Urticaria, also known as hives, is a vascular reaction of the skin characterized by raised red welts (wheals) that are often surrounded by pale halos. Wheals are caused by localized swelling in the skin (edema). Urticaria can be acute (lasting less than 6 weeks) or chronic (lasting more than 6 weeks). Physical urticarias are induced by stimuli like cold, heat, sunlight, pressure, or water. Treatment involves eliminating the cause, if known, and using antihistamines to reduce symptoms. Anaphylaxis is a severe, potentially life-threatening allergic reaction that requires emergency epinephrine treatment. Erythema multiforme is a

1. urticaria
Dr.Fadhil abbas

2. Erythemas
The term erythema means blanchable redness
(hyperemia) of the skin.
A number of reactive skin conditions are referred
to as erythemas.
These include:
A. Toxic erythemas related to viral and bacterial
infections.
B. Erythema muItiforme (EM).
C. Erythema nodosum.
.

3. URTICARIA
DEFINITION
Urticaria is a vascular reaction of the skin
characterized by the appearance of wheals
generally surrounded by a red halo or flare and
associated with severe itching, stinging,
or pricking sensations.
These wheals are caused by localized edema.
Clearing of the central region may occur and
lesions may coalesce, producing an annular or
polycyclic pattern.

4. Subcutaneous swellings (angioedema) may
accompany the wheals.
Angioedema may target the gastrointestinal
and respiratory tracts, resulting in abdominal
pain, coryza, asthma, and respiratory
problems.
Respiratory tract involvement can produce
airway obstruction.
Anaphylaxis and hypotension may also occur.

5. -The evolution of urticaria is a dynamic
process.
-New lesions evolve as old ones resolve.
-Hives result from localized capillary
vasodilation, followed by transudation of
protein-rich fluid into the surrounding
tissue; they resolve when the fluid is slowly
reabsorbed.
-The edema in urticaria is found in the
superficial dermis.

6. Lesions of angioedema are less well
demarcated.
The edema in angioedema is found in
the deep dermis or
subcutaneous/submucosal locations.

7. Acute urticaria evolves over days to weeks,
producing evanescent wheals that individually rarely
last more than 12 h, with complete resolution of the
urticaria within 6 weeks of onset.
Daily episodes of urticaria and/ or angioedema
lasting more than 6 weeks are designated chronic
urticaria.

8. CLINICAL PRESENTATION.
The sudden appearance of pink itchy
wheals, which can come up anywhere
on the skin surface .
Lesions vary in size from the 2- to 4-mm
edematous papules to giant hives, a single
lesion of which may cover an extremity.
They may be round or oval; when confluent,
they become polycyclic.
A portion of the border either may not form or
may be reabsorbed, giving the appearance of
incomplete rings

10. The most characteristic presentation is uniformly red
edematous plaques surrounded by a faint white halo.
.

11. Urticarial plaques in different stages of formation.

12. Polycyclic pattern

13. Superficial hives vary in color

14. Hives have become
more extensive and
confluent

15. Angioedema is
a deeper, larger
hive
It is caused by
transudation
of fluid into the
dermis and
subcutaneous
tissue.
The lip
is a common site.

16. PATHOPHYSIOLOGY
Histamine is 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.
A variety of immunologic, nonimmunologic,
physical, and chemical stimuli may be
responsible for the degranulation of mast cell
granules and the release of histamine into the
surrounding tissue and circulation.

18. Histamine causes endothelial cell contraction,
which allows vascular fluid to leak between the
cells through the vessel wall, contributing to
tissue edema and wheal formation.

19. When injected into skin, histamine produces
the “triple response” of Lewis, the features of
which are
1.local erythema (vasodilation),
2.the flare(axon reflex) with pruritus
characterized by erythema beyond border of the
local erythema,
and a 3.wheal produced from leakage of fluid
from the postcapillary venule.

