Angioedema (see Angioedema)

  • Well-Demarcated, Localized Edema Involving the Subcutaneous/Submucosal Layers of the Skin, Pharynx/Larynx, and/or Gastrointestinal Tract
    • Angioedema May Occur in Isolation or in Conjunction with Urticaria or Anaphylaxis


  • Inflammation Confined to the Superficial Dermis
    • Wheals with Raised Serpiginous Borders and Blanched Centers



  • Urticaria Occurs in up to 20% of the Population (at Some Point in Their Lifetimes)


Mast Cell-Mediated Urticaria

IgE-Mediated Mast Cell Activation (Type I Hypersensitivity) (see Immune Hypersensitivity)

  • Foods/Food Additives
    • General Comments
      • Specific Food Triggers Vary by Age
        • Most Commonly-Implicated Foods in Children: milk, eggs, peanuts, tree nuts, soy, and wheat
        • Most Commonly-Implicated Foods in Adults: fish/shellfish, peanuts, and tree nuts
      • Specific Food Triggers Vary Geographically: due to different foods consumed and methods of preparation
        • North America/Some Countries in Europe and Asia: cow milk, hen’s egg, peanut, tree nuts, shellfish, and fish are common triggers
        • European Countries: peach is a common triggers
        • Middle East: sesame is common trigger
        • Asia: buckwheat, chickpea, rice, and bird’s nest soup are common triggers
    • Annatto (see Annatto): yellow food colorant
    • Carmine: insect-derived red colorant
    • Eggs
    • Legumes: beans, lentils, peanuts, peas, soybeans/soy
    • Milk: cow milk, goat milk, sheep milk
    • Peach
    • Seafood: crustaceans, shellfish, finned fish, shrimp
    • Sesame
    • Spices
    • Tree Nuts: almonds, cashews, walnuts
    • Vegetable Gums
    • Wheat
  • Stings/Bites/Envenomations
    • Phylum Arthropoda -> Class Insecta -> Order Hymenoptera
    • Phylum Arthropoda -> Class Insecta -> Order Hemiptera
      • Bed Bug (Cimex) Bite: may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
      • Kissing Bug Bite (Triatoma)
    • Phylum Arthropoda -> Class Insecta -> Order Diptera
      • Black Fly Bite
      • Deer Fly Bite
      • Mosquito Bite (see Mosquito Bite)
      • Tsetse Fly Bite
    • Phylum Arthropoda -> Class Insecta -> Order Lepidoptera
      • Pine Processionary Caterpillar Envenomation
      • Puss Caterpillar Envenomation (see Puss Caterpillar Envenomation): may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
    • Phylum Arthropoda -> Class Arachnida
      • Australian Paralysis Tick Bite
      • Pigeon Tick Bite
      • Scorpion Sting (see Scorpion Sting): particularly Centruroides (common striped scorpion)
      • Western Black-Legged Tick Bite
    • Phylum Cnidaria
      • Box Jellyfish (Carybdea Alata) Sting (see Jellyfish Sting): may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
      • Portuguese Man-of-War (Physalia Physalis) Sting: may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
      • Sea Nettle Sting
    • Phylum Chordata -> Class Reptila
      • European Viper (Vipera) Snake Bite
      • Gila Monster Bite (see Poisonous Lizard Bite): may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
      • Mexican Beaded Lizard Bite (see Poisonous Lizard Bite): may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
      • Rattlesnake (Crotalus) Bite (see Rattlesnake Bite)
    • Phylum Chordata -> Class Mammalia
      • Gerbil Bite
      • Hamster Bite
      • Mouse Bite
      • Rat Bite
  • Contact Allergens (Contact Urticaria-Immunologic/Allergic Type)
    • General Comments
      • Allergic Mechanism: IgE-dependent, complement-mediated, requires prior sensitization
        • Urticaria may involve non-contacted areas
        • May be severe, resulting in anaphylaxis
      • Onset: urticaria usually appears within 30 min of exposure
    • Animal Saliva
      • Mechanism: allergic mechanism
    • Bacitracin (see Bacitracin): antibiotic
      • Mechanism: allergic or non-allergic mechanism
    • Benzoic Acid: used as preservative
      • Mechanism: allergic or non-allergic mechanism
    • Chlorhexidine (see Chlorhexidine)
      • Mechanism: allergic mechanism
    • Copper (see Copper)
      • Mechanism: allergic mechanism
    • Formaldehyde (see Formaldehyde)
      • Mechanism: allergic or non-allergic mechanism
    • Nickel (see Nickel)
      • Mechanism: allergic mechanism
    • Parabens
      • Mechanism: allergic mechanism
    • Paraphenylenediamine (PPD) (see Paraphenylenediamine): used in hair dyes, inks, photographic chemicals, black henna tattoos
      • Mechanism: allergic mechanism
    • Natural Rubber Latex (see Latex): found in condoms, balloons, gloves, etc
      • Mechanism: allergic mechanism
    • Salicylic Acid (see Salicylic Acid)
      • Mechanism: allergic mechanism
    • Short-Chain Alcohols
      • Mechanism: allergic mechanism
  • Drugs
  • Other
    • Aeroallergens: rarely involved in angioedema/anaphylaxis
      • Cat Dander
      • Grass Pollen
      • Horse Dander
    • Allergen Immunotherapy (see Allergen Immunotherapy)
    • Blood Products
    • Fluorescein (see Fluorescein)
    • Hemodialysis (see Hemodialysis): due to reaction to dialysis membranes
      • Cellulose Membranes: predominant type of membrane associated with anaphylaxis
        • Membranes are ethylene oxide sterilized
        • Membranes can activate complement
      • Polyacrylonitrile AN69 High Flux Membranes: fewer reported cases of anaphylaxis
    • Human Seminal Fluid
      • Epidemiology: rare etiology of anaphylaxis in females
    • Intradermal Allergen Skin Testing
    • Vaccines

