When the road gets bumpy: Managing chronic urticaria

May 1, 2000

In four out of five children with chronic urticaria, it's not possible to identify a cause. Still, serious problems must be ruled out, triggers sought, and itching alleviated. Here's how to focus the history and physical, decide which tests are and aren't worth doing, and choose the appropriate medications.

When the road gets bumpy: Managing chronic urticaria

Jump to:Choose article section... What is a hive? Facts and features What causes urticaria? Table 1 Causes of chronic urticaria: A short listTable 2 Changes in causes of chronic urticaria over time A practical approach to evaluation Table 3 What to ask children with chronic hivesTable 4 Tests to considerTable 5 Rate of return on screening tests Treatment is step-wise Table 6 Therapeutic medications When to refer Wrapping it up


By Frederick E. Leickly, MD

In four out of five children with chronic urticaria, it's not possible to identify a cause. Still, serious problems must be ruled out, triggers sought, and itching alleviated. Here's how to focus the history and physical, decide which tests are and aren't worth doing, and choose the appropriate medications.

Children who suffer from urticaria, especially chronic urticaria, deserve all the sympathy, support, and empathy that those who care for them can muster. It is difficult to describe the discomfort, disability, and emotional distress caused by urticaria to those who have never experienced the disorder themselves. Not only does the child feel miserable because of the disease process itself; he or she can also suffer side effects from the therapy. Extensive evaluations in pursuit of the cause—the pokes, the prods, the time spent in the office—add to the misery, as do worried parents who fear that there is something terribly wrong with their child.

The list of causes of acute and chronic urticaria is perhaps miles long, and almost every laboratory test that exists in medicine has been ordered for children with "hives." Treatment can be as simple as avoidance, if the instigating culprit is discovered, and may also include antihistamines and oral corticosteroids, with consequent sedation and weight gain. Diets have been altered in order to avoid artificial sweeteners, preservatives, and a rainbow of food dyes (rarely an appropriate treatment). Life is truly miserable for children in the throes of urticaria, and for those who take care of them.

My intent here is to provide a practical framework for the diagnosis and management of chronic urticaria. I will start by defining what a hive is and then provide some encouraging statistics that can be passed along to families. After exploring the various causes for chronic urticaria, I will share with you key elements of what I feel is a practical evaluation and what tests need to be considered. Finally, I will offer a few pearls for treating these children.

What is a hive?

A hive is a well-circumscribed, raised, evanescent area of edema on the skin (Figure 1). The size varies from 1 or 2 mm in cholinergic urticaria to many centimeters in so-called giant urticaria. These lesions almost always itch, and tend to come and go in crops with individual lesions lasting usually 24 and rarely 48 hours. Once a lesion clears, the underlying skin is normal. The duration of the lesions is critical to the diagnosis. Lesions that last beyond two days may be urticarial vasculitis rather than urticaria.



Facts and features

Chronic urticaria is defined as lesions that continue to appear for more than eight weeks, whereas acute urticaria lasts less than eight weeks. Once the verdict is reached that a child indeed has chronic urticaria, it may be reassuring to the family to know that in half the children affected it resolves within a year. If that year passes and parents ask again how long this will go on, you can share with them that in only 20% of patients (adults and children) will the disorder last for more than 10 years. It is estimated that 44% of children with chronic urticaria have daily manifestations, whereas only 14% have an episode less often than once a month.1

Urticaria occurs in 0.1% of the population. Although some infants and children have the disorder, fortunately for the pediatrician it is more common in adults. It also is seen more frequently in females than in males. The earliest case report of acute urticaria was in a 1-month-old infant.2

Urticaria is occasionally accompanied by angioedema, a sign of deeper tissue involvement. Those who suffer from urticaria and angioedema have a worse prognosis than those who have urticaria alone. As many as 75% of those affected continue to have symptoms after five years of illness.3

Chronic urticaria may go into remission. Relapses and return of the condition have been associated with infection, stress, medications, and menses. When chronic urticaria has a physical cause, it may persist for two to four years in children.

What causes urticaria?

Urticaria may occur through an immune mechanism involving IgE or through activation of the complement cascade. A variety of non-immunologic mechanisms also elicit urticarial lesions. Unfortunately, 80% of patients with chronic urticaria are said to have idiopathic urticaria. Among the remaining 20%, for whom a cause is found, approximately 5% have an IgE­mediated cause and 15%, according to most estimates, have a physical cause for the condition: cold, heat, light pressure, heavy pressure, sunlight, vibration, or even water.