20. Blood vessels contain two (and possibly
more) receptors for histamine.
H 1 receptors, when stimulated by histamine,
cause an axon reflex, vasodilation, and pruritus.
Acting through H 1 receptors,
histamine causes Smooth muscle contraction
in the respiratory and gastrointestinal tracts
and pruritus and sneezing by sensory nerve
stimulation.

21. H 1 receptors are blocked by antihistamines
called H 1 antagonists (e.g., chlorpheniramine),
which occupy the receptor site and prevent
attachment of histamine.
H 2 RECEPTORS:
When H 2 receptors are stimulated,
vasodilation occurs.
H 2 receptors are also present on the mast
cell membrane surface.

22. Activation of H 2 receptors alone increases
gastric acid secretion.
Cimetidine (Tagamet), ranitidine (Zantac), and
famotidine (Pepcid) are H 2 blocking agents
(antihistamines).
Activation of both H 1and H 2receptors
causes hypotension, tachycardia, flushing, and
headache.

23. ETIOLOGY OF ACUTE URTICARIA
Acute urticaria is IgE-mediated, complement-
mediated, or nonimmune-mediated.
1.IgE-MEDIATED REACTIONS:
Type I hypersensitivity reactions are probably
responsible for most cases of acute urticaria.
Circulating antigens such as foods, drugs, or
inhalants interact with cell membrane–bound IgE
to release histamine.
Food allergies are the most common cause of
anaphylaxis.

26. 2.IMMUNE-COMPLEX MEDIATED,
ACUTE URTICARIA:
Complement-mediated acute urticaria can be
precipitated by administration of whole
blood, plasma, immunoglobulins, and drugs or
by insect stings.
Type III hypersensitivity reactions (Arthus
reactions) occur with deposition of insoluble
immune complexes in vessel walls.
The complexes are composed of IgG or IgM
with an antigen such as a drug.

27. Urticaria occurs when the trapped
complexes activate complement to produce
anaphylotoxins C5a and C3a which are potent
releasers of histamine from mast cells.
Serum sickness (fevers , urticaria,
lymphadenopathy, arthralgia , and myalgia),
and systemic lupus erythematosus are
diseases in which hives may occur as a result of
immune complex deposition.

28. 3.NONIMMUNOLOGIC RELEASE OF
HISTAMINE:
Pharmacologic mediators, such as
acetylcholine, opiates, polymyxin B, and
strawberries, react directly with cell
membrane–bound mediators to release
histamine.
Aspirin/NSAIDs cause a nonimmunologic
release of histamine.
The physical urticarias may be induced by
both direct stimulation of cell membrane
receptors and immunologic mechanisms.

29. The main types of urticaria.
1.Ordinary urticaria
A. Acute ( up to 6 wks of continuous activity)
B. Chronic (more than 6 wks of continuous activity)
- Autoimmune chronic ordinary urticaria
-Idiopathic chronic ordinary urticaria
C. Episodic ( acute intermittent or recurrent activity)
2.Physical
cold ,solar ,heat ,cholinergic
dermographism (immediate pressure urticaria)
delayed pressure
3.Hypersensitivity 4.Autoimmune
5.Pharmacological 6.Contact

30. Classification
PHYSICAL URTICARIAS
Physical urticarias are induced by physical
and external stimuli, and they typically affect
young adults.

31. Cold urticaria
Patients develop wheals in areas exposed to
cold (e.g. on the face when cycling in a cold
wind).
TREATMENT.
a. Patients must learn to protect themselves from a
sudden decrease in temperature.
b. Cyproheptadine , loratadine, cetirizine, and other
antihistamines may be effective.

32. Cold urticaria.
The hive
occurred
within
minutes
of holding an
ice cube
against the
skin.

33. Solar urticaria
Hives that occur in sun-exposed areas
minutes after exposure to the sun and
disappear in less than 1 hour are called
solar urticaria.
This photoallergic disorder is caused by
both sunlight and artificial light.
Systemic reactions that include syncope can
occur.

