urticaria
URTICARIA
Urticaria is characterized by sudden appearance of wheals and/or angioedema.
The intensity of the pruritus varies but may be severe enough to disrupt sleep, work or school.
It is classified acute if the urticaria has been present for <6 weeks and chronic if >6 weeks. A specific cause is more likely to be identified in acute cases.
It can be triggered by immunological or nonimmunological mechanism.

Pharmacotherapy

Antihistamines (Oral)

  • 1st-line treatment because histamine is an important mediator of symptoms in most types of urticaria
  • Effective in controlling the symptoms of pruritus, reducing the number, size & duration of urticarial lesion
  • Choice of product will depend on adverse effect profile, cost & patient preference
  • Continuous daily use is more efficacious
  • Up-dosing may be done to control symptoms in majority of patients w/ urticaria but care must be taken since side effects occur more frequently at higher dosages (esp w/ sedating antihistamines)
    • It is preferred to up-dose a single antihistamine agent than to combine different antihistamines
  • If one antihistamine fails, another may be tried
  • It is recommended to wait for 1-4 wk before changing to alternative treatments (including expert referral) to allow full effectiveness of the antihistamines

2nd Generation Antihistamines

  • Eg Cetirizine, Loratadine, Desloratadine, Fexofenadine, Levocetirizine, Rupatadine, Bilastine
  • Recommended 1st-line treatment for urticaria
  • Preferred over 1st generation antihistamines because of less adverse effects (eg drowsiness)
  • Not given to children <6 mth of age

1st Generation Antihistamines

  • Eg Promethazine, Diphenhydramine, Ketotifen, Chlorpheniramine
  • Effective & inexpensive
    • Should no longer be used unless in rare places where nonsedating antihistamines are not available or in special cases where they are better tolerated than nonsedating antihistamines
    • Use is limited by side effects (anticholinergic and sedative effects) which last longer (12 hr) than its antipruritic effects (4-6 hr)
  • Avoided in children <2 yr due to paradoxical agitation

Immunomodulatory Therapy

  • Eg Cyclosporine, Omalizumab (anti-IgE)
  • Recommended 2nd-line treatment as an add-on therapy to high-dose 2nd generation antihistamines
  • Cyclosporine may be given only in cases of severe urticaria refractory to any dose of antihistamines
    • Not recommended as a standard treatment for urticaria due to high cost & incidence of adverse effects
  • Omalizumab has been proven by several studies to be an effective option for cases of chronic spontaneous urticaria, refractory chronic urticaria, cholinergic, cold, & solar urticaria, or failure w/ high-dose antihistamine
    • Not recommended as a standard treatment for urticaria due to high cost & low level of evidence of efficacy, although w/ good safety profile

Leukotriene Antagonists

  • Eg Zafirlukast, Montelukast, Zileuton
  • Montelukast is recommended as 2nd-line treatment & add-on therapy to high-dose 2nd generation antihistamines
  • May be used as an add-on therapy in cases of poorly controlled chronic urticaria
  • W/ good safety profile but response may take days to wks
  • Appear to benefit patients w/ chronic urticaria that is exacerbated by aspirin or other NSAIDs

Tranexamic Acid

  • A second-line pharmacotherapeutic agent, it may be considered in patients w/ higher dose antihistamine-resistant angioedema
    • Reduces frequency of angioedema attacks

H2 Antagonists (Oral)

  • Cimetidine, Ranitidine & Famotidine have been used in combination w/ H1 antihistamines
  • The addition of H2 antagonist may reduce pruritus & wheal formation among patients w/ chronic urticaria
    • Monotherapy w/ H2 antagonists has not shown benefit

Corticosteroids (Oral)

  • Use should be reserved for severe exacerbations of chronic urticaria that have failed to respond to full-dose antihistamines or when rapid clinical relief is needed
    • May also be required in patients who suffer from delayed pressure urticaria or urticarial vasculitis which respond poorly to antihistamines
  • Long-term administration should be avoided
  • Low-dose alternate-day regimens may be appropriate when applied carefully

Epinephrine (IM/SC)

  • May be used if laryngeal edema accompanies exacerbation of chronic urticaria
    • Not effective for hereditary angioedema

Other Anti-inflammatory Agents

  • Eg Dapsone, Intravenous immunoglobulin (IVIG)
  • No longer recommended as a standard treatment for urticaria due to low level of evidence for efficacy
  • High doses of IVIG have shown some benefits for patients w/ chronic urticaria
  • Other anti-inflammatory agents (eg Sulfasalazine, Methotrexate, interferon, IVIG) have only been tested in uncontrolled trials & further studies are needed

Non-Pharmacological Therapy

Avoidance of Trigger Factors

  • Identify potential trigger factors by careful history & selective allergy tests
    • Have patient stop any suspected foods, drinks or medications
  • Patient should avoid the potential allergens/trigger factors
  • Known or suspected chronic inflammatory & infectious diseases should be treated

Chronic Urticaria

  • Counsel the patient to avoid aggravating factors (eg heat, tight clothing, stress, alcohol) & trigger stimuli (eg sun in solar urticaria)
    • Provide information & advice about preventive measures (eg cool showers for cholinergic urticaria, covering of exposed skin in patients w/ cold urticaria)
    • Medications suspected to trigger urticaria attacks should be substituted if maintenance is a must
  • Avoidance of aspirin & other NSAIDs is usually recommended since these drugs aggravate chronic urticaria in approx 30% of patients
  • Avoidance of codeine & other opiates may also be recommended since there is enhanced skin test reactions to these drugs found in chronic urticaria patients
  • ACE inhibitors should be avoided since angioedema & rarely, urticaria, are adverse effects
  • UV-A, Psoralen plus ultraviolet A (PUVA), & UV-B may be used as add-on therapy for chronic spontaneous urticaria & symptomatic dermographism
  • Restrictive dietary measures such as avoidance of dietary pseudoallergen (eg food coloring, preservatives, etc) have no role in most forms of chronic urticaria
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