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Urticaria
Lecturer Dr. Kholod Abbas

Objectives
1Define urticaria & other related Conditions.
2 Classify urticaria and describe its pathogenesis.
3 Identify the etiological (provoking) factors of urticaria.
4Describe clinical features, Investigations, differential diagnoses &
management of urticaria and anaphylaxis.
5 Define angioedema & describe its clinical variants, clinical
features& management. 1
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Urticaria (Hives)

Wheal(lesion): pruritic evanescent pink or pale swelling

of superficial dermis surrounded by erythema (flare)

Angioedema(lesion): swelling of deep dermis and

subcutaneous or submucosal tissue

Urticaria (disease):
transient, recurrent, circumscribed,wheal or/and
angioedema of skin that changes in size and shape by
peripheral extension or regression during the few hours
(1-24 h)

Urticaria “hives”
• Vascular reaction of the skin characherized by
wheals surrounded by erythema
• Chardinal symptom is PRURITUS
• is an extremely common disease
• Male > female
• Affects 20% of population
• Occurs across the age spectrum 2
• More than 2/3 of cases are self-limiting
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Pathophysiology
 Immunologic Urticaria: antigen binds to IgE on the
mast cell surface causing degranulation, which results
in release of histamine
• Histamine binds to H1 and H2 receptors to cause
causes localized capillary vasodilatation and increased
capillary permeability leading to tissue edema and
wheal formation
 Non-Immunologic Urticaria: not dependent on the
binding of IgE receptors
• For example, aspirin may induce histamine release
through a pharmacologic mechanism where its effect on
arachidonic acid metabolism causes a release of
histamine from mast cells. • Physical stimuli may induce
histamine release through direct mast cell
degranulation.

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Etiological (Provoking) factors:

1. Drugs: most frequent causes especially penicillin, NSAID
2. Food:
Especially in acute cases like chocolates, nuts, tomatoes,cheese,fish, spices
….etc.
3. Food additives:
A. The natural types especially salicylates, yeasts……..…etc.
B. The synthetic types like azodyes, benzoic acid derivatives,
tetrazines …..etc.
4. Infections and infestations:
• Like localized infection in the tonsils, teeth, sinuses, gall bladder, UTI
• upper respiratory tract infection
• GI infection,
• hepatitis B, hepatitis C,
• fungal infection,
• helminthic infestations and other parasitic infection, Insect bites …..etc.

5. Emotional (stress).
6. Malignancies: (Hodgkin’s lymphoma, CLL .….etc.)
7. Inhalants:
Like grass pollens, house dust mites, feathers, tobacco
smoking …..etc.
8. Systemic diseases: collagen vascular diseases (as SLE),
thyroid diseases ..…etc.
9. Menstruation and pregnancy.
10. Implants: Like metal pin in the bone, metal dental prosthesis,
dental 4
amalgam …..etc.
11. Alcohol
12. Physical factors ( cold,heat,light, pressure)
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Classification
I. Classification based on clinical factors:

1. Ordinary urticaria
A. Acute (< 6 weeks) B. Chronic (>6 weeks) .
more likely to have an identifiable • less likely to have an identifiable
trigger trigger

2. Immune complex urticaria:

A. Serum sickness.
B. Urticarial vasculitis. (defined by vasculitis as shown by skin biopsy specimen)

3. Physical urticaria: (defined by the triggering stimulus):

 Cholinergic urticaria  Exercise-induced anaphylaxis
 Cold urticaria  Localized heat urticarial
 Heat urticaria  Solar urticarial
 Delayed pressure urticaria
 Dermographism

3. Contact urticaria (induced by biologic or chemical skin contact)

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4. Angioedema (without wheals)
5. Syndromes resemble urticaria or angioedema
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II. Classification based on pathogenesis:

1. Immunological:
A. IgE dependant.
B. Type I hypersensitivity.
C.Complement mediated forms. Administration of whole blood, plasma,
immunoglobulins, and drugs (pencillin)or by insect stings.

2. Non immunological:
Includes direct and indirect mast cells degranulation.e.g. opiates, NSAIDS

3. Idiopathic:
In more than 50% of cases.

ACUTE URTICARIA
(Urticaria for less than 6 weeks)
1. IgE-MEDIATED REACTIONS
• Circulating antigens such as foods, drugs, insect stings, natural
rubber latex or inhalants interact with cell membrane–bound IgE
to release histamine.
2. COMPLEMENT-MEDIATED, OR IMMUNE-COMPLEX-
MEDIATED.
Administration of whole blood, plasma, immunoglobulins, and
drugs or by insect stings,vasculitis,. 6

3. NONIMMUNOLOGIC RELEASE OF HISTAMINE

Acetylcholine, opiates, polymyxin B, and strawberries,
aspirin/NSAIDs.
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CHRONIC URTICARIA
• (lasting for 6 weeks or more )
• The etiology is often unclear. results from the
cutaneous mast cell release of histamine.
• The morphology is similar to that of acute urticaria
but lesions are slightly deeper.
• more common in middle-aged women and is
infrequent in children.
• Individual lesions remain for less than 24 hours but
the disease continues for weeks, months, or years

CHRONIC URTICARIA
• Angioedema occurs in 50% of cases
and rarely affects the larynx.
• Aspirin/NSAIDs, penicillin, ACEIs,
opiates, alcohol, fever, and stress
exacerbate CU.
• About 70% of patients with CU have
physical urticaria.
• There is a significant association 7
between chronic urticaria and
autoimmune thyroid disease.

