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Effective treatment of idiopathic chronic cold urticaria with omalizumab: Report of 3 cases

Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the prevalence, management, and prevalence of associated anaphylaxis of cold urticaria.

To evaluate the prevalence of cold urticaria among CIndU and chronic urticaria (CU) cases, to assess the management of cold urticaria, and to determine the prevalence of associated anaphylaxis.

We searched PubMed and EMBASE for studies pertaining to cold urticaria and/or CIndU published in the past 10 years. We conducted meta-analyses to evaluate the prevalence of cold urticaria among CIndU and CU cases, the management of cold urticaria with H1-antihistamines and omalizumab, and the prevalence of associated anaphylaxis.

Twenty-two studies were included in the systematic review and 14 in the meta-analysis. The pooled prevalence of cold urticaria among patients with CU and CIndU was 7.62% (95% confidence interval [CI], 3.45% to 15.99%; I² = 98%) and 26.10% (95% CI, 14.17% to 43.05%; I² = 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95% CI, 92.47% to 97.54%; I² = 38%) of patients and omalizumab in 5.95% (95% CI , 2.55% to 13.27%; I² = 83%) of patients. The pooled prevalence of anaphylaxis among patients with cold urticaria was 21.49% (95% CI, 15.79% to 28.54%; I² = 69%).

Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines; few patients receive omalizumab. Anaphylaxis is common, and an epinephrine autoinjector prescription may be considered.

Acquired cold-induced urticaria (ACU) has not been well evaluated in pediatrics.

To further evaluate the presentation of ACU in children and associated risk of anaphylaxis.

A retrospective chart review was performed in children 18 years or younger diagnosed with ACU at Boston Children's Hospital (US, Northeast) from 1996 to 2017.

A total of 415 patients with ACU were identified, aged 4 months to 18.3 years at the time of diagnosis, with similar male:female distribution. Most patients had a history of atopic disease (78.3%), and 25.8% had other urticaria. Around two-third of patients experienced only localized cold-induced symptoms (grade 1), whereas 14.0% had diffuse cutaneous symptoms (grade 2) as the most severe reaction, and 18.6% experienced anaphylaxis (grade 3). Swimming triggered 77.6% of grade 3 reactions, whereas the rest were secondary to ingestion of cold food or beverages, or cold air or cold water exposure. Seven percent of subjects had more than 1 episode of anaphylaxis. Cold stimulation test (CST) was performed in 61.7% of patients, and the result was positive in 69.9% of those tested. Positive CST result was significantly associated with increased risk of anaphylaxis. There was a 11.7% rate of anaphylaxis among patients with negative CST result. Disease resolution at any point in the study period was documented in 8.9% of patients and was associated with a negative history of anaphylaxis.

In the largest study to date on ACU, grade 3 reactions occurred in about a fifth of patients. Positive CST result was associated with a higher risk for anaphylaxis from ACU. Epinephrine prescription and patient/family counseling about risk factors for grade 3 reactions are recommended.

Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H₁-antihistamine resistant.

From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs.

We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria.

Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children.

A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted.

Data about special phenotypes, natural course, and prognostic variables of patients with acquired cold urticaria (ACU) are scarce.

We sought to describe the clinical features and disease course of patients with ACU, with special attention paid to particular phenotypes, and to examine possible parameters that could predict the evolution of the disease.

This study was a retrospective chart review of 74 patients with ACU who visited a tertiary referral center of urticaria between 2005 and 2015.

Fourteen patients (18.9%) presented with life-threatening reactions after cold exposure, and 21 (28.4%) showed negative results after cold stimulation tests (classified as atypical ACU). Nineteen patients (25.7%) achieved complete symptoms resolution at the end of the surveillance period and had no subsequent recurrences. Higher rates of atypical ACU along with a lower likelihood of achieving complete symptom resolution was observed in patients who had an onset of symptoms during childhood (P < .05). In patients with atypical ACU, shorter disease duration and lower doses of antihistamines required for achieving disease control were detected (P < .05). Age at disease onset, symptom severity, and cold urticaria threshold values were found to be related to disease evolution (P < .05).

This study was limited by its retrospective nature.

The knowledge of the clinical predictors of the disease evolution along with the clinical features of ACU phenotypes would allow for the establishment of an early and proper therapeutic strategy.