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Urticarie

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New-onset urticaria

Author:
Riccardo Asero, MD
Section Editors:
Sarbjit Saini, MD
Jeffrey Callen, MD, FACP, FAAD
Deputy Editor:
Anna M Feldweg, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2019. | This topic last updated: Oct 04, 2019.
INTRODUCTIONUrticaria, or hives (sometimes referred to as welts or wheals), is a common
disorder, with a prevalence of approximately 20 percent in the general population [1]. A typical
urticarial lesion is an intensely pruritic, erythematous plaque (picture 1). Urticaria is sometimes
accompanied by angioedema, which is swelling deeper in the skin. A presumptive trigger, such
as a drug, food ingestion, insect sting, or infection, may be identifiable in patients with new-
onset urticaria, although no specific cause is found in many cases, particularly when the
condition persists for weeks or months. (See 'Etiologies' below.)

The epidemiology, clinical manifestations, etiologies, diagnosis, and management of new-onset


urticaria will be reviewed here. Chronic urticaria and isolated angioedema are discussed
separately. (See "Chronic spontaneous urticaria: Clinical manifestations, diagnosis,
pathogenesis, and natural history" and "Chronic spontaneous urticaria: Standard management
and patient education" and "An overview of angioedema: Clinical features, diagnosis, and
management".)

CATEGORIZATION OF URTICARIAUrticaria (with or without angioedema) is commonly


categorized by its chronicity:

Acute urticaria — Urticaria is considered acute when it has been present for less than six
weeks.

Chronic urticaria — Urticaria is considered chronic when it is recurrent, with signs and


symptoms recurring most days of the week, for six weeks or longer.

The period of six weeks is somewhat arbitrary and simply represents a timeframe in which new
cases of urticaria usually resolve. More than two-thirds of cases of new-onset urticaria prove to
be self-limited (acute) [2]. The lesions of acute and chronic urticaria are identical in appearance,
so when the problem first develops, it is not possible to differentiate the two disorders [3].

EPIDEMIOLOGYUrticaria affects up to 20 percent of the population at some point in their


lives and occurs across the age spectrum [1].
CLINICAL MANIFESTATIONSUrticarial lesions are circumscribed, raised, erythematous
plaques, often with central pallor (picture 2). Lesions may be round, oval, or serpiginous in
shape and vary in size from less than 1 centimeter to several centimeters in diameter. They are
intensely itchy. Pruritus may disrupt work, school, or sleep. Symptoms often seem most severe
at night.

Individual lesions are transient, usually appearing and enlarging over the course of minutes to
hours and then disappearing within 24 hours. Lesions may coalesce as they enlarge. Urticarial
lesions are not normally painful and resolve without leaving residual ecchymotic marks on the
skin, unless there is trauma from scratching. If lesions are long-lasting, painful, or leave residual
bruising, the diagnosis of urticarial vasculitis should be considered. (See 'Differential
diagnosis' below.)

Any area of the body may be affected, although areas in which clothing compresses the skin
(eg, under waistbands) or skin rubs together (axillae) are sometimes affected more dramatically.
Typically, compressed areas become more severely affected once the restricting clothing has
been removed.

Angioedema, when associated with urticaria, usually affects the face and lips, extremities,
and/or genitals. Angioedema without urticaria should prompt consideration of other
angioedema disorders, such as drug-induced angioedema (eg, angiotensin-converting enzyme
[ACE] inhibitors), idiopathic angioedema, and hereditary and acquired C1 inhibitor deficiency.
(See "ACE inhibitor-induced angioedema" and "An overview of angioedema: Pathogenesis and
causes".)

PATHOPHYSIOLOGYUrticaria is mediated by cutaneous mast cells in the superficial


dermis. Basophils have also been identified in lesional biopsies [4]. Mast cells and basophils
release multiple mediators upon activation including histamine (which causes itching) and
vasodilatory mediators (which cause localized swelling in the uppermost layers of the skin). The
same process gives rise to angioedema when mast cells deeper in the dermis and
subcutaneous tissues are activated. (See "Mast cells: Development, identification, and
physiologic roles".)
ETIOLOGIESThe potential causes of new-onset urticaria are numerous, although no specific
etiology can be identified in many patients. Acute urticaria is more likely to have an identifiable
etiology compared with chronic urticaria. The different etiologies activate mast cells through
various mechanisms.

Common causes — Common causes of new-onset urticaria include infections; allergic


reactions to medications, foods, or insect stings and bites; reactions to medications that cause
nonallergic mast cell activation (eg, narcotics); and ingestion of nonsteroidal anti-inflammatory
drugs (NSAIDs) (table 1).

Infections — Viral, bacterial, and parasitic infections are associated with new-onset urticaria.

