This document provides information on urticaria (hives), including its definition, classification, clinical presentation, pathophysiology, diagnosis and management. Some key points: - Urticaria is defined as a raised, itchy skin lesion consisting of wheals (swellings) and flares caused by localized swelling in the skin. Individual hives can last 30 minutes to 36 hours. - Urticaria is classified as acute (lasting less than 6 weeks) or chronic (daily or almost daily for over 6 weeks). Common types include ordinary, physical, cholinergic, urticarial vasculitis, and angioedema. - Diagnosis is based on history and physical

1. ASHRAF OKBA
PROF. OF INTERNAL MEDICINE
AIN SHAMS UNIVERSITY
CAIRO - EGYPT

2. 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.

3. 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.

4. Photo Images of Hives

5. Angioedemas (quinkes edema) affect deeper
dermal ,subcutaneus and sub mucosal tissues.
They are usually painfull rather than itchy ,poorly
defined and pale or normal in color

6. 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
Larynx virtually never involved

8. 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.

9. CLINICAL CLASSIFICATION OF URTICARIA:
1)ORDINARY URTICARIA (acute or chronic)
2)physical and cholinergic
3)Urticarial vasculitis
4)Contact Urticaria
5)angioedema

10. Up to 50%of patients previously diagnosed as chronic
idopathic urticaria have an autoimune bases.

11. Acute ordinary urticaria may be due to allergy
especially in atopics but not in chronic.

12. 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

13. 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

14. GENETICS
Hereditary C1 Estrase defficiency angioedema
Muckle Well Syn
Familial cold urticaria
Highly significant linkage of HLA DR4 and HLA DQ8
in chronic ordinary urticaria.

15. 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.

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

17. 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.

18. 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

19. 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

20. 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

21. 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

22. ACUTE URTICARIA:
1) Idiopathic:
Most common type: >50% of cases
Sometimes is observed following URTI

23. 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).

24. 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

25. 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

26. 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

27. Bee sting allergy usually require multiple exposure.

28. 3- None-allergic causes: ASA, NSAIDS, Codein,
Morphine, Radiocontast media,
Vancomycin,Ciprofloxacin,Polymyxin, Anesthetics
can cause histamine release.

29. Urticaria may follow:
EBV,
HBV,
STREPTOCOCAL THROAT infection in child,
Campylobacter

30. 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

31. 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.

32. 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.

33. 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.

34. 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.

35. Physical factors should be evaluated.
The presence of angioedema should be noted
especially in pharynx or larynx.
Enquire about infection, drug, medication, and food.

36. 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.

37. 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.

38. 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.

40. Physical Urticarias
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
Physical urticaria

41. 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
Symptomatic Dermatographism

42. Cholinergic Urticaria

43. Cholinergic Urticaria
Goal of raising body temperature (oral) by 0.7o
C
Hot bath to 420
C 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
Methacholine skin test insensitive (positive result
in only 33% of patients with cholinergic urticaria)
Cholinergic urticaria

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

45. 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
Diagnosis of cold-induced urticaria

46. Delayed Pressure Urticaria

47. 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

48. Vibratory angioedema
Lawlor F et al Br J Dermatol 1989; 120: 93-99
Vortex to induce angioedema in a patient
with swelling of hands while driving car

51. 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.

52. 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.

53. 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

54. 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.

55. 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

59. SECOND LINE THERAPIES:
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
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

60. 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

61. 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

62. 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

63. 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(4-8h)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.

64. 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

65. 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

66. 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.

67. 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.

68. Photo Images of Hives

69. Photo Images of Hives

70. Photo Images of Hives

71. Photo Images of Hives

72. Photo Image of Angioedema of Face