Factors Associated with Symptomatic Dermographism: Findings from the UCARE PREVALENCE-D Study.

Dermographism or 'simple' dermographism, which has been noted in about 1.5% to 5% of healthy individuals, is regarded as a normal physiological phenomenon. However, in symptomatic dermographism (SD), even light pressure or rubbing from clothes may provoke widespread weal-and-flare reactions with itching and burning. It is one of the dermatologic diseases that negatively impacts quality of life. We aimed to reveal triggering factors and/or associated clinical conditions in patients with SD. Forty patients (28 women and 12 men) with SD whose ages varied between 7 and 65 (30.3 +/- 10.7) participated in the study. Patients having chronic idiopathic urticaria, other types of physical urticaria and cutaneous/systemic mastocytosis were excluded. The diagnosis of SD was confirmed by stroking the skin of the back with a tongue blade. This procedure elicited within minutes a linear weal with a flare and severe itching. In light of the history, physical examination, skin prick test (SPT) with aeroallergens and laboratory results, a possible relationship of certain triggering factors and/or associated diseases (psychic factors, atopy, thyroid diseases, diabetes, menopause, infectious, systemic or malignant diseases, history of scabies, and history of drug reaction) to SD were investigated. The duration of SD varied between 10 days and 10 years (mean: 20.8 months). Psychic factors were found to play the initial triggering role in 12 patients (30%). Five patients (12.50%) were atopic, and they had SPT reactivity to house dust mites. Three female patients (7.50%) defined that their complaints began following drug-induced urticarial rash. Two patients (5%) had hyperthyroidism, and one of the patients with SD of 1-month duration had type-II diabetes mellitus. A female patient defined that her complaints began during the onset of menopausal period. SD was observed with scabies in one patient; and after poststreptococcal glomerulonephritis in a 7-year-old girl. No autoimmune, malignant or other systemic diseases were found in patients with SD. Contrary to commonly held opinion, SD may be associated with some diseases and/or triggered by some conditions. In this study, a close temporal relationship between the appearance of SD and psychic factors, drug reactions and scabies was documented. The relation between SD and atopy, hyperthyroidism, diabetes mellitus, menopause and glomerulonephritis seemed unclear.

Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria induced by a physical stimulus. To evaluate the clinical features, prognostic factors, and natural course of childhood CIndU subtypes. Patients (1-18 years old, n = 117) diagnosed with CIndU between March 2011 and March 2019 were analyzed. Patients (n = 101) were re-evaluated for the status of their CIndU at least 6 months after the initial evaluation. The study population comprised of 117 children with a median (inter-quartile range) age of 10.3 (6-14.8) years at admission and a male predominance (53%). Symptomatic dermographism was the most common type of CIndU, affecting 65% of the group, followed by cold urticaria and cholinergic urticaria, which affected 17% and 15.4%, respectively. Baseline serum tryptase levels in cholinergic urticaria and cold urticaria were higher than those in symptomatic dermographism [7.0 (3.3-10.7) μg/L, 4.2 (2.8-9.3) μg/L, and 2.7 μg/L (1.8-5.9), respectively; P = .020]. Recovery was observed in 9.6%, 25.3%, and 34.7% of the CIndU children after 12, 36, and 60 months, respectively. Of the patients with symptomatic dermographism, 40% had remission in 5 years, whereas this rate was only one-fifth in patients with cold urticaria. The worst prognosis was observed in patients with cholinergic urticaria. This study concluded that nearly one-third of children with CIndU recovered within 5 years and symptomatic dermographism has the best prognosis. Cholinergic urticaria is the CIndU type with the worst prognosis, male dominance, and highest baseline serum tryptase levels.