●Viral and bacterial infections – Acute urticaria may develop during or following a viral or
bacterial infection, particularly in children. Infections are associated with over 80 percent of
cases of acute urticaria in some pediatric series [2,5-8]. Immune activation, involving
immune complex formation and/or complement activation, is a proposed mechanism,
although the exact pathogenesis is unclear.
•In one study, common viral illnesses and bacterial infections (eg, urinary tract
infections) were the leading identifiable trigger for acute urticaria in 57 children
between the ages of one and three years who presented to an emergency department
[5]. Many of these children had also received antibiotics, so it was not clear in these
patients if the infection, the drug, or the combination had triggered urticaria.
•In another study, 88 children presenting to an emergency department with delayed
cutaneous reactions while taking beta-lactam antibiotics were evaluated. Of these, 47
of 88 had urticarial eruptions. All were tested for common childhood viral infections
and then later evaluated for drug allergy with testing followed by drug challenge
(regardless of test results) [9]. Two-thirds had one or more positive viral studies,
demonstrating infections with picornavirus (most common), coronavirus, respiratory
syncytial virus, and several others. When the children were later challenged with the
culprit antibiotic, only 4 had recurrent urticaria. Thus, urticaria was related to the viral
infection or the combination of the viral infection and the antibiotic in most, and only 4
of 88 had a drug allergy. (See "Penicillin allergy: Delayed hypersensitivity reactions",
section on 'Delayed urticarial eruptions'.)
•Acute urticaria, refractory to antihistamines but responsive to azithromycin, has been
associated with documented Mycoplasma pneumoniae infection in children [10,11].
•Acute urticaria can occur in the prodromic, preicteric phase of hepatitis A or B
infection and less commonly with hepatitis C [12]. Urticaria may be an initial
manifestation of human immunodeficiency virus (HIV) infection [13]. (See "Acute and
early HIV infection: Pathogenesis and epidemiology".)
●Parasitic infections – Parasitic infections generally cause acute, self-limited urticaria in
association with prominent eosinophilia [14].
•Infections
with Ancylostoma, Strongyloides, Filaria, Echinococcus, Trichinella, Toxocara, Fasciol
a, Schistosoma mansoni, and Blastocystis hominis have all been associated with
urticaria. Stool examination is probably only indicated in travelers to endemic areas
and in patients with peripheral blood eosinophilia. (See "Approach to the patient with
unexplained eosinophilia".)
•Ingestion of fish contaminated with the parasite Anisakis simplex can also cause
urticaria. Anisakis can be transmitted through the ingestion of sushi [15].
(See "Seafood allergies: Fish and shellfish", section on 'Anisakis'.)

IgE-mediated allergic reactions — Immunoglobulin E (IgE)-mediated, type I immediate


allergic reactions often involve urticaria. Urticaria that is caused by an allergic reaction usually
occurs within minutes to two hours of exposure to the culprit allergen. Causes include
medications, foods and food additives, insect stings and bites, latex, and blood products.

Allergic reactions may be limited to the skin or part of a systemic allergic reaction (eg,
anaphylaxis) (table 2 and table 3). Generalized urticaria or angioedema following exposure to a
potential allergen should be interpreted as a systemic reaction with an attendant risk of
anaphylaxis upon subsequent exposure, and patients should be advised to avoid the potential
cause until further evaluated. (See 'Referral' below.)

●Medications – The antibiotics most frequently implicated in causing IgE-mediated


urticaria include beta-lactams (penicillins and cephalosporins), although antibiotics from
virtually all classes have been reported (picture 3). (See "Penicillin allergy: Immediate
reactions".)
●Stinging and biting insects – Stinging insects that can cause true urticarial lesions as
part of an allergic reaction include Hymenoptera (eg, bees, wasps, hornets, and imported
fire ants) and Triatoma (eg, kissing bugs).
Bedbugs, fleas, and mites can cause papular urticaria, usually on the lower extremities.
The lesions of papular urticaria resolve over the course of weeks. (See "Bee, yellow jacket,
wasp, and other Hymenoptera stings: Reaction types and acute
management" and "Reactions to bites from kissing bugs (primarily genus
Triatoma)" and "Bedbugs".)
●Latex – Occupational, recreational, dental, or surgical exposure to latex may cause
urticaria, angioedema, asthma, or anaphylaxis in susceptible individuals [16]. Everyday
scenarios in which patients may be exposed to significant amounts of latex include inflation
of balloons and use of latex gloves. Penile and vulvar/vaginal urticaria and angioedema are
seen upon exposure to latex condoms, with vulvar/vaginal symptoms resembling acute
vaginitis. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis".)
●Foods and certain food additives – Allergic reactions to foods can cause urticaria,
typically within 30 minutes of ingestion. Milk, eggs, peanuts, tree nuts, soy, and wheat are
the most common foods to cause generalized urticaria in children. In adults, fish, shellfish,
tree nuts, and peanuts are most often implicated [17]. In Mediterranean areas, the most
frequent cause of food-induced urticaria is the peach, due to sensitization to lipid transfer
protein [18]. (See "Clinical manifestations of food allergy: An overview".)
Synthetic additives in commercially prepared foods are believed to be a relatively rare
cause of urticarial reactions. In contrast, certain natural compounds, such as the yellow
food dye annatto and the red dye carmine red, have been well-documented causes of
urticaria and anaphylaxis. Adverse reactions to food additives are discussed in detail
elsewhere. (See "Allergic and asthmatic reactions to food additives".)
●Contact with allergens – Physical contact with a number of agents may result in
urticaria, including plant products and resins, raw fruits and vegetables, or raw seafood.
People employed in food processing can develop contact urticaria from various exposures
[19]. Children sometimes develop urticaria upon contact with animal saliva, if allergic to
those allergens. In contrast, detergents, soaps, and lotions are more likely to cause contact
dermatitis than urticaria. (See "Clinical features and diagnosis of allergic contact
dermatitis" and "Contact dermatitis in children".)
●Urticarial transfusion reactions – Acute urticaria in the setting of transfusion may arise
from several mechanisms, including IgE-mediated allergic reactions, complement-mediated
reactions, and other immunologic events. These reactions are discussed elsewhere.
(See "Immunologic transfusion reactions".)

