AUTHOR AND EDITOR INFORMATION

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• Workup
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• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Urticaria, or hives, is a common skin condition that affects 15-25% of the population at some point in their lives. Most cases of urticaria are self-limited and of short duration, but when urticaria becomes chronic, it can be a very problematic and frustrating condition, both for the patient and for the clinician.

Urticaria is classified as either acute or chronic. Acute urticaria is defined as urticaria that has been present for less than 6 weeks. Chronic urticaria is defined as urticaria that has been continuously or intermittently present for at least 6 weeks. The 6-week period is a guide and not an absolute demarcation.

When no underlying cause is found, chronic urticaria is referred to as chronic idiopathic urticaria (CIU).

Angioedema is a condition that involves swelling of the deep dermal and subcutaneous/submucosal tissues. Some patients can have both urticaria and angioedema, occurring simultaneously or separately. Approximately 50% of patients have both urticaria and angioedema, while 40% have urticaria alone, and 10% have angioedema alone. See Angioedema for more details.

Pathophysiology

Skin lesions and pruritus occur, caused by an allergic or nonallergic mechanism.

Histamine is thought to be the most important biochemical mediator in urticaria. It is known to cause the classic wheal-and-flare response that is observed with urticaria and with positive results on allergy skin tests. Studies have shown that histamine is present in fluid taken from urticarial wheals.

Mast cells are the major histamine-releasing cells of the skin. Some studies report increased numbers of mast cells in urticarial lesions. The mast cell possesses high-affinity receptors for immunoglobulin E (IgE). In allergic reactions, adjacent IgE molecules, which are bound to the surface of mast cells by the high-affinity IgE receptors, are cross-linked by allergens, leading to the release of histamine and other mediators.

Histamine and the other mediators can be released by other nonallergic mechanisms as well. For example, neuropeptides are known to cause mast cell degranulation by a nonallergic mechanism. Neuropeptides may well be involved in dermographism and in emotional exacerbation of urticaria. In addition to histamine, other mast cell mediators are also thought to play a role in urticaria.

Basophils also possess the high-affinity IgE receptor and may be involved in urticaria. Other inflammatory cells (ie, vide infra) are recruited into the lesional area in urticaria, particularly in chronic urticaria. These cells can release cytokines and chemokines that can cause histamine release or otherwise contribute to the pathology.

Histopathology

A lymphocytic infiltrate is commonly found in the lesions of both acute and chronic types of urticaria. Some urticarial lesions have a mixed cellular infiltrate, ie, a mixture of lymphocytes, polymorphonuclear leukocytes (PMNs), and other inflammatory cells. This mixed type of infiltrate seems to be particularly characteristic of certain refractory forms of chronic urticaria, such as autoimmune-mediated urticaria (see Causes).

The mixed infiltrate is similar to the histopathology of the allergic late-phase response. Some patients with particularly severe or atypical urticaria are found to have vasculitis on skin biopsy. Indeed, a spectrum in histopathology seems to exist, ranging from lymphocytic to vasculitic, that correlates approximately with disease severity, from mild to severe.

Frequency

International

Urticaria (chronic, acute, or both) affects 15-25% of the population at some time in their lives. CIU affects up to 3% of the population at some time in their lives. The incidence of acute urticaria is higher in people with atopy. The incidence of chronic urticaria is not increased in people with atopy.

Mortality/Morbidity

• Mortality is rare, unless the condition is accompanied by severe anaphylaxis or severe respiratory tract angioedema.
• Morbidity depends on the severity and duration of the condition. Of patients who have CIU, up to 20% can have symptoms for longer than 10 years. Some studies show chronic urticaria to be quite debilitating. One study finds that urticaria patients can have as much psychological, social, and occupational distress as patients who are awaiting triple coronary artery bypass surgery.

Sex

Chronic urticaria affects females more often than males (the female-to-male ratio is approximately 4:1).

Age

Acute urticaria occurs most commonly in children and young adults. CIU is more common in adults; middle-aged women seem to be most affected.

