Chris McCrossin Thanks to Bruce MacLeod Ian Rigby

Chris McCrossin Thanks to Bruce MacLeod Ian Rigby
Anaphylaxis & Allergy Chris McCrossin Thanks to Bruce MacLeod Ian Rigby

Outline: Anaphylaxis and Allergy
Pathophysiology Diagnosis Management (treatment & disposition) Related Issues Angioedema Anaphylactoid Reactions Drug Hypersensitivity Reactions Several cases to highlight the various reactions Antibiotic Allergies Sulfonamide Allergies

Definition Definition
Proposed at the first symposium on the defn and mgmt of anaphylaxis Believed this will capture ~95% of patients with the syndrome Not validated, keep an open mind in unclear cases Ann Emerg Med 2006; 47: Essentially: skin findings with either respiratory compromise or shock or both

Epidemiology Most fatalities from insect bites occur with the first reaction Most fatalities from food allergies occur in patients with hx of previous mild reactions Alberta Fatalities Due to Anaphylaxis 11 deaths over 10 years at the foothills

Immunology 101 Type I Reactions
Antigen bridges two IgE molecules on the surface of basophils and mast cells to release histamine and leukotrienes in the Skin Blood vessels GI tract Respiratory tract Symptoms Urticaria, angioedema, nausea, vomiting, SOB, wheezing, hypotension Symptoms are related to the organ systems where mast cells predominate

Immunology 101 Shows how IgE is related to histamine release

Anaphylactic Signs & Symptoms
We’ll talk about this later but non-specific abdominal symptoms we usually relate to intolerance rather than allergy can actually be related to an IgE mediated process

Immunology 101 Type II Reactions (cytotoxic rxns)
Antigen specific IgG or IgM antibodies bind with drug antigens that are bound to the surface of native cells. Once antibodies bind to the cell coated in drug antigens the complement & reticuloendothelial system help destroy/remove the Ab coated cells RBC’s Platelets Keratinocytes Consequences Antibiotic induced hemolytic anemia & thrombocytopenia Autoimmune bullous disease (pemphigus vulgaris) dru

Immunology 101 Type III Reactions
Complexes of IgG (or IgM) antibodies + drug antigens form in the blood then deposit in tissue. This activates the complement system and causes local tissue destruction in Skin Joints Other tissues Consequences Serum Sickness

Immunology 101 Type IV Reactions (delayed-type hypersensitivity reactions) Mediated by activated T lymphocytes that recognize antigens from numerous sources (drugs, ingested foods, creams/lotions, etc) Now divided into 4 subtypes. Look this up if you are a NERD Examples Contact dermatitis SJS TEN Maculopapular rashes Your severe dermatological reactions tend to be mediated by type 4 reactions

Immune Mediated Reactions
Extended Gell and coombs classification Type of Immune Response Pathologic Characteristics Clinical Symptoms Cell Type Type I IgE Mast-cell degranulation Urticaria, Anaphylaxis B cells/Ig Type II IgG FcR dependent cell destruction Blood cell dyscrasia Type III IgG & Complement Immune complex deposition vasculitis Type IV IVa Th1 Monocyte activation Eczema T cell IVb Th2 Eosinophilic inflammation Maculopapular Bullous exanthema IVc Cytotoxic T lymphocytes CD4 or CD8 mediated killing IVd T cells Neutrophil recruitment and activation Pustular exanthema Any reaction mediated by these mechanisms represents an “allergy” but it is only the IgE mechanism that results in anaphylaxis. Anaphylactoid reaction also causes mast cell degranulation; however, it doesn’t involve IgE

Pathophysiology Histamine
Present in most tissues of the body, particularly high concentration in lungs, skin, & GI tract. Stored in mast cells and basophils Increasing cAMP levels in the cell inhibits histamine release Four receptors H1, H2, H3, H4 Trivia: why do you get itchy with morphine? Releases histamine by non-receptor action

