1. Urticaria, Angioedema and Anaphylaxis
MAGED M. REFAAT,MD,FAAAAI
PROFESSOR OF MEDICINE,ALLERGY &CLINICAL IMMUNOLOGY
AIN SHAMS UNIVERSITY

2. Case One
A 7 year old comes in to the ED after a meal which includes fish and shrimp with itchy rash.
He has a severe fish allergy .
He was recently admitted to ICU for a severe asthma attack but was not intubated
His mother gave him some oral antihistaminic 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 needs a CT abdomen .
She is given both oral and IV contrast for her CT
She becomes hypotensive .
What do you do now?
There is no rash

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

7. Case Three: Do you transport?
He went to 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

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

10. 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

11. 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

12. Urticaria
=HIVES

13. URTICARIA
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.

15. Urticaria (or hives)

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
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
Glucocorticoids e.g. prednisone
Stabilize mast cells, stopping histamine release
Anti-inflammatory effect

25. Pruritus in certain internal diseases

26. Angioedema
+\- URTICARIA

27. Angioedema
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

31. 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

32. 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

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

34. 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

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
Anyaphylactic 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. 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

40. 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

41. 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
Hereditary angioedema

42. 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

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

44. Key Management of Anaphylaxis
1st line of therapy:
AWARENESS
RECOGNITION
TREAT QUICKLY
CALL

45. 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)

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

47. 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!)

48. 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

49. Management: Do all patients need Corticosteroids?
Corticosteroids take 4-6 hours to work
Blunt the multi-phasic reaction of anaphylaxis

50. 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

51. Case One
A 7 year old comes in to the ED after a meal which includes fish and shrimp with itchy rash.
He has a severe fish allergy .
He was recently admitted to ICU for a severe asthma attack but was not intubated
His mother gave him some oral antihistaminic and he is no longer itchy but still has lip swelling

53. 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?

54. 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)

55. Case Two
A 45 y o woman needs a CT abdomen .
She is given both oral and IV contrast for her CT
She becomes hypotensive .
What do you do now?
There is no rash

56. 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

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

58. Case Three: Do you transport?
He went to 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

60. 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

61. 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

62. 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

63. EpiPen

64. 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

66. REFERENCES http://www.aacijournal.com/content/7/S1/S9

67. THANK YOU