CLINICAL

Section 3 of 11  

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History

• Typical features
• • Typical lesions are described as edematous pink or red wheals of variable size and shape, with surrounding erythema. The lesions are often described as welts or hives.
  • The lesions are generally pruritic. A painful or burning sensation may be described (such lesions are often associated with angioedema). Pruritus of nonlesional skin may also occur.
  • Dermographism is often observed in conjunction with urticaria. Itching, erythema, and a raised wheal occur in areas that are scratched or stroked (see Image 1). Patients also may report pressure-induced hives, which can occur with elastic or tight clothing.
  • Individual lesions usually fade within 24 hours, but new lesions may be developing continuously. With delayed pressure urticaria, lesions may last as long as 48 hours. The lesions of urticarial vasculitis, which are palpable and purpuric, may last for several days or more and may lead to residual hyperpigmented changes.
• Questions asked to determine possible allergic and nonallergic causes
• • Are the hives associated with any foods? Have any new foods been added to the diet?
  • Is the patient taking any regular medications or have any new medicines been started? In particular, ask about aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, over-the-counter medications, herbs, and supplements.
  • Does the patient have any recent or chronic infections?
  • Are the hives caused by any physical stimuli (eg, heat, cold, pressure, vibration)?
  • Does the patient have any chronic medical conditions?
  • Is the urticaria associated with any substances that are inhaled or in contact with the skin (which may occur in an occupational setting)?
  • Is the urticaria associated with insect bites or stings?

Physical

• If any features of anaphylaxis (eg, hypotension, respiratory distress, stridor, gastrointestinal distress) are present, immediate medical intervention should occur.
• Look for typical skin lesions, which are edematous pink or red wheals of variable size and shape, with surrounding erythema. Also, look for any atypical skin lesions. Lesions that are purpuric, nonblanchable, and palpable are characteristic of urticarial vasculitis. These lesions may leave residual pigmented changes. Tiny pinpoint hives are characteristic of cholinergic urticaria.
• Examine for dermographism. The skin can be scratched with the end of a tongue blade or similar blunt object and observed over the next 5-15 minutes for the development of whealing with erythema (see Image 1).
• Look for any features of angioedema (deep tissue or submucosal edema).
• The remainder of the physical examination should be used to investigate any suspicions that were raised by the history.