Recently, our research team found a strong and significant association between loss-of-function (LOF) mutations in filaggrin (FLG), a gene that encodes a skin barrier protein, in European and Canadian individuals with peanut allergy (PA).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar These mutations result in a barrier defect and have been associated with atopic dermatitis, asthma, and allergic rhinitis.2Irvine A.D. McLean W.H. Leung D.Y. Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (812) Google Scholar This finding represents the strongest genetic risk factor found to date for PA, a highly heritable disease,3Sicherer S.H. Furlong T.J. Maes H.H. Desnick R.J. Sampson H.A. Gelb B.D. Genetics of peanut allergy: a twin study.J Allergy Clin Immunol. 2000; 106: 53-56Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar with an estimated odds ratio (OR) between 1.9 (Canadian) and 5.3 (English, Dutch, and Irish combined).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar Because there is no uniformly accepted definition of PA short of oral food challenge, it is worthwhile to examine whether the association between the FLG LOF mutations and PA varies with the diagnostic criteria for PA. Furthermore, the frequent coexistence of PA with other atopic conditions may mean that the association between PA and FLG LOF mutations is confounded. Although we controlled for eczema in the European populations in our previous work, data on eczema were not available for the Canadian control group; however, data on asthma were available. Asthma is a potential confounder, as it has known relationships with both PA4Liu A.H. Jaramillo R. Sicherer S.H. Wood R.A. Bock S.A. Burks A.W. et al.National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006.J Allergy Clin Immunol. 2010; 126: 798-806.e13Abstract Full Text Full Text PDF PubMed Scopus (379) Google Scholar and FLG mutations.5Palmer C.N. Ismail T. Lee S.P. Terron-Kwiatkowski A. Zhao Y. Liao H. et al.Filaggrin null mutations are associated with increased asthma severity in children and young adults.J Allergy Clin Immunol. 2007; 120: 64-68Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar By using statistical sensitivity analyses, we examined the effect of PA diagnostic criteria and asthma on the relationship between PA and FLG LOF mutations in a Canadian PA case group. Because the PA case group was composed of both English- and French-speaking individuals, we also investigated whether the difference in OR between the Canadian and European populations could be due to some common French-Canadian mutations not yet identified in FLG.Caucasian subjects from a well-described Canadian pediatric PA case group were recruited (n = 679), and DNA was isolated from salivary samples.1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar One control group consisted of adult Caucasians recruited from the general population of Ontario, Canada; DNA was provided by the Ontario Population Genomics Platform at The Centre for Applied Genomics (Toronto) (n = 894). A second control group of newborn babies from Quebec City was sampled on the basis of French-Canadian surname (stored blood; n = 268).6Girouard J. Giguere Y. Delage R. Rousseau F. Prevalence of HFE gene C282Y and H63D mutations in a French-Canadian population of neonates and in referred patients.Hum Mol Genet. 2002; 11: 185-189Crossref PubMed Scopus (18) Google Scholar All samples were genotyped in Dundee, Scotland, for the 4 most common FLG LOF mutations found in Caucasians (R501X, 2282del4, R2447X, and S3247X). rs and accession numbers for mutations are available in the Online Repository at www.jacionline.org (see Table E1)."Mutation carriers" were defined as those with heterozygous, homozygous, or compound heterozygous mutations. Those individuals with none of the 4 FLG mutations were classified as "nonmutation carriers." The association between mutation status and PA was compared with the Ontario control group, the Quebec control group, and the combined control group. To evaluate whether the association between PA and mutation status changed with case definition, a continuum of PA case definitions was constructed and the resulting OR trends with case definition were examined by using the combined control groups. The methodology and rationale for these definitions are given in the Online Repository available at www.jacionline.org (see Tables E2 and E3). To increase power, case definitions were transformed into an ordered variable and the association between PA and FLG mutations was examined by using regression modeling through increasingly stringent definitions of PA to see whether the OR changed significantly.We also examined the effect of asthma on FLG mutation status and PA. Logistic regression using the Ontario control group was conducted with PA status, age, sex, asthma, and interaction terms for PA and age, PA and sex, and PA and asthma. Because there may be interaction between mutation status, asthma, and smoking,7Berg N.D. Husemoen L.L. Thuesen B.H. Hersoug L.G. Elberling J. Thyssen J.P. et al.Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.J Allergy Clin Immunol. 