1. Urticaria, Angioedema and Anaphylaxis in the Emergency Department
Back to Basics 2011
Jennifer Clow MD, CCFP (EM)
With slides by: Anita Pozgay, MD, FRCPC EM

2. Case One
A 7 year old comes in to the ED after an possible exposure to peanut butter
He has a severe nut allergy for which he was prescribed an EpiPen
He was recently admitted to PICU for a severe asthma attack but was not intubated
Mom gave him some oral Benadryl and he is no longer itchy but still has lip swelling

4. Case One continued
He is sent for a CXR due to decreased air entry in the lower lobes
While in radiology, he becomes acutely SOB and his lip becomes more swollen
What do you do now?

5. Case Two
A 45 y o woman involved in a MVC needs a CT abdo after she is stabilized in the ED
She received 2 L NS for a hypotensive episode and her BP is now 120/70
She has a positive FAST U/S
Although her CXR is normal she has palpable lower rib fractures & a distended abdomen

6. Case Two continued She is given both oral and IV contrast for her CT
She becomes hypotensive again!
What do you do now?
There is no rash

7. Case Three A 67 y o man is stung by an insect while gardening
He developed pruritus, dizziness, and SOB 20 min later so he called 911
He self-treated with Benadryl po and was given another 50 mg IV by EMS due to persistent sx and rash
He is now asymptomatic and refusing transport to hospital

8. Case Three: Do you transport?
EMS convinced him to get “checked out” in the hospital
On arrival, he becomes hypotensive, and his hives reappeared, along with facial edema
An ECG shows T wave inversion in his lateral leads
PHx: MI, HTN, IV contrast allergy
Meds: ASA, metoprolol, lisinopril

10. Allergic Reactions Generalized: anaphylaxis/anaphylactic shock
Localized:
Skin – dermatitis, urticaria, angioedema
Respiratory – rhinorrhea, angioedema, wheezing
GI – food intolerance (as contrasted with food allergy)

11. Definitions
Anaphylaxis: a severe systemic allergic reaction involving 2 or more systems
* hives/angioedema NOT universally present!
Anaphylactic Shock: above, plus hypotension and other signs of shock
Allergic reactions: localized reaction, involving a single system; e.g. urticaria, angioedema, contact dermatitis, rhinoconjunctivitis

12. Urticaria versus Angioedema
Both characterized by transient, pruritic, red wheals on raised serpiginous borders
urticaria due to edema of dermis
angioedema due to edema of subcutaneous tissues

13. Urticaria

14. AKA Hives
Raised, well-circumscribed areas of edema and erythema involving the dermis and epidermis
Intensely pruritic
May be acute or chronic (>6 weeks)
Multiple types: IgE-mediated, chemical-induced, cholinergic, cold-induced, autoimmune, etc.

20. Pathophysiology
Mast cells and basophils release histamine, bradykinin, leukotrienes, prostaglandins into the dermis
Causes fluid extravasation… leads to lesion
Pruritis is due to histamine release into the dermis
Multiple triggers: IgE mediated, others

21. Causes
Causes: found in 40-60% of acute urticaria, and 10-20% chronic urticaria
Include:
Infections, pregnancy, other medical conditions
Foods, drugs, latex
Environmental factors
Stress
Cold/heat, exercise

22. History Previous episodes/causative factors
Medical history, medications, allergies
Possible precipitants:
Recent illness or travel
New medications or IV contrast
Foods, pets, exposures
Changes in perfumes, lotions, clothes
Exercise, temperature extremes, stress

23. Physical Exam Identify and confirm urticarial diagnosis Dermographism?
Look for precipitants/other illnesses:
Signs of infections: e.g. URTI, fungal infection
Signs of liver/thyroid disease
Angioedema, respiratory changes (edema, wheezes)
Joint examination
Ensure no signs of anaphylaxis are present

24. Treatment H1-blockers i.e. diphenhydramine, hydroxyzine
H2-blockers i.e. ranitidine
Act synergistically with H1 blockers
Doxepin 10-25mg tid-qid
Glucocorticoids e.g. prednisone
Stabilize mast cells, stopping histamine release
Anti-inflammatory effect