Pathophysiology Histamine Main actions in humans:
Stimulation of gastric secretion H1 Contraction of most smooth muscle (except for blood vessels)  H1 Cardiac stimulation  H2 Vasodilatation  H1 Increased vascular permeability  H1 These are the effects important to histamine as it pertains to anaphylaxis and allergy. Other histaminic functions: Cell proliferation and differentiation, Hematopoiesis, Embryonic development, Regeneration and wound healing. Furthermore histamine is produced in neurons that have cell bodies located in hypothalamus that are involved in the sleep wake cycle, endocrine function, cognition, and memory (a bit more on this later)

Pathophysiology Additional Mediators of Inflammation

For reference

Differential Diagnosis
Also keep anaphylaxis on your differential for syncope Keep Anaphylaxis on your differential for syncope - few case reports Think about foreign body aspiration - especially in pediatrics and if asymmetric lung exam (can mimic anaphylaxis because of its sudden onset a first time presenter to hospital)

Case 24 yo F with history of peanut allergy
Arrives via EMS after eating one of Dimmer’s samosas (which cost her $6!) Apparently he used peanut oil to deep fry these delicacies

Approach The obvious ABC’s
Maintaining a patent airway and managing shock from vasodilation are the key areas of concern Patient condition can change rapidly

Case (cont) Airway Breathing Circulation Derm
Talking, no stridor, no drooling, no apparent soft tissue swelling Breathing Somewhat anxious and slightly tachypenic, no wheeze but subjectively SOB Circulation Normotensive, tachycardic (105) Derm Urticarial rash

Case (cont) Now onto the drugs…
What is the drug of choice in anaphylaxis?

Epinephrine Stimulation of α-adrenoceptors increases peripheral vascular resistance thus improving blood pressure and coronary perfusion, reversing peripheral vasodilation, and decreasing angioedema. Stimulation of β1 adrenoceptors has both positive inotropic and chronotropic cardiac effects. Stimulation of β2 receptors causes bronchodilation as well as increasing intracellular cyclic adenosine monophosphate production in mast cells and basophils, reducing release of inflammatory mediators. From Dr Rigby

Management Epinephrine When do we give it? Less Likely More Likely
Courtesy Ian Rigby Ask Jrs if they want to give epi to our patient - why/why not? Symposium recommendations are based on the definition provided earlier. They recommend treatment with epi in anyone meeting those criteria however they should not be entirely exclusive (ie patient with known allergy and previous severe reaction who presents early with another exposure but not yet severely symptomatic). • Known CAD • Presence of CAD RF’s • Advancing Age • Absence of cardio-respiratory symptoms • Airway symptoms • Cardiovascular instability • Acuity of Onset • Hx of previous severe allergic rxns

Management Epinephrine Bottom Line:
Consider giving it in anyone with more than just cutaneous symptoms Be cautious in patients with CAD

Management Epinephrine How do we give it? Where do we inject?
Courtesy Ian Rigby J Allergy Clin Immunol 2001; 108:871-3

Management Epinephrine Give it in the thigh Give it IM (NOT SQ!)
Peak absorption ~8 +/- 2 minutes Evidence for this isn’t perfect - done in healthy volunteers, not in symptomatic anaphylactic patients - however no prospective trial will ever be done and it is the best evidence we have.

Management Epinephrine Available in two dilutions:
1: (0.1 mg/mL or 100 mcg per mL) 1: is the crash cart epi and used for IV administration 1:1000 (1 mg/mL) 1:1000 is used for IM The volume of 1 mg of crash cart epinephrine is 10 cc’s The volume of 1 mg of 1:1000 epinephrine is 1 cc 1 cc of the 1:1000 = 10 cc of the 1:10 000

Management Epinephrine Adult dosing Pediatric dosing
mL ( mg) of 1:1000 IM in the vastus lateralis (thigh) q 5 min prn Pediatric dosing 0.01 mg/kg of 1:1000 IM in the vastus lateralis q 5 min prn Where do we give it? How much? In some situations may need to give more frequently than every 5 minutes.

