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]])
- 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
- 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
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]]):
H2-Histamine Receptor Antagonists (see H2-Histamine Receptor Antagonists, [[H2-Histamine Receptor Antagonists]]):
Corticosteroids (see Corticosteroids, [[Corticosteroids]])
References
- Occupational contact urticaria. Clin Rev Allergy Immunol. 2006 Feb;30(1):39-46 [MEDLINE]