Urticaria (Hives) (Clinical)

Overview

Definition^[1,12]

Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) 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 patches Patches Vitiligo (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^[1,4]

• Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) is the most common dermatologic disorder seen in the ED.
• About 15%–20% of the general population experience acute urticaria Acute Urticaria Urticaria (Hives) 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 Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives): 2%–3%.
• Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) can occur in any age group.
• Categories:
  • Acute urticaria Acute Urticaria Urticaria (Hives):
    • Duration < 6 weeks
    • Similar for men and women
  • Chronic urticaria Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives):
    • Signs and symptoms appearing 2–3 days per week
    • Duration > 6 weeks
    • More frequent in females (60%)
    • Chronic urticaria Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives) is more common between 40 and 60 years of age.

Etiology^[1,7,11,13]

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 (list is not exhaustive):

• 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 Non–IgE-mediated urticaria Urticaria (Hives) (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)

Pseudoallergy ( urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) without immune activation):

• Certain foods:
  • Tomatoes
  • Strawberries
• Drugs:
  • Opiates Opiates Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
  • Radiocontrast media
  • NSAIDs NSAIDS Primary vs Secondary Headaches

Physical urticarias:

• Occur as both acute and chronic forms
• Wheals develop within minutes after exposure to physical factors:
  • Stroking/scratching 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 ( dermographism Dermographism Dermatologic Examination)
  • Exercise 
  • Emotional upset 
  • Cold temperature
  • Heat Heat Inflammation
  • Vibration Vibration A continuing periodic change in displacement with respect to a fixed reference. Neurological Examination ( vibratory urticaria Vibratory Urticaria Urticaria (Hives)) 
  • Pressure ( pressure urticaria Pressure Urticaria Urticaria (Hives))
  • Water ( aquagenic urticaria Aquagenic Urticaria Urticaria (Hives))
  • Sunlight ( solar urticaria Solar Urticaria Urticaria (Hives))

Classification^{[1,8,10,12,13]} 

• Acute (< 6 weeks’ duration):
  • 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: men = women
  • Wheals usually evolve and dissipate in < 24 hours. 
  • In adults, urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) is usually spontaneous/ idiopathic Idiopathic Dermatomyositis. 
  • In newborns and infants, acute urticaria Acute Urticaria Urticaria (Hives) is usually related to exposure to a particular allergen/ trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation.
• Chronic (> 6 weeks’ continuous activity):
  • More common in females (60%)
  • More common between 40 and 60 years of age
  • Can be spontaneous or induced by provoking stimuli (e.g., physical factors)
  • Chronic spontaneous urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) is mainly idiopathic Idiopathic Dermatomyositis but may have an underlying autoimmune cause.

Pathophysiology

Pathogenesis^[9,14]

• Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) is mediated by cutaneous mast cells Cutaneous Mast Cells Urticaria (Hives).
• 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 Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) 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^[7,9,14]

• 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 (formed in a prior sensitizing event) 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 (acting predominantly on H₁ and H₂ 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):
  • Smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction → bronchospasm Bronchospasm Asthma Drugs 
  • Extravasation of blood into capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology → erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion 
  • Fluid shift Fluid Shift Translocation of body fluids from one compartment to another, such as from the vascular to the interstitial compartments. Fluid shifts are associated with profound changes in vascular permeability and water-electrolyte imbalance. The shift can also be from the lower body to the upper body as in conditions of weightlessness. Volume Depletion and Dehydration into interstitial space → 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 
  • Vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs → hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) 
• 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

Nonallergic urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)^[1,7,11,13]

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

Clinical Presentation

Clinical observations^[1,3,7]

• 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
  • 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
• 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 Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives).

Diagnosis

History and examination will usually lead to an accurate clinical classification.^[8]

History^[7,11,12]

• Wheals:
  • Morphology, color, shape, size, pattern 
  • Duration of onset and time to dissipation 
  • Timing in relation to medication and other exposures
  • Cutaneous findings are often transient; therefore, photographs Photographs Ultrasound (Sonography) and patient documentation Documentation Systematic organization, storage, retrieval, and dissemination of specialized information, especially of a scientific or technical nature. It often involves authenticating or validating information. Advance Directives may be helpful.
• Associated symptoms:
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) 
  • Systemic symptoms; headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, GI symptoms 
• Exposure:
  • Precipitating factors (see above) 
• Medication history 
• Comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus:
  • Autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency 
• Family and personal history:
  • Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) 
  • Atopy Atopy Atopic Dermatitis (Eczema)

Challenge tests^[6,12,15]

Challenge/provocation tests can be used to elicit symptoms of inducible physical urticaria Physical Urticaria Urticaria (Hives).