Direct mast cell activation — Certain drugs, foods, and plants can cause urticaria due to mast
cell degranulation through a non-IgE-mediated mechanism. The most frequently implicated are
narcotics, muscle relaxants, vancomycin, and radiocontrast media. Some berries and nettle
plants are examples of plants and plant foods that cause direct mast cell activation.

●Narcotics – Opiate analgesics, such as morphine and codeine, cause direct mast cell


activation. Dextromethorphan, an opiate derivative ingredient in cough suppressant syrups,
can also cause urticaria [20].
●Muscle relaxants – Anesthetic muscle relaxants,
including atracurium, vecuronium, succinylcholine, and curare, may cause urticaria. Muscle
relaxants can also cause IgE-mediated anaphylaxis. Allergic reactions to these
medications are reviewed in greater detail elsewhere. (See "Perioperative anaphylaxis:
Clinical manifestations, etiology, and management".)
●Vancomycin – The "red man" syndrome is seen after rapid vancomycin infusion and
presents as diffuse erythema or flushing, sometimes with accompanying urticaria. The
concomitant use of opiates and vancomycin may increase the likelihood of a reaction.
(See "Vancomycin hypersensitivity".)
●Radiocontrast medium – Radiocontrast agents are associated with urticaria and
angioedema. (See "Diagnosis and treatment of an acute reaction to a radiologic contrast
agent".)
●Certain foods – Tomatoes, strawberries, and a small number of other foods can cause
generalized urticaria or contact urticaria through nonimmunologic mechanisms, particularly
in young children [6]. These foods are sometimes referred to as "pseudoallergens." IgE-
mediated allergies to these foods are also possible.
●Stinging nettle – The nettle plant (Urtica dioica), after which the disorder "urticaria" was
named, is a common weed found in Europe, North and South America, and parts of Africa
that causes hives and a stinging sensation immediately following contact with the skin [21-
23]. These symptoms may be due to histamine in the nettle plant itself, in addition to
mediators that cause pain [24].

Nonsteroidal anti-inflammatory drugs — Nonsteroidal anti-inflammatory drugs (NSAIDs),


such as aspirin, ibuprofen, naproxen sodium, and others, can trigger urticaria and/or
angioedema by two distinct mechanisms:

●Pseudoallergic/pharmacologic – NSAIDs cause urticaria in some individuals,


presumably due to underlying abnormalities in arachidonic acid metabolism. This form of
NSAID reaction is called a pseudoallergic reaction because the mechanism is
nonimmunologic. NSAID pseudoallergy can be seen with any agent (eg, aspirin, ibuprofen)
that inhibits the cyclooxygenase 1 (COX-1) enzyme and rarely occurs with agents that are
very weak inhibitors of COX-1. Patients with pseudoallergy usually
tolerate acetaminophen and the selective cyclooxygenase 2 (COX-2) inhibitors.
Pseudoallergic reactions attributed to NSAIDs are discussed in more detail separately.
(See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions", section on
'Pseudoallergic reactions'.)
●Allergic – A specific NSAID can also cause acute urticaria in patients who are allergic to
that one agent. These reactions are presumed to represent true, immunologic allergy.
(See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions", section on
'Allergic reactions (presumed IgE-mediated)'.)

Both pharmacologic and allergic reactions to NSAIDs can be severe. However, the
management differs. (See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions",
section on 'Management'.)

Scombroid syndrome — The ingestion of poorly preserved fish (tuna in most cases, but
sometimes mackerel or sardines) containing large amounts of histamine may cause acute
symptoms that resemble those of an IgE-mediated allergic reaction characterized by flushing,
urticaria, diarrhea, headache, and sometimes bronchospasm. (See "Scombroid (histamine)
poisoning".)

Uncommon causes — Uncommon causes of new-onset urticaria include various physical


