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“Sulfa Allergy” 8/24/16 Drug Allergy! Now What Drug is Safe? Speaker has no relationship to disclose. Prescribing Pearls for Primary Care Amelie Hollier, DNP, FNP-BC, FAANP Lafayette, LA President, APEA Objectives What is a Drug Allergy? • Identify symptoms of drug allergies in • “Immunologic reaction to a drug” patients who exhibit possible allergic • Gell And Coombs Classification System is reactions. used • Develop a strategy for continuation of pharmacologic treatment after allergy is identified • Identify “culprit” drugs involved in reactions Gell and Coombs Classification System Type I Mechanism Ty pe I IgE-mediated Anaphylaxis, Activation of mast cells, basophils, release of (occurs angioedema, Immediate-type vasoactive substances: histamines, prostaglandins, within 1 hives, hypersensitivity cytokines, and leukotrienes hour) bronchospasm Type II IgG antibodies and Hemolytic complement anemia Type III Immune complex Serum sickness disease; IgG and IgM Type IV Cell mediated or Contact What we delayed dermatitis don’t see!! What we do see!! hypersensitivity 1 8/24/16 Characteristics of Type I Reactions Type I Reactions Manifestations are due to ruptured mast cells MOST SEVERE: • Classic finding: Urticaria, pruritis, flushing, • Angioedema angioedema, wheezing, hypotension, GI • Anaphylaxis-involves at least 2 body systems symptoms • Classic wheal and flare hallmark signs of mast cell degranulation True or False Anaphylaxis Epinephrine is the drug Epinephrine: • Drug of choice of choice to treat • Prevent or reverses airflow obstruction in upper and lower airways anaphylactic reactions. • Prevents or reverses cardiovascular collapse Anaphylaxis Anaphylaxis Bronchodilators: Histamines H1: • Given to relieve symptoms not relieved by • Relieve itch and hives epinephrine • DO NOT RELIEVE airway symptoms, shock, etc. • Adjunctive treatment • Onset of action is slow (even if given IV) • No effect on mucosal edema 2 8/24/16 Anaphylaxis Anaphylaxis Histamines H2: Glucocorticoids: • Minimal evidence to support use • Onset of action takes several hours • Guidelines don’t include these • Given to prevent the biphasic reactions that • Ranitidine usually infused take place in 23% of adults with anaphylaxis • Cimetidine infusion can produce hypotension (11% of children) • Stop at 72 hours because all biphasic reactions take place by 72 hours Take Home Point Type 1: When? • Anaphylaxis almost NEVER occurs • Rapidly! multiple days in to therapy IF doses • IV: seconds to minutes have been continuous • • If doses were skipped, then possible Oral on empty stomach: 3- 30 minutes • Oral with food: 10- 60 minutes Type 1: When? Type I Reactions are COMMON!!!! Ty pe I IgE-mediated Anaphylaxis, • Urticarial rashes after multiple days of (within 1 Immediate-type angioedema, exposure are possible if drug is known to be hour) hypersensitivity hives, allergenic (beta-lactams) bronchospasm • Consider T cell involvement if rash occurs Type II IgG antibodies and Hemolytic several days into treatment complement anemia Type III Immune complex Serum sickness disease; IgG and IgM Type IV Cell mediated or Contact delayed dermatitis hypersensitivity 3 8/24/16 Types II and III are Uncommon Type IV is Common Ty pe I IgE-mediated Anaphylaxis, Type I IgE-mediated Anaphylaxis, (within 1 Immediate-type angioedema, (within 1 Immediate-type angioedema, hour) hypersensitivity hives, hour) hypersensitivity hives, bronchospasm bronchospasm Type II IgG antibodies and Hemolytic Type II IgG antibodies and Hemolytic complement anemia complement anemia Type III Immune complex Serum sickness Type III Immune complex Serum sickness disease; IgG and IgM disease; IgG and IgM Ty pe I V Cell mediated or Contact Ty pe I V T Cell mediated or Contact delayed dermatitis delayed dermatitis hypersensitivity hypersensitivity Type IV Mechanism Type IV Cell Mediated Reaction T-cell mediated, delayed at least 24-48 hours but may begin weeks to months after treatment starts, not • Prominent skin findings (skin is a huge mediated by antibodies but involves activation of T repository for T cells) cells • Skin reacts rapidly if allergens penetrate skin or diffuse into the skin via circulation • Other organ involvement What we don’t see!! What we do see!! Type IV Cell Mediated Reaction Type IV Cell Mediated Reaction Common Skin Reactions: MOST SEVERE: • Contact dermatitis • Stevens-Johnson syndrome (SJS) • Morbilliform eruptions (other mechanisms can produce morbilliform rashes) • Toxic epidermal necrolysis (TEN) • Others • Drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS) 4 8/24/16 When? Type IV Reactions When? Type IV Reactions • Delayed by at least 48-72 hours • SJS, DRESS can occur after weeks • Could even occur 1-3 days after 10 of unremarkable treatment