Complex Vascular Lesions at Autopsy in a Patient With Phentermine-Fenfluramin

Abstract

To the Editor.—In the June 1999 issue of the Archives, Strother et al1 reported the case of a middle-aged woman who had ingested phentermine and fenfluramine for weight reduction during 8 months. The lesions of pulmonary muscular arteries shown in Figure 1, A and B, which the authors interpreted as focal organizing thrombi, are, in my opinion, plexiform lesions. The lesion in Figure 1, A, is intimal hyperplasia, and Figure 1, D, represents arterial necrosis. These lesions correspond to grades IV, II, and VI, respectively, in the grading system established by Heath and Edwards2 for the lesions of muscular arteries of 100 μm to 1000 μm diameter in pulmonary hypertensive vascular disease or to pulmonary plexogenic arteriopathy as proposed by a World Health Organization Working Group.3 My opinion is established on the morphologic study of the lungs of 37 patients who died in Switzerland after having ingested aminorex fumarate (another weight-reducing pill)4 during the so-called aminorex epidemic reviewed by Gurtner.5 Pulmonary hypertensive vascular disease affected 582 patients in Austria, former West Germany, and Switzerland during a limited period: from 1965, when the drug was introduced, until 1968, when it was withdrawn from the market. None of our cases showed arterial thromboses.In 2 cases of phentermine-related pulmonary hypertensive vascular disease submitted for assessment (unpublished data), I found similar vascular lesions. However, none of the patients (aminorex or phentermine cases) showed any correlation between the severity of the lesions and the drug intake (quantity or duration).In the absence of any serious experimental model published, the mechanism by which the lesions related to anorexigens (aminorex, phentermine, or fenfluramine hydrochloride) remains unexplained. One can only hypothesize that in some people (about 0.2% in the aminorex cases), some factors did cause an increase in the tonus of muscular pulmonary arteries, which was followed by a vasospasm, resulting in an endothelial lesion on which fibrinoid material was deposited, producing intimal proliferation. The latter, rich in myointimal cells and smooth muscular cells, might have contributed to the aggravation of the pulmonary hypertension induced by the vasospasm.I agree with the question Strother et al raised about the risk-benefit operation of the new anorexigens, which in turn leads to the more serious inquiry into unrecognized cases of pulmonary hypertensive disease in the countries where these drugs are marketed.