factors, serum sickness, and hormone-associated disorders.
●Physical stimuli – Physical urticarial syndromes are forms of chronic urticaria that are
triggered by specific physical factors, such as cold exposure, sudden changes in body
temperature, pressure or vibration against the skin, exercise, exposure to sunlight, or other
stimuli. These disorders are reviewed separately. (See "Physical (inducible) forms of
urticaria" and "Cold urticaria".)
●Serum sickness – Serum sickness and serum sickness-like reactions to exogenous
proteins or medications may present with an urticarial rash accompanied by fever,
polyarthralgias, polyarthritis, and/or lymphadenopathy. This typically develops within one to
three weeks after administration of the causative agent. Proteinuria, edema, and abdominal
pain may also be present. These reactions are discussed elsewhere. (See "Serum
sickness and serum sickness-like reactions".)
●Progesterone-associated urticaria – There are rare reports of progesterone-containing
oral contraceptives, hormone replacement therapy, or
endogenous progesterone associated with cyclic urticaria [25,26]. The disorder is
sometimes called autoimmune progesterone dermatitis [27-30]. Lesions usually appear
during the second half of the menstrual cycle and resolve with menstruation.
SYSTEMIC DISORDERS THAT MAY INCLUDE URTICARIAUncommonly, urticaria
or urticaria-like lesions may be an early feature of a systemic disorder, including the following:
●Urticarial vasculitis – Urticarial vasculitis should be suspected when individual lesions
are painful, are long-lasting (longer than 24 to 36 hours), appear purpuric or ecchymotic, or
leave residual ecchymosis or hyperpigmentation upon resolution (in the absence of trauma
from scratching) (picture 4 and picture 5 and picture 6). Vasculitis should also be
suspected in patients with urticaria accompanied by fever, arthralgias, arthritis, weight
changes, bone pain, or lymphadenopathy. Urticarial vasculitis may be a cutaneous or
systemic disease, and it may occur in the setting of another rheumatologic disorder or
rarely, a malignancy. (See "Urticarial vasculitis" and "Cutaneous manifestations of internal
malignancy".)
●Mastocytosis – Mastocytosis and mast cell disorders are rare conditions in which
patients present with apparent allergic reactions and anaphylaxis to a variety of triggers.
Characteristic skin findings are helpful in diagnosis. These disorders are reviewed
separately. (See "Mastocytosis (cutaneous and systemic): Epidemiology, pathogenesis,
and clinical manifestations".)
●Systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, celiac
disease, autoimmune thyroid disease, and other autoimmune diseases – Urticaria
may be a presenting manifestation or occur sporadically over time in patients with
autoimmune conditions [31]. The etiology of this remains unclear but may be due to direct
mast cell activation via complement receptors or due to the generation of autoantibodies
that may result in anaphylactoid degranulation. Screening for these disorders in the setting
of an acute episode of urticaria is not indicated, unless there are other preceding
symptoms that suggest that one of these disorders may be present.
●Cutaneous small vessel vasculitis – Some forms of cutaneous small vessel vasculitis
can appear urticarial during early stages. Urticarial lesions that are persistent in a single
location for >24 hours, have bruising, are painful, or are accompanied by systemic
symptoms (eg, fever) should raise a concern for vasculitis.
•Urticarial vasculitis is a disorder characterized by urticarial lesions with vasculitic
findings on skin biopsy (picture 5). The disorder may be systemic or limited to the
skin. (See "Urticarial vasculitis".)
•Immunoglobulin A (IgA) vasculitis (Henoch-Schönlein purpura) is a systemic
vasculitis with a prominent cutaneous component characterized by purpuric lesions,
particularly involving the lower extremities. The skin lesions can be urticarial initially,
although the development of systemic disease with arthralgias, abdominal pain, and
renal involvement should prompt investigation for this condition. (See "IgA vasculitis
(Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Skin
manifestations'.)
•Patients with lupus may also develop urticarial lesions that persist and become
vasculitic. Skin biopsy may show evidence of vasculitis. (See "Overview of cutaneous
lupus erythematosus".)
●Malignancies – Urticaria may also be seen with malignancies, especially immunoglobulin
M (IgM) and sometimes immunoglobulin G (IgG) paraproteinemias. The etiology is also
unclear but may be due to complement-mediated pathways. In these cases, the urticaria is
persistent and becomes chronic. (See "Chronic spontaneous urticaria: Clinical
manifestations, diagnosis, pathogenesis, and natural history", section on 'Unclear
association with malignancy'.)

The urticaria associated with systemic disorders is usually recurrent, persistent, and relatively
difficult to treat, so patients with these disorders typically present with chronic urticaria. Clinical
features that can help distinguish these disorders from uncomplicated chronic urticaria are
reviewed separately. (See "Chronic spontaneous urticaria: Clinical manifestations, diagnosis,
pathogenesis, and natural history", section on 'Differential diagnosis'.)

EVALUATION AND DIAGNOSISUrticaria is diagnosed clinically, based upon a detailed


history and physical examination confirming the presence of characteristic skin lesions [32-35].

Clinical history — The clinical history should determine the following:


