Urticarie
Urticarie
Urticarie
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.)
Acute urticaria — Urticaria is considered acute when it has been present for less than six
weeks.
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].
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".)
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'.)
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.)
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.
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".)
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'.)
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".)
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:
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'.)
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.)
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.