1. URTICARIA, ANGIOEDEMA นสพ.อาทิ ต ย์ เชยคาดี
AND ANAPHYLAXIS

2. URTICARIA
Definition
Urtica in Latin is Nettle rash
Urticaria (or hives)
 irregularly shaped wheal with a blanched center
surrounded by a red flare
 itchy rash consisting of a raised
 Rapid disappear to normal skin in 1-24 hr.
 But can appear in other area

3. URTICARIA

4. URTICARIA
Classification
Spontaneous urticaria
Acute Urticaria
 Episodes of hives that continue for <6 wk
Chronic Urticaria
 persist for >6 wk
 Chronic continuous urticaria
 Chronic recurrent urticaria

5. URTICARIA
Classification
 Physical urticaria
 Cold contact urticaria
 Delayed pressure urticaria
 Heat contact urticaria
 Solar urticaria
 Urticaria factitia/dermographic urticaria
 Vibratory urticaria/angioedema
 Aquagenic urticaria
 Cholinergic urticaria
 Contact urticaria
 Exercise-induced urticaria

6. ETIOLOGY OF ACUTE URTICARIA
 Foods Egg, milk, wheat, peanuts
 Medications Suspect all medications
 Insect stings Hymenoptera (honeybee, yellow jacket,
hornets, wasp, fire ants), biting insects ( papular
urticaria)
 Infections
 Contact allergy Latex, pollen, animal saliva, nettle
plants, caterpillars
 Transfusion reactions Blood, blood products, or IV
immunoglobulin administration
 Idiopathic
 EBV, Epstein-Barr virus.

7. ETIOLOGY OF CHRONIC URTICARIA
 Idiopathic 75–90%
 Rheumatologic
 Systemic lupus erythematosus
 Juvenile rheumatoid arthritis
 Endocrine Hyperthyroidism
 Hypothyroidism
 Neoplastic Lymphoma
 Mastocytosis
 Leukemia
 Angioedema Hereditary angioedema
 Acquired angioedema
 Angiotensin-converting enzyme inhibitors

8. URTICARIA - MECHANISMS
Immunologic
IgE-mediated – histamine, PAF, PGD 2, LTC, LTD
 Foods/food additives
 Medications
 Hymenoptera venom
Complement system activation
 Blood/blood products
Neuropeptides
 Substance-P, Somatostatin, VIP
Cytokines

9. MECHANISMS OF URTICARIA
Non-Immunologic
Direct mast cell activation
 Radio contrast dye, opiates, polymyxin
Modulation of the mast cell responsiveness
 Arachidonic acid metabolism (NSAIDs, Aspirin)
Miscellaneous
 Physical, Cold, Pressure

10. DIFFERENTIAL DIAGNOSIS OF URTICARIA
 Urticaria pigmentosa
 Urticaria Vasculitis
 Erythema multiforme
 Insect bite reaction = papular urticaria
 Collagen vascular
 Immunobullous disease  Bullous pemphigoid
 Annular erythema
 Erythema marginatum
 Pityriasis Rosea
 Guttate psoriasis
 Erythema annulare centrifugum
 Erythema chronicum migrans

11. DIFFERENTIAL DIAGNOSIS OF URTICARIA
 Juvenile rheumatoid arthritis
 Kawasaki disease
 Viral examthems
 Acute febrile neutrophilic dermatosis (Sweet’s
syndrome)
 Scabies
 Parasite  S.stercoralis  larva currens

12. Urticaria pigmentosa Urticaria Vasculitis

13. Erythema multiforme
Sweet’s syndrome

14. Erythema annulare centrifugum larva currens

15. DIAGNOSIS

16. ANGIOEDEMA
Definition
Angioedema is the swelling of deep dermis,
subcutaneous, or submucosal tissue due to
vascular leakage
Pain > itchy
Often at Mucous membrane
Recovery slower than wheal Duration 72 hr.