2012; 129 (e1-2): 374-380Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar and self-identified asthmatic patients may have significant misclassification, analyses controlled for smoking history in the controls and misclassification in the asthma variable in both controls and cases. A constructed atopic asthma variable was used to control for the effect of smoking with 4 assumptions: (1) Those individuals who have atopic asthma in childhood are less likely to smoke as adults. (2) Those adults who have asthma and have never smoked are more likely to have atopic asthma. (3) If a patient reports bronchial emphysema, he or she does not have atopic asthma. (4) Asthma reported in the case group is atopic. To examine the possibility of error due to self-report of asthma, we completed a sensitivity analysis taking into account data from the PA registry that found that 6% had "forgotten" previously noted atopic history, while 12% more reported atopic history on the current questionnaire than at baseline registry recruitment. Random sampling and subsequent logistic regression modeling was completed 100 times to see the overall effect of error in asthma reporting on the relationship of PA and FLG LOF mutations using these parameters.Finally, a similar sensitivity analysis of PA status was conducted, as PA status could be affected by the age disparity between the Ontario control group and the cases, because it is estimated that up to 20% of individuals with PA may have resolution of their allergy.8Skolnick H.S. Conover-Walker M.K. Koerner C.B. Sampson H.A. Burks W. Wood R.A. The natural history of peanut allergy.J Allergy Clin Immunol. 2001; 107: 367-374Abstract Full Text Full Text PDF PubMed Scopus (467) Google Scholar This sensitivity analysis also took into account the 1% prevalence of PA in the general population.9Ben-Shoshan M. Harrington D.W. Soller L. Fragapane J. Joseph L. St Pierre Y. et al.A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada.J Allergy Clin Immunol. 2010; 125: 1327-1335Abstract Full Text Full Text PDF PubMed Scopus (174) Google ScholarOf the 679 cases eligible to participate, 99.3% had good quality DNA. Demographic information is presented in Table I. The 674 cases had approximately twice as many mutations as the controls (20% vs 11%), and the OR for PA and FLG mutation status was similar in the Ontario and Quebec control groups (Table II). The genotype frequencies in cases and controls are shown in the Online Repository available at www.jacionline.org (see Table E4). Among the 13 case definitions, there was no significant difference in the OR for the relationship between PA and FLG mutation status. Seven representative case definitions are shown in Table III. Logistic regression of the ordered case definition criteria variable produced similar results.Table IDemographics: PA cases and controlsCharacteristicPA casesOntario controlsQuebec controlsNo. of subjects674894268Age (y)∗Age on January 1, 2009. Mean ± SD9.3 ± 4.065.5 ± 10.29.7 ± 0.5 Range0-2133-847-10 No. with missing data020Sex No. of males416281157 Proportion of males (CI)0.617 (0.580-0.654)0.315 (0.284-0.346)0.586 (0.526-0.645)∗ Age on January 1, 2009. Open table in a new tab Table IIFLG genotypes and statistical tests of PA cases compared with control groupsPA casesOntario controlsQuebec controlsCombined controlsNo. of analyzed subjects∗Genotyping failures occurred in 11 PA cases, 5 of the Ontario controls, and 1 of the Quebec controls.6638892671156No. of FLG heterozygotes†One FLG mutation detected.1129429123No. of FLG homozygotes/compound heterozygotes‡Two of the same (FLG homozygote) or 2 different (compound heterozygote) FLG mutations detected.18415Total no. with 1 or 2 FLG mutations1309830128Proportion with 1 or 2 FLG mutations0.1960.1100.1120.110ORNA1.971.931.9695% CINA1.47-2.651.24-3.061.49-2.58χ2 test (P value)NA22.33 (2.30 × 10−6)9.37 (2.21 × 10−3)25.22 (5.12 × 10−7)NA, Not applicable.∗ Genotyping failures occurred in 11 PA cases, 5 of the Ontario controls, and 1 of the Quebec controls.† One FLG mutation detected.‡ Two of the same (FLG homozygote) or 2 different (compound heterozygote) FLG mutations detected. Open table in a new tab Table IIIPA case definition analysis (PA cases compared with the combined control group)No. of subjectsOR95% CIMinimum criteria to be considered for inclusion:a.Convincing history of PA∗A convincing history was defined as a minimum of 2 mild symptoms/signs or either 1 moderate or 1 severe symptom/sign occurring within 120 min after peanut contact or ingestion. (1) Mild: pruritus, urticaria, flushing, and/or rhinoconjunctivitis. (2) Moderate: angioedema, throat tightness, change in voice, coughing, difficulty breathing (other than wheeze), nausea and/or vomiting, and/or abdominal pain. (3) Severe: wheezing, stridor, cyanosis, and/or circulatory collapse. and (i) SPT ≥3 mm or (ii) psIgE ≥ 0.35 kU/L orb.No history of peanut ingestion/uncertain history of allergy and (i) SPT ≥3 mm and (ii) psIgE ≥15 kU/L orc.Any history suggestive of an IgE-mediated reaction not compatible with anaphylaxis and (i) SPT ≥8 mm or (ii) SPT ≥4 mm if <2 y old or (iii) psIgE ≥15 kU/L ord.Positive OFC6741.961.49-2.58psIgE ≥15 kU/L or SPT ≥8 mm, or positive OFC†The definition used in our previous work1 required a history of anaphylaxis or a history suggestive of type I hypersensitivity to peanut along with SPT ≥8 mm and psIgE ≥15 kU/L.5261.971.47-2.65psIgE ≥57 kU/L or SPT ≥8 mm, or positive OFC4862.071.53-2.78psIgE ≥57 kU/L or SPT ≥15 mm, or positive OFC2672.071.42-2.96psIgE ≥15 kU/L, or SPT ≥8 mm AND anaphylaxis, or positive OFC2662.091.44-3.00psIgE ≥57 kU/L, or SPT ≥8 mm AND anaphylaxis, or positive OFC2532.211.52-3.18psIgE ≥57 kU/L, or SPT ≥15 mm AND anaphylaxis, or positive OFC1222.281.38-3.69OFC, Oral food challenge; psIgE, peanut-specific immunoglobulin E; SPT, skin prick test.∗ A convincing history was defined as a minimum of 2 mild symptoms/signs or either 1 moderate or 1 severe symptom/sign occurring within 120 min after peanut contact or ingestion. (1) Mild: pruritus, urticaria, flushing, and/or rhinoconjunctivitis. (2) Moderate: angioedema, throat tightness, change in voice, coughing, difficulty breathing (other than wheeze), nausea and/or vomiting, and/or abdominal pain. (3) Severe: wheezing, stridor, cyanosis, and/or circulatory collapse.† The definition used in our previous work1 required a history of anaphylaxis or a history suggestive of type I hypersensitivity to peanut along with SPT ≥8 mm and psIgE ≥15 kU/L. Open table in a new tab The self-reported prevalence of asthma was 11% in the Ontario controls, compared with 65% in the PA cases (see Table E5 in this article's Online Repository at www.jacionline.org). Univariate analysis found PA status to be the strongest predictor of a mutation, followed by asthma. Neither age nor gender had an appreciable relationship with the presence of FLG mutations on univariate or multivariate analysis and were not included in the final model. Multivariate logistic regression found no evidence for an effect of asthma (OR, 1.12; 95% CI, 0.79-1.59) on the relationship between PA (OR, 1.81; 95% CI, 1.29-2.55) and FLG LOF mutations. The proportion of mutations was similar in those PA cases with and without asthma. Peanut-allergic individuals with asthma had at least 1 mutation in 19.8% of the cases (95% CI, 0.159-0.236), while 18.7% (95% CI, 0.136-0.238) of the PA cases without asthma had at least 1 mutation.An additional analysis using a constructed atopic asthma variable to control for the effect of smoking yielded similar results. PA status remained significant (OR, 1.88; 95% CI, 1.27-2.80), while history of atopic asthma was not (OR, 1.44; 95% CI, 0.59-3.53). Results were also unchanged after the sensitivity analysis of the self-reported asthma variable, with only PA status remaining significant in the multivariate analysis. The sensitivity analysis on PA status similarly had little effect on the findings. While 20% resolution in cases alone finds that both PA and asthma status are nonsignificant, modeling 20% resolution of cases with 1% prevalence in the general population finds that only PA status remains significant in the multivariate model.This study substantiates the relationship between PA and FLG LOF mutations, and moreover this relationship appears independent of diagnostic criteria of PA and history of asthma, although residual confounding is always possible. All sets of diagnostic criteria used in this study were intended to define individuals with clinical allergy, although it is possible that some individuals who were merely sensitized could have been included in the less stringent definitions of PA. Despite this possibility, the association between the FLG LOF mutations and PA does not appear to vary with the diagnostic criteria for PA. Although the point estimates for the OR increase as the PA definition becomes more stringent, the sample size decreases and the CIs overlap; thus, the differences are not statistically significant.The similarity of the OR in the 2 control groups provides indirect evidence that it is unlikely that there are common FLG mutations not yet identified in French-Canadians, under the assumption of similar prevalence of PA. If unidentified common French-Canadian FLG variants exist, one would expect the observed OR to be higher when the PA cases were compared with the Quebec controls, due to a lower detection of mutations in the control group. However, further evidence such as the sequencing of FLG in French-Canadians would be of interest.Limitations of this study include the inability to verify ethnicity by using genetic markers of ethnicity, which were not available for either the cases or controls. However, of the 47 identified FLG mutations, those examined here are shared in many European populations2Irvine A.D. McLean W.H. Leung D.Y. Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (812) Google Scholar (see Table E6 in this article's Online Repository at www.jacionline.org), including the expected ancestries of our case and control groups, giving us confidence that population stratification is not the cause of the difference in mutation frequency in the cases and controls. The rate of mutations in the control groups is comparable to the number seen in other Caucasian general populations (Table E6), which also leads us to believe that we have not overestimated the association. This study was also impeded by the inability to confirm asthma status by diagnostic means and that the only control group for which we had asthma and smoking history was a group of adults. While genotype will not change with age, the age difference could have affected ethnicity (eg, through different times of immigration) and PA status because of generational lifestyle, dietary, or environmental differences. Asthma status could also be affected by this age difference, because of smoking history, failure to remember a history of childhood asthma, as well as the possibility that cases have not yet developed asthma, although there is already a large proportion of PA cases who report asthma. In an effort to address these issues, sensitivity analyses of both PA and smoking status were undertaken, which found no appreciable effects on the findings of this study.The results of this study lend credence to the hypothesis that sensitization in allergic in at least some patients may through the J. J. I. R. to peanut oral and allergic PubMed Scopus Google Scholar peanut is a risk factor for the of H. peanut as a risk factor for the of peanut allergy.J Allergy Clin Immunol. Full Text Full Text PDF PubMed Scopus Google Scholar and may be a for the of peanut for a young to peanut may be to to such as that with peanut R. M. The prevalence of peanut sensitization in childhood is due to to 2011; PubMed Scopus Google Scholar filaggrin is not the to these through the skin or could result in to If the to either barrier or may allergic research in barrier and environmental is to further of the of atopic Recently, our research team found a strong and significant association between loss-of-function (LOF) mutations in filaggrin (FLG), a gene that encodes a skin barrier protein, in European and Canadian individuals with peanut allergy (PA).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar These mutations result in a barrier defect and have been associated with atopic dermatitis, asthma, and allergic rhinitis.2Irvine A.D. McLean W.H. Leung D.Y. Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (812) Google Scholar This finding represents the strongest genetic risk factor found to date for PA, a highly heritable disease,3Sicherer S.H. Furlong T.J. Maes H.H. Desnick R.J. Sampson H.A. Gelb B.D. Genetics of peanut allergy: a twin study.J Allergy Clin Immunol. 2000; 106: 53-56Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar with an estimated odds ratio (OR) between 1.9 (Canadian) and 5.3 (English, Dutch, and Irish combined).1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar Because there is no uniformly accepted definition of PA short of oral food challenge, it is worthwhile to examine whether the association between the FLG LOF mutations and PA varies with the diagnostic criteria for PA. Furthermore, the frequent coexistence of PA with other atopic conditions may mean that the association between PA and FLG LOF mutations is confounded. Although we controlled for eczema in the European populations in our previous work, data on eczema were not available for the Canadian control group; however, data on asthma were available. Asthma is a potential confounder, as it has known relationships with both PA4Liu A.H. Jaramillo R. Sicherer S.H. Wood R.A. Bock S.A. Burks A.W. et al.National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006.J Allergy Clin Immunol. 2010; 126: 798-806.e13Abstract Full Text Full Text PDF PubMed Scopus (379) Google Scholar and FLG mutations.5Palmer C.N. Ismail T. Lee S.P. Terron-Kwiatkowski A. Zhao Y. Liao H. et al.Filaggrin null mutations are associated with increased asthma severity in children and young adults.J Allergy Clin Immunol. 2007; 120: 64-68Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar By using statistical sensitivity analyses, we examined the effect of PA diagnostic criteria and asthma on the relationship between PA and FLG LOF mutations in a Canadian PA case group. Because the PA case group was composed of both English- and French-speaking individuals, we also investigated whether the difference in OR between the Canadian and European populations could be due to some common French-Canadian mutations not yet identified in Caucasian subjects from a well-described Canadian pediatric PA case group were recruited (n = 679), and DNA was isolated from salivary samples.1Brown S.J. Asai Y. Cordell H.J. Campbell L.E. Zhao Y. Liao H. et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar One control group consisted of adult Caucasians recruited from the general population of Ontario, Canada; DNA was provided by the Ontario Population Genomics Platform at The Centre for Applied Genomics (Toronto) (n = 894). A second control group of newborn babies from Quebec City was sampled on the basis of French-Canadian surname (stored blood; n = 268).6Girouard J. Giguere Y. Delage R. Rousseau F. Prevalence of HFE gene C282Y and H63D mutations in a French-Canadian population of neonates and in referred patients.Hum Mol Genet. 2002; 11: 185-189Crossref PubMed Scopus (18) Google Scholar All samples were genotyped in Dundee, Scotland, for the 4 most common FLG LOF mutations found in Caucasians (R501X, 2282del4, R2447X, and S3247X). rs and accession numbers for mutations are available in the Online Repository at www.jacionline.org (see Table carriers" were defined as those with heterozygous, homozygous, or compound heterozygous mutations. Those individuals with none of the 4 FLG mutations were classified as "nonmutation carriers." The association between mutation status and PA was compared with the Ontario control group, the Quebec control group, and the combined control group. To evaluate whether the association between PA and mutation status changed with case definition, a continuum of PA case definitions was constructed and the resulting OR trends with case definition were examined by using the combined control groups. The methodology and rationale for these definitions are given in the Online Repository available at www.jacionline.org (see Tables E2 and E3). To increase power, case definitions were transformed into an ordered variable and the association between PA and FLG mutations was examined by using regression modeling through increasingly stringent definitions of PA to see whether the OR changed also examined the effect of asthma on FLG mutation status and PA. Logistic regression using the Ontario control group was conducted with PA status, age, sex, asthma, and interaction terms for PA and age, PA and sex, and PA and asthma. Because there may be interaction between mutation status, asthma, and smoking,7Berg N.D. Husemoen L.L. Thuesen B.H. Hersoug L.G. Elberling J. Thyssen J.P. et al.Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.J Allergy Clin Immunol. 