●Were there other signs and symptoms of a generalized allergic reaction or anaphylaxis?
Patients may fail to report more subtle symptoms unless specifically asked. The clinician
should ask about chest tightness or difficulty breathing, hoarse voice or throat tightness,
nausea, vomiting, crampy abdominal pain, lightheadedness, and other symptoms of
anaphylaxis (table 2). (See "Anaphylaxis: Emergency treatment".)
●Has the patient had hives previously in the past? Some children develop acute urticaria
repeatedly with infections. Adults may develop urticaria following nonsteroidal anti-
inflammatory drug (NSAID) ingestion but may not recognize the association until it has
occurred several times. Does the patient have other allergic disorders?
●Were there any symptoms or signs to suggest an underlying systemic disorder?
Specifically, has the patient recently had unexplained fever, weight loss, arthralgias,
arthritis, or bone pain [36,37]? Diseases that may include hives as part of the clinical
presentation are reviewed separately. (See 'Systemic disorders that may include
urticaria' above.)
●Is a possible etiology apparent from the patient's history (table 1)?
(See 'Etiologies' above.)
•Was the patient in his/her usual state of health when the hives appeared or has the
patient been ill recently with viral or bacterial infections? Has the patient experienced
any recent health events, such as musculoskeletal injuries for which he/she was
taking NSAIDs or new diagnoses requiring unfamiliar medications or treatments?
•The patient should be asked to review events in the hours before the urticaria
appeared. What had the patient ingested (foods, beverages, candy)? Was the patient
involved in exercise or physical exertion? Was the patient exposed to extremes of
temperature or stung by an insect? The answers may reveal clues to allergic or
physical causes of urticaria.
•Patients should be questioned about any new medications or supplements in the
preceding days or weeks [38,39]. Were any medications taken in the hours before the
urticaria appeared?
•Inquiries should be made about recent travel (and symptoms of parasitic infection)
and sexual history. (See 'Infections' above.)
•A complete review of systems is valuable in the patient with new-onset urticaria.

Physical examination — Lesions should be visualized directly in order to make the diagnosis


with certainty, since the term "hives" is used nonspecifically by patients. If the patient has no
lesions at the time of evaluation, showing patients photographs of urticaria and asking if their
lesions look similar can be helpful, although the diagnosis will need to be confirmed at some
point in the future (picture 2).

Individual urticarial lesions usually appear and resolve completely within 24 hours. If the patient
is unsure of the duration of the lesions, a lesion can be circled with a pen and time to resolution
noted.

Laboratory studies — Laboratory studies are typically normal in patients who lack any history
or physical findings to suggest an underlying disease process [3].
●For patients presenting with new-onset urticaria (with or without angioedema) in whom the
clinical history and physical exam do not suggest an underlying disorder or urticarial
vasculitis, international, European, and British practice parameters state that laboratory
testing is not indicated [40-42]. American practice parameters state that a limited
evaluation "may be considered" in such patients, primarily for the purpose of detecting
underlying disorders earlier in the one-third of patients in whom urticaria will prove
persistent (ie, initial presentation of chronic urticaria) [43]. In this setting, complete blood
count with differential, urinalysis, erythrocyte sedimentation rate, and liver function tests are
suggested. However, the author's approach is to obtain these tests in patients with
persistent symptoms.
●In patients in whom a specific etiology is suspected, laboratory studies and further
evaluation should be directed at establishing or excluding that cause.
(See 'Etiologies' above.)

Tests for allergic causes — An allergic cause is possible if the clinical history reveals a
specific trigger to which the patient was exposed shortly before the onset of symptoms (usually
within one to two hours). If the history does suggest a possible allergy, serum tests for allergen-
specific immunoglobulin E (IgE) antibodies are appropriate, if commercially available. For
example, if a patient who does not normally eat seafood but did so at a special occasion
develops hives within 10 minutes of eating a crab cake, it would be reasonable to obtain a crab-
specific IgE test, particularly if there were no other new foods ingested and the patient is
avoiding seafood for fear of a repeat reaction. However, the interpretation of allergy tests can
require some expertise. A positive result is suggestive, although not diagnostic, of allergy, and a
negative result does not exclude allergy. Because of this, we suggest that patients suspected of
having an allergy be referred to an allergist/immunologist for further evaluation when possible.
Skin tests with fresh food, which should be performed by an allergy specialist, is probably the
most convenient, inexpensive, and sensitive way to detect food hypersensitivity.
(See 'Referral' below and "Overview of in vitro allergy tests".)

DIFFERENTIAL DIAGNOSISThe conditions discussed in this section are those that may
mimic various features of urticaria [44]. The presence or absence of pruritus is a helpful clinical
feature that can be used to narrow the differential.

Nonpruritic conditions — Nonpruritic conditions that may resemble acute urticaria include viral
exanthems, the skin changes of auriculotemporal syndrome, and Sweet syndrome.
●Viral exanthems – Viral exanthems are common in children and can occur with many
different infections, including erythema infectiosum (fifth disease), Epstein-Barr virus,
enteroviruses, and measles. However, viral exanthems are generally not pruritic and
usually consist of erythematous maculopapular eruptions that persist for days. Fever is
often present. The macules are relatively fixed compared with urticarial lesions, which
continually change, with new lesions appearing as older lesions resolve. (See topic reviews
on specific infections.)
●Auriculotemporal syndrome – Auriculotemporal syndrome is a nonpruritic flushing
and/or sweating of the skin over the cheeks or jawline (the areas supplied by the
auriculotemporal nerve) that occurs transiently after eating and may be mistaken for
urticaria associated with food allergy [45]. It can be seen in children or adults and may
develop following damage to the nerve secondary to forceps delivery, viral infection,
surgery, or other local trauma. Unilateral distribution is typical, although bilateral cases
have been reported [46].
●Sweet syndrome – Sweet syndrome is an uncommon disease characterized by recurrent
episodes of painful, long-lasting inflammatory papules and plaques associated with fever,
arthralgias, and peripheral leukocytosis. There may be a history of a febrile illness one to
three weeks before the onset of skin lesions in some cases. (See "Sweet syndrome (acute
febrile neutrophilic dermatosis): Pathogenesis, clinical manifestations, and diagnosis".)

