Opioid reaction

There is no indication for skin testing in this situation since opiods will likely cause a false-positive result due to the opiate receptor on cutaneous mast cells. An excerpt from the Practice Parameter “Drug Allergy: An Updated Practice Parameter (1).

L. Opiates
Summary Statement 138: Opiates and their analogs are a common cause of pseudoallergic reactions that are generally mild, are not life-threatening, and can be attenuated by preadministration of histamine1 receptor antihistamines. (C)
Opiates such as morphine, meperidine, codeine, and narcotic analogs can stimulate mast cell–mediated release directly without a specific immunologic mechanism. Patients who exhibit this tendency may experience generalized pruritus and urticaria after administration of a narcotic analgesic.
Occasional mild wheezing may be noted. Skin test results to opiates are difficult to interpret because these agents cause release of histamine from skin mast cells in all patients.
Dilute skin test concentrations have been recommended if an IgE-mediated reaction is suspected.580 A single case of a documented IgE-mediated reaction to morphine has been reported.581 Some opiate reactions can be attenuated by preadministration of antihistamines. Narcotic-induced pseudoallergic reactions are rarely life-threatening. If there is a history of such a reaction to an opiate and analgesia is required, a nonnarcotic alternative pain medication should be selected. If this does not control pain, graded challenge with an alternative opiate up to a dose that will control pain should be tried.
Fentanyl may be less likely to activate cutaneous mast cells via the opiate receptor (2) and thus may have a lower risk of causing generalized urticaria. Opiods may cause generalized urticaria but very rarely cause angioedema or significant decrease in blood pressure (3).
In summary, I do not consider opiods to be a risk for anaphylaxis though they may cause urticaria or generalized flushing. I would not skin test with this history due to the likely false positive results. I would consider pretreating with H1 inhibitors prior to the administration of an essential narcotic. I think fentanyl is less likely to result in urticaria.

1. Annals of Allergy Asthma Immunol 2010;105:273e1-78.

2. Wheal and flare responses to opioids in humans.
Levy JH, Brister NW, Shearin A, Ziegler J, Hug CC Jr, Adelson DM, Walker BF
Anesthesiology. 1989 May;70(5):756-60.
Certain opioids release histamine from cutaneous mast cells to produce local wheal and flare responses and adverse hemodynamic effects. In vivo responses to opioids suggest that cutaneous responses result from the interaction of opioids with opioid receptors on human mast cells. There are no data evaluating or comparing the opioids currently used in anesthesia. Volunteers were injected intradermally with different opioids as well as with naloxone and antihistamines to evaluate their effects on cutaneous mast cell reactivity and cutaneous vascular responses. Fentanyl and morphine produced concentration-dependent wheal and flare responses in the range of 5 X 10(-6) M to 1.5 X 10(-3) M. Volunteers were then tested intradermally with different opioids and histamine at a 5 X 10(-4) M concentration to determine their relative cutaneous effects. Morphine, meperidine, fentanyl, and sufentanil produced both wheal and flare responses that were significantly greater than those due to saline (P less than 0.05). Naloxone, alfentanil, and nalbuphine did not produce significant wheal or flare responses. Butorphenol was followed by a significant wheal but no flare. Naloxone attentuated cutaneous wheal and flare responses to fentanyl and the flare response to morphine. Intradermal antihistamines (diphenhydramine and cimetidine) produced significant wheal and flare responses. Electron micrographs of biopsies from fentanyl-induced wheals demonstrated normalmast cell architecture with no evidence of mast cell degranulation. Opioid effects on wheal and flare responses and mast cell degranulation appear independent of opioid analgesic potency. Opioids produce cutaneous vascular responses dependent on both histamine release from mast cells and direct effects on the vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

3. Mechanisms of nonimmunological histamine and tryptase release from human cutaneous mast cells.
Veien M, Szlam F, Holden JT, Yamaguchi K, Denson DD, Levy JH
Anesthesiology. 2000;92(4):1074.
BACKGROUND If mast cells are stimulated they release multiple mediators that delineate markers for immunologic and nonimmunologic reactions; histamine and tryptase are the two best known. Although histamine can be assayed in plasma, it is a nonspecific marker with a very short half-life. Tryptase has a longer half-life, but its release has not been proven to be specific for anaphylaxis. The authors investigated the mechanisms of nonimmunologic histamine release from human cutaneous mast cells to understand the mechanisms of mediator release and to determine whether tryptase was specific for allergic mediated activation.
METHODS Dispersed mast cell suspensions isolated from neonatal foreskins underwent challenge with vancomycin, calcium ionophore A23187, morphine, and atracurium, and histamine tryptase release was measured. The effects of calcium and magnesium, along with phospholipase C and phospholipase A2 inhibitors, also were investigated.
RESULTS Tryptase and histamine both were released by the known nonimmunologic stimuli (pharmacologic agents used in the current study; r2 = 0.6). Furthermore, vancomycin- and atracurium-induced histamine release was calcium dependent. Phospholipase C and phospholipase A2 inhibitors decreased vancomycin-induced histamine release, but not calcium ionophore A23187-induced release.
CONCLUSIONS Tryptase is not a specific marker of mast cell activation (ie., anaphylaxis), and signaling mechanisms for mast cell activation involve activation of phospholipase C and phospholipase A2 pathways that are also involved in other cellular activation mechanisms.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI