Chronic urticaria and atopic disorders: a cross-sectional study of 11 271 patients

Dear Editor, Chronic urticaria (CU) and atopic disorders such as atopic dermatitis (AD), allergic rhinoconjunctivitis (AR) and asthma are related to aberrant immune function. The relationship between atopic disorders and CU is controversial, mostly as epidemiological data are lacking. The aim of our study was to investigate the association between CU and asthma, AD and AR using the database of Clalit Health Services (CHS) – the largest healthcare provider organization in Israel. Our study was designed as a cross‐sectional study of patients with CU and age‐ and sex‐matched controls. CU was defined as four pairs of urticaria diagnoses, each recorded within a period of 6 weeks, registered by physicians in the primary‐care setting or during hospitalization from January 2002 to December 2012. The control group consisted of age‐ and sex‐matched patients without urticaria extracted from the general population of CHS enrolees. Asthma, AD and AR are all recorded as independent codes in the CHS database and are registered by a dermatologist, an immunologist, a pulmonologist or a general practitioner. The patient demographics at baseline and concomitant atopic morbidities were described and compared. Continuous variables were compared using t‐tests; dichotomous variables were compared by Pearson's χ2‐test. A logistic regression model was used to assess the associations between CU and atopy in a multivariate analysis. Interaction terms for statistically significant effect modifiers were added to the multivariate model when appropriate. All statistical tests performed were two sided; P‐values < 0·05 were considered statistically significant. The study included 11 271 patients with CU and 67 216 age‐ and sex‐matched controls. The mean age was 47·4 years. Patients with CU were more likely to be female (66%) and obese (22·6% vs. 18·8%, P < 0·001), and had a higher Charlson Comorbidity Index (2·03 ± 2·6 vs. 0·95 ± 1·6, P < 0·001) in comparison with controls. Additionally, patients with CU were more likely to be of Arabic ethnicity (21·5% vs. 20·9%, P < 0·001) and of intermediate socioeconomic status (39·4% vs. 37·6%, P < 0·001) compared with the control group. No other demographic differences were observed. Of 11 271 patients with CU, 1215 (10·8%), 1100 (9·8%) and 2238 (19·9%) had had asthma, AD and AR, respectively, vs. 4342 (6·5%), 2471 (3·7%) and 6807 (10·1%) of 67 216 controls (all significantly different). In a multivariate analysis CU was significantly associated with all of the investigated morbidities adjusting for age, sex, body mass index, smoking status and ethnicity (Table 1). Multivariate logistic regression models for the association between asthma, allergic rhinitis and atopic dermatitis in the study population (n = 78 487) The models were adjusted for age, sex, body mass index, smoking status and ethnicity. P‐values < 0·05 are statistically significant. OR, odds ratio; CI, confidence interval. Multivariate logistic regression models for the association between asthma, allergic rhinitis and atopic dermatitis in the study population (n = 78 487) The models were adjusted for age, sex, body mass index, smoking status and ethnicity. P‐values < 0·05 are statistically significant. OR, odds ratio; CI, confidence interval. CU and atopy share some similarities. Atopy is associated with various autoimmune morbidities,1,2 similarly CU.3 IgE sensitization is higher among patients with CU than in the general population, resembling many atopic conditions.4,5,6 Consistently with this, previous epidemiological observations reported an association between CU and atopy.7,8 On the other hand, other opposing epidemiological studies reported no such association.4,7 Nevertheless, these inconsistent epidemiological studies were mostly limited by relying on small series and restricted paediatric populations, or applied nonvalidated questionnaires. Moreover, some of the studies refer to urticaria diagnosis and not to CU explicitly. Thus our report augments the possibility of such an association. The association between CU and atopic disorders may reflect an aberrant cross‐talk between T helper cells and mast cells, an interaction that is not yet fully understood. For example, Shefler et al. reported that the activity of mast cells might be indirectly affected by remote T cells.9 Perhaps delicate aberrations in this cross‐talk may lead to co‐occurrence of CU and atopy in the same patients. Our study has some limitations. Case definition was strict and conservative with high specificity (four pairs of urticaria diagnoses, each recorded within a period of 6 weeks), which may thus have led to an underestimation of the actual prevalence of CU in Israel. Specific screening tests such as peak flow meter, IgE sensitization or prick tests were not a precondition to include the atopic diagnoses in our study, and therefore overdiagnosis is possible and represents another limitation. In light of this limitation we avoided the use of the term ‘atopy’ for describing the investigated conditions and instead used the term ‘atopic disorders’. While not all cases of asthma, AR and AD in our study are truly atopic (i.e. IgE mediated), the extrapolation that most of them are atopic is reasonable. As in any cross‐sectional study, incidence–prevalence bias and temporal bias are also potential limitations. In spite of these limitations the present study reveals important data regarding the association between CU and asthma, AD and AR. In conclusion, we observed an association between CU and asthma, AD and AR. These observations may open new avenues in the understanding of the aetiopathogenesis of CU and atopy, and also impact on the management of atopy in the setting of CU and vice versa. Funding sources: the present research was sponsored by an unrestricted research grant from Novartis AG. The company was not involved in any part of the study or writing; manuscript approval was not required prior to its submission. Conflicts of interest: A.D.C. has received research grants from Novartis, and in the last 3 years has served as a consultant, advisor or speaker at AbbVie, Dexcel Pharma, Janssen, Novartis, Perrigo, Pfizer and Rafa. All of the other authors state no conflicts of interest. G.S., E.M., N.A.L. and A.D.C. contributed equally.