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Physical urticaria
• Characterized by the • Wheals typically fade within
development of wheals and 30-60 minutes. The exception is
itching promptly after delayed pressure urticaria
exposure to appropriate when the wheals take several
physical stimulus hours to appear after sustained
pressure and can last up to 48
hours.

Classification of physical urticaria

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1. Pressure urticaria

• Large painful or itchy red swelling

at sites of pressure (soles, palms, or
waist).
• application of susteaied pressure
perpendicular to skin produces red
swelling after a latent period of 1 to 4
hours.

• The swelling may last up to 48 h and

bradykinins or prostaglandins, rather
than histamine, probably mediate it.

2.Heat urticaria

• A rare form of urticaria.

• Induced by direct contact of the
skin with warm objects or warm
air.
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• The eliciting temperature ranges
from 38º C to more than 50 º C .
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Cold urticaria

• Itchy pale or red swelling at sites of • some can also occur as a result of
contact with cold surfaces or fluids- ten infections, neoplasia or autoimmune
minutes application of an ice pack diseases.
causes a wheal within five minutes of
the removal of ice. • Infectious: syphilis, measles
hepatitis ,mononucleosis, HIV

• More frequent in women than men.

• Majority is idiopathic

Dermographism

• This is the most common type of physical

urticaria, the skin mast cells releasing
extrahistamine after rubbing or scratching.
• Affect mainly young adults
• Itchy, linear wheals with surrounding
bright-red flare at sites of scratching or
rubbing

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CHOLINERGIC URTICARIA

• develops after an increase in core body

temperature,
• such as during a warm bath, prolonged
exercise, or episodes of fever.
• The highest prevalence is observed in
individuals aged 23–28 years.
• The eruption appears as multiple distinctive,
pruritic, monomorphic small, 1- to 2-mm
wheals that are surrounded by large areas of
erythema

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SYNDROMYES THAT CAN BE ASSOCIATED WITH urticaria

1-Muckle-Wells syndrome
• Familial –dominantly inherited.
• progressive nerve deafness

• Urticaria

• arthritis

• Limb pain
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• Recurrent fever
• Hypergammaglobulinemia
• amyloidosis
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2Schnitzler syndrome (SS), first reported in 1972, is characterized by

chronic, nonpruritic urticaria in association with recurrent fever, bone
pain, arthralgia or arthritis, and a monoclonal immunoglobulin M (IgM)
gammopathy in a concentration that is usually less than 10 g/dL

3Gleich's syndrome - the episodic angioedema with eosinophilia

syndrome

Clinical features:

• Urticaria presents clinically with wheals occur anywhere on the body including the scalp, the
palms and the soles, it usually presents in variable numbers, sizes and patterns.
• The wheals usually last for few hours and resolve within 24 hours and are generally very itchy
especially the superficial ones.

• In about one half of the cases, an associated angioedema presents as pale or pink swelling most
frequently on the face affecting the eyelids and the lips but other areas also as the ears, the neck,
the hands, the feet and the genitalia may be affected as well as the mucous membranes of the
mouth, the tongue and the larynx.

• Urticaria may be preceded by or associated with other systemic symptoms like vomiting,
abdominal pain, headache, arthralgia .…etc and in it’s sever form with anaphylaxis. The
diagnosis of the disease depends usually on full history and on the clinical picture.
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• warning signs:
lesions lasting >24 hours, appear ecchymotic, purpuric, or are painful and/or
occur in association with lymphadenopathy, fever, weight loss, joint or muscle
pain
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Evaluation and Management

• Detailed history . Physical Exam
• Investigations:
• 1. Acute cases usually need no investigations.
• 2. Chronic cases usually need investigations to exclude certain disease ,as chronic infection especially sinus
infection, UTI, connective tissue diseases, intestinal warms, internal malignancy, lymphoma, autoimmune
thyroiditis, chronic exposure to external allergen
• Laboratory testing
• CBC
• UA
• ESR
• LFTs,
• ANA, Complement study,
• TSH, Antithyroglobulin,
• Allergy testing if specific trigger can be implicated (would possibly include skin prick
testing or immunocap testing for IgE to specific food or drug, radioallergosorbent assay test
(specific Ig-E)

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Delayed pressure
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Skin Prick Test (SPT)

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• DDX:
• 1. Erythema multiforme.
• 2. Pre bullous eruption of bullous pemphigoid, Dermatitis
herpetiformis..
• 3. Skin lymphoma.
• 4. Acute contact dermatitis.
• 5. Dermatomyositis.
• The last two conditions simulate angioedema.

