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Managing Comorbidities in Chronic Urticaria

— Identification and treatment are key to optimal patient outcomes

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Illustration of comorbidities such as autoimmune disease, cancer, etc. over a person itching the hives all over their body
Key Points

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The link between chronic urticaria and atopic diseases, autoimmune diseases, and psychiatric disorders has significant implications for clinical practice. Managing comorbidities is key to optimizing patient outcomes, say experts.

"Patients with chronic urticaria should be recognized as a multimorbid group," noted the authors of a recent in Frontiers in Allergy. "Management should involve recognizing and treating any comorbid disorders in addition to urticaria management."

The relationship between chronic spontaneous urticaria (CSU) and comorbid conditions and diseases is complex, and many questions remain, the team noted. "Prospective well-designed studies addressing the impact of various comorbidities on chronic urticaria course and severity, as well as the impact of therapeutic interventions of comorbidities on both chronic urticaria activity and natural course, are of urgent need."

Autoimmune Disorders

In an of 1,199 patients with CSU, 28% had autoimmune disease, mostly Hashimoto's thyroiditis (25.4%), followed by vitiligo (2.3%), and rheumatoid arthritis (1.0%). Chronic inflammatory bowel disease, peptic ulcer disease, gastroesophageal reflux disease (GERD), and gastritis are also common in patients with CSU. A retrospective cross-sectional survey of GERD and urticaria overlap syndrome found the combination to be three times higher in patients presenting with CSU and two times higher in those presenting with long-duration GERD compared with acute urticaria or short-duration GERD.

Up to 35% of patients with CSU have chronic inducible urticaria (CIndU) -- most frequently dermatographism, cold urticaria, and cholinergic urticaria subtypes. The showed that patients with CSU and CIndU were younger than those with CSU alone, had earlier onset and longer disease duration, higher rates of comorbid allergic disease, and lower rates of concomitant autoimmune disease, and experienced a higher impact on quality of life compared with patients with CSU alone.

Infections

Infection with Helicobacter pylori, dental infections, sinusitis, tonsillitis, and urinary tract infection is reported in up to 77% of patients with CSU. "Since infections can be easily treated, some diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori," advised the authors of one .

Asthma, Rhinitis, Food Allergies

Atopic comorbidities are common in patients with chronic urticaria. In the Scandinavian arm of the in 158 adults with chronic urticaria, asthma was reported in 19.6% of patients, allergic rhinitis in 16.5%, atopic dermatitis in 6.3%, and food allergy in 8.2%.

Atopic dermatitis is a risk factor for CSU in children. Results from a 2018 of epidemiological data from 633 children with CSU, including 522 younger than 12 years, showed that 28.1% had comorbidities and laboratory findings associated with atopy. These included asthma (15.4% of the children), allergic rhinitis (13.8%), and atopic dermatitis (9.4%).

Psychiatric Disorders

"In patients with urticaria, there are many different things that can impact on quality of life and what many would argue would be comorbidities," Jonathan Silverberg, MD, PhD, MPH, director of Clinical Research and Contact Dermatitis at George Washington University School of Medicine and Health Sciences in Washington, D.C., told 鶹ý. "We think about symptoms of anxiety and depression, sleep disturbance, social stigma and social isolation, mental health burden, and functional impact."

The authors of a 2019 review and meta-analysis calculated the overall to be 31.6%. Obsessive-compulsive disorders, somatic symptoms, and disorders related to trauma, stress, and addiction were also reported in patients with chronic urticaria. "This suggests that screening for psychological difficulties/mental health problems among chronic urticaria patients is a necessity," the team said.

Perhaps not surprisingly, young children with urticaria were especially vulnerable to the risk of psychiatric comorbidity. One retrospective study of 25 urticaria patients younger than age 15 showed that 70.4% had at least one psychiatric disorder. In this subgroup, 17 patients were . "Specific tools for the assessment of disease activity and impairment of quality of life in pediatric chronic urticaria are needed for prospective studies aimed to define treatment strategies for children with CU," the authors concluded.

In 2021, an Israeli cohort study of 12,539 CSU patients and 60,510 matched controls showed that younger patients -- ages 18 to 29 -- and those with a higher socioeconomic status (SES) were at highest risk for anxiety. Older patients -- ages 50 to 69 -- and those with lower SES had the highest .

"In light of the clinical implications of a comorbid mental disorder, dermatologists should consider employing mental health screening procedures, especially for patients from specific risk groups," the authors wrote.

. Not only is CSU associated with an increased risk of psychiatric disorders, but a history of anxiety, dissociative, and somatoform disorders is correlated with CSU risk.

"Our study supports that psychological status is not merely a consequence of CSU, as the presence of pre-existing anxiety, dissociative, and somatoform disorders significantly augmented the risk of CSU," the researchers wrote.

A of patients with chronic urticaria and at least one known mental disorder bears this out; 58.1% had comorbid depression, followed by anxiety in 29.8%, attention deficit hyperactivity disorder in 11.3%, post-traumatic stress disorder in 8.9%, personality disorders in 6.4%, and obsessive compulsive disorder in 5.6%.

Cardiometabolic Disorders

The relationship between chronic urticaria and hypertension, hyperlipidemia, metabolic syndrome, and cardiovascular orders remains the focus of ongoing research. A 2021 German cross-sectional study in 17,524 patients diagnosed with chronic urticaria found in 43.5%, and lipoprotein metabolism disorders in 32.1%.

Similarly, the findings from a 2022 Swedish registry-based cohort study in 10,642 adults with chronic urticaria found co-existing diagnoses, along with asthma, allergy, psychiatric, and behavioral disorders.

Cancer

Research also continues into possible associations between CSU and cancer. A noted that "malignancies are generally not considered to cause urticaria or to be a rare cause of urticaria." Still, showing that CSU disappeared after remission of cancer indicates that "chronic urticaria can be caused by cancer and resolves with its cure," the writers said.

Pavel Kolkhir, MD, of the IM Sechenov First Moscow State Medical University and co-authors offered this explanation in a 2022 "primer" in Nature Reviews: "CSU development in patients with cancer might be including activation of complement and coagulation cascade. Therefore, return to normal homeostatic conditions might parallel CSU improvement after cancer treatment," the team wrote.

Read previous installments in this series:

Part 1: Urticaria/Hives: The Search Continues for Causes

Part 2: Keys to Diagnosis of Urticaria

Part 3: Chronic Spontaneous Urticaria and Autoimmunity

Part 4: Case Study: Terrible Recurrent Itchy Wheals All Over This Woman's Body

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    Kristin Jenkins has been a regular contributor to 鶹ý and a columnist for Reading Room, since 2015.

Disclosures

Silverberg reported relationships with AbbVie, AnaptysBio, Asana, Arena, Boehringer-Ingelheim, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, and Regeneron-Sanofi.