25. Angioedema

26. Deep, subcutaneous, submucosal edema due to increased vascular permeability
May be episodic and self-limited, or recurrent
May involve skin, buccal mucosa/tongue, larynx or GI mucosa
Usually presents with urticaria: mast-cell mediated in these cases

30. Types Hereditary C1-esterase inhibitor deficiency
Acquired: autoimmune/lymphoprolif. disorders
Drug-induced (e.g. ACEI)
Urticaria-associated
Idiopathic (most cases)
Urticaria-associated is mast-cell mediated, all others are kinin-mediated

31. History Hereditary/idiopathic/drug-induced: Urticaria-associated:
Episodic, self-limiting episodes of edema
Skin swelling, tongue swelling, abdominal pain
Look for triggers
Urticaria-associated:
Look for potential triggers: drugs, allergens, food allergies, hymenoptera
History of atopy

32. Physical Exam
Acute onset of well-demarcated cutaneous edema of distensible tissues
Usually face, limbs, genitals
Assess airway
Abdominal examination

33. Treatment AIRWAY management Mild Angioedema Severe Angioedema
Intubate early if any question
Mild Angioedema
Remove offending agent; self-limited
Severe Angioedema
H1, H2 blockers, corticosteroids
Epinephrine

34. Anaphylaxis

35. Definition Severe allergic reaction (IgE-mediated)
Requires prior-sensitization and re-exposure
Rapid in onset, may cause death
Usually includes prominent dermal and systemic manifestations
Full syndrome involves urticaria/angioedema, respiratory manifestations +/- GI upset
Anaphylactic shock: above + hypotension

36. Anaphylactic vs. Anaphylactoid
Anaphylactoid has the same clinical features as anaphylaxis but is not IgE mediated
Instead it is due to direct mast cell degranulation and thus, does not require prior sensitization

37. Pathophysiology
Sensitization occurs when IgE adheres to the mast cell Ag (allergen)
IgE specific
Degranulation of mast cell
mediators

38. Pathophysiology
Re-exposure leads to antigen binding, and rapid release of mediators:
Histamines, leukotrienes, prostaglandins, tryptase
Leads to rapid onset of:
Increased secretion from mucus membranes
Increased bronchial smooth muscle tone
Decreased vascular smooth muscle tone
Increased capillary permeability

39. Epidemiology
Likely under reported due to lack of recognition or self treatment in the field
in Ontario: 4 cases/ 1 million
in Germany: 10 cases/
in Minnesota, U.S.A.: 17/19,122 visits
in Brisbane, Australia: 1/440 visits

40. Common Causative Agents
Drugs: Antibiotics, ASA, NSAIDS, sulfa, opioids, IV contrast dye
Foods: Peanuts, Seafood, Eggs, milk
Latex gloves
Insect Stings
Physical Factors: Exercise (FDEIA), Cold/Heat

41. SMOOTH MUSCLE CONTRACTION
Clinical Features
SMOOTH MUSCLE CONTRACTION
abdominal cramps
nausea
rhinitis
conjunctivitis
CAPILLARY LEAK
urticaria
angioedema
laryngeal edema
hypotension/syncope
MUCOSAL SECRETIONS
bronchospasm
diarrhoea
vomiting

42. DDx: Anaphylaxis MI/arrhythmia/cardiogenic shock
Airway obstruction due to other causes: FB aspiration, asthma, COPD, epiglottitis, peri-tonsillar abscess, etc.
Flushing syndromes (eg: carcinoid)
Vasovagal syncope
Panic attack
Scombroid poisoning
Hereditary angioedema

43. History Skin: pruritis, edema
Respiratory: upper and lower tract symptoms
Rhinorrhea, congestion, dyspnea
GI complaints
Nausea, vomiting, diarrhea, abdominal pain
Try to elicit causes/triggers
PMHx, allergies, previous episodes

44. Physical Examination Vitals, ABC’s General appearance Skin Respiratory
Cardiovascular

45. Grading of Anaphylaxis
Grade
Skin
GI tract
Resp CV
Neuro 1
Local pruritus, hives, mild lip swelling
Oral “tingling”, pruritus 2
Generalized pruritus, hives, flushing, angioedema
Above plus nausea +/- emesis
Nasal congestion/
sneezing
Activity change 3
Any of above
Any of above + repetitive vomiting
Rhinorrhea, sensation of throat tightness
Tachy
( > 15 bpm)
Above plus anxiety 4
Any of above + diarrhea
Hoarseness
dysphagia, SOB, cyanosis
Above + arrhythmia +/- dec BP
dizziness
Feeling of impending doom 5
Any above + stool incont.
Any above + resp arrest
Brady +/- card arrest
LOC

