J Clin Oncol. alpha-gal after tick bites, developing alpha-gal specific IgE that is detected commercially using a solid phase immunoassay.3 We present three clinical cases to illustrate this new syndrome. In addition, we review the discovery of alpha-gal specific IgE and how it impacts the current approach to anaphylaxis. CASES Case 1 An 82-year-old Caucasian man presented to clinic with a one-day history of a pruritic rash on his trunk and ankles. Past medical history was significant for hypertension, a transient ischemic attack, and polymyalgia rheumatica in remission. His wife thought the rash was an allergic reaction to amoxicillin which had been prescribed for a recent dental infection. The patient reported a history of occasional hives while playing golf, which he attributed to pesticide exposure. The last episode had been three years earlier. Physical exam revealed mild erythema and edema of his ankles and an urticarial rash on bilateral axillae and trunk. His wife also commented that ten days prior to the visit, she had removed a lone star tick from his back, which may have been attached for as long as 36 hours. Given the high prevalence RITA (NSC 652287) of Lyme disease in central Virginia, he was prescribed a ten-day course of doxycycline. The day after the clinic visit, the patient traveled to Canada. On the day before his return, he ate beef tenderloin at 6 PM, went to bed at 10 PM, and woke up around 11 PM covered with intensely pruritic hives and had the urge to urinate. He took 48?mg of liquid diphenhydramine and collapsed en route to the bathroom. He was unresponsive for 15 minutes. Emergency Medical Services (EMS) arrived and measured his supine blood pressure at 86/40?mmHg. He was treated with intravenous (IV) fluids and 50?mg of IV diphenhydramine, with complete resolution of his symptoms. Work-up in the Emergency Department (ED) was negative for myocardial infarction and stroke. Shortly after the trip, his wife incidentally read an article in a local newspaper regarding red meat ingestion causing anaphylaxis and discussed it with his primary care physician, who referred him to an allergist. The allergy/immunology work-up revealed IgE alpha gal 100 kU/L (Viracor-IBT, reference range 0.35 kU/L), specific IgE to beef 45 kU/L and to pork RITA (NSC 652287) 53 kU/L (ImmunoCAP, Phadia, reference range 0.35 kU/L). Since the Canadian incident seven months prior, he has remained symptom-free while avoiding beef, pork RITA (NSC 652287) and lamb. He continues to tolerate chicken, turkey, and fish without problem. Case 2 A 54-year-old Caucasian man was seen in a tertiary allergy/immunology clinic for a history of anaphylaxis to insect stings. Notes from previous allergists indicated multiple episodes of allergic reactions without clear cause. Reactions involved pruritic hives, sensation of lip and tongue swelling, and occasional wheezing. He had multiple ED visits for these allergic reactions and has intermittently required epinephrine. On one occasion, he had prime rib for dinner and awoke at approximately 2 AM with hives on his thighs, which then became generalized. He took 25?mg of Mouse monoclonal to KARS diphenhydramine and went back to bed. At 7:30 AM, he awoke with the progression of hives affecting his entire body, and with associated lip and tongue swelling. Despite additional diphenhydramine, he became dizzy and felt his throat closing. He gave himself an epinephrine injection and called 911. EMS administered another dose of epinephrine, which was repeated a third time in the ED. He was observed in the hospital for a day before he was discharged with a course of prednisone. His subsequent skin prick test was negative to beef and pork. His IgE alpha-gal was 3.94?IU/mL (University of Virginia, reference range 0.35?IU/mL), specific IgE to beef 1.5 kU/L and to pork 0.7 kU/L. He now avoids beef and pork, but has tolerated chicken, turkey and fish without incident for over a year. Case 3 A 29-year-old Caucasian woman presented with a several year history of intermittent large hives. These occurred in the middle of the night and resolved two to three hours after taking diphenhydramine. They were often preceded by a prodrome of abdominal cramping. She recalled being bitten by ticks many years ago, but did not recall recent bites. She experienced two episodes.