Oral Immunotherapy With Extensively Hydrolyzed Milk for a 12-Year-Old Child With Persistent, Severe Cow's Milk Allergy.

A 12-year-old girl with severe cow's milk allergy (CMA) was able to safely consume 300 mL of unhydrolyzed cow's milk after three and a half years of oral immunotherapy (OIT) with extensively hydrolyzed milk. The treatment consisted of gradually increasing the intake of hydrolyzed and partially hydrolyzed milk and reintroducing cow's milk. Despite some allergic reactions during treatment, the patient was able to consume more than 200 ml of milk consistently for more than six months without recurrence of symptoms. This case suggests the possibility of an alternative treatment for persistent CMA: not only OIT with cow's milk alone but also a safer introduction to treatment with extensively hydrolyzed formulas.

Low-Dose Oral Challenge Test in Pediatric Patients With Peanut Allergy: Tolerance Assessment of a Trace 5 mg Peanut Test After Symptom Induction With a 500 mg Test.

Introduction Peanut allergy (PA) represents a significant public health concern, particularly prevalent in Western countries. Children at high risk for PA may undergo a low-dose oral food challenge (OFC). However, if the result is positive, complete elimination of peanuts from the diet is recommended, and further trace OFC is typically not performed.  Material and methods This cross-sectional study retrospectively examined the rate of positive peanut OFC with a total peanut load of 5 mg in children who tested positive with a total peanut load of 500 mg. Patient information was gathered from medical records. The primary endpoint was the rate at which children who tested positive in the OFC with 500 mg of peanut butter also tested positive with 5 mg of peanut butter equivalent.  Results Among 32 children who underwent an OFC with a total peanut load of 500 mg, two were excluded for not meeting the criteria. Among the remaining 30 children, 14 (46.7%) had a positive 500 mg peanut OFC test, and three (10%) experienced an anaphylactic reaction. Those who tested positive for the OFC had higher peanut-specific and Ara h2-specific immunoglobulin E (IgE) antibodies. An OFC with 5 mg of peanuts performed on 10 of the 14 patients who tested positive for 500 mg of peanuts showed no positive results. Conclusion The results of this study suggest that children with severe PA who exhibit positive symptoms to a total peanut load of 500 mg can tolerate a 5 mg dose of peanuts and should be considered for an OFC.

Transepidermal Water Loss and T-helper 2 (Th2)-Associated Inflammatory Markers in Two Pediatric Patients During the First Four Weeks of Treatment With the Oral Janus Kinase Inhibitor Upadacitinib.

Few studies have evaluated the effects of upadacitinib on skin barrier function and T-helper 2 (Th2)-associated inflammatory biomarkers in severe atopic dermatitis (AD). In this study, we followed two pediatric patients with AD who had previously failed to respond to conventional treatment and measured their serum Th2-associated chemokine thymus and activation-regulated chemokine (TARC) and serine protease inhibitor squamous cell carcinoma antigen (SCCA) 2 levels and transepidermal water loss (TEWL) during the first four weeks of upadacitinib treatment. Both patients showed marked clinical improvement and decreased TEWL, blood eosinophil counts, and serum TARC and SCCA2 levels after four weeks of upadacitinib treatment. These findings suggest that upadacitinib attenuates Th2-associated inflammatory markers and promotes skin barrier integrity.

Pranlukast treatment and the use of respiratory support in infants with respiratory syncytial virus infection.

BACKGROUND: In infants, respiratory syncytial virus (RSV) infection occasionally causes severe symptoms requiring respiratory support; however, supportive care is the primary treatment. This study compared the use of respiratory support among infants with RSV infection treated with or without pranlukast. METHODS: This retrospective cohort study included infants aged <10 months with RSV infection who were admitted to three secondary level hospitals in Japan between 2012 and 2019. The infants were divided into two groups depending on whether they were treated with pranlukast. The primary outcome was the receiving respiratory support (high-flow nasal cannula, nasal continuous positive airway pressure, or ventilator). The secondary outcomes were the length of hospital stay, and the Global Respiratory Severity Score (GRSS) on starting respiratory support or at the time of the worst signs during hospitalization. We performed a propensity score-matched analysis. RESULTS: A total of 492 infants, including 147 propensity score-matched pairs, were included in the analysis. The use of respiratory support was significantly lower in infants treated with pranlukast (3.4% [5/147]) than those treated without pranlukast (11.6% [17/147]; P = 0.01). In the propensity score-matched analysis, pranlukast use was associated with a significantly lower chance of needing respiratory support (odds ratio: 0.27, 95% confidence interval: 0.08-0.79; P = 0.01); however, the length of hospital stay (median: 4 days) and the GRSS (median: 2.804 and 2.869 for infants treated with and without pranlukast, respectively) did not differ significantly between propensity score-matched pairs. CONCLUSIONS: Pranlukast use was associated with a reduced likelihood of requiring respiratory support in infants aged <10 months with RSV infection.

Susceptibility to serious skin and subcutaneous tissue disorders and skin tissue distribution of sodium-dependent glucose co-transporter type 2 (SGLT2) inhibitors.

Objectives: In Japan, sodium-glucose co-transporter type 2 (SGLT2) inhibitors have been reported to be associated with serious skin and subcutaneous tissue disorders. A post-marketing surveillance (PMS) study suggested that the association was specific for ipragliflozin and, to a lesser extent for dapagliflozin. These studies were performed to confirm the association of 6 SGLT2 inhibitors with serious skin disorders in a clinical setting, to elucidate the role of melanin in serious skin disorders and to understand the underlying mechanisms. Methods: The latest PMS records were retrieved from the Japanese Adverse Drug Event Report (JADER) database, and the associations were analyzed by data mining techniques. In silico 3-D docking simulation of SGLT2 inhibitors with melanin was performed using the MOE software. The skin tissue distribution of SGLT2 inhibitors was evaluated using albino rats after oral administration at clinical doses. Results: The adjusted reporting odds ratio (95% confidential limit) was 1.667 (1.415, 1.963) for ipragliflozin, 0.514 (0.317, 0.835) for dapagliflozin, 0.149 (0.048, 0.465) for tofogliflozin, 0.624 (0.331, 1.177) for luseogliflozin, 0.590 (0.277, 1.257) for canagliflozin and 0.293 (0.073, 1.187) for empagliflozin, when drugs other than the SGLT2 inhibitors were referred, and the association was detected only for ipragliflozin in clinical use. In silico 3-D docking simulation suggested the influence of melanin in ipragliflozin-specific serious skin disorders. The skin tissue-to-plasma concentration ratio of ipragliflozin was 0.45 ± 0.20 (±SD) at 1 hr after administration and increased in a time-dependent manner to 5.82 ± 3.66 at 24 hr (p<0.05), but not in case of other SGLT2 inhibitors. Conclusions: Serious skin disorders were suggested to be specific for ipragliflozin. Interaction with melanin might be implicated in ipragliflozin-specific serious skin disorders. Ipragliflozin was retained in the skin tissue, which suggested its interaction with the skin tissue in serious skin disorders.