Description

• A cutaneous lesion involving transient edema of the epidermis and/or dermis characterized by the acute onset of a polymorphic lesion with central pallor and edema with an erythematous flare ranging in size from millimeters to centimeters
• Pathophysiology is primarily mast cell degranulation and subsequent histamine release.
• Lesions subside within 24 hours, whereas angioedema, a dermal lesion of similar pathophysiology, may take up to 72 hours to remit.
• Pruritus and burning are more commonly associated with urticaria; pain more often with angioedema.
• Commonly referred to as hives or wheals
• Spontaneous urticaria:
  • Acute: Persists <6 weeks:
    • Specific extrinsic triggers commonly are the cause, although a vast number of possible causes exist (e.g., drugs, foods, infections [esp. Streptococci], envenomation, allergens)
    • Underlying etiology may be difficult to pinpoint
  • Chronic: Persists >6 weeks with >2 episodes/week off treatment:
    • Unlike acute urticaria, 80% of cases have no obvious external stimulus.
    • If symptoms occur less than twice a week, this is more likely recurrent acute urticaria and should be approached as such.
    • For those with chronic urticaria, 40% have concurrent angioedema.
    • Chronic infection, pseudoallergy, malignancy including mastocytosis, autoimmunity (esp. thyroid), and medications may underlie the remaining 20%.
    • Half of those with chronic idiopathic urticaria have sera positive for IgG that releases histamine through binding of IgE or its receptor.
    • The other 50% are truly idiopathic.
  • Physical urticaria: Urticaria due to mechanical stimuli:
    • Dermatographism: “Skin writing” or the appearance of linear wheals at the site of friction, scratching, or any type of irritation. This is the most common physical urticaria.
    • Cold urticaria: Wheals occur within minutes of rewarming after cold exposure; 95% idiopathic, but can be due to infections (mononucleosis, HIV), neoplasia, or autoimmune diseases.
    • Delayed pressure urticaria: Urticaria occurs 0.5–12 hours after pressure to skin (e.g., from elastic or shoes), may be pruritic and/or painful, and may not subside for several days.
    • Solar urticaria: From sunlight exposure, usually UV; onset in minutes; subsides within 2 hours
    • Heat urticaria: From direct contact with warm objects or air; rare
    • Vibratory urticaria/angioedema: Very rare; secondary to vibrations (e.g., motorcycle)
  • Special forms of urticaria:
    • Cholinergic urticaria: Due to brief increase of core body temperature from exercise, baths, or to emotional stress; small pin-sized (5–10-mm) wheals surrounded by an erythema, but also can have larger wheals. This is the 2nd most common form.
    • Adrenergic urticaria: Also caused by stress; extremely rare; vasoconstricted, blanched skin around pink wheals as opposed to cholinergic’s erythematous surrounding
    • Contact urticaria: Wheals at sites where chemical substances contact the skin, may be either IgE dependent (e.g., latex) or IgE independent (e.g., stinging nettle)
    • Aquagenic and solar urticaria: Small wheals after contact with water of any temperature or UV light, respectively; rare
    • Urticarial vasculitis: Urticaria >24 hours and more painful than pruritic. A leukocytoclastic vasculitis; may be palpable and purpuric; arthralgias

Epidemiology

• Equally distributed across all ages: Children more likely to have acute, whereas adults and elderly predisposed to chronic urticaria.
• Predominant gender: Female predilection; 2:1 in chronic urticaria
• In 20% of patients, chronic urticaria lasts >10 years.

• Affects anywhere from 5–25% of the population
• Of people with urticaria, 40% have no angioedema, 40% have urticaria and angioedema, and 20% have angioedema with no urticaria (1).
• Up to 3% of the population at some point has chronic idiopathic urticaria.
• Chronic urticaria affects only 0.1–3% of children.

Risk Factors

• Atopic diseases, asthma, allergic rhinitis, other allergies
• Of patients, >50% possess an atopic disease, >40% with allergic rhinitis, and >15% have atopic dermatitis or allergic asthma in chronic urticaria (1).

Genetics
No consistent pattern known: Chronic urticaria has increased frequency of HLA-DR4 and HLA-D8Q MHC II alleles.

General Prevention

Treatment of any underlying atopic or other disease; avoidance of known triggers

Pathophysiology

• Mast cell degranulation with release of inflammatory reactants, which leads to vascular leakage, inflammatory cell extravasation, and dermal (angioedema) and/or epidermal (wheals/hives) edema
• Histamine, cytokines, leukotrienes, and proteases are main active substances released
• Mast cell degranulation may be caused by allergen cross-linkage of IgE, autoimmune activation of FcεRI (IgE receptor), substance P, C5a, opiates, or physical stimuli.

Etiology

• Spontaneous acute urticaria:
  • Bacterial infections: Strep throat, sinusitis, otitis, urinary tract
  • Viral infections: Rhinovirus, rotavirus, hepatitis B, mononucleosis, herpes
  • Foods: Peanuts, tree nuts, seafood, milk, soy, fish, wheat, and eggs; tend to be IgE-mediated; pseudoallergenic foods, such as strawberries, tomatoes, preservatives, and coloring agents contain histamine.
  • Drugs: IgE-mediated (e.g., penicillin and other antibiotics), direct mast cell stimulation (e.g., aspirin, NSAIDs, opiates)
  • Inhalant, contact, ingestion, or occupational exposure (e.g., latex, cosmetics)
  • Parasitic infection; insect bite/sting
  • Transfusion reaction
• Spontaneous chronic urticaria:
  • Chronic subclinical allergic rhinitis, eczema, and other atopic disorders
  • Chronic indolent infections: Helicobacter pylori, fungal, parasitic (Anisakis simplex, strongyloidiasis), and chronic viral infections (hepatitis)
  • Collagen-vascular disease (cutaneous vasculitis, serum sickness, lupus)
  • Thyroid autoimmunity, especially Hashimoto
  • Hormonal: Pregnancy and progesterone
  • Autoimmune antibodies to the IgE receptor α chain on mast cells and to the IgE antibody
  • Chronic medications (e.g., NSAIDs, hormones, ACE inhibitors)
  • Malignancy
  • Physical stimuli (cold, heat, vibration, pressure) in physical urticaria

Commonly Associated Conditions

• Angioedema
• Anaphylaxis