Anaphylaxis

1
Anaphylaxis Allergy

• Chris McCrossin
• Thanks to
• Bruce MacLeod
• Ian Rigby

2
Outline Anaphylaxis and Allergy

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

3
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 47373-380

4
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 1984-2004
5
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

6
Immunology 101
7
Anaphylactic Signs Symptoms
8
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
• RBCs
• Platelets
• Keratinocytes
• Consequences
• Antibiotic induced hemolytic anemia
  thrombocytopenia
• Autoimmune bullous disease (pemphigus vulgaris)

9
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

10
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

11
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 B cells/Ig
Type III IgG Complement Immune complex deposition vasculitis B cells/Ig
Type IV
IVa Th1 Monocyte activation Eczema T cell
IVb Th2 Eosinophilic inflammation Maculopapular Bullous exanthema T cell
IVc Cytotoxic T lymphocytes CD4 or CD8 mediated killing Maculopapular Bullous exanthema T cell
IVd T cells Neutrophil recruitment and activation Pustular exanthema T cell
12
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

13
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

14
Pathophysiology

• Additional Mediators of Inflammation

15
(No Transcript)
16
Differential Diagnosis
Also keep anaphylaxis on your differential for
syncope
17
Case

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

18
Approach

• The obvious
• ABCs
• Maintaining a patent airway and managing shock
  from vasodilation are the key areas of concern
• Patient condition can change rapidly

19
Case (cont)

• Airway
• 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

20
Case (cont)

• Now onto the drugs
• What is the drug of choice in anaphylaxis?

21
Epinephrine

• Stimulation of a-adrenoceptors increases
  peripheral vascular resistance thus improving
  blood pressure and coronary perfusion, reversing
  peripheral vasodilation, and decreasing
  angioedema.
• Stimulation of ß1 adrenoceptors has both positive
  inotropic and chronotropic cardiac effects.
• Stimulation of ß2 receptors causes
  bronchodilation as well as increasing
  intracellular cyclic adenosine monophosphate
  production in mast cells and basophils, reducing
  release of inflammatory mediators.

22
Management

• Epinephrine
• When do we give it?

More Likely
Less Likely
Known CAD Presence of CAD RFs Advancing
Age Absence of cardio-respiratory symptoms
Airway symptoms Cardiovascular instability
Acuity of Onset Hx of previous severe allergic
rxns
23
Management

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

24
Management

• Epinephrine
• How do we give it? Where do we inject?

J Allergy Clin Immunol 2001 108871-3
25
Management

• Epinephrine
• Give it in the thigh
• Give it IM (NOT SQ!)
• Peak absorption 8 /- 2 minutes

26
Management

• Epinephrine
• Available in two dilutions
• 110 000 (0.1 mg/mL or 100 mcg per mL)
• 110 000 is the crash cart epi and used for IV
  administration
• 11000 (1 mg/mL)
• 11000 is used for IM

27
Management

• Epinephrine
• Adult dosing
• 0.3-0.5 mL (0.3-0.5 mg) of 11000 IM in the
  vastus lateralis (thigh) q 5 min prn
• Pediatric dosing
• 0.01 mg/kg of 11000 IM in the vastus lateralis q
  5 min prn

28
Management

• Peds Weight Memory Aid
• Age Wt
• 1 10 kg
• 3 15 kg
• 5 20 kg (threshold for adult epi dosing)
• 7 25 kg
• 9 30 kg

29
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 11000 0.1 cc

30
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 11000 0.15 cc

31
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 11000 0.2 cc

32
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 11000 0.25 cc

33
Cases

• A 9 yo with a probable anaphylactic reaction how
  much epi do you want to give?
• 9 yo 30 kg
• Give adult dosing (0.3-0.5 mg)

34
Case (cont)

• Your patients 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 patients BP
  and resp symptoms resolve transiently but then
  starts to deteriorate again
• What do you want to do now?

35
Management

• Epinephrine Drips
• IV (adults)
• Can give 1/2 cc of the 110 000 (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 EMRAP showing how to mix a drip

36
Management

• Epinephrine
• Pediatrics

37
Drugs in Anaphylaxis

• Additional Considerations

38
Management

• Antihistamines
• Diphenhydramine (Benadryl) ? H1
• Ranitidine (Zantac) ? H2
• Inverse Competitive Antagonists

39
Management

• Antihistamines
• Always given
• Recent Cochrane review failed to demonstrate
  evidence for or against the use of H1
  antihistamines
• Allergy 2007 62830-837
• Possible benefit from using a combination of H1
  2 antihistamines
• Ann Emerg Med 2000 36482-8

40
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

41
Steroids

• Are we going to pump this patient up like Arnie?

42
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)

43
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?

44
Patients on Beta-Blockers

• Patients on BB with anaphylaxis may be refractory
  to treatment
• Both epinephrine and glucagon activate cAMP but
  through different receptors

45
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 22 272-276

46
Summary of Tx

1. Epinephrine 0.5 mg IM lat thigh
2. Diphenhydramine (Benadryl) 50 mg IV
3. Ranitidine 50 mg IV
4. Methylprednisone 125 mg IV x 1 then, Prednisone
   50 mg PO
5. Consider Glucagon in patient on BB
6. Consider Ventolin if asthmatic or if patient
   continues to struggle

47
Disposition
48
Disposition

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

49
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

50
Biphasic Anaphylaxis

• Study
• 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 9864-69.

51
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 didnt help
• Theoretical advantage

52
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

53
Case

• 5 yo child
• HPI
• 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?)

