Tina Dominguez

Omalizumab facilitates rapid oral desensitization for peanut allergy

Background: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti‐IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. Objective: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods: Thirty‐seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1‐day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab‐treated subjects versus 22.5 mg for placebo‐treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty‐three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000‐mg food challenge. Overall reaction rates were not significantly lower in omalizumab‐treated versus placebo‐treated subjects (odds ratio, 0.57; P = .15), although omalizumab‐treated subjects were exposed to much higher peanut doses. Conclusion: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.

Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired

&NA; Figure. No caption available. Background: Peanut allergy (PA) is a life‐threatening condition that lacks regulator‐approved treatment. Regulatory T type 1 (TR1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen‐specific TR1 cell induction has not been established. Objectives: We sought to determine whether peanut‐specific TR1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut‐specific TR1 cells induced from healthy control (HC) subjects. Methods: Tolerogenic dendritic cells were differentiated in the presence of IL‐10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen‐presenting cells for autologous CD4+ T cells (CD4+ T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea‐T10 cells]). Pea‐T10 cells were characterized by the presence of CD49b+ lymphocyte‐activation gene 3 (LAG3)+ TR1 cells, antigen‐specific proliferative responses, and cytokine production. Results: CD49b+LAG3+ TR1 cells were induced in pea‐T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea‐T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high TH2 cytokine production upon peanut‐specific restimulation. Conclusions: Peanut‐specific TR1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable TR1/TH2 ratio is discussed as a possible cause of PA TR1 cell impairment.

The Use of Epinephrine in Acute Allergic Reaction to Food

CASE 1 A 2-year-old boy presents in the emergency department (ED) for hives on his torso and arms. His medical history is unremarkable except for an egg allergy. His parents are certain he has not been in contact with egg. The pruritus and hives appeared spontaneously about 20 minutes prior. The last meal was more than 2 hours ago and contained no suspect ingredient. The patient is in no apparent distress and vital signs are within normal limits. His lungs are clear. Ear-nose-throat (ENT) exam reveals conjunctivitis and rhinitis. He is given oral diphenhydramine, but within 5 minutes, he reports throat pruritus and the mother notes a change in voice. The nurse asks whether she should administer the intramuscular (IM) epinephrine. CASE 2 A father calls the on-call service concerning his teenage daughter who is allergic to peanuts. He is worried that she may have accidently eaten a cookie that contained peanuts. He sounds very anxious and is asking what to do and whether he should administer the epinephrine auto-injector. The daughter does not report any itching or skin symptoms. Her breathing appears to be normal with no wheezing and she does not report any gastro-intestinal symptoms. Upon realizing that she may have eaten something containing peanut, she began to panic, cry, and feel dizzy. The father is wondering if he should drive to the hospital rather than wait for the paramedics. CASE 3 A 7-year-old boy has been admitted for a severe asthma attack that is refractory to treatment with albuterol and ipratropium bromide nebulization. Although the parents report the patient had previous wheezing with viral infections when younger, he has had no symptoms in the last 2 years. He does have a history of hay fever, but no known food allergy. The respiratory symptoms first began after the family left the restaurant where the patient had eaten pesto pasta, suspected to have contained pine nuts. Shortly after dinner, he complained of a “tummy ache” and began to vomit. A medical student asks whether this could be an allergic reaction to a food and if intraThe Use of Epinephrine in Acute Allergic Reaction to Food