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Chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU) are 2 types of chronic urticaria that have similarities and differences and can also occur individually or together. Both types are marked by wheals and/or angioedema for > 6 weeks. Symptoms develop without triggers in CSU, whereas CIndU has specific triggers for all of its subtypes. When they occur together, it鈥檚 likely that the burden on patients is higher than in CSU alone. Past studies have preliminarily looked at this phenomenon鈥攊ts incidence, duration, and other comorbidities occurring with CSU plus CIndU鈥攁nd how this affects treatment.¹

To increase clinicians鈥� knowledge in this area, investigators in Berlin and Moscow compared patients with CSU, with and without comorbid CIndU, to look at the differences between them regarding their demographics, clinical features, and laboratory studies. The researchers鈥� study was recently published online in the Journal of Allergy and Clinical Immunology: In Practice.¹

The investigators used clinical data from the Moscow Urticaria Center of Reference and Excellence and laboratory results from patients鈥� medical records from September 2018 to October 2022. The efficacy of the treatments received was assessed from patient-reported outcomes obtained from their medical records and certain scales/questionnaires used to track therapy, symptom activity, level of disease control, and impact on quality of life.

What were the associations?

Among the 708 patients with CSU included in the study, 247 (35%) had comorbid CIndU, which occurs more often when there鈥檚 disease onset at a younger age (35 versus 45 years), longer disease duration (20 versus 12 months), lower rates of angioedema (53% versus 72%), and reduced quality of life, as assessed by the Dermatology Life Quality Index (P < .001 for all).

Moreover, there are different types of CIndU, including:

• Symptomatic dermographism, which was found to occur in 18% of all patients and 51% of patients with CSU + CIndU
• Delayed pressure urticaria (DPU): 14% of all patients and 40% of those with CSU + CIndU
• Cold urticaria (ColdU): 5% of all patients and 13% of those with CSU + CIndU
• Cholinergic urticaria (CholU): 4% of all patients and 11% of patients with CSU + CIndU.

Additionally, 5% of all patients (and 14.6% of patients with CSU + CIndU) had 2 or more comorbid CIndUs. The combinations found most frequently were symptomatic dermographism + DPU (25%), ColdU + CholU (16.7%), symptomatic dermographism + CholU (13.9%), and DPU + ColdU (11.1%). In addition, 5 patients in the study group had 3 CIndU types, with 3 of these patients having a combination of symptomatic dermographism + DPU + ColdU.

The investigators also found that when CIndU occurs with CSU, they usually start at the same time (in 67.4% of the patients with CSU + CIndU). The most common subtypes starting at the same time as CSU were symptomatic dermographism (78.9%) and CholU (64%), followed by DPU (59.5%) and ColdU (44.8%). However, at times, CIndU started later than CSU (21.5% of patients with CSU + CIndU); the most common subtype for which this occurred was ColdU (34.5%). CIndU also started before CSU in 11.1% of patients with CSU + CIndU (20.7% in ColdU and 20% in CholU).

Autoimmune and atopic disease

Another important finding was that concomitant autoimmune diseases occur more commonly with CSU alone (21%) than with CSU + CIndU (14.2%, P = .03), and atopy occurs more frequently in patients with CSU + CIndU than in those with stand-alone CSU (18.6% versus 13.4%, P = .041). The most common comorbid atopic disease was allergic rhinitis (18.2% with CSU + CIndU and 12.8% with CSU alone). Regarding the subtypes of CIndU, atopy was most common in those with comorbid ColdU (40.6%), and less common in patients with symptomatic dermographism (16.8%), CholU (15.4%), and DPU (14.1%) (P = .007).

Autoimmune thyroiditis was the most common autoimmune comorbidity, affecting 17.8% with CSU alone and 11% with CSU + CIndU (P = .016). Vitiligo was found in 2.2% of patients with CSU alone but not in any patients with CSU + CIndU. Similar findings were seen for type 1 diabetes, Sj枚gren鈥檚 disease, and pernicious anemia. Ankylosing spondyloarthritis occurred in 1 patient with CSU + CIndU.

Looking at markers of autoimmune CSU, the investigators found that patients with CSU alone showed markers of type IIb autoimmune CSU more often than patients with CSU with comorbid CIndU. CSU-alone patients had lower levels of total immunoglobulin E (IgE) (P = .002), higher anti-thyroid peroxidase IgG combined with low total IgE (P = .005), and lower levels of eosinophils in the blood (P = .011). Eosinopenia occurred more often with CSU alone than with CSU + CIndU (P = .001). Lower IgE levels were also seen in patients with CSU alone versus patients with CSU + CIndU who did not have comorbid atopy (P = .012).

Limitations and conclusions

The authors mentioned some limitations to their study, related to the design of real-world registry studies. Some data, they said, may have been missing for some patients. Additionally, there could have been bias related to clinical practice, as this was a single-center study.

The investigators recommended that future studies be done to look at the non-autoimmune pathogenic mechanisms that drive CSU when there鈥檚 comorbid CIndU. Additionally, investigating the level of IgE autoantibodies in patients with comorbid CIndU may help in discerning whether autoallergic CSU is more common in these patients than in those without this comorbidity.

鈥淥ur findings confirm and demonstrate novel and important clinical and laboratory differences of patients with CSU with and without comorbid CIndU,鈥� the authors concluded in their report. 鈥淜nowledge of these differences may guide routine clinical practice and help predict the course of CSU and develop personalized recommendations and treatment plans.鈥�¹

Published: February 28, 2024