1. Urticaria and skin allergy tests
Dr. Mohammad Alghamdi
Dermatology and Plastic surgery module
2. Goals and Objectives
The purpose of this lecture is to help medical students develop a clinical approach to the initial
evaluation and treatment of patients with urticaria.
After completing this lecture, the medical student will be able to:
Describe the morphology of urticaria and angioedema
Identify the Pathophysiology of urticaria
Distinguish between acute and chronic urticaria
Distinguish between 1st and 2nd generation H1 antihistamines with regard to
sedation.
Recognize the signs and symptoms of anaphylaxis.
Describe Prick and Patch Tests, methods and uses.
3. Introduction
• Urticaria is a descriptive term for recurrent whealing of the skin
• Urticaria is characterized by transient skin or mucosal swellings due to
plasma leakage.
• Superficial dermal swellings are wheals
• Deep swellings of the skin or mucosa are angioedema
• Anaphylaxis is a serious allergic reaction that is rapid in onset and
may cause death
• Prevalence 8-22%
• Any age
• Female>Male (overall)
• Acute & chronic
4. Wheals
• Pruritic
• Pink or pale swellings of the superficial
dermis
• Initial erythematous flare around them
• Hallmark : individual lesions come and go
rapidly, by definition, in general within 24
hours.
5. Angioedema
• Swellings occur deeper in the dermis and in the
subcutaneous or submucosal tissue.
• May also affect the oropharynx and rarely
the bowel in hereditary angioedema
• Area of involvement tend to be normal or faint
pink in color, rather than red
• Painful rather than pruritic
• Larger and less well defined than wheals
• Often last for 2 to 3 days
6. Pathophysiology
Mast cell dependent Mast cell independent
The mast cell is the major effector cell in urticaria
Immunological Nonimmunological Immunological Nonimmunological
7. Mast cell dependent
Degranulation of mast cells to release its mediators
A. Immunological:
1. Cross-linking of mast cell bound specific immunoglobulin E (IgE) by
exogenous allergens (mostly in acute spontaneous urticaria)
2. Functional IgG autoantibodies against IgE or the high-affinity IgE
receptor
B. Non-Immunological:
1. Direct mast cell releasing agents (eg. C5a, codeine)
2. Dietary food additives and natural salicylates as well as nonsteroidal
anti-inflammatory drugs (NSAIDS) may cause urticaria via the diversion
of arachidonic acid metabolism from prostaglandin to leukotriene
formation
8. Mast cell independent
1. C1 esterase inhibitor (C1 inh) deficiency (hereditary or acquired) will
lead to increased bradykinins
2. Activating mutation in gene that encodes FXII, leading to increased
formation of bradykinin. (Type III HAE)
3. Angiotensin-converting enzyme (ACE) inhibitor-induced urticaria is
believed to result from the inhibition of endogenous kininase II (also
known as ACE), which leads to increased production of bradykinin via
inhibition of its metabolism
4. Immune complex deposition in urticarial vasculitis
5. Prostaglandins in cases of non immunologic contact urticaria
12. Spontaneous (Ordinary) Urticaria
• All urticarias are acute initially
• The term “chronic urticaria" should only be applied to continuous
urticaria occurring at least twice a week off treatment for more than 6
weeks
• Urticaria occurring less frequently than this over a long period is better
called episodic (or recurrent), because this presentation may be more
likely to have an identifiable environmental cause.
13. Acute spontaneous urticaria
• Common in young children with atopic dermatitis
• Multiple pruritic wheals of different sizes erupt anywhere on the body
and then fade within 2–24 hours without bruising
• Angioedema may last up to 72 hours when severe
• Systemic symptoms of fatigue, lassitude, sweats and chills, indigestion,
myalgia or arthralgia may occur with severe attacks, but the occurrence
of pyrexia or arthritis should alert the clinician to another explanation,
such as urticarial vasculitis, Schnitzler syndrome
14.
15. Chronic Spontaneous Urticaria
• Chronic urticaria peaks in the fourth decade
• Has been associated with autoimmune thyroid disease and other
autoimmune conditions
• Possible association with H pylori
• Parasitic infections, such as intestinal strongyloidiasis, are an
uncommon cause of urticaria in developed countries, but may be a
significant problem where they are endemic
16.
17.
18. Dermographism
• skin writing
• most common type of physical
urticaria
• Sharply localized wheal
• Within seconds after skin has been
stroked
19. Cold urticaria
• Primary
(common , idiopathic)
• Secondary
Due to serum abnormalities e.g.
Cryoglobulins
May have other manifestations as
Raynaud’s phenomenon
20. Cholinergic urticaria
• multiple, transient, papular wheals
• Occur within 15 minutes of sweat-
inducing stimuli, such as any form
of physical exertion, hot baths, or
sudden emotional stress
21. Aquagenic urticaria
• Due contact with water
irrespective its temperature
• May be due to water soluble
antigen in the horny layer which
diffuses into the dermis and active
mast cell
23. Contact Urticaria
• Occur when substance is applied to intact skin
• Non immunologic:
1. No prior sensitization
2. May be due to PGD2 rather than histamine (Blocked by NSAID)
3. Eg: Cosmetics, food additives, occupational exposure
• Immunologic:
1. Less common
2. Type I hypersensitivity reaction
3. Eg: latex
24. Diagnosis
• Urticaria is a clinical diagnosis
• Acute urticaria:
1) with no cause is suggested in the history , investigations rarely
provides an answer
2) To identify environmental allergen as a cause Skin prick test,
specific IgE antibodies.
