Angioedema Due to Angiotensin Converting Enzyme Inhibitors
Author: V. Dimov, M.D., Fellow, Creighton University Division of Allergy & Immunology
Reviewer: S. Randhawa, M.D., Fellow, LSU (Shreveport) Department of Allergy & Immunology
Faculty Adviser: A. Bewtra, M.D., Professor, Creighton University Division of Allergy & Immunology
A 41-yo AAF presented to the ER with upper lip swelling which she noted when she woke up in the morning. She denied shortness of breath, change in voice or wheezing. She had been taking Lotrel (amlodipine/benazepril) for HTN for 6 months. She had one previous episode of angioedema affecting the the upper lip 7 years ago while she was taking Zestril (lisinopril). The previous episode did not involve any airway compromise and was treated as an outpatient.
PMH
HTN, DM2, obesity.
Medications
Lotrel (amlodipine/benazepril), metformin.
FMH
No history of serious allergic reaction in family.
Physical examination
VSS, in NAD.
HEENT: upper lip swelling, no skin rash, no tongue or eyelid swelling.
Chest: CTA (B).
CVS: Clear S1S2.
Abdomen: Soft, NT, ND, +BS.
Extremities: no c/c/e.
ACE-inhibitor-induced angioedema affecting the upper lip
Laboratory results
CBC and BMP were normal.
What is the most likely diagnosis?
Angioedema due to ACEi without airway compromise, second episode.
What diagnostic test would you order?
C1q, C4, C2
C1-esterase inhibitor - qualitative and quantitative
CH50
ANA
What is the most appropriate treatment?
Stop ACEi and start amlodipine (Norvasc) as a BP medication.
Solu-Medrol 40 mg iv q 6 hr, when better, switch to oral steroids.
Benadryl 25 mg po q 6 hr (H1-blocker).
Pepcid 20 mg po bid (H2-blocker).
Continuous monitoring of SpO2.
What happened?
The patient was seen by an ENT specialist who did not find any laryngeal edema and she was admitted for 23-hour observation.
She was given Solu-Medrol (methylprednisolone) 120 mg iv x 1, and then 40 mg iv q 6 hr. H1- and H2-blockers were continued.
What happened next?
The upper lip swelling has completely resolved by next morning. The patient had no further complaints and was discharged home with oral prednisone taper for 7 days and Benadryl po q 6 hr x 3 days, then prn for itching, rash or swelling. She was advised to avoid driving while taking Benadryl and to follow-up with her PCP in 3-5 days to check the pending laboratory test done on admission.
Final diagnosis
Angiodema due to Angiotensin Converting Enzyme Inhibitors (ACEi).
Summary
ACE inhibitors are the most common cause of drug-induced angioedema. Several reports have also linked angiotensin II receptor blockers (ARBs), such as losartan and valsartan, with the development of angioedema. ACE-inhibitor induced angiodema typically resolves within 24 to 48 hours.
ACE-inhibitor induced angiodema is an example of idiosyncratic reaction, from Greek, "a peculiar temperament."
Classification of adverse reactions to drugs: SOAP III
SOAP III:
Side effect
Overdose
Allergy
Pseudoallergy
Interaction
Intolerance
Idiosyncrasy
In a recent study of 42,000 patients (1) treated with antihypertensive medications, angioedema occurred in 0.13% of (53 people). The distribution was as follows:
- 70% were receiving lisinopril (an ACEI)
- 15% received chlorthalidone (a diuretic)
- 9% received doxazosin (an alpha blocker)
- 6% received amlodipine (a Ca++ channel blocker)
What is the cross-reactivity risk when prescribing ARB to a patient with ACE-inhibitor-related angioedema?
Less than 5 %.
A literature review of ACEi/ARB angioedema cross-reactivity, shows incidence of 3 to 8%. In a risk-benefit assessment, ARBs should be used cautiously in patients with a history of ACE inhibitor-induced angioedema
Can you prescribe ARB to a patient with ACE-inhibitor-related angioedema?