Immunologic Non-IgE-Mediated Mast Cell Activation

  • Heparin Contaminated with Oversulfated Chondroitin Sulfate (see Heparin)
    • Physiology: mediated by coagulation system activation
  • Dextrans
    • Dextran (see Dextran)
    • Iron Dextran (Dexferrum, INFeD) (see Iron Dextran)
      • Risk of First-Exposure Anaphylaxis (see Anaphylaxis) [MEDLINE]): 68 per 100k patients
      • Cumulative Risk of Anaphylaxis (Over 12 wk Period) [MEDLINE]: iron dextrose has highest risk of all of the intravenous iron agents
  • Idiopathic Histaminergic Angioedema
    • Clinical: recurrent angioedema often associated with chronic spontaneous urticaria or inducible (physical) urticaria
  • Infliximab (Remicade) (see Infliximab)
    • Physiology: IgG-mediated
  • Packed Red Blood Cells (PRBC) (see Packed Red Blood Cells)
    • Epidemiology: rare cases of patients with very low levels of IgA and anti-IgA Ab’s, may develop anaphylaxis upon receiving blood with IgA present (these patients need IgA-deficient blood products)

Non-Immunologic Direct Mast Cell/Basophil Activation

  • Contact Allergens (Contact Urticaria-Non-Immunologic/Non-Allergic Type)
    • General Comments
      • Non-Allergic Mechanism: substance directly induces mast cell mediator release (substances do not require prior sensitization)
        • Urticaria remains localized to site of contact
      • Onset: urticaria usually appears within 30 min of exposure
    • Balsam of Peru: used as perfume
      • Mechanism: non-allergic mechanism
    • Benzoic Acid: used as preservative
      • Mechanism: allergic or non-allergic mechanism
    • Formaldehyde (see Formaldehyde)
      • Mechanism: allergic or non-allergic mechanism
    • Sorbic Acid: used as preservative
      • Mechanism: non-allergic mechanism
    • Cinnamic Acid
      • Mechanism: non-allergic mechanism
    • Nicotinic Acid
      • Mechanism: non-allergic mechanism
  • Ethanol (see Ethanol): rarely induces anaphylaxis by itself, but may augment mast cell activation
  • Foods: these “pseudoallergens” may cause urticaria (or contact urticaria) via IgE-mediated or via non-immunologic mechanisms, especially in children
    • Strawberries
    • Tomatoes
  • Neuromuscular Junction Antagonists (see Neuromuscular Junction Antagonists)
  • Opiates (see Opiates)
  • Physical Factors
    • Cold
    • Heat
    • Exercise: usually associated with a co-trigger (such as a food, NSAID, or exposure to cold air or water)
    • Sunlight/Ultraviolet Radiation
  • Radiographic Contrast (see Radiographic Contrast)
  • Some Nonsteroidal Anti-Inflammatory Drugs (NSAID) (see Nonsteroidal Anti-Inflammatory Drug)
  • Stinging Nettle (Urtica Dioica) (see Stinging Nettle): urticaria was named after this weed (which is commonly found in North America, South America, Europe, and parts of Africa
    • Physiology: histamine (and pain-causing mediators) contained in the plant
  • Vancomycin (see Vancomycin)

Altered Arachidonic Acid Metabolism


General Comments

  • Infection-Associated Urticaria Occurs Most Commonly in Children: may involve immune complex formation (although the exact mechanism is unclear)




