The mechanisms underlying the role of periodontal tissue damage in patients with HAE involving downregulation of immune responses45 or upregulation by production of glucocorticoids.4 During stressful periods, the hypothalamic–pituitary–adrenal axis increases its release of corticotrophin-releasing hormone (CRH) and this stimulates the pituitary gland to release adrenocorticotrophic hormone (ACTH) and β-endorphin. The gene discussed is CRH; the disease is hereditary angioedema.