Yes, but only for populations that have demonstrated a clear benefit from angiotensin II antagonism, for example, patients with CHF and CKD.
The above recommendation has been adopted by the National Kidney Foundation guidelines and the American College of Cardiology and American Heart Association (ACC/AHA) consensus guidelines. Given the strong potential for harm with drug-induced angioedema, however, close monitoring is necessary to ensure that repeat angioedema does not occur with ARB.
ACE inhibitor-related cough
Cough associated with ACE inhibitors was first reported with captopril in 1985. Early reviews reported a frequency of 1-2% but recent reviews found it to be as high as 15-39%. Cough related to ACE inhibitors usually resolves within 2 weeks of stopping the medication but the median time is 26 days.
References
Incidence of angioedema with different antihypertension treatments. JACI, Beyond Our Pages, Volume 119, Issue 5, Pages 1287-1288 (May 2007). Primary source: Diller et al. J Clin Hypertension 2006;8:649-56
New therapies for hereditary angioedema (HAE). Allergy Notes, 01/2008.
Hereditary angioedema, Supplement of Annals of Allergy, Asthma and Immunology, 01/2008.
Cross-Reactivity of ACE Inhibitor–Induced Angioedema with ARBs. U.S. Pharmacist. Vol. No: 32:2 Posted: 2/20/2007.
Valsartan-Induced Angioedema. The Annals of Pharmacotherapy: Vol. 37, No. 7, pp. 1024-1027, 2003.
Adverse Reactions to Drugs: A Short Review
Treatment of ACE Inhibitor-Induced Cough. Medscape, 1999.
Cough and Angioedema From Angiotensin-Converting Enzyme Inhibitors: New Insights Into Mechanisms and Management. Medscape, 2004.
ACE inhibitor- versus angiotensin II blocker-induced cough and angioedema. The Annals of Pharmacotherapy, 1998.
Angioedema. Maurice Reid, MD. eMedicine.
Angioedema. Nedra R Dodds, MD. eMedicine.
Multiple choice questions
Chapter 57: Drug Allergy. Allergy and Immunology Review Corner: Chapter 57 of Pediatric Allergy: Principles & Practices, edited by Donald Y.M. Leung, et al.
Published: 06/23/2007
Updated: 07/21/2009
The photographed patient gave a permission for her photograph be taken and used for medical education.
Labels: Angioedema
17 Comments:
I am 51 today with the same upper lip swelling for no reason. The last swelling which started yesterday was not as severe as the picture I see here but I'm quite familiar with this. I don't take medication and I can't quite figure out what causes this but I believe for me this is stress related. My mother died of asmetha so I believe I have inherited some allergies also. I found out when I went to college in the US and lived in a cold (snow) climate for the first time, that I was allergic to ICE so I found out applying ice would make my body swell. I had to wear a ski mask to protect my face and ears. I think this is when it all started. Maybe the shock of the climate change from tropical to snow was too severe.
Hi,
Can ACE induced angioedema occur years after the drug has been started?
Yes, the angioedema can start at any time during the treatment with ACEi.
My son, who is 22, started taking an ACE inhibitor at least 10 years ago and last week ended up in the ER with severe swelling of his uvula(enlarged to the size of a pinky finger), soft palet and tongue. He is fine now but had never suffered any type of swelling previous to this. He has transposition of the great arteries, a congential heart defect, which required the use of this type of drug. he has since been prescribed an angiotensin II type drug. We need to question his dr. a little more before he takes this drug. He is very afraid this will happen again. It was scary. Just wanted to share our story. good luck to you.
I have had angioedema for 10 months now. I had taken Avapro 75mg per day for borderline hypertension 3 years and got anaphylaxis and angioedema when the dose was increased to 150mg per day (happened after first increased dose). It won't go away and despite multiple tests via a specialist no other cause can be found. It is being called "brittle" angioedema and has given me episodes of laryngeal obstruction and anaphylaxis but not "giant lip or face" swelling. I have to take oral cortisone, H1 and H2 blockers and now I am to start a leukotrine inhibitor. I keep an Epipen on me at all times. I also seem to have become hypersensitive to all sorts of things since getting this allergic drug reaction and have to avaoid perfumes, make up, many foods, pollens etc!
