Urticaria

Definitions

  • Angioedema (see Angioedema, [[Angioedema]]): well-demarcated, localized edema involving subcutaneous/submucosal layers of the skin, pharynx/larynx, and/or gastrointestinal tract
    • Angioedema May Occur in Isolation or in Conjunction with Urticaria or Anaphylaxis
  • Urticaria: inflammation confined to the superficial dermis
    • Wheals with Raised Serpiginous Borders and Blanched Centers

Epidemiology

  • Prevalence: urticaria occurs in up to 20% of the population (at some point in their lifetimes)

Etiology

IgE-Mediated Mast Cell Activation (Type I Hypersensitivity) (see Immune Hypersensitivity, [[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, [[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
    • Bumble Bee Sting (see Bee Sting, [[Bee Sting]])
    • Fire Ant Bite
    • Honey Bee Sting (see Bee Sting, [[Bee Sting]])
    • Hornet Sting (see Hornet Sting, [[Hornet Sting]])
    • Paper Wasp Sting (see Wasp Sting, [[Wasp Sting]])
    • Wood Ant Bite
    • Yellowjacket Sting (see Bee Sting, [[Bee Sting]])
  • 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, [[Mosquito Bite]])
    • Tsetse Fly Bite
  • Phylum Arthropoda -> Class Insecta -> Order Lepidoptera
    • Pine Processionary Caterpillar Envenomation
    • Puss Caterpillar Envenomation (see Puss Caterpillar Envenomation, [[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, [[Scorpion Sting]]): particularly Centruroides (common striped scorpion)
    • Western Black-Legged Tick Bite
  • Phylum Cnidaria
    • Box Jellyfish (Carybdea Alata) Sting (see Jellyfish Sting, [[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, [[Poisonous Lizard Bite]]): may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
    • Mexican Beaded Lizard Bite (see Poisonous Lizard Bite, [[Poisonous Lizard Bite]]): may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
    • Rattlesnake (Crotalus) Bite (see Rattlesnake Bite, [[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, [[Bacitracin]]): antibiotic
    • Mechanism: allergic or non-allergic mechanism
  • Benzoic Acid: used as preservative
    • Mechanism: allergic or non-allergic mechanism
  • Chlorhexidine (see Chlorhexidine, [[Chlorhexidine]])
    • Mechanism: allergic mechanism
  • Copper (see Copper, [[Copper]])
    • Mechanism: allergic mechanism
  • Formaldehyde (see Formaldehyde, [[Formaldehyde]])
    • Mechanism: allergic or non-allergic mechanism
  • Nickel (see Nickel, [[Nickel]])
    • Mechanism: allergic mechanism
  • Parabens
    • Mechanism: allergic mechanism
  • Paraphenylenediamine (PPD) (see Paraphenylenediamine, [[Paraphenylenediamine]]): used in hair dyes, inks, photographic chemicals, black henna tattoos
    • Mechanism: allergic mechanism
  • Natural Rubber Latex (see Latex, [[Latex]]): found in condoms, balloons, gloves, etc
    • Mechanism: allergic mechanism
  • Salicylic Acid (see Salicylic Acid, [[Salicylic Acid]])
    • Mechanism: allergic mechanism
  • Short-Chain Alcohols
    • Mechanism: allergic mechanism