54
Disposition

• Recent systematic review found no universally
  accepted anaphylaxis management plan
• J Allergy Clin Immunol 2008 22353-361
• All patients who experience cardiovascular or
  respiratory symptoms should receive an epi-pen
• J Allergy Clin Immunol 2005 (Practice Guidelines)

55
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

56
Disposition

• Epi-Pen
• Adult Dose
• 0.3 mg
• Pediatric
• 0.15 mg
• If lt 20 kg prescribe epi-pen jr
• If gt 20 kg prescribe adult epi-pen

57
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 115 575-583

58
Epi-Pen

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

59
Disposition

• Other considerations
• Medic alert bracelet
• F/u with allergist
• Advise on biphasic rxn
• When to call 911
• Refer pt to community education
  www.foodallergy.org

60
Additional Notes and Considerations
61
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?

62
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 115 575-83

63
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 115 575-583

64
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 641367-72

65
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

66
Immunotherapy for Hymenoptera

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

67
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 3511978-84
• Protection may last for gt 20 years

68
Immunotherapy

• Who should be referred
• Pts who experience anaphylaxis
• Controversial Adults with exclusively dermal
  reactions (urticaria and angioedema)
• Who doesnt need to be referred
• Local reactions even if they are large
• Children under 16 with exclusively dermal
  reactions (urticaria and angioedema)

69
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

70
Anaphylactoid Reactions

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

71
Anaphylactoid Reactions

• 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

72
Drug Reactions

1. Drug Hypersensitivity Reactions
2. Penicillin Allergies
3. Sulfur Medication Allergies

73
Drug Hypersensitivity Reactions
74
Drug Hypersensitivity Reactions

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

75
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

76
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?

77
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, Kawasakis, disseminated gonococcal/meningococ
  cal infections

Ann Emerg Med 2007 50350
78
Case

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

79
Case

• Diagnosis?
• TEN

80
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 gt 65 of the time PCN
  sulfonamide most common

81
Drug Reactions

• Stevens-Johnson Syndrome
• Widespread purpuric macules and targetoid lesions
• Rate of epidermal detachment is less than 10,
  mucosal involvement is common (gt90)
• Mortality rate less than that for TEN (5)

82
Drug Reactions

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

83
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)

84
Antibiotic Allergies
85
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?

86
Antibiotic Allergies

• Confusing topic these are the issues
• Some literature, pretty much all retrospective
• Guidelines dont always reflect clinical practice
• How good is the patients 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?

87
Antibiotic Allergies

• The Guidelines

88
Antibiotic Allergies

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

89
Antibiotic Allergies

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

90
Antibiotic Allergies

• AAP endorse the use of cephalosporin antibiotics
  for patients with PCN allergies
• Pichinchero reviewed evidence on the topic in 2005

91
Antibiotic Allergies

• The Facts

92
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 83655-700

93
Antibiotic Allergies

• True penicillin allergy occurs 1/5000-1/10000
  courses administered
• NEJM 2006 354601-609
• J Allergy Clin Immunol March 2005

94
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

95
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) 601-609

96
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 345804-809

97
Antibiotic Allergies

• Study
• Retrospective cohort analysis databank of gt
  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

98
Study Protocol
99
Antibiotic Allergies

• The Problems

100
Antibiotic Allergies

• How do I know if a patients reaction is immune
  mediated?

101
Antibiotic Allergies

• Three classes of reactions
• Immediate
• Accelerated
• Delayed
• May take gt72 hours to occur
• TEN
• Interstitial nephritis
• Serum sickness
• Maculopapular rashes (most common)

102
Antibiotic Allergies
NJEM 2006 354(6) 601-609
103
Antibiotic Allergies

• How good is a patients self reported history at
  identifying a true allergy?
• Can I rely on a benign history as being truly
  benign?

104
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 85195-199

105
Antibiotic Allergies

• Patient history (cont)
• Results
• 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 85195-199

106
Antibiotic Allergies

• Additional Considerations

107
Antibiotic Allergies

• Special Cases
• HIV
• 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

108
Antibiotic Allergies

• An Approach

109
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 2445-461
• NEJM 2006 354 601-609

110
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

111
Antibiotic Allergies

• Bottom line
• Although biologically plausible there is no good
  evidence to support cross reactivity between
  PCNs 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

112
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

113
Antibiotic Allergies
114
Antibiotic Allergies
115
Sulfur Medication Allergies
116
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?

117
Sulfur Medication Allergies

• 8 of patients treated with SMX have an adverse
  reaction
• 3 rxn represent hypersensitivity
• Largest abx induced cases of TEN and SJS

118
Sulfur Medication Allergies

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

119
Sulfur Medication Allergies

• 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 354 601-609

120
Sulfur Medication Allergies

• Loop diuretics
• Ethacrynic Acid is the only loop diuretic that
  doesnt 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)

121
Sulfur Medication Allergies

• Commonly prescribed non antibiotic sulfur
  containing medications in Canada

122
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?

123
Angioedema

• Pathology
• 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 (lt6 weeks) or chronic (gt 6 weeks)

124
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

125
Summary

• The dose of epi in adults is 0.3-0.5 cc of 11000
• The dose of epi in peds is 0.01 mg/kg which is
  the same as 0.01 cc/kg of 11000
• 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

126
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
  47373-380.
• Lieberman P, et al. The diagnosis and management
  of anaphylaxis an updated practice parameter. J
  Allergy Clin Immunol. 2005 115571-574.
• 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 115 575-583.
• McKenna JK, Leiferman KM. Dermatologic drug
  reactions. Immunol Allergy Clin N Am 2004
  24399-423.