Specific causes of chronic urticaria are listed in Table 1. Foods deserve special attention. All too often a parent suspects food as the trigger, and all too often it is a food the child loves. Foods do account for 5% of acute urticaria episodes. In acute urticaria, the cause-and-effect relationship is obvious to the parent, and the symptoms are reproduced with every repeated challenge. Foods are a rare cause of chronic urticaria, however. Poorly documented case reports suggest caffeine, sulfites, monosodium glutamate (MSG), and nickel as causative agents for chronic urticaria, but as advocates for children we must be very cautious regarding food claims and the need for elimination and rotation diets. Although fasting and aggressive elimination diets may have a mystical appeal, we must insist on strong evidence before embarking on the murky path of food allergy as a likely cause of chronic urticaria.4


Table 1
Causes of chronic urticaria: A short list


A child may have chronic urticaria because a substance is in contact with the skin. Frequently—especially when exposed areas of skin are affected—the history and physical examination suggest contact urticaria. Certain occupations are associated with an increased incidence of contact urticaria, and the parent's occupation may be related to the child's symptoms. For example, occupational contact urticaria is seen in 44% of those who work with cows; 24% of those who work with natural rubber latex; 11% of those who work with flour, grain, or feed; 3% of those who handle food; 2% who work with industrial enzymes; and 1.5% who work with decorative plants. The professional groups most likely to experience contact urticaria are, in order, farmers, animal attendants, bakers, nurses, chefs, and dental assistants.5

Infections are also associated with chronic urticaria, although more commonly the urticaria is acute. Dental abscesses, otitis media, streptococcal pharyngitis, and sinusitis have all been accompanied by urticaria. Recent reports identify Helicobacter pylori as a cause, though the evidence is not strong.6 Indolent fungal infections are another possible cause. Candida is frequently listed in the textbooks; rarely is it found in clinical practice. An exciting literature is evolving associating trichophyton infection (athlete's foot) with chronic urticaria. Viruses such as Epstein-Barr, hepatitis C, coxsackievirus, and herpesvirus have been associated with chronic hives, but the supporting evidence is not strong. Chronic parasitic infection with Ascaris, Filaria, Echinococcus, Schistosoma, Trichinella, and Toxocara may have accompanying urticarial lesions. Insects—fleas (I refer to urticaria with this cause as fleabitus), mosquitoes, chiggers, and mites from birds or rodents—may be responsible for papular urticaria, which can be bullous if the child is very sensitive. Fleas from household pets are the most common cause of papular urticaria, but sand fleas from the beach can also cause the condition.

Urticarial vasculitis associated with collagen vascular disease is important in the differential. The lesions of urticarial vasculitis last for more than 24 hours. They are seldom pruritic and may even be painful.

A very popular notion is that dyes, preservatives, antioxidants, flavor enhancers, and naturally occurring salicylates cause chronic urticaria. These agents are referred to in the literature as pseudo-allergens: They act by a non­IgE mechanism, and skin testing is not possible. A technique that can establish them as causing urticaria is to have the child undergo a double-blind placebo-controlled food challenge after two or three weeks without eating pseudo-allergens. A few small studies have shown resolution of the condition with this diet. In one study, a small number of children were hospitalized to help with the stringent avoidance of these agents, and strict avoidance did control the urticaria. The challenge procedure helped identify the specific precipitating agents. Some children were sensitive to four or more pseudo-allergens. The pursuit of pseudo-allergens requires highly motivated parents and strict adherence to the protocol.7

New research shows that chronic urticaria may be an autoimmune problem. In some patients, an autoimmune antibody is directed against an IgE receptor located on basophils and on mast cells.8 When IgE receptors are cross-linked by this antibody, the cells release mediators that cause urticaria. An IgG antibody to IgE has also been described in a small subset of patients with idiopathic chronic urticaria.

Over the years our perspective on the causes of chronic urticaria has changed significantly. Table 2 compares two articles that list common causes for chronic urticaria.9,10 The time difference between these reports is 27 years. Over the years the likelihood of finding a cause for chronic urticaria has decreased, probably because of the use of more exacting criteria, better laboratory tests, and double-blind, placebo-controlled challenges. Differences in the populations studied may play a role as well. The 1992 data help support the current thought that a specific cause is frequently never found. Interestingly, the frequency of physical causes was lower at 6.2% than the 15% found in other studies.


