1. Introduction:
Urticaria and Angioedema
Urticaria Angioedema

2. Etiology of Urticarial Reactions:
Allergic Triggers
Acute Urticaria
Drugs
Foods
Food additives
Viral infections
–hepatitis A, B, C
–Epstein-Barr virus
Insect bites and stings
Contactants and inhalants
(includes animal dander and latex)
Chronic Urticaria
Physical factors
–cold
–heat
–dermatographic
–pressure
–solar
Idiopathic

3. Chronic Urticaria & Angioedema
Definition: Hives occurring greater than 6 weeks
Hives and angioedema (40%)
Hives alone (40%)
Angioedema alone (20%)
Etiology:
Difficult to determine, cause rarely found
Common in 3rd
and 4th
decade of life
Usually not foods, drugs, pollens, infections, “dyes”
Bad News: May last years….

4. HEURISTIC SUBDIVISIONSca
1. Acute urticaria - less than 6 weeks; history implicates
cause in approx. 50%; difficult to study in clinical trials; good
prognosis.
2. Chronic urticaria - greater than 6 weeks; workup
indicated; easier to study; often persistent.
3. Chronic idiopathic urticaria - subset of chronic urticaria in
which workup fails to pinpoint cause; diagnosis by exclusion; not
homogeneous.

5. • Immune-mediated urticaria
• The type I allergic immunoglobulin (Ig) E response is
initiated by antigen-mediated IgE immune complexes that
bind and cross-link Fc receptors on the surface of mast cells
and basophils, thus causing degranulation with histamine
release.
• The type II allergic response is mediated by cytotoxic T cells,
causing deposits of immunoglobulins, complement, and
fibrin around blood vessels. This leads to urticarial
vasculitis.
• The type III immune-complex disease is associated with
systemic lupus erythematosus and other autoimmune
diseases that cause urticaria.[

6. • Non--immune-mediated urticaria
• Complement-mediated urticaria includes viral and bacterial
infections, serum sickness, and transfusion reactions.
Urticarial transfusion reactions occur when allergenic
substances in the plasma of the donated blood product react
with preexisting IgE antibodies in the recipient. Certain
drugs (opioids, vecuronium, succinylcholine, vancomycin,
and others) as well as radiocontrast agents cause urticaria
due to mast cell degranulation through a non-IgE-mediated
mechanism

10. Physical Urticarias
Reproducible by environmental factors
Physical stimuli
Most frequently in young adults
Episodic and often limited to areas of inciting stimulus
Usually, unresponsive to corticosteroids
Overall, treatment with non-sedating antihistamines

11. Examples of Physical Urticarias
Answer: Dermatographism
1. If you stroke the skin, and a hive occurs?
2. If you place an ice cube on the forearm, and after
removal of ice cube, hive occurs?
Answer: Cold-induced urticaria
3. If hives occur when the patient sweats or
exposure to heat?
Answer: Cholinergic urticaria or localized heat
urticaria

12. Urticarial Vasculitis (Rare)
Inflammatory injury of capillaries and postcapillary
venules in the skin.
Etiology: Manifestation of systemic disease
Clinically:
Hives persisting > 24 hours
± pruritic
Painful, stinging, burning sensation
“Leaves a trace”
–Faint residual hyperpigmentation, indicating red blood
cell extravasation

13. The Pathogenesis of Chronic Urticaria:
Cellular Mediators

14. Histamine as a Mast Cell Mediator

15. Role of Mast Cells in Chronic Urticaria:
Lower Threshold for Histamine Release
Release threshold decreased by:
Cytokines & chemokines
in the cutaneous
microenvironment
Antigen exposure
Histamine-releasing factor
Autoantibody
Psychological factors
Release threshold increased by:
Corticosteroids
Antihistamines
Cromolyn (in vitro)
Cutaneous mast cell

16. An Autoimmune Basis for Chronic
Idiopathic Urticaria: Antibodies to IgE

17. Angioedema (Swelling)
Edema of the deep layers of the dermis and subcutaneous
tissue.
Non-pitting edema
Skin is not hot
Non-dependent areas
It is not: “pre-tibial pitting edema”

18. • The swelling of the affected area of angioedema is a result of
the fast onset of increase of local vascular permeability in
submucosal and subcutaneous tissue. IgE-mediated mast
cell activation and degranulation, key elements of an allergic
reaction, often manifest as urticaria and angioedema. Non–
IgE-mediated mast cell activation/mediator release may
explain certain autoimmune-mediated and idiopathic
angioedema

19. • Patients usually describe swelling of the face (eg, eyelids,
lips), tongue, hands, and feet. It can be acute or chronic, and
each episode of angioedema may last a few hours to a few
days. A local burning sensation and pain can be observed
without pronounced itchiness or local erythema.

