2. Urticaria Dr.Amirhossein Siadat Associated Professor
Isfahan University of Medical Sciences

3. DEFINITION
Urticaria is defined as a skin lesion consisting of a wheal-and-flare reaction in which Iocalized intracutaneous edema (wheal) is surrounded by an area of redness (erythema) that is typically pruritic.

4. Individual hives can last from as briefly as 30 minutes to as long as 36 hours.
They can be as small as a millimeter or 6 to 8 inches in diameter (giant urticaria).
They blanch with pressure as the dilated blood vessels are compressed, which also accounts for the central pallor of the wheal.

5. Photo Images of Hives

6. Angioedemas : deeper dermal ,subcutaneus and sub mucosal tissues.
They are usually painfull rather than itchy ,poorly defined and pale or normal in color

7. Angioedema Swelling of lips, face, hands, feet, penis or scrotum
Facial swelling most prominent in periorbital area
May be accompanied by swelling of the tongue or pharynx

9. Urticaria is classified to acute and chronic with a time devision between 6w and 3m.
When urticaria is present daily or almost daily for less than 6w it is acute.

11. PREVALANCE: POINT PREVALANCE=0.1%
Cumulative life time prevalance: % in general population but a range of 1-5% is more realistic
72% ordinary urticaria,20%physical and choloinergic,3.4%allergic(exept stings and injected drug),2.1% u.vasculitis,0.5% hereditary angioedema

14. Clinical features of acute or chronic urticaria:
Ithcing erythematous macules develop into weals consisting of pale to pink edematous raised areas of skin often with a surrounding flare
It occurs any where (scalp and palms),in any number and size, any shape even bulla.

15. Wheals are often very itchy especially at night and resolve in a few hour without any residue.
Patient always rub not scratch so excoriation is absent.
Sometimes they bruise like in thigh.
Wheals are more prominent at evening and premens

16. In 50% of of urticaria: there may be angioedema.
Angioedema color is like skin ,most frequently on the face but any other area such as ear ,genitalia,hand and feet
It may last for several days,
It is not always itchy and and may be painful

17. Urticaria may be proceeded with vomiting.
It may be associated with:
malaise
loss of concentration
feeling hot or cold
headache
vomiting
abdominal pain
diarrhoea
arthralgia
dizziness
scyncope
And even anaphylaxies

20. EM like

26. Erythema Multiforme

27. 1) Central dusky purpuric area 2) Elevated edematous pale ring 3) Surrounding macular erythema

28. Dermatitis Herpetiformis

29. Bullous Pemphigoid

32. Insect Bite

33. Insect Bite

34. Pathophysiology

35. Histamine: the most important mediator of urticaria.
Histamine is produced and stored in mast cells.
There are several mechanisms for histamine release via mast cell surface receptors.

36. Phathophysiology:
Urticaria is due to a local increase in permeability of capillaries of venules.
It is due to activation of cutaneus mast cells that contain many mediators predominantly histamin.

37. Non-immunologic factors Anaphylatoxins (C3a, C5a)
Pathophysiology of Urticaria
Non-immunologic factors
Immunologic factors
Chemical histamine liberators
eg. Opiates, polymyxin antibiotics,
thiamine
Types II and III
complement
activation
Alternative
complement
pathway action
Anaphylatoxins (C3a, C5a)
Type I IgE
mediated
Physical agents, e.g.
cold, heat, sunlight
genetic factors
Cholinergic
released mediators
(particularly histamine)
modulating factors
endogenous
hormone
Small blood
vessel
vasodilation
vasodilating
factors
URTICARIA

42. Infantile Urticaria
Food origin is important in the etiology of infantile urticaria.
Food allergyfor 62% of patients
drug etiology (22%)
physical urticaria (8%)
contact urticaria (8%).

44. Lab test For Acute Urticaria

46. Antibiotics especially penicilin and cephalosporin are common causes.
Risk factors:
previous exposure
reaction to a drug or chemically related drug
intermittant and multiple drug therapy ,
familial predisposition

48. Chronic Urticaria

50. History of Chronic Urticaria

53. Physical examination of Chronic Urticaria

55. Lab for chronic urticaria

56. Lab for chronic urticaria

57. Treatment of chronic Urticaria

67. are first-line agents and are given once daily
Antihistamines are the preferred initial treatment for urticaria and angioedema
Cetirizine, loratadine, or fexofenadine
are first-line agents and are given once daily

68. Higher doses than suggested by the manufacturers may be required

69. Patients with daytime and nighttime symptoms can be treated with combination therapy

70. These patients can be treated with: a low-sedating antihistamine in the morning e.g., loratadine 10 mg, or fexofenadine 180 mg, or cetirizine 10 to 20 mg and a sedating antihistamine e.g., hydroxyzine 25 mg in the evening. Cetirizine can be mildly sedating

71. The initial dose is 10 to25 mg.
Doxepin is an alternative bedtime medication especially effective for anxious or depressed patients.
The initial dose is 10 to25 mg.
Gradually increase the dose up to 75 mg for optimal control

