ARTICLE IN PRESS The Journal of Emergency Medicine, Vol. xx, No. xx, pp. xxx, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/07 $–see front matter doi:10.1016/j.jemermed.2007.06.018 Selected Topics: Toxicology ANIMAL BITES AND STINGS WITH ANAPHYLACTIC POTENTIAL John H. Klotz, PHD,* Stephen A. Klotz, MD,† and Jacob L. Pinnas, MD† *Department of Entomology, University of California, Riverside, Riverside, California and †Department of Medicine, University of Arizona School of Medicine, Tucson, Arizona Reprint Address: John H. Klotz, PHD, Department of Entomology, University of California, Riverside, CA 92521 e Abstract—Anaphylaxis to animal bites and stings poses INTRODUCTION a significant medical risk of vascular or respiratory reac- tions that vary according to the patient’s response and Historical Perspective and Definition nature of the insult. Emergency Physicians frequently see patients who complain of an allergic reaction to an animal bite or sting. Although Hymenoptera stings, specifically Anaphylaxis, meaning “without protection,” was coined those of wasps, bees, and hornets, account for the majority in the early 1900s by Richet, who, with Portier, dis- of these cases, other invertebrates and vertebrates are ca- covered the phenomenon while conducting experi- pable of causing allergic reactions and anaphylaxis. Many ments on venom from the Portuguese man-of-war and of the causative animals are quite unusual, and their bites sea anemone. They exposed dogs to small doses of and stings are not commonly appreciated as potential venom and then, several weeks later, repeated the causes of anaphylaxis. We conducted a literature review to injection on these healthy dogs. Within seconds of the identify documented reports of anaphylaxis and anaphylac- second injection the dogs became ill, and shortly toid reactions to animal bites and stings. This summary is thereafter, died. Richet and Portier proposed two fac- meant to heighten awareness of the diversity of animals that may cause anaphylaxis, hopefully leading to more rapid tors that were necessary and sufficient to cause an diagnosis and treatment of this dangerous condition. A anaphylactic reaction: “increased sensitivity to a poi- diverse group of animals was found whose bites and stings son after previous injection of the same poison, and an cause anaphylaxis and anaphylactoid reactions. Some case incubation period necessary for this state of increased summaries are presented. A potentially life-saving plan is to sensitivity to develop” (1). direct patients to proper follow-up care to prevent a future Modern definitions of anaphylaxis reflect our more life-threatening reaction, including: prescribing epineph- advanced understanding of its physiological basis: an rine and antihistamines with proper instructions for their acute systemic allergic reaction occurring as a result use; referral to an allergist to determine if skin testing, of the release of chemical mediators after an immu- radioallergosorbent test, and immunotherapy are indicated; nologic reaction, typically IgE-mediated. Since its dis- and reporting the case to state or local Poison Control Centers. In covery, numerous causative agents in addition to some cases it may be helpful to consult an entomologist or a pest control service for help in identification and elimination of certain venom have been implicated, including anaphylactic offenders. © 2007 Elsevier Inc. reactions to foods, medications, latex, vaccines, aller- genic extracts, hormones, animal or human proteins, e Keywords—anaphylaxis; anaphylactoid; systemic reac- colorants, polysaccharides, and exercise (2). Insect tions; insect venoms; animal venoms; bites and stings sting allergies, however, are the only form of anaphy- RECEIVED: 1 August 2005; FINAL SUBMISSION RECEIVED: 6 December 2006; ACCEPTED: 11 February 2007 1 ARTICLE IN PRESS 2 J. H. Klotz et al. laxis for which allergen-specific immunotherapy is METHODS currently available (3). Literature Review Clinically, anaphylactic or anaphylactoid (resembling anaphylaxis but mechanism unknown) reactions can take This article summarizes the various cases that have been almost any form but most commonly present with urti- reported of anaphylactic and anaphylactic-like reactions caria and angioedema, followed by respiratory distress, to animal bites and stings. A MEDLINE search was dizziness, syncope, and shock. In some, death may occur conducted to find these reports employing a keyword (2,4). Gastrointestinal manifestations may accompany search with OVID, using the following terms: anaphy- any of the above signs and symptoms. Toxic reactions laxis, anaphylactoid, systemic reactions, insect venoms, may be caused by multiple stings, up to hundreds or and animal venoms. The search