Abstract
We report the rare case of angioedema (also known as Quincke edema), which was induced by valsartan, an angiotensin II receptor blocker (ARB). ARBs are a new class of antihypertensive agent that is developed to exclude the adverse effects of angiotensin-converting enzyme inhibitors. In theory, ARBs do not contribute to the occurrence of angioedema because they do not increase the serum level of bradykinin, the responsible substance for angioedema. However, some reports of ARB-induced angioedema have recently been published. In this study, we present the forth case and the first Asian case of angioedema due to valsartan, which is one of the ARBs. Otolaryngologist should be wary of the prescribing ARB and discontinue ARBs treatment soon, if angioedema is recognized.
1
Introduction
Angioedema, which is also known as Quincke edema, is a potentially life-threatening condition, because it sometimes involves swelling of the oral floor, tongue, and larynx, leading to upper airway obstruction. There are several factors associated with its occurrence, such as a hereditary deficiency of same genes, trauma, food sensitivity, and drugs. Although antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) often induce angioedema, angiotensin-converting enzyme (ACE) inhibitors are one of the most common causes. The incidence of angioedema derived from ACE inhibitors has been reported to range from 0.1% to 0.5% . Furthermore, 25% to 38% of angioedema patients were prescribed an ACE inhibitor . In some cases, angioedema due to ACE inhibitors recurred as a result of continuous administration because physicians were not aware that they triggered angioedema. Roberts et al reported that the recurrence rate was 6.2%. Recurrent angioedema is also associated with patient factors such as age, sex, race, and smoking history as well as physician factors. ACE metabolizes bradykinin, a potent vasodilatory substance, and converts angiotensin I to angiotensin II, which is a powerful vasoconstrictive agent. ACE inhibitors decrease the level of angiotensin II and increase the level of serum bradykinin simultaneously. A high level of serum bradykinin leads to fluid extravasation, which causes angioedema. Angiotensin II receptor blocker (ARB), a new class of antihypertensive drug, is developed to eliminate the cough and angioedema associated with ACE inhibitors. ARBs have a therapeutic benefit without an increase in the serum bradykinin level, thereby avoiding angioedema. However, as ARBs have begun to be more widely prescribed, cases of ARB-induced angioedema have been reported . Nevertheless, reports that identify the responsible agent of angioedema as valsartan are still three. Moreover, the racial difference of occurring ARB-induced angioedema is not investigated. In this study, we report the forth case and the first Asian case of angioedema induced by valsartan, which is one of the well-known ARBs in the world.
2
Case reports
An 81-year-old man was referred to our hospital from the emergency department of another hospital with dysarthria resulting from a 3-hour history of tongue and oral floor swelling. His medical history included hypertension, the implantation of a temporal pacemaker due to arrhythmia, cerebral infarction, and spinal stenosis. Therefore, he had taken many kinds of medication as follows: valsartan (ARB) 80 mg/d, nifedipine (calcium-channel blocker) 20 mg/d, bisoprolol fumarate ( β 1 antagonist) 5 mg/d, isosorbide mononitrate 40 mg/d, acetylsalicylic acid 100 mg/d, furosemide 20 mg/d, digoxin 0.05 mg/d, limaprost alfadex 15 mg/d, omeprazole 2 mg/d, sodium azulenesulfonate1.5 g/d, etodolac 400 mg/d, and rebamipide 300 mg/d. These drugs had been prescribed by several clinics for more than 3 years. He had no history of taking ACE inhibitors and allergic diseases such as bronchial asthma and urticaria and reaction for radiographic contrast materials. There was no allergic episode in his family history. On physical examination, his severely enlarged tongue was pushed out by symmetrical watery edema of the mouth floor ( Figs. 1 and 2 ). However, he had no symptoms of respiratory distress, sore throat, and hoarseness. He displayed no signs of cyanosis, and his vital signs were stable. His face and lips were not reddish or swollen, and no skin rash was noted. Gastrointestinal disorder such as nausea, vomiting, and diarrhea was not observed. Flexible fiberscopic laryngoscopy revealed severe swelling of the epiglottis that obstructed upper airway ( Fig. 3 ). On the other hand, his vocal cords, false vocal cords, and arytenoids were almost normal. The results of a computed tomographic study were consistent with the findings of the physical and fiberscopic examinations and showed neither symptoms of abscesses formation nor malignant tumors. A blood examination showed that C-reactive protein (CRP) was 3.1 mg/dL (reference value, <0.1 mg/dL), and white blood cell (WBC) count was 6800/ μ L. Prothrombin time (PT) was slightly prolonged, and PT international normalized ratio (PT-INR) was 1.30. Activated partial thromboplastin time (APTT) was also prolonged (51.7 seconds; reference range, 28.0–40.0 seconds). A diagnosis of angioedema (Quincke edema) was made on the basis of the findings mentioned above. The responsible factor for angioedema was suspected to be valsartan; therefore, it was discontinued from next morning. To prevent the complete obstruction of upper airway, conservative treatment was immediately begun with the intravenous administration of 300 mg hydrocortisone, 8 mg dexamethasone, and 1 g cefazolin. Therapeutic effect of steroid was rapid and remarkable, so that watery edema of the epiglottis improved quickly and the tracheostomy was not needed. The other reason why we selected the conservative therapy but not surgical treatment was that the antiplatelet drug he took daily might induce severe bleeding, and implanted pacemaker restricted to electrosurgical scissors. Within 8 hours after admission, the angioedema was greatly improved. Then, the dosage of steroids was reduced, and the other intravenous medications were stopped. The angioedema was completely resolved after 48 hours. His subsequent clinical course was uneventful, and he was discharged 8 days later.
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