10/11/17

Allergy and Immunology Nothing to declare Pearls for Clinical Practice 2017 No discussion of non-FDA approved medication use Katherine Gundling, MD FACP Professor, Section Chief Allergy and Immunology UCSF

Perioperative Anaphylaxis Update in Drug Adverse Reactions (2) Intermission (with 2 Cool Immunology videos)! Reactions can be severe or fatal Hygiene hypothesis update News flash

1 10/11/17

Perioperative Anaphylaxis Perioperative Anaphylaxis

Exposure to many agents occurs during a short time Exposure to many agents occurs during a short time period: period: – Antibiotics – Antibiotics – Neuromuscular blocking agents – Neuromuscular blocking agents – Propofol – Propofol – Latex – Latex – Chlorhexidine – Chlorhexidine – Dyes – Dyes – Opioids – Opioids – Blood transfusions – Blood transfusions – Benzodiazepines – Benzodiazepines – Others – Others

Commercial products that contain More chlorhexidine containing products chlorhexidine (to name a few): § Antiseptic dressings § Skin washes/cleansers § Antiseptic mouthwashes § Topical disinfectants § Antiseptic sore throat lozenges and sprays § Bladder washouts § Antiseptic toothpastes § Eye drops § Topical eczema creams § Contact lens solution § Acne creams § Anesthetic gels for catheterization § Antiseptic powders such as athletes foot powder § Some creams and sprays (such as nasal sprays) § Antiseptic creams include chlorhexidine as a preservative § Antiseptic wipes § Some sunscreens

2 10/11/17

Clinical Pearls Clinical Pearls

****Chlorhexidine is embedded in some central line For any severe anaphylactic reaction history, catheters**** consider obtaining serum tryptase level to help rule out a mast cell disorder. If your patient develops a rash upon exposure to chlorhexidine, consider avoiding its use during the perioperative period.

A patient with a previous allergic reaction to A patient with a previous allergic reaction to which agent is most likely to experience a drug which agent is most likely to experience a drug allergic reaction to furosemide? allergic reaction to furosemide?

A. Acetazolamide A. Acetazolamide B. Atenolol B. Atenolol C. Penicillin C. Penicillin D. Trimethoprim-sulfamethoxazole D. Trimethoprim-sulfamethoxazole

3 10/11/17

Partial list of sulfonamide medications Reactions to sulfonamide non-antibiotics are likely due to predispostion to allergic reactions, not due to cross-reactivity with sulfonamide antibiotics! Arylamine Sulfonamides Non-arylamine Sulfonamides – Sulfamethoxazole Carbonic anhydrase inhibitors On the sulfonamide molecule it is the arylamine – Sulfadiazine Sulfonylureas component that is most allergenic, hence the vast – Sulfacetamide Loop diuretics majority of patients who react to arylamine – Sulfasalazine Thiazide diuretics sulfonamides will not react to non-arylamine • Sulfonamide antiretrovirals sulfonamides. Anti-inflammatory – Amprenavir Others – Fosampranavir

From the furosemide package insert, noted in 2017: The Drug Allergy Practice Parameters from “patients allergic to sulfonamides may also be the AAAAI state: allergic to furosemide.” “There is no evidence to suggest allergic cross- Updated recommendations: reactivity between sulfonamide antibiotics and “The weight of evidence suggests that withholding nonantibiotic sulfonamides.” non-antibacterial sulfonamides from patients with prior reactions to antibacterial sulfonamides or other non-antibacterial sulfonamides is not clinically justified.” AAAAI.org Drug Allergy: An Updated Practice N Engl J Med 349;17 Paramenter Am J Health-Syst Pharm 70:1483-94

4 10/11/17

Clinical Pearls Adverse Drug Reactions The term “sulfa” allergy should be dropped! Intermission (with 2 Cool Immunology videos)! § Endeavor to determine and report the exact medication Hygiene hypothesis update to which a reaction occurred. News flash

§ When that information is not available, inquire as to the condition that was being treated, and document the information.

Early life exposure to which of the following is most associated with the prevention of atopic Adverse Drug Reactions disease (atopic dermatitis, food allergy, allergic Intermission (with 2 Cool Immunology videos)! rhinitis, asthma)? Hygiene hypothesis update A. A household dog News flash B. An older brother C. Barn animals D. Dust mites in the pillow

5 10/11/17

Early life exposure to which of the following is most associated with the prevention of atopic Early exposure to barn animals is strongly disease (atopic dermatitis, food allergy, allergic associated with less atopy rhinitis, asthma)? Exposure to pets from infancy might also A. A household dog be helpful, as are older siblings B. An older brother Exposure to dust mites is associated with C. Barn animals increased atopic conditions (is this still D. Dust mites in the pillow true??)

Von Mutius E. Proc Am Thorac Soc 2007; Vol 4 pp 212-216

Farming, Bavarian Style

+ =

Images: Wikipedia dogs

6 10/11/17

Current Opinion Immunology 2016,42:41-47 Image by K. Gundling

Hot off the presses… Higher indoor levels of pet or pest allergens in infancy Environmental exposures and development were associated with lower risk of developing asthma. of asthma The abundance of a number of bacterial taxa in house Background: dust was associated with increased or decreased -Environmental exposure in early life appears to play an asthma risk. important role in the pathogenesis of childhood asthma Sampling of the association with taxa: -What exposures can be modified to decrease the -Homes without asthma: Kocuria genus more abundant; likelihood of developing asthma? produces kocurin, a potent macrolide with activity against Staphylococcus species -Homes with asthma: potent pathogens such as Staphylococcus, -442 high risk, inner-city children Haemophilus, Corynebacterium, (others) Evaluated the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 -It may not be just about diversity of the microbiome (popular years. theory) J Allergy Clin Immunol; Sept 2017 -Much work to be done to define cause and effect…..

7 10/11/17

Prevention of atopic conditions Other risk factors for the development of Clear: childhood asthma that confirmed previous – Infants should be breast fed observations: – New guidelines in 2017 for introduction of peanuts to infants (http://www.annallergy.org/article/S1081- 1206(16)31164-4/fulltext) – Early exposure to animals and a broad variety of Prenatal tobacco smoke exposure (umbilical proteins is associated with decreased likelihood of cord cotinine concentration) developing asthma – Allergen immunotherapy can prevent the Higher maternal stress and depression scores development of new sensitization and asthma

Gathering data: – Influence of food/microbiome of the gut and airways – Role of early exposures to pollution, infections, medications

JACI 122:114-8

8 10/11/17

News Flash

Adverse Drug Reactions Dust mite sublingual tablets have just been approved to treat allergic respiratory disease! Intermission (with Cool Immunology videos)! Hygiene hypothesis update Consider this type of immunotherapy for patients who: News flash -have year round allergy symptoms -who have a limited number of allergic triggers -who are tired of taking medication -who don’t have time to dedicate 3-5 years to allergy shots

Summary of Key Points

• Watch out for sneaky exposures to chlorhexidine, which can be associated with severe anaphylaxis • “Sulfa allergy” is a term that should be dropped • Immune cells at work are truly awe inspiring • Early life exposures play a key role in training a healthy immune system • For those people who already have allergy to dust mites, immunotherapy tablets are a new option to retrain the immune system

9