34. Heat urticaria
Within 5 min of the skin being exposed to heat
above 43°C, the exposed area begins to burn and
sting, and becomes red, swollen, and indurated.
This rare type of urticaria may also be generalized
and is accompanied by cramps, weakness, flushing,
salivation, and collapse.

35. Cholinergic urticaria
Cholinergic urticaria, produced by the action of
acetylcholine liberated from sympathetic nerves on
the mast cell, is characterized by minute, highly
pruritic, punctate wheals or papules 1-3 mm in
diameter and surrounded by a distinct erythematous
flare.
These lesions occur primarily on the trunk and
face.
The condition spares the palms and soles.
Lesions persist for 30-90 min and are followed by a
refractory period of up to 24 h.
Bronchospasm may occur.

36. The lesions may be induced in the susceptible
patient by exercise, emotional stress, increased
environmental temperature.
Treatment with antihistamines is often effective .
Antihistamines have been combined with other
agents, such as montelukast and propranolol.
Attenuated androgens, such as danazol, may be of
benefit in refractory cases.

37. Round, red, papular wheals that occur in response
to exercise, heat, or emotional stress.

38. Aquagenic urticaria
This resembles cholinergic urticaria and is
precipitated by contact with water, irrespective of
its temperature.
Dermographism (immediate pressure urticaria)
This is the most common type of physical
urticaria ,the skin mast cells releasing extra
histamine after rubbing or scratching.
The linear wheals are therefore an exaggerated
triple response of Lewis.

39. They can readily be reproduced by rubbing the
skin of the back lightly at different pressures, or
by scratching the back with a fingernail or blunt
object.

40. Hives are created
by rubbing and linear lesions are
produced by scratching

41. Delayed pressure urticaria
Pressure urticaria is characterized by the
development of swelling with pain that occurs 3-12h
after sustained local pressure has been applied.
It occurs most frequently on the feet after
walking and on the buttocks after sitting.
It is unique in that there may be a latent period of as
much as 24 h before lesions develop.
Kinins or prostaglandins rather than histamine
probably mediate.
Arthralgias, fever, chills, and leukocytosis can occur.
The pain and swelling last for 8-24 h.

42. Hives form
under the
edge of the
bra and
waistband.

43. Course
The course of an urticarial reaction depends on
its cause.
If the urticaria is allergic, it will continue until
the allergen is removed, tolerated or metabolized.
Most such patients clear up within a day or two,
even if the allergen is not identified.
Urticaria may recur if the allergen is met again.
.

44. Complications
Urticaria is normally uncomplicated, although
its itch may be enough to interfere with sleep or
daily activities and to lead to depression.
In acute anaphylactic
reactions, oedema of the larynx may lead to
asphyxiation, and oedema of the tracheo-
bronchial tree to asthma.

45. Some endogenous causes of urticaria.
1.Infection
-Viral (e.g. hepatitis, infectious mononucleosis, HIV
infection)
-Bacterial
-Mycoplasma
-Intestinal parasites
2.Connective tissue disorders
3.Hyperthyroidism
4.Cancer
-Lymphomas
5.Emotional stress
Persons under severe emotional stress may have more
marked urticaria, no matter what the primary cause is.

46. Some exogenous causes of urticaria.
1.Drugs, Penicillin, sulfonamide and related
antibiotics are the most frequent offenders. Aspirin.
(both topical and systemic)
2.Preservatives in lotions.
3.Foods and food additives :
The most allergenic foods are chocolate, shellfish,
nuts, peanuts, tomatoes, strawberries, melons, pork,
cheese, garlic, onions, eggs, milk, and spices.
4.Bites. 5.Inhalants. 6.Pollens.
7.Insect venoms. 8.Animal dander.
9. Alcohol.

47. Treatment
The ideal is to find a cause and then to
eliminate it.
In addition, aspirin – in any form – should be
banned.

48. In general, antihistamines are the mainstays
of symptomatic treatment.
1. New generations : Cetirizine 10 mg/ day
and loratadine10mg/day, both with half-lives of
around 12 h, are useful.
If necessary, these can be supplemented with
shorter acting antihistamines
(e.g. hydroxyzine 10–25 mg up to every 6 h;,
or acrivastine 8 mg three times daily).