46. Management Questions? What is the first line of therapy?
When do you give IV vs IM epi?
Do all patients need Epinephrine; corticosteroids?
What is the role of combined H1 & H2 blockers?
Who needs to be monitored? Referred?
Who needs an EpiPen?

47. Key Management of Anaphylaxis
1st line of therapy:
AWARENESS
RECOGNITION
TREAT QUICKLY
CALL FOR BACK-UP!

49. Management: Adult Epi dosing
Epinephrine:
0.3 mg (0.3 ml) 1:1000 solution IM
(NOT SC or IV)
may repeat in 5 min X 1
(empirical only but safe)

50. Epi: Pediatric Dosing (0.01 ml/kg)
Age (yrs) Volume of Dose (mg)
1:1000(1mg/ml)
ml 0.1
ml 0.2
> ml 0.3

51. EPI cautions: Co-morbidities
Thyroid disease
Cocaine addicts
CAD on BBlockers, ACEi
Depression using MAOIs or TCAs
Bblockers blunt the response to epi and this is both B1 and B2. ACEi blunt the catecholamine response ( ACE/Nor-Epi/Epi rise) with shock.

52. Mechanisms of Epinephrine
Alpha agonist effects increase peripheral resistance, raise BP, reduce vascular leakage
Beta agonist effects cause bronchodilation, positive cardiac inotropy/chronotropy (caution in CAD pts!)

53. Dangers of Epinephrine IV
Only use IV Epi if patient has refractory shock not responding to fluid bolus first
dose 0.1 mg (10 ml) 1:100,000 dilution over 10 minutes
must be on cardiac monitor
caution in elderly or those with CAD
may cause supraventricular/ventricular dysrhythmias!

54. Management Do all patients need Epi?
Epinephrine reverses mediator release while antihistamines (H1) do not
Epinephrine should be used for all systemic signs of allergy: airway edema (includes tongue/lips), SOB, cyanosis, hypotension

55. Management: Do all patients need Corticosteroids?
Corticosteroids take 4-6 hours to work
theoretically blunt the multi-phasic reaction of anaphylaxis
the quicker the onset of anaphylaxis the worse the reaction/quicker resolution less likely to relapse
Caution in IV steroids esp if given in bolus doses; case reports of anaphylaxis!
Oral form preferred if possible

56. Histamine Classes
H1 receptor: stimulates bronchial, intestinal, smooth muscle contraction, vascular permeability, coronary artery spasm
H2 receptor: increase rate & force of ventricular & atrial contraction, gastric acid secretion, airway secretions, vascular permeability, bronchodilation, & inhibition of histamine release

57. Management: What is the role of combined H1 & H2 Antagonists?
RCT, N=91 w/ allergic syndromes
50 mg Benadryl (H1) & saline vs. 50 mg Benadryl & 50 mg Ranitidine (H2) IV
Endpoints of resolution of urticaria, angioedema, or erythema
also measured subjective improvement & vitals
Lin et al., Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 & H2 antagonists, Annals of Emergency Medicine 36(5) 2000.

58. Histamines: Results
Statistically significant diminution of angioedema and/or urticaria with addition of H2 blocker
study too small to determine if H2 blockers helpful in anaphylaxis (those with respiratory compromise &/or hypotension)
also significant decrease in HR in Rx group

59. Back to Cases: Management Case 1

60. Case One: Peanut allergy in asthmatic
A 7 year old comes in to the ED after an possible exposure to peanut butter
He has a severe nut allergy for which he was prescribed an EpiPen
He was recently admitted to PICU for a severe asthma attack but was not intubated
Mom gave him some oral Benadryl and he is no longer itchy but still has lip swelling

61. Case One continued
He is sent for a CXR due to decreased air entry in the lower lobes
While in radiology, he becomes acutely SOB and his lip becomes more swollen
What do you do now?