Causes

• Food allergies
• • Food allergy should be considered in acute urticaria and urticaria in children.
  • Food allergy is unlikely to be a cause in adults with chronic urticaria, especially if it is not obvious by the history. It occurs in fewer than 2% of cases.
  • Food additives or preservatives have been reported to be a cause of chronic urticaria in 3-4% of cases. Data are scarce and questionable.
• Drug allergies
• • Allergic reactions to a wide variety of drugs can occur. Theoretically, almost any drug can cause an allergic reaction.
  • Antibiotics, such as penicillin, have been implicated most frequently. Urticarial reactions to penicillin can occur as long as 14 days after a course of treatment has stopped. In this situation, serum sickness may be present.
• Contact urticaria is an allergic reaction to a substance that comes into contact with the skin (eg, an occupational exposure).
• Papular urticaria is a variation of urticaria caused by insect bites; the lesions may last longer than 24 hours.
• Other immediate hypersensitivity allergic reaction to an ingested, inhaled, or percutaneously inoculated substance (eg, latex, stinging insects, occupational exposures)
• Nonallergic release of mediators
• • A number of drugs, such as aspirin, NSAIDs, opiates, succinylcholine, and certain antibiotics (eg, polymyxin, ciprofloxacin, rifampin, vancomycin, some beta-lactams) can cause urticaria by a nonallergic mechanism rather than by IgE-mediated hypersensitivity.
  • Certain foods or beverages, such as spoiled fish (scombroidosis), aged cheeses, or red wine: These foods can contain histidine, which is closely related to histamine. These foods often are listed as causes of urticaria in the literature, but experimental evidence is scarce.
  • Certain venoms
  • Radiocontrast media sensitivity is not related to iodine, fish, or shellfish allergy.
• Medical causes
• • Infectious causes
  • • Urticaria has been reported with certain viral infections, such as acute viral syndromes, hepatitis (A, B, and C), Epstein-Barr virus, and herpes simplex virus. Urticaria has also been reported with chronic parasitic infections.
    • Urticaria may possibly be caused by sinusitis, cutaneous fungal infections, Helicobacter pylori infection, or other occult infection. These causes have been reported in the literature, but data are not strongly supported.
  • Hormonal causes
  • • Endocrine tumors (rare)
    • Ovarian pathology (rare)
    • Oral contraceptive use or changes in the menstrual cycle: Patients commonly report worsening of hives with the menstrual cycle. Be sure to consider cyclical use of analgesics as a possible etiology.
  • Cryoglobulinemias (eg, associated with hepatitis C, chronic lymphocytic leukemia)
  • Serum sickness
  • Other immune complex–mediated inflammation
  • Systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, or other rheumatological diseases (these are rare causes of urticaria)
  • Urticaria has been reported with both hypothyroidism and hyperthyroidism and in euthyroid patients with antithyroid antibodies (ie, vide infra).
  • Lymphoreticular malignancies (eg, chronic lymphocytic leukemia
• Physical causes (physical urticaria)
• • Cold
  • Pressure: A delayed response to pressure (delayed pressure urticaria) occurs in up to 40% of patients with CIU.
  • Vibration
  • Cholinergic (triggered by heat, exercise, or emotional stress)
  • Sunlight
  • Water
  • Dermographism can occur concomitantly with CIU.
  • Exercise
• Chronic idiopathic urticaria
• • Urticaria is classified as idiopathic when no specific cause is identified by history, physical examination, or laboratory findings.
  • Eighty to 90% of cases of chronic urticaria can be classified as idiopathic.
  • These patients may have concomitant physical urticaria.
  • Causes are separated into 2 categories, autoimmune or unknown.
• • Autoimmune causes
  • • Studies have shown that as many as 40-60% of cases of CIU have an autoimmune component. These studies found that sera from many of these patients, when injected intradermally, cause a wheal-and-flare reaction. This is called an autologous serum skin test. Furthermore, these sera can cause a release of histamine from basophils in vitro.
    • Further studies have found that 25-60% of patients have autoantibodies directed against their high-affinity IgE receptors. The role of these autoantibodies is still unclear. They may bind to the high-affinity IgE receptors on mast cells and basophils, triggering the release of mediators, in a process that is thought to be complement-dependent.
    • Five to 10% of patients have autoantibodies directed against the IgE molecule. The role of these autoantibodies is still unclear. They may attach to IgE molecules that are bound to mast cells (or basophils), triggering the release of mediators.
  • Unknown causes
  • • In the remaining 40-60% of cases of CIU, the cause is unidentified. Numerous other possible causes have been suggested but have not been substantiated in the literature.
    • A higher frequency of thyroid autoimmunity occurs in patients with chronic urticaria. These patients have autoantibodies directed against thyroid proteins but may be euthyroid. Some authors have found that treatment of these euthyroid patients with thyroxine leads to an improvement in urticaria, but other authors have not been able to reproduce this finding. Some have speculated that the thyroid autoantibodies cause inflammation in the thyroid, leading to release of cytokines, which, in turn, decreases the threshold for mast cell mediator release. Others have suggested that the thyroid autoantibodies are merely markers for autoimmunity. For example, patients with thyroid autoantibodies are more likely to have other autoantibodies, such as the anti-IgE receptor and anti-IgE discussed above.
    • Occult infections and food additives have been reported to be causes of CIU in a small number of patients, but the data are scarce and questionable, as discussed previously.
    • Other histamine-releasing factors in the serum that cause a wheal-and-flare reaction independent of IgE or the high-affinity IgE receptor may be present. Experimental evidence for this is lacking.

DIFFERENTIALS

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Other Problems to be Considered

Bullous pemphigoid
Dermatitis herpetiformis
Chronic pruritus (nonurticarial)
Hypersensitivity vasculitis and/or urticarial vasculitis
Urticaria pigmentosa or other mast cell releasability syndromes
Pruritic urticarial papules and plaques of pregnancy (PUPPP), also referred to as polymorphic eruption of pregnancy (PEP)

WORKUP

Section 5 of 11  

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• Clinical
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• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Lab Studies

