Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown

Clopidogrel Desensitization After Drug-Eluting Stent Placement

ObjectivesWe hypothesized that a standardized outpatient clopidogrel desensitization protocol would be safe and effective.BackgroundAdverse reactions to clopidogrel are not uncommon, and affected patients must switch to ticlopidine after drug-eluting stent placement, despite its more malignant side-effect profile, because of the risk of ischemic events associated with premature discontinuation of dual antiplatelet therapy.MethodsPatients with suspected clopidogrel sensitivity were treated with escalating doses of clopidogrel administered orally in solution until either a clinically significant reaction occurred or the full 75-mg tablet of clopidogrel was tolerated. Desensitization was performed on an outpatient basis except in cases in which the subjects were inpatients at the time of enrollment. Follow-up was performed at 2 to 4 weeks and 6 months after treatment. Successful desensitization was defined as the ability to take clopidogrel 75 mg daily without a mucocutaneous, bronchial, or anaphylactic response.ResultsWe enrolled 24 consecutive patients with suspected reactions to clopidogrel after DES implantation, 20 of whom were outpatients. During desensitization, allergic-type reactions occurred in 4 patients and angina occurred in 1 patient. Desensitization was acutely successful in all 24 patients, and by 6-month follow-up, 1 patient had persistent but improved pruritus controlled with oral antihistamines and 23 remained asymptomatic, with only 2 patients requiring repeat desensitization.ConclusionsClopidogrel desensitization is safe and effective, induces a sustained remission, and could be advantageous in treating outpatients who are at-risk for premature discontinuation of dual antiplatelet therapy

Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. OBJECTIVE: To quantify risk associated with genes and environment on familial clustering of EoE. METHODS: Family history was obtained from a hospital-based cohort of 914 EoE probands, (n=2192 first-degree “Nuclear-Family” relatives) and the new international registry of monozygotic and dizygotic twins/triplets (n=63 EoE “Twins” probands). Frequencies, recurrence risk ratios (RRRs), heritability and twin concordance were estimated. Environmental exposures were preliminarily examined. RESULTS: Analysis of the Nuclear-Family–based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10–64, depending on the family relationship, and were higher in brothers (64.0; p=0.04), fathers (42.9; p=0.004) and males (50.7; p<0.001) compared to sisters, mothers and females, respectively. Risk of EoE for other siblings was 2.4%. In the Nuclear-Families, combined gene and common environment heritability (h(gc)(2)) was 72.0±2.7% (p<0.001). In the Twins cohort, genetic heritability was 14.5±4.0% (p<0.001), and common family environment contributed 81.0±4% (p<0.001) to phenotypic variance. Proband-wise concordance in MZ co-twins was 57.9±9.5% compared to 36.4±9.3% in DZ (p=0.11). Greater birth-weight difference between twins (p=0.01), breastfeeding (p=0.15) and Fall birth season (p=0.02) were associated with twin discordance in disease status. CONCLUSIONS: EoE recurrence risk ratios are increased 10–64-fold compared with the general population. EoE in relatives is 1.8–2.4%, depending upon relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, Twins cohort analysis revealed a powerful role for common environment (81.0%) compared with additive genetic heritability (14.5%)