72. Some patients with chronic urticaria respond when an H2-receptor antagonist such as cimetidine is added to conventional antihistamines

73. Side Effects
Antihistamines are structurally similar to atropine; therefore they produce atropine-like peripheral and central anticholinergic effects :
dry mouth, blurred vision, constipation, and dizziness.
First-generation antihistamines (H1-receptor antagonists) such as chlorpheniramine, hydroxyzine, and diphenhydramine cross the blood-brain barrier and produce sedation.
Antihistamines may produce stimulation in children, especially in those ages 6 through 12

74. H1 and H2 Antihistamines
Cimetidine, ranitidine, and famotidine are H2 antagonists that are used primarily for the treatment of gastric hyperacidity. Approximately 85% of histamine receptors in the skin are the H1 subtype, and 15% are H2 receptors.
It would seem that the combination of H1 and H2 antihistamines would provide optimal effects.
The results of studies are conflicting but generally show that the combination is only slightly more effective than an H1-blocking agent used alone.

75. First-Generation (Sedating) H1 Antihistamines
.The first-generation H1 antihistamines are divided into five classes
lipophilic, cross the blood-brain barrier, and cause sedation, weight gain, and atropine-like complications including dry mouth, blurred vision, constipation, and dysuria. Metabolism occurs via the hepatic cytochrome P-450 (CYP) system.
In patients with liver disease, or in patients who are taking CYP 3A4 inhibitors such as erythromycin or ketoconazole, the plasma half-life may be prolonged.
Antihistamines given during or after the onset of a hive are less effective.

76. They cause little sedation and little or no atropine-like activity
Second-Generation (Low-Sedating) H1 Antihistamines
The second-generation antihistamines are not lipophilic and do not readily cross the blood-brain barrier
They cause little sedation and little or no atropine-like activity

77. Fexofenadine (Allegra)
Fexofenadine in a single dose of 180 mg daily or 60 mg twice daily is the recommended dosage for treating urticaria
Dosage adjustment is not necessary in the elderly or in patients with mild renal or hepatic impairment
Fexofenadine may offer the best combination of effectiveness and safety of all of the low-sedating antihistamines

78. Cetirizine (Zyrtec)
Cetirizine is a metabolite of the first-generation H1-antihistamine hydroxyzine
The adult dose is 10 mg daily. A reduced dosage (5 mg daily) is recommended in patients with chronic renal or hepatic impairment.
No drug interactions are reported, and there is no cardiotoxicity
A dose higher than recommended may be required.

79. Loratadine (Claritin)
Loratadine is a long-acting second-generation H1-histamine antagonist
A 10-mg dose suppresses whealing for up to 12 hours; suppression lasts longer after a larger dosage
A reduced dosage may be required in patients with chronic liver or renal disease. There are no significant adverse drug interactions
A special form of the medication, RediTabs (10 mg)rapidly disintegrates in the mouth
A dose higher than recommended may be required.

80. Desloratadine (Clarinex)
Desloratadine is an active metabolite of loratadine
A 5-mg dose each day is effective
There is no evidence that it offers any advantage over loratadine

81. Tricyclic Antihistamines (Doxepin)
Tricyclic antidepressants are potent blockers of histamine H1 and H2 receptors.
When taken in dosages between 10 and 25 mg three times a day
doxepin is effective for the treatment of chronic idiopathic urticaria. Doxepin is a good alternative for patients with chronic urticaria not controlled with conventional antihistamines and for patients who suffer anxiety and depression associated with chronic urticaria
Side effects:
Lethargy
Dry mouth and constipation
Doxepin can interact with other drugs that are metabolized by the cytochrome P-450 system (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin)

82. Severe urticaria angioedema requires epinephrine
Epinephrine solutions have a rapid onset of effect but a short duration of action
The dosage for adults is a 1:1000 solution (0.2 to 1.0 ml) given either subcutaneously or intramuscularly
the initial dose is usually 0.3 ml

83. Second-Line Agents

84. Oral Corticosteroids Leukotriene Modifiers
Because of toxicity, corticosteroids are reserved for antihistamine failures or the most severe cases
They are reliable and effective
The patient receives 5 days each of 60 mg, 40 mg, and 20 mg
Leukotriene Modifiers
Leukotriene modifiers may provide improvement in some cases of antihistamine-resistant chronic urticaria
Excellent safety, absence of required monitoring in the cases of montelukast and
zafirlukast, and wide availability make leukotriene modifiers the preferred alternative agent
Montelukast was demonstrated to be effective for patients with NSAID-exacerbated chronic urticaria. Patients with positive autologous serum skin test (ASST) results may predict better response to leukotriene modifiers
Experience in physical urticarias has also been promising.

