A 51-year-old nurse reported 8 episodes of anaphylaxis over 5 months and most required ambulance transfer to hospital. They occurred while eating but no particular foods were suspected. At least 6 episodes were witnessed by physicians, and emergency treatment resulted in rapid resolution. Each episode comprised feeling throat obstruction, stridor, and occasional pruritus, but no rash or hypotension. One episode occurred at work and was treated by her employer physicians. She was evaluated by a local allergist (Table 1). Skin prick testing (SPT) on two visits was negative, but on both occasions she developed severe stridor that immediately resolved with epinephrine. She was referred to our clinic to identify the cause.

Our history-taking revealed she had numerous hospital admissions for a variety of medical and surgical reasons. She has been a divorcee for 25 years and living alone. She admitted work-related stress, and was recently placed on disability because of concern about the risk of fatal anaphylaxis at work. Her physical examination did not reveal any abnormal findings. She agreed on performing "certain" allergy tests on stages and the results to be discussed at the end. While being monitored, SPT was done with normal saline on 4 sites and histamine on 2 sites. She immediately developed severe stridor, without pruritus, rash, gastrointestinal symptoms, or dizziness. She maintained normal vital signs, blood pressure, pulse oximetry, and peak expiratory flow rate. She demanded immediate epinephrine injection. Her symptoms resolved immediately upon injecting 0.1 mL normal saline. On her second visit, after applying SPT with 16 food extracts she exhibited stridor and insisted on receiving epinephrine. Again, 0.1 mL normal saline injection resulted in immediate resolution. On her third visit, SPT with 16 other food extracts were negative and she had no symptoms. The nature of tests were tactfully revealed but she exhibited displeasure. We discussed the possibility of vocal cord dysfunction to be evaluated at her city, which was ruled out and no anatomic abnormality was noted. She angrily rejected psychiatric evaluation.

Case 2 is a 42-year-old policeman whose work exposed him to skin contact with narcotics. At age 35, 2 days after receiving oxycodone and hydrocodone for an injury he reported transient rash on one arm. Post-surgery (placing shoulder plate), immediately after receiving hydromorphone complained of throat swelling and breathing difficulty that resolved after epinephrine intramuscularly and corticosteroids. A few hours later, immediately after a dose of oxycodone he reported the same symptoms. He was transferred to the ICU and improved after IV diphenhydramine, ranitidine and methylprednisolone. He was discharged next day on acetaminophen and prescription for epinephrine auto-injector , and was advised to avoid all narcotics.

Three years later, he felt throat tightness after administering a morphine-containing tablet to his dog. A few months later, he touched his lips after handling methamphetamine then felt local numbness and throat tightness. He administered epinephrine and went to the emergency department where he received prednisone though he had normal vital signs and physical examination. He was referred for allergy evaluation (Table 2) because he became concerned about occupational exposure or future need for pain medications or local anesthetics (he believed related to narcotics). He showed negative skin tests to fentanyl and xylocaine, yet within 5 minutes of application he felt his mouth as "cotton balls" and throat tightness, but no objective signs. He improved following epinephrine, then chlorpheniramine and solumedrol. On another visit, skin testing with bupivacaine was negative, yet he complained of throat tightness. He seemed anxious during testing. Normal saline intradermal test reproduced throat symptoms. After he was informed of the nature of the test and reassured, the symptoms quickly subsided spontaneously.

After he was reassured, his fear was alleviated and testing with novocaine and bupivacaine was negative and had uneventful titrated subcutaneous challenge with up to 2 mL of each. He underwent a procedure using 2 local anesthetics without any symptoms. He remained concerned about future potential risk from pain medications. He passed intradermal re-testing with fentanyl then uneventful titrated subcutaneous challenge. He had normal pre-test serum histamine (<1.5 ng/mL) and tryptase (4 ng/mL). Skin testing was not done with opioids because of their direct histamine release.