Hereditary Angioedema With Normal C1 Inhibitor: A Quarter Century of Forward Progress and Persisting Obstacles

Hereditary angioedema with normal C1 inhibitor (HAE-nl-C1INH) was initially described almost a quarter century ago. Considerable progress toward unraveling the mysteries of this complex disease has been made during the intervening years. The ability to diagnose, classify, and treat HAE-nl-C1INH, however, continues to present daunting clinical challenges. In this article we have attempted to summarize current areas of scientific consensus and provide some insights to assist physicians caring for affected individuals. Coherently describing the field of HAE-nl-C1INH in many ways embodies a precarious balance between assertions anchored by data versus conjecture. In this Rostrum we have tried to encapsulate the numerous scientific developments over the past 25 years into a proposed classification schema intended to facilitate decisions when evaluating patients with recurrent angioedema. Founded on an accurate diagnosis in conjunction with an appreciation of the underlying pathomechanism, targeted patient treatment strategies can be appropriately designed. It is hoped that this approach will lay the groundwork for future advances in our understanding of HAE-nl-C1INH while bringing patients ever closer to the goal of leading a normal life.