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Urticaria (Hives)

Urticaria is raised, well-circumscribed areas (wheals) of edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema ( swelling Swelling Inflammation) and erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion ( redness Redness Inflammation) involving the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions and epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions with associated pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell Mast cell Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Angioedema degranulation resulting in the release of histamine and other vasoactive substances from mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation and basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions resulting in extravasation of plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products into the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions. Urticaria can be caused by myriad inciting events, such as allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions, infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, exposure, and many others. The diagnosis is made clinically. H1-antagonists are used as 1st-line treatment.

Last updated: May 17, 2024

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Urticaria is a vascular reaction of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions noted as a transient appearance of slightly elevated plaques (wheals) that are redder or paler than adjacent skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and often accompanied by significant itching.

Epidemiology

  • Urticaria is the most common dermatologic disorder seen in the ED.
  • About 15%–20% of the general population experience acute urticaria during their lifetime.
  • Lifetime incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of chronic urticaria: 2%–3%.
  • Urticaria can occur in any age group.
  • Categories:
    • Acute urticaria:
      • Duration < 6 weeks
      • Similar for men and women
    • Chronic urticaria:
      • Signs and symptoms appearing 2–3 days per week
      • Duration > 6 weeks
      • More frequent in females (60%)
      • Chronic urticaria is more common between 40 and 60 years of age.

Etiology

IgE-mediated urticarias (type I hypersensitivity, release of histamine from mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation) are often due to exposure to certain allergens:

  • Foods: fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing, shellfish, eggs, tree nuts, peanuts, milk, soy 
  • Drugs: penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins, cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
  • Insect venom: bee stings
  • Inhalants: dust mites Mites Any arthropod of the subclass acari except the ticks. They are minute animals related to the spiders, usually having transparent or semitransparent bodies. They may be parasitic on humans and domestic animals, producing various irritations of the skin (mite infestations). Many mite species are important to human and veterinary medicine as both parasite and vector. Mites also infest plants. Scabies, pollens, molds, animal danders
  • Blood products
  • Latex
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions pressure, cold, or heat Heat Inflammation
  • Emotional stress
  • Exercise
  • Occurs within minutes to 2 hours after exposure

Non–IgE-mediated urticaria (histamine release secondary to):

  • Narcotics
  • Muscle relaxants:
    • Atracurium Atracurium A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents. Neuromuscular Blockers
    • Vecuronium Vecuronium Monoquaternary homolog of pancuronium. A non-depolarizing neuromuscular blocking agent with shorter duration of action than pancuronium. Its lack of significant cardiovascular effects and lack of dependence on good kidney function for elimination as well as its short duration of action and easy reversibility provide advantages over, or alternatives to, other established neuromuscular blocking agents. Neuromuscular Blockers
    • Succinylcholine Succinylcholine A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for. Cholinomimetic Drugs
    • Curare
  • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
  • Radiocontrast media
  • Pseudoallergens (certain foods):
    • Tomatoes
    • Strawberries
  • NSAIDs NSAIDS Primary vs Secondary Headaches
  • Autoimmune complex–mediated reactions (type III hypersensitivity)

Physical urticarias:

  • Occur as both acute and chronic forms
  • Wheals develop within minutes after exposure to physical factors:
    • Cold temperature
    • Heat Heat Inflammation
    • Vibration Vibration A continuing periodic change in displacement with respect to a fixed reference. Neurological Examination (vibratory urticaria) 
    • Pressure (pressure urticaria)
    • Water (aquagenic urticaria)
    • Sunlight (solar urticaria)

Pathophysiology

Pathogenesis

  • Urticaria is mediated by cutaneous mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation.
  • These mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation release multiple mediators (histamine and other substances) in the superficial dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions.
  • When mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation release vasoactive mediators in deeper dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions and subcutaneous tissues, angioedema Angioedema Angioedema is a localized, self-limited (but potentially life-threatening), nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators triggering significant vasodilation and increased capillary permeability. Angioedema results.
  • Angioedema Angioedema Angioedema is a localized, self-limited (but potentially life-threatening), nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators triggering significant vasodilation and increased capillary permeability. Angioedema that accompanies urticaria usually affects face, lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, extremities, and genitalia.

