Medical Literature - 1999

Angioedema due to angiotensin-converting enzyme inhibitors

Agostoni A, Cicardi M, Cugno M, Zingale LC, Gioffre D, Nussberger J 10/1999 Immunopharmacology

Angiotensin-converting enzyme (ACE) inhibitor associated angioedema was detected in 39 subjects (17%) of 231 consecutive patients examined in the last 5 years at our out-patient clinic for symptoms of angioedema without urticaria. In these patients, angioedema was most commonly localized to the face. The duration of ACE-inhibitor treatment at the onset of angioedema ranged from 1 day to 8 years with a median of 6 months. The time elapsed between onset of angioedema and withdrawal of ACE-inhibitor ranged from 1 day to 10 years with a median of 10 months. Delayed diagnosis is explained by the unusual characteristics of this adverse reaction: angioedema may start years after beginning the treatment and then it recurs irregularly. In fact, ACE-inhibitors seem to facilitate angioedema in predisposed subjects, rather than causing it with an allergic or idiosyncratic mechanism. Thus, while Cl-inhibitor levels are usually normal in subjects developing ACE-inhibitor-dependent angioedema, we found that ACE-inhibitors caused angioedema in Cl-inhibitor-deficient patients. Because the main inactivator of bradykinin is kininase II, which is identical with ACE, it is believed that bradykinin mediates ACE-inhibitor-dependent angioedema. We had the possibility to examine the plasma bradykinin levels in one ACE-inhibitor-treated patient during an angioedema attack and we found very high levels, but we did not find an increase of break-down products of high-molecular-weight-kininogen as observed during acute attacks in hereditary angioedema. Bradykinin fell to normal levels during remission after withdrawal of the drug. These observations indicate that in ACE-inhibitor-induced angioedema, contrary to hereditary angioedema, the reduction of bradykinin catabolic rate plays a predominant role.

Oct 15;44(1-2):21-25

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C1 inhibitor in anti-inflammatory therapy: from animal experiment to clinical application

Kirschfink M, Nurnberger W 3/1999 Molecular Immunology (Mol.Immunol.)

Potentially life-threatening consequences due to severe inflammatory tissue destruction are often closely associated with an excessive activation of the complement system. Various clinical disorders, including capillary leak syndrome, septic shock, multiple organ failure and hyperacute graft rejection are at least in part driven by an overactivated complement system. Therapeutic support of complement regulation appears to be a logical approach to reduce undesirable inflammatory reactions. C1 inhibitor, a multifunctional regulator of all major kinin-generating protein cascade systems, is frequently observed to be reduced in patients suffering from severe inflammation, due to ligand-induced inactivation of the regulatory protein. After C1 inhibitor has for many years been proven beneficial in acute treatment of hereditary angioedema, a growing number of reports now suggests that C1 inhibitor provides an effective means to protect against complement-mediated inflammatory tissue damage. These studies not only include pathophysiologically relevant animal models but also first attempts to prove the benefits of C1 inhibitor as a novel therapeutic approach in clinical trials. [References: 85].

1999 Mar-Apr;36(4-5):225-232

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The efficacy of short-term danazol prophylaxis in hereditary angioedema patients undergoing maxillofacial and dental procedures

Farkas H, Gyeney L, Gidofalvy E, Fust G, Varga L 4/1999 Journal of Oral & Maxillofacial Surgery

PURPOSE: This study evaluated the efficacy of short-term danazol prophylaxis in hereditary angioedema patients undergoing maxillofacial or dental procedures.

PATIENTS AND METHODS: Twelve patients with a history of edema after dental procedures were administered danazol (600 mg/d) 4 days preoperatively and 4 days postoperatively. The serum levels of complement components were determined preoperatively and postoperatively as well as at 6, 12 and 24 hours in six patients.

RESULTS: None of the 12 patients developed angioneurotic edema. The serum levels of the complement components were decreased immediately after surgery and returned to normal within 24 hours.

CONCLUSION: The short-term prophylactic use of danazol in patients with hereditary angioedema undergoing oral surgery is an effective preventive measure.


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Funding for Canadian Hereditary Angioedema Network has been generously provided by unrestricted grants from:


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