Conclusion: Negative skin test and subcutaneous challenge with a history of generalized cutaneous symptoms and/or systemic symptoms during the reaction to LA can be attributed to many causes, such as an IgE-mediated reaction against a component other than lidocaine (e.g., latex), medication side effects (adrenaline in combined preparations), and/or symptoms of primary disease (chronic spontaneous urticaria/angioedema). The gene discussed is IGHE; the disease is chronic idiopathic urticaria.