Omalizumab effectively treats chronic cold urticaria
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Omalizumab effectively treated chronic cold urticaria and prevented further episodes of anaphylaxis, according to a single-center study published in The Journal of Allergy and Clinical Immunology: In Practice.
The number of people with chronic cold urticaria (CCU) — a physical subtype of chronic inducible urticaria defined as urticaria and/or angioedema after the skin is exposed to cold — is difficult to determine due to a lack of population-based studies, according to Nicholas L. Hartog, MD, an allergy and immunology specialist with Spectrum Health.
“We currently estimate as many as 1% of adults have chronic urticaria,” Hartog told Healio. “Within that population with chronic urticaria, we estimate 20% to 30% fall into the category of inducible urticaria.”
There also is no clear explanation why people develop CCU, though some monogenetic immunodysregulatory diseases can include cold urticaria as a component, Hartog said. These diseases must be ruled out before CCU is diagnosed.
“But, once you have it, triggers are cold exposure to the skin. Everyone varies on how cold it must be to trigger symptoms. Some will be triggered by air conditioning, whereas others will need to have exposed skin on a cold winter day. It is usually the active rewarming after cold exposure that triggers the symptoms,” he said, adding that some patients also have symptoms, which can persist for hours, after water has evaporated from their skin from a shower or swimming.
Most patients who have chronic urticaria do not have specific risks, Hartog said, but they are treated because of the decreased quality of life that it can cause.
“However, in CCU, there is a risk for life-threatening anaphylaxis upon sudden exposure to cold in a large body surface area,” Hartog said. “One such situation could include jumping into a cold body of water. Because of this risk, we do counsel patients about the risk for anaphylaxis and prescribe an epinephrine autoinjector.”
Currently, the researchers said, there are no clear guidelines for specifically treating CCU or if it should be treated differently from chronic spontaneous urticaria, although second-generation nonsedating H1-antihistamines often are used as the first line of treatment. Case studies have shown that omalizumab (Xolair; Genentech, Novartis), a humanized monoclonal anti-IgE antibody, may be a viable alternative therapy for patients refractory to antihistamine therapy.
The researchers conducted a retrospective review of 19 patients with isolated CCU at Allergy and Immunology Clinic at Spectrum Health in Grand Rapids, Michigan. The patients were aged 5 to 35 years, and there were 11 males and 8 females in the study.
All patients received maximum oral antihistamine therapy, and 11 achieved adequate symptom control. Seven of the remaining patients — five of whom had a history of anaphylaxis — then received 300 mg (n = 6) or 150 mg (n = 1) monthly omalizumab. The eighth remaining patient was lost to follow-up.
“The patients who went on omalizumab had failure of symptom resolution, so we proceeded to omalizumab. It is unclear if a history of cold-induced anaphylaxis should trigger a physician to more actively pursue omalizumab treatment,” Hartog said.
Median follow-up for patients receiving omalizumab was 14 months.
Overall, four of the six patients who had a history of anaphylaxis had no further anaphylactic episodes with omalizumab.
One patient continued to have significant urticaria with cold exposure although their anaphylaxis completely resolved. Researchers observed initial improvement after increasing the patient’s therapy frequency to every 2 weeks. The patient did not follow up again.
Another patient required epinephrine use due to continued anaphylaxis even with monthly omalizumab therapy. When insurance declined the use of omalizumab every 2 weeks, clinicians added 100 mg daily cyclosporine (1.12mg/kg/day), leading to resolution of this recurrent anaphylaxis but persistent urticaria. The clinicians then increased the cyclosporine dose to 200 mg (2.24 mg/kg/day) and continued omalizumab, and symptoms completely resolved.
The researchers reported no adverse events among the patients receiving omalizumab.
The researchers noted questions remain regarding the proper time for initiating omalizumab, the adequate treatment duration and dosage, and use of alternative immunomodulatory therapies.
“This retrospective review of treatment was provided as part of clinical care. This was not prospective, placebo-controlled or blinded, and the number of patients was small, so it is hard to make conclusions between subgroups,” Hartog said, adding that additional prospective research is needed to evaluate the treatment response.
He also said three key unresolved questions remain, including defining the ideal treatment algorithm; whether omalizumab affects the rate of cold-induced anaphylaxis or, rather, whether controlling the CCU decreases its rate; and if a history of cold-induced anaphylaxis should prompt clinicians to consider omalizumab earlier, even if symptoms are controlled with a second-generation H1-antihistamine.
Perspective
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This study by Choi and colleagues focuses on a relatively uncommon condition in most allergists’ practice: CCU. But, the study is important, as CCU sometimes can be very difficult to control and it can lead to more severe outcomes such as anaphylaxis, which is uncommon in most urticarial conditions.
The diagnosis can be tricky, especially among patients with anaphylaxis, as they are typically focused on some type of allergen, food or inhalant causing their reaction. Sometimes, they may not associate the reaction with exposure to cold.
One of my patients presented after being seen in the ED and treated for anaphylaxis. His parents wanted food testing to determine what he ate that caused his reaction.
However, after taking a detailed history, it was apparent that he started having issues after swimming in a cold lake. His ice cube test was positive, confirming the diagnosis. He has since done well, avoiding cold exposure and taking antihistamines.
I believe this small study does mirror the experience of most allergists, as there is a range of severity of the disease, and patients’ response to conventional medications can be suboptimal. Oftentimes, these patients are difficult to control with the typical first-line therapies used for urticaria.
My only concern with the study would be the lack of patient numbers to draw firm conclusions. I would like to see it replicated in a larger patient population, but it certainly provides insight into the possible use of omalizumab in the patients with more refractory CCU.
Further research into other alternative therapies with either immunomodulating medications or other biologics would be an area for future study into this unique condition.
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