Page 616 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 42 Urticaria, Angioedema, and Anaphylaxis 593

to relevant antigens (FcεRIα or IgE) do not correlate well with
Workup in Acute Urticaria the results of functional assays. 10
When allergens are suspected as the cause there should be a
close temporal relationship to the time of exposure, usually MANAGEMENT OF URTICARIA
starting within minutes, a history of previous exposure causing
sensitization and prompt resolution on allergy withdrawal. IgE Finding effective treatment for urticaria can be challenging.
sensitization can be assessed by skin prick testing or fluoroen- Treatment should be tailored to the clinical pattern, duration,
zymatic immunoassay (FEIA) (also known as serum specific IgE and severity of the urticaria. Management should include
testing). nonpharmacological measures and drug therapy with a stepwise
approach. 1
Workup in Physical Urticarias
When physical urticaria is suspected, appropriate challenge testing
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should be performed to confirm the diagnosis. Generally, there THEraPEUTiC PriNCiPLES
is no need for further investigation, except for cold urticaria, Management of Urticaria
where blood cryoglobulins should be assayed.
• Eliminate infectious, drug, or food causes.
Workup in Chronic and Episodic • Minimize nonspecific aggravators, including heat, stress, alcohol,
Spontaneous Urticarias nonsteroidal antiinflammatory drugs, and pressure.
No laboratory workup is recommended for patients with mild • Regular oral H1 antihistamines are the first line of therapy for all
spontaneous and inducible urticarias.
CSU that is easily controlled by antihistamines, unless the history • Second-line treatments, including short courses of oral corticosteroids,
points to an underlying disease. Studies have shown that random may be necessary for specific clinical situations.
laboratory testing very rarely yields evidence of unsuspected • Immunosuppressive therapies should be reserved for patients with
internal diseases as a cause of CSU, and this should therefore severe autoimmune urticaria or steroid-dependent urticaria that has
be discouraged. 21 not responded to other first- and second-line measures.
Screening laboratory evaluation can be considered in patients • Omalizumab (monoclonal anti-IgE) is effective in chronic spontaneous
urticaria refractory to H1 antihistamines
with poor response to first-line antihistamine treatment. A
complete blood count (CBC) with differential, ESR, thyroid-
stimulating hormone (TSH), thyroid antibodies, liver function
tests, and urinalysis will exclude most diseases associated with General Measures
urticaria. Causes, triggers, and aggravating factors should be avoided or
Other evaluations should be guided by abnormal findings minimized, whenever possible. Patients with CSU should minimize
in the history and physical examination in patients with CSU. exposure to nonspecific aggravating factors, such overheating,
Additional tests may include stool examination for ova and wearing tight clothes and shoes, stress, alcohol, dietary pseudoal-
parasites and Helicobacter pylori, antinuclear antibody titer, lergens, and some drugs. NSAIDs aggravate up to 30% of patients
hepatitis viral screening, and skin prick or blood tests for with CSU and are usually avoided. This does not apply to the
specific IgE in episodic urticaria if there is a story of intermit- physical urticarias, in particular DPU, where NSAIDs may be
tent allergen exposure. Tests for immediate hypersensitivities used as treatment. ACEIs are contraindicated in angioedema
should not be undertaken in chronic continuous urticaria unless without wheals that may be mediated by kinins but not in other
there are compelling reasons for doing so. Rarely, CSU can be patterns of urticaria. Although it is often recommended that
caused by a specific food additive, which should be confirmed patients with CSU avoid codeine and penicillin, clinical experience
by dietary exclusion and double-blind, placebo-controlled oral suggests that this is not necessary. Cooling lotions and creams,
challenge. such as 1% menthol in aqueous cream, may help relieve pruritus.
Some patients with spontaneous but not inducible CU appear
The Diagnosis of Autoimmune Chronic Urticaria to respond to a low-pseudoallergen diet. However, controlled
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The diagnosis of autoimmune CU is not straightforward and clinical trials are lacking.
involves in vivo and in vitro approaches. Autologous serum skin
testing (ASST) is a simple and useful screening method for First-Line Therapy
autoreactivity in patients with CU. For skin testing, 0.05 mL of Antihistamines are the cornerstone of treatment for all types of
the patient’s own serum should be injected intradermally into histaminergic urticaria. Second-generation antihistamines offer
clinically uninvolved forearm skin, together with an equal volume several advantages over classic H1 antihistamines, including lack
of saline as a negative control. Histamine 10 mg/mL can be used of sedation and impairment of performance, longer duration
as a positive control. The reaction is considered positive if the of action, and absence of anticholinergic side effects. Meta-analysis
serum skin test forms a pink wheal at least 1.5 mm greater than indicates that antihistamines are effective in 40–90% of patients
the negative control at 30 minutes. The test is 80% specific and with CU. Second-generation antihistamines are inverse agonists
70% sensitive for autoimmune CU as defined by a positive of H1 receptors, which stabilize H1 receptors in the inactive
basophil histamine release assay. 23 conformation and are, therefore, most effective in CU when
The current diagnostic gold standard in autoimmune CSU taken regularly for prophylaxis. The timing of antihistamine
is a functional release assay using whole sera on healthy donor intake should be adjusted to suit the diurnal pattern of urticaria
basophils or mast cells, but these only give indirect evidence of for each individual. Although the evidence base for combining
functional autoantibodies. Being technically difficult, these assays H1 and H2 antihistamines is poor, this may be helpful. H2
are mainly confined to research centers. Nonfunctional immunoas- antihistamines also suppress the dyspepsia that often accompanies
says (Western blot, ELISA) based on binding of autoantibodies severe urticaria.