Allergy & Anaphylaxis (why, where, and what to do) Robert H. Brown, M.D., M.P.H. Professor Departments of Anesthesiology, Environmental Health Sciences, Medicine, and Radiology The Johns Hopkins Medical Institutions Baltimore, Maryland
Goals and Objectives 1) Recognize the clinical presentation of anaphylactic reactions. 2) Summarize the management of an anaphylactic reaction. 3) List the common agents responsible for anaphylactic reactions. 4) Describe desensitization therapies to reduce the incidence of anaphylactic reactions.
Publications 1000 Anaphylaxis Anaphylaxis Number of Publications 800 600 400 200 0 1900 1920 1940 1960 1980 2000 year (http://www.ncbi.nlm.nih.gov/pubmed)
250 Publications pediatric anaphylaxis Number of Publications 200 150 100 50 0 1940 1950 1960 1970 1980 1990 2000 2010 year (http://www.ncbi.nlm.nih.gov/pubmed)
Overview of the Allergic Cascade B lymphocyte Release of Allergic mediators ε-switch Plasma cell Release of IgE Allergens Anaphylaxis Mast cells Basophils
IgE-dependent Release of Inflammatory Mediators IgE Allergens Immediate Release Granule contents: Histamine, TNF-α, Proteases, Heparin, Tryptase Over Minutes Lipid mediators: Prostaglandins Leukotrienes Over Hours Cytokine production: Specifically IL- 4, IL-13
Signs and Symptoms Skin: hives, erythema, urticaria, pruritis, localized or general Eyes: red, itching, angioedema Upper respiratory: stuffy or runny nose Lower respiratory: shortness of breath, cough, wheezing GI: cramps, nausea, vomiting, diarrhea CV: hypotension, tachycardia, cardiovascular collapse
Intraoperative Symptoms (Anesth Analg 2011;113:1202 12)
Immediate Treatment Stop exposure (determine causative agent) Airway management, intubate if necessary Volume expansion with balanced salt solution Epinephrine, starting dose 0.5-1.0 µg/kg, titrate as needed Bronchodilators (if needed) See (Dewachter et al. Anesthesiology 103:40, 2005)
This reluctance to administer epinephrine is even reflected in our study of the treatment of anaphylaxis during anesthesia, where anesthetists chose to administer antihistamines and steroids before epinephrine in 16.8% of patients and did not administer epinephrine at all in 17.2% of patients having C3 and C4 reactions with cardiovascular instability. Reasons for this are unclear, but could be because of limited knowledge of the treatment algorithm for anaphylaxis, lack of experience with the use of epinephrine outside the cardiac arrest setting, or a reluctance to treat a tachycardic patient with a drug with a positive chronotropic effect. Because there is no proven benefit of antihistamines and steroids in anaphylactic shock the administration of epinephrine should always precede treatment with antihistamines and steroids once the diagnosis of anaphylaxis has been made. Anesthesiology 2011; 115:111 6
Differential Diagnosis (Liccardi et al. J Investig Allergol Clin Immunol. 18: 1, 2008)
Postoperative Care Check that environment is safe Transfer to monitored area
Diagnosis History: timing of events, previous reactions. Nonspecific markers in the blood: Serum tryptase: peak ~1 hr (t 1/2 2 hrs) (red top, collect within 4 hrs) Serology: IgE specific antibodies (if available) Skin Test: (when available, with caveats) (Gomez et al. Allergol Immunopathol (Madr). 43:203, 2015) (Guyer et al. J allergy Clin Immunol 3:94, 2016) (Kuhlen et al, J Allergy Clin Immunol Pract. 4: 697, 2016)
Diagnosis N=111 referred to clinic for suspected allergic reaction while under anesthesia N=5 suggestive agent confirmed N=67 suggestion of a causative agent N=13 partial match (add n causative agents) N=49 suggestive agent not confirmed N=44 no suggestion of a causative agent N=31 no agent confirmed N=18 other agent confirmed (Krøigaard et al., Brit J Anaesth. 95: 468, 2005)
Causative agents (General) Pediatric Emergency Care. 29(2):131-135, 2013.