17. ANGIOEDEMA

18. ANGIOEDEMA
 Hereditary
 Type I
 Type II
 Hereditary angioedema with normal C1 INH in woman
 Acquired
 Allergic : food, drug, insect venoms, radiocontrast media etc.
 Idiopathic angioedema
 Drug : NSAID induced
 Angioedema associated with idiopathic or autoimmune urticaria
 Angioedema associated with enzyme-inhibitor-induced
 Angioedema associated with eosinophilia
 Angioedema associated with physical urticaria and with cholinergic
urticaria

19. ANGIOEDEMA
 Acquired
 Angioedema associated with allergic contact urticaria
 Angioedema associated with urticarial vasculitis
 Angioedema associated with infection and infestation
 Acquired C1 INH deficiency

20. ANGIOEDEMA
 Normal or elevated serum complement levels
 IgE-mediated (atopic, specific antigen, exercise)
 Induced by physical agents
 Drug : Aspirin, NSAID, contrast media, opiates, polyanionic antibiotic
 Low serum complement levels
 Low C1 INH
 Genetic (Hereditary C1 INH deficiency; HAE)
 C1 INH deficiency type I and II
 Acquired (Acquired C1 INH deficiency; AAE)
 Lyphoproliferative disorders
 Anti-C1 INH antibodies
 Normal C1 INH
 Serum sickness, blood product reaction
 Necrotizing vasculitis
 Dyes : contrast media
 Idiosyncratic

21. HEREDITARY ANGIOEDEMA
 Autosomal dominant with incomplete penetrance.
 Spontaneous mutations in 50%
 Diminished C4 between attacks
 Very low C4 during attacks
 HAE I
 Low levels of C1 esterase inhibitor
 HAE II
 Dysfunctional C1 INH
 HAE III (estrogen-dependent angioedema)
 Normal C1 INH amount and function
 Normal complement levels

22. DIFFERENTIAL DIAGNOSIS OF ANGIOEDEMA
CHF
Lymphedema
Thrombophlebitis
Erysipelas
Cellulitis
Child abuse
Nephrotic syndrome

23. DIFFERENTIAL DIAGNOSIS OF ANGIOEDEMA
Superior vena cava syndrome
Myxedema from congenital hypothyroidism
Dermatomyositis
Scleroderma
Parasite  Trichinella spiralis
Allergic contact dermatitis
Crohn’s disease
Melkersson-Rosenthal syndrome
Cheilitis granulomatosa

24. Thrombophlebitis
Cellulitis

25. DIAGNOSIS OF URTICARIA/ANGIOEDEMA
History
 Time of onset of disease
 Frequency and Duration of healing
 Size, shape, area and distribution
 Urticaria and angioedema
 Pruritus or pain
 Family history (atopy)
 Present illness and past history about allergy
 Physical stimulation or exercise

26. DIAGNOSIS OF URTICARIA/ANGIOEDEMA
History
 Drug used history
 Food
 Smoking
 Occupation
 Relati onship to the menstrua l cycle
 Travel
 Surgical implantations
 Insect bite
 Stress
 Response to treatment

27. Urticaria/angioedema
superficial deep
> 24 hr. < 24 hr. + Urticaria - Urticaria
Biopsy
Urticaria+angioedema
Unknown
/phatology cause
< 6 WK > 6 WK
Vasculitis Abnormal Pressure
Drug
C1INH test +
Yes No
History/
Demographism test Delayed
HAE AAE
Urticaria pressure
Vasculitis urticaria
Acute urticaria
Work up / Physical / Cholinergic
Chronic urticaria
autoimmune urticaria

28. MANAGEMENT
Identification and elimination of the underlying
cause and/or trigger
Symptomatic therapy
 Drug
 Cold pack
 Avoid drug is trigger urticaria (NSAID, morphine, ACE
inhibitor, ingredient  alcohol )

29. MANAGEMENT
 First-line drug therapies
 Antihistamine
 H1 –antihistamine first generation
 Chlopheniramine
 Diphenhydramine
 Hydroxyzine
 H1 –antihistamine second generation
 Cetirizine
 Desloratadine
 Fexofenadine
 Ketotifen
 Loratadine
 Levocetirizine

