Transcript Cholinergic Urticaria

Urticaria and
Angioedema
Dr Amir Hossein Siadat
DEFINITION
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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 (quinkes edema) affect
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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Larynx virtually never involved
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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.
CLINICAL CLASSIFICATION OF
URTICARIA:
1)ORDINARY URTICARIA (acute or
chronic)
 2)physical and cholinergic
 3)Urticarial vasculitis
 4)Contact Urticaria
 5)angioedema
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Up to 50%of patients previously
diagnosed as chronic idopathic urticaria
have an autoimune bases.
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Acute ordinary urticaria may be due to
allergy especially in atopics but not in
chronic.
ASSOCIATIONS
1)an association between chronic ordinary u and
autoimune thyroid disease
 2)there is a higher frequency of autoimune diseases in
patients with autoimune u
 The older litrature suggest that chronic idiopathic u may
be associated with chhronic infection especially dental
and candida of the bowel but now it occures rarely if at
all
 4)it has been proposed that H.PYLORI infection may play
an indirect role in autoimune chronic u by molecular
mimicry in genetically predisposed individuals
 5)no association with malignancies was found in a large
study
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PREVALANCE:
POINT PREVALANCE=0.1%
 Cumulative life time prevalance:0.0523.6% 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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GENETICS
Hereditary C1 Estrase defficiency
angioedema
 Muckle Well Syn
 Familial cold urticaria
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Highly significant linkage of HLA DR4 and
HLA DQ8 in chronic ordinary urticaria.
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
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
Urticaria in infancy:
Cows milk allergy is the commonest
etiology of urticaria in infants under 6m
 In infants there may be less itching and
more tendency to purpuric wheals,
 Bizzarly shaped wheals are more common
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ACUTE URTICARIA:
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1) Idiopathic:
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Most common type: >50% of cases
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Sometimes is observed following URTI
2)ALLERGIC:
 Is due to interaction of allergen with IgE
bound to mast cells
 more common in atopics,
 Although it is unusual to find an allergic
cause, any drug ,food, inhalatant and
foreign substance( implants, contactants
and injection should be considered).
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In an IgE mediated reaction there have
been a previous exposure and the reaction
will occur in minutes (less than 60 min)
 Acute urticaria from drug is common and
usually occur within 36h (it is unusual for
a drug that is contiuously taken for
months
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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
Food: common within minutes but
occasionally many hours after due to slow
absorption or metabolism
 Common food: Shrimp, Crab, Fish, Milk,
Nuts, Beans, potatoes, Carrots, Spices,
Rice, Banana, Apples, Oranges,
 Bee sting allergy usually require multiple
exposure but wasp sting allergy is
unpredictable
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Bee sting allergy usually require multiple
exposure.
3- None-allergic causes: ASA, NSAIDS,
Codein, Morphine, Radiocontast media,
Vancomycin,Ciprofloxacin,Polymyxin,
Anesthetics can cause histamine release.
Urticaria may follow:
EBV,
HBV,
STREPTOCOCAL THROAT infection in child,
Campylobacter
CHRONIC URTICARIA:
 1)Most cases are idiopathic
 2)drugs:mostly attributable to acute type:
 Aspirin can aggravate 20-30% of CH.U
 The relationship with penicilin is complex
and non-confirmed.
 ACEIs can cause angioedema or
aggravate urticaria
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3)reaction to additives in less
than10%(tartrazin)
4)Infection:CH.U is frequently flared by viral
infections.
Incidence of bacterial infections such as
sinusitis, UTI ,and others are variable,
But if present the treatment of the
infection,does not improve urticaria.
H.Pylori, candida and intestinal parasites and
toxocara are suggested but not confirmed.
5)Inhalants:Grass,pollens,mould
spores,animal danders,house dust and
even tobacco smoke are trigger of A or CH
U.
 If pollen allergy is proven desensitization
may be succesfull.
 6)Systemic dis:CVD(SLE and Sjogren),IgM
macroglu.
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Neither hypo nor hyperthyroidism is commonly
associated with CHU,but increased incidence of thyroid
autoAb and disturbance of throid function have been
reported.
 There is no evidence of association with malignancy.
 7)U may worsen premense but if it occures
predominantly ,it has been attributed to progestrone
sensitivity.
 8)Flare up of U do occur at times of psychological
stress.Depression and anxiety were found more
frequently in CHU.
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DIAGNOSIS
1)HX taking(onset,duration,and course)
 Weals lasting more than 24-48hr particularly if
painful or tender suggest the possibility of
U.vasculitis or delayed pressure U.
 Location, number and shapes of wheals are
usually not helpful in most urticarias except for
small uniform short lasting weals of cholinergic
urticaria or linear lesions of dermatographism .
 A family history of atopy ,autoimmunity or
angioedema may be useful.
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Physical factors should be evaluated.
 The presence of angioedema should be
noted especially in pharynx or larynx.
 Enquire about infection, drug, medication,
and food.
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INVESTIGATION
1)Acute U: In patients with life threatening
reactions to an allergen ,confirmation is possible
with RAST (radioallergosorbent test).
 For moderately severe acute reaction, skin prick
test may be helpful but is potentially dangerous
in a background of anaphylaxis .
 2)Chronic U: history ,specially medications like
NSAIDS.
 If weals are painful and persist,with present of
systemic symptoms ,U vasculitis should be
considered.
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Allergy to foods is rare,but a food diary may be
helpful (time may vary from few second to 24
hr).
 Only a CBCdiff ,ESR (SLE,UV,MG), screening test
for thyroid autoAB(%14)may be worthwhile.
 If angioedema is a major component, screening
test for C1 sterase inhibitor deficiency ,should be
performed by C4.It is reduced between attacks
of angioedema.
