Correspondence

Successful treatment of idiopathic anaphylaxis in an adolescent

The severity of anaphylaxis is determined by many factors. The allergenic source as well as the age of the affected individual and the route of allergen exposure encompass the major contributors of the clinical outcome. Moreover, the severity can be modulated further by intrinsic and extrinsic factors. Among these, the genetic predisposition, certain comorbidities such as uncontrolled asthma, and hormonal fluctuations have been proposed as intrinsic and antihypertensive medications or physical activity as extrinsic factors. Recent advances have highlighted immunologic pathways that may exacerbate the response to allergens through receptors on mast cells, basophils, platelets, and other granulocytes. Atopy, platelet-activating factor acetylhydrolase deficiency, hereditary alpha tryptasemia, and clonal mast cell disorders are examples associated with genetic alterations that may predispose to severe anaphylaxis. Identifying risk factors that lower the threshold of reactivity or increase the severity of multisystem reactions is important in the management of this patient population.

Idiopathic anaphylaxis (IA) is a diagnosis of exclusion, thus taking away the option of therapeutic management focused on eliminating the inciting agent. Epinephrine and antihistamines followed by systemic corticosteroids are the mainstays of therapy for acute events. There is no prophylactic therapy that reliably prevents anaphylaxis.

We sought to determine the efficacy of omalizumab in the management of patients with frequent episodes of IA in a double-blind, placebo-controlled trial.

We prospectively enrolled 19 patients with frequent IA (≥6 episodes/y) who then underwent a medical evaluation that included a serum tryptase determination, mutational analysis for KIT D816V, and bone marrow evaluation to rule out a clonal mast cell disorder. Computer-generated random numbers were provided by the study pharmacist. The primary end point was anaphylactic events in the 6 months after baseline. Sixteen patients completed the primary trial.

No statistically significant difference was demonstrated between the placebo and treated groups. There was a trend for efficacy in the treatment group, particularly after 60 days. Overall, the safety profile was favorable without long-term side effects.

Omalizumab was safely administered to a difficult-to-treat patient population with IA. The efficacy results trended modestly in favor of the treatment group, but no statistically significant differences were detected.

Anaphylaxis is considered idiopathic when there is no known trigger. The signs and symptoms of idiopathic anaphylaxis (IA) are identical to those of anaphylaxis because of a known cause and can include cutaneous, circulatory, respiratory, gastrointestinal, and neurologic symptoms. Idiopathic anaphylaxis can be a frustrating disease for patients and health care providers. Episodes are unpredictable, and differential diagnosis is challenging. Current anaphylaxis guidelines have little specific guidance regarding differential diagnosis and long-term management of IA. Therefore, the objective of the Idiopathic Anaphylaxis Yardstick is to use published data and the authors' combined clinical experience to provide practical recommendations for the diagnosis and management of patients with IA.

Patients with mast cell diseases may suffer from various distressing symptoms, which can be insufficiently controlled with available therapies, severely affecting their quality of life. There is a need for new and safe treatment options for these patients.

We aimed to evaluate safety and efficacy of omalizumab administration in patients with a symptomatic mast cell disorder.

We included 55 patients with a mast cell disorder associated with debilitating symptoms who received omalizumab treatment between January 2015 and December 2017, after a multidisciplinary team meeting at the French National Reference Center for Mastocytosis.

A complete response was achieved for 1 patient (1.8%), a major response for 30 patients (54.5%), and a partial response for 12 patients (21.8%), resulting in an overall best response rate of 78.2% (43 of 55 patients). The response was persistent at least 3 months in 33 of 43 responding patients (76.7%). At the last follow-up, the final overall response rate was 58.2% (32 of 55 patients). Median time to first response was 2 months and median time to best response was 6 months. Omalizumab was dramatically effective on all superficial and general vasomotor symptoms and on most gastrointestinal or urinary symptoms, and partially effective on most neuropsychiatric symptoms. Safety profile was acceptable, except for one severe adverse event (edema of the larynx and dyspnea after the first injection of omalizumab). Side effects were reported in 16 patients (29%), mainly of low to mild intensity, yet causing interruption of treatment in 5 patients (9%).

Omalizumab seems to be a useful therapeutic option to control mast cell–mediator symptoms and displays a favorable safety profile.