After taking lisinopril for a couple of months I started experiencing a cough I related to sinus issues which I have regularly. I took claritin and tylenol pm and soon after started swelling in my lips and on the left side of my face. The swelling was not of the nature of this picture but was enough that the characteristics of my face changed completely. The swelling continued over a two day period and involved the tissue around my eye. I started taking Benadryl consistantly for 48 hours and the swelling went away. Now I am concerned that this swelling may return if I continue to take the lisinopril. Any suggestions..
The best person to address your condition is your physician. Not an online community or a website.
I'll give you my advice, STOP now and tell your doctor about this webpage and your swelling. I had to go through the hell of swell 4x, 3 that required ER trips to stop before the wonderful Dr at Scripps diagnosed me correctly and put me on Metopolol.. not sure of spelling.
"Metopolol" -- I guess you meant "Metoprolol" -- the name should be on the bottle/container... :-)
I had been taking Lisinopril for about six years when suddenly last weekend I had a violent allergic reaction (my tongue was so swollen that I couldn't close my mouth over it) that required a trip to the ER and an overnight hospital stay. So yes, the angioedema can occur even after years of uneventful use of ACE inhibitors.
I had been taking enlapril for several years and on-and-off again I would get swelling of my lower lip, tongue, and some unmentionable places. I had no idea what was going on and had seen my gp several times about this...not a clue from them. Well, my allergist figured it out on my first visit...stoptaking ACEi immediately. I switched to Beta Blockers and haven't had a problem with antiodema since. Thank you Dr. J....!
I just had a very scary awakening at 3;00 on March 30 '09 when I awoke to a swollen tongue which was about to cut off my airway. I was rushd to the E.R. and was told this was angio-edema caused by the Benazaphrill I had been on for 10 years. I was admitted to the hospital for 23 hour observation and sent home on Benedryl. This was a very scary situation to say the least. After telling a friend about this she called her Dr. and told her about the dry cough she had had for awhile. The Dr. told her to stop this drug immediately. Thank You. God is Good.
cold urticaria is a condition wear ice or cold induces swelling. this is for Hazel. ask your doctor.
I'm 41 years old. I'm also having swelling of my lips and cheek. I don't think I'm allergic to any food. The swelling used to happen every week, lately it had been daily. I noticed this happens whenever I feel hot or warm because of the weather. The swelling goes after at least 12 hours. According to some doctors, heat could be the cause. But nothing is definite. I hope I find out soon what causes my swelling so at least I could avoid it.
I'm a 45 year old male,army retired due to reconstruction of right shoulder then after several months diagnose with RSD in the right side of my body due to damage to the small nerves,living with severe pain and disconfort 99% of the time and then after three started having severe hives due to the heat of the rsd,then one day my lips were like a ballon and my tonge so huge that close my airway,my nephew took me to the ER and they inmediatly starting treatment and about 6 hours back to normal,I have this episodes 13 times the first year and about 3 times year since this started in 2004.taking medication on the daily to prevent outbreak (lorantadine twice a day,Prednisone 20 mg daily,Benadryl every 4 hrs,Cimentadine twice a day,albuterol inhaler twice a day clarinex once a day need to carry Epi Pen and bottle of Benadryl at all time for emergency,also a Meditag with all medical information
You need to see an allergist who may recommend the appropriate testing in your case.
I have been having unusual lip swelling for about 6 months which moves around to different areas of my lips. First the lower left lip, then the upper right, then over to the upper left and finally the lower right lip swelled up hugely and it was difficult to talk. Then my right eyelid swelled hugely and still has an ugly pocket of fluid over the tear duct. The "moving swelling" went on for about 8 hours. I have been on Lotrel for about 4 years. What is going on!
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