Table 2
Changes in causes of chronic urticaria over time



A practical approach to evaluation

If a specific cause is discovered through a detailed history and physical examination, you are indeed having a good day and should stop to get a lottery ticket on the way home. Families that come to my specialty clinic are seeking the cause of the disorder, but all too frequently my evaluation does not identify one. Instead, I try to rule out serious disorders that are associated with chronic hives. This is a point of frequent dissatisfaction for families, who want to know what the culprit is and not what it is not. At the beginning of the encounter it is a good idea to explain why the "is not" is as important as the "is."

A second issue often not understood by families is that the history and the physical examination are the most important diagnostic tools, not elaborate tests. The laboratory tests that you choose should be based on evidence in the history and physical examination. Laboratory tests frequently have a very low yield in finding a cause.

Sample questions that need to be asked appear in Table 3. Your questioning will be exhaustive and include information as to exactly when the hives started, whether they are present every day, and if so, at what time of day. What makes them worse or better? How long does each spot last? (If need be, have the parent circle a new lesion and mark the time until the lesion disappears.) How does the skin look after the hive goes away? Is it discolored or purple? What locations do the lesions tend to favor—areas that are covered or uncovered, under straps or belts, perhaps on the forearms where the juice of a fruit has dripped? Are the hives any different at night from the way they are during the day? Does angioedema also occur? Can the lesions be brought on by rubbing, pressure, exercise, heat, cold, or immersion in water? Are there any associated systemic symptoms such as fever, joint pain, abdominal pain, weight loss, or pallor, tingling, and pain in the hands and feet on exposure to cold (possible signs of Raynaud's phenomenon)? Is there a recent history of insect bite, infection or other illness, asthma, or allergic rhinitis? Is the child taking nonsteroidal anti-inflammatory medications?


Table 3
What to ask children with chronic hives


A few pearls regarding hives may help with your evaluation:

  • It is imperative that the duration of the individual wheal be established. Ordinary hives last for less than 24 hours.

  • Remember the lengthy list of stimuli and illnesses associated with hives: allergens, contactants, infections, insects, collagen vascular disease, malignancy, hereditary disorders, and thyroid disease.

  • The initial allergic urticarial reaction to a drug is usually seen after a few days of exposure, but it can occur with the first dose when there has been a previous reaction. Serum sickness reactions are accompanied by fever, joint aches, and lymphadenopathy. This type of reaction usually occurs after the tenth day of therapy. There have been some reports of urticarial drug reactions occurring months after exposure, but this is rare.

  • Beware of erythema multiforme. These lesions are frequently confused with acute urticaria (Figure 2). The hallmarks of erythema multiforme are the acral distribution, the eventual appearance of target lesions, and their persistence for seven to 10 days. A biopsy will confirm the diagnosis if necessary.

  • In most cases of chronic urticaria, no underlying cause is found.



The history and physical examination may suggest the need for certain screening tests. Simple tests for the child with chronic urticaria focus on physical causes. Once I hear that the chief complaint is hives, I bring out a tongue blade and stroke the forearm, first gently and then more vigorously. I then ask the child or parent to scratch as hard as she can without drawing blood. Recheck these strokes in 15 or 20 minutes. Linear urticarial lesions help with the diagnosis of dermatographism. If the history suggests, you could also cool the skin with an ice pack, use heat, apply water, or even have the child exercise and look for the appearance of hives during the cool-down phase.

Almost every medical laboratory test developed has been used in the pursuit of the cause(s) for chronic urticaria, but the return on extensive and expensive laboratory tests is low. The history should direct the selection of tests, which are done for the most part to rule out serious conditions. As shown in Table 4, a cost-effective set of screening tests may include an ESR as a non-specific measure of inflammation, a CBC with differential specifically looking for eosinophilia, liver function tests, and a urinalysis.


Table 4
Tests to consider


Occasionally, more extensive testing is called for. A cause for chronic urticaria that is so old and established that it may not even be mentioned in current articles is streptococcal infection.10 A throat culture for b-hemolytic streptococcus or an anti-streptolysin O titer may point to streptococcus as a cause. Connective tissue and autoimmune disorders are screened with an ANA, a rheumatoid factor, and levels of complement C3 and C4 or a CH50. Cryoglobulins are responsible for some forms of cold-induced urticaria. Immune complex disease can be determined by the Raji test. Thyroid antibodies can be obtained if you suspect thyroid disease, and neoplastic disease may be revealed with a CBC and differential.

