Mortality risks increase with chronic spontaneous urticaria
Key takeaways:
- Higher mortality rates persisted across stratifications based on comorbidities, sex, age, race and treatment.
- Patients with chronic spontaneous urticaria were three times more likely to die by suicide.
Adults with chronic spontaneous urticaria experienced greater mortality, probably due to increased risks for comorbidities, compared with a control group, according to a study published in The Journal of Allergy and Clinical Immunology.
These higher mortality rates were more pronounced among patients who were white and who were aged 18 to 40 years, Pavel Kolkhir, MD, head of the chronic spontaneous urticaria program, Institute of Allergology, Charité University Medicine, Berlin, and colleagues wrote.
The researchers launched the study “to better define and investigate the so called ‘urticarial march’ in patients with chronic spontaneous urticaria (CSU), including development of different comorbidities over time,” Kolkhir told Healio.
The global, population-based, retrospective cohort study examined the electronic health records of 264,680 adults with CSU and 264,680 adults who did not have CSU (both groups: mean age, 47.5 years; 71.5% women; 73% white).
“We were surprised to see increased mortality rates in patients with CSU,” Kolkhir said.
Rates of all-cause mortality included 1.35% for the CSU group and 0.63% for the control group (HR = 2.1; 95% CI, 1.97-2.22) at 3 months; 3.33% for the CSU group and 1.82% for the control group (HR = 1.77; 95% CI, 1.71-1.83) at 1 year; and 9% for the CSU group and 5.14% for the control group (HR = 1.69; 95% CI, 1.65-1.73) at 5 years. The researchers called these differences significant.
Higher mortality rates persisted for the CSU group in a sensitivity analysis that accounted for 16 comorbidities. These rates included 1.23% vs. 0.41% (HR = 3.04; 95% CI, 2.57-3.61) at 3 months, 2.35% vs. 1.27% (HR = 1.97; 95% CI, 1.78-2.19) at 1 year and 2.61% vs. 1.69% (HR = 1.71; 95% CI, 1.56-1.88) at 5 years.
A sensitivity analysis that stratified by sex found higher mortality rates for men and women with vs. without CSU as well. For example, rates at 5 years included 7.88% vs. 5.92% (HR = 1.31; 95% CI, 1.28-1.34) for women and 11.68 vs. 9.22% (HR = 1.22; 95% CI, 1.18-1.26) for men.
Higher mortality rates also persisted through age groups at 12 months, including 1.36% vs. 0.62% (HR = 2.14; 95% CI, 1.92-2.38) at age 18 to 40 years, 2.19% vs. 1.41% (HR = 1.52; 95% CI, 1.41-1.64) at age 41 to 60 years, and 4.56% vs. 3.43% (HR = 1.32; 95% CI, 1.25-1.39) at age 61 to 80 years.
Mortality rates at 12 months also increased for the CSU group when stratified by race, with hazard ratios including 1.19 (95% CI, 1.06-1.33) for African American or Black patients, 1.37 (95% CI, 1.01-1.87) for Asian patients and 2.14 (95% CI, 2.04-2.25) for white patients.
In a direct comparison, mortality rates included 2.97% for white patients and 2.5% for African American or Black patients (HR = 1.25; 95% CI, 1.12-1.38).
Propensity score matching yielded 227,477 patients with CSU and 227,477 controls (both groups: mean age, 49.5 years; 71.7% women; 75.7% white). Suicide rates included 3.89% for the CSU group and 1.25% for the controls (HR = 3.14; 95% CI, 3-3.28).
Hazard ratios with comorbidities among the CSU group also included 1.86 (95% CI; 1.79-1.92) for ischemic heart diseases and 2.27 (95% CI, 2.19-2.35) for cerebrovascular diseases.
Rates of malignant neoplasms included 5.8% for the CSU group and 2.79% for the control group (HR = 2.09; 95% CI, 2.02-2.16). Rates of diabetes mellitus included 6.03% for the CSU group and 2.98% for the control group (95% CI, 1.98-2.12).
However, the researchers noted, there were no differences between the groups in risks for hypertensive diseases following correction for multiple testing.
Treatment for CSU included oral corticosteroids (n = 117,372), second-generation H1 antihistamines (n = 113,334), omalizumab (n = 1,514) and cyclosporine A (n = 356), with 19,839 patients not receiving any prescriptions.
Mortality rates among patients using oral corticosteroids included 0.9% at 3 months, 2.43% at 12 months and 7.73% at 60 months. Mortality rates for the cyclosporine A group included 3.01% at both 3 months and 12 months and 4.52% at 60 months.
Among patients with second-generation H1 antihistamines, rates included 0.48% at 3 months, 1.13% at 12 months and 3.24% at 60 months. The omalizumab group had rates of 0.66% across all time points.
Mortality rates were higher for patients with no prescriptions than patients with second-generation H1 antihistamines (2.28% vs. 1.01%; HR = 1.84; 95% CI, 1.37-2.46). Rates also were higher for patients with second-generation H1 antihistamines than those with omalizumab (2.62% vs. 0.69%; HR = 3.99; 95% CI, 1.78-8.97).
Based on these findings, the researchers concluded that patients with CSU had higher mortality rates than those who did not have CSU, particularly patients who were white and who were aged 18 to 20 years.
Noting that CSU itself is not life-threatening, the researchers attributed these higher rates of mortality to comorbidities associated with CSU, such as autoimmune diseases, mental health disorders, metabolic syndrome and cancer.
“Increased mortality rates/risk in patients with CSU may be explained by increased risk for comorbidities and consequences of having CSU, such as suicide, and probably by the long-term use of systemic corticosteroids,” Kolkhir said. “Effective urticaria guideline-recommended treatment may decrease the risk of mortality.”
However, he continued, additional studies should investigate these findings using other populations. These findings also may inform improved approaches to care, he added.
“Our findings indicate the need for screening of comorbidities in CSU patients and use of urticaria guideline-recommended treatment such as second-generation H1-antihistamines and omalizumab,” Kolkhir said. “Furthermore, systemic corticosteroids should be used only in case of acute severe CSU exacerbation and not longer than 10 days.”
For more information:
Pavel Kolkhir, MD, can be reached at pavel.kolkhir@charite.de.
Perspective
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Whenever studied, patients with CSU have been reported to have significant increases in mental health issues. Talking to patients often reveals episodes of sleeplessness, anxiety and depression.
CSU is a disease in which we rarely find a cause. It can last for years, and it can spontaneously exacerbate, causing significant symptoms. In addition, the lack of sleep due to itchiness can result in poor work and school productivity.
It is not surprising, therefore, that patients have more depression and unfortunately suicidal ideation. It was encouraging to see that treatment with antihistamines and omalizumab reduced those risk factors. I think this points to the need to recognize this disorder and treat it appropriately as soon as possible.
These data point to the need for clinicians to do baseline screening on patients with CSU for anxiety and depression. Appropriate treatment might reduce their risk for increased mortality.
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