• Treatment:
• *Avoidance of the triggering causes (if known) is important.
• *Antihistamines are the main stay of treatment.

Treatments include:
1. Antihistamines:
• A. H1 blockers which include:
I. First generation (sedative) antihistamines. diphenhydramine ,hydroxyzine, cetirizine
II. Second generation (non sedative) antihistamines. (loratadine, desloratdin, Fexofenadine)
• B. H2 blockers :
Not used alone in urticaria like cimitedine, ranitidine, famotidin.
• *For acute cases, use H1 blockers.
• *For chronic cases, use H1 blockers and H2 blockers.
2. Drugs with antihistamine effect may be helpful as doxepin.
3. Systemic corticosteroids:
Are used for refractory and sever cases and for short term treatment in acute 16
conditions but it should be avoided in treating chronic urticaria.
4. Mast cells stabilizers (Leukotriene antagonist) :
Are used in combination with histamine blockers. Zafirlnkast, Montelukast
5. Resistant chronic urticaria – Cyclosporin, Methotrexate, Omalizumab
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Treatment of chronic spontaneous urticaria

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Anaphylaxis:
• A serious allergic reaction, rapid in onset and may lead to death.
• Is a life threatening condition induced by an IgE mediated allergic reaction, it
consists of combination of symptoms and signs including diffuse erythema,
pruritis, urticaria, angioedema, hypotension, cardiac arrhythmia,
bronchospasm and laryngeal edema. nasua,vomittig, abd. pain
Treatment of anaphylaxis
• Anaphylaxis is an emergency condition.
• ABCs first
• Treatment (especially for disease with respiratory problems) includes:
• 1. Epinephrine s.c or i.m.( 0.3-0,5mg)
• 2. Oxygen therapy.
• 3. Intravenous fluid.
• 5. Antihistamines i.m.
• 6. Systemic steroids.
• 7. Aminophylline.

Angioedema
• Transient, rapid, swelling in the deeper dermal, subcutaneous and submucosal
tissues, occurs often together with urticaria
• Similar process to urticaria, resolve within 24-48 h
• The swelling typically seen in areas with little connective tissue such as lips, face,
mouth, uvula and genitalia
• The overlying skin is unaltered, edematous or rarely ecchymotic.
•there may be diffuse swelling on the hands, forearms, feet ankles
• Can occur in bowel wall which manifests as colicky abdominal pain
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* There are two distinct subsets of angioedema, the 1st is considered a deep form of
urticaria & may be observed as solitary or multiple sites of angioedema alone or in
combination of urticarial (idiopathic, drugs reaction)
The 2nd type associated with C1 esterase inhibitor deficiency is not associated with
hives & there is no pruritus.
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Angioedema

With weals Without weals

• Acute allergic angioedema • Non allergic drug reaction -

Ass. All kinds of urticaria NSAIDs ,ACEI s (kini
except dermographism0 production and nitic oxide
• Idiopathic chronic generation)
angioedema
• C1 eterase deficiency

Angioedema without wheals

C1 estrase inhibitor deiciency( C4)

Hereditary angioedema Acquired angioedema

(Autosomal dominant)
Type 1 : low level of C1 estrase inhibitor Type 1: lymphoproliferative disease
Type 2: normal level of dysfunctional C1 INH protein Type 2: autoAb to C1 estrase inhibitor e.g. SLE
Type III: coagulation factor XII gene mutation
C4 : decreased C4: decreased
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C1q: normal C1q: decreased

Provocative factors: surgery, stress, trauma Provocative factors: surgey, trauma and stress
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Hereditary Angioedema:
• autosomal-dominant. (1;50 000-1:150 000)
• Mutation in chromosome 11
• appears in chidhood or 2nd-4th decade.
• sudden attacks as frequently as every 2 weeks, lasting 2-5 days.
• swelling is typically asymmetrical, & urticaria or itching does not occur
• Decreased C1 inhibitor activity leads to excessive kallikrein, which in turn produces
bradykinin, which we know is a potent vasodilator
• patients may experience local swelling in subcutaneous tissues (face, hands, arms, legs,
genitals & buttocks), abdominal organs (stomach, intestines, bladder) mimicking surgical
emergencies,with nausea, vomiting and abdominal colic &the upper air way (larynx) that can
be life threatening.

Acquired Angioedema:
• patients indistinguishable from hereditary Angioedema but:
• the onset after the 4th decade of life & lacking family history.
• there is no associated pruritus or urticaria.
• associated with lymphomas (B cell), chronic lymphcytic leukemias,
myloma, myelofibrosis.
• there is acquired C1 Esterase inhibitor deficiency.
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TREATMENT OF HEREDITARY ANGIOEDEMA

• Patient education very important; test family

• No regular medication needed in many cases
• Prophylactic stanozolol or danozol
• Fresh frozen plasma before emergency surgery
• C1 inhibitor
• Symptomatic treatment during attacks
• Steroids and antihistamines are NOT effective
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Prophylactic and maintenance therapy

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Management of acute angioedema

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Quick Review
Diagnostic approach for urticaria

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