Transcript Urticaria and Angioedema

Urticaria and Angioedema
Urticaria
Angioedema
Etiology of Urticarial Reactions:
Allergic Triggers
Acute Urticaria
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Drugs
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Foods
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Food additives
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Viral infections
– hepatitis A, B, C
– Epstein-Barr virus
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Insect bites and stings
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Contactants and inhalants
(includes animal dander and latex)
Chronic Urticaria
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Physical factors
– cold
– heat
– dermatographic
– pressure
– solar
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Idiopathic
The Pathogenesis of Chronic Urticaria:
Cellular Mediators
Histamine as a Mast Cell Mediator
Role of Mast Cells in Chronic Urticaria:
Lower Threshold for Histamine Release
Cutaneous mass cell
Release threshold decreased by:
Cytokines & chemokines
in the cutaneous
microenvironment
 Antigen exposure
 Histamine-releasing factor
 Autoantibody
 Psychological factors
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Release threshold increased by:
Corticosteroids
 Antihistamines
 Cromolyn (in vitro)
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An Autoimmune Basis for Chronic
Idiopathic Urticaria: Antibodies to IgE
Initial Workup of Urticaria
Patient history
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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
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Skin
Eyes
Ears
Throat
Lymph nodes
Feet
Lungs
Joints
Abdomen
Laboratory Assessment for
Chronic Urticaria
Initial tests
CBC with differential
 Erythrocyte sedimentation rate
 Urinalysis
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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
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RAST for specific IgE
 Complement studies: CH50
 Cryoproteins
 Thyroid microsomal antibody
 Antithyroglobulin
 Thyroid stimulating hormone (TSH)
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Histopathology
Polymorphous perivascular infiltrate
 Neutrophils
 Eosinophils
 Mononuclear cells
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Sparse perivascular
lymphocytes
Urticaria/Angioedema
Definition
– affects more than 20% of the population at some time in their lives
– smooth, evanescent, edematous lesion (wheals)
– heat, drugs, infections, and emotional stress are the most frequent
triggers
Classification
– acute if duration < 6 wks, otherwise chronic
– 3 major groups: (a) immunologic urticaria; (b) non-immunologic
urticaria; c: idiopathic urticaria
Allergic reactions: Angioedema
Usually localised (to head & neck) but may be
more generalised (especially GI) +/- urticaria.
Presents as swelling of the face, neck and
oropharynx. Represents mast cell degranulation
in skin deep to dermis vs. superficial dermis in
urticaria.
• Inherited - C1 esterase inhibitor deficiency due
to mutation (autosomal dominant) of the C1-INH
gene.
• Acquired - usually autoantibodies to C1-INH in
the context of autoimmune disease or
lymphoproliferative disorders. Rarer reports of
hypercatabolism of C1-INH in infection.
• Drug-induced - commonest culprit ACE
inhibitors.
ACE inhibitors & Angioedema
• Mechanism probably related to massive elevation of BK but unclear
why it can appear days to years after 1st dosing.
• Incidence probably <0.1% - Afro-Caribbean and renal/cardiac
transplant patients may be at increased risk.
• Treatment is usually with standard therapy for an anaphylactic reaction
+/- inhaled Epi but not mast cell dependent! If airway threatened,
intubation or tracheostomy needed.
• Under recognised especially in milder forms. ACE inhibitors should be
stopped and an AT2 receptor antagonist substituted if necessary (e.g.
Losartan) BUT isolated reports have appeared of angioedema with these
agents!
• New combined ACE/NEP inhibitors suffer same problem.
Common Causes of Acute Urticaria
Idiopathic
Immune-mediated (IgE)
– foods (shellfish, nuts)
– drugs
Noimmune-mediated
– opiates
Nonspecific
– viral infections (influenza)
– bacterial infections (occult abscess, mycoplasma)
Urticaria Associated With
Other Conditions
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Collagen vascular disease (eg, systemic lupus erythematosus)
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Complement deficiency, viral infections (including hepatitis B
and C), serum sickness, and allergic drug eruptions
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Chronic tinea pedis
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Pruritic urticarial papules and plaques of pregnancy (PUPPP)
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Schnitzler’s syndrome
Therapy for Urticaria
Abbreviated search for triggers
– treat the treatable causes
Anti-histamines
– Short-acting (Benadryl, Atarax)
– Long-acting (Claritin, Reactine)
Corticosteroids
– start around 1 mg/kg/day (single or divided doses)
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
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Beta-adrenergic agonists
Epinephrine for acute urticaria
(rapid but short-lived response)
 Terbutaline
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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)
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Miscellaneous
PUVA
 Hydroxychloroquine
 Thyroxine
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H1-Receptor Antagonists:
Pros and Cons for Urticaria and Angioedema
First-generation antihistamines (diphenhydramine
and hydroxyzine)
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Advantages: Rapid onset of action, relatively inexpensive
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Disadvantages: Sedating, anticholinergic
Second-generation antihistamines (astemizole,
cetirizine, fexofenadine, loratadine)
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Advantages: No sedation (except cetirizine); no adverse
anticholinergic effects; bid and qd dosing
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Disadvantages: Prolongation of QT interval; ventricular
tachycardia (astemizole only) in a patient subgroup
Four-week Treatment Period:
Fexofenadine HCl
Mean Pruritus Scores/Mean Number of
Wheals/Mean Total Symptom Scores
An Approach to the Treatment of
Chronic Urticaria