• Skin tests or radioallergosorbent assay test (specific IgE)
• • Selected allergy tests can be performed if food allergy or stinging insect hypersensitivity is suspected. Skin testing can be performed to detect hypersensitivity to a limited number of antibiotics. Testing for pollen or other inhalants is generally not helpful unless a severe allergy may be causing the urticaria, such as a severe allergy to pollens, cats, or latex (these may manifest as contact urticaria).
  • Routine allergy testing with a large battery of screening tests is not recommended.
  • A few research centers perform an autologous serum skin test, but it is not a well-established procedure currently.
• Screening laboratory studies
• • Which laboratory tests, if any, to order for routine screening is very controversial.
  • Many specialists order only a few select screening studies for patients who have chronic urticaria lasting at least 6 weeks with no apparent etiology.
  • Some choose to perform no testing at all. Laboratory testing for acute urticaria is not indicated, unless a particular medical condition is suspected.¹
  • Common screening laboratory tests that are ordered are as follows:
    • CBC with differential
    • Total eosinophil count
    • Sedimentation rate
    • Urinalysis
    • Liver function tests
  • Evaluation of the complement system, including total hemolytic complement (CH₅₀), C3, and C4 should be considered in patients with prominent angioedema and in patients with urticarial lesions lasting more than 24 hours. These tests are of no value in patients with classic chronic urticaria.
  • Thyroid studies, including thyroid autoantibody levels (antimicrosomal, antithyroglobulin) can be considered, particularly in women or in patients with a family history of thyroid disease or other autoimmune diseases.
  • Order other laboratory tests only if an abnormal result is found on the initial screening tests or if a specific medical condition is suspected. Evaluation for possible occult infection can be considered, but evidence that infections cause chronic urticaria is limited.
  • Other tests to consider if the history and physical examination findings are suggestive of specific problems include the following:
    • Chemistry panel
    • Stool analysis for ova and parasites
    • H pylori workup
    • Hepatitis B and C workup
    • Sinus radiography (if symptomatic)
    • Antinuclear antibody (ANA)
    • Rheumatoid factor
    • Cryoglobulin levels
    • Other imaging studies
  • Assays for serum histamine–releasing factors and evaluation for specific autoantibodies (anti-IgE receptor and anti-IgE) are performed by some research centers. These tests are not commercially available currently.
  • Patients with cold urticaria should be evaluated for cold agglutinins and cryoproteins because these are found in 5% of cases. The presence of a cryoglobulin suggests an underlying cause such chronic hepatitis (B or C) or lymphoreticular malignancy.

Other Tests

• Physical challenge tests can be performed if a physical urticaria is suspected. These include challenge with an ice cube, heat, pressure, light, scratching of the skin (dermographism), exercise, and vibration.

Procedures

• Skin biopsy is not indicated on a routine basis, but it should be considered if the urticaria does not respond to usual treatment or if any atypical features are present.

TREATMENT

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Medical Care

• Food/symptom diaries
• • For cases of acute urticaria (<6 wk) or to try to pinpoint a trigger, having the patient complete a food diary or symptom diary is sometimes helpful. For a preestablished duration (eg, 2 wk), the patient should record all foods that were eaten and all activities in which the patient was involved for 6-8 hours prior to the onset of an episode of urticaria.
  • In a small number of cases, a pattern may emerge, pinpointing the offending agent.
  • Excessive or prolonged use of a food or symptom diary is unlikely to be of benefit.
• Avoidance
• • If a trigger can be identified, avoidance is the most effective form of management. This would include any food, medication, physical agent, or other factor that triggers the urticaria.
  • Aspirin, NSAIDs, opiates, and alcohol have been reported to be nonspecific triggers of urticaria and might lower the threshold for urticaria in selected patients. Therefore, some specialists advise all patients with urticaria to avoid these agents. However, little experimental evidence is available to support this recommendation.
• Most cases of urticaria respond to pharmacotherapy (see Medication).
• Immunomodulatory and anti-inflammatory therapy
• • Intravenous gammaglobulin, plasmapheresis, and cyclosporin have been shown to be effective in urticaria in a limited number of studies. They can be a consideration in severe urticaria, particularly of the autoimmune type that is unresponsive to medications.
  • Colchicine and dapsone have also been reported to be useful for refractory urticaria and urticarial vasculitis, perhaps because of their ability to modulate PMN function. PMNs and a mixed infiltrate can be present in some urticarial lesions, particularly urticaria that is severe or refractory to antihistamine treatment.
  • Some reports describe the effectiveness of the antileukotriene agents in urticaria, but extensive clinical trials have not been performed, so their usefulness is still questionable. Clinical trials may support the theory that the antileukotriene agents can provide a synergistic response when used in conjunction with antihistamines.
  • Because the use of the aforementioned agents is not widespread, details of dosage and administration are not provided, but references are listed in the bibliography. The use of corticosteroids is more common and is discussed in Medication.
• Complementary and alternative medicine: Alternative therapies for urticaria have not been properly evaluated and, therefore, are not recommended.
• Potential therapies in the future: Because physicians now know that a large number of cases of CIU are actually autoimmune, targeting the autoimmune process may be a potential form of therapy.

Consultations

A primary care physician can manage most cases of acute urticaria, as well as uncomplicated cases of chronic urticaria.

If a trigger is easily identified and avoidance leads to resolution, then referral is not necessary. If an allergic trigger is suspected but not easily identified, then referral to an allergy specialist is warranted. Similarly, if avoidance of a trigger does not lead to resolution or if the patient does not respond well to antihistamines, then referral to an allergist or dermatologist is warranted.

