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Omalizumab, a savior in long term prevention of idiopathic anaphylaxis with urticaria: A case series

Dear Editor, Anaphylaxis is a serious, acute, potentially life-threatening generalized type 1 hypersensitivity reaction that frequently brings the patients to emergency department with severe urticaria, pruritus, choking sensation, sinking feeling, vomiting, loose motion, and rarely in unconscious state. It is most often caused by stinging insects and medications in adults and by foods in children and adolescents. Approximately 2% to 16.8% of the U.S. population suffer from an anaphylactic reaction each year with 0.002% annual risk of death. Approximately 13%– 18% of total anaphylactic patients, no trigger can be identified despite detailed clinical evaluation and extensive laboratory work-up such patients are diagnosed as having idiopathic anaphylaxis (IA). Acute such episodes get managed by injection epinephrine, hydrocortisone, phenarimine maleate, and management of airways and circulation with good outcome, but patients may require long term systematic steroids and oral antihistamines thereby severely compromising the quality of life. Injection omalizumab is a humanized, monoclonal anti IgE antibody, FDA approved for management of chronic moderate to severe persistent asthma, widely used and recommended as second line drug for management for chronic spontaneous urticaria and various reports of its efficacy in IA. We present a case series of five patients who were administered omalizumab 300 mg monthly for IA. All these case were extensively worked-up to rule out any systemic mastocytosis, mast cell activation syndrome or any underlying known triggers. Prior ethical approval from the institute (78/acad/2020) and written consent taken from the patients. The details of the patients are mentioned in Table 1. All the patients have recovered fully with varied duration of omalizumab administration. Anaphylaxis with urticaria is usually caused by cross linking of IgE bound allergens to FcεRI receptors and release of histamine, prostaglandins and other inflammatory mediators from the preformed granules of mast cells and basophils. At times, there is direct release of mast cells bypassing the FcεRI receptors known as anaphylactoid reaction. Omalizumab binds to all free IgE antibodies which blocks its interaction with FcεRI receptors present on the mast cells and basophils and dendritic cells resulting in prevention of release of histamines and other inflammatory mediators and also down regulating the receptors for future such interaction. Omalizumab has been used in IA earlier also but interestingly anaphylaxis has been reported as adverse effects especially among those with a history of anaphylaxis. Remotely, anaphylaxis with urticaria can be a manifestation of clonal mast cell disorders, such as systemic mastocytosis and monoclonal mast cell activation syndrome which can be ruled out by persistent high serum tryptase level during the episode or following the episode of anaphylaxis, 24 h urine 5-hydroxy indoleacetic acid (5-HIAA), bone marrow biopsy with immunohistochemistry. Dose of omalizumab to be used in anaphylaxis have not been recommended even though a doubled blind control trial was done to know the efficacy of omalizumab in management of idiopathic anaphylaxis. In this study, omalizumab was administered over 6 months to patients with idiopathic anaphylaxis, which did not find statistically significant difference versus placebo, although there was a trend for efficacy in the treatment group. Limitations of this study was small number of cases and natural course of IA, which become normal as such after long period. In a retrospective study of 35 patients of idiopathic anaphylaxis who did not have evidence of mast cell clonality and failed to respond to antihistamines and mast cell stabilizers where omalizumab was administered 300 mg monthly found complete response in (63%, n = 22), partial response (28.5%, n = 10), with three nonresponders. Our case series had excellent recovery from IA. Case 1 took maximum time, that is, 14 months to become very asymptomatic but since first dose of omalizumab, no patient had anaphylaxis requiring emergency admission. All patients had breakthrough urticarial lesions, case 1, 2, and 5 had additionally mild abdominal discomfort, case 3 & 4 had additionally anxiety, which subsided with course of oral type 1 and type 2 antihistamines. All patients except case 5 are now totally symptom free since last 1 year. Injection omalizumab proved to be quite promising in long term management of the idiopathic anaphylaxis. Our all cases have responded completely. Due to rarity of condition and ethical concern, study on larger population will always remain a challenge. Our experience suggests that omalizumab can be used to prevent life threatening anaphylaxis and its consequences on the patients on long run.