day course of antibiotic • Usually days to weeks • Very impressive!!!! • Reaction depends on how many T cells are stimulated by the drug (a lotà quickly) (fewà slowly) Type IV Reaction are COMMON!!!! “Other” Reactions Ty pe I IgE-mediated Anaphylaxis, Ty pe I IgE-mediated Anaphylaxis, (within 1 angioedema, (within 1 angioedema, Immediate-type Immediate-type hour) hives, hour) hives, hypersensitivity hypersensitivity bronchospasm bronchospasm Type II IgG antibodies and Hemolytic Type II IgG antibodies and Hemolytic complement anemia complement anemia Type III Immune complex Serum sickness Type III Immune complex Serum sickness disease; IgG and IgM disease; IgG and Ty pe I V Cell mediated or Contact IgM delayed dermatitis Ty pe I V Cell mediated or Contact hypersensitivity delayed dermatitis Other Various Various hypersensitivity “Other” Types of Reactions are Pretty Common Example 1: Opiates Pseudoallergic Reactions Pseudoallergic Reactions • Don’t be fooled by the name!!!!! • Range from mild to fatal • Opiate analgesics: • Uncertain how these reactions occur Morphine and codeine • Probably mast cell degranulation by a cause direct mast cell non-IgE mediated mechanism activation • Don’t worsen with repeated exposure 5 8/24/16 Common Culprits Case: “John” Pseudoallergic Reactions John has taken guafenesin with • Radiocontrast medium • Opiates dextromethorphan. He • NSAIDs develops urticaria. • Muscle relaxants (atracurium, vecuronium, succinylcholine, curare) • Chemo agents Etiology? • Vancomycin: “Red man” syndrome Case: “John” Other Common Culprits Dextromethorphan PseudoallergicReactions in Children • To m at o e s Codiene • Strawberries Viral Infections Case “Emma” Can predispose patients to reactions Emma is a college student who to certain drugs presents with cough, fever, and • Epstein-Barr plus amoxicillin feeling “lousy” after studying for 24 • Amoxicillin in children can produce hours for a “big” exam. She receives exanthematous reactions a Rx for azithromycin. She returns • CMV plus antibiotics the next day with acute urticaria. • HHV 6 Etiology? • HIV (sulfa drugs) 6 8/24/16 Allergic Reaction Allergic Reaction Penicillins • Most common allergies are to • 5.1/1000 patients is antibiotics allergic (0.5%) • 5-10% of patients report PCN allergy • PCN can cause all 4 types of reactionsbut Type 1 is most common The truth is……. The problem is……. Self reported “PCN allergic” Most (85-90%) patients are more likely to patients who receive broad spectrum state PCN allergy antibiotics: DO NOT have a true allergy to FQs, clindamycin, vancomycin, rd PCN 3 gen cephalosporins. Macy E, Contreras R. Healthcare use and serious infection prevalence associated with penicillin “allergy” in hos pitaliz ed patients : a cohort s tudy. J Allergy Clin Immunol. 2014; 133:790-796. Another problem is……. Most Common PCN Reaction Self reported “PCN allergic” IgE Mediated patients are: Presents with intense 30% more likely to have VRE itching, urticaria, angioedema, wheezing, 23% more likely to have C diff abdominal distress 14% more likely to have MRSA (emesis or diarrhea), Reddy V, Baman NS, Whitener C, Ishmael FT. Drug resistant infections with methicillin resistant Staphylococcus aureus, Clostridium difficile, and vancomycin resistant Enterococcus are associated with a hypotension higher prevalence of penicillin allergy. J Allergy Clin Immunol. 2013;131(Suppl):AB1 70. 7 8/24/16 IgE Mediated Symptoms Risk Factors for PCN Allergy • Symptoms appear within minutes to 4 • Age: 20-49 years at greatest risk for hours of exposure to the IgE, especially anaphylactic allergen • Frequent repeated courses • It can happen on the • Route: IV, IM more associated with second exposure or the anaphylaxis 22nd exposure Hereditary Factors A 24 year old receiving amoxicillin-clavulanate • Children of parents with for acute sinusitis antibiotic allergy 15 develops raised rash and times more likely to be nd antibiotic allergic (by urticaria on 2 day of history) treatment. What now? J Allergy Clin Immunol. 2000;105(1 Pt 1):184. Clinical Action Clinical Action • Bring her into the office for evaluation • If a true reaction: Treat it! (Epinephrine, of the symptoms! antihistamines, steroids, etc.) • Patients tend to be poor historians • Get detailed history from patient about skin rashes • Skin testing is available • Able to test for PCN allergy; and allergy to clavulanate 8 8/24/16 Clinical Action Suppose this happened 3 years ago? • Strongly consider referral to allergist for confirmatory testing 24 year old receiving amoxicillin- • Complete test could take 2 hours (Skin test; if clavulanate for acute sinusitis negative, then oral amoxicillin challenge with nd 1 hour observation) develops urticaria on 2 day of treatment. What now? Clinical
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