Allergic IgE-mediated urticarias

  • Generally related to an exogenous allergen ( type I hypersensitivity reaction Type I hypersensitivity reaction Type I hypersensitivity reaction is an abnormal immune response triggered by exposure to specific antigens known as allergens. In this type of hypersensitivity reaction, the presentation of the antigen to the T-helper cells (Th cells) initiates a cascade of immunologic events leading to the production of antigen-specific IgE antibodies. Type I Hypersensitivity Reaction) or acute infection
  • Usually acute onset:
    • Immediate development (within minutes) of edematous, erythematous wheal-and-flare lesion
    • Evolve and dissipate in < 24 hours
  • Allergens bind BIND Hyperbilirubinemia of the Newborn to IgE antibodies IgE antibodies An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Type I Hypersensitivity Reaction on mast Fc Fc Crystallizable fragments composed of the carboxy-terminal halves of both immunoglobulin heavy chains linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (complement fixation, binding to the cell membrane via fc receptors, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme papain. Immunoglobulins: Types and Functions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors → release of vasoactive substances with extravasation of plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products into the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions
  • Histamine:
    • Most important vasoactive substance
    • Stimulation of H1-receptors:
      •  Endothelial and smooth muscle sites
      •  Increased capillary permeability
    • Stimulation of H2-receptors:
      •  Dilation of arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology and venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology
      •  Extravasation of fluid in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions
  • Other vasoactive substances:
    • Bradykinin Bradykinin A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. Hereditary Angioedema (C1 Esterase Inhibitor Deficiency)
    • Leukotriene Leukotriene Asthma Drugs C4
    • Prostaglandin D2 Prostaglandin D2 The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects. Eicosanoids
Mechanism of type 1 hypersensitivity reaction involved in ige mediated urticarias

Mechanism of type 1 hypersensitivity reaction involved in IgE-mediated mast cell degranulation

Image by Lecturio.

Nonallergic urticaria

  • Non–IgE-mediated histamine release: secondary to exposure to specific substances
  • More likely to be associated with autoimmune disorders

Clinical Presentation

Onset

  • Acute:
    • Develops within minutes to 2 hours after exposure
    • Edematous and erythematous wheal formation:
      • Central pallor with surrounding red flare
      • Single or multiple lesions
      • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables size and shape
      • Typically blanch with pressure
    • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) (severe) is common.
    • Duration < 6 weeks
  • Chronic:
    • Duration > 6 weeks
    • 2 or more episodes per week
    • Appearance is identical to that of the acute form.
    • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), sometimes severe, is common.
    • Many potential triggers
    • Idiopathic Idiopathic Dermatomyositis etiology common

Clinical observations

  • Wheals classically exhibit:
    • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Well-demarcated edges
    • Central pallor
    • Surrounding red flare
    • Can be localized or generalized
  • Wheals dissipate rapidly (< 24 hours).
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema): most common associated symptom
  • Angioedema Angioedema Angioedema is a localized, self-limited (but potentially life-threatening), nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators triggering significant vasodilation and increased capillary permeability. Angioedema is simultaneously present in half the patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with urticaria.

Diagnosis

History

  • Wheals:
    • Rapid onset
    • Dissipate rapidly (< 24 hours)
    • Not normally painful
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
  • Duration:
    • Acute: < 6 weeks
    • Chronic:
      • > 6 weeks
      • Several episodes per week
  • History of exposure to triggering agents:
    • Foods
    • Drugs
    • Insect bites/stings
    • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (upper respiratory)
    • Blood products
    • Latex
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions pressure
    • Emotional stress
    • Exercise
    • Radiocontrast media
  • Comorbid autoimmune disease
  • Family history Family History Adult Health Maintenance:
    • Autoimmune disease
    • Urticaria

Physical exam

  • Wheals may or may not be present at the time of the exam.
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions wheal appearance:
    • Central pallor 
    • Surrounding red flare
    • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Well-demarcated edges
    • Single or multiple lesions
    • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables size and shape
    • Wheal blanches with pressure.