Drugs

  • Abacavir (see Abacavir, [[Abacavir]])
  • Acetaminophen (Tylenol) (see Acetaminophen, [[Acetaminophen]])
    • Epidemiology: cases of anaphylaxis have been reported
  • Angiotensin Converting Enzyme (ACE) Inhibitors (see Angiotensin Converting Enzyme Inhibitors, [[Angiotensin Converting Enzyme Inhibitors]])
  • Acyclovir (Zovirax) (see Acyclovir, [[Acyclovir]])
  • Anti-Thymocyte Globulin (ATG) (see Anti-Thymocyte Globulin, [[Anti-Thymocyte Globulin]])
  • Antivenoms
  • β-Lactam Antibiotics (see β-Lactam Antibiotics, [[β-Lactam Antibiotics]]): most common antibiotic-associated cause of urticaria
    • Cephalosporins (see Cephalosporins, [[Cephalosporins]])
    • Imipenem (see Imipenem, [[Imipenem]]): cross-reactivity in 50% of patients with allergy to penicillins
    • Penicillins (see Penicillins, [[Penicillins]]): occurs in 0.05% of cases, fatal in 5-10% of cases
  • Demeclocycline (see Demeclocycline, [[Demeclocycline]])
  • Gemcitabine (Gemzar) (see Gemcitabine, [[Gemcitabine]]): cases of laryngeal edema have been reported
  • Heparin (see Heparin, [[Heparin]]): anaphylaxis is a manifestation of heparin-induced thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])
  • Insulin (see Insulin, [[Insulin]])
  • Intradermal Allergen Immunotherapy
  • Iodinated Drugs/Contrast (see Radiographic Contrast, [[Radiographic Contrast]])
  • Local Anesthetics
    • Lidocaine (see Lidocaine, [[Lidocaine]])
    • Procaine (Novocaine, Novocain) (see Procaine, [[Procaine]])
  • Monoclonal Antibodies/Biologics
  • N-Acetylcysteine (Mucomyst, Acetadote, Fluimucil, Parvolex) (see N-Acetylcysteine, [[N-Acetylcysteine]])
    • Epidemiology: associated with intravenous administration
    • Physiology: histamine release has been implicated
  • Non-Dextran Intravenous Iron
    • Ferumoxytol (Feraheme) (see Ferumoxytol, [[Ferumoxytol]])
      • Risk of First-Exposure Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]]) [MEDLINE]: 24 per 100k patients
    • Iron Gluconate (Ferrous Gluconate, Fergon, Ferralet, Simron) (see Iron Gluconate, [[Iron Gluconate]])
      • Risk of First-Exposure Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]]) [MEDLINE]: 24 per 100k patients
    • Iron Sucrose (Venofer) (see Iron Sucrose, [[Iron Sucrose]])
      • Risk of First-Exposure Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]]) [MEDLINE]: 24 per 100k patients
      • Cumulative Risk of Anaphylaxis (Over 12 wk Period) [MEDLINE]: iron sucrose has lowest risk of all of the intravenous iron agents
  • Non-Steroidal Anti-Inflammatory Drugs (NSAID’s) (see Non-Steroidal Anti-Inflammatory Drug, [[Non-Steroidal Anti-Inflammatory Drug]])
    • Epidemiology: NSAID’s rarely cause allergic reactions via this mechanism
  • Platins
    • Carboplatin (see Carboplatin, [[Carboplatin]])
    • Cisplatin (see Cisplatin, [[Cisplatin]])
    • Oxaliplatin (Eloxatin, Oxaliplatin Medac) (see Oxaliplatin, [[Oxaliplatin]]): anaphylaxis occurs in 1.3% of cases
  • Progesterone (Progesterone-Associated Urticaria) (see Progesterone, [[Progesterone]])
  • Protamine (see Protamine, [[Protamine]])
  • Prothrombin Complex Concentrate-3 Factor (Profilnine SD) (see Prothrombin Complex Concentrate-3 Factor, [[Prothrombin Complex Concentrate-3 Factor]])
  • Sorafenib (Nexavar) (see Sorafenib, [[Sorafenib]])
  • Streptomycin (see Streptomycin, [[Streptomycin]])
  • Sulfobromophthalein
  • Taxanes (see Taxanes, [[Taxanes]])
    • Docetaxel (Taxotere) (see Docetaxel, [[Docetaxel]])
    • Paclitaxel (Taxol) (see Paclitaxel, [[Paclitaxel]])
  • Tiotropium + Olodaterol (Stiolto Respimat) (see Tiotropium + Olodaterol, [[Tiotropium + Olodaterol]])
  • Vaccines: may be due to either egg or gelatin components of the vaccine
  • Vitamin K (see Vitamin K, [[Vitamin K]])

