We describe the case of a 30-year-old woman who reported several episodes of anaphylaxis with angioedema and relapsing urticaria.  Some events were related to nonsteroidal anti-inflammatory drug intake and one episode followed alcohol ingestion, but in most cases  no triggers could be identified. Specific immunoglobulin E determination was negative for food and drug allergens, C3 and C4 were in  the normal range, C1 inhibitor was slightly reduced and serum tryptase was undetectable. In vivo autologous serum skin test and in vitro  basophil histamine release assay were positive indicating the presence of circulating histamine-releasing factors. When oral tolerance
tests were performed, only doxycycline was tolerated whereas levofloxacin, clarithromycin, nimesulide and tramadol caused mild urticaria.
Premedication with cetirizine allowed the patient to tolerate levofloxacin, clarithromycin and nimesulide. The demonstration of circulating  histamine-releasing factors in a patient with idiopathic anaphylaxis and multiple drug allergy syndrome provides a new mechanistic insight  and might open the way to new therapeutic approaches.

Key words: Autologous serum skin test. Chronic urticaria. Histamine-releasing factors. Idiopathic anaphylaxis. Multiple drug allergy   syndrome.