2012; 129 (e1-2): 374-380Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar and self-identified asthmatic patients may have significant misclassification, analyses controlled for smoking history in the controls and misclassification in the asthma variable in both controls and cases. A constructed atopic asthma variable was used to control for the effect of smoking with 4 assumptions: (1) Those individuals who have atopic asthma in childhood are less likely to smoke as adults. (2) Those adults who have asthma and have never smoked are more likely to have atopic asthma. (3) If a patient reports bronchial emphysema, he or she does not have atopic asthma. (4) Asthma reported in the case group is atopic. To examine the possibility of error due to self-report of asthma, we completed a sensitivity analysis taking into account data from the PA registry that found that 6% had "forgotten" previously noted atopic history, while 12% more reported atopic history on the current questionnaire than at baseline registry recruitment. Random sampling and subsequent logistic regression modeling was completed 100 times to see the overall effect of error in asthma reporting on the relationship of PA and FLG LOF mutations using these a similar sensitivity analysis of PA status was conducted, as PA status could be affected by the age disparity between the Ontario control group and the cases, because it is estimated that up to 20% of individuals with PA may have resolution of their allergy.8Skolnick H.S. Conover-Walker M.K. Koerner C.B. Sampson H.A. Burks W. Wood R.A. The natural history of peanut allergy.J Allergy Clin Immunol. 2001; 107: 367-374Abstract Full Text Full Text PDF PubMed Scopus (467) Google Scholar This sensitivity analysis also took into account the 1% prevalence of PA in the general population.9Ben-Shoshan M. Harrington D.W. Soller L. Fragapane J. Joseph L. St Pierre Y. et al.A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada.J Allergy Clin Immunol. 2010; 125: 1327-1335Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar the 679 cases eligible to participate, 99.3% had good quality DNA. Demographic information is presented in Table I. The 674 cases had approximately twice as many mutations as the controls (20% vs 11%), and the OR for PA and FLG mutation status was similar in the Ontario and Quebec control groups (Table II). The genotype frequencies in cases and controls are shown in the Online Repository available at www.jacionline.org (see Table E4). Among the 13 case definitions, there was no significant difference in the OR for the relationship between PA and FLG mutation status. Seven representative case definitions are shown in Table III. Logistic regression of the ordered case definition criteria variable produced similar results. Not Oral food challenge; psIgE, peanut-specific immunoglobulin E; SPT, skin prick The self-reported prevalence of asthma was 11% in the Ontario controls, compared with 65% in the PA cases (see Table E5 in this article's Online Repository at www.jacionline.org). Univariate analysis found PA status to be the strongest predictor of a mutation, followed by asthma. Neither age nor gender had an appreciable relationship with the presence of FLG mutations on univariate or multivariate analysis and were not included in the final model. Multivariate logistic regression found no evidence for an effect of asthma (OR, 1.12; 95% CI, 0.79-1.59) on the relationship between PA (OR, 1.81; 95% CI, 1.29-2.55) and FLG LOF mutations. The proportion of mutations was similar in those PA cases with and without asthma. Peanut-allergic individuals with asthma had at least 1 mutation in 19.8% of the cases (95% CI, 0.159-0.236), while 18.7% (95% CI, 0.136-0.238) of the PA cases without asthma had at least 1 additional analysis using a constructed atopic asthma variable to control for the effect of smoking yielded similar results. PA status remained significant (OR, 1.88; 95% CI, 1.27-2.80), while history of atopic asthma was not (OR, 1.44; 95% CI, 0.59-3.53). Results were also unchanged after the sensitivity analysis of the self-reported asthma variable, with only PA status remaining significant in the multivariate analysis. The sensitivity analysis on PA status similarly had little effect on the findings. While 20% resolution in cases alone finds that both PA and asthma status are nonsignificant, modeling 20% resolution of cases with 1% prevalence in the general population finds that only PA status remains significant in the multivariate

BackgroundDry eye disease (DED), a chronic ocular disease, is associated with numerous medical issues, including asthma. However, studies on these associations are limited. In this study, we investigated the incidence of DED among patients with asthma and its correlation with other allergic comorbidities.MethodsWe retrospectively analyzed data from the National Health Insurance Research Database of Taiwan. We compared the data of 41,229 patients with asthma with those of 164,916 sex- and age-matched non-asthma controls. We followed up the patient and control groups from 1998 to 2010, and compared the rate of DED in these two groups. We further analyzed the allergic comorbidities and asthma-related medication use among the patients with asthma to verify whether these factors were associated with DED.ResultsThe patients in the asthma group were more likely to have DED than were the controls (6.35% vs. 4.92%, p < 0.0001). In the asthma group, female had a higher risk of DED (odds ratio (OR) = 1.70, 95% confidence interval (CI) [1.57–1.85]) than males did. After adjustment for sex, age, income, urbanization, and the other two allergic comorbidities, patients with allergic rhinitis (adjusted OR = 1.58, 95% CI [1.46–1.72]) and urticaria (adjusted OR = 1.25, 95% CI [1.12–1.38]) were more likely to have DED, but not patients with atopic dermatitis (adjusted OR = 1.17, 95% CI [0.98–1.40]). Patients with asthma who had prescriptions of leukotriene receptor antagonists (LTRAs) (adjusted OR = 1.29, 95% CI [1.01–1.64]), oral antihistamines (adjusted OR = 2.02, 95% CI [1.84–2.21]), and inhaled corticosteroids (adjusted OR = 1.19, 95% CI [1.04–1.36]) exhibited association with DED.DiscussionOur findings reveal that patients with asthma—particularly females—were more likely to have DED, with comorbidities such as allergic rhinitis and urticaria, and prescriptions including LTRAs, antihistamines, and inhaled corticosteroids. The results suggest that in clinical practice, physicians should pay attention to DED, particularly in patients with a high risk of DED.

