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

ABSTRACT

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.

KEYWORDS:

• Angioedema
• histamine-mediated
• histamine
• treatment
• guidelines
• pathophysiology
• mechanism

Article highlights

• Angioedema presents as a sudden onset of localized swelling

• Angioedema can be histamine mediated or bradykinin mediated; treatments and treatment responses differ between these two groups

• Angioedema in the acute setting can be difficult to differentiate from anaphylaxis and therefore should be treated accordingly until proven otherwise

• The history is the best resource for identifying an underlying cause

• If angioedema episodes persist greater than 6 weeks then they are chronic

• Treatment chronic histamine mediated idiopathic angioedema should follow the current US or European guidelines for treatment of chronic urticaria as no guideline are available for isolated non-HAE angioedema

• All patients presenting with isolated angioedema should have a C4 level to exclude bradykinin mediated angioedema

• More research is required to better understanding idiopathic non-HAE angioedema unresponsive to first line agents like H1- and H2- antagonists and leukotriene modifying agents.

This box summarizes key points contained in the article.

Declaration of interest

J A Bernstein is a Principal Investigator, Consultant and Speaker for Shire, CSL Behring, Novartis and Genentech. He is also a Researcher and a Consultant for Biocyrst and Pharming. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper is not funded