• Chronic urticaria:
1. Inducible urticaria by appropriate testing(25% os CU)
2. Wheal persist, painful with systemic symptom of fever or arthralgia
urticarial vasculitis
3. If angioedema only suspect HAE (C4 level)
25. Diagnosis
Chronic urticaria:
1. CBC : eosinophilia should prompt a search for parasitic disease
2. ESR: elevated suggest an underlying systemic disease
3. H pyloria antigen in stool
4. Stool analysis for parasitic infestations
5. Thyroid autoantibodies and thyroid function tests
26. Treatment
1. Treat the cause ( treat infection , withdraw offending drug)
2. Recognize and avoid aggravating factors Minimize overheating, stress,
avoid NSAIDs, minimize dietary pseudoallergens
3. Pharmacological:
1st line: antihistamines
2nd line: Steroids, Epinephrine, Montelukast, Colchicine, Sulfasalazine, Dapsone
3rd line: Cyclosporine, Omalizumab, Other immunosuppressives
4. Specific treatment for angioedema without wheals (hereditary)
27. Antihistamines
• H1 antihistamines are the first line treatment of all types of urticaria
They are rapidly absorbed, reaching peak serum concentrations in 1–3
hours
• The second generation of potent specific low-sedation H1
antihistamines is now the treatment of choice. Their main advantage is
low sedation at doses recommended
• Taken on a daily basis, the frequency depending on their half-life. In
other words, they should not be taken only when the patient is
symptomatic (Reassess after 2-3 weeks)
• Increasing the dose of second-generation H1 antihistamines up to
fourfold above license in adults when lower doses do not provide
adequate symptom control
28. Antihistamines
• The addition of H2 antagonists to conventional H1 antihistamines may
be helpful in some patients with chronic urticaria, although the
evidence for combining H1 and H2 antihistamines is poor and not all
authorities recommend this therapeutic approach
• No H1 antihistamine can be advertised as being safe during pregnancy,
but recent urticaria guidelines suggest loratadine and cetirizine
(traditional category B drugs) as preferred medications, especially in
the second and third trimesters
29.
30. Systemic Steroids
• Prednisone or prednisolone is effective for nearly all presentations of
chronic urticaria, but often needs to be used at reasonably high doses
(30–50 mg daily) to achieve good initial control of severe disease
• It should be considered primarily for the short-term management of
“crisis" urticaria and serious angioedema of the throat as a rescue
medication, when, often, a single dose or several daily doses will be
sufficient to re-establish control with regular full- dose antihistamines
• Regular treatment with oral corticosteroids should be avoided
31. Epinephrine
• Subcutaneous or intramuscular injection is the treatment of choice for
anaphylactic shock or severe anaphylactoid reactions, whether due to an
allergy, pseudoallergy, or physical urticaria.
• Epinephrine may also be necessary for angioedema of the oropharynx
in severe acute allergic urticaria and idiopathic angioedema
32. Prick test
• Prick/puncture testing remains one of the most
common and popular methods for allergy testing.
• It is an indirect measure of cutaneous mast cell
reactivity due to the presence of specific IgE.
• Mast cells reside in the subepithelial layer of the
skin and the respiratory, nasolacrimal, and
gastrointestinal tracts.
33. Prick test
• Skin testing detects allergen-specific IgE bound to mast
cells.
• The allergen cross-links specific IgE bound on the mast cell.
• This causes degranulation of preformed mediators,
including histamine and tryptase.
34. Prick test
• Histamine release is the major
mediator that results in a hive at the
prick site and surrounding
erythema, called a wheal and flare.
35. Patch tests
• used in patients with allergic contact dermatitis, to find out whether their skin
condition may be caused or aggravated by a contact allergy.
• Patch tests are not the same as skin prick tests, which are used to diagnose hay
fever allergy (house dust mite, grass pollens and cat dander).
• Skin prick tests have very limited value for patients with skin rashes.
38. Patch testing
• The appointments
• The first appointment will take about half an hour.
• Tiny quantities of 25 to 150 materials in individual square plastic or
round aluminium chambers are applied to the upper back.
• They are kept in place with special hypoallergenic adhesive tape.
• The patches stay in place undisturbed for 48 hours.
39. Patch testing
• At the second appointment, usually two days later, the patches will be
removed. Sometimes further patches are applied.
• The back is marked with an indelible black felt tip pen or other suitable
marker to identify the test sites.
• These marks must still be visible at the third appointment, usually two days
later (4 days after application).
• The back should be checked and if necessary remarked on several
occasions between the 2nd and 3rd appointments.
40. Patch testing
• The results
• Complete a record form at the second and third appointments (usually 48
and 96 hour readings).
• The result for each test site is recorded. The system we use is as follows:
• Negative (-)
• Irritant reaction (IR)
• Equivocal / uncertain (+/-)
• Weak positive (+)
• Strong positive (++)
• Extreme reaction (+++)