 If the weals persist for more than 48hr,and not
respond to antihistamines a skin biopsy may be
helpful.
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NATURAL HISTORY
There is no way of predicting the duration
of an attack but the severity is often
greatest at the onset.
 In general spontaneous improvement can
occur in%50 within 6months.But %50 of
those associated with angioedema can still
be expected to have their condition 10 yrs
later.
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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
 Physical Urticarias
– Symptomatic Dermatographism
– Cholinergic
– Cold Induced (Familial or Acquired)
– Vibratory (angioedema)
– Pressure – induced, Solar, Aquagenic
Symptomatic Dermatographism
Symptomatic
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
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 exerciseinduced anaphylaxis from cholinergic urticaria
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Methacholine skin test insensitive (positive result
in only 33% of patients with 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
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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
MANAGEMENT
Explanation and nonspecific measures like
minimizing overheating, stress and alcohol
may be helpful.
 ASA, NSAIDS,and opiates should be
avoided (paracetamol is safe).
 If allergy to food additives is present ,a
modified diet may be helpful.
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MANAGEMENT
First line therapy:
 1)H1 ANTIHISTAMIN:H1 is the main mediator of
urticaria which cause weal, itch and flare.H1
antihist are rapidly absorbed reach to peak
serum level in 2h
 Traditional antihistamine have side effects like
sedation and anticholinergic and paradoxical
excitation in children.
 HYDROXYZINE is the most potent of the classic
antihist.
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DOXEPIN is both TCA and ANTIHIST so can be used in
anxious patients at night but not with MAO INH
Now the low sedative antihist are the treatment of
choice.
They are as effective as hydroxyzine and no tolerance
after continued use
Terfenadin,astemizole and mizolastin is better not be
used because of Q-T prolangation
Loratadin and cetirizin are used with the dosage of 10
mg/d but cetirizin is sedative and should be used at
night
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NOTE THAT ANTIHIST CROSS THE
PLACENTA BUT THERE IS NO EVIDENCE
OF TERATOGENICITY BUT THEY SHOULD
BE AVOIDED IN PREGNANCY ESPECIALLY
IN THE FIRST TRIMEST .IF WE HAVE AN
OBLIGATION THEN CHLORPHENIRAMIN
IS THE LEAST RISKY.
WE CAN USE LOW SEDATIVE ANTIHIST
AT DAY AND HIGH SEDATIVES AT
NIGHT.
 A COMBINATION OF HI AND H2
BLOCKERS ARE MORE EFFECTIVE THAN
H1 ALONE.HERE RANITIDIN IS A BETTER
CHOICE THAN CIMETIDIN
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SECOND LINE THERAPIES:
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1)ORAL CS: in sever urticaria they are effective in higher
doses like 0.5-1mg/kg/d short courses are usefull but
they shouldn’t be used in long term (they are especially
effective in delayed pressure u and u.vasculitis
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In non hereditary anioedema with respiratory distress
the emergency treatment is epinephrin as an inhalor or
IM or SC injection that can be repeated each 10-15 min
2)The choice of other second line therapies
depend on the clinical presentation .these
include leukoterian receptor antagonist that can
be used in ASA sensitivity
 3)mast cell stabilizers such as the Beta agonist
TERBUTALIN and and Ca chanel antagonist
NIFEDIPINE has been combined with H1
blockers in some patients
 4)narrow band phototherapy may help some
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THIRD LINE THERAPY:
In patients with sever ,nonremitting
urticaria ,not responding to conventional
therapy immunomodulatory strategies can
be used.
 Plasmaphoresis improved some patients
for 3-8w only
 IVIG 0.4g/kg/d for 5 day
 Cyclosporin 2.5-3.5mg/kg/d for 1-3m
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Physical and cholinergic u
In physical urticaria a specific physical
stimulus is present
 Cholinergic urticaria occurs in response to
sweating and is usually associated with
physical urticaria
 Wealing usually occurs in minutes at the
site of contact and lasts for 2h
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Delayed pressure urticaria occurs in 30% of
patients with CH.U.
 Wealing occurs at the site of sustained pressure
to the skin after a delay of 30min to 9h(48h)and lasts for 12-72h.
 lesions may be itchy but are often tender .they
often occur under tight clothing ,hands, buttock
,lower back and feet.
 It may have systemic symptoms like arthralgy
,malaise and flu like.
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Delayed P.U respond poorly to antihist.
 Cetirizin in high doses (10mg tds),
NSAIDS, MONTELUKAST, Colchicine
,DAPSON may be effective.
 SYS CS can be used for short courses.
 The prognosis is variable and may
improve spontaneously
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DERMOGRAPHISM(the response that
result from firm stroke of the skin
)responds well to low sedative antihist but
in refractory cases there is no benefit from
the addition of H2 blockers.
 UVB or PUVA may be effective
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In CHOLINERGIC urticaria partial relief may
acheived from antihist but most have to modify
their life style by reducing exercise.
 KETOTIFEN is more effective than usual antihist
and DANAZOL may also be effective.
 After each attack there may be a rafractory
period for 24h
 In COLD urticaria, low sedative antihist,
induction of tolerance by exposure to cold and
warning against cold bathing are useful.
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IN HEREDITARY ANGIOEDEMA RESPONSE
TO ORDINARY TRAETMENTS ARE POOR.
 LONG TERM PROPHYLAXIES IS WITH
DANAZOL OR STANOZOL AND SHORT
TERM WITH EPSILON AMINOKAPROIC
ACID OR TRANERXAMIC ACID.
 A PARTIALLY PURIFIED C1 EST INH MAY
BE USED DURING ATTACKS.
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Photo Images of Hives
Photo Images of Hives
Photo Images of Hives
Photo Images of Hives
Photo Image of Angioedema of Face