Urticaria
Definitions
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
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
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 AgeMost 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 preparationNorth 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 colorantCarmine : insect-derived red colorantEggs Legumes : beans, lentils, peanuts, peas, soybeans/soyMilk : cow milk, goat milk, sheep milkPeach Seafood : crustaceans, shellfish, finned fish, shrimpSesame Spices Tree Nuts : almonds, cashews, walnutsVegetable 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 sensitizationUrticaria 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 ): antibioticMechanism: allergic or non-allergic mechanism Benzoic Acid : used as preservativeMechanism: 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 tattoosMechanism: allergic mechanism Natural Rubber Latex (see Latex ): found in condoms, balloons, gloves, etcMechanism: allergic mechanism Salicylic Acid (see Salicylic Acid )Mechanism: allergic mechanism Short-Chain Alcohols Mechanism: allergic mechanism Drugs Abacavir (see Abacavir )Acetaminophen (Tylenol) (see Acetaminophen )Epidemiology: cases of anaphylaxis have been reported Angiotensin Converting Enzyme (ACE) Inhibitors (see Angiotensin Converting Enzyme Inhibitors )Acyclovir (Zovirax) (see Acyclovir )Alpha-1 Antitrypsin (Aralast, Glassia, Prolastin, Zemaira) (see Alpha-1 Antitrypsin ): occurs in 3.2-4.1% of casesAnti-Thymocyte Globulin (ATG) (see Anti-Thymocyte Globulin )Antivenin β-Lactam Antibiotics (see β-Lactam Antibiotics ): most common antibiotic-associated cause of urticariaCephalosporins (see Cephalosporins ) Imipenem (see Imipenem ): cross-reactivity in 50% of patients with allergy to penicillins Penicillins (see Penicillins ): occurs in 0.05% of cases, fatal in 5-10% of cases Demeclocycline (see Demeclocycline )Gemcitabine (Gemzar) (see Gemcitabine ): cases of laryngeal edema have been reportedHeparin (see Heparin ): anaphylaxis is a manifestation of heparin-induced thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia )Insulin (see Insulin )Intradermal Allergen Immunotherapy (see Allergen Immunotherapy )Iodinated Drugs/Contrast (see Radiographic Contrast )Local Anesthetics Monoclonal Antibodies/Biologics N-Acetylcysteine (Mucomyst, Acetadote, Fluimucil, Parvolex) (see N-Acetylcysteine )Epidemiology: associated with intravenous administration Physiology: histamine release has been implicated Non-Dextran Intravenous Iron Ferumoxytol (Feraheme) (see Ferumoxytol ) Iron Gluconate (Ferrous Gluconate, Fergon, Ferralet, Simron) (see Iron Gluconate ) Iron Sucrose (Venofer) (see Iron Sucrose )Risk of First-Exposure Anaphylaxis (see 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 Platins Progesterone (Progesterone-Associated Urticaria) (see Progesterone )Protamine (see Protamine )Prothrombin Complex Concentrate-3 Factor (Profilnine SD) (see Prothrombin Complex Concentrate-3 Factor )Sorafenib (Nexavar) (see Sorafenib )Streptomycin (see Streptomycin )Sulfobromophthalein Taxanes (see Taxanes )Tiotropium + Olodaterol (Stiolto Respimat) (see Tiotropium + Olodaterol )Vaccines : may be due to either egg or gelatin components of the vaccineVitamin K (see Vitamin K )Other Aeroallergens : rarely involved in angioedema/anaphylaxisCat Dander Grass Pollen Horse Dander Allergen Immunotherapy (see Allergen Immunotherapy )Blood Products Fluorescein (see Fluorescein )Hemodialysis (see Hemodialysis ): due to reaction to dialysis membranesCellulose Membranes: predominant type of membrane associated with anaphylaxisMembranes 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 activationDextrans 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) urticariaInfliximab (Remicade) (see Infliximab )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 perfumeMechanism: non-allergic mechanism Benzoic Acid : used as preservativeMechanism: allergic or non-allergic mechanism Formaldehyde (see Formaldehyde )Mechanism: allergic or non-allergic mechanism Sorbic Acid : used as preservativeMechanism: 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 activationFoods : these “pseudoallergens” may cause urticaria (or contact urticaria) via IgE-mediated or via non-immunologic mechanisms, especially in childrenNeuromuscular 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 AfricaPhysiology : histamine (and pain-causing mediators) contained in the plantVancomycin (see 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
Bacterial
Parasitic
Physical Stimuli
Aquagenic Urticaria Epidemiology : associated with water contact (regardless of temperature)Cholinergic Urticaria Epidemiology : associated with fever, hot bath or shower, exercisePhysiology : probably related to increase in body temperatureClinical : distinctly small 1-2 mm wheals surrounded by large area of erythemaCold-Induced Urticaria Epidemiology : acquired or hereditaryClinical : 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 populationPeak Prevalence: teens-20’s Usually lasts <5 years Clinical : linear wheal at site of a firm skin strokeHeat-Induced Urticaria Epidemiology : associated with local heat applicationExercise-Induced Urticaria Clinical : begins with erythema and pruritic urticaria -> progresses to angioedema of face/larynx/intestine/vascular collapsePressure-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 lightVibratory 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 degranulationAutoimmune Thyroid Disease Celiac Disease (see Celiac Disease )Henoch-Schonlein Purpura (see Henoch-Schonlein Purpura ): lesions may appear urticarial in early stagesIgM (and Sometimes IgG) Paraproteinemia : may be due to complement-mediated pathwaysRheumatoid Arthritis (RA) (see Rheumatoid Arthritis )Sjogren’s Syndrome (see Sjogren’s Syndrome )Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus )Other
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) Physiology
Activation of Superficial Dermis Mast Cells (and Basophils) : release of inflammatory mediators (histamine, etc)Histamine : causes pruritusVasodilatory Mediators : localized edema in superficial dermisAngioedema : represents the same pathologic process, except involving the mast cells deeper in the dermis and subcutaneous tissuesDiagnosis
Clinical Manifestations
General Comments
Onset Food-Associated Urticaria : onset is usually within 30 min of ingestionClassification of Urticaria Based on Chronicity Acute Urticaria : urticaria present for <6 wksChronic 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 pallorShape : round, oval, or serpiginousSize : vary from <1 cm to several cm in diameterDistribution : predominate in areas where clothing compresses the skin (under waistband, etc) or where skin rubs together (axilla)Number : wheals may occur individually or coalesceTime 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 nightUrticarial 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/anaphylaxisTreatment
References
Occupational contact urticaria. Clin Rev Allergy Immunol. 2006 Feb;30(1):39-46 [MEDLINE ]
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