Management Peds Weight Memory Aid Age Wt 1 10 kg 3 15 kg
kg (threshold for adult epi dosing) kg kg If patient 7 years old may give adult dosing

Cases A 1 year old with a probable anaphylactic reaction; How much epi do you want to give? 1 year old ~ 10 kg 10 kg x 0.01 mg/kg = 0.1 mg (100 mcg) 0.1 mg of 1:1000 = 0.1 cc 0.01 mg/kg is the same as 0.01 cc/kg when using 1:1000 epi dilution (1 mg/cc is the concentration)

Cases 3 year old child with a probable anaphylactic reaction; how much epi do you want to give? 3 yo ~ 15kg 15 kg x 0.01 mg/kg = 0.15 mg 0.15 mg of 1:1000 = 0.15 cc

Cases 5 yo with a probable anaphylactic reaction; how much epi do you want to give? 5 yo ~ 20 kg 20 kg x 0.01 mg/kg = 0.2 mg 0.2 mg of 1:1000 = 0.2 cc

Cases A 7 year old child with a probable anaphylactic reaction; how much epi do you want to give? 7 yo ~ 25 kg 25 kg x 0.01 mg/kg = 0.25 mg 0.25 mg of 1:1000 = 0.25 cc

Cases A 9 yo with a probable anaphylactic reaction; how much epi do you want to give? 9 yo ~ 30 kg Give adult dosing ( mg)

Case (cont) Your patient’s responded initially to your IM epinephrine
20 minutes later you are called back to the bedside because the patient is feeling lightheaded, nauseated, and is having more difficulty breathing O/E BP 90/50, HR 110, SaO2 89%, diffuse wheezing bilat You give another IM dose of epi, the patient’s BP and resp symptoms resolve transiently but then starts to deteriorate again What do you want to do now?

Management Epinephrine Drips IV (adults)
Can give 1/2 cc of the 1: (crash cart epi) if patient is crashing before your eyes This means you are giving 50 mcg with each 1/2 cc For a drip you want 10 mcg per minute and titrate up as you need Good video on EM:RAP showing how to mix a drip Nurses should be the ones mixing the drips but in a pinch it is helpful to know how to do this (peripheral hospital or Inexperienced nurses)

Management Epinephrine Pediatrics For reference

Drugs in Anaphylaxis Additional Considerations

Management Antihistamines Diphenhydramine (Benadryl)  H1
Ranitidine (Zantac)  H2 Inverse Competitive Antagonists Often given in an attempt to down-regulate the magnitude of the allergic response Inverse agonists meaning they stabilize the inactive form and shift the state to the inactive state

Management Antihistamines Always given
Recent Cochrane review failed to demonstrate evidence for or against the use of H1 antihistamines Allergy 2007; 62: Possible benefit from using a combination of H1 & 2 antihistamines Ann Emerg Med 2000; 36:482-8 Theoretical benefit. Lots of potential side effects although we think of benadryl as fairly benign. Antihistamines are not specific for histamine recepters - they bind to several other receptors Human muscarinic receptors are very similar to histamine receptors which is why antihistamines also have antimuscarinic effects

Management Antihistamines Bottom line:
Should not replace epinephrine in the management of anaphylaxis May alleviate dermatologic symptoms May play a role in secondary prevention before exposure

Steroids Are we going to pump this patient up like Arnie?
Need to look up types of steroids How long should we treat the patient with steroids?

Management Steroids Onset 4-6 hours after administration
Theoretically prevents biphasic reaction; standard in guidelines IV methylprednisone 125mg; then PO prednisone for one week (practice varies)

Case HPI: 50 yo M with prev anaphylactic rxn to shellfish Presents now with rapidly progressive mucosal edema and swelling, SOB, tachycardic, hypotensive PMHx: IHD, DMII, HTN He is on an epi infusion and not getting better, what is happening? What else can we do? BB case

Patients on Beta-Blockers
Patients on BB with anaphylaxis may be refractory to treatment Both epinephrine and glucagon activate cAMP but through different receptors Mechanism: A means of bypassing the adrenergic receptors but activating the same downstream cascade

Patients on Beta-Blockers
Glucagon Dosing 1-5 mg (20-30 mcg/kg in peds) IV over 5 minutes; then infusion of 5-15 mcg/min titrated to response Side Effect: Vomiting! Give ondansetron prophylactically Does it work? Two case reports; both report success EMJ 2005; 22: Ask how they want to give it? Do they want to pre-treat with anything???