Diet

Dietary modification is only necessary if food allergy or food additive hypersensitivity has been established. Food additives or preservatives have been reported to cause chronic urticaria in 3-4% of cases, but the data are scarce and questionable (see Causes).

MEDICATION

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Most cases of acute and chronic urticaria respond to pharmacotherapy. Use of antihistamines is the mainstay of therapy. In acute cases, a short course of steroids can be very effective. Long-term treatment with steroids should be avoided, if possible, but may be necessary in severe cases. A number of other classes of medicines have been found to be effective, mostly on an experimental basis. If urticaria does not respond to antihistamine treatment (with the possible addition of a short course of steroids), then referral to a specialist is indicated.

Drug Category: H1 antagonists (antihistamines)

Primary agents used for urticaria.² The older, first-generation H1 antagonists (eg, diphenhydramine, hydroxyzine) are effective in reducing the lesions and pruritus but can produce a number of adverse effects, such as drowsiness and anticholinergic effects.

They can be used as primary treatment of acute episodes, but the adverse effects may limit their usefulness for chronic urticaria. Some patients seem to develop a tolerance to the adverse effects with prolonged use, but they may still experience cognitive impairment, and their driving skills may still be affected.

The first-generation agents can sometimes be useful if administered at bedtime because the sedative effects can help with sleep, but the sedation and cognitive effects may continue until the next day. The newer second-generation antihistamines are nonsedating in most patients, with very few side effects reported (cetirizine can cause drowsiness in up to 10% of patients). Therefore, many specialists prefer the use of second-generation agents for chronic urticaria, with first-generation agents reserved for acute or refractory cases.

Any patient who is taking a medication that has potential sedative effects should be cautioned about driving and operating heavy machinery. Commonly used first-generation agents include diphenhydramine, hydroxyzine, doxepin, chlorpheniramine, and cyproheptadine. The second-generation agents that are currently available in the United States are cetirizine, levocetirizine, desloratadine, loratadine, and fexofenadine. All 4 are active in chronic urticaria. They have not been extensively compared with each other for this indication.

Drug Category: H2 antagonists (antihistamines)

These drugs are usually used to decrease gastric acid secretion. When used as a single agent for urticaria, they are not effective. However, the combination of an H1 antagonist with an H2 antagonist has been shown to be more effective than an H1 antagonist alone. Any of the H2 blockers can be used. Two of the most commonly used agents are ranitidine and cimetidine.

Drug Category: Corticosteroids

In some instances of acute or chronic urticaria, antihistamines may fail. Mediators other than histamine may be involved. In such situations, urticaria should respond to corticosteroids. If not, then consider the possibility of another disease process (eg, malignancy, mastocytosis, vasculitis). Corticosteroids may also be used in urticarial vasculitis, which usually does not respond to antihistamines.

A short course of an oral corticosteroid (administered daily for 5-7 d, with or without a taper) or a single dose of a long-acting injectable steroid is not usually associated with long-term sequelae and can be helpful when used for an acute episode of urticaria nonresponsive to antihistamines.

Because of adverse effects of chronic or recurrent use of systemic corticosteroids, the long-term use of these agents should be avoided in chronic urticaria, when possible. If urticaria is severe and cannot be safely controlled with other medications, low-dose therapy and/or alternate day therapy can be considered.

A large number of preparations are available. Representative examples are prednisone, prednisolone, methylprednisolone, and triamcinolone.

Drug Category: Adrenergic agents

For use if urticaria is accompanied by a potentially life-threatening condition, such as anaphylactic shock, respiratory tract angioedema (which may manifest as stridor), or significant wheezing.

FOLLOW-UP

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Prognosis

• Acute urticaria usually resolves with only symptomatic treatment. If a known triggering factor is present, the urticaria should resolve with appropriate avoidance. If a patient continues to be exposed to a known trigger, the condition may become chronic.
• The prognosis of patients with chronic urticaria is highly variable. Episodes can last for days, weeks, months, or even years at a time. Some patients may only have one episode and never have urticaria again. Others have recurrences after months or years. Recurrences are more likely to occur during periods of stress and illness. As many as 20% of patients with chronic urticaria have symptoms for more than 10 years. In many of these patients, the condition can become quite debilitating and psychologically distressing.

Patient Education

• For excellent patient education resources, visit eMedicine's Allergy Center and Skin, Hair, and Nails Center. Also, see eMedicine's patient education article Hives and Angioedema.