was limited to articles in thousands, and vary with the toxins introduced and the English from 1966–2005. Secondary sources of infor- makeup and size of the individual. Therapy for anaphy- mation on anaphylaxis were identified from references in laxis includes H1 and H2 antihistamines and epinephrine these articles and also were included in this review. by injection, with steroids for the more persistent or The cases of anaphylaxis are categorized taxonomi- refractory cases (5). cally by the offending organisms in Tables 1 and 2. Also Hymenoptera stings are one of the most common shown is evidence for an IgE-mediated basis: i.e., (ϩ)in causes of anaphylaxis (4). Anaphylactic reactions to bites vivo skin test, or (ϩ) in vitro RAST (radioallergosorbent and stings of other arthropods are less common, and even test) reactivity, and the pertinent references. Case pre- fewer have been reported for non-arthropod groups (6). sentations that to date lack evidence for IgE-mediated Taken together, these organisms pose a significant med- reactivity are listed as anaphylactic-like in Table 3. Some ical risk. cases are not covered in the text but are listed in the Table 1. Anaphylactic Reactions to Insect Bites and Stings Evidence for IgE Mediation† Scientific Nomenclature (Common Name)* In Vivo Tests In Vitro Tests References Phylum: Arthropoda Class: Insecta Order: Hymenoptera Family: Vespidae Genus: Vespula (ground-nesting yellowjackets) ϩϩ8–12 Dolichovespula (aerial-nesting yellowjackets) ϩϩ11,12 Vespa (hornets) ϩϩ8,23 Polistes (paper wasps) ϩϩ19,20 Family: Apidae Genus: Apis (honey bees) ϩϩ11,13,14 Bombus (bumble bees) ϩϩ24 Family: Formicidae Genus: Solenopsis (fire ants) ϩϩ16,17 Pogonomyrmex (harvester ants) ϩϩ21,22 Tetramorium ϩ 31 Myrmecia (bulldog ants) ϩϩ32–35 Pachycondyla (Chinese needle and Samsum ants) ϩϩ37–41 Formica (wood ants) ϩϩ43 Order: Hemiptera Family: Reduviidae Genus: Triatoma (kissing bugs) ϩϩ44–46 Order: Diptera Family: Tabanidae Genus: Chrysops (deer flies) ϩϩ52,54 Family: Simuliidae (black flies) ϩϩ48 Culicidae (mosquitoes) ϩ 55 Muscidae Genus: Glossina (tsetse flies) ϩ 60 Order: Lepidoptera Family: Notodontidae Genus: Thaumetopoea (pine processionary caterpillars) ϩϩ62–64 * Common names in parentheses were reported to induce the reaction. † Empty spaces indicate no evidence for IgE mediation. ARTICLE IN PRESS Anaphylactic Reactions to Animals 3 Table 2. Anaphylactic Reactions to Bites and Stings of Invertebrates (Non-insect) and Vertebrates Evidence for IgE Mediation† Scientific Nomenclature (Common Name)* In Vivo Tests In Vitro Tests References Phylum: Arthropoda Class: Arachnida Order: Acari Family: Ixodidae Genus: Ixodes holocyclus (Australian paralysis ticks) ϩϩ67 Ixodes pacificus (western black-legged ticks) ϩ 69,70 Ixodes ricinus ϩ 72 Rhiphicephalus ϩ 71 Family: Argasidae Genus: Argas (pigeon ticks) ϩϩ73,74 Order: Scorpiones Genus: Centruroides (common striped scorpions) ϩϩ77,78 Phylum: Cnidaria Class: Scyphozoa Genus: Chrysaora (sea nettles) ϩ 87,88 Phylum: Chordata Class: Reptilia Order: Squamata Family: Viperidae Genus: Crotalus (rattlesnakes) ϩ 93 Vipera (vipers) ϩϩ94,95 Family: Elapidae Genus: Hemachatus (rinkhals) ϩ 100 Class: Mammalia Order: Rodentia Family: Muridae Genus: Rattus (rats) ϩϩ106,107 Mus (mice) ϩϩ107,109 Gerbillus (gerbils) ϩ 110 Phodopus (hamsters) ϩϩ111,113 * Common names in parentheses were reported to induce the reaction. † Empty spaces indicate no evidence for IgE mediation. tables along with references numbered according to their United States are yellowjackets (Vespula and Dolicho- taxonomic category. Common toxic reactions that do not vespula) and honey bees (Apis), followed by fire ants resemble anaphylaxis are not included in this review (Solenopsis) and paper wasps (Polistes)(8–20). Har- (e.g., spider envenomations). vester ants (Pogonomyrmex), the introduced European hornet (Vespa crabro), bumble bees (Bombus), and sweat bees (Halictids) are of lesser importance (21–26). RESULTS AND DISCUSSION Ant stings, an emerging problem. Ants are not generally Anaphylactic and Anaphylactic-like Reactions to appreciated as causes of anaphylaxis, but a growing Insects (Tables 1 and 3) number of species in North America and on other con- Hymenoptera (bees, wasps, and ants). Of the inverte- tinents are being reported as causes of this medical brates, insects, particularly Hymenoptera, most com- emergency. The following case describes an anaphylac- monly cause anaphylaxis. In stinging bees, wasps, and tic reaction to a sting from a rough harvester ant, ants, the ovipositor of females has been modified into a Pogonomyrmex rugosus (27). stinger. This venom delivery system is a powerful de- fense against vertebrates, which, in the case of humans, Case summary 1. A 41-year-old