Furthermore, the observed stepwise and parallel increase in Tot-IgE and EBC values, from the lowest in GERD-patients without urticaria to the highest in patients with overlap syndrome of CSU and GERD, suggests a progressively increasing activation of a Th2-like profile of immune-inflammatory responses because of a CSU appeared months or years after a longstanding GERD that had previously been poorly characterized as well as discontinuously managed. The gene discussed is IGHE; the disease is gastroesophageal reflux disease.