticaria by using UAS. We translated UAS into Japanese version, and evaluated usefulness of UAS by comparing with QOL score. METHODS: Subjects were 42 patients who had received treatments in our clinic from February to September in 2014. They wrote UAS at home. They wrote Children's Dermatology Life Quality Index (CDLQI) when they visited hospital. We assessed correlation UAS7 with CDLQI. RESULTS: Male/Female ratio was 1:1. Median age was 7.5 years old. Duration of chronic urticaria was 5.5 months. Anti-histamine was used in 75%. UAS7 values reflected chronic urticaria patients' quality of life impairment. Change in UAS7 values reflected change in chronic urticaria patients' quality of life impairment. CONCLUSION: UAS may be a useful tool for assessing QOL in pediatric patients with chronic urticaria.

Natural history of immediate-type hen's egg allergy in Japanese children.

BACKGROUND: Hen's egg (HE) allergy develops during infancy. We investigated tolerance acquisition in Japanese children allergic to HE aging <6 years. METHODS: In this retrospective study, 226 children born in 2005 with a history of immediate-type HE allergy underwent an oral food challenge (OFC). Tolerance was defined as no reaction to an OFC with half of whole heated HE or accidental HE consumption at home. Participants were divided into three groups based on age at tolerance acquisition: group I (<3 years) (n = 66), group II (3-6 years) (n = 98), and group III (prolonged allergic groups) (n = 62). RESULTS: Tolerance acquisition occurred in 30% (66/226) by 3 years of age, 59% (133/226) by 5 years of age, and 73% (164/226) at 6 years of age. At 3 years, incidences of allergy-related complications (bronchial asthma, p = 0.02; atopic dermatitis, p = 0.04) were higher in the group III than in the group I. Anaphylaxis to any food occurred more frequently in the group III than in the group I (p = 0.03); anaphylaxis to HE was more common in the group III (p = 0.04). Egg white (EW)- and ovomucoid (OM)-specific immunoglobulin E (IgE) levels were higher in the group III than in the group I (p < 0.05). CONCLUSIONS: The group III experienced HE-related anaphylaxis and complications more frequently and exhibited sustained, high EW- and OM-specific IgE levels.

[THREE CASES OF ACCIDENTAL AUTO-INJECTION OF ADRENALINE].

PURPOSE: Reports on accidental auto-injection of adrenaline are few. We encountered three cases of accidental injection of adrenaline. In this study, we have examined and reported the clinical courses and symptoms of our cases. CASE: CASE 1 involved a female physician in her 50s who had attended an explanatory meeting on auto-injection of adrenaline. She mistook EpiPen® to be the EpiPen trainer and accidentally injected herself with 0.3 mg EpiPen®. Her systolic/diastolic pressure peaked at 7 min to reach 144/78 mmHg and decreased to 120/77 mmHg at 14 min. Except for palpitation after 7 min, the only subjective symptom was local pain at the injection site. CASE 2 was noted in a 6-year-old boy. He accidentally pierced his right forefinger with 0.15 mg EpiPen®, and after 20 min, his right forefinger was swollen. The swelling improved 80 min after the accidental injection. CASE 3 was noted in a 4-year-old girl. She accidentally injected herself with 0.15 mg EpiPen®. Her systolic/diastolic pressure peaked at 23 min to reach 123/70 mmHg and decreased to 96/86 mmHg at 28 min. DISCUSSION/CONCLUSION: Severe adverse effects of accidental auto-injection of adrenaline were not observed in these three cases. Our findings suggest that while handling adrenaline auto-injectors, we should keep in mind the possibility of accidental injection.

Immunotherapy in food allergy: towards new strategies.

Allergen avoidance is the standard treatment for managing food allergies. Complete avoidance is difficult, and accidental exposure often occurs. Immunotherapy is a significant focus for treating food allergies, and oral immunotherapy (OIT) appears to be particularly effective in inducing desensitization. The majority of patients who receive OIT show increased threshold doses of their food allergen. The efficacy of OIT is different among food antigen, and milk OIT is relatively difficult to achieve tolerance. OIT may induce mild to moderate symptoms during the therapy, widespread acceptance of OIT for long-term therapy is unclear. Recently, novel immunotherapies for food allergies, such as sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) and using an anti-IgE monoclonal antibody (omalizumab), have been assessed. In addition, a combination of OIT with omalizumab, which was found to increase the threshold doses of the offending foods without producing adverse reactions, may be effective and useful in the treatment of food allergies. These treatments have been used only in research settings; further studies in large numbers of patients are needed to demonstrate their long-term safety and benefits in clinical practice.

Clinical studies in oral allergen-specific immunotherapy: differences among allergens.

Oral immunotherapy (OIT) is a significant focus of treatment of food allergy. OIT appears to be effective in inducing desensitization, however, patients receiving OIT frequently developmild/moderate symptoms during the therapy. It has not been clearly established whether the clinical tolerance induced by OIT resembles natural tolerance. According to our data, the efficacy of OIT is different among food antigens, and it is comparatively difficult to achieve the clinical tolerance in milk OIT. Moreover, the definitive evidence of efficacy and safety with long-term therapy is limited. Further studies need to be offered to patients in clinical practice. Recently, novel treatments for food allergy, sublingual and epicutaneous immunotherapy, and combination treatment with an anti-IgE monoclonal antibody (omalizumab), have been examined in some studies. OIT combined with omalizumab increased the threshold doses of food without adverse reactions and may be of benefit in food allergy treatment. More studies are needed to demonstrate long-term safety and treatment benefits in a larger patient cohort.

Peripheral blood mononuclear cells from patients with bronchial asthma show impaired innate immune responses to rhinovirus in vitro.

BACKGROUND: Asthmatic patients have a higher susceptibility to rhinovirus (RV) infection, and impaired IFN-ß and IFN-λ production has been demonstrated in bronchial epithelial cells from asthmatic adults upon exposure to RV. However, the mechanisms underlying the increased susceptibility of asthmatic patients to RV infection remain poorly understood. The present study aimed to elucidate the characteristics of the immune responses of asthmatic patients' peripheral blood mononuclear cells (PBMCs) to RV exposure. METHODS: PBMCs obtained from 3 different age groups (2-6 years: young-children group; 7-19 years: youth group; ≥20 years: adult group) of asthmatic patients and nonasthmatic control subjects were stimulated with RV-14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-α, IL-6, TNF-α, IL-10, and soluble Fas ligand (sFasL) in the culture supernatants were measured by ELISA. RESULTS: When compared with age-matched control subjects, IFN-α production was significantly lower in the asthmatic youth group. IL-6, TNF-α, IL-10, and sFasL productions were significantly lower in both the asthmatic youth group and the adult group. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatics and controls in the young-children group, whereas young asthmatic children with persistent wheeze during a 2-year follow-up showed significantly lower IL-10 production than those without wheeze. CONCLUSIONS: These results imply the involvement of impaired production of both IFN-α and inflammatory cytokines seen in asthmatic patients' PBMCs upon exposure to RV in the higher susceptibility of those patients to RV infection.