MISCELLANEOUS

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Medical/Legal Pitfalls

• The major potential pitfall is failure to recognize when urticaria is accompanied by life-threatening angioedema or anaphylaxis. Discuss a detailed management plan with patients who have had previous life-threatening events or who are at risk for life-threatening angioedema or anaphylaxis, and prescribe injectable epinephrine.
• Another potential pitfall is failure to diagnose one of the related medical conditions noted in Differentials.

MULTIMEDIA

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Media file 1:  Photograph of dermographism.
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REFERENCES

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• References

1. Beltrani VS. Urticaria: reassessed. Allergy Asthma Proc. May-Jun 2004;25(3):143-9. [Medline].
2. Sheikh J. Advances in the treatment of chronic urticaria. Immunol Allergy Clin North Am. May 2004;24(2):317-34, vii-viii. [Medline].
3. Beltrani VS. Urticaria and angioedema. Dermatol Clin. Jan 1996;14(1):171-198. [Medline].
4. Bensch G, Borish L. Leukotriene modifiers in chronic urticaria. Ann Allergy Asthma Immunol. Oct 1999;83(4):348. [Medline].
5. Bindslev-Lensen C, Finzi A, Greaves M, et al. Chronic urticaria: diagnostic recommendations. J Eur Acad Dermatol Venereol. May 2000;14(3):175-80. [Medline].
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7. Ellis MH. Successful treatment of chronic urticaria with leukotriene antagonists. J Allergy Clin Immunol. Nov 1998;102(5):876-7. [Medline].
8. Fagiolo U, Kricek F, Ruf C, et al. Effects of complement inactivation and IgG depletion on skin reactivity to autologous serum in chronic idiopathic urticaria. J Allergy Clin Immunol. Sep 2000;106(3):567-72. [Medline].
9. Ferrer M, Kinet JP, Kaplan AP. Comparative studies of functional and binding assays for IgG anti-Fc(epsilon)RIalpha (alpha-subunit) in chronic urticaria. J Allergy Clin Immunol. May 1998;101(5):672-6. [Medline].
10. Ferrer M, Nakazawa K, Kaplan AP. Complement dependence of histamine release in chronic urticaria. J Allergy Clin Immunol. Jul 1999;104(1):169-72. [Medline].
11. Finn AF Jr, Kaplan AP, Fretwell R, et al. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. Nov 1999;104(5):1071-8. [Medline].
12. Gallardo MA, Thomas I. Hypersensitivity reaction to erythromycin. Cutis. Dec 1999;64(6):375-6. [Medline].
13. Grattan CE, Francis DM, Hide M, Greaves MW. Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria. Clin Exp Allergy. Nov 1991;21(6):695-704. [Medline].
14. Grattan CE, Francis DM, Slater NG, et al. Plasmapheresis for severe, unremitting, chronic urticaria. Lancet. May 2 1992;339(8801):1078-80. [Medline].
15. Grattan CE, O'Donnell BF, Francis DM, et al. Randomized double-blind study of cyclosporin in chronic "idiopathic" urticaria. Br J Dermatol. Aug 2000;143(2):365-72. [Medline].
16. Grattan CE, Sabroe RA, Greaves MW. Chronic urticaria. J Am Acad Dermatol. May 2002;46(5):645-57; quiz 657-60. [Medline].
17. Greaves M. Chronic urticaria. J Allergy Clin Immunol. Apr 2000;105(4):664-72. [Medline].
18. Greaves MW, O'Donnell BF. Not all chronic urticaria is "idiopathic"!. Exp Dermatol. Feb 1998;7(1):11-3. [Medline].
19. Heymann WR. Chronic urticaria and angioedema associated with thyroid autoimmunity: review and therapeutic implications. J Am Acad Dermatol. Feb 1999;40(2 Pt 1):229-32. [Medline].
20. Hide M, Francis DM, Grattan CE, et al. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med. Jun 3 1993;328(22):1599-604. [Medline].
21. Horn MP, Gerster T, Ochensberger B, et al. Human anti-FcepsilonRIalpha autoantibodies isolated from healthy donors cross-react with tetanus toxoid. Eur J Immunol. Apr 1999;29(4):1139-48. [Medline].
22. Joint Task Force on Practice Parameters. The diagnosis and management of urticaria: a practice parameter part I: acute urticaria/angioedema part II: chronic urticaria/angioedema. Ann Allergy Asthma Immunol. Dec 2000;85(6 Pt 2):521-44. [Medline].
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Article Last Updated: Nov 20, 2007