20. • Abdominal pain can sometimes be the only presenting
symptom of angioedema. Throat tightness, voice changes,
and trouble breathing may indicate airway involvement.
• For acute and new-onset angioedema, special attention
should be directed to the potential relationship with food or
drug intake, insect stings, or other unusual exposures. For
chronic and recurrent cases, ask the patient about potential
triggers, medication use and associated medical history,
family history, and past evaluation.

21. Allergic angioedema
• Allergic angioedema is often associated with urticaria. It is
typically observed within 30 minutes to 2 hours after
exposure to the allergen (eg, food, drug, venom, latex).

22. Pseudoallergic angioedema
• Pseudoallergic angioedema is not IgE-mediated. However,
its clinical course and presentation is very similar to allergic
angioedema. Typical examples are angioedema induced by
nonsteroidal anti-inflammatory drugs (NSAIDs) and
intravenous contrast material; aspirin (ASA) is the most
common culprit.

23. Nonallergic angioedema
• Nonallergic angioedema does not involve IgE or histamine;
urticaria is generally not associated with this type of
angioedema.
• Hereditary angioedema (HAE) is perhaps the prototype of
this type of angioedema. Decreased functional C1-INH
production leading to unchecked bradykinin production are
believed to be the fundamental changes in HAE types I and
II.[20]
Acquired angioedema (AAE) also has decreased C1-INH
function due to autoantibody production or accelerated
consumption of C1-INH.

24. Idiopathic angioedema
• The causes of idiopathic angioedema are, by definition, not
identifiable. Furthermore, the exact mechanisms are unclear.
[11, 12]
Some may be associated with urticaria. Based on
responses to medication, some cases are thought to be
mediated by mast cell activation, albeit IgE-independent.
• Physical urticaria/angioedema: Common triggers include
heat, cold, emotional stress, and exercise. Nonspecific mast
cell activation and degranulation are suspected causes.

25. Treatment
• Histamine-mediated angioedema
• Histamine-mediated angioedema is either IgE-dependent (eg,
allergic reaction due to food or drug) or IgE-independent (eg,
radiocontrast media). NSAIDs related and most idiopathic
angioedema are treated with same measures.
• Most cases can be managed well with outpatient treatment
alone. Antihistamines as described in the urticaria article are
often used as the first-line treatment for angioedema

26. • For moderate to severe cases, close monitoring is often
necessary. Diphenhydramine (50) mg IM/IV is helpful.
Hydrocortisone (200 mg) or Solu-Medrol (40-60 mg) IV may
reduce the possibility of relapse.
• For laryngeal swelling and airway obstruction, close
monitoring of the airway is mandatory. Epinephrine (1:1,000)
should be administrated IM at 0.01 mg/kg or 0.3 mg repeated
every 10-15 min, if necessary. Occasionally, intubation or
even tracheostomy may be necessary. These patients
should be admitted for at least 24 hours of observation.

27. • Bradykinin-mediated angioedema
• Antihistamines do not work for these patients.
• Cortical steroids have limited or no value.
• Monitor and support airway as in histamine-mediated
angioedema.
• Epinephrine does not work as well as in histamine-mediated
angioedema. Its value for treating acute HAE attacks is
limited.
• Severe abdominal pain may sometimes be the only
presenting symptom for these patients when seeking
emergency medical care.
• Supportive care includes pain control and relief of nausea.

28. • Fresh frozen plasma (2 units) has been shown to be helpful
in certain patients. However, fresh frozen plasma worsening
an acute attack of laryngoedema has also been reported. If
this treatment is used, be ready to intubate or perform a
tracheostomy, if necessary.
• Antifibrinolytics (eg, Amicar or Traxeminic acid) may be
helpful.