Summary of Tx Epinephrine 0.5 mg IM lat thigh
Diphenhydramine (Benadryl) 50 mg IV Ranitidine 50 mg IV Methylprednisone 125 mg IV x 1; then, Prednisone 50 mg PO Consider: Glucagon in patient on BB Consider Ventolin if asthmatic or if patient continues to struggle

Disposition Ask one of the juniors/EM’s what they need to consider for disposition

Disposition Things to consider Biphasic Reactions Epi-pen prescription
Medic alert bracelet Referral to allergist When to return to ED When to call 911

Biphasic Anaphylaxis Occur 1-20% of patients
No way to predict who will get it Tend to have same organ systems involved as with first reaction Questions: Can we predict who will get a biphasic reaction? How many people will get biphasic reactions?

Biphasic Anaphylaxis Study* Results & Conclusions
Prospective analysis done to look at biphasic reactions; N = 134 Results & Conclusions 20% had biphasic reactions 35% milder; 40% life threatening; 20% required more aggressive measures Range of biphasic onset between 2-38 hours; mean 10 hours Found an association between time to resolution of first episode and chance of recurrence Some association with less epi and steroid treatment Ann Allergy Asthma Immunol 2007; 98:64-69. *This is the only prospective study ever done to evaluate this!

Biphasic Anaphylaxis Macleod Approach
Decisions based on judgment not science Observation Period Observe those with serious initial symptoms in ED Extra caution with asthmatic patients Advise not to leave city for 24 hours Reliable companion is desirable Discharge Medications Epi pen Corticosteroids - 24 hour coverage is standard No clinical trials to support Many case reports where it didn’t help Theoretical advantage

Disposition Bottom Line:
Risk of recurrence of anaphylaxis is unpredictable (but atopic type/asthmatic patients are at a higher risk) Severity of initial reaction is NOT a good predictor of future reactions

Case 5 yo child HPI: PMHx:
Experiences generalized urticaria after a hymenoptera sting. Has no other symptoms. PMHx: Asthma Does this patient need an epi-pen prescription when he goes home? If yes which one (Jr or adult?)

Disposition Recent systematic review found no universally accepted anaphylaxis management plan J Allergy Clin Immunol 2008; 22: All patients who experience cardiovascular or respiratory symptoms should receive an epi-pen J Allergy Clin Immunol 2005 (Practice Guidelines) Beyond cardiovascular or resp symptoms there is little consensus as to how one should manage disposition in anaphylaxis

Disposition Epi-Pen No clear cut guidelines on when to prescribe
Not indicated for local insect sting reactions Risk of anaphylaxis in children presenting with generalized cutaneous symptoms have 10% risk of future anaphylaxis Children with asthma are at higher risk of adverse outcomes

Disposition Epi-Pen Adult Dose Pediatric 0.3 mg 0.15 mg
If < 20 kg prescribe epi-pen jr If > 20 kg prescribe adult epi-pen

Disposition Epi-Pen You decide to give the patient a prescription for an epi-pen because of his hx of asthma. Mom asks: Doctor, when should my child use the epi-pen? Two extremes: Inject after any possible exposure even in the absence of symptoms Wait until patient experiences progressive respiratory and/or cardiovascular symptoms Truth is somewhere in between: consider comorbid illness, specific allergy (peanut, shellfish, insects tend to cause the most severe reactions) J Allergy Clin Immunol 2005; 115:

Epi-Pen Bottom line Clinical judgment call when to prescribe epi-pens
J Allergy Clin Immunol March 2005

Disposition Other considerations Medic alert bracelet
F/u with allergist Advise on biphasic rxn When to call 911 Refer pt to community education Anyone experiencing respiratory or cardiovascular symptoms should receive an epi-pen. Beyond this who else should receive an epi-pen it is unclear.

