Combination of H1 and H2 Histamine Receptor Antagonists: Current Knowledge and Perspectives of a Classic Treatment Strategy.

Histamine receptor antagonists, which can bind to specific histamine receptors on target cells, exhibit substantial therapeutic efficacy in managing a variety of histamine-mediated disorders. Notably, histamine H1 and H2 receptor antagonists have been extensively investigated and universally acknowledged as recommended treatment agents for numerous allergic diseases and acid-related disorders, respectively. Historically, the combination of H1 and H2 receptor antagonists has been considered a classic treatment strategy, demonstrating relatively superior efficacy compared with single-drug therapies in the treatment of diverse histamine-mediated diseases. The latest emerging studies have additionally suggested the underlying roles of histamine and H1R and H2R in the development of anxiety disorders, arthritic diseases, and postexercise hypotension. Nevertheless, there is still a lack of systematic reviews on the clinical efficacy of combination therapy, greatly limiting our understanding of its clinical application. Here, we present a comprehensive overview of the current knowledge and perspectives regarding the combination of H1 and H2 histamine receptor antagonists in various histamine-mediated disorders. Furthermore, we critically analyze the adverse effects and limitations associated with combination therapy while suggesting potential solutions. Our review can offer a systematic summary and promising insights into the in-depth and effective application of the combination of H1 and H2 receptor antagonists.

Recognition and Differential Diagnosis of Hereditary Angioedema in the Emergency Department.

BACKGROUND: Angioedema (AE) is a clinical syndrome marked by localized swelling of the subcutaneous layer of the skin or the submucosal layer of the respiratory or gastrointestinal tracts. While AE is commonly mediated by histamine (allergic AE), some types result from excessive bradykinin activity, including hereditary AE (HAE), acquired AE, and angiotensin-converting enzyme inhibitor-induced AE. These are less common but important to consider given different treatment requirements and potentially serious outcomes, including death from laryngeal swelling. OBJECTIVE: This review describes the pathophysiology and clinical features of AE as well as the diagnosis and treatment of AE in the emergency department (ED). DISCUSSION: Bradykinin-mediated AE does not respond to antihistamines and corticosteroids. By contrast, several targeted, effective therapies are available, including C1-inhibitor (C1-INH) concentrates, which replace the missing protein activity underlying some bradykinin-mediated AE, and medications that directly lessen bradykinin activity (eg, ecallantide and icatibant). Urticaria is generally absent in bradykinin-mediated AE and serves as a primary differentiating factor in the clinical diagnosis. Relevant laboratory assessments may include C1-INH levels, C1-INH function, and C4 complement. Patients with HAE or a family member can communicate their known diagnosis when presenting to the ED, and some may even bring their own medication(s) with them. Patients newly diagnosed with HAE in the ED should be referred for specialized outpatient care upon ED discharge. CONCLUSIONS: There is a great need for ED clinicians to be aware of HAE, its differential diagnosis, and appropriate treatment to ensure that patients receive optimal and timely treatment.

Angioedema in the emergency department: a practical guide to differential diagnosis and management.

BACKGROUND: Angioedema is a common presentation in the emergency department (ED). Airway angioedema can be fatal; therefore, prompt diagnosis and correct treatment are vital. OBJECTIVE OF THE REVIEW: Based on the findings of two expert panels attended by international experts in angioedema and emergency medicine, this review aims to provide practical guidance on the diagnosis, differentiation, and management of histamine- and bradykinin-mediated angioedema in the ED. REVIEW: The most common pathophysiology underlying angioedema is mediated by histamine; however, ED staff must be alert for the less common bradykinin-mediated forms of angioedema. Crucially, bradykinin-mediated angioedema does not respond to the same treatment as histamine-mediated angioedema. Bradykinin-mediated angioedema can result from many causes, including hereditary defects in C1 esterase inhibitor (C1-INH), side effects of angiotensin-converting enzyme inhibitors (ACEis), or acquired deficiency in C1-INH. The increased use of ACEis in recent decades has resulted in more frequent encounters with ACEi-induced angioedema in the ED; however, surveys have shown that many ED staff may not know how to recognize or manage bradykinin-mediated angioedema, and hospitals may not have specific medications or protocols in place. CONCLUSION: ED physicians must be aware of the different pathophysiologic pathways that lead to angioedema in order to efficiently and effectively manage these potentially fatal conditions.

Current and future therapies for the treatment of histamine-induced angioedema.

INTRODUCTION: Angioedema, a sudden, self-limited swelling of localized areas of any part of the body that may or may not be associated with urticaria, is thought to be the result of a mast-cell mediated process versus a bradykinin etiology. Understanding the mechanism is key in determining the proper treatment. Areas Covered: Clinical presentation of varying angioedema types may be similar; however, the appropriate treatment algorithm is dependent upon clinicians' knowledge of the underlying pathophysiology and classification of angioedema. Literature review of recent guidelines, available medications, and alternative therapies was completed to provide an overview of options. CONCLUSION: There are no formal guidelines for treatment of acute or chronic histamine-mediated angioedema, and therefore, algorithms for the treatment of acute and chronic urticaria should be followed until such information becomes available. Differentiating histamine-mediated versus bradykinin mediated angioedema is essential, as treatments and treatment responses are quite different. Further research is needed to better understand idiopathic angioedema that is unresponsive to H1/H2 antagonists, LTMAs, or medications designed to treat bradykinin-mediated angioedema.