Renal manifestations of hereditary angioedema

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following transplantation. Certainly, some of the patients in this study had pulmonary obstruction as determined by the FEVI:FVC ratio. Immunosuppressive therapy in the form of prednisone after transplantation may improve this airways obstruction and the decreased gas trapping or residual volume may as a consequence increase the FVC. In summary, I think it is unjustified to attribute the increase in vital capacity following transplantation to a decrease in heart size, as a plethora of other factors are Almost certainly involved.

surface area) was represented. Furthermore, as donor/recipient body size matching usually allows for a 30% discrepancy, additional variability in postoperative cardiac volume is possible, and based on previous data it appears that the donor heart does not adapt in size to the recipient after transplantation [1]. All of these factors allow for a marked degree of variability between pre- and post-transplant cardiac volume. The fact that a correlation coefficient of 0.83 is present between changes in cardiac and lung volumes in this sort of biologic data is certainly the greatest argument that the two volumes are interdependent. Calculating the coefficient of determination (r 2) allows us to predict that 69% of the change in lung volume is determined by the change in heart volume. This of course leaves 31% of the change to be due to the other factors mentioned by Dr. McCormack as well as by us in our discussion. These are well-established statistical methods [2].

festations were discovered 6 and 17 years, respectively, before the onset of episodes of swelling. In the first patient, these manifestations consisted of proteinuria together with hematuria, fortuitously detected at the time of a school medical examination; and in the second patient, they consisted of a nephrotic syndrome. Histologic examination in the first case revealed lupus-like nephritis associated with a rare and disseminated wire-loop pattern, and in the other case showed type I membranoproliferative glomerulonephritis. Both patients developed chronic renal failure reDAVID G. MCCORMACK, M.D., quiring dialysis, with secondary F.R.C.P.C. successful renal transplantation Victoria Hospital - University of in the second patient. Western Ontario London, Ontario, Canada Moreover, in regard to HAEassociated autoimmune diseases, 1. Hosenpud JD, Stibolt TA, Atwal K, Shelley D. Abnormal pulmonary function specifically related to Sire and Grant did not report the congestive heart failure: comparison of patients beonset of Guillain-Barr6 synfore and after cardiac transplantation. Am J Med drome in our first patient after 1990; 88: 493-6. management of combined HAE 2. Cosby RS, Stowell EC, Hartwig WR, Mayo M. Pulmonary function in left ventricular failure, including and lupus-like glomerulonephri. cardiac asthma. Circulation 1957; 15: 492-501. tis with both danazol and cortico3. Christie RV, Meakins JC. The intrapleural pressteroids. The occurrence of Guilsure in congestive heart failure and its clinical signifiJEFFREY D. HOSENPUD, M.D. lain-Barr~ syndrome, an autoimcance. J Clin Invest 1934; 13: 323-45. Oregon Health Sciences University m u n e - r e l a t e d condition, Submitted September 24, 1990, and accepted NoPortland, Oregon following danazol therapy is a vember 19, 1990 1. Hosenpud JD, Pantely GA, Morton MJ, Norman feature of more than academic inDJ, Cobanoglu AM, Starr A. Relationship between The Reply: terest; indeed, this case led us, recipient:donor size matching and hemodynamics 3 We have no doubt that other fac- months following cardiac transplantation. J Heart like Fretwell and Altman [4], to tors such as interstitial edema, Transplant 1989; 8: 241-4. question danazol as a safe treatpleural effusions, and debility 2. Phillips DS. Basic statistics for health science stu- ment for HAE with a suspected have an influence on spirometric dents. San Francisco: WH Freeman, 1978. autoimmune association. Danam e a s u r e m e n t s of p u l m o n a r y zol could enhance immune comfunction. As there was no signifiplex production and complement cant change in obstructive physisynthesis, thereby providing adology in our patient population, a ditional substrate for the undercorticosteroid bronchodilatory lying immune complex disease. effect would be unlikely. In addi- RENAL MANIFESTATIONS OF Finally, urinalysis and evaluation, these patients were studied HEREDITARY ANGIOEDEMA ' ~ - ] t i o n for any associated autoima mean of 15 months after their To the Editor: mune condition should be carried transplant operation and were re- In their recent review of heredi- out in all cases of HAE. ceiving very low doses of predni- tary angioedema (HAE), Sire and BERNARD HORY, M29. sone (0.1 mg/kg). The patients we Grant [1] emphasized edema-reDOMINIQUEBLANC, M~D. investigated had a broad spec- lated clinical features as the most H6pital St. Jacques trum of underlying cardiac dis- striking characteristics of this Besancon Cedex, France eases, from hypertrophic and re- condition, whichever organ was strictive cardiomyopathy to di- involved. We personally reported 1. Sire TC, Grant JA. Hereditary angioedema: its diand management perspectives, Am J Med l a t e d c a r d i o m y o p a t h y a n d two cases of HAE with the kidney agnostic 1990; 88: 656-64. ischemic heart disease. A reason- as the original target organ [2,3]. 2. Hory B, Blanc D, Boillot A, Panouse-Perrin J. Guilable range of body sizes (body Indeed, in both cases, renal mani- lain-Barr~ syndrome following danazol and corticoMay 1991