Additional Notes and Considerations

Case 40 yo F presents with mild oral itching and swelling of the lips and mouth after eating an apple PMHx: Healthy, seasonal hay fever, no previous food or drug reactions What is the diagnosis? Throw this one out to the crowd

Pollen-Food Syndrome Triggered in patients with a pollen allergy who eat raw fruit or vegetables Local IgE mediated response Symptoms rarely involve other organs ~2% of patients with this syndrome develop anaphylaxis Epi-pen prescription is optional J Allergy Clin Immunol 2005; 115:

Anaphylaxis and Asthma
Concomitant asthma increases the risk for adverse outcome in anaphylaxis 50% risk of possible peanut allergy with asthmatics J Allergy Clin Immunol 2005; 115:

Exercise Induced Anaphylaxis
Epidemiology Only one reported death in the literature* Most are unaware of their condition Clinical Features Varies from mild urticaria to anaphylaxis May present as syncope during exercise Resp symptoms (59%), GI (30%), Headache, dermatologic symptoms Am Fam Phys 2001; 64: Likely under-reported

Exercise Induced Anaphylaxis
Treatment Recognition is key As per any anaphylactic presentation Prevention Activity modification Prophylactic antihistamines may blunt skin symptoms making diagnosis more difficult

Immunotherapy for Hymenoptera
What insects are included in the taxonomic order Hymenoptera? Ants Bees Hornets Wasps Yellow Jackets

Immunotherapy for Hymenoptera reactions
Venom immunotherapy may reduce the risk of systemic reaction after a subsequent sting from 32% in untreated patients to less than 5 % NEJM 2004; 351: Protection may last for > 20 years Yellow jacket - most common hymenoptera to cause anaphylaxis

Immunotherapy Who should be referred: Who doesn’t need to be referred:
Pts who experience anaphylaxis Controversial: Adults with exclusively dermal reactions (urticaria and angioedema) Who doesn’t need to be referred: Local reactions; even if they are large Children under 16 with exclusively dermal reactions (urticaria and angioedema)* Although immunotherapy isn’t recommended for these cases an epi pen is still indicated because of subsequent anaphylactic risk of 10%

Anaphylactoid Reactions
Pathophysiology Direct degranulation of mast cells May occur with first time exposure Clinical features Dose dependent reactions Can be clinically indistinguishable from anaphylaxis

Common etiologies NAC Radiologic contrast material Some antibiotics (Vancomycin; so called “red man syndrome”)

Management Treat severe symptoms same as anaphylaxis Stop offending agent for a period of time then restart by infusing at a slower rate Prophylactic antihistamines

Drug Reactions Drug Hypersensitivity Reactions Penicillin Allergies
Sulfur Medication Allergies

Drug Hypersensitivity Reactions

Drug Hypersensitivity Reactions
Anaphylaxis Angioedema Urticaria Serum Sickness SJS TEN Drug Hypersensitivity Syndrome …These are not all encompassing

Drug Reactions How drugs stimulate the immune system
Drugs (or their metabolites) can bind to native proteins and change their shape so that they become immuogenic and induce cell-mediated or humoral immune responses Drugs can directly stimulate the immune system by binding to T-cells that have receptors able to recognize the drug Drug reactions that don’t stimulate the immune system occur via cumulative toxicity, drug-drug interactions, or metabolic alterations

Case 14 mo old M Started on amoxil 6 days previous for sinusitis
Presented yesterday with an “urticarial like rash” - Amoxil d/ced and benadryl prescribed What is this rash?