Background and Objectives: Studies investigating the types of dietary supplements associated with the atopic triad using large-scale data remain limited. We assessed the prevalence of the atopic triad, the types of dietary supplements used, and their associations in Korean adults using a 4-year national survey data. Materials and Methods: This cross-sectional study utilized data from the Korea National Health and Nutrition Examination Survey (2018-2021). Adults aged ≥ 19 years were included. Descriptive statistics were used to summarize participants' overall characteristics and estimate the national prevalence of the atopic triad, defined as a diagnosis of asthma, allergic rhinitis, or atopic dermatitis. Logistic regression analyses were conducted using each atopic condition as a dependent variable, with the types of dietary supplements currently used as independent variables. Covariates included socioeconomic status, lifestyle factors, frailty, and diet. Dietary supplements were categorized as multivitamins/minerals, vitamin C, vitamin D, vitamin A/lutein, propolis, omega-3, probiotics, red ginseng, calcium, or iron. Results: A total of 18,182 adults were analyzed, representing an estimated 52.8 million adults (mean age: 47 years; 50% male). Of these, 21% reported a history of any atopic triad, and 61% were current supplement users. Logistic regression showed significantly higher odds of all three atopic conditions among users of propolis (asthma: OR 1.90, 95% CI 1.04-3.47; allergic rhinitis: OR 1.64, 95% CI 1.25-2.17; atopic dermatitis: OR 2.04, 95% CI: 1.18-3.52), and higher odds of allergic rhinitis among users of probiotics (OR 1.21, 95% CI 1.06-1.38) and vitamin D (OR 1.43, 95% CI 1.16-1.75). Conclusions: A positive association was found between propolis use and all three atopic conditions. Also, a positive association was found between probiotics or vitamin D use and allergic rhinitis. We did not find significant associations with the other supplements. Further research in establishing causal relationships between the dietary supplements and atopic conditions are needed.

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Effects of diet on the childhood gut microbiome and its implications for atopic dermatitis

In order to explore the genetic risk of a child with a family history of allergies developing asthma, allergic rhinitis, or atopic dermatitis, questionnaires filled in by 6665 families were analysed. The data were collected in a population based cross sectional survey of 9-11 year old schoolchildren living in Munich and southern Bavaria. The relation between asthma, allergic rhinitis, and atopic dermatitis and the number of allergic first degree relatives, and the type of allergic disease was examined. Analyses were done separately for families with single or multiple allergic diseases. In families with one allergic parent the risk of the child developing asthma was increased by asthma in a parent, with an odds ratio (OR) of 2.6 (95% confidence interval 1.7 to 4.0) but not by parental allergic rhinitis with OR 1.0 (0.7 to 1.5) or atopic dermatitis, OR 1.0 (0.6 to 1.6). For allergic rhinitis the highest risk with OR 3.6 (2.9 to 4.6) was observed with allergic rhinitis of one parent, apparently lower for asthma of one parent, OR 2.5 (1.6 to 4.0) or atopic dermatitis, OR 1.7 (1.1 to 2.5). Children with parental atopic dermatitis had a high risk for atopic dermatitis, OR 3.4 (2.6 to 4.4), compared with children with parental asthma, OR 1.5 (1.0 to 2.2), or parental allergic rhinitis, OR 1.4 (1.1 to 1.8). Risk factors in families with combined allergies of two relatives (parents and siblings) were analysed separately for the different combinations. These results support the hypothesis that asthma, allergic rhinitis, and atopic dermatitis are multifactorial diseases brought about by various familial and environmental influences.

Snoring and atopic disease: a strong association.

Comorbidity profiles among patients with alopecia areata: The importance of onset age, a nationwide population-based study

Chronic inducible urticaria (CIndU) is characterized by mast cell (MC)-mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism (SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX-0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose-dependent plasma tryptase suppression indicative of systemic mast cell ablation. This is an open-label, trial in patients with antihistamine refractory ColdU or SD, receiving one IV dose of barzolvolimab (3 mg/kg), with a 12-week follow-up. Primary endpoint was safety/tolerability; pharmacodynamic (PD)/clinical endpoints included serum tryptase, plasma SCF, skin MC histology, provocation tests, urticaria control test (UCT), and dermatology life quality index (DLQI). Analysis populations were safety (n=21) and pharmacodynamics/clinical activity (n=20). Barzolvolimab was well tolerated; most adverse events were mild and resolved. Treatment resulted in significant depletion of skin MCs, decreased tryptase (<limit of detection), and increased soluble SCF through Week 12. Complete responses (negative provocation test) occurred in 95% (n=19/20) of patients (n=10/10 ColdU; n=9/10 SD), and all (n=20/20) showed improvement in urticaria control (UCT ≥ 12). The kinetics of clinical activity mirrored that of MC and tryptase reduction. DLQI-measured impairment significantly decreased to minimal/none in 93% of patients on study. In CIndU patients, barzolvolimab was well tolerated, demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, and reductions in clinical activity with significant improvements in disease control and quality of life (QoL) demonstrating potential therapeutic effects for MC-mediated disorders.