Challenge tests

Challenge tests can be used to elicit symptoms of physical urticaria.

  • Pressure:
    • Stroke skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions with blunt object; development of wheals within minutes ( dermographism Dermographism Dermatologic Examination)
  • Delayed pressure:
    • Application of sustained pressure with hanging weight or calibrated dermographometer at 100 g/mm²
    • Development of urticaria within 24 hours
  • Core temperature:
    • Increase body temperature Body Temperature The measure of the level of heat of a human or animal. Heatstroke by 1.0°C.
    • Rapid development of wheals
  • Surface temperature:
    • Cold: Apply ice bag for up to 20 minutes.
    • Heat Heat Inflammation: Apply heated object for 2–5 minutes.
  • Solar: development of wheals within minutes after sunlight exposure
  • Water: Apply water to skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions.
  • Vibration Vibration A continuing periodic change in displacement with respect to a fixed reference. Neurological Examination: Apply a laboratory vortex to the forearm Forearm The forearm is the region of the upper limb between the elbow and the wrist. The term “forearm” is used in anatomy to distinguish this area from the arm, a term that is commonly used to describe the entire upper limb. The forearm consists of 2 long bones (the radius and the ulna), the interosseous membrane, and multiple arteries, nerves, and muscles. Forearm: Anatomy for 1–5 minutes.

Laboratory studies

  • More commonly done with chronic urticaria
  • Usually done to evaluate for the underlying disease process:
    • CBC with differential
    • ESR ESR Soft Tissue Abscess
    • CRP
    • Thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy 
    • ANAs
    • Serum cryoglobulins (cold urticaria)
    • Allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction evaluation
    • Anti-IgE, anti-FcεRI antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions, and autologous serum skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions test (ASST) for autoimmune urticaria
    • Punch biopsy Punch Biopsy Actinic Keratosis (suspected urticarial vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus)

Management

Supportive/prophylactic measures

  • About ⅔ of acute new-onset urticarias will resolve spontaneously and do not require medications.
  • Avoidance of triggers
  • Application of topical cooling moisturizing to reduce itching
  • Repeated controlled exposure to physical factors to induce tolerance Tolerance Pharmacokinetics and Pharmacodynamics

Medications

  • H1-antagonists:
    • Nonsedating:
      • 1st-line treatment
      • Loratadine Loratadine A second-generation histamine h1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines (histamine h1 antagonists) it lacks central nervous system depressing effects such as drowsiness. Antihistamines
    • Moderately sedating:
      • 2nd-line treatment: cetirizine Cetirizine A potent second-generation histamine h1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. Antihistamines
    • Sedating:
      • 1st-generation antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines
      • Diphenhydramine Diphenhydramine A histamine h1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. Antihistamines
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids:
    • Prominent angioedema Angioedema Angioedema is a localized, self-limited (but potentially life-threatening), nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators triggering significant vasodilation and increased capillary permeability. Angioedema or persistent symptoms despite antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines
    • Prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants
    • Prednisolone Prednisolone A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. Immunosuppressants
  • Leukotriene-receptor antagonists:
  • Omalizumab Omalizumab An anti-ige, recombinant, humanized monoclonal antibody which specifically binds to the c epsilon3 domain of immunoglobulin e, the site of high-affinity ige receptor binding. It inhibits the binding of ige to mast cells and basophils to reduce the severity of the allergic response and is used in the management of persistent allergic asthma. Asthma Drugs: monoclonal antibody against IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
  • Immunosuppressant drugs:
  • Antiinflammatory agents:
    • Dapsone Dapsone A sulfone active against a wide range of bacteria but mainly employed for its actions against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. Antimycobacterial Drugs
    • Sulfasalazine Sulfasalazine A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid released in the colon. Sulfonamides and Trimethoprim
    • Hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants

Association with anaphylaxis Anaphylaxis An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. Type I Hypersensitivity Reaction

If associated with anaphylaxis Anaphylaxis An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. Type I Hypersensitivity Reaction:

Differential Diagnosis

  • Atopic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema) ( eczema Eczema Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema)): cutaneous disorder with intensely pruritic erythematous patches Patches Vitiligo with papules and some scaling with a more prolonged course: Atopic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema) is often associated with elevated serum levels of IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions and a personal or family history Family History Adult Health Maintenance of atopy Atopy Atopic Dermatitis (Eczema). Most frequently appears in children. Treatment includes avoidance of triggers and use of emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea and moisturizers, topical antiinflammatory agents, antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines, and topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors.
  • Contact dermatitis Contact dermatitis A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Male Genitourinary Examination: an erythematous, papular dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema), often with areas of vesiculation: Occurs due to direct skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions exposure to an offending irritant with a direct cytotoxic Cytotoxic Parvovirus B19 effect. Diagnosis is made by history and physical exam findings. Treatment includes avoidance of offending irritants and adoption of protective measures, as well as the use of emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea and moisturizers. Topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors are the 1st-line intervention.
  • Bullous pemphigoid Bullous pemphigoid Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In bullous pemphigoid, autoantibodies attack the hemidesmosomes, which connect epidermal keratinocytes to the basement membrane. This attack results in large, tense subepidermal blisters. Bullous Pemphigoid and Pemphigus Vulgaris: a blistering autoimmune disease: Autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques attack the hemidesmosomes, which connect epidermal keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions to the basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN). This results in large, tense subepidermal blisters. Diagnosis is made with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma and immunofluorescent staining to identify and localize the antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions. Management involves immunosuppression with corticosteroids Corticosteroids Chorioretinitis and other steroid-sparing immunomodulatory agents.
  • Viral exanthems: generally not pruritic and usually consist of erythematous maculopapular Maculopapular Dermatologic Examination eruptions that persist for days: Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever is often present. The macules are relatively fixed, with new lesions appearing as older lesions resolve. More common in children. Diagnosed clinically. Treatment is symptomatic.
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme minor: a syndrome characterized by erythematous, iris-shaped macules and vesiculobullous lesions with a target appearance: these lesions may be painful or pruritic and have a symmetrical Symmetrical Dermatologic Examination distribution on the extensor surfaces of the extremities, especially on the palms and soles, and last for days, potentially with accompanying fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and malaise Malaise Tick-borne Encephalitis Virus. The clinical course is usually self-limited without significant sequelae. Diagnosis is made clinically, and skin biopsy Skin Biopsy Secondary Skin Lesions is sometimes required. Treatment is usually symptomatic.

References

  1. Asero R. (2020). New-onset urticaria. In Saini S, Callen J. (Eds.), UpToDate. Retrieved March 14, 2021, from https://www.uptodate.com/contents/new-onset-urticaria
  2. Khan D. (2020). Chronic spontaneous urticaria: standard management and patient education. In Saini S, Callen J. (Eds.), UpToDate. Retrieved March 14, 2021, from https://www.uptodate.com/contents/chronic-spontaneous-urticaria-standard-management-and-patient-education
  3. Saini S. (2021).  Chronic spontaneous urticaria: clinical manifestations, diagnosis, pathogenesis, and natural history.  In Callen J. (Ed.), UpToDate.  Retrieved March 14, 2021, from https://www.uptodate.com/contents/chronic-spontaneous-urticaria-clinical-manifestations-diagnosis-pathogenesis-and-natural-history
  4. Wong H. (2020). Urticaria. In Elston D. (Ed.), Medscape. Retrieved March 14, 2021, from https://reference.medscape.com/article/762917-overview
  5. Schwartz R. (2021). Cholinergic urticaria. In Elston D. (Ed.), Medscape.  Retrieved March 14, 2021, from https://reference.medscape.com/article/1049978-overview
  6. Diakow, M., (2018). Chronic Urticaria. In James, W. (Ed.), Medscape.  Retrieved March 14, 2021, from https://reference.medscape.com/article/1050052-overview
  7. Frigas E, Park MA. (2009). Acute urticaria and angioedema: diagnostic and treatment considerations. Am J Clin Dermatol 10(4):239–50.

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