WORKSHOP in HANOI on April 29, 2017 Chang-Keun Kim, M.D., Ph.D Asthma & Allergy Center Inje University-Sanggye Paik Hospital Seoul, Korea • Total reported: about 230,000 Events in 2016 • Mild 68.3%, • Moderate 26.8% • Severe 4.9% Year Source: open KFDA Reports 2016 Top list in Korea • Anti-inflammatory Analgesics - 13.6%, most common • Anticancer drug - 9.3% • Antibiotics - 8.1% • X-ray contrast media - 8.0% • Synthetic drug - 7.8% Source: open KFDA Reports 2016 Usually experience some of the following symptoms • Skin rash • Hives • Itchy skin • Difficulty breathing • Light headedness, dizziness, loss of consciousness • Chief complaint : worsening dyspnea after corticosteroids treatment at ER • Age/sex : years old boy • Family History : Mother-B-asthma • PHx : B-asthma • Five to 10 minutes after the IV hydrocortisone infusion he developed worsening dyspnea and wheezing • 30 minutes later, he immediately presented with nausea, dizziness, weakness • At ICU admission, the patient was comatose, with dyspnea, generalized edema, arterial hypotension, and bradycardia After tracheal intubation, cardiopulmonary resuscitation, and infusions of dopamine and norepinephrine, and he was placed on mechanical ventilation due to respiratory failure Immediate hypersensitivity to corticosteroids: a case series in New Zeland • From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5) • Skin tests were positive in 8/23 patients, • 7/8 of these patients had a history of corticosteroid-associated anaphylaxis • Skin tests were positive at either the skin prick test or intradermal stages Baker at al Clin Exp Allergy 2015 A patient Case (admission : 2017 April 15) • Chief complaint : Skin rash, Difficult breathing dizziness after Amoxicillin treatment • Age/Sex : yrs, Boy • FHx : Mother (34 yrs), Hx of penicillin allergy Grandmother ( 62 yrs), Hx of penicillin allergy • PHx : Milk allergy On admission After days • The antibiotics most likely to cause an allergic reaction are penicillins and cephalosporins • Mild symptoms include red, itchy, flaky, or swollen skin • Severe symptoms include skin that blisters or peels, vision problems, and severe swelling or itching Severe reactions include conditions such as toxic epidermal necrolysis (TEN) • Anaphylaxis symptoms include throat tightness, trouble breathing, tingling, dizziness, and wheezing • Anaphylaxis is a sudden, life-threatening reaction ** Anaphylaxis may occur if you exercise after exposure to a trigger, such as after taking an antibiotic • Other allergies, such as to cats • A family history of antibiotic allergies • Frequent use of antibiotics • A long-term illness that makes your immune system more sensitive • Egg allergy has been regarded as a potential risk for anaphylaxis after administration of certain vaccines • Such as influenza and measles that are produced by means of inoculation of the viruses into embryonated hen eggs • Correct diagnosis of anaphylaxis based on a standardized case definition Vaccine 2007; 25: 5675-5684 • Proper management for safe vaccination • Identification of the “culprit” vaccine/vaccine component Anaphylaxis is a clinical syndrome characterized by • Sudden onset AND • Rapid progression of signs and symptoms AND • Involving multiple (≥2) organ systems Ruggeberg JU, Vaccine 2007; 25: 5675-5684 • Major dermatologic symptoms (DER) • Generalized urticaria • Angioedema • Generalized pruritus with skin rash • Major cardiovascular symptoms (CDV) • Measured hypotension • Clinical diagnosis of uncompensated shock • • • • • Major respiratory symotoms (RES) Bilateral wheeze Stridor Upper airway swelling Respiratory distress Ruggeberg JU, vaccine 2007; 25: 5675-5684 • Correct diagnosis of anaphylaxis based on a standardized case definition by the Brighton Collaboration – Vaccine 2007; 25: 5675-5684 • Proper management for safe vaccination • Identification of the “culprit” vaccine/ vaccine component Risk assessment Emergency kit available Vaccination Observation for 30 Anaphylaxis Lie patient on back with leg raised Insure airway, Assess breathing and circulation CPR R/O vasovagal syncope, panic attack Adrenaline (epinephrine) i.m in the anterolateral thigh 0,01 mg/kg body weight (0,01 ml/kg) up to a maximum of 0,5 mg Repeat injections of adrenalin in 5min if no improvement • Risk assessment is important – Hx of severe vaccine allergy? – Hx of antibiotics allergy? – Hx of severe food allergy? • Just “allergy” in a wide sense should not be a reason to postpone or dissuade vaccination • Out of 446 vaccine administration in 374 patients at “risk”, only minor reactions, such as rash, occurred, patient received anti-histamine and the others needed no treatment Review of the incidence of reactions to MMR in children with a history of egg allergy gives evidence for safety of MMR for children with egg allergy Cronin J Acta Paediatr 2012; 101: 941-945 • Greenhawt MJ Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy Ann Allergy Asthma Immunol 2012;109:426-430 • Owens G Higher-ovalbumin-content influenza vaccines are well tolerated in children with egg allergy J Allergy Clin Immunol 2011;127:264-265 • Erlewyn-Lajeunesse M Influenza immunization in egg allergy: an update for the 2011-2012 season Clin Exp Allergy 2011;41:1367-1370 • James JM Safe administration of influenza vaccine to patients with egg allergy J Pediatr 1998;133:624-628 2011/12 (whole product) from manufacturer A Nagao M, Fujisawa T, Ihara T, Kino Y Highly increased levels of IgE antibodies to vaccine components in children with influenza vaccine-associated anaphylaxis J Allergy Clin Immunol 2016; 137: 861867 Nagao M, Fujisawa T, Ihara T, Kino Y Highly increased levels of IgE antibodies to vaccine components in children with influenza vaccine-associated anaphylaxis J Allergy Clin Immunol 2016; 137: 861-867 Vaccine dilutions Thimerosal did not affect the basophil reactions Nagao M, Fujisawa T, Ihara T, Kino Y Highly increased levels of IgE antibodies to vaccine components in children with influenza vaccine-associated anaphylaxis J Allergy Clin Immunol 2016; 137: 861-867 • Anaphylaxis to previous year vaccine is the absolute contraindication for the next vaccination • This study indicated that one of additives Phenoxyethanol (PE) may have enhanced the reaction leading to anaphylaxis • Manufacturer A decided not to use PE in the vaccines for the next season • Anaphylaxis after administration of inactivated influenza vaccines may be caused by specific IgE to influenza vaccine component, namely HA protein, and not to contaminating egg protein • However, specific IgE to HA protein itself may not be sufficient to cause anaphylaxis, other factors, such as phenoxyethanol, in this case, is important • Drug Allergy and Anaphylaxis in Children is a significant problem • keys are • Correct clinical diagnosis • Prompt treatment • Identification of the culprit ... cephalosporins • Mild symptoms include red, itchy, flaky, or swollen skin • Severe symptoms include skin that blisters or peels, vision problems, and severe swelling or itching Severe reactions include... probably not related or definitely not related 1st injection 0.1 ml 2nd injection 0.2 ml 3rd injection 0.4 ml 4th injection 0.8 ml 5th injection 0.1 ml 6th injection 0.2 ml 7th injection 0.4 ml Local... necrolysis (TEN) • Anaphylaxis symptoms include throat tightness, trouble breathing, tingling, dizziness, and wheezing • Anaphylaxis is a sudden, life-threatening reaction ** Anaphylaxis may occur