Causative agents (Perioperative) (USA, Mayo, n=38 adults) Agents Antibiotics Latex Induction agents Neuromuscular Agents Opioids Other agents No. events (%) 9 (50.0%) 3 (16.7%) 3 (16.7%) 2 (11.1%) 1 (%) 4 (%) (Gurriari, Anes Analg 113: 1202, 2011)
Causative agents (Perioperative) (USA, Cleveland Clinic, n=30 adults) Agents Antibiotics Neuromuscular Agents Latex No agent identified No. events (%) 10 (33%) 4 (13%) 3 (10%) 13 (43%) (Gonzalez-Estrada et al., J Allergy Clin Immunol Pract. 3: 101, 2015)
Causative agents (Perioperative) (USA, MGH, n=25 adults; only 9 ST+) Agents Antibiotics Latex Induction agents Neuromuscular Agents Opioids Other agents No. events (%) 9 0 0 0 0 0 (Kuhlen et al, J Allergy Clin Immunol Pract. 4: 697, 2016)
Causative agents (Intraoperative) (Singapore, n=34 adults) Total 22 36 27 26 14 2 1 3 16 4 rank 4 1 2 3 5 7 8 6 (Chenet al., Singapore Med J. 57: 126, 2016)
Causative agents (Perioperative) (France, n=477 adults) Agents Neuromuscular Agents Latex Antibiotics Hypnotics Opioids Colloids Other agents No. events (%) 336 (69.2%) 59 (12.1%) 39 (8.0%) 18 (3.7%) 7 (1.4%) 13 (2.7%) 14 (2.9%) (Laxenaire, Br J Anaesth 87: 549, 2001)
Causative agents (Perioperative) (Norway, n=83 adults) (Harboe et al., Anesthesiol. 102: 897, 2005)
Causative agents (Perioperative) (France, n=68 children) Allergy 2005: 60: 828 834
(Harboe et al. Allergy, 62:1445, 2007)
Cross Reactivity among allergic reactions to NMBA Anaesth Intensive Care 2012; 40: 861-866
Publications Natural rubber latex allergies (http://www.ncbi.nlm.nih.gov/pubmed)
Goal Make Johns Hopkins Hospital a latex safe institution. (Brown et al. Joint Commission Journal on Quality and Safety 29:113-123, 2003) (Brown et al. Joint Commission Journal on Quality and Safety 35: 224-228, 2009) Definitions At Risk - Any individual with identified risk factors who, if exposed to a significant amount of latex allergen, are likely to develop a latex allergy. Latex Safe Environment - An area with minimal latex allergen, insufficient to elicit a latex allergic reaction. Latex Free Environment - An area with no latex allergen. (A handful of products are still used at JHH that contain latex)
Wikipedia Latex allergy
Potential New Approaches to the Treatment of (Food) Allergy Anti-IgE antibodies (Xolair) Immunotherapy intact allergen modified allergens homologous proteins plasmid vaccines Ingestion of extensively heated milk and egg From Robert A. Wood, MD Professor of Pediatrics and International Health; Director, Pediatric Allergy and Immunology, JHMI
Summary of Immunotherapy Study Results In small studies of children with significant milk, peanut, and egg allergy, oral immunotherapy is capable of inducing significant changes in threshold for clinical reactivity Tolerance is only accomplished in a minority of patients Rates of adverse reactions (~30%, GI, skin, respiratory, multisystem) are significant but likely acceptable, especially if most develop long term tolerance Further study is clearly warranted to decrease adverse reactions and improve efficacy, including more consistent induction of long term tolerance
Acknowledgement Robert Hamilton, Ph.D. James Schauble, M.D. Kathy Hale, R.N. Steven Kleeberger, Ph.D. Margaret Mintz, B.A. Anne Jedlicka, B.S. Mary McAllister, M.A. Alan Scott, Ph.D. Timothy Buckley, Ph.D. Kannika Taenkhum, M.H.S. Connie Monitto, M.D. Colleen Cusick Linda Bushell-English Betty Gibula William Kennett Johns Hopkins Hospital Latex Task Force Associations of School of Public Health/CDC S1208