49. Alternatively, they can be combined with a
longer acting antihistamine old generations
(e.g. chlorphenamine [chlorpheniramine]
maleate 12 mg sustained-release tablets
every 12 h)
so that peaks and troughs are blunted, and
histamine activity is blocked throughout the
night.

50. If the eruption is not controlled, the dose of
hydroxyzine can often be increased and still
tolerated.
H2-blocking antihistamines (e.g. cimetidine)
may add a slight benefit if used in conjunction
with an H1 histamine antagonist.

51. Chlorphenamine or diphenhydramine
are often used during pregnancy because of
their long record of safety, but cetirizine,
loratadine and mizolastine should be avoided
2. Sympathomimetic agents can help urticaria,
although the effects of adrenaline (epinephrine)
are short lived.
Pseudoephedrine (30 or 60 mg every 4 h) or
terbutaline (2.5 mg every 8 h) can sometimes
be useful adjuncts.

52. 3.A tapering course of systemic corticosteroids
may be used, but only when the cause is known
and there are no contraindications, and certainly
not as a panacea to control chronic urticaria or
urticaria of unknown cause.
4.Low doses of ciclosporin may be used for
particularly severe cases

53. Anaphylaxis reaction
Anaphylaxis is an acute and often life-threatening
immunologic reaction, frequently heralded by
scalp pruritus,
diffuse erythema,
urticaria, or angioedema.
Bronchospasm,
laryngeal edema,
hyperperistalsis,
hypotension, and
cardiac arrhythmia may occur.

54. Antibiotics, especially penicillins, other drugs, and
radiographic contrast agents are the most common
causes of serious anaphylactic reactions.
Hymenoptera stings are the next most frequent
cause, followed by ingestion of crustaceans
and other food allergens.

55. Causative agents can be identified in up to two-
thirds of cases and recurrent attacks are the rule.
Exercise-induced anaphylaxis is often
dependent on priming by prior ingestion of a specific
food, or food in general, and aspirin may be an
additional exacerbating factor.

56. Treatment
1-For severe reactions, including anaphylaxis,
respiratory and cardiovascular support is essential.
2-A 0.3 mL dose of a 1 :1000 dilution of epinephrine
is administered every 10-20 min as needed.
3-In young children, a half-strength dilution is used.

57. 4-In rapidly progressive cases, intubation or
tracheotomy may be required.
5-Adjunctive therapy includes intramuscular
antihistamines (25-50 mg hydroxyzine or
diphenhydramine every 6 h as needed)
6-and systemic corticosteroids(250mg hydrocortisone
or 50 mg methylprednisolone intravenously every 6 h
for 2-4 doses).

58. Erythema multiforme
It is a skin condition of unknown cause,
possibly mediated by deposition of immune
complex (mostly IgM) in the superficial
microvasculature of the skin and oral mucous
membrane that usually follows an infection with
herpes simplex or drug exposure.

59. Erythema
multiforme:
bullous and
target lesions
occurring in a
favorite site

62. Some causes of erythema multiforme.
-1.Viral infections, especially:
herpes simplex, hepatitis A, B and C ,orf
-2.mycoplasma
-3.Bacterial infections
-4.Fungal infections
coccidioidomycosis
-5.Parasitic infestations
-6.Drugs
-7.Pregnancy
-8.Malignancy, or its treatment with radiotherapy
-9.Idiopathic

63. Presentation
EM minor is a self-limited, recurrent disease,
usually of young adults, occurring seasonally in the
spring and fall, with each episode lasting 1-4 weeks.
-The symptoms of an upper respiratory tract
infection may precede the eruption.
-

64. Typically, annular non-scaling papules and
plaques appear on the palms, soles, forearms and
legs.
-This lesion is the classic “target” or “iris”
lesion with three zones:
1.central dusky purpura;
2.an elevated, edematous, pale ring; and
3.surrounding macular erythema
-Lesions generally appear symmetrically and
acrally .
-Some lesions blister.

