This is a case of a 12-year-old Thai boy who developed lip swelling, rash and itching 5 minutes after receiving an intravenous injection of ceftriaxone for diarrhea. He has a history of rash after taking an antibiotic for a sore throat 1 year ago. The symptoms suggest he may have experienced anaphylaxis reaction to the antibiotic injection. Further evaluation and management are needed to confirm the diagnosis and treat the reaction.

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.