Physical Stimuli

  • Aquagenic Urticaria
    • Epidemiology: associated with water contact (regardless of temperature)
  • Cholinergic Urticaria
    • Epidemiology: associated with fever, hot bath or shower, exercise
    • Physiology: probably related to increase in body temperature
    • Clinical: distinctly small 1-2 mm wheals surrounded by large area of erythema
  • Cold-Induced Urticaria
    • Epidemiology: acquired or hereditary
    • Clinical: usually occurs locally at the cold-exposed site (but can lead to vascular collapse in cases with whole-body cold water immersion during swimming)
  • Dermatographism
    • Epidemiology: occurs in 1-4% of population
      • Peak Prevalence: teens-20’s
      • Usually lasts <5 years
    • Clinical: linear wheal at site of a firm skin stroke
  • Heat-Induced Urticaria
    • Epidemiology: associated with local heat application
  • Exercise-Induced Urticaria
    • Clinical: begins with erythema and pruritic urticaria -> progresses to angioedema of face/larynx/intestine/vascular collapse
  • Pressure-Induced Urticaria
    • Epidemiology: associated with a sustained stimulus from shoulder strap, running (on feet), or manual labor (on hands)
  • Solar Urticaria: three subtypes, distinguished by spectrum of UV light
  • Vibratory Urticaria
    • Epidemiology:
      • Can occur after years of oocupational exposure or may be idiopathic
      • Can be accompanied by cholinergic urticaria

Autoimmune Disease

  • General Comments: unclear pathophysiology, but possible mechanisms include direct mast cell activation via complement receptors or generation of autoantibodies that cause anaphylactoid degranulation
  • Autoimmune Thyroid Disease
  • Celiac Disease (see Celiac Disease)
  • Henoch-Schonlein Purpura (see Henoch-Schonlein Purpura): lesions may appear urticarial in early stages
  • IgM (and Sometimes IgG) Paraproteinemia: may be due to complement-mediated pathways
  • Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis)
  • Sjogren’s Syndrome (see Sjogren’s Syndrome)
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)


  • Cytokine Release Syndrome (see Cytokine Release Syndrome)
  • Scombroid (see Scombroid)
  • Serum Sickness (see Serum Sickness)
  • Systemic Mastocytosis (see Systemic Mastocytosis)
  • Hypocomplementemic Urticarial Vasculitis
    • Physiology
      • Presence of Anti-C1q IgG Antibody
    • Clinical
      • Fever (see Fever)
      • Urticarial Lesions: may be painful, eccyhmotic, and purpuric (leaving ecchymoses after resolution)


  • Activation of Superficial Dermis Mast Cells (and Basophils): release of inflammatory mediators (histamine, etc)
    • Histamine: causes pruritus
    • Vasodilatory Mediators: localized edema in superficial dermis
  • Angioedema: represents the same pathologic process, except involving the mast cells deeper in the dermis and subcutaneous tissues


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Clinical Manifestations

General Comments

  • Onset
    • Food-Associated Urticaria: onset is usually within 30 min of ingestion
  • Classification of Urticaria Based on Chronicity
    • Acute Urticaria: urticaria present for <6 wks
    • Chronic Urticaria: urticaria present for 6 wks or longer (recurrent and occurring on most days of the week)

Dermatologic Manifestations

  • Urticaria: localized, well-circumscribed, erythematous plaques with central pallor
    • Shape: round, oval, or serpiginous
    • Size: vary from <1 cm to several cm in diameter
    • Distribution: predominate in areas where clothing compresses the skin (under waistband, etc) or where skin rubs together (axilla)
    • Number: wheals may occur individually or coalesce
    • Time Course: urticarial lesions progress over min-hrs, regressing over 24 hrs (without leaving any residual ecchymoses)
      • Presence of residual ecchymoses suggests the alternative diagnosis of vasculitis
    • Symptoms: may be particularly severe at night
    • Urticarial Lesions are Intensely Pruritic (see Pruritus)
      • Urticarial lesions are not usually painful: presence of pain suggests the alternative diagnosis of vasculitis
    • Association with Angioedema/Anaphylaxis (see Angioedema and Anaphylaxis): urticaria may occur without associated angioedema/anaphylaxis


Antihistamines (H1-Histamine Receptor Antagonists) (see H1-Histamine Receptor Antagonists)

  • xxxx

H2-Histamine Receptor Antagonists (see H2-Histamine Receptor Antagonists)

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Corticosteroids (see Corticosteroids)

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  • Occupational contact urticaria. Clin Rev Allergy Immunol. 2006 Feb;30(1):39-46 [MEDLINE]