The avoidance of allergens and allergen-specific immunotherapy (AIT) are the only curative treatments of allergic diseases. This requires identification of the offending allergens based on the clinical history and the results of allergy tests, but also on prior attempts to stabilize the disease with drugs. AIT in polysensitized patients with severe allergic diseases which are difficult to control is a major challenge. We report the case of a 16-year-old girl with rhinitis and severe asthma attributed to mites (Dermatophagoides pteronyssinus and Dennatophagoides farinae), grass pollen and cat dander. The addition of Omaluzimab to the pre-established optimal treatment helped to control the disease and allowed us to initiate sublingual immunotherapy (SLIT). SLIT was well tolerated during Omaluzimab administration and also after the drug was discontinued, and the treatment led to complete control of her allergic disease (symptoms, respiratory function and immunoassays). Several studies have shown that omalizumab increases tolerance to and efficacy of AIT in patients with respiratory and hymenoptera venom allergies. However, in most studies, omalizumab treatment was maintained during AIT. Our results in this young polysensitized girl with severe asthma agree with results reported in other studies which showed that pretreatment with omalizumab could lead to better tolerance and efficacy of AIT. Moreover, it was also reported that AIT can act synergistically with omalizumab and involves only the induction mechanisms of immune-regulation. (C) 2016 Elsevier Masson SAS. All rights reserved.