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Urticaria
Dr.Amirhossein Siadat
Associated Professor
Isfahan University of Medical Sciences
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.
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.
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PHOTO IMAGES OF HIVES
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Angioedemas : deeper dermal ,subcutaneus
and sub mucosal tissues.
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They are usually painfull rather than itchy
,poorly defined and pale or normal in color
ANGIOEDEMA
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Swelling of lips, face, hands, feet, penis or scrotum
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Facial swelling most prominent in periorbital area
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May be accompanied by swelling of the tongue or pharynx
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Urticaria is classified to acute and chronic with
a time devision between 6w and 3m.
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When urticaria is present daily or almost daily
for less than 6w it is acute.
PREVALANCE:
POINT PREVALANCE=0.1%
 Cumulative life time prevalance:0.05-23.6% 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
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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.
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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
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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
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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
EM LIKE
ERYTHEMA MULTIFORME
1) Central dusky purpuric area
2) Elevated edematous pale ring
3) Surrounding macular erythema
DERMATITIS HERPETIFORMIS
BULLOUS PEMPHIGOID
INSECT BITE
INSECT BITE
PATHOPHYSIOLOGY
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.
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PHATHOPHYSIOLOGY:
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Urticaria is due to a local increase in
permeability of capillaries of venules.
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It is due to activation of cutaneus mast cells
that contain many mediators predominantly
histamin.
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)
Physical agents, e.g.
cold, heat, sunlight
Type I IgE
mediated
genetic factors
modulating factors
Cholinergic
released mediators
(particularly histamine)
endogenous
hormone
vasodilating
factors
Small blood
vessel
vasodilation
URTICARIA
INFANTILE URTICARIA
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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%).
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LAB TEST FOR ACUTE URTICARIA
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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
CHRONIC URTICARIA
HISTORY OF CHRONIC URTICARIA
PHYSICAL EXAMINATION OF CHRONIC
URTICARIA
LAB FOR CHRONIC URTICARIA
LAB FOR CHRONIC URTICARIA
TREATMENT OF CHRONIC URTICARIA
Antihistamines are the preferred
initial treatment for urticaria and
angioedema
Cetirizine, loratadine, or fexofenadine
are first-line agents and are
given once daily
Higher doses than suggested by the
manufacturers may be required
Patients with daytime and nighttime
symptoms can be treated with
combination therapy
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
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
Some patients with chronic urticaria
respond when an H2-receptor antagonist
such as cimetidine is added to
conventional antihistamines
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
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.
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.
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
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
Cetirizine (Zyrtec)
Cetirizine is a metabolite of the first-generation H1antihistamine 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.
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.
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
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 P450 system (e.g., ketoconazole, itraconazole, erythromycin,
clarithromycin)
Epinephrine
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
Second-Line Agents
Oral Corticosteroids
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 NSAIDexacerbated 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.
Other second line Drugs:
Dapsone, Cyclosporine,
Mycophenolate Mofetil
Third Line Treatments:
IVIg, MTX (10 to 15 mg weekly)
Topical Measure:
Calamine
Menthol
Avoid factors that enhance pruritus
Taking aspirin, drinking alcohol, or
wearing tight elasticized apparel or
coarse woolen fabrics
PHYSICAL URTICARIAS
20% of all urticarias
 Dermatographism
 Cholinergic/Adrenergic
 Cold/Heat
 Solar
 Pressure
 Exercise induced
 Aquagenic
 Vibratory Angioedema
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Physical
urticaria
PHYSICAL
URTICARIAS
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May occur so intermittently as to appear
acute but typically are chronic entities – most
idiopathic
SYMPTOMATIC
Symptomatic Dermatographism
DERMATOGRAPHISM
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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
Cholinergic Urticaria
CHOLINERGIC URTICARIA
Cholinergic urticaria
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Goal of raising body temperature (oral) by 0.7oC
Hot bath to 420C or having patient exercise
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Small pruritic papules result surrounded by
erythema (but without hypotension) result
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Passive heat challenge may separate exerciseinduced anaphylaxis from cholinergic urticaria
COLD-INDUCED URTICARIA
Cold-induced urticaria
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Familial (autosomal
dominant) vs
acquired (usually
infection associated)
Acquired form positive ice-cube
challenge
Usually responds to
cyproheptadine
DIAGNOSIS OF COLD-INDUCED URTICARIA
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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 coldinduced urticaria may have negative CSTT
DELAYED PRESSURE URTICARIA
DELAYED PRESSURE ANGIOEDEMA
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~ 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
VIBRATORY ANGIOEDEMA
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
THE END
ANGIOEDEMA
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
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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
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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.
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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.
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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.
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THE END