Serum Sickness Typically develops 1-2 weeks after exposure to the offending agent Clinical Features Fever, rash, polyarthralgias (child refusing to walk), lymphadenopathy, proteinuria, edema, abdominal pain Typically non toxic appearance Pathophysiology Type III, occurs with a number of Abx and drugs Differential diagnosis: EM, Kawasaki’s, disseminated gonococcal/meningococcal infections Type III reaction occurs when circulating soluble complexes of drug antigens and specific IgG or IgM antibodies deposit in tissue. Tissue damage occurs when the complement system is activiated Ann Emerg Med 2007; 50:350

Case 8 year old boy Clinical symptoms Diagnosis? Mgmt? Pruritic, T38.0
Morbilliform drug rxn to ampicillin Increased likelihood to react like this with concurrent viral illness Mgmt? Stop offending agent Benadryl/steroids

Case Diagnosis? TEN

Drug Reactions TEN Widespread erythematous or purpuric macules & targetoid lesions Full thickness epidermal necrosis with involvement of more than 30% of BSA Common to have mucous membrane involvement Drugs involve > 65% of the time; PCN & sulfonamide most common

Drug Reactions Stevens-Johnson Syndrome
Widespread purpuric macules and targetoid lesions Rate of epidermal detachment is less than 10%, mucosal involvement is common (>90%) Mortality rate less than that for TEN (~5%)

Drug Reactions Erythema Multiforme Targetoid lesions
May have oral mucosal involvement Low morbidity and no mortality

Drug Reactions Pathophysiology of TEN, SJS, EM
Thought to be a combination of patient factors (genetic defects) that allows accumulation of toxic metabolites and the ability of drugs to alter proteins and stimulate an immunologic response (Type II and or III reactions) Cytotoxic T lymphocytes may also invade the epidermis and cause local tissue destructions (Type IV reactions) Steroids & IVIG have been used as treatment because of this hypothesized immunopathophysiology (controversial) Although these reactions are not IgE mediated and are not anaphylaxis, having a reaction like TEN or SJS would be a contraindication to receiving the drug in the future

Antibiotic Allergies

Antibiotic Allergies Case
47 yo F with a cellulitis. You are considering starting her on cefazolin (ancef) PMhx: Allergy to penicillin Reaction: makes my stomach upset Is cefazolin safe in this situation? What about cloxacillin?

Antibiotic Allergies Confusing topic; these are the issues:
Some literature, pretty much all retrospective Guidelines don’t always reflect clinical practice How good is the patient’s history? What % of patients who report allergy have a true allergy? What % of patients who report allergy but describe a benign history could potentially suffer an anaphylactic reaction? How often does a patient with a true PCN allergy have a true allergy to cephalosporins? Does it matter what generation of cephalosporin?

Antibiotic Allergies The Guidelines

Antibiotic Allergies Guidelines from the diagnosis and management of anaphylaxis: An updated practice parameter J Allergy Clin Immunol March 2005

Antibiotic Allergies AAP endorse the use of cephalosporin antibiotics for patients with PCN allergies Pichinchero reviewed evidence on the topic in 2005 However, AAP says it is ok to use cephalosporins for patients with PCN allergies

Antibiotic Allergies The Facts

Antibiotic Allergies “Only 15% of patients with a history of allergy to penicillin have positive skin tests and, of those, 98% will tolerate a cephalosporin. However, those patients who react (less than 1%) may have fatal anaphylaxis”. Ann allergy Asthma Immunol 1999; 83: Fatalities have occurred when patients are not skin tested for penicillin and given cephalosporins. There are distant case reports of cephalosporin induced reactions in patients with a history of pcn allergy, but these patients did not undergo pcn skin testing and early cephalosporins were also known to contain trace amounts of penicillin.

Antibiotic Allergies True penicillin allergy occurs 1/5000-1/10000 courses administered NEJM 2006; 354: J Allergy Clin Immunol March 2005

Antibiotic Allergies The most common allergic type reactions to antibiotics are maculopapular skin eruptions, urticaria, and pruritus and are typically delayed* Not all of these reactions are IgE mediated *These reactions are not IgE mediated but do represent “allergy” *does this mean that we can reliably rule out true allergy based on patient’s history???? - NO! NEJM 2006; 354: J Allergy Clin Immunol March 2005

Antibiotic Allergies Common quote of ~10% cross-reactivity of cephalosporins in patients with PCN allergy is an over estimate because historically 1st generation cephalosporins used to contain small amt of PCN NEJM 2006; 354(6):

