Correspondence

Angioedema of the Intestine

N Engl J Med 1996; 335:1534-1535November 14, 1996

Article

To the Editor:

In their image entitled “Angioedema of the Intestine” (June 20 issue),1 Gregory and Davis did not mention the duration of lisinopril treatment. Since the diagnosis of recurrent swelling of the tongue and pharynx associated with the administration of an angiotensin-converting–enzyme (ACE) inhibitor was missed (lisinopril was continued and angioedema of the intestine developed), I assume that the patient had been treated with lisinopril for a relatively long period.

Although the early onset of the ACE-inhibitor–induced angioedema should not be a diagnostic problem, many physicians are not familiar with late-onset angioedema, and it frequently goes unrecognized.2-4 The potentiation of the bradykinins is believed to be the pathophysiologic mechanism of this side effect.5 If this proves to be true, ACE-receptor antagonists may be an alternative therapy for patients who cannot tolerate ACE inhibitors, as implied by Goodfriend et al. (June 20 issue).6

Adriana Pavletic, M.D.
University of Nebraska Medical Center, Omaha, NE 68198

6 References

1
Gregory KWP, Davis RC. Angioedema of the intestine. N Engl J Med 1996;334:1641-1641
Full Text | Web of Science | Medline

2
Litman RS, Sher WH, Hausman SA. Life threatening acute airway obstruction due to enalapril induced angioedema. Immunol Allergy Pract 1992;14:21-24

3
Frontera Y, Piecuch JF. Multiple episodes of angioedema associated with lisinopril, an ACE inhibitor. J Am Dent Assoc 1995;126:217-220
Web of Science | Medline

4
Finley CJ, Silverman MA, Nunez AE. Angiotensin-converting enzyme inhibitor-induced angioedema: still unrecognized. Am J Emerg Med 1992;10:550-552
CrossRef | Web of Science | Medline

5
Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: a review of the literature and pathophysiology. Ann Intern Med 1992;117:234-242
Web of Science | Medline

6
Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. N Engl J Med 1996;334:1649-1654
Full Text | Web of Science | Medline

To the Editor:

Gregory and Davis highlight an unusual presentation of angioedema associated with ACE-inhibitor therapy — namely, angioedema of the intestine. It is of interest that the patient had recurrent episodes of swelling of the tongue and pharynx while taking an ACE inhibitor without the treatment's being stopped. These may have been presentations of angioedema that went unrecognized.

The role of ACE inhibitors in patients presenting with angioedema is poorly recognized. This may be because the onset of angioedema can occur after a long period (months to years) of uneventful therapy with ACE inhibitors.1 In only one of nine cases of ACE-inhibitor–associated angioedema treated at public hospitals was the patient advised to discontinue taking the ACE inhibitor.2

Ongoing care of patients with ACE-inhibitor–associated angioedema is a problem. The ACE inhibitor must be stopped to avoid recurrence of this life-threatening event, meaning that alternative therapies must be found. Recently, a new class of drug has become available, the orally effective blockers of angiotensin II receptors (e.g., losartan). These agents provide an alternative means of blocking the renin–angiotensin system. They exert hemodynamic effects similar to those of ACE inhibitors in cardiac failure and are effective antihypertensive drugs.3 Goodfriend et al. suggested a role for this new class of drug in the treatment of patients unable to tolerate ACE inhibitors.4 They also state, “It is apparent that these drugs . . . do not have two side effects that can interrupt therapy with ACE inhibitors — cough and angioedema.” Angioedema, however, has been reported with losartan.5

Genevieve M. Gabb, M.B., B.S.(Hons.)
Australian Medicines Handbook, Adelaide SA 5000, Australia

5 References

1
Pigman EC, Scott JL. Angioedema in the emergency department: the impact of angiotensin-converting enzyme inhibitors. Am J Emerg Med 1993;11:350-354
CrossRef | Web of Science | Medline

2
Weiner JM. Failure to recognise the association of life-threatening angio-oedema and angiotensin-converting enzyme inhibitor therapy. Aust N Z J Med 1995;25:241-242
CrossRef | Medline

3
Johnston CI. Angiotensin receptor antagonists: focus on losartan. Lancet 1995;346:1403-1407
CrossRef | Web of Science | Medline

4
Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. N Engl J Med 1996;334:1649-1654
Full Text | Web of Science | Medline

5
Acker CG, Greenberg A. Angioedema induced by the angiotensin II blocker losartan. N Engl J Med 1995;333:1572-1572
Full Text | Web of Science | Medline

To the Editor:

The image submitted by Gregory and Davis is a computed tomographic (CT) scan showing angioedema of the small intestine due to lisinopril. It would have been interesting, as well as clinically relevant, if the authors had included amylase or lipase values as well as an image of the pancreas, since lisinopril has been associated with acute pancreatitis.1-3 The authors note that the patient presented with abdominal pain, nausea, vomiting, and distention, which are consistent with the presence of acute pancreatitis.