Chronic urticaria (CU) diagnosis includes the patient's clinical history and physical examination. However, atypical presentations or misdiagnosis can lead to diagnostic delay (DD). The impact and contributing factors of DD in CU are unknown and were assessed in the present study. We retrospectively analysed data from CU adult patients from the international, multicenter Chronic Urticaria Registry (CURE). Of 4332 CU patients, 61% had standalone chronic spontaneous urticaria (sCSU), 18% had ≥ 1 form of chronic inducible urticaria (CIndU), and 21% had a combination of both (CSU + CIndU). Diagnosis of CU was delayed in 24% of patients by at least 1 year. CIndU patients showed a longer DD compared to those with sCSU or CSU + CIndU (median, [IQR]: 4, [0-22] vs. 1, [0-6] vs. 2, [0-9] months, p < 0.001). Among CIndU patients, symptomatic dermographism (n = 264) and cholinergic urticaria (n = 103) patients had the longest DD compared to all other CIndU subgroups (median: 4 months, p = 0.005 for both). In CIndU patients, a longer DD was associated with having an additional CIndU (OR: 12.8, p = 0.03), younger age, comorbidities, lower disease control, and lack of second-generation H1-antihistamine treatment. In CSU patients, a DD of ≥ 6 months was associated with lower CSU activity (median weekly Urticaria Activity Score of 14 vs. 21, p = 0.02) compared to that of DD < 6 months. Diagnosis of CU is delayed in one out of four patients. Greater awareness of the guideline-recommended CU classification, clinical presentation, and diagnostic work-up can facilitate CU diagnosis.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition that significantly impairs patients’ quality of life as a result of intense itching and persistent eczematous lesions. Although AD has a multifaceted etiology—including genetic predisposition, environmental triggers, barrier dysfunction, and dysregulated immune responses—interleukin-4 (IL-4) has a recognized central role in its pathogenesis. This narrative review explores the role of IL-4 in the pathophysiology of AD, its contribution to the atopic march, and the therapeutic impact of IL-4 inhibition. IL-4 plays a critical role in skin barrier dysfunction, dysbiosis, pruritus, and inflammation, all of which contribute to the debilitating symptoms of AD. Moreover, IL-4 is implicated in other atopic conditions, such as asthma, allergic rhinitis, and food allergies, underscoring its role beyond AD and its importance in the atopic march. Recent advances in targeted therapies, particularly IL-4/IL-13 signaling inhibitors, have changed AD management. Dupilumab, an IL-4 receptor antagonist, has demonstrated significant efficacy in reducing AD symptoms and enhancing patient outcomes in both children and adults. In addition to symptomatic relief, suppressing IL-4 signaling may also offer potential for disease modification, altering AD’s progression and possibly preventing the onset of other atopic conditions. This review highlights the crucial role of IL-4 as a therapeutic target in AD. By understanding the role of IL-4 in AD pathogenesis and exploring the therapeutic implications of targeting IL-4 pathways, this work can contribute to guide future research concerning treatment approaches and also emphasize the need for early and targeted interventions to mitigate disease impact and ultimately improve patient quality of life.

Chronic urticaria (CU) is a rare disease in childhood, and studies in children are limited. In this study, the aim was to investigate the clinical and laboratory findings and demographic characteristics of children with CU and to determine the factors affecting prognosis. The study included 141 patients aged 0-18 years who were diagnosed with CU in the pediatric allergy outpatient clinic between January 1, 2013, and December 31, 2018. Risk factors related to prognosis were investigated by comparing the duration of CU and treatment response with clinical and etiological features. IBM SPSS version 24 was used for statistical analyses. In the study group, the female/male ratio was 69/55, and the median age at first visit was 9.5 years (min:1, max:17). Among patients, 63 (44.5%) had an accompanying atopic disease, and 23 (16.3%) had chronic disease. Of the patients, 124 (88%) had chronic spontaneous urticaria, and 17 patients (12%) had chronic inducible urticaria (CIU). Of those with CIU, 72.2% had symptomatic dermographism, 16.7% had cholinergic urticaria, and 11.1% had cold urticaria. After the evaluations, the most common pathological findings in our patients were intestinal parasitosis (n=14), anemia (n=10), and urinary tract infection (n=8). The median total duration of urticaria was 47 weeks (min:8, max:284). The duration of urticaria was longer in patients with atopy (p < 0.05), and the group that went into remission with standard-dose antihistamine was the group with highest eosinophil count (p=0.022). In most children with CU, the underlying cause/disease cannot be determined. In our study, treatable triggers were found in some of the patients. Therefore, it is appropriate for each patient to be evaluated with selected laboratory tests after detailed history and physical examination.

Lung function trajectories from birth through puberty reflect asthma phenotypes with allergic comorbidity