Pruritic conditions — Pruritic conditions that are more likely to be confused with urticaria are
discussed here. An overview of the causes of pruritic dermatoses is found separately.
(See "Pruritus: Etiology and patient evaluation".)
●Atopic dermatitis – Atopic dermatitis is a common disorder that presents initially as
intensely pruritic erythematous patches with papules and some scaling. In children, the
face, scalp, extremities, or trunk are typically involved, while the diaper area is spared. In
older children and adults, the flexural areas (neck, antecubital fossae, and popliteal fossae)
are most commonly involved. Other sites include the face, wrists, and forearms (picture 7).
Erythematous areas of involvement last for days or weeks and have ill-defined borders.
Scaling and xerosis develop with time. (See "Atopic dermatitis (eczema): Pathogenesis,
clinical manifestations, and diagnosis".)
●Contact dermatitis – Contact dermatitis refers to any dermatitis arising from direct skin
exposure to a substance. The dermatitis may either be allergic or irritant-induced. The
latter is more common. Contact dermatitis is an erythematous, papular dermatitis, often
with areas of vesiculation (picture 8). It is distributed in the areas of direct contact.
(See "Contact dermatitis in children" and "Irritant contact dermatitis in
adults" and "Common allergens in allergic contact dermatitis".)
●Drug eruptions – Drug eruptions, also called morbilliform or exanthematous drug
eruptions, are cutaneous drug reactions that closely mimic viral exanthems but occur in
association with a medication. These dermatoses may or may not be pruritic and begin as
small macules and/or papules that become larger and confluent with time (picture 9). The
individual lesions are persistent, unlike urticaria. (See "Drug eruptions".)
●Insect bites – Insect bites produce individual lesions that persist for days in most cases
(see "Insect and other arthropod bites"). However, the stings of some insects can cause
true urticaria as part of a systemic allergic reaction. (See 'IgE-mediated allergic
reactions' above.)
●Bullous pemphigoid – In older adults, bullous pemphigoid may start with pruritus, with or
without urticarial lesions. Blistering usually becomes evident eventually. (See "Clinical
features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid",
section on 'Bullous pemphigoid'.)
●Erythema multiforme minor – Erythema multiforme minor is a syndrome characterized
by erythematous, iris-shaped macules and vesiculobullous lesions with a target
appearance (picture 10). The lesions may be painful or pruritic and distributed
symmetrically on the extensor surfaces of the extremities (particularly the palms and
soles). Individual lesions last several days, unlike urticaria. There may be accompanying
fever and malaise. (See "Erythema multiforme: Pathogenesis, clinical features, and
diagnosis".)
●Plant-induced reactions – Poison ivy and poison oak can present with urticaria-like
lesions initially that evolve into vesicular lesions. (See "Poison ivy (Toxicodendron)
dermatitis".)
TREATMENTInitial treatment of new-onset urticaria (with or without angioedema) should
focus on the short-term relief of pruritus and angioedema, if present. Approximately two-thirds of
cases of new-onset urticaria will be self-limited and resolve spontaneously. The literature on
management of acute urticaria is sparse, probably because the condition is so often self-limited
[47]. The agents discussed below have mostly been evaluated in the treatment of chronic
urticaria, and in some cases, their use in acute urticaria is extrapolated from those studies,
which are presented separately. (See "Chronic spontaneous urticaria: Standard management
and patient education".)

H1 antihistamines — H1 antihistamines may be divided into older, first-generation agents


(eg, diphenhydramine, chlorpheniramine, hydroxyzine) and newer, second-generation agents
(eg, cetirizine, loratadine, fexofenadine, others). Second-generation agents are preferred for
both adults and children.

Second-generation agents — The newer, second-generation H1 antihistamines are


recommended as first-line therapy by published guidelines from both allergy and dermatology
expert panels [48,49]. These drugs are minimally sedating, are essentially free of the
anticholinergic effects that can complicate use of first-generation agents, have few significant
drug-drug interactions, and require less frequent dosing compared with first-generation agents
[50-54]. We know of no data demonstrating that any specific agent is more effective than
another for the treatment of acute urticaria, although a few studies in patients with chronic
urticaria suggest that cetirizine and levocetirizine may be modestly more effective than other
agents. (See "Chronic spontaneous urticaria: Standard management and patient education",
section on 'Agents and efficacy studies'.)

Some patients require higher than standard doses (shown below in parentheses) for control of
urticarial symptoms and may experience drowsiness at these higher doses. Caution is therefore
warranted until effects upon the individual are understood. The higher doses may have better
efficacy in some adults, although this has not been conclusively demonstrated. Studies of
higher-dose antihistamines for chronic urticaria are reviewed separately. (See "Chronic
spontaneous urticaria: Standard management and patient education", section on 'H1
antihistamines'.)

Treatment with H1 antihistamines results in clearance of the lesions in some patients, but in
others, treatment may only achieve flattening of the lesions and reduction in pruritus, with
persistence of erythematous macules. Patients in the latter group can begin to reduce
medications after the erythematous lesions clear.