• 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; wheals develop 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 Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) 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.

Allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction testing^[7,8,11,12]

Useful if an underlying allergic cause of urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) is suspected.

• 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 testing:
  • Skin-prick tests 
  • Positive result = wheal Wheal Urticaria (Hives) 3 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma ≥ negative control (diluent)
• Allergen-specific IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions blood tests:
  • Originally measured using radioallergosorbent test (RAST) 
  • Replaced by more sensitive fluorescence immunoassays Fluorescence immunoassays The use of fluorescence spectrometry to obtain quantitative results for the fluorescent antibody technique. One advantage over the other methods (e.g., radioimmunoassay) is its extreme sensitivity, with a detection limit on the order of tenths of microgram/liter. Immunoassays 

Laboratory studies^{[6,7,12,13,15]}

Routine laboratory tests are not necessary for simple, acute urticaria Acute Urticaria Urticaria (Hives). However, they should be performed for cases of chronic urticaria Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives) and/or if systemic symptoms are present. Testing should be guided by the clinical presentation but may include:

• CBC with differential (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, autoinflammatory disease)
• Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess)
• C-reactive protein (CRP)
• Thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy and anti-thyroid peroxidase (TPO) 
• ANA ( solar urticaria Solar Urticaria Urticaria (Hives) or 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)
• Serum cryoglobulins (cold urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)):
  • Rarely present
  • More commonly associated with infection or hematologic disease^[12]
• Porphyrins ( solar urticaria Solar Urticaria Urticaria (Hives))
• Total IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
• 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):
  • Investigational studies for autoimmune urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)
  • Not routinely done, but may be considered for chronic spontaneous urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) that does not respond to treatment (if available)
• Punch biopsy Punch Biopsy Actinic Keratosis (rule out 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

Management for urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) may vary depending on practice location. The following information is based on US, UK, and European recommendations for urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) without 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 or 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 (these are discussed separately) in adults. See your local guidelines for additional information.

General measures

Supportive management:^{[7,8,10,12,15]} 

• About ⅔ of acute new-onset urticarias will resolve spontaneously and do not require medications.
• Avoid triggers.
• Apply topical cooling moisturizer or antipruritic agents to reduce itching (e.g., menthol-containing emollient)
• Use repeated controlled exposure to physical factors to induce tolerance Tolerance Pharmacokinetics and Pharmacodynamics.

Holistic care:^[8]

• For chronic urticaria Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives), consider using appropriate validated scoring systems to assess disease activity and impact:
  • Dermatology Life Quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement Index (DLQI)
  • Weekly Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) Activity Score 7 (UAS7)
  • 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 Activity Score (AAS)
  • Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) Control Test (UCT)
• Provide educational material or a patient information leaflet on urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)

Referral:^[7,8]

• Who to refer:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with chronic urticaria Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives) that fails to respond to maximum-dose 2nd-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 (taken regularly for 4 weeks)
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with suspected allergic cause
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with acute urticaria Acute Urticaria Urticaria (Hives) and persistent symptoms despite therapy (> 1‒2 weeks)
• Consultants may include:
  • Dermatology
  • Allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction and Immunology 

Medications

1st line:

• 2nd-generation H₁-antagonists:^{[7,8,10,12,15]}
  • Preferred 1st option for urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)
  • Options:
    • 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 (10 mg once daily)
    • Fexofenadine Fexofenadine Antihistamines (180 mg once daily)
    • 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 (10 mg once daily)
  • Dosing information:
    • Taken once daily in the morning (rather than on demand)
    • If symptoms not controlled → can increase dose after a few days
    • Can updose (increase dose above licensed dose) by up to 4-fold, provided it is well tolerated.
    • Once symptoms are controlled, attempt stepwise dose.
    • Dose titration speed is based on clinical judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment. 
  • Use in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care should be guided by the patient’s obstetrician.
• Oral 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:^[8,10,12]
  • Consider adding to antihistamine therapy for:
    • Severe acute urticaria Acute Urticaria Urticaria (Hives) (e.g., with 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)
    • Acute urticaria Acute Urticaria Urticaria (Hives) with persistent symptoms
    • Acute exacerbations of chronic urticaria Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives) 
  • For short-term use only (up to 10 days)
  • Options:
    • Prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants (20–50 mg/day)
    • 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 (0.5 mg/kg)
  • Note: 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 have not been found to be effective for urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives).

2nd line (most often used for chronic urticaria Chronic urticaria Wheals and/or angioedema presented with daily symptoms lasting for more than 6 weeks. It may be classified into chronic spontaneous and chronic inducible urticaria depending on whether a specific trigger can be linked to the development of vascular reaction. Urticaria (Hives)):

• 1st generation H₁-antagonists:^[7,15]
  • May be added to 1st-line therapy if symptoms are uncontrolled.
  • Options:
    • Hydroxyzine Hydroxyzine A histamine h1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. 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
    • Doxepin Doxepin A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine h(1)- and h(2)-receptors. Tricyclic Antidepressants
  • Do not updose this class of medications.
  • Sedating → often prescribed for use before bedtime
  • Increased sedation associated with concurrent use of:
    • Alcohol
    • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
    • Hypnotics
  • Associated with anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs effects
  • Once symptoms are controlled:
    • Continue dose for 4–6 weeks
    • Then gradually taper off
  • Not recommended by the National Institute for Health and Care Excellence (NICE) unless there is no alternative (due to CNS side effects)^[8]
• Leukotriene-receptor antagonists:^[7,8,12,15]
  • In the US and UK, added to antihistamine therapy for uncontrolled symptoms. 
  • European guidelines consider this class to be 3rd-line therapy.^[12]
  • Options:
    • Montelukast Montelukast Asthma Drugs
    • Zafirlukast Zafirlukast Asthma Drugs
• H₂-antagonists:^[8,12,15]
  • US: may be added to 1st-line therapy for uncontrolled symptoms
  • UK and Europe: considered an alternative therapy (insufficient evidence to recommend)
• 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:^[8,12,15]
  • UK and Europe: offered when symptoms are inadequately controlled by 1st-line therapy
  • US:
    • Considered an alternative agent
    • Added when above options do not fully control symptoms
  • Dosing:
    • 300 mg every 4 weeks 
    • If not responding, consider off-label updosing to 600 mg every 2 weeks
• Cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants:^[8,12,15]
  • UK and Europe:
    • Currently off-label for use in urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)
    • Recommended for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe disease refractory to 1st-line therapy and 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
  • US:
    • Considered an alternative therapy
    • Added when above options do not fully control symptoms
  • Better risk–benefit ratio compared with long-term steroid use
  • Avoid long-term use.

3rd line:^[8,12,15]

• Evidence for the use of other therapies is weak, and they should be considered only by specialists for use in the appropriate clinical context.
• 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
  • Colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs
• Immunosuppressive medications:
  • Methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy
  • Mycophenolate Mycophenolate Immunosuppressants mofetil
  • Cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants
  • Rituximab Rituximab A murine-derived monoclonal antibody and antineoplastic agent that binds specifically to the cd20 antigen and is used in the treatment of leukemia; lymphoma and rheumatoid arthritis. Immunosuppressants
• Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn (narrowband UVB)

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.
• 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: a rare disease presenting with an urticaria-like rash Rash Rocky Mountain Spotted Fever resulting from inflammatory injury to small vessels 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. Unlike urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives), wheals are painful, tend to last > 24 hours, and can cause bruising or postinflammatory 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 changes. Additionally, systemic involvement (e.g., renal, pulmonary musculoskeletal) is common. Inflammatory markers will be elevated, and the diagnosis is confirmed with skin biopsy Skin Biopsy Secondary Skin Lesions. Management varies depending on the severity, but it may include antiinflammatory medications and immunosuppressive drugs Immunosuppressive drugs Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. Organ Transplantation.
• 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.