29. Initial Workup of Urticaria
Patient history
Sinusitis
Arthritis
Thyroid disease
Cutaneous fungal infections
Urinary tract symptoms
Upper respiratory tract infection
(particularly important in children)
Travel history (parasitic infection)
Sore throat
Epstein-Barr virus, infectious
mononucleosis
Insect stings
Foods
Recent transfusions with
blood products (hepatitis)
Recent initiation of drugs
Physical exam
Skin
Eyes
Ears
Throat
Lymph nodes
Feet
Lungs
Joints
Abdomen

30. Laboratory Assessment for
Chronic Urticaria
Possible tests for selected patients
Stool examination for ova
and parasites
Blood chemistry profile
Antinuclear antibody titer (ANA)
Hepatitis B and C
Skin tests for IgE-mediated
reactions
Initial tests
CBC with differential
Erythrocyte sedimentation rate
Urinalysis
RAST for specific IgE
Complement studies: CH50
Cryoproteins
Thyroid microsomal antibody
Antithyroglobulin
Thyroid stimulating hormone (TSH)

31. Histopathology
Group 2:
Polymorphous perivascular
infiltrate
Neutrophils
Eosinophils
Mononuclear cells
Group 3:
Sparse perivascular lymphocytes

32. Urticaria Associated With
Other Conditions
Collagen vascular disease (eg, systemic lupus erythematosus)
Complement deficiency, viral infections (including hepatitis B
and C), serum sickness, and allergic drug eruptions
Chronic tinea pedis
Pruritic urticarial papules and plaques of pregnancy (PUPPP)
Schnitzler’s syndrome

33. H1-Receptor Antagonists:
Pros and Cons for Urticaria and Angioedema
First-generation antihistamines (diphenhydramine
and hydroxyzine)
Advantages: Rapid onset of action, relatively inexpensive
Disadvantages: Sedating, anticholinergic
Second-generation antihistamines (astemizole,
cetirizine, fexofenadine, loratadine)
Advantages: No sedation (except cetirizine); no adverse
anticholinergic effects; bid and qd dosing
Disadvantages: Prolongation of QT interval; ventricular
tachycardia (astemizole only) in a patient subgroup

34. An Approach to the Treatment of
Chronic Urticaria

35. Treatment of Urticaria:
Pharmacologic Options
Antihistamines, others
First-generation H1
Second-generation H1
Antihistamine/decongestant
combinations
Tricyclic antidepressants
(eg, doxepin)
Combined H1 and H2 agents
Beta-adrenergic agonists
Epinephrine for acute urticaria
(rapid but short-lived response)
Terbutaline
Corticosteroids
Severe acute urticaria
–avoid long-term use
–use alternate-day regimen
when possible
Avoid in chronic urticaria
(lowest dose plus antihistamines
might be necessary)
Miscellaneous
PUVA
Hydroxychloroquine
Thyroxine

36. Atopic Dermatitis: Acute, Subacute,
and Chronic Lesions
Acute Cutaneous Lesions
Erythematous, intensely pruritic papules and vesicles
Confined to areas of predilection
–cheeks in infants
–antecubital
–popliteal
Subacute Cutaneous Lesions
Erythema excoriation, scaling
Bleeding and oozing lesions
Chronic Lesions
Excoriations with crusting
Thickened lichenified lesions
Postinflammatory hyperpigmentation
Nodular prurigo

37. Atopic Dermatitis:
Physical Distribution by Age Group

38. Immune Response in Atopic Dermatitis
Markedly elevated serum IgE levels
Peripheral blood eosinophilia
Highly complex inflammatory responses > IgE-dependent
immediate hypersensitivity
Multifunctional role of IgE (beyond mediation of specific
mast cell or basophil degranulation)
Cell types that express IgE on surface
–monocyte/macrophages
–Langerhans’ cells
–mast cells
–basophils

39. Atopic Dermatitis:
Tests to Identify Specific Triggers
Skin prick testing for specific environmental
and/or food allergens
RAST, ELISA, etc, to identify serum IgE directed to specific
allergens in patients with extensive cutaneous involvement
Tzanck smear for herpes simplex
KOH preparation for dermatophytosis
Gram’s stain for bacterial infections
Culture for antibiotic sensitivity for staphylococcal infection;
supplement with bacterial cultures
Cultures to support tests bacterial, viral, or fungal

40. Topical Corticosteroids
Ranked from high to low potency in 7 classes
–Group 1 (most potent): betamethasone dipropionate 0.05%
–Group 4 (intermediate potency): hydrocortisone valerate 0.2%
–Group 7 (least potent): hydrocortisone hydrochloride 1%
Local side effects:
Development of striae and atrophy of the skin, perioral
dermatitis, rosacea
Systemic effects:
Depend on potency, site of application, occlusiveness,
percentage of body covered, length of use
May cause adrenal suppression in infants and small children
if used long term

41. Antihistamines and Other Treatments
Standard Treatment
Oral antihistamines to relieve itching
Moisturizer to minimize dry skin
Topical corticosteroids
Hard-to-manage Disease
Antibiotics
Coal tar preparations (antipruritic and anti-inflammatory)
Wet dressings and occlusion
Systemic corticosteroids
UV light therapy
Hospitalization