Outcome of prophylactic therapy for idiopathic anaphylaxis. OBJECTIVE: To determine the efficacy of a prophylactic regimen (prednisone, H1 blockade, and sympathomimetic amine therapy) in patients with idiopathic anaphylaxis. DESIGN: Clinical trial before and after treatment. SETTING: Referral-based allergy clinic at a major medical center. PATIENTS: Fifty-three patients with a history compatible with idiopathic anaphylaxis for at least 6 months before presentation to the allergy service and with subsequent management by the service for at least 6 months. INTERVENTIONS: Patients with frequent life-threatening symptoms were treated with a prophylactic regimen. Patients with infrequent episodes of idiopathic anaphylaxis were only treated acutely for each episode of anaphylaxis. MEASUREMENTS AND MAIN RESULTS: The results favored prophylactic treatment with prednisone for patients who were classified as generalized-frequent in the clinical outcome measures of frequency (per patient per year) of episodes (mean before treatment, 7.31 +/- 6.46; after treatment, 3.61 +/- 4.73; P less than 0.02) and emergency room visits (mean before treatment, 1.94 +/- 3.42; after treatment, 0.21 +/- 0.44; P less than 0.005) and for patients classified as angioedema-frequent in the frequency of episodes (mean before treatment, 14.93 +/- 15.89; after treatment, 2.58 +/- 2.18; P less than 0.003) and emergency room visits (mean before treatment, 0.76 +/- 1.01; after treatment, 0.07 +/- 0.11; P less than 0.025). No statistically significant difference was found for patients classified as generalized-infrequent in the frequency of episodes (mean before treatment, 2.01 +/- 1.30; after treatment, 1.36 +/- 1.79) or of the emergency room visits (mean before treatment, 0.56 +/- 0.71; after treatment, 0.32 +/- 0.75) or for patients classified as angioedema-infrequent in the frequency of episodes (mean before treatment, 1.94 +/- 1.55; after treatment, 2.03 +/- 2.16) or of emergency room visits (mean before treatment, 0.27 +/- 0.44; after treatment, 0.37 +/- 0.59). CONCLUSIONS: Prophylactic treatment with prednisone and H1 antihistamines with or without sympathomimetic amines improves clinical outcome in patients who are classified as idiopathic anaphylaxis-angioedema frequent and idiopathic anaphylaxis-generalized frequent. 