Novelties in the Diagnosis and Treatment of Angioedema

Abstract

Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis. Key words: Angioedema. Bradykinin. Histamine. C1 inhibitor. Coagulation factor XII. Angiotensin-converting enzyme inhibitors. Urticaria. ResumenAngioedema se define como un edema local, autolimitado, no-inflamatorio. Se trata de un edema circunscrito debido a la trasvasación de plasma de los capilares localizados en los sustratos profundos de la piel y de las mucosas. En la mayoría de los casos están implicados dos mediadores, la histamina y la serotonina. Puede manifestarse en forma de habones como en la urticaria de origen alérgico. El angioedema de origen no alérgico es el motivo de esta revisión. Se puede presentar bajo 3 formas adquiridas y 4 formas hereditarias. La histamina es el mediador implicado en el angioedema adquirido de etiología desconocida (angioedema adquirido idiopático histaminérgico). En las otras formas se sospecha que es la serotonina el mediador principal. La etiología del angioedema puede ser identificado en 4 tipos: una deficiencia de C1-inhibidor (C1-INH-angioedema hereditario y C1-INH-angioedema adquirido), mutaciones en el factor XII de coagulación (FXII-angioedema hereditario), tratamiento con inhibidores del enzima convertidor de la angiotensina (ACEi-angioedema adquirido). En uno de los adquiridos (angioedema adquirido idiopático no histaminérgico) y en el hereditario de origen desconocido, no se ha identificado todavía su etiología. Varios tratamientos están aprobados para revertir los síntomas clínicos y se aplican en la deficiencia de angioedema hereditario por déficit de C1-INH: Derivados de plasma y C1-IN...

Recurrent Angioedema: Occurrence, Features, and Concomitant Diseases in an Italian Single-Center Study

“…Diminished C1-INH is the hallmark of C1-INH-HAE (types 1 and 2) due to mutations in the C1-INH gene ( SERPING1 ) that result in deficiency or functional impairment of C1-INH [10] . The deficiency in C1-INH in C1-INH-AAE does not depend on genetic defects but on protein consumption [11] . It is well known that C1-INH-AAE is frequently associated with lymphoproliferative diseases and/or anti-C1-INH inactivating autoantibodies, and patients with C1-INH-AAE present with a higher risk than the general population for B cell malignancies [12,[13][14][15] .…”

“…A common cause of recurrent AAE is ACEI treatment; patients who develop AE during this treatment most likely have an altered metabolism in which bradykinin episodically accumulates in the plasma [17,18] . Even though recurrent AE is a well-documented side effect of ACEI treatment, its features still frequently go unrecognized, which may lead to an extensive workup before clinical recognition [11] .…”

Angioedema 2 months after Administration of Rivaroxaban (Xarelto)

“…Neither Endotracheal intubateion, trachestomy nor epinephrine were required. As part of the management of angioedema all her previous medications were stopped including rivaroxaban which was replaced with Tinzaparin for a short period and the patient was observed for resolution of the angioedema [1,2]. Few days after the treatment of angioedema the symptoms resolved completely with the swelling in the lower lip and tongue disappearing.…”

“…Pulmonary embolism is a common disease, with an estimated annual incidence of 70 cases per 100,000 population [1][2][3]. The condition usually leads to hospitalisation and may be fatal.…”

Urticaria and Angioedema

“…Idiopathic angioedema is a diagnosis of exclusion. C1 inhibitor deficiency, factor XII mutation, treatment with ACE inhibitors must be ruled out [49]. The condition is mostly well-controlled with prophylactic antihistamines [5].…”