30. MANAGEMENT
Second-line drug therapies
 H2 –antihistamine
 Cimetidine
 Ranitidine
Tricyclic antidepressant
 Doxepin
Corticosteroids
Leukotriene receptor antagonist
 Montelukast

31. MANAGEMENT
Third-line therapies
Cyclosporine 2.5-5mg/kg/day
Intravenous immnuoglobulin
Immunosuppressive drugs
 methotrexate

32. Acute urticaria
• History talking
• Infection, drug, food, insect,
physical
• Physical examination
• Severity
• LAB investigation
• Eliminate underlying cause
Not severe
Severe
Epinephine inj,
- H1 antagonist Anaphylaxis ?
chlorpheniramine inj, Admit
- Soothing lotion
dexamethasone inj

33. ผู้ป่วยมีภาวะ Anxiety หรื อผื่นเห่อช่วงกลางคืน
ใช่ ไม่ใช่
Sedating H1-antihistamine Non-sedating H1-
antihistamine
มีอาการมาก มี Angioedema
ใช่ ไม่ใช่
เพิ่ม prednisolone 25mg/day
ให้ antihistamine ต่อ
แล้ วหยุดยาใน 1-2 สัปดาห์
ยังควบคุมไม่ได้ หมด

34. ยังควบคุมโรคไม่ได้ หมด
ใช่ ไม่ใช่
Add Leukotriene ให้ antihistamine
ยังควบคุมไม่ได้
ใช่ ไม่ใช่
เพิ่ม prednisolone 25mg/day Anti histamine +
ลดลงจนควบคุมอาการได้ leukotriene
ยังควบคุมไม่ได้ หมด

35. ยังควบคุมโรคไม่ได้ หมด
ใช่ ไม่ใช่
ยาทางเลือกอื่นๆ เช่น cyclosporine Anti histamine +
corticosteroid

36. CHRONIC URTICARIA

37. TREATMENT OF HEREDITARY
ANGIOEDEMA
 Patient education very important; test family
 No regular medication needed in many cases
 Prophylactic stanozolol or danozol
 Fresh frozen plasma before emergency surgery
 C1 inhibitor
 Symptomatic treatment during attacks
 Steroids and antihistamines are NOT effective

38. SUMMARY OF TREATMENTS FOR C1
ESTERASE INHIBITOR DEFICIENCY

39. CASE STUDY

40. CASE
 ผู้ป่ วยเด็ ก ชายไทย อายุ 12 ปี ภู มิ ลาเนา จัง หวัด แพร่
 CC : ปากบวมมี ผื่ น คั น หลั ง ฉี ด ยา 5 นาที
 PI : 1 วั น ก่ อ นมาโรงพยาบาล มี ไ ข้ ถ่ า ยอุ จ จาระเหลวเป็ นมู ก ปริ ม าณไม่ ม ากวั น ละ
3 – 4 ครั ง มี อ าการอ่ อ นเพลี ย ได้ มาตรวจและแพทย์ ใ ห้ admit รั ก ษาด้ วยการให้
้
สารน ้าทางหลอดเลื อ ดดาและยาฉี ด ceftriaxone 500 mg IV q 12 hr.
หลั ง ฉี ด ยา5 นาที ผู้ ป่ วยมี ริ ม ฝี ปากบวม ผื่ น แดงคั น ตามตั ว และเวี ย นศี ร ษะคล้ ายจะ
เป็ นลม
 PH : ปฏิ เ สธโรคประจาตั ว แต่ เ มื่ อ 1 ปี ก่ อ น เคยกิ น ยาฆ่ า เชื อ รั ก ษาอาการเจ็ บ คอ
้
กิ น แล้ วมี ผื่ น ขึ น ตามตั ว อาการไม่ รุ น แรง หายไปเอง ไม่ ไ ด้ ไปพบแพทย์ ไม่ มี ป ระวั ติ แ พ้
้
ยาในครอบครั ว

41. CASE
 Physical examination
 V/S BT = 38.5 C , PR 120/min, RR = 20 /min, BP =80/40mmHg
 BW = 20 kg , Height 155 cm
 GA : A thai boy with good consciousness, no pallor, no
jaundice, no cyanosis
 Skin : dry and swollen lips, flushing, generalized urticaria
rash with facial angioedema
 Heart : tachycardia wit normal S1 S2, no murmur
 Lungs : expiratory Wheezing on both lungs, no crepitation
 Other : unremarkable