Other

  • Aeroallergens: rarely involved in angioedema/anaphylaxis
    • Cat Dander
    • Grass Pollen
    • Horse Dander
  • Allergen Immunotherapy (see Allergen Immunotherapy, [[Allergen Immunotherapy]])
  • Blood Products
  • Fluorescein (see Fluorescein, [[Fluorescein]])
  • Hemodialysis (see Hemodialysis, [[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, [[Heparin]])
    • Physiology: mediated by coagulation system activation
  • Dextrans
    • Dextran (see Dextran, [[Dextran]])
    • Iron Dextran (Dexferrum, INFeD) (see Iron Dextran, [[Iron Dextran]])
      • Risk of First-Exposure Anaphylaxis (see Anaphylaxis, [[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 Anti-TNF Therapy, [[Anti-TNF Therapy]])
    • Physiology: IgG-mediated
  • Packed Red Blood Cells (PRBC) (see Packed Red Blood Cells, [[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, [[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, [[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, [[Neuromuscular Junction Antagonists]])
  • Opiates (see Opiates, [[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, [[Radiographic Contrast]])
  • Some Non-Steroidal Anti-Inflammatory Drugs (NSAID) (see Non-Steroidal Anti-Inflammatory Drug, [[Non-Steroidal Anti-Inflammatory Drug]])
  • Stinging Nettle (Urtica Dioica) (see Stinging Nettle, [[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, [[Vancomycin]])

Altered Arachidonic Acid Metabolism

Infection

General Comments

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

Viral

  • Hepatitis A (see Hepatitis A Virus, [[Hepatitis A Virus]]): urticaria may occur during the prodrome (preicteric) phase
  • Hepatitis B (see Hepatitis B Virus, [[Hepatitis B Virus]]): urticaria may occur during the prodrome (preicteric) phase
  • Hepatitis C (see Hepatitis C Vius, [[Hepatitis C Virus]]): urticaria may occur during the prodrome (preicteric) phase
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])

Bacterial

Parasitic

  • General Comments: acute self-limited urticaria is usually accompanied by prominent eosinophilia in these cases
  • Ancylostoma (see Ancylostoma, [[Ancylostoma]])
  • Anisakis Simplex (see Anisakiasis, [[Anisakiasis]]): associated with sushi ingestion
  • Blastomycosis (see Blastomycosis, [[Blastomycosis]])
  • Echinococcosis (see Echinococcosis, [[Echinococcosis]])
  • Fasciola (see Fasciola, [[Fasciola]])
  • Schistosomiasis (see Schistosomiasis, [[Schistosomiasis]]): due to Schistosoma Mansoni
  • Strongyloidiasis (see Strongyloidiasis, [[Strongyloidiasis]])
  • Toxocariasis (see Toxocariasis, [[Toxocariasis]])
  • Trichinellosis (see Trichinellosis, [[Trichinellosis]])

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, [[Celiac Disease]])
  • Henoch-Schonlein Purpura (see Henoch-Schonlein Purpura, [[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, [[Rheumatoid Arthritis]])
  • Sjogren’s Syndrome (see Sjogren’s Syndrome, [[Sjogrens Syndrome]])
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])

Other

  • Cytokine Release Syndrome (see Cytokine Release Syndrome, [[Cytokine Release Syndrome]])
  • Scombroid (see Scombroid, [[Scombroid]])
  • Serum Sickness (see Serum Sickness, [[Serum Sickness]])
  • Systemic Mastocytosis (see Systemic Mastocytosis, [[Systemic Mastocytosis]])
  • Hypocomplementemic Urticarial Vasculitis
    • Physiology: presence of anti-C1q IgG antibody
    • Clinical
      • Fever (see Fever, [[Fever]])
      • Urticarial Lesions (see Urticaria, [[Urticaria]]): may be painful, eccyhmotic, and purpuric (leaving ecchymoses after resolution)

Physiology

  • 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

Diagnosis

  • xxxx

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, [[Pruritus]])
      • Urticarial lesions are not usually painful: presence of pain suggests the alternative diagnosis of vasculitis
    • Association with Angioedema/Anaphylaxis (see Angioedema, [[Angioedema]] and Anaphylaxis, [[Anaphylaxis]]): urticaria may occur without associated angioedema/anaphylaxis

Treatment

Antihistamines (H1-Histamine Receptor Antagonists) (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]]):

  • xxxx

H2-Histamine Receptor Antagonists (see H2-Histamine Receptor Antagonists, [[H2-Histamine Receptor Antagonists]]):

  • xxx

Corticosteroids (see Corticosteroids, [[Corticosteroids]])

  • xxx

References

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