Simvastatin: A Risk Factor for Angioedema?

Abstract

Angioedema is the abrupt onset of swelling involving the mucosa and submucosa of the skin. It can affect the face, lips, tongue, pharynx, and larynx, causing lifethreatening airflow obstruction. 1,2 Angioedema is mediated by inflammatory cytokines, such as prostaglandin D 2 , leukotrienes, cytokines, bradykinin, and complement components, which cause vasodilation and increase the permeability of capillaries. This allows plasma to leave the intravascular space and cause submucosal swelling. 2 It may be accompanied by urticaria, identifying it as an acute allergic response mediated by histamine. Urticaria differs from angioedema in that it only affects the skin and not the subcutaneous or submucosal tissue and is almost always pruritic. 2 Angioedema without urticaria can be a result of an adverse drug reaction as is the case with angioedema due to angiotensin-converting enzyme (ACE) inhibitors. 1 Approximately 17.5% of patients with cutaneous drug eruptions have angioedema. 3 In addition, it is estimated that angioedema is caused by a drug in 32% of cases. 4 Lastly, ACE-inhibitor use is associated with 25-38% of all angioedema-related emergency department (ED) visits. 5 Simvastatin, as well as atorvastatin, fluvastatin, lovastatin, rosuvastatin, and pravastatin have been associated with postmarketing reports of hypersensitivity reactions, including angioedema. 6-11 A review of the literature reveals 4 case reports of statin-induced angioedema. These reports described a case of atorvastatin-induced angioedema with dermographism and urticaria, atorvastatin-induced angioedema with rash and eosinophilia,

Inhibition of Protein Prenylation of GTPases Alters Endothelial Barrier Function

“…Finally, the authors conclude that prior statin-treatment does not ameliorate mildly increased vascular permeability in patients undergoing cardiovascular surgery. Accordingly, ankle and face edema are occasionally reported adverse effects of statin treatment [24][25][26][27].…”

Drug-induced Angioedema: A Rare Side Effect of Rosuvastatin

“…These reports described a case of atorvastatin-induced angioedema with rash and eosinophilia, pravastatin-induced angioedema, lovastatin-induced angioedema with urticaria, and simvastatin-induced angioedema. Time of onset of these reactions varies from two days to nine months (Table 1 ) [ 2 , 7 - 9 ].…”

“…Drug-induced non-inflammatory angioedema is a self-resolving but distressing side effect of some medications, e.g., angiotensin-converting enzyme inhibitors. There is an association between drug-induced angioedema and statin use in postmarketing reports [ 2 ]. There are no published cases of drug-induced angioedema involving rosuvastatin.…”

Pathogenesis of Drug Induced Non-Allergic Angioedema: A Review of Unusual Etiologies

“…The patient facial, lip and tongue swelling resolved over the next 36 hours without the use of any further corticosteroid treatment. In the following six months, the patient reported only one episode of daytime angioedema but no new episode of nighttime angioedema [ 21 ]. In this case report, bradykinin is most likely the mediator of angioedema episode because of at least four facts; there was no urticarial rash, the relatively long delay of angioedema onset after the simvastatin administration, the lack of improvement of the swelling with diphenhydramine, and the resolution of angioedema after simvastatin discontinuation.…”