42. CASE
 Positive finding
 Fever
 Tachycardia
 Hypotension
 Hx of Drug allery
 Angioedema
 Urticaria
 expiratory Wheezing on both lungs
 Negative finding
 No stress
 No redness of body
 No brown macule
 No hx of psychological disorder

43. CASE
 Problem list
 Angioedema with generalize urticaria rash with anaphylaxis
 Fever with mucous diarrhea

44. PROVISIONAL DIAGNOSIS
Anaphylactic shock
Acute gastroenteritis

45. TREATMENT IN THIS CASE
Stop ceftriaxone
Adrenaline (1:1000) IM
0.9 % NaCl IV loading
Antihistamine

46. ANAPHYLAXIS

47. DEFINITION OF ANAPHYLAXIS
 systemic, immediate hypersensitivity
 Affects body as a whole
 Multiple organ systems may be involved
 Onset generally acute
 Manifestations vary from mild to fatal
 immunoglobulin E (IgE)-mediated
 Anaphylatoid
 Non – immunoglobulin E (IgE)-mediated

48. ANAPHYLACTOID REACTIONS
 Non–IgE-mediated
 Complement-mediated
 Anaphylatoxins, eg, blood products
 Direct stimulation
 eg, radiocontrast media
 Mechanism unknown
 Exercise
 NSAIDs

49. COMMON TRIGGERS OF PEDIATRIC
ANAPHYLAXIS
 Foods (most common cause in children) – Milk, eggs,
wheat, soy, fish, shellfish,
 Medicinals – Antibiotics (penicillins, cephalosporins),
local anesthetics, NSAID, opiates,dextran, radiocontrast
media
 Biologics – Venoms (bee sting, ant or snake bite), blood
and blood products, vaccines, allergen extracts
 Preservatives and additives – Metabisulfite,
monosodium glutamate
 Other – Latex, unknown/idiopathic

51. CLINICAL MANIFESTATIONS OF ANAPHYLAXIS
Skin: Flushing, pruritus, urticaria, angioedema
Upper respiratory: Congestion, rhinorrhea
Lower respiratory: Bronchospasm, throat or
chest tightness, hoarseness, wheezing,
shortness of breath, cough

52. CLINICAL MANIFESTATIONS OF
ANAPHYLAXIS
Gastrointestinal tract:
Oral pruritus
Cramps, nausea, vomiting, diarrhea
Cardiovascular system:
Tachycardia, bradycardia, hypotension/shock,
arrhythmias, ischemia, chest pain

53. CRITERIA FOR ANAPHYLAXIS
Criterion 1 – Acute onset of an illness
involving the skin, mucous membranes
 at least one of the following:
Respiratory compromise
Decreased blood pressure or associated symptoms
of end-organ dysfunction

54. CRITERIA FOR ANAPHYLAXIS
Criterion 2 – Two or more of the following that
occur rapidly after exposure to an allergen that is
likely for that patient
Involvement of the skin and/or mucous
membranes
Respiratory compromise
Decreased blood pressure or associated symptoms
Persistent gastrointestinal symptoms

55. CRITERIA FOR ANAPHYLAXIS
Criterion 3 – Decreased blood pressure after
exposure of a known allergen for that patient
 Decreased blood pressure is defined in adults as a systolic
BP of less than 90 mmHg or >30% decrease from that
patient’s baseline.
 In infants and children, decreased BP is defined as low
systolic
 BP of less than 70 mmHg from one month up to one
year
 less than (70mmHg + [2 x age]} from one to ten years
 less than 90 mmHg from 11 to 17 years.

