Differences and Similarities in the Mechanisms and Clinical Expression of Bradykinin-Mediated vs. Mast Cell–Mediated Angioedema

Abstract

Angioedema (AE), transient localized swelling due to extravasated fluid, is commonly classified as mast cell mediator-induced, bradykinin-mediated or of unknown cause. AE often occurs more than once, and it is these recurrent forms of AE that are challenging for patients and physicians, and they are the ones we focus on and refer to as AE in this review. Since effective treatment depends on the causative mediator, reliable and early diagnosis is essential. Although their clinical presentations bear similarities, many forms of angioedema exhibit specific patterns of clinical appearance or disease history that may aid in diagnosis. Here, we describe the most common differences and similarities in the mechanisms and clinical features of bradykinin-mediated and mast cell mediator-induced types of angioedema. We first provide an overview of the diseases that manifest with mast cell mediator-induced versus bradykinin-mediated angioedema as well as their respective underlying pathogenesis. We then compare these diseases for key clinical features, including angioedema location, course and duration of swelling, attack frequency, prevalence and relevance of prodromal signs and symptoms, triggers of angioedema attacks, and other signs and symptoms including wheals, age of onset, and duration. Our review and comparison of the clinical profiles of different types of angioedema incorporate our own clinical experience as well as published information. Our aim is to highlight that mast cell mediator-induced and bradykinin-mediated angioedema types share common features but are different in many aspects. Knowledge of the differences in underlying pathomechanisms and clinical profiles between different types of angioedema can help with the diagnostic approach in affected patients and facilitate targeted and effective treatment.

Identification of novel biomarkers to distinguish bradykinin‐mediated angioedema from mast cell‐/histamine‐mediated angioedema

“…Clinical and routine laboratory characteristics (Table ) are in line with published data 18,28‐37 Regarding AAS7 and AE‐QoL, we did not find a significant difference between the three angioedema types. To the best of our knowledge, we were not able to find published reports of AAS7 or AE‐QoL in HAE, ACE‐AE, or in CSU‐AE (without wheals).…”

“…Clinical and routine laboratory characteristics (Table S1) are in line with published data 18,[28][29][30][31][32][33][34][35][36][37] Regarding AAS7 and AE-QoL, we did not find a significant difference between the three angioedema types.…”

“…Psychological stress was most commonly reported as a trigger factor of attacks in all three angioedema types. This trigger is well known in HAE and CSU 6,9,18,40 , whereas the triggering factors of ACE‐AE are far from being clear.…”

Recognition and Management of Hereditary Angioedema: Best Practices for Dermatologists

“…Abdominal and laryngeal attacks Fig. 1 Simple schematic comparing the different pathophysiologic pathways underlying A mast cell-mediated (allergic) angioedema and B bradykinin-mediated angioedema, with sites of C1INH regulation [7,8,12]. C1INH C1 inhibitor, HMW high molecular weight, IgE Immunoglobulin E, NSAIDs nonsteroidal anti-inflammatory drug.…”

Hereditary Angioedema

“…[ 3 ] Angioedema associated with wheals is commonly encountered in patients having acute or chronic urticaria or anaphylaxis, and the chief mediator for its development is histamine, which is released from the mast cells, either through immunological pathways (IgE-mediated type-1 hypersensitivity) or by agents that act directly on the mast cells to cause their degranulation. [ 4 ]…”