Postgrad MedJ 1998;74:571-572 C The Fellowship of Postgraduate Medicine, 1998 Adverse drug reaction of the month Postgrad Med J: first published as 10.1136/pgmj.74.875.571 on 1 September 1998. Downloaded from ACE inhibitor use and severe angioedema

A Murray, J Crowther

The prescribing of angiotensin-converting en- arrangements for tracheostomy were made, as zyme (ACE) inhibitors in the management of no clear airway could be identified on fibre- hypertension and cardiac failure has increased optic examination. This was performed under greatly since their introduction in the 1980s. local anaesthetic. Medical treatment was con- Generally, these drugs are considered safe,' 2 tinued for 48 hours. The patient had been tak- but they are known to precipitate angioedema ing enalapril for 6 months and this was discon- as a side-effect, with an incidence of tinued. She has had no further episodes of 0. 1-0.2%.2 Angioedema is a non-pitting, ery- angioedema, after 6 months. Twice prior to thematous oedema in the skin and subcutane- admission the patient had been aware of her ous tissues, which is well-defined and results in tongue being swollen, but had not sought rapid, and often profound, soft tissue swelling advice. C 1 esterase inhibitor levels were which may be life-threatening, as the head and normal. neck region is almost always affected.2 4 The numbers of reported cases of this association Case 3 are increasing as usage of this group of drugs A 71-year-old man was admitted to the Ear, increases and it is now the most frequently Nose & Throat ward with swelling of the floor identified cause in patients admitted with of his mouth. He was taking trandolopril 4 mg angioedema.2-10 (an ACE inhibitor) as part of a clinical study in essential hypertension, and had been for the Case reports previous two years. A fibre-optic examination revealed no airway involvement. He had expe- Case 1 rienced minor episodes of angioedema over the A 73-year-old hypertensive woman presented preceding 8 months, including one admission to Accident and Emergency (A&E) with to hospital. His C1 esterase inhibitor levels left-sided tongue swelling. She had had many were normal. The ACE inhibitor was stopped. episodes of angioedema over the previous 3 Due to worsening cardiac function, though, the years, once requiring admission, and carried man was recommenced on ACE inhibitors by a her own injectable adrenaline, though the rea- cardiologist (ramipril 2.5 mg). He has reported son for her angioedema had not been identi- to the dermatology clinic that he has had a fied. She had been taking lisinopril 2.5 mg for recurrence of his angioedema. We have since 3.5 years. She was admitted and given that an alternative to an ACE

recommended http://pmj.bmj.com/ intravenous chlorpheniramine 10 mg and inhibitor is used. hydrocortisone 200 mg. Her airway was satisfactory on fibre-optic examination. Over Discussion the next 2 hours she became stridulous. Repeat examination showed the base ofher tongue and Angioedema in ACE inhibitor users is a rare supraglottis to be swollen. Arrangements were complication, although it is acknowledged in made for her airway to be secured and repeat the Summaries ofproduct characteristics of ACE intravenous chlorpheniramine 10 mg, hydro- inhibitors. The symptoms are frequently mild on October 5, 2021 by guest. Protected copyright. cortisone 200 mg, and intramuscular adrena- and self-limiting2A and the episodes often occur line 1 mg were administered. Within 20 upon the commencement of treatment, al- minutes the patient's condition had dramati- though delays of months and even years have cally improved and intubation/tracheostomy been reported.5 6 was averted. A further fibre-optic examination The mechanism for ACE inhibitors to revealed much less oedema. Medical treatment produce angioedema is not clear but is was continued over the next 48 hours. The probably through a tissue accumulation of Department of patient had been previously assessed for bradykinin which is a potent vasodilator, as Otolaryngology, hereditary angioedema and had normal levels ACE is a bradykinin degrading (kininase) Victoria Infirmary, of C1 esterase inhibitor and complement. Her Glasgow G42 9TY, UK enzyme and the drugs inhibit this action.8 It is A Murray ACE inhibitor was stopped and she has had no also clear that different ACE inhibitors have J Crowther further episodes of angioedema in 6 months. slightly different structures, and possibly differ- ing levels of side-effects. For instance, captopril Correspondence to Mr A Case 2 induces tissue-specific auto-antibodies much Murray, Specialist Registrar in Otolaryngology, A 72-year-old woman with acute angioedema, more frequently than enalapril, though the sig- Department of also ofher tongue and supraglottis, was sent by nificance of this is uncertain.2 Present infor- Otolaryngology, Royal ambulance from her general practitioner to mation is not adequate to identify clearly Hospital for Sick Children, Yorkhill, Glasgow, UK A&E. Intravenous hydrocortisone 200 mg and whether or not the true incidences of an- chlorpheniramine 10 mg were administered, gioedema differ,3 and given the small percent- Accepted 16 December 1997 with intramuscular adrenaline 1 mg, and ages, a randomised controlled trial to answer 572 Adverse drug reactions

this question would be difficult. It is obviously important, though, to notify the Committee on Learning points of of Safety Medicines, any possible drug reac- Postgrad Med J: first published as 10.1136/pgmj.74.875.571 on 1 September 1998. Downloaded from * in patients admitted to hospital with tions, even recognised ones, as was done with angioedema, ACE inhibitor usage is the most our patients, to allow possible patterns of side- frequently identified cause effects to be assessed. * it should therefore be the first diagnosis The differential diagnoses of angioedema considered by any clinician seeing a patient with includes upper respiratory, or dental, infec- angioedema * angioedema almost always affects the head and tions, epiglottitis, asthma or anaphylaxis but neck and therefore the airway is at risk the critical history of ACE inhibitor use must * angioedema is not an allergic reaction and can be elicited. If this is missed, and ACE inhibitor occur many months after starting an ACE use continues, further episodes of angioedema inhibitor may occur7 which may be life-threatening, as * patients with idiopathic angioedema should not receive ACE inhibitors, as their condition can happened in two of our patients. A further worsen critical point in the history is to ensure that patients previously suffering from idiopathic angioedema, are not commenced on ACE inhibitors, as this has clearly been shown to worsen the condition.'0 have been used to modify the reaction and Angioedema secondary to ACE inhibitors is intravenous fluids and oxygen may also be not an allergic reaction and so management needed. aimed solely at modifying the allergic response In spite of the increasing body of literature will not always be effective. Neither is there an available on this subject, doctors dealing with abnormality of the complement system, as in this emergency condition still appear to be hereditary angioedema, and C 1 esterase inhibi- unfamiliar with its features. The failure to tor and C4 fraction levels can be measured to change these patients' medication may be exclude this, where there is any doubt. exposing them to significant risk. Treatment requires that the airway is secured and subcutaneous or intramuscular adrenaline Keywords: angioedema; angiotensin-converting given. The ACE inhibitor is stopped. Steroids enzyme inhibitor; airway obstruction

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