56. DIFFERENTIAL DIAGNOSIS
 Vasovagal reactions
 Flush syndrome
 Carcinoid
 Pheochromcytoma
 Medullary thyroid carcinoma
 Resturant syndrome
 Monosodium glutamate
 Excessive production of histamine
 Systemic maastocytosis
 Basophilic leukemia
 Shock
 Hemorrhagic / hypovolemic
 Cardiogenic
 Septic

57. DIFFERENTIAL DIAGNOSIS
 Acute respiratory failure
 Status asthmaticus
 Foreign body aspiration
 Pulmonary embolism
 Epiglottitis
 Non organic disease
 Panic attack
 Munchausen’s stridor
 Vocal cord dysfunction
 Other
 Red man syndrome (Vancomycin)
 Hereditary angioedema

58. LAB INVESTIGATION
 Serum tryptase
 Peak at 60- 90 min
 > 10 nanogram/ml
 > 1.4 times or 2 nanogram/ml at 1-2 wk after anaphylaxis
 Sensitivity 73% specific 98 %
 In some case are normal but mastocytosis  rise
 Specific – IgE
 Skin test 6 wk after anaphylaxis
 Serum specific IgE antibody

59. TREATMENT
 Support the airway and ventilation; and Give
supplementary oxygen.
 Intramuscular 1: 1000 (1 mg/ml) adrenaline at a dose of
0.01 mg/kg (0.01 ml/kg) body weight up to a maximum
dose of 0.5 mg (0.5 ml)
 Resuscitate with intravenous saline (20 ml/kg body
weight)
 Bronchodilator
 Systemic corticosteroid
 Hydrocortisone (5mg/kg q 6 hr.)
 Methylprednisolone (1mg/kg q 6 hr.)

60. TREATMENT
 Antihistamine
 Chlorpheniramine 0.1mg/kg q 6 hr.
 Cimetidine 4mg/kg max 300mg q 8-12 hr.
 Refractory anaphylaxis in patient used beta -blocker
 Glucagon 20-30 mcg/kg max 1 mg slow push in 5 min and IV drip 5-15
mcg/min until BP stable
 Bradycardia
 Atropine 0.5 mg q 10 min cumulative dose 2 mg

62. PREVENTION
 Agents causing anaphylaxis should be identified when possible
and avoided
 Individuals at high risk for anaphylaxis should be issued
epinephrine syringes for self -administration and instructed in
their use
 Beta-adrenergic antagonists should be avoided, whenever
possible.
 Children and their care -givers should be offered a written
emergency plan in case of accidental ingestion.
 Pre-treatment with glucocorticosteroids and H1 and H2
antihistamines when used radio contrast media in some case

63. PREVENTION
 Patients with egg allergy should be tested before receiving
measles, influenza or yellow fever vaccines which contain egg
protein.
 In cases of food-associated exercise-induced anaphylaxis,
children must not exercise within 4 hours of ingesting the
triggering food
 Reactions to medications can be reduced and minimized by using
oral medications in preference to injected forms.
 The use of powder-free, low allergen gloves and materials should
be used in children undergoing multiple surgeries.

64. REFERENCE
 Zuberbier T, Bindslev-Jensen C, Canonica W, Grattan CE, Greaves
MW, Henz BM, et al. EAACI/GA2LEN/EDF guideline: definition,
classifica tion and diagnosis of urticaria. Allergy 2006; 61:316-20.
 Zuberbier T, Bindslev-Jensen C, Canonica W, Grattan CE, Greaves
MW, Henz BM, et al. EAACI/GA2LEN/EDF guideline: management of
urticaria. Allergy 2006; 61:321-31.
 Grattan CEH, Humphreys. Guidelines for evaluation and
management of urticaria in adults and children. Br J Dermatol 2007;
157: 1116-23.
 M. Scott Linscott, Anaphylaxis: Diagnosis and Management in the
Rural Emergency Department. American Journal of Clinical Medicine
2012 ; 91.
 Donald Y.M. Leung, Stephen C. Dreskin. Urticaria (Hives) and
Angioedema. In: Behrman RE, Kliegman RM, Jenson HB. Nelson
Textbook of Pediatrics. 18th ed. Philadelphia PA: W.B. Saunders;
2007.
 Elham Hossny. Anaphylaxis in children. Egypt J Pediatr Allergy
Immunol 2007; 5(2): 47-54.