Urticaria, an autoimmune condition of the skin, affects an estimated 15% to 25% of the population, most commonly adults aged 30 to 50 years and with a higher frequency of occurrence in women than men.1 Presenting as defined areas of pruritic wheals on the skin with surrounding edema, urticaria is often accompanied by angioedema.2

Clinical Forms

Amy Kassouf, MD, dermatologist at Cleveland Clinic in Rochester, New York, told us that at her facility, “We see acute urticaria (also referred to as hives) most frequently. They appear as short-term welts usually lasting only hours or evolving over a 24-hour period, while some last for several days. But if they come and go for more than 6 weeks, then we consider them chronic.”

Pathophysiology


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Urticaria is associated with the activation of mast cells and basophils that produce a proinflammatory reaction. The causes are not well understood, although autoimmune factors may contribute to more than 50% of chronic cases.1,3 Triggers may include food intolerances, genetic factors, and infections.3 Contact urticaria occurs as a result of sensitivities to latex, cosmetics, and chemical substances.4

About 20% to 30% of chronic inducible urticaria is triggered by exposure to environmental challenges, including heat, cold, sun, vibrations, and pressure.4 Dr Kassouf explained that she sees patients with urticaria throughout the year, although it is more likely to appear during allergy seasons, as many cases of hives are related to insect bites and other seasonal allergens and foods. “Once the hives are chronic, it is unlikely that there is a single allergen causing it, and we evaluate patients for other conditions including autoimmune diseases,” Dr Kassouf said.

A type I genetic hypersensitivity to immunoglobulin (Ig)-E is a common predisposing factor in acute urticaria, as the IgE antigen binds to antibodies on mast cells, releasing a cascade of histamine and other inflammatory mediators.2,4 A review found that the spontaneous form of chronic urticaria is driven by the combined development of autoantibodies to IgE and a high affinity for its receptor.1 Type II autoimmunity, in which IgM or IgM antibodies bind to antigen on the target cell, is also believed to contribute to symptoms in a subset of patients.3

Treatment Strategies

The mainstays of current pharmacotherapy for chronic spontaneous urticaria (CSU) are antihistamines.1 “Initially we start with antihistamines since histamine is the chemical released by the body most closely related to the hives,” explained Dr Kassouf, noting that the most frequent choices of treatment include diphenhydramine, cetirizine, loratadine, and other similar allergy medications, as well as other classes of allergy medications such as montelukast. “These can be augmented by adding some of the common heartburn medications such as ranitidine and famotidine, as they are a different type of antihistamine and can add to the overall improvement,” she said.

Sonali J. Bracken, MD, PhD, a researcher at Duke University Medical Center in Durham, North Carolina, reports that in the past when she saw patients in clinic, “we would typically treat with higher than standard doses of antihistamines. In refractory patients, one can consider such treatments as hydroxychloroquine, tacrolimus, dapsone, mycophenolate, or cyclosporine. Most of these therapies are not [US Food and Drug Administration] approved, although this was never an issue because we could get access to anti-IgE therapy (eg, omalizumab) in most cases. The latter is the preferred agent for refractory CSU, particularly in those with high baseline IgE levels,” she said, pointing out that omalizumab also has a relatively good safety profile. “My suspicion is that most of these refractory patients would be funneled to an allergy clinic,” she added.

European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma Recommendations and European Network/European Dermatology Forum/World Allergy Organization guidelines recommend a short course of systemic corticosteroids for acute urticaria and acute exacerbations of refractory CSU; a short course of oral corticosteroids is treatment for a maximum of 10 days.5

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Additional Therapeutic Strategies

“If there is a known allergen, then allergen avoidance, if possible, or desensitization is the treatment of choice. If not, then combination treatments or use of other allergy medications or medications with antihistamine effects such as doxepin or anti-inflammatory properties such as dapsone can be helpful. In extreme cases we may need immunosuppressive agents such as cyclosporine,” said Dr Kassouf, adding that, “When hives are severe, they may require treatment with prednisone, although this is only a short-term use medication and should not be used for chronic cases, if possible. Newer medications such as omalizumab are designed for long-term use for treating chronic urticaria.”

Hives usually itch terribly, and itching is often more distracting and uncomfortable than pain, explained Dr Kassouf. “Nighttime is the worst time for itching because our natural anti-inflammatory hormones in our body are at a low point. Helping people sleep at night can improve the quality of life” if chronic hives are an issue. To aid in sleeping, “A cool room with other biofeedback routines can help bridge the gap between what medication can do and what helps comfort the patient with the fewest side effects.”

“Most chronic urticarial episodes resolve spontaneously, but it may be weeks or even years before that happens,” Dr Kassouf pointed out. She recommends using over-the-counter anti-itch creams and additives for the bath to soothe irritated and scratched skin and treat other itchy conditions such as dry skin that add to patients’ overall discomfort. “Oftentimes we need a multifaceted and even a multispecialty approach to get the best results.”

References

1. Bracken SJ, Abraham S, MacLeod AS. Autoimmune theories of chronic spontaneous urticaria. Front Immunol. 2019;10:627.

2. Min TK, Saini SS. Emerging therapies in chronic spontaneous urticaria. Allergy Asthma Immunol Res. 2019;11(4):470-481.

3. Kolkhir P, Church MK, Weller, K, et al. Autoimmune chronic spontaneous urticaria: What we know and what we do not know. J Allergy Clin Immunol. 2017;139:1772-1781.

4. Kayiran MA, Akdeniz N. Diagnosis and treatment of urticaria in primary care. North Clin Istanb. 2019;6(1):93-99.

5. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy 2018;73:1393-1414.