Skin tests are frequently performed with varied results. A high total IgE, positive skin tests, and positive in vitro tests such as RAST are only as good as the history that supports them. Tests for specific IgE—IgE directed against a specific antigen—are done only to support a clinical impression of a particular cause or causes, such as cat allergy; otherwise their yield is low. For unusual presentations, refractory cases, persistent lesions, and urticarial lesions with associated pigment changes, refer the patient to a dermatologist for a skin biopsy. The rate of return on various laboratory tests is shown in Table 5.


Table 5
Rate of return on screening tests

TestNumber performedNumber with an abnormal resultPercent positive
Total IgE1965227%
C3, C4, CH5011200
C1 inhibitor1800
Cold agglutinins22314%
ASO titer561221%
Protein electrophoresis8600
Stool for O/P18974%
Throat culture2229%
Chest radiograph8700
Sinus radiograph3925%


Treatment is step-wise

The pediatrician can institute some therapies; others are better left to the specialist.

First-line approaches. One of the most effective and essential forms of treatment is avoidance. If a specific physical or allergic cause can be determined, nothing will work better. A second potential remedy is the treatment of any underlying condition associated with the chronic urticaria, such as occult infection or thyroid disease.

The next level of treatment is the use of a wide range of medications. Therapy can be directed against released histamine with H-1 receptor antagonists or even H-2 receptor antagonists. Oral steroids can deal with mediators other than histamine or immune modulate.

Potential referral or specialist approaches. Another approach uses calcium-channel blocking agents to prevent mediator release. Plasmapharesis has been shown to produce temporary improvements by decreasing immunoglobulin levels and perhaps by decreasing histamine releasing factors.11,12 Cyclosporin at a dose of 4 mg/kg/day for four weeks caused improvement from a combination of immunomodulation and its anti-inflammatory effect, although the side effects profile and cost limit the use of this agent.13

Better living through chemistry. I approach treatment in a series of steps. The first agent I introduce is an antihistamine, specifically an H-1 receptor antagonist. In choosing one, I take into consideration the age of the patient, whether or not the patient attends school, the constraints of dosing intervals, taste, and ease of administration.

Urticaria is often worse at night, when the distractions of the day are gone and the child is trying to fall asleep. Despite all we hear about the advantages of non-sedating second-generation antihistamines, sedation can be a good thing for some children with chronic urticaria. I often choose hydroxyzine, 2.0 mg/kg divided qid. The half-life of hydroxyzine is long and permits qid dosing. I start with 0.5 mg/kg at night and gradually increase to 2.0 mg/kg. The dose is increased to find the minimal amount that controls the itch. For the school child and those in whom sedation is an issue, loratadine or cetirizine is a good choice. These agents are available in pill or liquid form and can be used for children of various ages.

If control is still not achieved, I add an H-2 blocking agent, usually cimetidine. One of the concerns with this agent is its effect on cytochrome P450. Cimetidine demonstrates potent blockade of this enzymatic pathway, perhaps more than any other H-2 receptor antagonist. Research has shown that this agent may provide clinical control because of the increase in levels of the H-1 antagonist.14 Cimetidine has been shown to increase the levels of hydroxyzine but not cetirizine. I recommend a three-week trial of cimetidine.

The role of glucocorticosteroids in treating chronic urticaria is controversial,4,11,15 and parents have significant concerns regarding this form of therapy. I sometimes add prednisone, 2 mg/kg to a maximum of 60 mg, to be taken once a day for five to seven days. If there is complete resolution the agent can be abruptly discontinued. If symptoms return a few weeks later, I repeat the steroid burst and begin a slow taper. I explain to the families and patients that the point of the taper is to find the minimum amount of steroid that controls the urticaria, and that in time I hope that amount will be none.

Other agents that can be tried if steroids fail to control the hives include terbutaline, tricyclic antidepressants, and anti-serotonergic agents. Reports on the effect of terbutaline are mixed. One study in adults showed efficacy when the dosage was 1.25 mg tid; however, a double-blind cross-over study showed no effect of 2.5 mg tid. Doxepin, a tricyclic antidepressant, is the agent of choice in this category, and cyproheptadine is a good anti-serotonergic agent with perhaps more effect in the physical forms of chronic urticaria. Cyproheptadine may cause significant stimulation of the appetite; warn patients and parents about this side effect. Table 6 lists the therapeutic agents and their doses.