62. Case 1 Conclusion He needs IM Epi!
(He weighs 30 kg and thus 0.3 mg IM is fine.)
O2, IV fluids, cardiac monitoring
Consider Ventolin neb (esp if concurrent asthma)

63. Case Two : MVC Management
A 45 y o woman involved in a MVC needs a CT abdo after she is stabilized in the ED
She received 2 L NS for a hypotensive episode and her BP is now 120/70, HR 100
She has a positive FAST U/S
Although her CXR is normal she has palpable lower rib fractures & a distended abdomen

64. Case Two continued She is given both oral and IV contrast for her CT
She becomes hypotensive again!
What do you do now?
There is no rash

65. Case 2: Conclusion
Is she in hypovolemic shock or anaphylactic? doesn’t matter b/c both require IV crystalloids!
There may be no rash initially
Look for airway compromise/swelling: intubate?
IV contrast reactions are anaphylactoid and so prior sensitization not necessary (thus may be no prior hx of anaphylaxis)
If no response to fluids give IV epi 1st via slow infusion, except if pulseless then may give IV bolus

67. Case 3: Gardener Management

68. Case Three A 67 y o man is stung by an insect while gardening
He developed pruritus, dizziness, and SOB 20 min later so he called 911
He self-treated with Benadryl po and was given another 50 mg IV by EMS due to persistent sx and rash
He is now asymptomatic and refusing transport to hospital

69. Case Three: Do you transport?
EMS convinced him to get “checked out” in the hospital
On arrival, he becomes hypotensive, and his hives reappeared, along with facial edema
An ECG shows T wave inversion in his lateral leads
PHx: MI, HTN, IV contrast allergy
Meds: ASA, metoprolol, lisinopril

70. Case 3 Management: Refractory Anaphylaxis
Biphasic (multi?) reactions can occur typically after 3-4 hours but as late as 72 hours later!
Beware of the patient with increased age and co-morbidities (eg. CAD) b/c anaphylaxis can cause cardiac ischemia
B-Blockers & ACEi blunt the catecholamine response

71. Management Refractory Anaphylaxis: Glucagon
Glucagon: increases inotropy/chronotropy & causes smooth muscle relaxation independent of B receptors
Dose: 1-5 mg in adults ( mg in kids) IV/IM

72. Management: Disposition & Follow-up
Inquire about possible antigen exposure
Those with systemic reactions require a prescription for and instruction on how to use a EpiPen
A Medic Alert Bracelet is useful
Follow-up with an allergist for skin testing should be arranged particularly if the allergen is unknown

73. EpiPen

74. Summary
Acute anaphylaxis is often poorly recognized & treated due to the protean clinical features and variation in the speed of onset
a trigger is often not found
Pruritis is a universal feature and should differentiate anaphylaxis from asthma
Expedious treatment w/ epi is necessary & thus patient education on its use is essential

76. Case of EIA
28 year old male, after eating spaghetti and then playing soccer 1 hr later, developed urticaria & dizziness
attempted to drive to hospital but pulled over because worse
EMS vitals: BP 80/42, HR 90, RR 24
Rx: w/ epi and 1 litre NS
In ED: BP 130/85, chest was clear and “hives” gone but skin still edematous

77. Exercise Induced Anaphylaxis
Clinical features indistinguishable from allergen induced anaphylaxis
food dependent & food independent forms (also cholinergic urticaria)
mechanism not fully known, but thought exercise lowers threshold for mast cell degranulation esp after a food allergen triggers an IgE response

78. Exercise-Induced Allergic Syndromes

79. Natural History of EIA
N= 365 respondents with 10 yr hx of EIA to 75 item questionaire
EIA if anaphylactic Sx with exercise but not with passive warming
Shadick, Nancy A., et al. The Natural History of Exercise-Induced Anaphylaxis: Survey results from a 10-year follow-up study, J Allergy Clin Immunol 1999; 104:

80. Results of Survey frequency of attacks lesson over time
a wide range of activities associated but more CV demand more likely
70% had atopy or family hx of it
subjects avoided attacks by not exercising in humid weather or high allergy seasons
no single trigger identified; most common food
H1 blockers/ epi were used by 30% emergently; Role of prophylaxis?