Contraindications to the use of ace inhibitors in patients with c1 esterase inhibitor deficiency

CORRESPONDENCE

CONTRAiNDiCATiONS TO THE deficiency. In the second patient, the striking correlation between USE OF ACE INHIBITORS IN captopril treatment and the epiPATIENTS WITH Cl ESTERASE sodes of angioedema clearly sugINHIBITOR DEFICIENCY To the Editor: We read with interest the letter by Dr. Shepherd (Am J Med 1990; 88: 446). In her letter she suggests that angioteusin-eonverting enzyme (ACE) inhibitors (captopril, enalapril, and lisinopril) might be contraindicated in patients with hereditary angioedema (HAE), a disease caused by a deficiency of Cl esterase inhibitor (Cl-INH). These drugs, by enhancing bradykinin levels, may be responsible for angioedema formation in these patients. We followed several patients with both HAE and acquired angioedema (AAE) Cl-INH deficiency [l]. One of our patients, a 38-year-old woman with type II HAE, was treated with captopril (12.5 mg) for hypertension. Immediately after initial administration of this drug, she developed severe hypotensive shock requiring hospitalization and treatment with plasma expanders. A second patient, a 68-yearold man with monoclonal gammopathy and AAE that was asymptomatic for 8 years, was treated with captopril25 mg/day for mild hypertension. Twentyfour hours after the beginning of treatment, episodes of angioedema occurred. Thereafter, he stopped and resumed taking captopril three different times, with an angioedema episode developing each time. In the first patient, we cannot draw the conclusion that the hypotensive shock after captopril administration depended on the presence of ClINH deficiency. It has been reported that kinin-mediated hypotension is minimized by the administration of Cl-iNH plasma concentrate [2]. Therefore, we hypothesize that in our patient with HAE, the hypotensiveeffect of the ACE inhibitor was maximixed by the presence of Cl-INH 27%

February

1991

The American

Journal

gests that they were drug-dependent. We agree with Dr. Shepherd that ACE inhibitors must be contraindi~ated in patients with HAE because of the risk of angioedema episodes and, we suggest, also of hypotensive shock. Moreover, we extend the contraindication to patients with acquired deficiency of Cl-INH. This last condition occurs in connection with B- and T-cell disorders, neoplasia, and autoimmune diseases, and without associated disease due to autoantibodies against Cl-INH [3,4]. AAE is reported to be a rare condition; however, extended studies on its actual incidence are not’ available. Therefore, we strongly suggest determining functional levels of Cl-INH before giving ACE inhibitors to patients with a disease potentially associated with AAE. ANGELO AGOSTONI. M.D. MARCO CICARDI; M.D. Clinica Medica Ospedale S. Paolo Vniversith di Milan0 Milan, Italy 1. Cicardi

M, Frangi D. Genetic and acquired Cl inhibitor deficiency. Baillieres Clin lmmunol Allergy 1989; 2: 405-16. 2. Van der Starre P, Sinclair D, Damen J. Brummelhuis H. fnh~bition of the hypotensive effect of piasma protein solution by Cl esterase inhibitor. J Thorac Cardiovasc Surg 1980; 79: 738-40. 3. Gelfand JR. Boss GR. Conely CL, Reinhart R. Frank MM. Acquired Cl esterase inhibitor deficiency and angioedema: a review. Medicine (BaJimore) 1979; 58: 321-8. 4. Afsenz J, Loos M. The acquired Cl-INH deficiency with autoantibodies (AAE type Ii). Behring lnst Mitt 1989: 84: 165-72. Submitted

August

15, 1990,

and accepted

August 28. 1990

DIFFUSEALVEOLAR HEMORRHAGEIN AUTOLOGOUS BONE MARROW TRANSPLANT RECIPIENTS

To the Editor: Robbins et al (Am J Med 1989; of Medicine

Volume

90

87: 511-8) described the occurrence of a syndrome called diffuse alveolar hemorrhage (DAH) in recipients of an autologous bone marrow transplant (ABMT). This syndrome, for which no specific etiology was found, caused respiratory compromise in 20% and death in 16% of their patients. The authors suggested that ABMT recipients treated for solid tumors were even more at risk for developing DAH, on account of a subgroup of 31 such patients in their study, We therefore evaluated a group of 100 consecutive patients with solid tumors who were treated in our dep~tment with highdose chemotherapy and ABMT. All patients, mean age 40 years, had received prior standard-dose chemotherapy for breast cancer (n = 38), nonseminomatous germ cell tumors (n = 18), small cell lung cancer (n = 18), ovarian cancer (n = 20), and other solid tumors (n = 6). Chemotherapeutic agents used in the ablative combination regimens included cyclophosphamide, etoposide (VP-LG), mitoxantrone, carboplatin, melphalau, dacarbaxine, and teniposide. Total body irradiation was performed in only two patients. The overall mortality was 9%. Septicemia with m~tiorg~ failure (including adult respiratory distress syndrome) was the cause of death in six patients. The following microorganisms were involved: Candida albicans (two patients), viridans streptococci (three patients), and a Corynebacterium species (one patient). Ten patients had primary pulmonary ~onso~dation on chest radiographs. Details on these patients are shown in Table I. Four patients had diffuse consolidation and hypoxemia requiring supplemental oxygen in one and mechanical ventilation in three. The serum lactate dehydrogenase (LDH) level was considerably increased in all four patients,