Table 6
Therapeutic medications

   Cetirizine:2-5 years old: 2.5-5.0 mg/day
>6 years old: 5-10 mg/day
     Maximum doses:2-6 years old: 12 mg/day
7-14 years old: 16 mg/day
Adults: 32 mg/day


When to refer

Consider a specialty referral for the following situations: peanut- or latex-induced urticaria, urticarial vasculitis, urticaria with systemic manifestations, urticaria that responds poorly to therapy, and urticaria accompanied by angioedema.

Refer either to an allergist or to a dermatologist. Each specialty offers its own unique twist and special tools. Both types of specialist will pursue a cause, and at times you may need both. As an allergist, I send children with lesions that last more than a day or two to the dermatologist, anticipating a skin biopsy. I get referrals from my dermatology colleagues for skin testing or when the patient has asthma or anaphylaxis. Whichever specialty is chosen, be sure the proper amount of time is spent on the history and examination.

Wrapping it up

Finding a cause of chronic urticaria is difficult, and all too frequently the treatment program achieves symptom control rather than cure. Inform your patients and parents that the most concerning and uncomfortable part of the urticaria, the itch, is usually controlled, though skin manifestations, erythema especially, may continue to appear.

Encourage families to keep in touch, and remind them that each patient has a 50/50 chance of "outgrowing" chronic urticaria within a year. In the meantime, offer psychological as well as medical support. Very rarely is the disorder a sign of something serious, but it's a miserable condition for the children who have it, and they need all the help you can give them.


1. Matthews K: Urticaria and angioedema. J Allergy Clin Immunol 1983;72:1

2. Mortureux P, Leaute-Labreze C, Legrain-Lifermann V, et al: Acute urticaria in infancy and early childhood. Arch Dermatol 1998;134:319

3. Champion RH: Urticaria, in Rook A, Wilkinson DS, Ebling FJG, et al (eds): Textbook of Dermatology. London, Blackwell Scientific Publications, 1986, pp 1099­1108

4. Charlesworth EN: Urticaria and angioedema: A clinical spectrum. Ann Allergy 1996;76:484

5. Kanerva L, Toikkanen J, Jolanki R, et al: Statistical data on occupational contact urticaria. Contact Dermatitis 1996;35:229

6. Wustlich S, Brehler R, Luger TA, et al: Helicobacter pylori as a possible bacterial focus of chronic urticaria. Dermatology 1999;198:130

7. Zuberbier T, Chantraine-Hess S, Hartmann K, et al: Pseudoallergen-free diet in the treatment of chronic urticaria: A prospective study. Acta Derm Vener Eol (Stockholm) 1995;75:484

8. Leung DYM, Diaz LA, DeLeo V, et al: Allergic and immunologic skin disorders. JAMA 1997;278:1914

9. Halpern S: Chronic hives in children: An analysis of 75 cases. Ann Allergy 1965;23:589

10. Volonakis M, Katsarou-Katsari A, Stratigos J: Etiologic factors in childhood chronic urticaria. Ann Allergy 1992;69:61

11. Greaves MW, Sabroe RA: Allergy and the skin I—Urticaria. BMJ 1998;516:1147

12. Gratten CE, Francis DM, Slater NG, et al: Plasmapharesis for severe unremitting chronic urticaria. Lancet 1992;339:1078

13. Toubi E, Blant S, Kessel S: Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. Allergy 1997;52:312

14. Simons FE, Sussman GL, and Simons KJ: Effect of the H2-antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H1-antagonists hydroxyzine and cetirizine in patients with chronic urticaria. J Allergy Clin Immunol 1995;95:685-93

15. Kanwar AJ, Greaves MW: Approach to the patient with chronic urticaria. Hosp Pract 1996; 31(3):175

Suggested Reading

Ehlers I, Niggemann B, Binder C, et al: Role of nonallergic hypersensitivity reactions in children with chronic urticaria. Allergy 1998;53:1074

O'Donnell BF, Lawlor F, Simpson J, et al: The impact of chronic urticaria on the quality of life. Br J Dermatol 1997;136:197

THE AUTHOR is Clinical Associate Professor of Pediatrics in the Section of Allergy and Clinical Immunology, Division of Pediatric Pulmonology and Critical Care Medicine, James Whitcomb Riley Hospital for Children, Indianapolis.


Frederick Leickly. When the road gets bumpy: Managing chronic urticaria. Contemporary Pediatrics 2000;5:58.