Antibiotic Allergies Another review found that allergic reactions to cephalosporins occurred in 4.4% of patients with positive skin tests to PCN vs 0.6% of patients with negative skin tests These authors did not discuss sulfonamide allergies in these patients NEJM 2001; 345:

Antibiotic Allergies Study Conclusions
Retrospective cohort analysis; databank of > 500,000 pts receiving cephalosporins after PCN in the UK Only 25 patients in their study had anaphylaxis, 1/25 had a second anaphylactic rxn with a cephalosporin Conclusions Allergic events with cephalosporins are increased with hx of rxn to penicillin but to a similar degree as those who have had rxns to SMX therefore unlikely that rxns are a class effect and it is safe to use cephalosporins in pts with reported allergy to pcn Am J Med 2006; 119: 354e11-354e20 Most extensive study done to look at the epidemiology of penicillin and cephalosporin allergies

Study Protocol

Antibiotic Allergies The Problems

Antibiotic Allergies How do I know if a patient’s reaction is immune mediated? Bottom line: this is difficult to do practically speaking

Antibiotic Allergies Three classes of reactions Immediate Accelerated
Delayed May take >72 hours to occur TEN Interstitial nephritis Serum sickness Maculopapular rashes (most common) Drug specific IgE antibodies cause immediate hypersensitivity reactions T-cells play the predominant role in delayed hypersensitivity reactions (maculopapular eruptions)

Antibiotic Allergies NJEM 2006; 354(6): 601-609 For reference
Urticaria, angioedema, and anaphylaxis - while they are typically IgE mediated direct mast cell degranulation (ie Anaphylactoid) can cause these signs/symptoms NJEM 2006; 354(6):

Antibiotic Allergies How good is a patient’s self reported history at identifying a true allergy? Can I rely on a benign history as being truly benign?

Antibiotic Allergies Patient history One study done on this topic
Solensky et al lit review to determine how many patients with a vague history of allergy had positive skin test reactions to penicillin Vague history defined as “rash, GI symptoms, or unknown reaction” Rational: many physicians proceed less cautiously if a patient provides a vague history of a penicillin reaction, is this appropriate? Ann Allergy Asthma Immunol 2000; 85:

Antibiotic Allergies Patient history (cont) Results: Conclusion:
33% of patients with a positive skin test reported a vague history of a penicillin reaction Conclusion: A large proportion of patients who have IgE antibodies on skin testing have vague PCN allergy histories Patients with vague histories should be treated the same as patients with more convincing histories Ann Allergy Asthma Immunol 2000; 85: 30 studies reviewed, range of incidence between 0% and 70% Remember that PPV of skin test is greater than 50% NPV of skin testing is ~99%

Antibiotic Allergies Additional Considerations

Antibiotic Allergies Special Cases HIV CF Infectious Mononucleosis
Higher frequency of allergic reactions to many Abx Frequency is declining with HAART CF 30% of pts with CF develop allergies to 1 or more Abx Infectious Mononucleosis Likelihood of cutaneous reaction to penicillins is increased in patients with mono Viral infection alters the immune status of the host Abx ok once infection has resolved What co-morbid illnesses put a patient at increased risk of having an allergy?

Antibiotic Allergies An Approach

Antibiotic Allergies An approach: Take the history
What rxn? Can the reaction be attributed to the abx? How quickly did the reaction occur? How long ago? First exposure? Severity? Was the reaction a known side effect of the drug? Look in the chart (preop abx may not be known by the patient) Patients with reactions that occurred a long time ago are less likely to still be allergic Immunol Allergy Clin N Am 2004; 24:45-461 NEJM 2006; 354:

Antibiotic Allergies An approach (cont):
Does it sound like a true IgE mediated reaction that happened recently? Hx of atopy and/or asthma? Yes: Avoid 1st generation cephalosporins, watch the patient regardless of the drug class Does it sound like a non-IgE mediated reaction non immune side effect? No comorbidities? Yes: Safe to give cephalosporin, watch the patient if in doubt