85. Dapsone, Cyclosporine, Mycophenolate Mofetil
Other second line Drugs:
Dapsone, Cyclosporine, Mycophenolate Mofetil

86. Third Line Treatments:
IVIg, MTX (10 to 15 mg weekly)

87. Topical Measure:
Calamine
Menthol

88. Avoid factors that enhance pruritus
Taking aspirin, drinking alcohol, or wearing tight elasticized apparel or coarse woolen fabrics

90. Physical Urticarias 20% of all urticarias Dermatographism
Cholinergic/Adrenergic
Cold/Heat
Solar
Pressure
Exercise induced
Aquagenic
Vibratory Angioedema

91. Physical Urticarias Physical urticaria
May occur so intermittently as to appear acute but typically are chronic entities – most idiopathic

92. Symptomatic Dermatographism
Simply scratching the skin promotes linear hives within minutes
Delayed form described
Typically is short-lived in duration (1/2 to 3 hours) and responds readily to antihistamines
Perhaps the most common of all chronic urticarias is dermatographism. In some instances, the dermatographism may be occult and only after firmly scratching the surface of the skin will it be defined. Most patients with dermatographism have a baseline pruritis. 92

95. Cholinergic Urticaria

96. Cholinergic Urticaria
Goal of raising body temperature (oral) by 0.7oC
Hot bath to 420C or having patient exercise
Small pruritic papules result surrounded by erythema (but without hypotension) result
Passive heat challenge may separate exercise-induced anaphylaxis from cholinergic urticaria

98. Cold-Induced Urticaria
Familial (autosomal dominant) vs acquired (usually infection associated)
Acquired form -positive ice-cube challenge
Usually responds to cyproheptadine

100. Diagnosis of cold-induced urticaria
Cold Stimulation Time Test (CSTT)
Positive in acquired cold-induced urticaria
Ice cubes and water in a plastic bag applied to patient’s forearm up to 10 minutes
Urticaria results after warming of area
Timing of cold stimulus indirectly proportional to severity (less time needed, worse symptoms upon exposure to cold)
Many patients with good history for cold-induced urticaria may have negative CSTT
A seperate entitiy, know as familial cold-induced anti-inflammatory syndrome was previously considered in the differential of cold-induced urticaria and angioedema . Hoffman, H, Wanderer A, Broide D. J Allergy Clin Immunol 2001; 108:
However, this particular entity is not only autosomal dominant, but also is characterized by fever and flu-like arthrlagias when the patient is chilled. Patients with urticaria and angioedema do not typically manifest other symptoms except the pruritis or discomfort (respectively) that accompanies their symptoms.
100

101. Delayed Pressure Urticaria

102. Delayed Pressure Angioedema
~ 37% incidence of delayed pressure urticaria in chronic urticaria
15 pound weight suspended by thick strap over the shoulder and worn for 15 minutes
Typically, erythema with induration and tenderness occurs at least 2 hours after the test
This is often considered but rarely demonstrated because of the predilection for involvement of pressure-dependent areas. Also consider delayed dermatographism in the differential. In some instances, it may be associated with a food allergy Davis KC, Mekori YA, Kohler PF, Schocket Possible role of diet in delayed pressure urticaria--preliminary report. J Allergy Clin Immunol Apr;77(4): This is one of the most difficult articarias to treat and often requires oral steroids for resolution.
102

103. Vibratory angioedema Vortex to induce angioedema in a patient
In some instances, patients may present with angioedema affecting one area of the body. Vibration, as in the case of a car whose wheels were out of balance, often induces the reaction. Antihistamines often will result in relief.
Vortex to induce angioedema in a patient
with swelling of hands while driving car
Lawlor F et al Br J Dermatol 1989; 120: 93-99
103

104. The End

105. Angioedema

106. Hereditary Angioedema
2nd to 4th decade, + Family history, AD
May occur q2 weeks, lasting 2 to 5 days
Eyelid and lip involvement NOT SEEN.
Face, hands, arms, legs, genitals buttocks, stomach, intestines, bladder affected.
N/V, Colic, may mimic Appendicitis
Triggers: minor trauma, surgery, sudden changes in temperature or sudden emotional stress
Presence of urticaria rules out HA

107. Hereditary Angioedema
aka Quincke’s Edema
NO PRURITIS OR URTICARIA, + PAIN
Low C4, C1, C1q, C2 levels
Low or dysfunctional plasma C1 esterase inhibitor protein.
25% of deaths from laryngeal edema
Tx of choice: fresh frozen plasma, stanazol, tranexamic acid

108. Type I and Type II HA
Type I – LOW serum levels of NORMAL C1 esterase inhibitor protein
Type II – NORMAL levels of DYSFUNCTIONAL C1 esterase inhibitor protein.
C4 best screening test, it will be low in both of the above cases.

109. HA - Treatment
25% of deaths due to HA are the result of laryngeal edema
TOC for acute HA is fresh frozen plasma
Stanazol useful for short-term prophylaxis in patients undergoing dental surgery, endoscopic surgery or intubation.
Tranexamic acid in low doses has few side effects and useful for acute or chronic HA.

110. Acquired Angioedema Symptoms same as HA, but NO family hx.
Aka Caldwell’s Syndrome
Occurs at night, pt wakes up with it.
Acute evanescent circumscribed edema
Affects most distensible tissues: eyelids, lips, earlobes, genitalia, mouth, tongue, larynx.
Swelling is subcutaneous, not dermal.
Overlying skin is not affected.

123. The End