65. -The Stevens–Johnson syndrome is a severe
variant of erythema multiforme associated with
fever and mucous membrane lesions.
The oral mucosa, lips and bulbar conjunctivae
are most commonly affected, but the nares, penis,
vagina, pharynx, larynx and tracheobronchial tree
may also be involved.
This merges with toxic epidermal necrolysis
where the whole skin is affected more than 30%
of the body surface area.

68. Stevens–Johnson type of erythema multiforme.
The eyelids were also severely involved.

69. Course
-Crops of new lesions appear for 1–2 weeks,
or until the responsible drug or other factor has
been eliminated.
-Individual lesions last several days.
-The site of resolved lesions is marked
transiently by grey or brown patches,
particularly in pigmented individuals.

70. Treatment:
- The best treatment for erythema multiforme is
to identify and remove its cause.
-In mild cases, only symptomatic treatment is
needed and this includes the use of
antihistamines.

71. -Herpes simplex infections should be
suspected in recurrent or continuous erythema
multiforme of otherwise unknown cause.
-Treatment with oral valaciclovir 500 mg once
or twice daily or famciclovir 250 mg once or
twice daily or acyclovir 10/kg/day may prevent
attacks, both of herpes simplex for at least 6
months.
and of the recurrent erythema multiforme that
follows it.

72. In extensive cases of EM minor, systemic
corticosteroids have been used, but because these
theoretically may reactivate HSV, steroids are best
given concurrently with an antiviral drug.

73. Erythema nodosum
-Erythema nodosum is an inflammation of the
subcutaneous fat (a panniculitis).
It is type 4 hypersensitivity reaction an
immunological reaction, elicited by
various bacterial,
-viral and fungal infections,
-malignant disorders,
-drugs
-and by a variety of other causes

74. Erythema
nodosum:
large painful
dusky
plaques on the
shins.

75. Some causes of erythema nodosum.
1.Infections
Bacteria (e.g. streptococci, tuberculosis, brucellosis,
leprosy, yersinia)
Viruses
Mycoplasma
Rickettsia
Chlamydia
Fungi (especially coccidioidomycosis)
2.Drugs (e.g. sulphonamides , penicillin , oral
contraceptive agents)
3.Systemic disease (e.g. sarcoidosis, ulcerative
colitis, Crohn’s disease, Behçet’s disease)
4.Pregnancy

76. Presentation
In most cases occurring in young adult women.
The eruption consists of bilateral, symmetrical,
deep, tender, bruise-like nodules, 1-10 cm in
diameter, located pretibially.
Initially, the skin over the nodules is red, smooth,
slightly elevated, and shiny.
The onset is generally acute, and frequently
associated with fever , malaise, leg edema, and
arthritis or arthralgia.

79. Over a few days, the lesions flatten, leaving a purple
or blue-green color resembling a resolving bruise.
The natural history is for the nodules to last
a few days or weeks, appearing in crops, and then to
involute slowly.
EN is a reactive process.
Lesions usually resolve in 6–8 weeks.

80. Investigations
-Erythema nodosum demands a careful
-history,
-physical examination,
-a chest X-ray,
-throat culture for Streptococcus,
-a Mantoux test
-and an antistreptolysin-O (ASO) titre.
- Serological testing for deep fungal infections.

81. Treatment
1 -The ideal treatment for erythema nodosum
is to identify and eliminate its cause if possible.
-For example, if culture or an ASO test
confirms a streptococcal infection, a suitable
antibiotic should be recommended.
2 -Bed rest and leg elevation are also
an important part of treatment.
3 -NSAIDs such as aspirin, indomethacin or
ibuprofen may be helpful.

82. 4. Systemic corticosteroids will result in rapid
resolution of lesions, if not contraindicated by
the underlying precipitating cause.
5. In acute lesions, colchicine is often rapidly
effective at a dose of 0.6 mg twice daily.