ACE inhibitors have recently been implicated as a potential cause of acute pancreatitis, with reports of cases associated with lisinopril, captopril, and enalapril.1,2 Cases of lisinopril-associated pancreatitis have been reported to occur from two weeks to two years after therapy is begun.1 A fatal case of acute pancreatitis associated with lisinopril was recently reported.2

Angioedema of the upper aerodigestive tract is a well-known adverse effect of ACE inhibitors and may be due to altered bradykinin metabolism.1,4 Angioedema of pancreatic tissue may result in obstruction of the ductal system and lead to pancreatitis.3,4 Clinicians should consider acute pancreatitis in any patient in whom abdominal pain develops who is taking lisinopril or another ACE inhibitor.

Mark A. Marinella, M.D.
University of Michigan Medical Center, Ann Arbor, MI 48109

4 References

1
Marinella MA, Billi JE. Lisinopril therapy associated with acute pancreatitis. West J Med 1995;163:77-78
Medline

2
Standridge JB. Fulminant pancreatitis associated with lisinopril therapy. South Med J 1994;87:179-181
CrossRef | Web of Science | Medline

3
Dabaghi S. ACE inhibitors and pancreatitis. Ann Intern Med 1991;115:330-331
Web of Science | Medline

4
Marinella MA. Angio-oedema induced by ACE inhibitors. J Intern Med 1996;239:371-372
CrossRef | Web of Science | Medline

To the Editor:

I found the abdominal CT scan submitted by Gregory and Davis interesting in a way that went beyond the pathologic process it demonstrated. In the case presented, a patient taking an ACE inhibitor who had angioedema of the upper airway was proved on CT scanning to have angioedema of the bowel wall as well. At a cost of approximately $500 per case at our institution, the CT has proved what clinical judgment could have deduced earlier. This patient was exposed to the risk associated with continued lisinopril therapy and was subjected to a procedure that might have been indicated had her condition not improved on withdrawal of the offending medication.

The need of physicians to visualize and prove with certainty what good clinical judgment suggests to be likely continues to be a problem that we must all come to terms with. Cumulatively, the costs to the system and at times to our patients are great.

Daniel C. Smith, M.D.
Baystate Medical Center, Springfield, MA 01199

Author/Editor Response

Drs. Gregory and Davis reply:

To the Editor: We appreciate the interest in our image expressed by Drs. Pavletic, Gabb, Marinella, and Smith.

In response to Dr. Smith: this patient presented with no known history of ACE-inhibitor–induced angioedema, and she reported having no past difficulties with these drugs. She reported four episodes of a “food allergy” involving swelling of the lips and tongue that had occurred approximately one year previously. That she was taking an ACE inhibitor was established only in retrospect. Several days before her presentation, she was given another prescription for lisinopril by a physician who was unaware of her previous angioedema. Thus, our patient presented with severe abdominal pain, nausea, and vomiting of unclear cause. Except for the recent use of lisinopril, the patient's history and the examination of the oropharynx were normal. Abdominal radiographs revealed only minor, nonspecific bowel dilation; routine laboratory tests were remarkable only for leukocytosis; and an abdominal ultrasound study was nondiagnostic. Because of the severity of the symptoms, we think abdominal CT scanning was appropriate and indicated.

Marinella describes the important association between ACE inhibitors and pancreatitis and notes the similarities between the presenting symptoms in our patient and those seen in acute pancreatitis. In our patient, CT images of the pancreas were unremarkable, and her amylase level was normal.

Kate W.P. Gregory, M.D.
Rufus C. Davis, M.D.
Vanderbilt University, Nashville, TN 37232

Citing Articles (2)

Citing Articles

1
Koichi Tsunoda, Fumikazu Hozaki, Jo Aikawa. (2000) Angioedema for the Epiglottis Associated With Enalapril. The Laryngoscope 110:12, 2147-2148
CrossRef
2
Gibbs, Lip, Beevers. (1999) Angioedema due to ACE inhibitors: increased risk in patients of African origin. British Journal of Clinical Pharmacology 48:6, 861-865
CrossRef