Second-generation H1 antihistamines are only available in oral formulations and include the
following:

●Cetirizine – Cetirizine demonstrates a rapid onset of action and some mast cell-stabilizing
activity. It can be mildly sedating, in a dose-dependent manner, although less so than first-
generation agents. The standard dose of 10 mg once daily is appropriate for adults and
children aged six years and older (and may be increased to 10 mg twice daily in adults if
needed).
The usual dose for children aged two to five years is 5 mg once daily. Smaller children
aged six months to two years may be given 2.5 mg once daily (can be increased to 2.5 mg
twice daily in children one year and older if needed). The maintenance dose for patients
with significant renal and/or hepatic insufficiency should be reduced by one-half.
●Levocetirizine – Levocetirizine is an active enantiomer of cetirizine that produces effects
equivalent to cetirizine at about one-half of the dose. For adults and children 12 years and
older, the standard dose is 5 mg once daily in the evening (or up to 5 mg twice daily in
adults if needed) or 2.5 mg once daily in the evening for children aged 6 to 11 years.
Levocetirizine is unlikely to be effective as an alternative for patients who did not have an
adequate response to cetirizine, and its sedative effects are similar to those of other
second-generation antihistamines [55]. Dose reductions are necessary in renal
insufficiency.
●Loratadine – Loratadine is a long-acting, selective H1 antihistamine. The standard dose is
10 mg once daily for ages six years and older, which is minimally sedating. It can be
increased up to 10 mg twice daily in adults if needed. For children aged two to five years,
the usual dose is 5 mg once daily. For patients with significant renal and/or hepatic
insufficiency, the usual dose is administered every other day.
●Desloratadine – Desloratadine is the major active metabolite of loratadine and produces
effects equivalent to loratadine at about one-half the dose. For adults and children 12 years
and older, the standard dose is 5 mg once daily (or up to 5 mg twice daily in adults if
needed).
For children aged 6 to 11 years, the dose is 2.5 mg once daily, and for those aged 1 to 5
years, the dose is 1.25 mg once daily. A lower dose of 1 mg once daily is approved in the
United States for small children aged 6 months to 1 year. For patients with significant renal
and/or hepatic insufficiency, the usual dose is administered every other day.
●Fexofenadine – Fexofenadine is minimally sedating. The suggested dose is 180 mg daily
for ages 12 years and older (or up to twice daily in adults if needed) or 30 mg twice daily for
children aged 2 to 11 years. A lower dose of 15 mg twice daily is approved in the United
States for small children aged six months to two years. For patients with significant renal
insufficiency, the adult dose should be reduced to 60 mg once daily. It is best taken without
food and specifically not with fruit juices.

There are additional nonsedating antihistamines that are available in many countries, although
not in the United States:

●Ebastine – Ebastine is a nonsedating antihistamine that is licensed for use in children


older than 12 years of age and adults. The usual dose is 10 mg daily, but it can be doubled
to 20 mg daily if needed, although not in patients with liver insufficiency. One study of
patients with acute urticaria found that 20 mg of ebastine was similar in efficacy to 5 mg
of levocetirizine and caused fewer adverse effects [56].
●Bilastine – Bilastine is a nonsedating antihistamine with efficacy similar to cetirizine and
higher than that of fexofenadine [57]. The initial dose is 20 mg daily for children older than
12 years of age and adults. Bioavailability is reduced approximately 30 percent by
grapefruit juice, ketoconazole, or erythromycin, and it should not be taken with food. The
drug minimally crosses the blood-brain barrier (because it is a zwitterion), does not cause
somnolence, and is not affected by alcoholic beverages [58].
●Rupatadine – Rupatadine antagonizes both histamine and platelet-activating factor (PAF)
receptors [59]. It is licensed at a dose of 10 mg daily for patients older than 12 years of
age, although it is safe in patients older than 2 years of age [60]. As is the case
for bilastine, the drug should not be taken with grapefruit juice, ketoconazole,
or erythromycin, but (unlike bilastine) it is not affected by food.

First-generation agents — The first-generation antihistamines


include diphenhydramine, chlorpheniramine, hydroxyzine, and others [61]. These agents are
lipophilic and readily cross the blood-brain barrier, causing sedating and anticholinergic side
effects that may be dose-limiting in some patients. Significant sedation and impairment of
performance (eg, fine motor skills, driving skills, and reaction times) occur in more than 20
percent of patients [62]. Anticholinergic side effects include dry mouth, diplopia, blurred vision,
urinary retention, or vaginal dryness. Patients should be warned specifically about these
adverse effects. Despite these adverse effects, patients at low risk of complications (eg, young,
healthy patients) may find a sedating H1 antihistamine at bedtime helpful, especially when
combined with a nonsedating H1 antihistamine during the day.
Some first-generation H1 antihistamines are available in parenteral preparations for use in
patients in whom a more rapid onset of action is desired, such as those who have presented to
the emergency department. Parenteral dosing of the first-generation agents is:

●Diphenhydramine – The dose in adults is 25 to 50 mg given by slow intravenous (IV)


administration or intramuscular (IM) injection every four to six hours as needed. Children
may receive 0.5 to 1.25 mg/kg (up to 50 mg per dose) IV/IM every six hours as needed.
OR
●Hydroxyzine – The dose in adults is 25 to 50 mg deep IM administration in adults every
four to six hours as needed. Do not administer intravenously. Children may receive 0.5 to 1
mg/kg (up to 50 mg per dose) IM every six hours as needed.