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muscle weakness and increased levels of serum aldolase" and that muscle inflammation "would also explain the elevated levels of aldolase." These two statements are certainly true. Aldolase, a c o m p o n e n t of t h e g l y c o l y t i c pathway, is present in skeletal myocyte8. However, it is imporSubmitted August 8, 1990, and accepted October tant to note that aldolase is not a 1, 1990 m u s c l e - s p e c i f i c enzyme. T h e presence of an elevated serum alThe Reply: This is in response to the letterby dolase level cannot in and of itself Hory and Blanc concerning our re- be used to specifically diagnose cent review of hereditary angioe- myositis. Aldolase is present in dema We are in agreement with many other cells of the body, intheir report [1] of the possible as- cluding hepatocytes and erythrosociation of HAE with autoim- cytes. Although the specific acmune diseases, especially those in- tivity (U/g of tissue) is lower in volving the kidney. We would erythrocytes than in muscle [2], again emphasize, as we did in our depending upon the briskness of review, that the cause of this rela- hemolysis and plasma clearance tionship is still debated and re- of the enzyme, serum levels may quires further careful observation increase. The enzyme creatine and studies. In another case re- phosphokinase (CPK) is a far more port, they described a patient with specific enzyme to demonstrate H A E who developed Guillain- muscle involvement in inflAmmaBarr~ syndrome following danazol tory disorders, once a brain source therapy [2]. We apologize for the has been ruled out. Unless the CPK om;asion of this article in our re- was also elevated in the case under view. We sincerely thank them for discussion, I would suggest that the elevated serum aldolase activity in their interesting contributions. TOMMY C. SIM, M.D. this particular case could be due to J. ANDREW GRANT, M.D. a non-muscle source. The University of Texas Medical These comments should in no Branch Hospitals Galveston, Texas way detract from the diagnosis properly made of T T P in associa1. Hory B, Haultier JJ. Glomerulonephritis and hereditary angioedema: report of two cases. Clin tion with an underlying connecNephrol 1989; 31: 259-63. tive tissue disorder. T h e y are 2. Hory B, Blanc D, Boillot A, Panouse-Perrin J. Guilonly to point out the fact that an lain-Barr~ syndrome following danazol and corticoelevated aldolase level, in the absteroid therapy for hereditary angioedema. Am J Med 1985; 79: 111-4. sence of an elevated CPK level, cannot be used as unequivocal evidence of muscle involvement, ALDOLASE IN THE DIAGNOSIS unless necrosis of other organs or OF MYOSITIS hemolysis can be ruled out.

steroid therapy for hereditary angioedema. Am J Med 1985; 79: 111-4. 3. Hory B, Haultier JJ. Glomerulonephritis and hereditary angioedema: report of two cases. Clin Nephrol 1989; 31: 259-63. 4. Fretwell MD, Airman LC. Exacerbation of a lupus erythematosus-like syndrome during treatment of non-Cl-esterase inhibitor dependent angioedema with danazol. J Allergy Clin Immuno11982; 69: 30610.

To the Editor:

In the excellent discussion of thrombotic thrombocytopenic purpura (TTP) as part of the Clinicopathologic Conference in the August 1990 issue [1], statements regarding the use of aldolase in the diagnosis of myositis need clarification. It was'suggested that the patient had muscle involvement "as judged by both ££9

May 1991

IRON REPLETION AS A CONTRIBUTION TO ERYTHROPOIETIN TREATMENT OF ANEMIA IN RHEUMATOID ARTHRITIS To the Editor:

We were very much interested in the recent report by Pincus et al [1] on the treatment of anemia in r h e u m a t o i d arthritis (RA). A great deal of research has been carried out on the pathogenesis of anemia of chronic disease (ACD) in RA. Various factors have been studied, such as decreased bone marrow iron availability, impaired iron absorption, and cytokines like tumor necrosis factor-~ and interleukins [2-4]. Indeed, the role of erythropoietin (EPO) responsiveness has been the subject of several recent studies [5,6]. M o s t p r o b a b l y , t h e E P O response to anemia in RA is relatively impaired, although decreased bone marrow sensitivity might be important as well [6]. All these studies dealt with the possible role of EPO response in ACD, but evidence can only be confirmed by treatment with recombinant h u m a n E P O (rHuEPO). Some reports already have been published [7,8]. Because of the theoretic aspects of studies on EPO response in anemia of RA, the study by Pincu8 et al [1] deserves major attention. The authors observed that all their patients had an increase in t h e h e m o g l o b i n level a f t e r 8 weeks of treatment with rHuEPO, which is encouraging. We think the EPO treatment schedule and the description of relevant parameters and follow-up BRIAN F. MANDELL, M.D., Ph.D. were carefully documented. In The Graduate Hospital their discussion, the a u t h o r s University of Pennsylvania School of Medicine state that a concern of the study Philadelphia, Pennsylvania involved the fact that some patients were iron-deficient` If the 1.Clinicopathologic Conference. Melena, anemia, criterion of an iron level, i.e., ferrenal insufficiency, and respiratory failure in a 47ritin level, lower than 60 ug/L year-old woman. Am J Med 1990; 89: 223-8. cited by the authors is used, anal2. Newsholme EA, Start C. Regulation in metabolism. New York: John Wiley and Sons, 1973: 98. ysis of the baseline characteristics of their patients shows that Submitted October 22, 1990, and accepted November 19, 1990 11 of 17 (65%; Table II) were iron-

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Volume 90