Dupilumab for treatment of food-dependent, exercise-induced anaphylaxisLiping Zhu#, MB, Rui Tang#, MD, Qing Wang, BSN, Hong Li *, MDAllergy Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.* Correspondence: Hong Li, E-mail: [email protected]# These authors contributed equally to this workClinical Implications: This case provides evidence of treatment with dupilumab which improve the severity of allergic reactions in a patient with food-dependent, exercise-induced anaphylaxis.TO THE EDITOR,Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and with a history of eating culprit foods within a few hours before onset, but eating or exercise alone does not induce symptoms.1This disease is exceedingly rare with a prevalence was approximately 0.02% .2 Food allergens can stimulate mast cells to release inflammatory mediators like histamine and cytokines such as IL-4 and IL-13 after entering the body, increase intestinal permeability by enhancing IL-4Ra signaling, and enhance sensitivity to food allergens.3 Therefore, blocking IL-4 and IL-13 signaling pathways may reduce the symptoms of anaphylaxis.Dupilumab is a monoclonal antibody that inhibits IL-4 and IL-13 signaling by specifically binding to the IL-4Rα subunit of the IL-4 and IL-13 receptor complex. It has been studied for the treatment of atopic dermatitis, uncontrolled asthma, severe chronic sinusitis with nasal polyps, and eosinophilic esophagitis.4 A case reported that a 23-year-old female patient with severe asthma and unexplained severe allergic reactions which is not related to exercise. After being treated with dupilumab for asthma in two doses, no serious anaphylaxis requiring epinephrine occurred within the next 2 years.5But there has been no published report to clarify the clinical implication of treatment for anaphylaxis with dupilumab, especially for FDEIA which is a rare disorder.CASE REPORTGeneral informationWe present an 11-year-old boy with a history of recurrent anaphylaxis, asthma, allergic rhinitis, and allergic conjunctivitis due to cat, mites, fungus sensitization, and attacks of anaphylaxis related to the triggers of activities combined with uncertain foods. In June 2019, when the patient was exercising after ingesting common foods for around 2 hours, he developed anaphylaxis demonstrating systemic wheals itching, facial edema, eyelid redness and swelling, nasal congestion, cough, chest tightness, dyspnea, lip cyanosis, wheezing. The child experienced more than 10 episodes of anaphylaxis for 2 years, and 2 times went to the hospital for emergency treatment. His family felt that the episodes were unrelated to the food type at the previous visits. The patient’s asthma (CSMS, 2.33), allergic rhinitis (ACT score, 20) allergic conjunctivitis were controlled after treatment with Ventolin and Budesonide Formoterol Powder for Inhalation, Cetirizine, and fluticasone propionate nasal spray. He had been given dust mite sublingual drops for allergen immunotherapy (AIT) for more than half a year. But the anaphylaxis was not improved after the traditional treatments including the above medications use, AIT, and allergens avoidance.Specific IgE (ImmunoCAP) showed Alternaria alternata (30.43 KUA/L), cat dander (14.9 KUA/L), and Dermatophagoides farinae (15.4 KUA/L). Total IgE: 621.0 KU/L. The acetylcholine bronchial provocation test was positive: FEV1 decreased by 37%, PEF decreased by 27%, and PD20FEV1:0.0961 mg. Pulmonary function: FEV1 (L), 1.77; FEV1predicted (%), 78.4%; FEV1/FVC, 82.07%; FEV1/FVC predicted (%), 97.1%.Diagnosis and treatmentDue to unknown etiology, the patient was given the subcutaneous injection of dupilumab 7 times for a period of 33 weeks. Dupilumab was administered 300 mg subcutaneously every 4 weeks for the first 14 weeks and then changed to 300 mg every 6-7 weeks for the next 19 weeks due to symptom improvement. During the follow-up period of dupilumab treatment, skin prick tests (SPT) were performed on the foods of ostrea gigas thunberg, scallops, soybeans, corn, whole grains, and raw/cooked peanuts based on the patient’s parent-reported medical history and associated food diary, and all results were negative. Of these, ostrea gigas thunberg and scallops were previously considered the most associated with patient morbidity. After the recommendation to avoid these two foods, the symptoms continued to recur, so the possibility of these food triggers was tentatively ruled out. At the 7th follow-up visit of the patient on Dupilumab treatment, SPT results were positive for Morchella esculenta, Russula vinosa Lindblad, and Pleurotus eryngii which were associated with the patient’s history. And we found the patient had consumed these mushrooms before several attacks, but never felt discomfort in the past when only mushrooms were consumed without exercise. The patient was advised to avoid these mushrooms and to stop dupilumab treatment simultaneously, after which he did not have any episodes of anaphylaxis. Based on positive SPT results, the patient’s attack history, and the efficacy of avoiding mushrooms, the patient was diagnosed with FDEIA, and the mushroom was considered as the causative food.EfficacyDuring dupilumab treatments, the patient had experienced 2 times of mild allergic reactions, such as itchy skin, eyelid edema, or itching throat with the trigger of mushroom plus exercise (exposures for mushrooms plus exercise about at least twice a month), but no anaphylaxis within this time, and after stopping dupilumab and avoiding mushrooms (Figure 1). The diagnosis standard of anaphylaxis is based on the WAO guideline.6 The patient returned to normal exercise (running 1-2 km, soccer, etc.) with an improvement in quality of life and no adverse reactions occurred.Total IgE and specific IgE decreased significantly after dupilumab treatments 6-7 times. Total IgE: 197.0 KU/L, Alternaria alternata: 16.4 KUA/L, cat dander: 2.36 KUA/L, and Dermatophagoides farinae: 3.78 KUA/L (Figure 2). Asthma (ACT score: 23), allergic rhinitis (CSMS, 2.17), and conjunctivitis were well controlled.Figure 1. Changes in Anaphylaxis Following different Treatments
