Urticaria and Angioedema

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Urticaria and Angioedema

• Urticaria

Angioedema
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Etiology of Urticarial ReactionsAllergic
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

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The Pathogenesis of Chronic UrticariaCellular
Mediators
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Histamine as a Mast Cell Mediator
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Role of Mast Cells in Chronic UrticariaLower
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

• Release threshold increased by
• Corticosteroids
• Antihistamines
• Cromolyn (in vitro)

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An Autoimmune Basis for Chronic Idiopathic
Urticaria Antibodies to IgE
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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

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Laboratory Assessment for Chronic Urticaria

• Initial tests
• CBC with differential
• Erythrocyte sedimentation rate
• Urinalysis

• 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

• 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

Sparse perivascular lymphocytes
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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 lt 6 wks, otherwise chronic
• 3 major groups (a) immunologic urticaria (b)
  non-immunologic urticaria c idiopathic urticaria

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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.
  

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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 lt0.1 - 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.

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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)

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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)
• Schnitzlers syndrome

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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)

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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

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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

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Four-week Treatment PeriodFexofenadine HCl
Mean Pruritus Scores/Mean Number of Wheals/Mean
Total Symptom Scores
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An Approach to the Treatment of Chronic Urticaria