Timing of initial symptom onset during milk and wheat challenges: A retrospective study.

BACKGROUND: Allergic reactions to milk appear sooner than those to hen's eggs, irrespective of the total dose of the oral food challenges (OFCs) and type of matrices. The reported median times for the first symptom occurrence are 20-30 min with milk and 50-60 min with eggs. However, allergic reactions due to wheat have not yet been fully investigated. METHODS: This study retrospectively collected data from OFC for milk and wheat conducted at Sagamihara National Hospital and Sendai Medical Center from 2009 to 2023. The time from the start of the OFC to the onset of symptoms was compared between children with cow's milk and wheat allergy. RESULTS: Twenty-five and 13 children reacted to single-dose OFCs with milk products equivalent to 25 mL of raw cow's milk or 15 g of udon noodles, respectively. The median ages of patients with positive challenges were 1.4 and 2.8 years for milk and wheat, respectively, and the median times for the first symptom occurrence were 20 min and 53 min, respectively (p = .006). CONCLUSION: This multicenter study was the first to examine the time of symptom appearance during single-medium-dose milk and wheat challenges. Allergic reactions to wheat appear later than those for milk during OFC. For multiadministration OFC for wheat, the dosing interval should be longer than 60 min. Our findings can help improve the safety of OFCs.

Three-year prognosis after low-dose oral food challenge for children with wheat allergy.

BACKGROUND: Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. METHODS: Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3-6 months. After failing LD-OFC, children repeated LD-OFC every 6-12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. RESULTS: The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kUA/L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p < 0.001). Predictors of persistent WA in the LD-tolerant group were older age (adjusted odds ratio, 1.63), ω-5-gliadin-specific IgE level (1.62 per 10-fold increase), and other food allergies (1.94). CONCLUSIONS: LD-tolerant patients frequently acquired wheat tolerance within 3 years. Even if once positive, one-third could pass the re-administered LD-OFC within 3 years.

[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

Facial redness in Japanese adolescents with atopic dermatitis treated with dupilumab: A case series.

This case series study is the first report of Japanese adolescents who experienced dupilumab facial redness after starting dupilumab treatment for refractory atopic dermatitis. In every case, dupilumab facial redness subsided without discontinuation of dupilumab within 3 months after onset.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

BACKGROUND: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. METHODS: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. RESULTS: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. CONCLUSIONS: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

Phenotyping of immediate-type food allergies based on 10 years of research: A latent class analysis.

BACKGROUND: Food allergy is a disease with a diverse and variable natural history, and some patients may react to two or more food antigens. This study aimed to classify and characterize the long-term prognosis of infantile-onset, immediate-type food allergies, focusing on three major antigens in Japan: egg, milk, and wheat. METHODS: All children who visited our hospital with food allergies, including suspected cases, were prospectively registered in our medical database. Among the children in this database, subjects registered by the age of 1 year with immediate-type symptoms or sensitization to the above three antigens were included. The course of the subjects up to the age of 6 years was analyzed. Cox regression analysis and repeated-measures latent class analysis (LCA) were performed to reveal risk factors and tolerance patterns for food allergies. RESULTS: We included 915 patients with immediate-type food allergy symptoms and 276 sensitized asymptomatic patients in this study. The number of patients with immediate-type symptoms to egg, milk, and wheat was 609, 443, and 235, respectively. The number of patients with multiple food allergies was 302. The proportion of patients with tolerance to egg, milk, and wheat at 6 years of age was 74%, 69%, and 75%, respectively. LCA revealed 7 classes of prognosis for food allergies. The largest class was transient egg allergy alone (19.6%), and there were severe cases of multiple food allergies (6.5%). CONCLUSIONS: This study demonstrated the prognosis of food allergy classes in Japan, including multiple food allergies, with 7 classes with its own characteristics.

Macadamia nut-specific IgE levels for predicting anaphylaxis.

BACKGROUND: Despite the high risk of anaphylaxis in patients with a macadamia nut allergy (MdA), little is known about the significance of macadamia nut-specific immunoglobulin E (Md-sIgE). Thus, this study aimed to investigate the utility of Md-sIgE for predicting anaphylaxis. METHODS: Children with suspected MdA who visited our hospital were included. MdA was defined as either failing the 3-g macadamia nut (Md) oral food challenge (OFC) or confirming obvious immediate symptoms following Md ingestion. Non-MdA was defined as passing the 3-g Md OFC. RESULTS: A total of 41 children (29 [71%] males) with a median age of 7.7 years were included. The median Md-sIgE level was 2.23 kUA /L. Among the 21 children diagnosed with MdA, eight and 13 children did (An group) and did not (non-An group) develop anaphylaxis. Twenty children were included in the non-MdA group. The Md-sIgE level was significantly higher in the An group relative to the others (7.97 vs. 1.92 kUA /L, p < .001). Furthermore, the Md-sIgE level was significantly higher in the An group than in the non-An group (7.97 vs. 1.92 kUA /L, p = .02). However, there was no significant difference in the Md-sIgE between the non-An and non-MdA groups (1.92 vs. 1.90 kUA /L, p > .99). The area under the curve for predicting anaphylaxis in Md-sIgE was 0.92 (95% CI: 0.83-1.00), and the optimal cut-off value was 3.76 kUA /L. CONCLUSION: Md-sIgE levels were useful in predicting anaphylaxis. Above the cut-off value, we emphasize paying careful attention to the risk of anaphylaxis.

Systemic lupus erythematosus presenting with mixed-type fulminant autoimmune hemolytic anemia.

We report the case of a 9-year-old girl who presented with mixed-type fulminant autoimmune hemolytic anemia (AIHA) at the onset of systemic lupus erythematosus (SLE). On admission, laboratory investigations indicated very severe anemia (Hb, 2.7 g/dL) with reticulocytosis and positive direct/indirect Coombs tests. In addition, agglutinative reaction was clinically observed. Based on further examinations, the patient was diagnosed with AIHA complicated with SLE, and mixed-type AIHA was clinically identified. With oral prednisolone and methylprednisolone pulse therapy, the patient entered remission.