Pregnant and lactating women — Pregnant women may be treated initially with loratadine (10


mg once daily) or cetirizine (10 mg once daily). There are reassuring human data for each of
these drugs in a large number of pregnant patients [63]. The first-generation
agent chlorpheniramine, 4 mg orally every four to six hours, may also be safely used in
pregnancy [64,65]. Safety issues surrounding the use of antihistamines in pregnancy are
reviewed separately. (See "Recognition and management of allergic disease during pregnancy",
section on 'Oral antihistamines'.)

Lactating women may be treated with either cetirizine or loratadine (both are dosed at 10 mg


once daily), which are minimally excreted in breast milk and should not cause sedation or poor
feeding in the infant. (See "Pharmacotherapy of allergic rhinitis", section on 'Breastfeeding
women'.)

H2 antihistamines — There are very few data examining the use of H2 antihistamines for
acute urticaria, but the practice is supported by one randomized trial of 91 adults presenting to
an emergency department with acute allergic reactions [66]. Subjects received 50 mg
IV diphenhydramine with either placebo or 50 mg IV ranitidine. At two hours, the number of
patients in whom urticaria had resolved was statistically greater in the ranitidine group
compared with the placebo group (25 of 29 and 13 of 24, respectively). Options for H2
antihistamines include ranitidine, nizatidine, famotidine, and cimetidine, although caution should
be used with cimetidine, since it can increase levels of other drugs. (See "Antiulcer medications:
Mechanism of action, pharmacology, and side effects".)

Studies of the use of H2 antihistamines in chronic urticaria are conflicting and are reviewed
elsewhere [67-69]. (See "Chronic spontaneous urticaria: Standard management and patient
education", section on 'H2 antihistamines'.)

Glucocorticoids — Glucocorticoids do not appear to be necessary for isolated urticaria.


However, a brief course (ie, usually a week or less) of systemic glucocorticoids may be added to
antihistamine therapy for patients with prominent angioedema or if symptoms persist beyond a
few days. Glucocorticoids do not inhibit mast cell degranulation but may act by suppressing a
variety of contributing inflammatory mechanisms.

A small number of trials have examined the utility of glucocorticoids in the management of acute
urticaria [70-72]. In the largest study, the addition of prednisone to levocetirizine did not speed
resolution of acute urticaria. In this randomized trial, 100 adults presenting to the emergency
department with urticaria of ≤24 hours duration without angioedema, anaphylaxis, or fever, were
treated with the H1 antihistamine levocetirizine (5 mg once daily for five days) plus either
placebo or prednisone (40 mg once daily for four days) and followed by phone for several days
[72]. The primary endpoint was complete relief of itching two days after the start of therapy, and
secondary endpoints included resolution of skin lesions, relapses, and adverse events. Most
subjects had resolution of itch by day 2, with a slightly lower percentage itch-free in the
prednisone group (79 versus 67 percent). Similarly, by day 2, skin lesions had resolved entirely
in 78 and 70 percent of those in the placebo and prednisone groups, respectively. Thus, the
addition of prednisone to levocetirizine did not speed resolution of acute urticaria. Between one-
quarter and one-third of patients experienced relapse in both groups, generally within the first
few days of therapy. Another smaller randomized trial found that glucocorticoids were helpful
when added to antihistamines, although the antihistamine regimen used in that study
(hydroxyzine 25 mg orally every four to eight hours) may have been more difficult to adhere to
[70].

Our approach is to treat all patients with H1 antihistamines, adding H2 antihistamines for more
severe symptoms and reserving oral glucocorticoids for those patients with prominent
angioedema or persistent symptoms despite antihistamines.

The optimal agent and dose have not been determined for acute urticaria, but we typically
administer:

●Inadults – Prednisone 30 to 60 mg daily, with tapering of the dose over five to seven days
●Inchildren – Prednisolone 0.5 to 1 mg/kg/day (maximum 60 mg daily), with tapering of the
dose over five to seven days

Antihistamine therapy should be continued during and after the course of glucocorticoids
because some patients experience an exacerbation as the glucocorticoids are tapered or
discontinued. If symptoms do not recur over several days after stopping glucocorticoids, then
antihistamines can be discontinued also. For patients whose symptoms recur when medications
are discontinued, antihistamines should be reinstituted and used at the lowest effective dose.
Repeated courses of glucocorticoids should be avoided, as the risks of adverse effects
outweigh the benefit for most patients. (See 'Referral' below.)

REFERRALPatients who are suspected of having an allergic etiology causing new-onset


urticaria, such as a food or medication allergy, should be referred to an allergy specialist who
will equip them with epinephrine for self-injection when indicated. These issues are discussed in
detail separately. (See "Anaphylaxis: Emergency treatment", section on 'Discharge care'.)

It should be explained to patients that about one-third of cases of new-onset urticaria will prove
persistent and that if they continue to have ongoing symptoms after several weeks, they should
seek re-evaluation in a primary care setting. Patients with difficult-to-control symptoms may also
be referred to a dermatology or allergy specialist.

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