Antibiotic Allergies Bottom line:
Although biologically plausible there is no good evidence to support cross reactivity between PCN’s and cephalosporins based on class effect alone Patients with a true anaphylactic history to penicillin are at risk of reacting to other abx, not just cephalosporins Patients with asthma generally have poorer outcomes (be more cautious with these patients) As Emerg docs we have the advantage of being able to treat adverse reactions quickly

Antibiotic Allergies Bottom line (cont)
Be reassured that true allergies occur infrequently Be cautious that when a reaction does occur it has the potential to be fatal Thoughts Dr MacLeod

Antibiotic Allergies Maculopapular rash associated with penicillin allergy

Antibiotic Allergies Urticaria With ampicillin Allergy

Sulfur Medication Allergies
Drug induced bullous pemphigoid from furosemide

“Sulfa” Allergies Mrs K is a 55 yo who presents with new symptoms consistent with CHF PMhx: DM II HTN Smoker Sulfa allergy Do you give her lasix? What drugs contain sulfa?

8% of patients treated with SMX have an adverse reaction 3% rxn represent hypersensitivity Largest % abx induced cases of TEN and SJS Oxidation of smx through the cyp450 pathway results in the hypersensitivity rxns to smx

Actually consists of three different classes Sulfonylarylamines (abx) Non-arylamine sulfonamides (thiazides, loop diuretics) Sulfones (Dapsone)

Sulfonamide antibiotics (ie Septra) differ from other sulfonamide containing medications (have an extra amine group) Despite drug label warnings it would be safe to give lasix in a patient with a septra allergy (patients with rxns to both drugs tend to have a general sensitivity unrelated to the drug itself) NEJM 2006; 354:

Loop diuretics Ethacrynic Acid is the only loop diuretic that doesn’t contain sulfur Loop diuretics that contain sulfur can cause allergic rxns but much less frequently than SMX Many anecdotal reports of furosemide safety in patients with known SMX sensitivity Rxns to other non-antimicrobial sulfur containing medication warrants graded dose challenges or alternative drug choice (e.g. ethacrynic acid)

Commonly prescribed non antibiotic sulfur containing medications in Canada

Case HPI 44 yo M presents with a 6 hour hx of a sore throat Awoke feeling like there was something stuck in his throat Exam Afebrile, no drooling Muffled voice, occasional gagging No lymphadenopathy Thoughts? Uvular angioedema (Quincke’s disease). Patient had been treated recently with amoxicillin for a tooth infection. No white count, no previous episodes. Patient was admitted to ENT, given benadryl and famotidine and dex. Also emperically given clinda.

Angioedema Pathology Clinical Features 1 IgE mediated Other mech:
Complement mediated (hereditary, serum sickness) Bradykinin (ACEI) Direct mast cell stimulation (opioids, abx) AA metabolism (NSAIDS, ASA) C1 inhibitor deficiency (Hereditary) Clinical Features Pruritis absent Can be acute (<6 weeks) or chronic (> 6 weeks)

Angioedema Management
Assess airway (voice change, stridor, drooling, dyspnea) ACEI increases likelihood of needing airway intervention Steroids & Antihistamines Epinephrine if concerning clinical picture FFP (controversial - may worsen laryngeal edema) ENT surgery may be indicated

Summary The dose of epi in adults is 0.3-0.5 cc of 1:1000
The dose of epi in peds is 0.01 mg/kg which is the same as 0.01 cc/kg of 1:1000 Give it IM in the thigh Use 1/2 a cc at a time of crash cart epi if patient crashing in front of you Giving 1/2 cc in adult. For peds your min dose is 0.1 cc, max dose is 0.5 cc of 1:1000

Further Reading Sampson HA, et al. Second Symposium on the Definition and management of anaphylaxis: summary report - second national institute of allergy and infectious disease/food allergy and anaphylaxis network symposium. Ann Emerg Med 2006; 47: Lieberman P, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005; 115: Sicherer SH, et al. Quantries in prescribing an emergency action plan and self injectable epinephrine for first-aid management of anaphylaxis in the community. J Allergy Clin Immunol 2005; 115: McKenna JK, Leiferman KM. Dermatologic drug reactions. Immunol Allergy Clin N Am 2004; 24:

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